Negative inotropic effect of cyclic GMP in cardiac fiber fragments. The force of spontaneously beating cardiac cellular fragments obtained from mice heart by homogenization was recorded in presence of cyclic guanosine -3'.5'-monophosphate (cGMP) and cyclic 8-bromguanosine -3'.5'-monophosphate in concentrations of 3 X 10(-6) M - 33 X 10(-6) M. The nucleotide decreased the force and reduced the rate of spontaneity. Eventually the preparation became quiescent. It is thought that this nucleotide either reduces the capacity to sequester calcium or affects its release from the sarcotubular system.


Conformations of A,T-rich DNAs.

Conformations of A,T-rich DNAs. DNAs from the genomes of Clostridium perfringens and Cytophaga johnsonii display orthodox A-DNA and B-DNA structures despite their high (A+L) nucleotide content. Unique structures, such as those found for synthetic DNAs having specific special sequences, do therefore not necessarily occur for DNAs having more random base sequence even if these have unusual base compositions. Clostridium perfringens DNA exhibits unusual structural properties only prior to purification by gel filtration.


Identification of the minor guanylated tRNA of rabbit reticulocytes. Two of the tRNA's found in rabbit reticulocytes are substrates for a post-transcriptional modification leading to the incorporation of guanine into the polynucleotide chain. The major guanylated tRNA was previously identified as tRNA (His). In the present report we show that the minor guanylated tRNA is tRNA (Asn), and that just as in the case of tRNA (His), the guanine is located in an internal position. There are only two tRNA (Asn) in reticulocytes. We further show that one of these, the one that is not labeled with guanine, contains the hypermodified base known as Q. tRNA (Asn) does not contain Q.


Studies on the interaction of H1 histone with superhelical DNA: characterization of the recognition and binding regions of H1 histones. The very lysine rich histone, H1, isolated from a variety of sources interacts preferentially with superhelical DNA compared to relaxed DNA duplexes. The nature of this specific interaction has been investigated by studying the ability of various purified fragments of H1 histone from calf thymus to recognize and bind superhelical DNA. The data suggest that the globular region of the H1 histone molecule (amino acid residues 72-106) is involved in the recognition of superhelical DNA. Thus, the H1 histone carboxy-terminal fragment, 72-212, resembles native H1 histone both quantitatively and qualitatively in its ability to discriminate between and bind to superhelical and relaxed DNA while the H1 histone carboxy-terminal fragment, residues 106-212, has lost this specificity, binding superhelical and relaxed DNA equally well. Furthermore, under conditions in which the globular region of the intact H1 histone has been unfolded, the molecule loses its ability to discriminate between superhelical and relaxed DNA, and binds both forms of DNA equally.


The mechanism of the chemical synthesis of oligonucleotides and its synthetic consequences. The data obtained mainly by pulsed NMR spectroscopy on phosphorus nuclei on the mechanism of the internucleotide phosphodiester (PDE) group formation are summarised. With arylsulphonyl chloride as condensing reagent monomeric nucleotide derivative B (nucleoside metaphosphate or its pyridinium adduct) is the highly reactive intermediate. In the presence of PDE groups in nucleoside or nucleotide component the significantly less reactive derivatives with trisubstituted pyrophosphoryl residues are formed both with arylsulphonyl chloride and dicyclohexylcarbodiimide (DCC). The reactive B form of nucleotide component may be obtained using greater excess of arylsulphonyl chloride with simultaneous convertion of PDE groups to tetrasubstituted pyrophosphates amenable to side reactions. The convertion of PDE groups to easily hydrolysable dicyclohexylurea derivatives by reaction with DCC is proposed to reversible blocking of PDE groups of nucleoside component. The B type derivatives of mononucleotides or oligonucleotides with blocked PDE groups seems to be the best nucleotide components.


Absence of 5' terminal capping in encephalomyocarditis virus RNA. The nature of the 5' terminus of encephalomyocarditis (EMC) virion RNA has been investigated. We have failed to detect any capped products or nucleoside polyphosphates arising upon complete digestion of the RNA with T1, T2, and pancreatic ribonucleases, and it would therefore appear that the 5' terminus of EMC virus RNA is not phosphorylated and not capped with m7G. EMC virions do contain, however, large amounts of all four 5'-monosubstituted nucleoside triphosphates (4.2M pppG; 16.4M pppA; 3.OM pppU and 2.5M pppC), of which at least a proportion (about 15-20%) appear to remain bound to fully denatured RNA in the presence of divalent cations.


Size and location of poly (A) in encephalomyocarditis virus RNA. Encephalomyocarditis (EMC) virus RNA contains a covalently bound sequence of polyriboadenylic acid (poly(A). This was determined by two-dimensional gel electrophoresis of complete T1 and pancreatic RNase digests of formamidesucrose gradient-purified RNA and subsequent analysis of the product by alkaline hydrolysis. The size of the EMC virus genomic poly(A) sequence was estimated by formamide-polyacrylamide gel electrophoresis of the RNase-resistant product, or by [3H-]poly(U) hybridization to freshly purified virion RNA, to be, on average, 40 nucleotides in length. The evidence obtained from [3H-]isoniazid labelling and other experiments would indicate that the poly(A) sequence is located at the 3'-terminus of EMC virus RNA.


The effect of administered corticosteroids on the growth of children. The growth-inhibiting effect of exogenous corticosteroids has been reported in many papers. Most of them have concerned the clinical problems of asthma and rheumatoid arthritis but it is probable that the underlying disease is relatively unimportant in determining the effect on growth. Steroid therapy on alternate days seems to produce less undesirable effects than steroid treatment every day and corticotrophin may be preferable. Although the mechanisms are uncertain it seems likely that the action is peripheral and certainly exogenous growth hormone does not prevent the steroid effect. A minimal dosage of corticosteroids should always be used in replacement therapy for hypopituitarism.


Immunological and compositional patterns of lipoproteins in chicken (Gallus domesticus) plasma. Immunological and compositional patterns of plasma lipoproteins in the laying and nonlaying hen (Gallus domesticus) and rooster plasmas were compared. Hen plasma contained three immunologically distinct lipoproteins: very low density (CLDL) and low density (LDL); high density (HDL); and lipovitellin (LV). Rooster plasma contained VLDL and LDL; and HDL. Laying hen plasma in comparison to the other groups of birds contained a high content of VLDL and LV. The plasma lipoprotein pattern of nonlaying hens and roosters were similar except for the relatively high content of LDL and the presence of low levels of LV in nonlaying hen plasma. In general, triglyceride, phospholipid and cholesterol contents were similar for each lipoprotein class in laying hen, nonlaying hen and rooster plasma.


Horizontal transmission of turkey herpesvirus to chickens. 5. Airborne transmission between chickens. Airborne transmission of turkey herpesvirus (HVT) between chickens was studied in two trials using an experimental line of White Leghorns. HVT either did not spread or spread poorly to chickens that had been exposed for 8 weeks to the exhaust air from a cage containing donor chickens inoculated with HVT at 8 weeks of age. There was no airborne transmission of HVT to chickens that had been exposed for 4 weeks. This study indicated a possible by an infrequent spread of HVT between chickens via airborne route.


Renal pathomorphology and histochemistry in dog after hemodilution as well as after administration of full blood in extracorporeal circulation in dog. Dog kidneys were studied morphologically and histochemically after hemodilution to a 10--20% hematocrict value and transfusion of whole blood under conditions of extracorporeal circulation ensuring constant (linear) flow. Marked interstitial edema in the dog kidneys after hemodilution was the most pronounced alteration, attributed to disorders in the capillary circulation depending upon the apparatus employed. This conclusion was supported by similar changes in animals subjected to various degrees of hemodilution. Widening of the glomerular space and compression of renal tubules were the direct consequences of interstitial edema. Histochemical reactions revealed damage of the cell membranes. Swelling of the ergastoplasm and lysosomes was interpreted as secondary to disorders in circulation of tissue fluid. The least pronounced changes concerned the mitochondria. After extracorporeal circulation with whole blood, thrombi and fat emboli were observed in the blood vessels of the renal glomeruli, attributable to damage of blood in the extracorporeal circulation apparatus.


Aldosteronemia in patients with acute renal failure. In 19 patients with acute renal failure the plasma renin activity and aldosterone were determined in the phase of anuria and oliguria. A highly increased plasma renin activity was found while aldosteronemia was only moderately raised. No significant correlation was demonstrated between plasma renin activity and aldosterone while a negative correlation was found between aldosteronemia and plasma sodium and bicarbonates concentrations. Lack of significant correlation between plasma renin activity and aldosteronemia in cases of acute renal failure suggests that factors other than renin participate in the regulation of aldosterone secretion in these patients.


[Activators of phospholipase D].

[Activators of phospholipase D]. The activation of phospholipase D from cotton seeds by diethyl ester, sodium dodecyl sulphate and silica gel during egg lecithin hydrolysis was investigated. In the presence of silica gel the enzymic reaction developed without calcium ions. The data were accumulated indicating that the main characteristics of phospholipase D obtained from the in vitro study of the enzymic hydrolysis of phospholipids depended at large on the activator applied.


