The interactive binding of two ligands by an allosteric protein. The equilibrium constants describing the simultaneous binding of the ligands AMP and 1-anilinonapthalene-8-sulfonate (ansyl) by phosphorylase b have been evaluated. The binding of a single molecule of AMP per dimer unit causes only a moderate reduction in the binding constant for a single molecule of ansyl, but reduces that for a second molecule of ansyl by 10-fold. The binding of two molecules of AMP per dimer unit almost abolishes the binding of a single molecule of ansyl.


Structural rearrangements due to ligand binding and haem replacement in myoglobin and leghaemoglobins. Structural rearrangements in sperm whale myoglobin and leghaemoglobins caused by changes in the spin or oxidation state of the iron as a consequence of ligand binding have been measured by difference spectroscopy in the ultraviolet. When compared with the high-spin acetate complex, ligands which cause a transition to the low-spin state also cause large perturbations of tyrosine(s) remote from the haem pocket in myoglobin but only minor perturbations of tryptophan (s) in leghaem calobin. This may indicate a weaker coupling between events at the haem site and conformational changes in the protein in leghaemoglobins. The absorption spectra of various haem-liganded forms of the two proteins as well as the binding of the dye rose Bengal to the two apoproteins are consistent with weaker interactions between the haem ano apoprotein and a more solvent-exposed haem pocket in leghaemoglobin compared with myoglobin.


Isolation and characterization of two methionine: tRNA ligases from wheat germ. Two methionine: tRNA ligases (here called ligase A and ligase B) with distinctly different enzymatic and molecular properties were isolated in homogenous form from extracts of raw wheat germ. Both the A and B enzyme are composed of single polypeptide chains of Mr 105000 and 70000 respectively. The smaller molecule (B) has been shown not to be a proteolytic fragment of the larger one (A). The catalytic properties of both the A and B enzymes have been established and the Mg2-dependent capacity to charge six purified methionine-accepting tRNAs have been compared to those of the methionine: tRNA ligases from Escherichia coli and bakers' yeast. The possible reasons for the presence of two methionine: tRNA ligases and their unusual monomeric nature are discussed.


Microtubule assembly in vitro. Purification of assembly-promoting factors. The role of microtubule-associated proteins in the assembly of tubulin to microtubules in vitro has been studied. 1. It has been confirmed that pure tubulin obtained by phosphocellulose column chromatography does not significantly assemble in vitro in the absence of minor components which co-polymerize with tubulin. Although tubulin aggregates in a morpholino-ethanesulfonate buffer containing high Mg2+ concentrations, this process was neither inhibited by Ca2+ or colchicine, nor reversed by cold exposure. 2. Microtubule-associated proteins were prepared, either by phosphocellulose column chromatography or by a direct method based on boiling reassembled microtubules in the presence of 2 mM dithiothreitol and 0.75 M NaCl. From each of these preparations two protein fractions were purified, either by Ultrogel ACA34 chromatography or by sucrose gradient ultracentrifugation. The first one, with a high molecular weight, did not promote tubulin assembly; ageing of this material did not induce any activity. On the other hand, the second fraction, with an apparent molecular weight of 70 000 (tau protein), when almost completely purified, was active in promoting assembly. Thus a single specific protein is able to promote assembly of pure tubulin.


The amino-acid sequence of trout-testis histone H1. The complete amino-acid sequence of 194 residues of trout testis histone H1 has been elucidated by automated Edman degradation of large peptides derived from specific cleavages at infrequent amino-acid residues. Trout testis histone H1 has a molecular weight of 19314, is only slighly microheterogeneous, and possesses pentapeptide sequences related to Ala-Ala-Ala-Lys-Lys repeated six times in the complete sequence. Although the N-terminus of histone H1 is known to be blocked, some 10% of intact trout testis H1 contains a free N-terminal alanine residue. Three seryl residues in the C-terminal half (97-194) of the molecule occur in the sequence Lys-Ser-Pro-Lys known to be phosphorylated in trout testis H1. The sequence has been compared to the known partial sequence of rabbit thymus H1. The results are consistent with a role for histone H1 in the maintenance of the higher-order structure of chromatin.


Glycolipids of the human gastric content. Structure of the sulfated glyceroglucolipid. A new sulfated glycolipid has been isolated from the lipid extract of human gastric content by the procedure involving column fractionation on silicic acid and thin-layer chromatography. Degradation studies revealed the presence of glucose, sulfate, fatty acids and glyceryl monoethers. The structure of this glycolipid was identified by partial acid hydrolysis, oxidation with periodate and chromium trioxide, and permethylation studies, as: SO3H-6Glcalphal leads to 6Glcalphal leads to 6Glcalphal leads to 3-diglyceride. The diglyceride portion of this glycolipid consists mostly of 1-O-alkyl-2-O-acyl-glycerol.


The incorporation of [14C]glucosamine into dolichol diphosphate N-acetyl[14C] glucosamine by unbroken liver cells in culture. Incubation of whole Chang liver cells with D-[1-14C]glucosamine results in incorporation of radioactivity into both proteins and lipids. A minor (approximately 3%) amount of the labelled lipid has the chromatographic, solubility and chemical properties of dolichol diphosphate N-acetylglucosamine. A similar compound is formed when membrane preparations of the cells are incubated with UDP-N-acetyl[14C]glucosamine. The same membrane fractions catalyse the transfer of [14C]-mannose from GDP-[14C]mannose to dolichol phosphate.


Evidence for an adenylate-cyclase activity in neurosecretory granule membranes from bovine neurohypophysis. Purified bovine neurosecretory granules and their corresponding membranes were prepared after fractionation and purification processes from bovine pituitaries. An adenylate cyclase activity was detected both in the granules (apparent Km = 0.5 mM) and the corresponding preparations of the membranes (apparent Km = 0.5 mM). This enzyme was activated by fluoride in a way markedly dependent on the concentration of this ion, and with a maximum for a concentration of F- = 3.5 mM. The cyclase activity was also significantly enhanced by GTP. The reaction rate showed a strong dependence on the molar ration [Mg2+]/[ATP] with maximal velocity for 7. It is suggested that this activity might play an important role in the control and regulation of neurosecretion in the neurohypophysis.


Proton-magnetic-resonance study of copper(I) complexes with peptides containing sulfhydryl and imidazole groups as possible model ligands for copper proteins. The copper(I) complexes of peptides containing sulfhydryl and imidazole groups have been investigated in aqueous solution by proton magnetic resonance (1H NMR). The N-mercaptoacetyl-L-histidine coordinates through the sulfhydryl sulfur and imidazole nitrogen atoms to form the unique 1:1 Cu(I) complex species containing bridged imidazole. The sulfhydryl and imidazole groups are adequate ligands for not only Cu(II) but also Cu(I). The 1H NMR spectra show that the peptide nitrogen group is not involved in complex formation of Cu(I) with N-mercaptoacetyl-L-histidine and 3-mercaptopropionyl-L-histidine. The results have been discussed with respect to the protein ligands for 'blue' copper centers.


A new purification procedure for fumarase based of affinity chromatography. Isolation and characterization of pig-liver fumarase. A new procedure has been developed for the isolation of fumarase (EC 4.2.1.2). It is described for the purification of pigheart and liver enzyme. Pyromellitic acid has been covalently coupled to Sepharose-4B with diaminopropanol as spacer arr. When a dialysed 0.55 saturated ammonium sulphate precipitate is applied to the column, in Tris-acetate buffer, pH 7.3, fumarase remains quantitatively bound. It is eluted by competition, together with a few other proteins, by the natural product L-malate. Malate is removed from the eluate by dialysis. After this highly efficient purification step the enzyme is very easily crystallized. The final yield by 67% for both pig heart and liver preparations. The specific activity of fumarase purified from both tissues is found to be the same. Polyacrylamide gel electrophoresis in dodecylsulphate shows one single band corresponding with a subunit molecular weightof 48500. A single band is also obtained by electrophoresis in acid urea. This new procedure based on biospecific affinity chromatography allows a fast and easy preparation of gram quantities of fumarase.


Binding of 4-methylumbelliferyl alpha-D-mannopyranoside to tetrameric concanavalin A Fluorescence temperature-jump relaxation study. The kinetics of saccharide binding to the treatment form of concanavalin A have been studies at pH 7.2 with the temperature-jump method. 4-Methylumbelliferyl alpha-D-mannopyranoside was used as a ligand; its fluorescence is totally quenched upon binding. A single relaxation of ligand fluorescence (tau = 20-400 ms) was observed and was investigated at three different temperatures, using kinetic titration and dilution types of experiments. The concentration dependence of the relaxation time and amplitude was consistent with a single-step bimolecular association and independent binding sites. In the temperature range 13-24 degrees C the association and dissociation rate parameters are in the range (6-10) X 10(4) M-1 s-1 and (1.4-3.2)s-1 respectively, corresponding to activation energies for the forward and reverse reactions equal to approx. 13 and 8 kcal/mol (54 and 33 kJ/mol) respectively. Two additional relaxations of protein fluorescence (3 ms and larger than 1 s at 25 degrees C) were unaffected by carbohydrate binding. Tetrameric concanavalin A shows carbohydrate binding parameters that are almost identical to those of native or derivatized dimeric concanavalin A.


Structural studies on the four repetitive Fc-binding regions in protein A from Staphylococcus aureus. The convalent structures of the four highly homologous Fc-binding regions in protein A, regions D, A, B, and C, have been studied by enzymic fragmentations of previously isolated fragments originating from these regions and subsequent isolation of the generated peptides by ion-exchange chromatography, molecular-sieve chromatography, high-voltage paper electrophoresis and paper chromatography. The complete seqeunce of region B was elucidated by combining the results of Edman degradations on isolated fragment B peptides with the previously reported N-terminal seqeunce of the same fragment. Furthermore, Edman degradations of fragments D, A and C peptides differing from the region B sequence provided the structures of subregions not identical to corresponding subregions within region B. Thus, it is possible to propose a highly probably covalent structure for the N-terminal 27000-molecular-weight portion of protein A responsible for the IgG-Fc-binding activities. However, it was not possible to assign the activities to specific structures within the regions. The sequence data indicate that not only mutual homology between the four regions exists, but also internal homologies within the regions. Furthermore, the data strongly supports the hypothesis of a stepwise gene fusion procedure being involved in the evolution of the protein.


Interaction of non-histone chromosomal proteins HMG1 and HMG2 with DNA. Interaction between non-histone protein HMG1 or HMG2 and DNA has been studied by using thermal denaturation and circular dichroism (CD) spectroscopy. We have made the following observations. 1. The binding of each of these two proteins to DNA stabilizes the latter, as shown by an increase in melting temperature of 20 degrees C (from 45 degrees C to about 65 degrees C). 2. There are 6.0 amino acids/nucleotide in HMG1-bound DNA and 5.0 in HMGI-bound DNA which suggests that each HMB1 moleculae would cover about 20 base pairs of DNA and each HMG2 molecule would cover about 25 base pairs. 3. The alpha-helical content of these two non-histone proteins in the complexes, estimated from the CD value at 220 nm, is about one third to one half that of total proteins in calf thymus chromatin. 4. DNA conformation is distorted only slightly by the binding of protein HMG1 or HMG2. 5. Neither the melting nor the CD properties of HMG1-DNA or HMG2-DNA complexes differ substantially whether they are prepared by NaCl-gradient dialysis in urea or by direct mixing of protein and DNA at 0.15 M NaCl, followed by dialysis against the same buffer i.e. 0.25 mM EDTA (pH 8.0).


Transcriptional units for ribosomal proteins in yeast. The effects of ultraviolet irradiation on the rates of synthesis of individual ribosomal proteins in yeast were examined and compared with the ultraviolet sensitivities of the synthesis of other yeast proteins. It was found that the synthesis of yeast ribosomal proteins is much more sensitive to ultraviolet irradiation than that of other yeast cellular proteins. Taking into account the half-life of yeast mRNA, the results obtained indicate that the genes coding for ribosomal proteins form part of long transcriptional units, which are much longer than the DNA stretch needed to code for a ribosomal protein of average molecular weight. Saturation hybridization of total poly(A)-containing mRNA with yeast nuclear DNA revealed that as much as 30% of DNA is complementary to yeast mRNA. Thus, the primary transcript of a protein gene on the average is about 1.7 times the length of the actual messenger. On the basis of the various experimental data we suggest a clustering of the yeast ribosomal protein genes in a number of common transcriptional units.


Synthesis of lens protein in vitro: formation of beta-crystallin. Upon addition of lens polyribosomes to a reticulocyte-cell-free system, alpha, beta L-, and gamma crystallin are synthesized, while beta H crystallin is not formed. This phenomenon is comparable to the biosynthetic events in the lens-cell-free system and in tissue culture. It is shown that beta H crystallin formation depends upon the presence of a polypeptide beta B1 b which arises by posttranslational modification. The putative precursor for beta B1 b is a polypeptide beta BU a of which the messenger with a sedimentation coefficient of 12.5 S has been isolated.


The effects of histidine starvation on the methylation of ribosomal RNA. The effect of amino acid starvation on the control of ribosome biosynthesis at the post-transcriptional level has been studied in Ehrlich ascites cells. A comparison of the turnover rates of ribosomal precursor RNA (pre-rRNA) and the degree of methylation of ribosomal RNA after histidine deprivation revealed that the slow down of ribosome formation is accompanied by a significant inhibition of rRNA methylation. Analysis of nucleolar and cytoplasmic RNA double-labelled with L-[Me-3H]methionine and [14C]uridine, as well as a quantitative determination of alkali-stable dinucleotides on DEAE-Sephadex, showed that methylation of rRNA species was inhibited by about 50% under shift-down conditions. This decrease in RNA methylation does not reflect an inhibition of rRNA methylases caused by amino acid starvation but is rather brought about by a shrinkage in the pool size of S-adenosylmethionine, the donor of methyl groups. It is suggested that amino acid starvation might exert its blocking effect on proper ribosome maturation by affecting the methylation of 45-S RNA.


Polypeptide chains of 19-S thyroglobulin from several mammalian species and of porcine 27-S iodoprotein. Undegraded 19-S thyroglobulin was purified from hog, ox, man, dog, sheep and rat thyroid glands. Sodium dodecylsulfate/ polyacrylamide gel electrophoresis of the reduced proteins showed that all are formed of peptide chains of molecular weight about 330000. Carboxypeptidase A digestion of porcine 19-S thyroglobulin released consecutively two moles of leucine and then two moles of serine, thus offering strong evidence in favour of the idea that the protein is formed of two identical chains. The same C-terminal amino acids were detected in sheep, ox, dog and man thyroglobulins. No N-terminal amino acid was found by appropriate chemical and enzymatic techniques. Porcine 27-S iodoprotein was shown by carboxypeptidase A analysis to be formed of four single-stranded 330000-Mr subunits identical to those constituting the 19-S protein. Identity, both qualitatively and quantitatively, of the peptides obtained by CNBr cleavage of the two proteins as shown by sodium dodecylsulfate/polyacrylamide gel electrophoresis has confirmed this conclusion. Since 19-S and 27-S thyroid iodoproteins are formed of two and four probably identical chains, they must be termed 19-S and 27-S thyroglobulins or alternatively thyroglobulin dimer and tetramer, respectively.


Inhibition of papain by N-acyl-aminoacetaldehydes and N-acyl-aminopropanones. Evidence for hemithioacetal formation by a cross-saturation technique in nuclear-magnetic resonance spectroscopy. N-Acyl-aminoacetaldehydes are potent inhibitors of the proteolytic enzyme, papain. Although they exist predominantly in their hydrated form in aqueous solution only the aldehyde is an effective inhibitor. The binding constants for related amides and methyl ketones confirm that it is principally the lower steric requirement of the aldehyde rather than its increased electrophilicity which is responsible for its powerful inhibitor properties. Using nuclear magnetic resonance spectroscopy, evidence is provided for an N-acetyl-aminoacetaldehyde-papain complex. Using a cross-saturation technique evidence is also provided for a hemithioacetal, formed from the aldehyde and the active-site thiol group. Hemithioacetal formation has also been detected between N-benzoyl-aminoacetaldehyde and papain. This provides the first direct evidence for a tetrahedral adduct with papain and supports the proposed involvement of such intermediates in papain-catalysed hydrolyses.


Quantitative determination of glycosphingolipids illustrated by using erythrocyte membranes of various mammalian species. A procedure for the quantative determination of glycosphingolipids is described, involving extraction of total lipids, fractionation on a column, acid cleavage and photometry of a complex formed between sphingosine and methyl orange. The level of glycosphingolipid sphigosine of erythrocyte membranes of a variety of mammals ranges from 59.1 (rat) to 410.1 (pig) nmol/ml packed cells.


Dependence of tRNA structure in solution upon ionic condition of the solvent. Fluorescence studies of monovalent cation binding to tRNAPhe from barley embryos. Dependence of barley phenylalanine tRNA (tRNAPhe) fluorescence intensity at 430 nm upon LiCl, NaCl, KCl, CsCl or NH4Cl concentration was measured in 0.01 M Tris-HCl, pH 7.5, 0.001 M Na2EDTA solutions. Increase of monovalent cation concentration in the solvent from 0 to 2 M induced about 3-fold fluorescence intensity enhancement. The fractional fluorescence change was used as a measure of bound ligand concentration. Fluorescence Scatchard plots revealed three classes of monovalent cation binding sites on the tRNA molecule: interacting (strong) and independent (weak and very weak) sites. Calculated from Scatchard plots binding constants (K), for strong and weak binding of monovalent cations (in the case of Na+ binding: Ks = 26 M-1 and Kw = 4.3 M-1 respectively) exhibit linear dependence upon ionic radius (r). Two limiting values obtained from the plot of K versus r: K(max) at r = 0 r(max) at K = 0, characterize additionally strong and weak monovalent cation binding sites (Ks(max) = 42 M-1 Kw(max) = 8.5 M-1, rs(max) = 0.23 nm and rw(max) = 0.22 nm). A model of the relationship between weak Mg2+ binding sites and monovalent cation binding sites as well as of monovalent cations binding to tRNA is proposed.


Frequency and pattern of radionuclide administration to medical patients in a general hospital. As part of a drug surveillance programme details of nuclide administration were recorded for 5288 consecutive patients admitted to the medical wards of a large general hospital. Overall use of nuclides amongst this group was found to be low, and multiple exposure to radiation as a result of nuclide administration is not a major hazard when compared to the diagnostic information provided.


Effect of aluminium impurities in the generator-produced pertechnetate-99m ion on thyroid scintigrams. Cases of reduced uptake of pertechnetate-99m ion in the thyroid gland due to the presence, in the injected solution, of aluminum species at concentrations higher than 4 microgram/cm3 are reported. This inconvenience can be avoided either by injecting chromatographically pure pertechnetate-99m ion or by allowing the eluate of high aluminium content to stand for about 4 h.


Lasting disappearance of autonomously functioning thyroid nodule (AFTN) following the TSH stimulation test. Two AFTNs in one thyroid lobe were detected in a eumetabolic woman, with complete suppression of uptake in the paranodular tissue. After TSH stimulation, performed 2 months later, uptake was found in paranodular tissue only, both nodules being cold on the 131I scan. The same distribution of 131I was found on the next scan after a further 2 months without stimulation. Cystic degeneration was found by sonography and confirmed by aspiration biopsy. The destruction of one of the AFTNs was incomplete, as witnessed by a reappearance of function after 16 months. No differences in the thyroid handling of pertechnetate and iodide were detected. It is believed that the TSH stimulation might have hastened the otherwise spontaneous degenerative changes in the AFTNs.


A new fast mathematical technique for resolution enhancement applied to simulated scans of the thyroid phantom. The authors present a new mathematical technique for resolution enhancement. It has been applied to scans of the international thyroid phantom simulated by computer, in standard measurement conditions. The effect of random fluctuations and the choice of the optimal image are investigated. The results obtained are satisfactory and superior to those of smoothings.


Positive 131cesium scanning in parathyroid adenoma. In a case of primary hyperparathyroidism, a palpable nodule, at the base of the right lobe of the thyroid, proved 'cool' during 99mTc scanning, but 'hot' when scanned with radiocesium. The uptake of this tracer was higher than the uptake of 75Seselenomethionine after suppression with T3. The authors discuss the possibility of cases of 'false-positive' radiocesium uptake in extrathyroid nodules, and in particular, the use of this tracer for the detection of parathyroid adenoma by scanning.