Biphasic stimulation of polyamine biosynthesis in primary mouse kidney cells by infection with polyoma virus:uncoupling from DNA and rRNA synthesis. Infection of primary cultures of mouse kidney cells with polyoma virus causes a biphasic increase in the activities of L-ornithine decarboxylase (ODC; L-ornithine carboxy-lyase; EC 4.1.1.17) and S-adenosyl-L-methionine decarboxylase (SAMD; S-adenoxyl-L-methionine carboxy-lyase; EC 4.1.50), as well as in the level of the polyamines putrescine, spermidine, and spermine. An early peak occurs during the period when early viral mRNA is synthesized and prior to the onset of virus-induced synthesis of host cell DNA. A late peak coincides in time with the maximum rate of virus-induced synthesis of cellular DNA. A similar biphasic stimulation of polyamine synthesis is induced even when DNA synthesis is prevented by 5-fluorodeoxyuridine. Actinomycin D (AMD) in a dose that inhibits rRNA synthesis causes no inhibition of ODC or SAMD. In a dose that inhibits mRNA synthesis as well, short-term AMD treatment causes "superinduction" of ODC but inhibition of SAMD. Prolonged treatment with the high dose of AMD inhibits ODC as well, indicating that late ODC activity may be dependent on mRNA synthesized during early infection. Cycloheximide effectively obliterates the ODC and SAMD activities during the entire infectious cycle. Uncoupling from DNA and rRNA synthesis suggests that polyamine synthesis is regulated independently of these events. The experiments with AMD and cycloheximide suggest that the formation of ODC is subject to post-transcriptional control, whereas that of SAMD is regulated primarily at the transcriptional level.


DNA gyrase: an enzyme that introduces superhelical turns into DNA. Relaxed closed-circular DNA is converted to negatively supercoiled DNA by DNA gyrase. This enzyme has been purified from Escherichia coli cells. The reaction requires ATP and Mg++ and is stimulated by spermidine. The enzyme acts equally well on relaxed closed-circular colicin E1, phage lambda, and simian virus 40 DNA. The final superhelix density of the DNA can be considerably greater than that found in intracellularly supercoiled DNA.


Dose-dependent depletion of nuclear receptors by L-triiodothyronine: evidence for a role in induction of growth hormone synthesis in cultured GH1 cells. The relationship between the binding of L-triiodothyronine (T3) to nuclear receptors and the induction of growth hormone synthesis was examined in cultured GH1 cells, a rat pituitary cell line. After 24 hr, T3 induced a maximal 4-fold increase in the rate of growth hormone wynthesis; the T3 concentration that induced a half-maximal increase was 0.22 nM. The biologic dose-response curve was shifted to the left of the receptor occupancy curve (Kd = 0.5 nM) by a factor of approximately 2 when receptor binding was examined for 4 hr but showed a significantly closer agreement when examined for the same 24-hr period as the biologic response. This shift in the fractional occupancy curve is not due to further equilibration but occurs as a result of a time- and dose-dependent depletion of the nuclear receptor by T3.


Regulation of dopamine stimulation of striatal adenylate cyclase by an endogenous Ca++ -binding protein. Membranes of rat caudate nucleus contain a dopamine-dependent adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] and a Ca++ binding protein that activates phosphodiesterase (3':5'-cyclic-AMP 5'-nucleotidohydrolase, EC 3.1.4.17). This activator can be released from the membranes by a phosphorylation with a 3':5' cAMP-dependent protein kinase (ATP-protein phosphotransferase, EC 2.7.1.37). Under the conditions of membrane phosphorylation and activator release, dopamine fails to activate striatal adenylate cyclase. The basal activity of this enzyme is not decreased by the release of the protein activator but the activation by NaF is reduced. Adenylate cyclase is not phosphorylated when the dopamine activation is blocked after the release of the activator, but other membrane proteins are phosphorylated. It is postulated that the endogenous protein stored in striatal membranes can regulate the intracellular concentration of cAMP by an activation of adenylate cyclase while stored in striatal membrane, and by an activation of phosphodiesterase when released into the cytosol after membrane phosphorylation.


Purification and characterization of 3':5'-cyclic GMP-dependent protein kinase. Guanosine 3':5'-cyclic monophosphate (cGMP)-dependent protein kinase has been purified to homogeneity from bovine lung by affinity chromatography and characterized. Partially purified protein kinase, specifically activated by low concentrations of cGMP (22 NM), was adsorbed onto 8-(2-aminoethyl)-amino-adenosine 3':5'-cyclic monophosphate-Sepharose. After washing to remove nonspecific proteins, cGMP-dependent protein kinase was specifically eluted by 0.1 mM cGMP. The purified protein contained cGMP-dependent protein kinase and specific cGMP binding activities. Purification of the holoenzyme was possible because subunit dissociation does not occur upon cyclic nucleotide binding. cGMP-dependent protein kinase holoenzyme has an apparent molecular weight of 150,000 as determined by glycerol density gradient sedimentation. On sodium dodecyl sulfate/polyacrylamide gel electrophoresis, a single protein band of 71,000 molecular weight was observed that suggested the holoenzyme is a dimer composed of subunits of identical molecular weight. cGMP-dependent protein kinase required high concentrations of Mg+2 for optimal activity; a heat-stable protein kinase modulator which inhibited adenosine 3':5'-cyclic monophosphate-dependent protein kinase activity had no effect on the activity of purified cGMP-dependent protein kinase.


Negative homotropic cooperativity and affinity heterogeneity: preparation of yeast glyceraldehyde-3-phosphate dehydrogenase with maximal affinity homogeneity. A three-step procedure including affinity chromatography on NAD+-azobenzamidopropyl-Sepharose has been designed for the purification of yeast glyceraldehyde-3-phosphate dehydrogenase [D-glyceraldehyde-3-phosphate: NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12] with maximized specific activity and maximized homogeneity with respect to affinity for the coenzyme, NAD+. Binding isotherms allow the analysis of cooperativity patterns that disclose both the average ligand affinity in the system and the distribution of ligands among the sites, only for systems with complete affinity homogeneity. The presence of affinity heterogeneity, resulting from multiple oligomeric species differing only in their affinity for coenzyme, gives rise to isotherms which falsely manifest apparent negative cooperativity. A method for distinguishing negative homotropic cooperativity from affinity heterogeneity is suggested.


Regulation of mitochondrial protein synthesis by cytoplasmic proteins. Isolated yeast mitochondria, which synthesize identifiable polypeptides identical to those made in vivo, have been used in an invitro system to study cytoplasmic control of mitochondrial protein synthesis. It has been found that protein synthesis in isolated mitochondria is dependent on an endogenous pool of cytoplasmically synthesized proteins present within mitochondria at the time of isolation, that protein synthesis ceases apparently when this pool of proteins is depleted, and that a cytoplasmic extract can restore protein synthesis in depleted mitochondria. By use of depleted mitochondria to assay for stimulatory factors it has been found that the bulk of the stimulatory activity in the cytoplasm is of a protein nature and resides predominantly in the postpolysomal supernatant. At least one cytoplasmic stimulatory protein appears to exert a specific effect on the synthesis of subunits I-III of cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase; EC 1.9.3.1).


Mapping oligonucleotides of Rous sarcoma virus RNA that segregate with polymerase and group-specific antigen markers in recombinants. The RNase-T1-resistant oligonucleotides of two Prague Rous sarcoma viruses with temperature-sensitive (ts) DNA polymerases (DNA nucleotidyltransferases), termed ts LA 337 and 335 of one leukosis virus, RAV-6, and 20 of their recombinant progeny have been mapped relative to the 3' poly (A) terminus of the viral RNA. The resulting oligonucleotide maps have been ocrrelated with markers of the four known viral genetic elements encoded in the RNA of 10,000 nucleotides. In accord with previous results recombinant RNAs contained (i) oligonucleotides characteristic of the src gene, coding for sarcoma formation, between the poly(A) end and 2000 nucleotides and (ii) olignucleotides characteristic of the env gene, coding for the envelope glycoprotein, between 2500 and 5000 nucleo tides from the poly(A) end. (iii) A cluster of four oligonucleotides that mapped between 6000 and 8000 nucleotides from the 3' poly(A) end of each RNA was shared by both parental viruses and all recombinants. Since all other map segments of our recombinants failed to segregate with the ts- or wild-type markers of the parental DNA polymerase gene (pol), it was concluded that the ts pol lesion maps in this RNA segment. (iv) The 5' segment of each recombinant RNA contained a cluster of four to five oligonucleotides whose parental origin correlated with an electrophoretic marker of one of the parental virion proteins, p27, a major product of the viral gag gene. The gene order 5'-gag-pol-env-src-poly(A) is consistent with our data.