Investigations into the use of 77Br labelled 5alpha-dihydrotestosterone for scanning the prostate. The potential use of a potent androgen labelled with a gamma emitting radionuclide for scanning the prostate was investigated. 2alphabromo 5alpha-dihydrotestosterone was synthesized and subsequently labelled with 77Br. The distribution of this compound was studied in rat and human tissues. The maximum concentration of radioactivity in the rat prostate at 1-4 h following the injection was found to be between 0.5-0.8% of the injected dose per gram of the tissue. In the human however, that value was 0.002-0.003%. Considering the overall results it was concluded that this compound is not appropriate for scanning the prostate.


A scintigraphic method of examining the patency of oviducts using 133Xe. Described below is the radioisotope method of examining the patency of oviducts using a solution of 133Xe. Scintigraphic pictures of the uterine cavity and oviducts were obtained with a Jumbo Toshiba gamma-camera; they were subsequently analysed by an Informatek SIMIS-3 data processing system. A total of 30 women aged between 20 and 36 with primary or secondary infertility were examined. The patency of oviducts and the shape of the uterine cavity was assessed on the basis of: the overall picture of the activity of 133Xe in the uterine cavity and oviducts, the isocontours of the overall picture, curves of increasing and decreasing activity in the fallopian tubes, and the spatial picture of activity distribution in the uterus and fallopian tubes. The results of the examinations corresponded in all cases with the diagnosis made on the basis of hysterosalpingography. An advantage of the isotope method of examining the patency of fallopian tubes and the shape of the uterine cavity is the fact that it is an examination of a dynamic nature, completely safe for the patient and exposes the patients to a considerably lower dose of irradiation than during hysterosalpingography.


The radiospirometric flow-volume diagram recording technique and comparative study with conventional spirometry. The spirometric flow-volume diagram recorded for a forced expiration gives information which is used in assessing obstructive or restrictive pulmonary diseases. Regional data of the same kind can be achieved using a simple radiospirometric technique and scintillation camera. A series of images during inspiration and expiration are defined and a time-activity curve with an integration time constant of about 100-200 ms is obtained from the images during the forced expiration phase. The equivalent of the flow-volume diagram, i.e., the time derivative of the activity vs. activity is computed. There were 21 subjects studied in this series. Normal subjects or patients with various diseases underwent classical spirometry, so that the global radioactive diagram could then be compared to the spirometric flow-volume diagram and its parameters expressed in terms of volumes and flow: vital capacity, peak flow, mean flow, flow at mean volume. The correlation with classical spirometry is highly significant. Similarly regional data are consistent with the pulmonary results.


Measurement of separate kidney clearance by means of 99mTc-DTPA complex and a scintillation camera. A new radioisotopic method of determining the separate glomerular clearance of the kidneys is described. After injection of 99mTc-DTPA, the data from a scintillation camera are recorded by computer. The renal curves are corrected for extrarenal activity and the plasma curve is obtained from a precordial curve. At each instant the slope of the renal curve divided by the corresponding plasma concentration gives the separate clearance value, in the period extending from 80 to 180 s after injection of the tracer. The error and correction factors introduced are discussed. Normal values are established on 25 patients and correspond to inulin clearance values. Left kidney: 60 ml/min (SD=13). Right kidney: 57 ml/min (SD=12). The method is simple for the patient, takes only 20 min, is not dangerous, is particularly applicable to young children and can be repeated frequently in the same patient.


The influence of circadian variations in plasma iron on the measure of plasma iron turnover. In 92 cases studied in vivo with 59Fe, the variations of plasma iron during the study were measured. Errors in calculation of plasma iron turnover of up to 25% can be made in normosideremic patients if such variations are not taken into account. In hypersideremic patients the variations of plasma iron are low or nil; in hyposideremic patients the slow variations of plasma iron concentration do not alter the rapid slope of radio-iron removal.


Direct radioimmunoassay of estradiol in serum extracts. The feasibility of direct radioimmunoassay of unconjugated estradiol in dried serum extracts in the assessment of ovarian function in the regulation of the menstrual cycle has been investigated. Using an antiserum to an estradiol-6-conjugate, assay reliability was evaluated and the procedure standardized through a series of tests aimed at assessing accuracy, sensitivity, and precision. These included multiple titration with competing steroids, the definition of blank effects from solvent and sample, the assay both of samples to which known amounts of estradiol had been added and of serially diluted samples, and clinical validation using as a reference samples related to well-defined physiological situations. The variability of replicate estimates and the repeatability of the calibration curve were evaluated to obtain information on assay precision and sensitivity. The analytical performances proved to be perfectly adequate for the clinical purposes for which the assay was intended, in terms both of reliability of results and of methodologic practicability.


Evaluation of cold areas on the thyroid scan with 99mTc solcocitran. Cold areas on a 99mTc pertechnetate thyroid scan were reevaluated using 99mTc Solcocitran in 31 patients. In 27 patients surgical specimens were obtained for histologic studies. Of 20 benign lesions, five showed a relatively increased uptake of 99mTc Solcocitran. Two of seven malignant lesions were interpreted as positive on the 99mTc Solcocitran scan. This study indicates that 99mTc Solcocitran is not a valuable radiopharmaceutical for differentiating cold areas.


New chromosomal dysmorphic syndromes. 2. Trisomy 10p. This is the report of a family in which a balanced translocation in the mother t(5;10)(p15;p13) led to an unbalanced chromosomal constitution in two children. It was identified by G-banding analysis as trisomy of the distal portion of the short arm of chromosome 10 (p13 leads to pter). Comparison with 15 previous reports of trisomy 10p confirms the existence of a characteristic dysmorphic syndrome.


Prognosis of Wilson's disease in childhood. Wilson's disease in childhood has several characters distinct from those in adults. The progression of the disease tends to be rapid, hepatic manifestations are common, cerebral symptoms related to dystonia are predominant, and tremor is rare. Forty-nine children with Wilson's disease under the age of 15 were treated with D-penicillamine for 2 to 15 years. None of the presymptomatic patients subsequently developed any symptoms of the disease. The results of treatment in patients who had exhibited only hepatic symptoms were also excellent. However, neurological manifestations associated with a history of jaundice or ascites responded less well to chelation. These observations clearly indicate that early diagnosis and treatment are extremely important to ensure normal lives for children with Wilson's disease.


"Fast isoamylases" in the parotid saliva of children with cystic fibrosis and heterozygous carriers. On electrophoresis, parotid saliva always exhibits a basic pattern of 6 isoamylases. Additional faster migrating isoamylases occur in varying numbers. These "fast isoamylases" are generated, at least in part, by deamidation. Compared with juvenile and adult controls, a significantly greater number of "fast isoamylases" was found in the parotid saliva of children with cystic fibrosis and their healthy heterozygous parents. A shift in the equilibrium between amidation and deamidation is discussed in terms of its possible connection with the metabolic defect responsible for cystic fibrosis.


Opsoclonus and palatal myoclonus during prolonged post-traumatic coma. A clinico-pathologic study. A case of opsoclonus and palatal myoclonus following blunt head injury is described. The syndrome appeared 1 month after the injury and lasted unchanged until death. Postmortem examination showed the presence of widespread lesions of the brain stem affecting the dentato-rubro-olivary system. The main clinical features of the syndrome and their anatomical correlates are discussed.


Vascularization and angioarchitecture of the human pes hippocampi. After studying the vascularization and the angioarchitecture of the pes hippocampi by means of selective arteriograms, the authors suggest a number of modifications to the classical concepts of arteriolar penetration into this area. Their most striking finding was the typical stratification of the paraventricular area as compared with the gyrus dentatus which is more monomorphically vascularized. The stratum granulosum appeared not to represent a vascular barrier between these two zones. The authors emphasize the remarkable correlation between the fibrillar and cytological construction of the various layers on one hand and their angioarchitectural characteristics on the other.


Critical assessment of the local curare test in myasthenia gravis. In a group of 60 patients of which 30 were affected by myasthenia, we used the regional curare test. The results were evaluated from a critical point of view and were then compared with the results obtained by the repetitive stimulation of the circumflex nerve, deriving from deltoid muscle. We considered too the specificity of the regional curare test for the evaluation of ocular myasthenia.


Neurological features as presenting manifestations of brucellosis. Four cases of brucellosis in whom acute neurological conditions were the first manifestations of the disease are presented. These cases are acute meningitis, acute encephalitis with generalized and focal signs, acute transverse myelitis with paraplegia, and acute radiculitis with "sciatica". The neurological manifestations, the laboratory findings, the treatment and certain features related to problems of diagnosis and differential diagnosis have been briefly discussed.


Myotubular (centronuclear) (neuro-)myopathy. I. Clinical, genetical and morphological studies. Five new cases of myotubular (centronuclear) (neuro-)myopathy are presented. Myometric studies revealed type I fibre atrophy and mispositioned nuclei, at various stages between the myotubular structure and the normal subsarcolemmic position. Certain morphological changes, for instance target structures, suggest denervation involving the fibres in an early stage of myogenesis; differentiation seems to be more affected than growth. The genetic defect has an autosomal recessive mode of inheritance with penetrance and degree of expressivity varying from one case to another in the three families.


Effect of salbumatol on acute gastric ulceration induced by indomethacin in the rat. Indomethacin produces gastric ulceration in the rat when given by subcutaneous injection. Salbutamol, a beta2-adrenergic agonist, provided full protection from the development of these lesions. This observation may have a bearing on the genesis and therapy of some forms of peptic ulceration.


Effect of dopamine in stress ulcer of rats. The effect of dopamine in stress-induced ulceration of stomach mucosa employing a hypoxia-immobilisation stress, was investigated in rats. Intravenous administration of small doses of dopamine (3 mug/kg body weight/min) significantly lowered the development of mucosa erosions. A bilious reflux which was observed after dopamine infusion but not in controls may be considered as a side effect of this agent.


Microsomal hexobarbital metabolizing enzymes in regenerating cholestatic rat liver. Microsomal changes were studied in regenerating liver cholestatic rats by measuring hexobarbital metabolzing capacity (HMC) in vitro. Total extrahepatic biliary obstruction was induced by ligating the common duct, 3 days later, a 70% liver resection was performed. Sham-operated animals served as controls. Analysis of HMC showed a similar pattern of microsomal regeneration in cholestatic as in sham-operated rats. This indicates that in the rat, cholestasis per se does not interfere with the development of this enzyme system during regeneration.


Therapeutic embolization of renal cell carcinoma. The technique of embolization of renal cell carcinoma is assessed on the basis of the authors' experience. The procedure is usually envisaged in case of hypervascularized extracapsular tumors, with the purpose of obtaining the preoperative occlusion of the renal artery. Nevertheless, it cannot replace surgery, which can accomplish it with much more safety. The technique of embolization itself, which should be as selective as possible, is also discussed and its clinicobiological (immunological) implications are introduced.


Urodynamic assessment of women with urethral syndrome. 43 women with urethral syndrome were investigated. A full urologic, gynecologic and urodynamic assessment was carried out. In 27 women an obstruction was demonstrated by urodynamic and other parameters. Two types of obstruction were seen: the first one occurred mainly in postmenopausal women. Here, a narrow distal segment of the urethra was noted. These women responded well to dilatation and external urethroplasty. The second type of obstruction was mainly seen in younger women. The cause was an incomplete relaxation or spasm of the external striated sphincter. This dysfunction was caused by various disorders like local inflammation, colpitis, etc. Dilatation and urethroplasty did not cure all patients of this group. Other causes of symptoms were instability and atony of the detrusor. In some women the cause for their symptoms and recurrent urinary infection could not be found.


Cystometric and urine flow studies on patients with calcified bladders and ureters. The urodynamic effects of calcification of the bladders and ureters secondary to schistosomiasis, have been studied in eight patients. Bladder calcification in this disease involves mainly the mucosa and submucosa. Calcification per se does not interfere with detrusor function. Ureteral calcification involves mainly the muscle layer and periureteral tissues leading to stasis of urine along such ureters. The layers involved may explain the disparity in the incidence of bilharzial related tumours in the bladders and ureters. The higher incidence of urinary calculi in patients with bilharziasis is probably due to stasis along involved ureters.


Renal function after ligation of the left renal vein. In animal experiments the ligation of the left renal vein after nephrectomy on the right side and the ligation of the suprarenal inferior vena cava is explored by four different methods. Degree and length of postoperative renal dysfunction depend on the preliminary ligation or the narrowing of the suprarenal inferior vena cava. The period of adaptation is correlated to the development of a collateral circulation of the left renal vein.


Urinary hydroxyproline concentration in primary hyperparathyroidism with and without renal stones. Eleven cases with histologically confirmed primary hyperparathyroidism have been studied. Although histologically, bone turnover increased in all but 1 patient, urinary hydroxyproline excretion and serum alkaline phosphatase in patients with renal stones were within the upper normal limits of slightly elevated (27.5 mg/24 h, concentration 19.5 microgram/ml, alkaline phosphatase 35.0 IU/l). On the contrary, 3 cases without renal stones exhibited an increased urinary hydroxyproline excretion (129 mg/24 h, concentration 95.6 microgram/ml) and elevated serum alkaline phosphatase (99.9IU/l). Serum total hydroxyproline was elevated in both groups (renal stones, 2.00 mg%; no renal stones, 3.16 mg%; p = 0.006). Hydroxyproline was determined under conditions of a very low proline diet and 1.5 liters of daily fluid intake. There were no statistically significant differences between serum calcium, phosphorus, and parathormone between urinary excretion of calcium and phosphorus. Creatinine clearance was within normal limits in all patients. The possible relevance of urinary hydroxyproline for stone formation is discussed.


Clinical and laboratory assessment of the efficacy of baclofen (Lioresal) on urethral sphincter spasticity in patients with traumatic paraplegia. A comparative clinical trial with oral and intravenous baclofen (Lioresal) was performed in a homogeneous group of 70 male patients, hospitalized with traumatic paraplegia. The dosage was 75 mg daily by mouth over a period of 10 days or 20 mg daily i.v. for 2 days. Drug efficacy was evaluated both clinically (residual urine; facilitation of micturition) and urodynamically (integrated cystosphincterometry, sphincter electromyography and micturition cysto-urethrograms). During oral therapy there were no significant changes in any of the studied parameters. Intravenous administration, on the contrary, proved highly effective and better tolerated.


A case of lithiasis of a persistent urachus. A rarely encountered case of lithiasis in a persistent urachus with asymptomatic course, in a patient with recurrent nephrolithiasis, is presented. Diagnosis was established by roentgenographic examination and was surgically confirmed.


Continent caecal bladder.

Continent caecal bladder. A new method of urinary diversion using the terminal ileum and the caecum as a reservoir, and an invaginated and sutured ileal segment interposed as a lid for the caecal portion has been experimented in 5 patients. Four of them are now completely continent and use a continence-enxuring device at regular intervals.


The treatment of advanced carcinoma of the bladder with a combination of adriamycin and 5-fluorouracil. 52 patients with advanced bladder cancer, no longer controlled by conventional therapy, have been treated by combination chemotherapy with Adriamycin and 5-fluorouracil. The objective remission rate has been 40%. The morbidity of the chemotherapy has not been excessive. The response has not been related to the histological grade of the primary tumour and previous treatment. Patients with a good performance status (Karnofsky index) have responded better than those with a poor performance status.


Treatment of renal adenocarcinoma by embolization: a follow-up of 38 cases. The experience from 38 patients treated with embolization are presented. The technique and results are discussed. Other techniques intended to cause embolization as well as further possibilities within this field are discussed.


Relationship between germinal cells function and dynamics of FSH secretion. Tubular histology was correlated to FSH levels assayed under basal conditions (8 cases) or in response to Gn-RH (24 cases) in 32 infertile males, in whom a testicular biopsy was indicated as part of the work-up. A good correlation was found between number of spermatogonia and primary spermatocytes and levels of FSH, under basal conditions or, even more, in response to Gn-RH; correlation was less close with respect to spermatids 1 and 2 and nonexistent with respect to Serotoli cells. In spite of those findings, when taking into account only mean counts of spermatogonia and primary spermatocytes, some overlapping of values in individual cases still existed. On the other hand, when correcting the above perameters for tubular diameter and number of tubules per LPF, a much closer correlation between parameters of tubular function and dynamics of FSH regulation was obtained; the overlapping of values was found only in 1 out of 32 cases.


The value of lymphography for the TNM classification of renal carcinoma. Preoperative lymphography is a basic condition for uniform tumor classification of renal carcinoma, according to the T, N and M categories. The comparison of 148 lymphographic findings with 170 intraoperative and histopathological lymph node results showed a satisfactory correlation. The total frequency of lymph node metastasis was of 21.6%. Carcinomas with positive lymph nodes showed a significant increase of far distant metastasis up to 50%. Lymph node metastases have to be considered in 10% of all carcinomas of the T1 and T2 categories and in 15.5% of the cases with unclear preoperative lymphographic diagnosis. These results point out the necessity of a radical lymphadenectomy in all T categories.


Diagnostic value of computerised isotopic section renal scanning. Isotope section renal scanning in the diagnosis of kidney disease has been compared with ultrasonic examination adn specialised radiological techniques. The computerised isotope tomographic section technique developed in Aberdeen has increased the accuracy and differential diagnosis of renal lesions especially cysts and tumours.


Combined mesterolon-clomiphene citrate therapy for treatment of oligospermia. 42 subfertile patients with normal levels of plasma testerone (26 subnormal, suffering from oligospermia) have been treated with a combination of clomiphene citrate (50 mg Clomid daily) and mesterolon (50 mg Proviron daily) over a period of at least 3-6 months. The treatment resulted in pregnancy in 6 cases and in a significant improvement of the sperm count in 16. In 7, however, whilst the sperm count improved the qualitative results were unsatisfactory as many sperms were immature. Restricted spermatogenesis and a sperm count below 5 million/ml must be considered unfavourable but does not constitute a counter-indication to the combined therapy. No hazardous complications were observed.


Sexual behaviour after prostatectomy.

Sexual behaviour after prostatectomy. Sexual behaviour after prostatectomy has been observed in 100 patients who have undergone a Millin prostatectomy with preventive haemostasis. The results have been compared with 100 patients subjected to other urological operations and 100 patients who have undergone general surgical operations. From the data obtained we conclude that: (1) one third of the patients who have undergone prostatectomy no longer have sexual activity; (2) prostatectomy does not affect sexual potency more than any other operation of the same gravity at the same age; (3) among the patients sexually active 6 months before prostatectomy, 45% have a better sexual life 6 months afterwards, 26% have a diminished sexual life and 3.5% have become impotent; (4) the development of an adenoma seems to have an unfavourable influence on sexual activity.


Erictile impotence, small-carrion prosthesis and the 'infrapubic' approach. Today erectile impotence is surgically best treated with the implantation of a Small-Carrion prosthesis through the infrapubic approach. A psychoanalysis or -therapy should always accompany the surgical approach.


Persistence of complementary afterimages as a function of adult age and exposure duration. The persistence of complementary afterimages was studied in 36 young (X age 18.8 years) and old (X age 62.1 years) male and female subjects. Afterimage persistence was found to be a direct function of exposure duration and to be greater for the older subjects as compared with the younger ones. The interactions between age and duration and between presentation order and duration were also significant. The data extend support for the "stimulus persistence" model to age differences in retinal function.


Differences in unconspicuous word identification as a function of age and reversible-figure training. Inconspicuous word identification was studied in 48 young (X age 19.3 years), middle-aged (X age 44.5 years) and old (X age 69.5 years) male and female subjects. Although this task appeared to be an easy one for the young subjects, it was strikingly difficult for the middle-aged and elderly subjects. Reversible-figure training apparently led to a small but significant overall improvement in inconspicuous word identification but did not at all diminish the age differences in such performance. The interactions of sex by reversible-figure training and age by first set-second set of words were also significant. Further research will be needed to fully examine the remediability of age-related perceptual skill deficits.


Simultaneous brightness contrast in young and old adults. The illusion of simultaneous brightness contrast was used to investigate age changes in contrast sensitivity under suprathreshold conditions. Contrary to findings for threshold measures of visual functioning in older adults, the 20 older adults (aged 60-79 yrs.) showed a significantly larger simultaneous brightness contrast effect (p less than .05) than the 20 younger adults (aged 17-26 yrs.). The increase in simultaneous brightness contrast in older adults is attributed to a degeneration of damping fibers in the visual system.


Behavioral-immunologic relationships in older men and women. Serum immunoglobulin levels (IgG, IgA and IgM) and intellectual performance were examined in a group of fourteen elderly men (mean age 74.2) and twenty-three women (mean age 73.2) who reported that they were in good health. Significant negative Pearson product-moment correlations between performance and IgG and IgA emerged for men. Among women the relationship was not significant.