Evidence for specific recognition sites mediating clearance of lysosomal enzymes in vivo. A study of the clearance of liver lysosomal enzymes was carried out in the rat. Purified rat liver lysosomal beta-D-glucuronidase (EC 3.2.1.31), N-acetyl-beta-D-glucosaminidase (EC 3.2.1.30), alpha-L-fucosidase (EC 3.2.1.51), and alpha-D-mannosidase (EC 3.2.1.24), as well as rat preputial gland beta-glucuronidase, were infused intravenously into anesthetized rats. All of the enzymes were rapidly cleared from the circulation. Sodium periodate oxidation of lysosomal beta-glucuronidase resulted in a near abolition of rapid clearance, a reduction in concanavilin-A-Sepharose binding, and a reduction in neutral sugar content, accompanied by alteration in isoelectric focusing properties. Similarly, periodate oxidation of lysosomal N-acetyl-beta-D-glucosaminidase resulted in a loss of the rapid clearance property. These results suggest that specific recognition sites occur on lysosomal hydrolases which mediate clearance following intravenous injection, and that these sites involve the carbohydrate portions of the enzymes.


Relationship of gangliosides to the structure and function of thyrotropin receptors: their absence on plasma membranes of a thyroid tumor defective in thyrotropin receptor activity. Plasma membranes derived from rat thyroid tumor (1-8R) which is unresponsive to thyrotropin but is responsive to dibutyryl adenosine 3':5'-cyclic monophosphate bind less than 20% of the [125I] thyrotropin which can be bound to plasma membranes from normal rat thyroids under conditions which optimize tumor membrane binding relative to normal thyroid membranes. In addition, the binding is different from thyrotropin binding to normal thyroid membranes both in its altered sensitivity to changes in hydrogen ion concentration and in a decreased sensitivity to competition by unlabeled thyrotropin. This reduced capacity to bind [125I] thyrotropin cannot be attributed to degradation of the hormone by membrane-associated proteases. Although the supernatant phase of the thyroid tumor homogenates contains a soluble component which inhibits [125I] thyrotropin binding to thyrotropin receptors on plasma membranes, its level is the same as in homogenates of normal thyroid tissue. Trypsin digestion does not expose thyrotropin receptors in a manner analogous to that seen in normal thyroid tissue. The major ganglioside in the tumor membranes is N-acetylneuraminylgalactosylglucosylceramide and the membranes lack the N-acetylgalactosaminyltransferase required for the synthesis of more complex gangliosides. In contrast, the normal rat thyroid membranes contain more complex gangliosides such as galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide and N-acetylneuraminylgalactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosyl ceramide as well as the glycosyltransferase activities required for their syntheses. Galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide can also be detected in normal membranes, but not in tumor membranes, by selective labeling with galactose oxidase (D-galactose: oxygen 6-oxidoreductase, EC 1.1.3.9) and [3H] sodium borohydride. These results support the hypothesis that gangliosides are important structural or functional components of thyrotropin receptors on thyroid plasma membranes.


Changes in microfilament organization and surface topogrophy upon transformation of chick embryo fibroblasts with Rous sarcoma virus. A series of morphological changes occurred when chick embryo fibroblasts infected with the NY68 mutant of Rous sarcoma virus were shifted from nonpermissive temperature (41degrees) to permissive temperature (37 degrees). We observed three distinct stages in cell morphology and surface topography that were correlated with a reduction in the organization and assembly of actin-containing microfilament bundles. Our observations suggest that control of microfilament organization and surface topography are responsive to the presence of a functioning transforming gene (src) product of Rous sarcoma virus.


Alterations in surface glycoproteins and level of sialyltransferase of cells transformed by a temperature-sensitive mutant of simian virus 40. Mouse cells transformed by a temperature-sensitive mutant of simian virus 40 belonging to complementation group A lost their ability to regulate cell growth when grown at the permissive temperature (35 degrees) but showed the low saturation density of cell growth at the restrictive temperature (39.5 degrees) that is characteristic of normal cells in vitro. Biochemical analysis of the membranes of cells grown under the restrictive and the permissive conditions demonstrated no qualitative temperature-dependent differences either in neutral glycolipids or in acidic glycolipids of the cells. Plasma membrane glycoproteins labeled with radioactive glucosamine showed significantly different patterns on both polyacrylamide gel electrophoresis and electrofocusing. When the levels of glycoprotein glycosyltransferases of the cells were examined, the level of sialyltransferase (CMP-N-acetylneuraminytransferase,EC 2.4.99.1) of the cells grown at the restrictive temperature was low compared with that of cells grown at the permissive temperature. Our results indicate that the level of sialyltransferase is under the control of the gene A function of simian virus 40 and consequently is related to alterations in the cell surface glycoproteins.


Quantitative studies of integration of murine leukemia virus after exogenous infection. Using a [3H]DNA probe prepared from AKR murine leukemia virus, we determined the number of copies of the AKR virus genome integrated into the cellular DNA after exogenous infection of NIH mouse, AKR mouse, and rat cells in tissue culture. NIH mouse cells, which lack a portion of the viral genome (referred to as Gross-AKR specific sequences), incorporated three to four copies of these sequences per haploid genome. AKR cells, in which the Gross-AKR specific sequences are already present as three to four copies per haploid genome, did not shwo any distinct change in copy number after infection. Rat cells, which lack DNA sequences homologous to murine leukemia virus, incorporated one copy of the viral genome per haploid genome. It is inferred that the presence of viral sequences may affect the efficiency of integration of exogenous provirus, and that there may be a limit to the number of copies that can be inserted.


Localization of gene functions in polyoma virus DNA. Polyoma virus mutants of four functionally distinct groups have been mapped by the marker rescue technique using restriction enzyme fragments of wild-type viral DNA. Nontransforming host-range mutants map in the proximal part of the early region of the viral genome. The same DNA fragment that restores a normal host range also restores normal transforming ability to these mutants. ts-25D, a temperature-sensitive (ts)-a class mutant, maps in the distal part of the early region. ts-3 and ts-1260 map in the proximal and distal parts of the late region, respectively.


beta-Endorphin: cross tolerance to and cross physical dependence on morphine. The effects of beta-endorphin on the antinociceptive responses and abrupt withdrawal jumping in morphine-dependent mice were studied. Mice were rendered morphine dependent by implantation of a morphine pellet (75 mg base) for 3 days. The analgesic response to beta-endorphin decreased after morphine pellet implantation, as evidenced by an eight-fold increase in the median antinociceptive dose of morphine was found. In small doses (0.09-0.17 mug per mouse), beta-endorphin suppressed abrupt withdrawal jumping. Met-enkephalin, even in high doses (200 mug per mouse), did not suppress abrupt withdrawal jumping.


Plasma levels of a viral protein as a diagnostic signal for the presence of tumor : the murine mammary tumor model. We used the mouse mammary tumor and its associated virus (murine mammary tumor virus) to examine the possibility of using plasma levels of a viral protein (gp52, the glycoprotein of 52,000 molecular weight) as a diagnostic indicator of the presence of a solid tumor. The following features have emerged from our studies: (a) tumor-bearing animals show markedly elevated (100-1000 ng/ml) plasma levels of gp52 and the mean concentration increases with tumor size; (b) mammary tumor tissues located outside the mammary gland are also detected by the elevated plasma gp52; (c) low (2-10 ng/ml) plasma levels of gp52 are found in tumor-free mice, whether they are derived from strains characterized by high or low frequencies of spontaneous mammary tumors; (d) tumor-free lactating females exhibit the normally low levels of plasma gp52 despite the fact that their milk contains an average of 20,000 ng/ml of this antigen; (e) thus, high levels of plasma gp52 are found only in the presence of tumor and are not induced by either predisposition for the disease or by normal production of the antigen during lactation; (f) the circulatory clearance time of gp52 is sufficiently rapid to require continued replenishment to maintain the high levels observed in tumor-bearing animals, a feature implying that the gp52 concentration can be a responsive parameter of disease status. The information obtained suggests that plasma gp52 is a potentially useful and specific systemic indicator of the presence and extent of murine mammary neoplasia.


alpha-Adrenergic regulation of secretion of mouse saliva rich in nerve growth factor. Nerve growth factor has been quantified by both bioassay and radial immunodiffusion in mouse saliva elicited by several secretagogues. The concentrations by bioassay of nerve growth factor in both epinephrine- and norepinephrine-induced saliva (3400 and 900 mug/ml, respectively) are higher than reported in any other source. In contrast, the concentrations of nerve growth factor in isoproterenol- and pilocarpine-induced saliva are relatively low (17 and 2 mug/ml, respectively). The specific activity of the salivary nerve growth factor was 41, 36, 2, and 0.6 mug/mg of protein in secretions elicited by epinephrine, norepinephrine, pilocarpine, and isoproterenol, respectively. Salivation after administration of either epinephrine or norepinephrine was completely inhibited by the alpha-adrenergic blocker, phenoxybenzamine. These results suggest that the release of saliva rich in nerve growth factor is primarily regulated through alpha-adrenergic receptors.


The opiate receptor: a model explaining structure-activity relationships of opiate agonists and antagonists. A model of the opiate receptor is proposed which explains structure-activity relationships of opiate drugs, including (i) the unique potency of certain opiates such as etonitazene, fentanyl, phenazocine, and oripavines; (ii) the role of N-allyl substituents in conferring antagonist properties; and (iii) chemical features that afford "pure" antagonists. The model indicates mlecular mechanisms for interconversion of the opiate receptor between respective states that bind agonists or antagonists with high affinity.