Long-term results following closure of isolated ostium secundum atrial septal defect in children and adults. Information is presented on 166 patients operated  for isolated atrial septal defect of secundum type with a mean follow-up time of 12 yr (range 8-21 yr). The mean age at operation was 23 yr (range 4-63 yr). The incidence of suspected mitral regurgitation is very low (4 cases). Postoperative flutter or fibrillation occurred in 24 cases, 20 out of these were operated after the age of 20 yr. In all 24 cases intermittent or permanent atrial dysrhythmia was present immediately postoperatively. The long-term results with regard to the occurrence of dysrhythmias and increased heart volumes is better in the younger age group.


The electrophysiological evaluation of intravenous acebutolol, a beta-blocking drug. The electrophysiological effects of acebutolol were studied in 12 patients. Heart rate and systemic arterial pressure were monitored. Plasma acebutolol levels were estimated. The first 6 patients (group A) received 0.3 mg/kg body weight I.V. The subsequent 6 patients (group B) received 0.5 mg/kg body weight I.V. Acebutolol delayed both antegrade and retrograde conduction through the AV node. The effect was greater in group B patients. Effective and functional refractory periods of the AV node were also increased after acebutolol. Intraatrial and intraventricular conduction and the effective refractory periods of the atrium and ventricle were not affected. Acebutolol did not alter significantly the sinus node recovery time or the QTc interval. Heart rate fell, especially where initial rates were fast. Systolic arterial pressure was lowered in group B patients. Peak mean levels of acebutolol were reached 5 min after injection of the drug. In the doses used, acebutolol, although well tolerated, failed to demonstrate electrophysiological evidence of a membrane-stabilizing effect and is therefore unlikely to add to the areas of success achieved by other beta-blocking drugs in the management of arrhythmias.


Evaluation of pressure-derived indices of right ventricular contractility. Myocardial function was studied in 23 subjects using indices of contractility based on the right ventricular pressure pulse. Pressure-velocity curves were plotted during early systole and contractile element velocity was derived. The pressure-velocity curves varied in shape and curves with single, linear descending slopes occurred in only 7 subjects. The other pressure-velocity curves were either biphasic or hyperbolic in form. The derivation of Vmax and Vpm and beat-to-beat analysis of these indices was therefore difficult. The effects of a number of physiological variables, e.g. right ventricular enddiastolic pressure, respiration and the infusion of isoprenaline were examined. It was demonstrated that Vmax and Vpm were not independent of the loading conditions of the ventricle. The infusion of isoprenaline changed the shape of the pressure-velocity curves and increased the problems of analysis. The theoretical and practical difficulties involved in this type of analysis are discussed.


Another look at Prinzmetal's variant angina. Prinzmetal's variant angina is commonly referred to as a syndrome apart from the usual spectrum of atherosclerotic disease. 2 well-studied patients with this form of angina gave past histories compatible with classical angina. They were found to have, in addition to severe atheromatous lesions, coronary artery spasm resulting in complete obstruction of the vessel during Prinzmetal attacks. The concomitant electrocardiographic ST segment elevations are probably the reflection of transmural ischemia injury resulting from the transient complete occlusion of the corresponding coronary artery. Electrocardiograms taken during milder resting anginal attacks showed minimal nonspecific changes of the electrocardiogram or T wave inversions which may possibly reflect less severe ischemia, secondary to milder coronary spasm. These observations support the possibility that at least in some cases, Prinzmetal's angina may just be a phase in the life history of patients with atherosclerotic disease, during which recurrent severe coronary spasms may occur.


Echocardiographic assessment of left ventricular function. Investigation of infants, children and teenagers without heart disease. Echocardiography was used to study left ventricular function in 75 infants, children and teenagers  without heart disease. Normal values for echocardiographic parameters of left ventricular contractility were obtained and are presented in Tables. Systolic time intervals were measured from aortic cusp echoes and the normal range and correlation to heart rate and age are given. Computer analyses of echocardiograms from the left ventricle and the anterior mitral leaflet were done and normal values for the instantaneous velocities thus derived are given. To test the normal variation of left ventricular function with time 12 children were examined repeatedly during 1 wk. 95% tolerance limits for the variation of the different functional parameters are given. To test the reproducibility of the echocardiographic measurements 11 children with various forms of heart disease were examined consecutively by two different observers and the 95% tolerance limits for the difference between measurements were calculated.


Bidimensional real-time echocardiological visualization of a ventricular right-to-left shunt following peripheral vein injection. Contrast techniques were used in the echocardiological evaluation of a 28-yr-old patient with congenital cyanotic heart disease; catheterization showed an association of an atrial septum defect, a ventricular septum defect, and a patent ductus arteriosus, with equalization of pulmonary artery and systemic pressures. Glucose 5% in water, injected as a 10-ml bolus into an antecubital vein, constituted an adequate echogenic contrast solution. The heart was examined with both a single-crystal transducer (echoes recorded in M mode) and with a 51-elements dynamically focuses multiscan system (echoes recorded on video-tape). Contrast echocardiology showed that right-to-left shunting occurred at the level of the ventricular septum defect and was not significant at the atrial level.


Adaptation of evoked potentials by patterns of texture-contrast. Visual evoked potentials (VEPs) to a briefly presented pattern in black-ahd-white are reduced by pre-exposure to the same pattern formed only by contrasting textures. When such texture-contrast patterns are used as stimuli, however, the VEP is different in latency and in its sensitivity to changes in pattern geometry.


Biases for oriented moving bars in lateral geniculate nucleus neurons of normal and stripe-reared cats. Visual receptive fields of 42 LGN cells from normal cats and 110 cells from striped cylinder-reared kittens were studied with the aid of a computer controlled optical system. In the normal cats, ten of the 42 cells were weakly biased for orientation of the visual stimulus when tested with bars swept through the receptive field. Of those ten, eight were classified as transient. The orientation preferences of the ten biased units appeared randomly distributed around the clock. Of the LGN cells from the cylinder-reared group, about half of the transient cells had weak biases for orientation; only 7% of the sustained cells had biases. The orientation preferences of the biased LGN cells in the stripe-reared animals were either parallel to or orthogonal to the stripes each animal saw during its time in the conditioning cylinder. In 16 out of 18 of the biased LGN cells it was found that increasing the velocity of the test target reduced or eliminated the bias apparent at the lower velocity. For some LGN cells special techniques, such as inhibition of activated discharge, were needed to reveal orientation biases. The results described here, considered with data from others, suggest a role for the corticofugal projection in modulating the responses of some LGN cells.


Thalamic inputs to the rabbit visual cortex: identification and organization using horseradish peroxidase (HRP). Horseradish peroxidase (HRP) has been injected in visual cortical area 1 (V1, striate cortex) of 33 rabbits (16 received a unilateral injection, 17 bilateral injections) in order to identify its thalamic inputs and to determine their retinotopic organization. This study has shown that when HRP is injected into different portions of V1: 1. Labeled cells are consistently seen in the dorsal lateral geniculate nucleus (LGNd) and are always organized into horizontal columns arranged perpendicularly to the long axis of the LGNd; although the columns are always present in the alpha sector of the LGNd, they extend into the beta sector of this nucleus only occasionally. 2. With a series of injection sites that lie on or near the medial edge of V1 and run rostrocaudally, cell columns shift from ventromedial to dorsolateral within the LGNd. With a series of injection sites that are located along the lateral border of V1 and run from rostral to caudal, columns of labeled cells move from ventral to dorsal along the medial edge of the LGNd. 3. In some of the experiments, with injections in either medial or lateral portions of V1, columns of HRP-labeled cells have also been found within the pulvinar.


Responses in the hypoglossal nucleus to delayed regeneration of the transected hypoglossal nerve, a quantitative ultrastructural study. Electron micrographs of the left hypoglossal nucleus of adult male albino rats were quantitatively analyzed from 9-70 days after allowing the transected left hypoglossal nerve to regenerate after an 84 day delay. Delay was achieved by implanting the proximal stump into already innervated sternomastoid muscle, where no regeneration occurred. Regeneration was then allowed by denervating the sternomastoid. During the regenerative period the initially high number of abnormally electron dense perikarya and dendrites decreased to almost normal values, but no cell removal was seen. This suggested that the degenerate appearance of many profiles after prolonged prevention of regeneration, was reversible. The neuropil bouton and dendrite counts, and the numbers of synapsing boutons per dendrite, increased steadily to normal values from the low values of suppressed regeneration. Somatic bouton frequencies, even though already low, decreased further at 32 days, and later increased but not to normal values. The decrease at 32 days coincided with the loss of many subsurface cisterns, and dispersion of Nissl substance, all suggestive of chromatolysis. Later the subsurface cisterns and Nissl substance returned. It was suggested that the delay of complete recovery of somatic bouton frequencies might be because of lack of sensory information from the denervated muscle into which the hypoglossal nerve was regenerating, or because of abnormally low starting values for the recovery phase. Astrocyte (or, occasionally microglial) sheaths persisted along bouton-free perikaryal surfaces.


The influence of the amygdala on the basal septum and preoptic area of the rat. Extracellular microelectrode recordings were made from single neurones in the medial preoptic area and basal septum of normal female rats anaesthetised with urethane and the effects of stimulation of the ipsilateral amygdala (AMY) was tested. 1. Quiescent cells were excited with latencies between 4 and greater than 40 msec with the majority being between 10 and 27 msec. Variable latency, changing latency and recruitment were observed and suggest that many pathways are oligo- or polysynaptic. 2. A minority of spontaneously active units (20.6%) were excited with latencies between 5 and 36 msec. The predominant initial response was inhibition (67.1%). The remaining 12.3% of neurones did not respond. 3. A predominantly positive complex field potential was associated with excitation, particularly of quiescent neurones. 4. Inhibitory responses were classified according to duration (short: 20-60 msec; long: 100-400 msec). All responses contained an inhibitory component. Responses were further described on the basis of presence and rhythmicity of post-inhibitory excitation. 5. The majority of action potentials evoked from quiescent neurones were of small amplitude (80-150 mu/V) and occurred in small groups. These characteristics and their occurrence at the onset of inhibition are consistent with the view that all or a proportion of them may be generated by inhibitory interneurones. 6. Only minor differences were observed between response characteristics evoked by stimulation of the corticomedial or basolateral AMY indicating that differential effects of these regions on adenohypophysial hormone secretion are determined at the septopreoptic level.


Time of origin and distribution of a new cell type in the rat cerebellar cortex. A new cell type was identified in the granular layer of the rat cerebellum. It has a lightly staining nucleus with a nucleolus, it is spherical in shape and is larger than granule cells and smaller than Golgi cells. These pale cells are preferentially concentrated in the nodulus, the ventral uvula, the lingula, the flocculus, and parts of the paraflocculus. According to autoradiographic (3H-thymidine) evidence, over 60% of these pale cells are formed on embryonic days 19 and 20, and their production comes to an end soon after birth, prior to the differentiation of granule cells. The possible relation of pale cells to vestibular afferents of the cerebellar cortex is discussed.


Electrophysiological studies on interpositus neurones in the normal and Lurcher mutant mouse. The response characteristics of interpositus neurones (IP) to sciatic nerve stimulation were studied in normal and Lurcher mutant mice under pentobarbitone anaesthesia. The response of IP neurones in the normal mouse was a short latency bimodal excitation (E1-I1-E2) followed by a depression of the firing rate (I2) and ending with a longer latency excitation (E3) which was completed within 225 msec. The response of the majority of IP neurones in the Lurcher mouse was a short latency unimodal excitation (LE1) which corresponded in time to the E1-I1-E2 phase in the normal. This was followed by a pause in the excitation. The response ended with a longer latency excitation (LE2) corresponding in time to the E3 phase in the normal mouse but which persisted for a considerably greater period of time. The response of IP neurones in normal and Lurcher mice appear to be similar to those observed in the normal and experimentally cerebellar decorticate cat, respectively.


Lack of centripetal connection between the lateral olfactory tract and the caudate nucleus. Evoked potential study in the rat. In rats under alpha-chloralose or without general anesthesia the effect of a lateral olfactory tract stimulus on the caudate nucleus electric activity was explored by bipolar macroelectrodes. The stimulation effectiveness and the reactivity of recording sites to somatic stimuli were systematically tested. Under these conditions, no functional connection from the lateral olfactory tract to the caudate nucleus was demonstrated.


Frequency transfer properties of three distinct types of cat horizontal cells. Intracellular responses of horizontal cells in the retina were recorded from the intact eye in situ of anesthetized and paralyzed cats. The responses to large (15 X 15 degrees) high modulation (0.6-0.9) photopic (140-200 cd/m2) sinewave light stimuli could be grouped unequivocally into three distinct classes on the basis of the critical flicker frequency (CFF); Hn-units had a CEF of 25-40 Hz, hm-units of 55-70 Hz and Hw-units of 95-110 Hz. For some stimulus situations small oscillations could be seen in Hm-responses (resonance frequency of about 43 Hz) and Hw-responses (resonance frequency 95 Hz). Hn-responses never showed such an oscillatory tendency. Frequency transfer functions are presented for the three types of H-units and a phenomenological model is discussed that describes these results quantitatively.


The response of cat horizontal cells to flicker stimuli of different area, intensity and frequency. In the cat's retina we analyzed the sinewave light flicker response nonlinearity of Hm-type horizontal cells. (For a description of the three types of dynamic responses of cat retinal H-units see Foerster et al., 1977). For equal decreases in the Hm-response amplitude an increase in stimulus frequency had a much stronger linearizing effect than a decrease in stimulus area. Thus the distortion is not simply proportional to response amplitude. Both Hm- and Hn-units had frequency dependent nonlinear area-response functions. The receptive field of Hm-units increased dramatically with stimulus frequency, e.g. from 1 degrees at 1 Hz to 8 degrees or more at 44 Hz. Intensity transfer data could be described by the function Lb-(sigmab + Lb)-1 with b approximately 1 for Hm-units and b approximately 0.5 for Hn-units. Distortion values predicted from intensity transfer data were too high. It was also found that higher harmonics were attenuated more than the first harmonic at increasing frequencies. Therefore it appeared that some filtering preceded the amplitude compression stage.


Analysis of the circuitry responsible for primary afferent depolarization in the trigeminal spinal nucleus caudalis of cats. Depth analysis was performed on the field potential evoked by stimulation of the infraorbital nerve in the trigeminal spinal nucleus caudalis and the subjacent lateral reticular formation of cats. It was shown by dye marking of the recording positions that each subnucleus of the nucleus caudalis (subnucleus marginalis, gelatinosus and magnocellularis) and the reticular formation could be differentiated from one another by the characteristics of the peripherally evoked field potentials. Responses of neurons were extracellularly recorded in the subnuclei gelatinosus and magnocellularis of the nucleus caudalis and in the reticular formation to stimulation of the trigeminal sensory branches (the frontal, infraorbital and lingual nerves), the nucleus ventralis posteromedialis of the thalamus and the cerebral cortex. The properties of the neurons were studied in relation to their thresholds, latencies, receptive fields (sensory branches effective for spike generation) and frequency-following capacities. These responses were then compared with properties of the PAD induced in the fibers terminating in the nucleus caudalis by similar peripheral and central stimulation. It was found that the neurons in the subnucleus magnocellularis were the most likely candidates for the interneurons mediating the peripherally evoked disynaptic PAD in the trigeminal nerve fibers terminating in the nucleus caudalis.


Visual movement perception in the cat is directionally selective. Behavioral experiments show that the visual system of cat contains mechanisms which are selective for direction of stimulus movement. The cat's contrast detection threshold for a drifting grating is unaffected by the addition of a grating moving in the opposite direction; this same pattern of results is found for human observers. The convergence of cat and human psychophysical data suggests that man's brain may hold direction-specific neurons, similar to those known to exist in the cat brain.


Representation of the cochlea in the neocortex of guinea pigs. By recording unit clusters and local evoked responses in the auditory cortex of guinea pigs the cortical representation of best frequencies was studied. In penetrations vertical to the cortical surface best frequencies were similar. Parallel to the cortical surface, however, different frequencies were found in the antero-posterior direction, whereas medio-laterally best frequencies usually remained in the same range (isofrequency stripes). Two auditory cortical fields could be distinguished, which are tonotopically organized. With increasing sound intensity the cortical response field for a given frequency and thus the frequency overlap increased. All along the isofrequency stripes in the medio-lateral direction, the stimulation of the contralateral ear produces larger responses than the same stimulus delivered to the ipsilateral ear.


Ultrastructural evidence for bouton proliferation in the partially deafferented dentate gyrus of the adult rat. A quantitative morphological study of the changes in the dentate gyrus molecular layer in response to the removal of perforant path afferents was made utilizing electron microscopic techniques. Alterations in 1. the population of remaining afferents, 2. glial cells, and 3. granule cell dendrites are reported. The major observation was an increase in intact bouton density in the region of denervation which began at 5 days post-lesion and continued through 11 days post-lesion, the longest post-lesion survival time studied.


Cholinergic involvement in cobalt-induced epilepsy in the rat. In rats with cobalt implanted in the right frontal cerebral cortex, acetylcholine (ACh) levels were depressed in the visually non-necotic, surrounding cortex at 7 and 14 days after surgery in comparison with values for controls treated with glass. At 21 days post-implantation, ACh levels were not different for glass and cobalt treatments. Effects of drugs affecting cholinergic function on electro-corticographic (ECoG) epileptiform activity were determined in rats implanted bilaterally with cobalt. The cholinesterase inhibitors, physostigmine and diisopropylfluorophosphate reduced both seizure activity and interictal spiking in these cobalt-treated rats. Hemicholinium-3 (HC-3), given subacutely initially inhibited seizures, but seizure frequency increased later during treatment. HC-3 did not appear to inhibit interictal spiking. These results suggest an involvement of brain cholinergic system in chronic cobalt experimental epilepsy. Seven days after cobalt implantation, HC-3 was less effective in depleting ACh in cerebral cortex adjacent to the cobalt-lesion than in similar tissue from rats with no cobalt implants. This suggests that the cholinergic neurons adjacent to the implant are not highly active at a time when seizure frequency is maximal.


Corticofugal influence on evoked activity of lateral geniculate neurons in the rabbit. Corticofugal influence upon lateral geniculate units was evaluated by inactivating the visual cortex with a topical application of 3M KCL in rabbits. The results revealed a decrease of spontaneous firing in slow P cells following cortical depression suggesting a tonic corticofugal influence. The most consistently observed alteration was an enhancement of the ON response with a decrease of the response to the opposite stimulus (OFF); and vice versa: the short latency excitation being augmented. It is suggested that the visual cortex exerts a powerful influence on intra-geniculate inhibitory processes.


The release of amino acids synthesised from various compartmented precursors in rat spinal cord slices. [14C]Glucose and [14C]acetate have been used to label amino acid pools believed to be localised in neurones and glia, respectively, in small slices of rat spinal cord. The effects of depolarising agents on the efflux of amino acids from these pools were compared and contrasted with their effect on the efflux of exogenous [3H]glutamate. Elevated (50 mM) potassium in the superfusing medium increased the release of glutamate, aspartate and GABA synthesised from either glucose or acetate and that of exogenous glutamate. These increases were not, however, abolished by tetrodotoxin (2 micron). Protoveratrine A (10(-4) M), on the other hand, elevated the efflux of glutamate, GABA and possibly aspartate when these amino acids were synthesised from glucose, but not when acetate was the labelled precursor. Furthermore, this effect was abolished by 2 micron tetrodotoxin. It is concluded that these techniques point to the existence in slices of spinal cord of neuronal pools of glutamate, GABA and possibly aspartate that may be released as a consequence of neuronal activity, and that these pools probably represent transmitter stores of these amino acids.


Light and electron microscopic study of hermorrhagic hepatitis induced by trimethyllysine and D-galactosamine. In the present paper the effect of the pretreatment with epsilon-amino-trimethyllysine (TML) 10 mg/kg on the DGA-induced hepatitis in mice is described. TML-pretreatment was chosen because experiments indicated that TML treatment elicits processes in the liver similar to that occurring during regeneration on one hand, on the other hand because it was shown that DGA proved to be ineffective in newborn or in partially hepatectomized animals, that is to say on regenerating liver. It was expected that TML pretreatment would protect the animals against the hepatitis inducing effect of DGA. Unexpectedly pretreatment with TML had just the opposite effect, resulting in a severe hemorrhagic hepatitis in several animals. Biochemical and morphological studies are in progress to elucidate the mechanism of this peculiar effect.