Chemical transmission between rat sympathetic neurons and cardiac myocytes developing in microcultures: evidence for cholinergic, adrenergic, and dual-function neurons. Electrophysiological studies were made on microcultures (300-500 mum in diameter) in which solitary sympathetic principal neurons from newborn rats grew on previously dissociated rat heart cells. Some neurons inhibited,some excited, and others first inhibited and then excited the cardiac myocytes. Application of drugs provided evidence for secretion of acetylcholine by the first group, catecholamines by the second, and both acetylcholine and catecholamines by the third. Solitary neurons which inhibited themyocytes usually excited themselves at nicotinic synapses (autapses).


Relation between oxidative metabolism and slow rhythmic potentials in mammalian intestinal muscle. Intact muscle layers separated from the small intestine of the cat were mounted in a specially designed chamber to measure electrical slow waves and NADH fluorescence simultaneously. Cooling the muscle to 17 degrees eliminated slow waves and simultaneously increased the level of fluorescence. Likewise, superfusing the muscle with a N2-bubbled glucose-free Krebs solution decreased the amplitude of slow waves and concomitantly increased fluorescence emission. In both cases, return to normal conditions reversed the effects on both slow waves and fluorescence. When signals were averaged over 30-70 slow waves, a pattern emerged with the fluorescence oscillations in phase with the electric oscillations. The NADH:NAD+ ratio reached a maximum at the most depolarized point of the slow waves and a minimum at the most polarized point between slow waves. This indicates maximum ATP utilization during the repolarization process. The correlation between redox oscillations and electrical slow wave generation is associated with cell metabolism.


Behavioral depression: thyroid interactions with norepinephrine-depleting drugs. Temporary suppression of rats' bar pressing, activity, and feeding by the dopamine beta-hydroxylase inhibitor FLA-63 was synergistically potentiated by triiodothyronine (T3) treatment. The increased severity of duration of behavioral depression from the combination of mildly-depressing doses of FLA-63 (10 mg/kg, SC) and T3 (200 mug/kg, SC, 4X) was most marked 36-72 hr after FLA-63 and closely resembled the depressive syndrome produced by higher (30-90 mg/kg) doses of FLA-63 alone in timing and specific behavioral features; these depressions were more likely due to toxicity than to depletion of brain norepinephrine. T3 did not potentiate behavioral depression induced by diethyldithiocarbamate (25 mg/kg, SC). This pattern of findings suggested an interpretation of the T3-FLA-63 synergism in terms of increased FLA-63 toxicity in hyperthyroidism.


Neurohumoral correlates of sleep: further biochemical and physiological characterization of sleep perfusates. Twenty cats were prepared surgically with electrodes for recording the EEG, Eye Movements and EMG and a push-pull cannula system in the midbrain reticular formation (MRF) allowing the extraction of perfusates during wakefulness or REM sleep. Proteins in the perfusates were analyzed by Isoelectric Focusing (IEF) polyacrylamide gels and Sodium Dodesyl Sulphate (SDS) slab gels. In addition analysis of glycoproteins was done by gas chromatography. In some cats the contribution of cerebrospinal fluid (CSF) proteins to perfusate proteins from brain tissue was studied by intraventricular injections of labelled leucine. The effect of sleep alterations on the protein cycle during sleep and wakefulness was also studied. The results of these experiments showed that most of the proteins in the perfusates are acidic, and that REM sleep perfusates contain 2 proteins M.W. 73.000 and 45.000 not present in awake perfusates, CSF or serum. It was also shown that CSF proteins do not appear to contribute to the proteins in perfusates, and that altering the sleep wake cycle, induces changes in the rhythm of protein release in perfusates. It is suggested that some relatively large polypeptides may participate in the regulation of REM sleep.


Butanediols: selection, open field activity, and NAD reduction by liver extracts in inbred mouse strains. Mice from the high-ethanol preferring C57BL strain and low-ethanol preferring DBA strain were tested for their preference for butanediols. The C57BL strain showed a significantly higher preference for a 10% (v/v) solution of 1,3-butanediol than the DBA strain. The C57BL strain also showed a significantly greater consumption of 1,2- and 2,3-butanediol, but the separation between strains was much smaller than with 1,3-butanediol. Both strains uniformly avoided 1,4-butanediol. Tolerance for 1,3-butanediol was tested in an open-field monitor at 3 doses. At the lowest dose the DBA strain was hyperactive and the C57BL were unaffected. At the highest dose both strains were equally depressed. The specific activity of NAD reduction on incubation of liver extracts with 1,3-butanediol and ethanol as substrates was higher with both compounds in extracts from the C57BL strain.


[Association of angiomas and osseous abnormalities excluding Klippel-Trenaunay disease]. The author shows that a combination of vascular diseases or anomalies with bone malformations other than the triad described by Klippel and Trenaunay or the Recklinghausen syndrome is not too rare. The author cites half-a-dozen such cases of different types, with anomalies in different parts of the body, from the cranium to the toes. The angiomas varied from naevus vinosus cavernoma, and the bone phy. In some cases the EEG shows pathological features.


[Association of Klippel-Trenaunay and Sturge-Weber syndromes]. A woman aged 46 years, an epileptic, with no family history of hereditary disorders consulted a doctor in 1972 because of an ulcer on the right foot. She presented varices, lengthening of the right leg, and an angioma. The three components of the Klippel-Trenaunay syndrome were present. The angioma also involved the trunk, the right arm and the head where there was predilection for the trigeminal region. Radiograms of the cranium show a "pumice-stone" appearance of the dome and deformation of the sella turcica. The electroencephalogram showed slow waves appearing during hyperpnoea in the right temporo-rolandic region. These different elements made it possible to diagnose the Sturge-Weber syndrome. This association of the Klippel-Trenaunay and Sturge-Weber syndromes did not appear clinically to have been due to chance but appeared to be one disease akin to the phakomatoses. Thus the two syndromes that were associated can each be considered as phakomatosis.


[Use of Doppler ultrasound in the examination of the extent of venous angiomas]. After emphasizing that the treatment of a strawberry naevus in a newborn is usually unnecessary, the author shows the value of the Sonar Doppler in delimiting the extent of pseudovaricose and cavernous, venous angiomas. Arterio-venous fistulas above a certain size can be localized by this procedure. Sometimes these disappear spontaneously (traumatism, thrombosis). On the other hand, the delicate arteriovenous fistulas found in cases of the Klippel and Trenaunay triad are inaccessible to this procedure.


Effect of thyrotropin-releasing hormone (TRH) and antidepressant agents on brain stem and hypothalamic multiple unit activity in the cat. The EEG and MUA (multiple unit activity) of mesencephalic reticular formation (MRF), area hypothalami posterior (PH), and area hypothalami anterior (AH) were studied in chronically implanted freely moving cats. The effects of thyrotropin-releasing hormone (TRH) and some antidepressant agents were tested on neuronal activity. Desipramine and imipramine resulted in a dose-dependent decline of MUA of all structures with the most significant decrease of activity in PH. A single injection of TRH resulted in slight or moderate gross behavioral changes and vegetative excitation lasting for 30-50 min with variable MUA levels. In the course of repetitive TRH treatment on consecutive days the gross behavioral changes and the vegetative symptoms failed to develop by the 3rd or 4th day. By that time the MUA changes of PH and MRF showed similar characteristics in response to TRH administration which was observed following the injection of desipramine and imipramine. The drugs, except for TRH, induced a suppression of paradoxical sleep cycles.


The effect of haloperidol on epinephrine-stimulated adenylate cyclase in humans. Administration of epinephrine in man has been shown previously to lead to a rise in plasma cyclic AMP levels by activation of the beta-adrenergic-stimulated adenylate cyclase. Therapeutic doses of lithium in humans block the epinephrine-induced rise in plasma cyclic AMP levels, suggesting that lithium inhibits beta-adrenergic adenylate cyclase. In contrast, ten subjects receiving haloperidol, a druh also effective in the treatment of mania, show a mean rise in plasma cyclic AMP levels after epinephrine administration and the magnitude of the response is the same as for non-drug treated individuals. These findings are discussed in relation to the possible pharmacological mechanisms of action of lithium and haloperidol in the control of mania.


Routes of calcium movement across the chick chorioallantois. The mechanism of calcium transport across the chick chorioallantois has been studied in vivo. The 15 day old membrane contains no calcium binding protein (CaBP) and attempts to stimulate transport by adding this protein or vitamin D metabolites did not enhance the normal transport process. The mitochondrial and microsomal fractions of transporting cells contain only a small percentage of the 45Ca actually moved across the epithelium and simultaneous measurements of 45Ca and 3H inulin indicate that the bulk movement of fluid is not involved in calcium transport. Calcium appears to be moved after being bound to a protein since strontium and PCMBS both interfere with transport and the membrane shows saturation kinetics. It is suggested that none of the existing theories provides an adequate explanation for the mechanism of calcium transport and some support is given to the possibility that intercellular routes are involved in part of the process.