[Image processing in pathology. III. Structure and use of an automatic morphometry system for recording morphometric features of nuclei (author's transl)]. An image processing system for morphological investigation of liver cell nuclei in biopsy specimens is demonstrated. The present study deals with the age dependence of normal hepatic nuclear areas. The results were compared with those of conventional methods. The image processing system consists of a microscope, an image dissector and a computer (central processing unit, display, teletype, magnetic tape devices and line printer). 74 liver biopsies were investigated. They sshowed no signs of acute or chronic diseases. Paraffin sections of 4 micron in thickness were prepared and stained by Feulgen method. 8-10 biopsies were available for each decade from 1-8. 18,000 liver cell nuclei from all specimens were isolated and measured automatically. Using the image processing system and adequate computer programs 20 parameters of all isolated nuclei were gained (parameters of shape, size and structure of the nuclei). For sampling and processing of the information the following programs are developed: PROBE Program for investigation of optimal parameters of scanning and processing. SAMPL Program for scanning, object isolation, feature extraction and storage of data records. KORRL Program for investigation of correlations between the features of objects. LISTE Program for listing of data records. ULTRA Program for search of objects with extremal features. CODER Program for correction od data records. ADAPT Program for training of classificators. SCHAU Program for demonstration and checking of the classificator. MORPH Program for output of feature distributions and statistical parameters. Following object features were calculated and investigated: features of size: KOFL area within the object contour; KKFL minimal covex area of the object; ZKFL object area without holes; KONL length of the object contour.


[Ultrastructural study on formal pathogenesis of experimentally induced rhabdomyosarcomas (author's transl)]. During oncogenesis the rhabdomyosarcomas pass different stages of differentiation. In experimentally induced rhabdomyosarcomas the chronological sequence of cytoplasmatic changes can be analysed. 10 mg 9,10-dimethyl-1,2-benz-anthracene were injected subcutaneously or intramuscularly in the hind-paw of Wistar rats with 100 gms weight. 30, 60, 105, and 150 days later the animals were killed and specimens withdrawn. The soft-tissue was prepared for light- and electron-microscopy. In the soft-tissue tumors, experimentally produced with DMBA, 4 different cell types can be observed, which--depending on exposition time--dominate in the histological picture: (1) The myofibrillar cells. These cells are similar to rhabdomyocytes and contain numerous cytoplasmatic fibrillae with sarcomere-like structure. (2) The myofilamentous cells. These cells contain the fibrillar structure, but without sarcomere-like arrangement. (3) The undifferentiated sarcoma cells. These cells show a pathologically changed ergastoplasm and chondrioma. (4) The matured fibrosarcoma cells are nearly similar to fibrocytes. Under the cytoplasmatic changes especially the hyperplasia of the chondrioma can be observed, in which dystrophic megamitochondriae are found. These possibly reflect the abnormal glycolysis in cancer tissue. Also mitochondrial antibodies are discussed at the form pathogenesis of this change in organelles. Regarding the change of the endoplasmatic reticulu, the annulatae lamellae can be noticed which are typical for tumor cells. Furthermore megacisterns are found, in which protein-containing material is condensed as a consequence of a disturbed synthesis and secretion.


The binding of 3-14C-coumarin to serum proteins in the rat: a comparison between in vitro and in vivo estimations. Like other benzo-pyrones, coumarin has been shown to bind to serum proteins. Under in vitro conditions irrespective of the dose which ranged from 50--3.31 microgramm/ml, the binding remained at approximately 40%. With intravenous administration an average of 4.6% of the injected dose remained in the vascular system, of this an average of 37% was bound to serum albumins. With intraperitoneal administration an average of 4% of the injected dose entered the vascular system of which an average of 36.5% was in the bound form.


Hepatic effect of two hypolipidemic drugs in rats. Some hepatic effects of the hypolipidemic agents 3,9-di-3-pyridyl-2,4,8,10-tetraoxaspiro-5,5-undecane (compound A) and 2-(4-dibenzofuranyloxy)-2-methylpropionic acid (compound B) were investigated in male rats. The animals were treated orally with these drugs and a reference compound-clofibrate for 10 weeks, the daily doses being 250, 300 and 300 mg/kg body weight respectively. All three drugs caused hepatomegaly with a normal microscopic appearance in liver cells. In rats given compound A, part of some liver cells could be occupied by numerous membranes of smooth endoplasmic reticulum. The hepatocytes of the rats treated with compound B or clofibrate showed a marked increase in microbody profiles and an elevated hepatic catalase activity in comparison to the control animals. Neither the microbodies nor the catalase activity were affected by compound A. Hypolipidemic effects were demonstrated with all three compounds, the most potent activity being shown by compound B. Treatment with this agent resulted in significantly higher catalse activity than with clofibrate.


The autoradiographic pattern of DNA synthesis in Papova virus- and N-methyl-N-nitroso urea (MNU)-induced skin tumors of the Syrian hamster (Mesocricetus auratus). In skin tumors induced in Syrian hamsters by Papova viruses or produced chemically by dripping of methylnitroso urea (MNU) the pattern of DNA synthesis was studied in vitro and in vivo by autoradiography. The greater part of DNA synthesis in the Papova tumor of the hamster is of cellular origin. Only the cells localized adjacent to keratinizing regions of the tumors may be considered as virus-infected with progressive maultiplication of viruses. This also applies to all nuclei with cellular DNA synthesis only in the marginal chromatin. Moreover viral DNA synthesis is supposed in the cytoplasm, too. In methylnitroso urea-induced squamous cell carcinoma labeled cells were likewise found adjacent to keratinizing tumor regions and the pattern of DNA synthesis is generally not limited to the "stratum basale". With increasing malignancy the pattern of DNA synthesis is changing also in chemically induced tumors and is no longer limited to the stratum basale where it still can be demonstrated in the papilloma.


[Fucosterol-24,28-epoxide, an intermediate in the oxidative biodegredation of fucosterol to cholesterol by the cricket (Locusta migratoria (R. and F.)]. beta-Sitosterol 1 is metabolised to cholesterol 5 by phytophagous insects. It has been previously shown that fucosterol-24,28 epoxide 3 is transformed into 5 in Locusta migratoria, desmosterol 4 being an intermediate. It is now established that locusts transform [3-3H]fucosterol propionate into the corresponding labelled epoxide 3, recovered as such or as an oxazoline derivative 11.


Structural determinants of glomerular permselectivity. Molecular size has been considered in the past to be the major factor in glomerular restriction of macromolecules. Ultrastructural tracer studies have suggested that the restrictive barriers(s) are present in the glomerular basement membrane (GBM), the epithelial filtration slits, or both. Recent morphologic and functional tracer studies have indicated that, in addition to size, molecular charge and possibly shape are important determinants in the ultrafiltration process. Negatively charged macromolecules are restricted by the glomerulus more than neutral molecules, while positively charged macromolecules of similar size are filtered in greater amounts. The elements responsible for this specific restriction of polyanions and facilitated transport of polycations are glycoproteins rich in carboxyl groups (sialic acid, dicarboxylic amino acids), which constitute the endothelial and epithelial cell coats and part of the matrix of the glomerular basement membrane. Ultrastructurally, the polyanionic elements of the GBM are localized in its subendothelial and subepithelial layers; the lamina densa, in contrast, appears more neutral, containing most likely a collagen-like glycoprotein.


Profound hypothermia in mammals treated with tetrahydrocannabinols, morphine, or chlorpromazine. The tetrahydrocannabinols are among the most potent hypothermic agents known. A comparison of the hypothermic action of delta9-tetrahydrocannabinol (delta9-THC) with chlorpromazine (CPZ) and morphine shows the following order of hypothermic potency: CPZ greater than delta9-THC greater than morphine. A marked depression of oxygen consumption is produced by delta9-THC both in vivo and in the isolated perfused liver preparation. Simultaneous measurement of core temperature and tail temperature after delta9-THC shows that tail temperature is decreased more by delta9-THC than it is in animals that attain comparable core hypothermia without drug treatment. From these results, it is concluded that delta9-THC-induced hypothermia results primarily from decreased heat production and not from increased heat loss. Therefore, the processes involved in the hypothermic response to delta9-THC appear to differ from those that mediate CPZ- or morphine-induced hypothermia. A hypothesis is discussed in which the hypothermic action of delta9-THC is related to inhibition of membrane ATPase.


Filtration dynamics in dogs: glomerular capillary pressure. Hydrostatic pressure in the glomerular capillaries, the primary driving force for glomerular ultrafiltration, is directly measurable only in those species with glomeruli present on the capsular surface of the kidney. Accordingly, this crucial measurement must be made indirectly in species not so endowed, such as the dog. Several different methods have been utilized in the dog; unfortunately each is indirect. This review deals with an assessment of the following methods for the determination of glomerular capillary pressure in dogs: a) reduction of arterial pressure method; b) ureteral occlusion method; c) the Winton or venous occlusion method; d) fraction of arterial pressure method; e) back calculation from forces opposing filtration; f) sieving method; and g) single nephron occlusion of the Gertz stop-flow method. Recent studies in the dog, utilizing single nephron occlusion techniques, provide estimates of glomerular capillary pressures of approximately 60 mn Hg in the autoregulatory range of blood pressure.


Determinants of the transglomerular passage of macromolecules. In addition to molecular size, at least two other factors influence the transglomerular passage of macromolecules. The hemodynamic determinants of glomerular filtration rate affect macromolecule transport by altering the volume flux through the glomerular capillary wall and the profile of macromolecule concentrations along a glomerular capillary. The electrostatic properties of the glomerular capillary wall markedly restrict the passage of circulating polyanions, relative to neutral macromolecules of similar size. In the normal animal, the combined effects of these various mechanisms ensure that only very small quantities of plasma proteins are filtered. In experimental proteinuric conditions such as nephrotoxic serum nephritis and puromycin-induced nephrosis, reduction in the fixed negative charges on the glomerular capillary wall appears to be largely responsible for the increased transglomerular passage of anionic macromolecules such as albumin. Other evidence suggests that hemodynamic factors may contribute to proteinuria under certain circumstance. The possibility of an increase in number and/or radius of glomerular "pores" being responsible for proteinuria, perhaps the most intuitively obvious and widely held view, has yet to receive direct experimental support.


Blood-tissue exchange in liver and heart: the influence of heterogeneity of capillary transit times. The single-injection multiple indicator-dilution technique has been used to explore blood-tissue exchange in the heart and the liver. Analysis of the classical description of exchange at the level of the single capillary following an impulse injection indicates that the loss of the material from the impulse in each capillary depends on the transit time of that capillary. Thus, in a multiple indicator-dilution experiment, early in time, for barrier-limited substances, the relation between the reference and diffusible substances as a function of time will reflect the manner in which the underlying capillary transit times have varied. In the heart, labeled sucrose exchange was used to quantitate the underlying pattern of capillary heterogeneity. With maximal coronary vasodilation, the capillary transit times appeared uniform (and there was a corresponding maximal heterogeneity of large vessel transit times). With more normal coronary tone, both the underlying capillary and large vessel transit times were found to increase along the outflow curve with the outflow arrival time. In the liver, in contrast, the transit times through the exchange area were found to show a maximal heterogeneity (and there was, in the large vessels, a corresponding uniform transit time).