The distribution and clearances of hormones and metabolites in the circulation of the foetal sheep. Plasma hormone and metabolite concentrations have been measured in the plasma of blood collected simultaneously from the femoral artery, umbilical vein and carotid artery of the exteriorized foetal sheep. The concentration of vasopressin and catecholamines was consistently lower and of glucose, lactate and corticosteroids consistently higher in the umbilical vein compared with the femoral artery. ACTH concentrations showed no consistent pattern and fluctuated widely at each site, but during synacthen infusion the concentration in the umbilical vein was consistently lower than in the femoral artery. For corticosteroids the concentration in the carotid artery was much lower than that in the umbilical vein; the converse was true for catecholamines. Concentrations in the carotid and femoral artery were similar for all compounds investigated. These results indicate that the placenta is a major site of vasopressin, catecholamine and ACTH clearance and of glucose, lactate and corticosteroid production. The foetal liver is probably a major site of corticosteroid and catecholamine clearance.


[Lymphography with oily contrast media. Complications and contra-indications (author's transl)]. Following lymphography pulmonary fat microembolization is regularly found. It is accompanied by hemodynamic pulmonary changes as well as by impairment of respiratory lung function and respiratory metabolism. The risks of complications and several contra-indications are described. To avoid complications explicit precautions are recommended.


Clinical, radiographic and pathologic abnormalities in calcium pyrophosphate dihydrate deposition disease (CPPD): pseudogout. Clinical, radiographic and pathologic abnormalities in calcium pyrophosphate dihydrate deposition disease (CPPD) (pseudogout) are outlined in an investigation of 85 patients with definite or probable disease and available cadaveric and human surgical material. Pyrophosphate arthropathy produced distinctive roentgenographic abnormalities with were most frequent in the knee, wrist and metacarpophalangeal joints. Although the alterations  superficially resembled osteoarthritis, they were frequently more severe and progressive with extensive fragmentation of bone, causing intra-articular osseous bodies. Pyrophosphate arthropathy occurred in unusual locations, such as the radiocarpal compartment of the wrist, elbow, and patellofemoral compartment of the knee. These characteristics allow the radiologist to suggest a probable diagnosis of CPPD even in the absence of articular calcification.


Ultrasound mammography.

Ultrasound mammography. Ultrasound mammography was performed with unique, high resolution equipment which displays changes in acoustic properties of tissues through a calibrated gray scale. Color-coded isodensitometry was used to assist in the differential diagnosis. The rate of agreement between the ultrasound and pathological diagnoses was 86.7%. The false negative and false positive rates were 7.6% and 18.5%, respectively. Three problems must be solved before ultrasound mammography can be used as a screening device: First, additional clinical data must be accumulated. Second, the number of ultrasonograms needed for diagnosis must be reduced. Third, special equipment designed for ultrasound mammography must be developed.


Gray-scale echography for breast cancer. Gray-scale echography offers considerable potential as a diagnostic modality for the visualization of pathological processes in breast diseases such as carcinoma, benign cyst, fibroadenoma, mastopathy and others and is complementary to conventional techniques. Differential diagnosis of breast tumors was carried out based upon the echographic findings such as the boundary echo and shape, internal echo, and retromammary or retrotumorous shadowing. Typical echographic displays for the differential diagnosis of breast tumors from other breast lesions are presented and discussed.


Angiographic demonstration of intrahepatic arterio-portal anastomoses in hepatocellular carcinoma. Hepatic angiograms of 114 patients with hepatocellular carcinoma (HCC) were studied, particularly changes in the portal vein branches. Arterio-portal shunts of varying sizes, evidenced by opacification of intrahepatic portal branches, were seen in 72 cases (63.2%), with retrograde opacification of the portal vein trunk in 29 (25.4%). At least four types of shunts were found: (a) through a tumor thrombus in the portal branch, (b) in a retrograde direction via a peripheral tumor nodule, (c) through a small tumor invading or amputating an artery, and (d) through a tumor located near a major portal vein branch and supplied by a large, coiling artery. Postmortem angiography of the liver in 50 patients with HCC suggests that arterio-portal shunts are the result of the special vasculature in HCC and are highly diagnostic when accompanied by other angiographic changes.


Non-tumorous adrenal hyperfunction: problems in angiographic-clinical correlation. Hyperfunctioning non-neoplastic adrenal glands may be associated with Cushing's syndrome, congenital adrenal hyperplasia, and aldosteronism. The problems in radiographic diagnosis may be resolved by correlation of the angiogram with the clinical and laboratory findings.


Enzyme histochemistry as a link between biochemistry and morphology. The presented paper describes the role of enzyme histochemistry in cell biological investigations. In the first chapter a general discussion has been given about enzyme histochemistry as a connecting link between biochemistry and morphology. The methods available for determination of enzymes in a particular cell or cell compartment have been reviewed. In this respect the characteristics of enzyme histochemistry have been discussed. Furthermore, attention has been paid to the possibilities and limitations of enzyme histochemistry. In chapter two a comparison has been made between histochemically judged and biochemically determined enzyme activities. Some fundamental differences between the biochemical and the histochemical approach in cell biological investigations are dealt with. To correlate histochemically and biochemically determined enzyme activities, a description has been given of the application of histochemical methods on isolated fractions and sucrose-ficoll gradients of these fractions. Several experimental results are described concerning the question whether a relation exists between histochemically and biochemically determined activities of respectively alkaline phosphatase, glucose-6-phosphatase, 5'-nucleotidase and 3ss-hydroxysteroid dehydrogenase. From these results the conclusion could be drawn that in general a good correlation exists between histochemically judged activity per volume (area X thickness) and biochemically determined activity per gram tissue. In chapter three the role of enzymes as markers of cellular particles and as parameters of metabolic pathways is described. Histochemical methods are available for most marker enzymes. Only activities of key enzymes can be regarded as parameters of metabolic pathways. The distribution in sucrose-ficoll gradients of enzymes, regarded as markers of mitochondria, lysosomes, endoplasmic reticulum and plasma membranes has been given. The changes occur ing under different experimental conditions for a number of marker enzymes in rat liver are described. Attention has been given to the contibution of enzyme histochemistry in the study of the heterogeneity of mitochondria, the dual localization of some (lysosomal) enzymes, the complexity of the microsomal fraction, the function of the Golgi apparatus and the heterogeneity and function of plasma membranes. Based on these results and on literature findings the possible role of some marker enzymes in cell metabolism has been discussed. In chapter four problems coherent with species and sex differences in enzyme activities are described. The interpretation of histochemical and biochemical results in view of these differences is discussed. Enzymes characteristic for a given cell type -3ss-hydroxysteroid dehydrogenase in steroid producing cells, ATP-ase in liver plasma membrane surrounding the bile canaliculi - do show less variations between species and sexes than enzymes not directly involved in specialized functions...


[Involution of the mammary gland. Enzyme histochemistry, elektron microscopy and radioautography (author's transl)]. A study has been made of the progress of involution of the mouse and rat mammary gland using histologic, electron microscopic, histochemical and autoradiographic methods. Particular emphasis has been placed on the morphology, metabolic alterations and activities of histochemically identifiable enzymes, and on the pharmacologic effects of lactation inhibiting agents and cytostatic drugs on lactation and involution. In order to allow a systematic investigation, involution was initiated in rats and mice by ligation of individual gland ducts at various time intervals. Both lactating glands and glands in different phases of involution were thus available in a given animal. The most important observation was that involution, which altogether takes approximately 2 weeks to be complete, involves a three-phase process, each phase being clearly distinguishable by morphologic and histochemical criteria. The first phase comprises approximately 4 days during which production of milk may be reinitiated. The second phase starts on day 5 of involution and constitutes the period of involution per se characterized by appreciable parenchymal cell degradation. The third phase, which starts around day 10, is the period of reorganization to the resting mammary gland. Early in the first phase of involution, substantial alveolar enlargement due to engorgement with milk, together with epithelial flattening, are prominent features. By day 3, the glandular contents decrease again in volume, the number of glandular cells and the constituent cytoplasmic organelles remaining unchanged during this period, except for the diminished appearance of fat droplets. In addition to normal appearing vacuoles with only occasional or sparse protein granules, giant vacuoles containing, in part, several hundred casein granules are found. Their formation appears to be due to increased stacking of granules in distended vacuoles prior to dissociation from the Golgi apparatus. In addition, however, the enhanced reactions of alP (alkaline phosphatase) and ATPase, which are found in the apical plasmalemma, are suggestive of resorptive activities. Protein particles absorbed from the glandular lumen equally appear to have a capacity for fusing into large vacuoles. The large protein granule-containing vacuoles regularly exhibit intense beta-Glu activity. This enzyme would appear to contribute actively to the degradation of excess milk during the first phase of involution. Autoradiographic studies reveal that the synthesis and release of proteins into the secretion is maintained for 3 days. While 3H-tyrosine uptake by the alveolar cells continues unchanged, the incorporation of 3H-palmitic acid into glandular lipoids, and of 3H-fucose into glandular polysaccharides is virtually blocked completely. An immediate reaction of the lipoid metabolism is also indicated by the decrease in 3HBDH activity on the first day of involution...