Studies on bone ion exchanges using multiple-tracer indicator-dilution techniques. Free diffusion appears to be the principal mechanism for movement of ions, known to concentrate in bone, across the capillaries of bone. The interstitial fluid space appears large enough to allow for determination of instantaneous fractional escape by the indicator-dilution method. The mechanism by which large molecules, such as the diphosphonate 99mTc-labeled EHDP or 99mTc-labeled pyrophosphate, pass through capillaries in bone is by passive diffusion. These molecules are larger than 85Sr and their lower extraction rate is presumably due to the effect of their sizes on passage through transcapillary clefts. A corollary of these studies might be that if transcapillary exchange is passive, then partition of anions and cations likely lies beyond the capillary and therefore is controlled by osteal cellular processes.


[Invariability of stimulus recognition by dolphins]. The echo-location characteristics were studied in dolphins with the aid of transformation of stimuli not altering the reception characteristics in analysing systems. The dolphin locator was shown to be able to single out a class of equivalent in respect to certain transformations echo-signals. The probability of the target recognition is invariable in respect to transformations of homothetic type and module transformations, i.e. the principle of invariability spreads over the work of dolphin's auditory analyser in active regimen too.


[Participation of vertical semicircular canals in the vestibulo-oculomotor response to the horizontal rotation test]. The horizontal rotatory test was shown to elicit in rabbits a complex three-plane vestibular oculomotor response with rotatory nystagmus (RN) in sagittal plane. The leftward accelerating rotation caused the clockwise RN of the right eye; during decelerating rotation the RN was directed counterclockwise. Its frequency may differ from that of the horizontal nystagmus. The cupulo-endolymphatic displacements seem to occur not only in the horizontal canal, i.e. in the plane of rotation, but also in the vertical canals as a result of a hypothetical hydrodynamic interaction between the canals. The displacements in the anterior and the horizontal canals of the labyrinth were analogous, whereas that in the posterior canal was of the opposite direction. That suggests that the utriculofugal displacements in the horizontal and the anterior canals are accompanied by an utriculofugal displacement in the posterior canal, and vice versa.


[Effect of a change in the temperature of the midbrain and skin on the activity of posterior hypothalamic neurons]. Changes of the mean firing rate of neurons in the posterior hypothalamus on a regional increase or decrease in the midbrain temperature (0.6-2.0 degrees C) and skin temperature (3-5 degrees C) were studied in unanesthetized rabbits. In the posterior hypothalamus, neurons were found which responded both to the midbrain and skin temperature changes. The data suggest that the posterior hypothalamus takes part in the integration of signals from different central and peripheral temperature sensitive agents.


[Effect of magnesium and calcium ions on the electrical activity of Pacinian corpuscles]. The effect of magnesium and calcium ions of the electrical activity of Pacinian corpuscles was studied in isolated decapsulated preparations. The sensitivity of the corpuscles and the amplitude of receptor potential increased in magnesium-rich solution (5-15 mM). The amplitude of receptor potential increased over the first 60 min and then decreased in calcium-free EDTA solution. Magnesium ions slow down or prevent the depressant effects of the lack of calcium on the receptor potential. Divalent cations are supposed to take no part in mechano-electrical transduction conduction in Pacinian corpuscles.


[Relationship between metabolic and hemodynamic characteristics during isometric tetanus of the cat gastrocnemius muscle]. In anesthetized cats, the increase in duration of the isometric tetanic contraction of the m. gastrocnemius from 7 to 30 sec elicited a 4-fold increase in the muscular mechanical performance. During the postcontraction hyperemia, a 5-6-fold increase in the rate of lactic acid and inorganic phosphates removal into venous blood were opposed to only a 1.5-2-fold increase in the blood supply and oxygen consumption by the muscle. The role of metabolic and metabolic factors in the mechanism of hyperemia in skeletal muscle after strong tetanic contractions is discussed.


[Chromotopography of ventricular depolarization in northern reindeer]. With the aid of intramural multipolar technique, the sequence of the heart ventricles depolarization was studied in deer. Electric potentials were led from 1500-1700 points in the myocardium. Primary foci of excitation were revealed in the subendocardium of the caudal and cranial areas of the middle third of left and cranial portions of the upper third of right side of the interventricle partition. Within 5-10 msec. the ventricles subendocardium is wholly involved into the wave of depolarization. For 10-20 msec., the main lot of free walls, the central and upper portions of the partition, are excited. This period is characterized by spreading of the depolarization wave from numerous foci of excitation in all directions. Last the upper portions of the pulmonary artery output cone (40-45 msec.) and portions of the interventricle partition adjacent to the ventricles basis (45-50 msec.), become excited.


[Adrenergic regulation and adrenoreactivity of the rat heart during adaptation to altitude hypoxia]. Male albino rats were adapted to 6 km "altitude" in barocamber. Responses of their hearts in open chest and on artificial respiration to noradrenaline and propranolol were studied. Values of the heart contractory function were by 32-140% higher in experimental animals than in control those. This excess could be eliminated by propranolol which shows it to be due to exaggerated effect of the adrenergic regulatory link. Adrenaline raises the heart function almost up to the maximal limit in adapted animals. This is followed by an increased rate of disappearance of the noradrenaline inotropic effect.


[Role of the vagus nerves in the respiratory rate changes in decerebrate cats]. Durations of respiratory cycle, of inspiration (TI), of expiration (TE) and tidal volume (VT) was measured. With vagus nerves intact increasing of lung ventilation was accompanied by increasing of breathing frequency (f) dependent on diminution of TI and TE. After bilateral vagotomy increasing of VT was accompanied by increasing of TE. In cases of well pronounced VT-TI relationship changes of f were determined by slope of contradictory changes of TI and TE. With increasing VT f could be constant or weakly increased or diminished. In cases of weak VT-TI relationship increase of VT was accompanied by f diminshing at the expense of TE increase. It is concluded that lungs mechanoreceptors cause f increment with VT increasing by 1) VT-TI curve displacement to left and down and 2) producing the linear relationship between TI and TE. After vagotomy TI and TE are determined by central mechanisms with certain degree of independence.


[Dynamics of emptying of the antral portion of the stomach]. In 3 dogs with antral and duodenal fistulas, the time of remaining of a portion of chyme in the antrum was constant and did not depend on the rate of gastric emptying. No retropulsion of antral contents into the fundus was observed. The data suggest that: 1) the antrum is only involved in discharge of chyme from the stomach into the duodenum during the period which depends but a little on the amount of food evacuated; 2) the rate of gastric emptying is determined by fundus and corpus of the stomach.


[Relationship between the amylolytic activity of the small intestine and the blood amylolytic activity]. In acute experiments on dogs and rats, soon after ligation of the bile-pancreatic duct or i.v. administration of alpha-amylase, the rise of the amylolytic activity, of amylase excretion with peripheral blood, was shown. The amylolytic activity of the small intestine mucose increased with higher hydrolysis of starch in the abdominal cavity rather than of the membrane. The amylolytic activity greatly increased in apical zone of the fibres rather than in their base, the amylolytic activity of enterocytes suspension increasing too. The great amount of amylase in the blood not only increases the recrement of alpha-amylase by the small intestine, but also induces the synthesis of the intestinal gamma-amylase. This can be observed in adrenalectomized rats, but not in the isolated in vitro small intestine.


[Relationship between temperature and the rate of reabsorption in the proximal tubules of the river lamprey kidney]. In conditions of temperature raising from 9 degrees C to 19 degrees C, Q10 of the NaCl reabsorption in the proximal tubule was 2.01; Q10 for the short-circuit current in the frog skin was 1.93. Different values of Q10 for reabsorption of isotonic solutions with different contents of NaCl and NaHCO3, were revealed. The data obtained suggest the primary importance of the active transport rather than of physical factors, for the mechanism of proximal reabsorption.


[Urea concentration and arginase activity in the organs of rats during acclimatization to cold]. Arginase activity in the brain and liver and the urine contents in the brain, liver, and blood of rats on the 1st, 3rd, 30th, and 45th days of the cold acclimation (+2--+4 degrees C), were studied. The arginase activity was also studied in the brain, liver, and kidneys of adrenalectomized rats. During the acclimation, the arginase activity decreases by 1.5--2 times in the brain and increases 202.5-fold in the liver. The urine contents in the tissues raised dur to arginase activation in the liver. The brain activity of adrenalectomized animals does not differ from the control, while decreasing in the liver and kidneys by 33% and 60% respectively. We suppose that the difference between responses of the brain and liver arginases to cold is based on their different regulation by the adrenal hormones.


[Correlation spectral analysis of the spontaneous impulse activity of cerebral cortex neurons]. Spontaneous unit activity in alert unrestrained rabbits was recorded simultaneously with two microelectrodes from the visual and sensorimotor cortex. The correlation analysis revealed that activity of majority of the neurons had no regular rhythm. But spectral analysis of the average correlograms showed existence of oscillations in the delta- and theta-ranges. The synergic type of interaction between cortical neurons was prevalent. Analysis of structure of the distant interaction showed the reduced probability of synergic spikes with periods 150-200 msec and less and the increased one with periods within 200-500 msec.


[Low-threshold mechanisms and pathways of corticofugal activation]. In chronic experiments of alert cats, moderate electrical stimulation of different points on the lateral cortical surface led to activation of different cerebral areas. Both the high-threshold and the low-threshold points were revealed in the sensorimotor cortex and in the Ep field of auditory area. The latter had as low a threshold of the activation response as the points within the mesencephalic RF and the thalamic CM, VPL and GM. In the morphological aspect, projections from the auditory Ep field to the thalamic intralaminar nuclei and to the brain stem RF, were revealed. Major projections spread from the dorsal part of the Ep field to the lateral tegmentum. The data obtained seem to provide better comprehending of the mechanisms for corticofugal activation. The functional role of the low-threshold loci in the cortex can involve triggering of unspecific apparatus of activation with a graduated volley which controls its excitation in accordance with biological significance of analysed signals.