Depression of REM sleep in cats by nisoxetine, a potential antidepressant drug. Nisoxetine, a potent and specific inhibitor of norepinephrine uptake, suppressed REM sleep in cats. Oral doses as small as 0.1 mg/kg were effective during the first 2 1/2 hours of a recording session; 0.25 mg/kg, for 5 hours. The amount of slow wave sleep increased in cats that received 0.1-1.0 mg/kg of nisoxetine. These changes in sleep pattern resemble those reported after treatment with somewhat higher doses of tricylic antidepressants.


Subsynaptosomal localization and biochemical characterization of serotonin binding sites in the brain. The subsynaptosomal distribution of the borohydride stabilizable binding of serotonin (5-HT) in the brain was investigated using various enzyme markers, such as NAD glycohydrolase (NADase), Na+, K+-activated ATPase for synaptic membranes, and monoamine oxidase (MAO) for outer mitochondrial membranes. The gross distribution of the activity of NADase and Na+, K+-activated ATPase in various membrane fractions was found to parallel the distribution of 5-HT binding in these fractions. Radioactivity bound to brain fractions was extractable with chloroform-methanol (2:1). The membranous material was solubilized by chloroform-methanol (2:1) and the recovered material, suspended in 0.32 M sucrose was found to retain its 5-HT binding capacity. The protein-phospholipid nature of the binding subcellular macromolecule was demonstrated with proteolytic and lipolytic enzymes.


Effects of methysergide in cats deprived of paradoxical sleep. Methysergide maleate, a 5-hydroxytryptamine receptor blocker, was administered to cats deprived of paradoxical sleep for 48 hours. During the first six hours after methysergide, the latency to the first slow-wave sleep and paradoxical sleep episodes was increased and total sleep time decreased. The decrease in sleep reflects a loss of paradoxical sleep, while the amount of slow-wave sleep remained unchanged. Slow-wave sleep time, though unchanged in amount, was displaced to the end of the six-hour recording period. These results suggest that paradoxical sleep in cats is more sensitive to methysergide action than is slow-wave sleep.


[Granular cell pituicytoma (choristoma) of the pituitary stalk]. A case of granular cell tumour in the pituitary stalk is described marked by the sudden loss of visual acuity in the left eye, followed by the right years later. A comparison with 17 cases previously published and with cases of asymptomatic granular cell nodules leads the authors to suggest the term granular cell pituicytoma. They discuss the place of this neoformation among other systemic granular cell tumours (granular cell myoblastoma). Fifteen patients were operated on, complete excision being carried out in only three (including the case published). Whether complementary cobalt therapy is useful remains problematical since very few cases have been published because of the slow development of the neoplasm.


Motilin and motilin analogues: mode of action. Natural porcine motilin (13-methionine-motilin) and its synthetic position 13-substituted analogues, 13-norleucine-motilin and 13-leucine-motilin, are of equal efficacy for gastrointestinal motor activity. Pharmacological in vitro analysis reveals that motilin effects on the gastrointestinal muscle are not mediated via nervous pathways but are brought about by direct action of the polypeptide on the muscle cell. As the contractile response to motilin can be abolished by the Ca++ antagonistic compound verapamil, a role for motilin in the transport of Ca++ to the cytosol of intestinal smooth muscle might be considered. Ca++ fluxes seem to be linked to intracellular cyclic guanosine-3':5'-monophosphate and the antagonistic cyclic adenosine-3':5'-monophosphate. By contrast, in motilin-stimulated gastric pepsin secretion, there is no evidence for a mediating role of cyclic nucleotides. It is more likely that the pepsigogic effect is brought about by augmented gastric mucosal blood flow.


Effect of salbutamol inhalations of plasma and urinary cyclic adenosine monophosphate levels in asthmatics and non-atopic controls. Twenty asthmatics and 14 non-atopic controls were given long-acting theophylline tablets, 400 mg twice daily, and were then challenged, after a control period, with 0.5 mg salbutamol as an inhalant, divided in two doses. Urinary and plasma cyclic adenosine monophosphate (cAMP) levels were determined at the beginning of the study, during theophylline treatment and after the challenge with salbutamol inhalation. In neither the asthmatics nor the controls did theophylline alone raise the concentration of cAMP in plasma or its excretion in urine. Inhalation of salbutamol caused a significant rise in plasma cAMP levels in the controls but not in asthmatics. The inhaled sympathomimetic aerosol caused a slight simultaneous rise in urinary cAMP excretion in non-atopic controls, but in the asthmatics. Our results show that sympathomimetics administered directly to the bronchial mucosa do not elicit the same metabolic cAMP response in asthmatics as in controls.


Flexible fiberopitc bronchoscopy in the diagnosis of bronchial carcinoma. Forty-eight patients with primary bronchial carcinomas have been examined, and 41 of these carcinomas (85%) were confirmed by histopathological or cytological tests on samples taken during flexible fiberoptic bronchoscopy. Thirty-seven patients (77%) were diagnosed histopathologically, based on forceps biopsy, and four cases cytologically, based on investigations of bronchial secretions and brush biopsies. In nine of 14 patients with peripheral tumours the diagnosis was verified by flexible fiberoptic bronchoscopy. We find this a very safe and useful method in the early diagnosis of bronchial carcinoma.


Diffusible cholesterol as a risk factor in the biochemical stage of atherosclerosis. The variations of diffusible cholesterol, considered as one of the risk factors involved in the biochemical processes of the subclinical, premorphologic stage of atherosclerosis, were studied in patients with cardiovascular disturbances. To this end, total cholesterol, diffusible cholesterol and beta-lipoproteins were assayed in the blood of 76 such patients and in their children. A correlation was observed between the increase of diffusible cholesterol values and those of beta-lipoproteins. In some of these cases, high diffusible cholesterol values showed a hereditary character.


[Radiological studies in otology].

[Radiological studies in otology]. Skull X-rays with special projections, particularly tomography of the temporal bone, are very helpful procedures in the differential diagnosis of diseases of the temporal bone. Tomography serves to delineate the size and distribution of tumors in the middle or inner ear. Furthermore, in fractures of the temporal bone the fracture line can be seen throughout the entire osseous structure. Special projections are reported for tomography of the temporal bone, with special emphasis on the indications for such procedures. Meatocisternography, a study in which the internal auditory canal is filled with contrast medium, shows defects caused by neurinomas. Indications for angiography (carotid or vertebral) are large neurinomas penetrating the posterior fossa or other tumors of the inner or middle ear, i.e. chemodectomas. A chemodectoma of the jugular bulb can also be demonstrated by jugular venography.


[Hyperlipemia: practical attitudes].

[Hyperlipemia: practical attitudes]. Serum cholesterol and triglyceride levels may vary widely in a given patient, and therefore both of these lipid determinations should be repeated for initial evaluation. Later, the response of lipid values to diet and to drugs provides more information on the individual characteristics of a hyperlipoproteinemia than "typing" from one lipid evaluation. The type may actually change with lipid levels, whereas the basic tendencies to increased betalipoproteins (evaluated as cholesteremia) or prebetalipoproteins (evaluated as triglycerides) are more constant features in a patient. Alimentary conditions in most cases influence hyperlipemias, whether primary or secondary. Total caloric intake is a major factor in inducing augmented triglycerides in predisposed people. Hypertriglyceridemia is rare before 20 and not frequent in women. On the other hand, familial hypercholesteremia is present from the first weeks of life. Diet is of little help in these cases. When hypercholesteremia is related to food habits it usually appears after the third decade. The amount of fats rich in saturated fatty acids appears to be the chief causative factor in this regard. However, it is possible that genetic factors also affect the degree of alimentary influence on cholesterol level over many years. The use of hypolipemic drugs does not obviate the need for appropriate diet. If the prevention of early coronary disease is to be successful it should start in young people before the first clinical symptoms appear.


[Hyperlipemia and diabetes].

[Hyperlipemia and diabetes]. There are several causes for hyperlipemia in the diabetic: (a) an increase in hepatic synthesis of prebetalipoproteins, and (b) reduced elimination of prebetalipoproteins and chylomicrons from the bloodstream, due to diminished activity of lipoprotein lipase in insulin deficiency. The role of heredity has been put in doubt by the observation that diabetes and hypertriglyceridemia are not transmitted by the same genetic factor. The shortterm and longterm implications of diabetic hyperlipemia are discussed, together with the treatment.


[Ambulatory diagnostic methods in disorders of sex maturation]. The most important investigative methods for study of disorders of pubertal development are simple. However, they require a detailed knowledge of the normal course of puberty. In most cases the family history (height of the parents, course of puberty in the father, age at menarche of the mother), personal history (growth curve, height velocity) and physical examination (height measurement, evaluation of stage of pubertal development, bone age) make it possible to decied whether there is benign delayed growth and development (a variation of normal) or whether the patient is suffering from one of the rare types of true hypogonadism (hormonal disorder or types of true hypogonadism (hormonal disorder or chromosomal anomaly). Only when there is strong suspicion of hypogonadism should the expensive and complicated laboratory and chromosome studies be carried out. They serve to detect a disorder of the end organ or of the hypothalamus-pituitary system (determination of testosterone or estradiol, determination of LH and FSH before and after stimulation with the releasing hormone LHRH, determination of growth hormone before and after insulin and arginine, determination of TSH before and after TRH). Although endocrine disorders are rarely the cause of delayed puberty, their diagnosis is important with a view to causal treatment.


[Recent developments in the etiology and diagnosis of Basedow's disease]. The etiology and diagnosis of Grave's disease are briefly reviewed with particular reference to newer discoveries in the wide range of immunoglobulins which might act as humoral stimulators of the thyroid. Diagnosis of hyperthyroidism has been greatly facilitated by radioimmunologic determination of serum T4 and T3 and indirect estimation of T4 (T4 index). In this way 85-90% of cases can be diagnosed with a single blood sample. TRH tests and T3 suppression tests are only rarely required.


Vertebrate central nervous system: same neurons mediate both electrical and chemical inhibitions. Identified goldfish medullary interneurons previously shown to inhibit the Mauthner cell electrically also produce a classical postsynaptic inhibition of that cell. Failure of active spike propagation in the processes of these interneurons underlies generation of the electrical component, and the resultant electrotonic terminal depolarization is sufficient to evoke inhibitory transmitter release.


The renin-angiotensin system and thirst: a reevaluation. Systemic injections of renin that stimulate substantial amounts of drinking in nephrectomized rats can produce plasma renin activities that fall well above the physiological range. Furthermore, increases in plasma renin activities that occur in rats with intact kidneys during experimental hypotension appear to be too low to provide the basis for the observed elevations in water intake. These findings question the contribution of the renin-angiotensin system to thirst under normal physiological conditions.


Synaptic facilitation and behavioral sensitization in Aplysia: possible role of serotonin and cyclic  AMP. The neural changes accompanying sensitization of the gill-withdrawal reflex in Aplysia are associated with presynaptic facilitation at monosynaptic connections between sensory neurons and motor cells. To analyze the molecular mechanisms underlying the facilitation, the pharmacological actions of serotonin, octopamine, and dopamine were examined. Only serotonin enhanced synaptic transmission between the sensory and the motor neurons. A serotonin antagonist, cinanserin, reversibly blocked the synaptic facilitation. The action of serotonin may be mediated by adenosime 3',5'-monophosphate (cyclic AMP). Exposing the ganglion to dibutyryl cyclic AMP or injecting cyclic AMP into the cell body enhances the synaptic action of a sensory neuron. The mechanism of presynaptic facilitation, therefore, may include activation of one or more serotonergic neurons, which enhance the release of a neurotransmitter by increasing the intracellular concentration of cyclic AMP in the terminals of the sensory neurons.


[Septicemia due to Torulopsis glabrata]. The authors report a case of fungal septicemia due to Torulopsis glabrata, an unusual cause of fungus infections. This case was of interest clinically in view of the duration and tenacity of the infection on a surgical unit, where repeated blood cultures were positive for Torulopsis glabrata and the fungus was isolated from other samples during the same period. In the laboratory, the species identified was a common saprophyte of the mucosae and natural cavities of man; it seems to be only rarely pathogenic. Finally the course marked by numerous relapses was later favourable thanks to the use of antifungal agents chosen in the light of laboratory examinations.


[Hodgkin's disease and pregnancy].

[Hodgkin's disease and pregnancy]. The onset of pregnancy raises special problems during Hodgkin's disease and renders difficult full assessment of the extent of the disease. Furthermore acute exacerbations are fairly common, except in patients with a complete remission for more than two years. The critical period seems to be labour and the following weeks. In fact when pregnancy occurs during Hodgkin's disease, one may decide to interrupt it. However, if the patient has been in remission for more than two years, one may allow the pregnancy to continue. The decision will be taken in the light of each case. After pregnancy contraception should be advised in all women with Hodgkin's disease.


[Femoral nerve paralysis complicating anticoagulant treatments. A propos of 3 cases]. The authors report 3 new cases of femoral nerve paralysis complicating anticoagulant treatment. The first sign was pain, the neurological signs occurred later and the patient usually recovered but recovery was sometimes incomplete. The pathogenesis is not clear : a muscle hematoma, ischemia of the nerve trunk, and intraneural hemorrhage are the commonest theories.


[Digestive lesions after abdominopelvic irradiation, in the treatment of cancers of the genital tract]. The authors report 15 cases collected over a few years on a gastroenterology unit, and emphasize the digestive complications occurring after pelvic or abdomino-pelvic irradiation for genital carcinoma. The rectum and pelvic colon are generally affected. The delays of onset after radiotherapy may reach or exceed several months. The vascular lesions, caused by ionising radiation, explain the tissue ischemia and, consequently the failure of local medical treatment. When severe hemorrhage or visceral perforation occur, surgery is necessary. However, sutures often break down on these insufficiently vascularised tissues and re-operation is always associated with a poor prognosis.


[Non-parasitic cysts of the spleen. 2 cases]. Although splenic cysts are benign, a gradual increase in volume of the liquid mass often leads to diagnosis owing to the large volume. The two cases reported are an example of this. A cure was obtained by splenectomy. It is usually easy to carry out and the prognosis is benign.


[Practical value of gastric intubation during peptic ulcer. Analysis of 410 cases, after Histalog stimulation]. This study was carried out in 410 subjects, collecting gastric fluid for one hour, after 15 minutes emptying and one hour, after 15 minutes emptying and one hour's study of basal secretion using, as stimulant, Histalog at a maximal dose of 2 mg/kg without exceeding 130 mg. The object of this statistical analysis was to determine the average figures and the standard deviations of the volumes of secretions, together with those of the output of hydrogen ions in 5 groups of subjects: controls (60), gastric ulcers (38), duodenal ulcers (200), patients suspected of duodenal ulcer (60) or affected by dyspeptic syndrome without radiological nor endoscopic lesions (52). In the normal subject, the hydrochloric acid output was situated between 5 and 27 mEq. The diagnosis of duodenal ulcer was very unlikely when secretion was less than 9 mEq in man and almost certain above 30 mEq.


[New data on the disease induced by laxatives]. The authors report 5 personal case and recall the physiopathological mechanisms of metabolic disorders observed during the abuse of laxatives. They emphasize the fact that electrolyte losses were not only fecal, but also aggravated by frequent use of diuretics or dietary restriction. One may oppose the constant, very marked fall in body potassium to the variation in sodium content of the organism. Oedema formed part of the clinical picture. The withdrawal of drastic laxatives and diuretics, led to rapid recovery of all the symptoms.


[Caustic burn and adenocarcinoma of the esophagus]. Adenocarcinoma of the esophagus is found almost exclusively at the level of the cardia. It is exceptional to find it in the middle part of the esophagus in the absence of involvement of the cardia. In the long term, caustic burns of the esophagus may favour malignant degeneration. The latter is always squamous cell carcinoma. In our patient, a 28 year old man, a cylindrical carcinoma of the thoracic esophagus was detected four years after the ingestion of concentrated sodium hypochlorite. The caustic burn followed by carcinoma were of special significance in this case owing to the development of an adenocarcinoma.


[Sacrocoxitis due to common bacteria].

[Sacrocoxitis due to common bacteria]. The authors report 11 cases of sacro-coxitis due to pyogenic bacteria observed over a period of seven years and emphasize that this is a disease of young women recently in labour, usually due to staphylococci which enter through the genital tract. The other methods of contamination are urinary, cutaneous and dental. The onset is usually acute, pseudoembolic and bacteremia. Whereas the diagnosis is purely clinical as X ray remains normal until the 15th or 20th day, all steps should be taken to identify the germ. With antibiotics, a cure is obtained without sequelae within 3 months. Surgery is only justified if tuberculosis is suspected and in exceptional cases with abscess formation.


[Colitis marginal to cancer. Apropos of 7 cases]. The authors report 7 new cases of colitis above a carcinoma. The study of these cases and of those reported in the literature shows the main pathological characteristics of the lesions and permits discussion of the pathogenesis. Chronic ischemia caused by an increase in intraluminal pressure above the neoplastic stenosis seems to be the main etiological factor.


[Intestinal lesions induced by radiotherapy of malignant pelvic tumors. Apropos of 2 cases]. Intestinal lesions after radiotherapy for pelvic malignant tumours are of two types: ulcerative colitis with stenosis and hemorrhage sometimes sevre and repeated, and ileal involvement with focal ischemic lesions and malabsorption responsible for nutritional disorders. It is difficult to distinguish them from a recurrence of the tumour in spite of endoscopy, arteriography and biopsy. The course in 3 stages is of great value in diagnosis. A reduction in the frequency of such complications may be hoped for by assessment and exclusion of predisposing factors, by strict observance of therapeutic rules. They are serious owing to the marked irreversible conjunctivo-vascular changes and the fragility of the irradiated tissues during operation.


[Value of identification of renal pedicles in the echotomographic study of the normal and pathological pancreas]. The renal pedicles were identified in 83.5% of pancreases during echotomography. The horizontal relations together with the vertical relations represented by the abdominal aorta and inferior vena cava permit one to localise with precision the cephalic and corporeal parts of the pancreas for they are situated just in front. Analysis of the echostructure of the pancreas thus localised is greatly facilitated.


[Conservative surgical treatment in stage 4 arteritis of the lower extremities. Apropos of 26 cases]. The authors report 26 cases (average age 69 years) of stage IV atheroma of the leg arteries for which a conservative surgical operation was attempted. Aortography (18 times) or femoral arteriography (8 times) were performed without difficulty before operation. During the same operation, a single procedure was performed in 15 cases, 2 or 3 procedures were performed in 11 cases. Thus were carried out: sympathectomy in 7 cases, endarterectomy in 8 cases, a by-pass operation in 23 cases. There were 4 deaths (15%) during the postoperative period. In 18 of the 22 patients who survived the operation, trophic disorders completely disappeared, and the functional result assessed with an average follow up of 15 months (1 to 25 months) on the degree of intermitent claudication was judged good or very good in 16 cases, mediocre in 2 cases. In 4 of these 22 patients, the trophic disorders persisted or reappeared in the short term and amputation was then carried out in 3 of these 4 cases. Conservative surgery remains possible and useful in stage IV arterial disease of the lower limbs. It is however important to operate early in the course of the disease after failure of adequate medical treatment.


[Hand, foot and mouth disease].

[Hand, foot and mouth disease]. Two characteristic cases encountered in young adults led the authors to present the hand foot and mouth syndrome. They report the characteristic distribution and vesicular appearance of the lesions. The course was benign. The viral origin of the disease was more or less easily confirmed by cell culture, inoculation in new born mice and demonstration of antibodies. Usually the virus was a Coxackie A 16. However in one of the authors cases, an Echo 11 was demonstrated. The apparent rareness of the disease may be explained by lack of recognition.


Fatal adenovirus pneumonia: Clinical and pathological features. A review of autopsies of 107 young children with pneumonia showed that 15 children (14%) had adenovirus infections, the diagnosis being based on characteristic histopathological and ultrastructural features in the lungs. Eleven (73%) of the cases of adenovirus infection followed on measles infection, and it is suggested that some became infected with adenovirus after admission to hospital. A review of clinical aspects revealed no unique features. Histopathological examination of tissues showed a common picture of necrotising bronchopneumonia, with minor degrees of rental tubular damage, infiltrates of large mononuclear cells in spleen and nodes, and an absence of lymphoid germinal centres. On light microscopy, "rosette" and "smudge" cells were seen in these cases, and two patterns of virus particle distribution in infected cells were seen ultrastructurally. It is postulated that "smudge" cells contain numerous crystalline viral arrays.


Time related response of urinary cyclic adenosine monophosphate to trauma. Urinary cyclic adenosine monophosphate levels were measured in 150 patients with accidental injury of varying causes. Thirty-eight healthy adults of both sexes serving as controls excreted 2.21 to 6.85 micromoles of cyclic adenosine monomphosphate per gram of creatinine, mean 4.34 +/- 1.25. In 120 patients with trauma on admission, the excretion was increased by 15.7 per cent, p less than 0.05, and the changes showed a time related pattern. In patients admitted within the first 30, 60 and 120 minutes after trauma, the mean excretion was changed by 19, 10 and minus 2.8 per cent, respectively, and in those admitted between two and 24 hours by 30 per cent. Twelve patients with differing types of trauma showed a mean 24 hour excretion reaching its peak on the first day, 44 per cent, and declining to its nadir of 2.25 micromoles per gram of creatinine on the third day, minus 47 per cent, p less than 0.01. A second rise reached its peak on the fifth day, p less than 0.05. Thereafter, the excretion fluctuated widely with peaks significantly above and below the control range, and we were unable to correlate these changes with any specific factors. In post-traumatic acute renal failure, the nucleotide excretion fell within several hours and usually reached low values, that is, below 0.25 micromoles per 1,000 milliliters per 24 hours within one to three days. In general, the excretory pattern for cyclic adenosine monophosphate followed that of creatinine clearance, but in the diuretic phase of the recovering kidney, the cyclic adenosine monophosphate levels remained more depressed than those of creatinine. The high sensitivity of urinary cyclic adenosine monophosphate to abnormalities in renal function suggests its potential as a clinical indicator.


Cultured cells in cystic fibrosis research: A review. Cystic fibrosis (CF) is a common inherited disorder which is characterized by the production of exocrine secretions with elevated ion content and abnormally viscous mucus. Over the last few years cells obtained from the peripheral blood or cultured from tissues of cystic fibrosis patients have been used increasingly in the study of the disease. Investigations of the following properties of cystic fibrosis cells are reviewed: morphology, ultrastructure, growth kinetics, cellular metachromasia, the production of ciliary inhibitors, cellular composition, plasma membrane composition, the transport of inorganic ions and small organic molecules, lysosomal enzyme content, and RNA methylation. Studies of the effects on cultured cells and erythrocyte membranes of factors in CF cell culture medium and biological fluids from CF patients are discussed.


Immunochemical studies of the plasma and cultured fibroblast media fractions containing the cystic fibrosis ciliary inhibitor. The cystic fibrosis ciliary inhibitor (CFCI) has been fractionated from plasma of cystic fibrosis (CF) homozygotes and from the media of cultured fibroblasts derived from CF homozygotes. Plasma and fibroblast media from normal controls have been fractionated in an identical manner. Fractions from plasma and fibroblast culture media that demonstrate ciliary inhibitory activity contain several proteins in a molecular weight range of approximately 5,000-11,000. These proteins have been partially characterized by immunochemical analysis with antisera to 33 human serum proteins. Immunological determinants of albumin, C3 (but not C3a), C4, C5, alpha1-lipoprotein, beta-lipoprotein, beta2-microglobulin and immunoglobulin light chains have been detected by hemagglutination in fractions of CF plasma that inhibited ciliary activity and in analogous fractions from normal sera. None of the proteins were detected in media of cultured fibroblasts from either genotype. Since the same proteins and protein fragments were identified in both CF and normal plasma fractions, and were not detected in CF fibroblast media, it appears that none of these proteins can be identified as the CFCI. Identification of these proteins will permit further purification of the CFCI by immunochemical methods.


Surface enzymes in cultured fibroblasts from cystic fibrosis patients. Membrane function was examined in cultured cells from cystic fibrosis patients by assaying several enzymes on intact skin fibroblasts attached to culture dishes. This technique required few cells and minimized disruption of cellular organization. Comparison of enzyme activities of intact and broken cells showed that 12% of total glucose-6-phosphate dehydrogenase, a cytoplasmic enzyme, was measurable using intact cells, while all adenosine monophosphatase was measurable using intact cells. Alkaline paranitrophenylphosphatase activity was divided between the cell surface and interior. Substrate competition experiments indicated that substrate specificities for adenosine monophosphatase and paranitrophenylphosphatase activities were different. Adenosine monophosphatase activities of 2 control and 2 cystic fibrosis strains fluctuated similarly during the cell culture cycle. The apparent Km values relative to adenosine monophosphate were similar in all strains. A chromatographic fraction of serum from a cystic fibrosis patient that was inhibitory to oyster ciliary activity had no effect on adenosine monophosphatase activity of normal fibroblasts. Furthermore, fractions of media from cystic fibrosis homozygote and heterozygote fibroblast cultures were not inhibitory to adenosine monophosphatase activities of intact normal fibroblasts or of part iculate fractions prepared from them. In light of previous studies that showed that factors from cystic fibrosis serum of culture medium disrupted specific membrane activities, it is proposed that the cystic fibrosis factor interacts with the plasma membrane, interfering most conspicuously with the protein functions that are sensitive to changes in their membrane environment.


Diagnostic value of serum angiotensin converting enzyme activity in lung diseases. Serum angiotensin converting enzyme (ACE) activity was measured in 10 patients with early active sarcoidosis, nine patients with inactive or resolving sarcoidosis, 10 patients with malignant pulmonary neoplasms, eight patients with miscellaneous lung diseases, and 18 control subjects with no known pulmonary disease. The serum ACE activity, expressed in units/ml, in control subjects (5-88 +/- 1-84), was no different from the values obtained in patients with inactive or resolving sarcoidosis (6-85 +/- 2-48) or miscellaneous lung diseases (4-61 +/- 3-20). However, the ACE activity was found to be markedly raised in patients with early active sarcoidosis (13-49 +/- 2-52), and there was no overlap with control values. The patients with pulmonary neoplasms had significantly lower values of serum ACE activity than the control subjects (2-80 +/- 3-30).


Effects of subsacute and chronic lead treatment on glucose homeostasis and renal cyclic AMP metabolism in rats. The effects of chronic oral ingestion of lead in doses ranging from 20-80 ppm were compared with those seen after the subacute exposure of rats to a 10 mg/kg daily dose of the heavy metal for 7 days. Irrespective of the treatment regimen used, lead treatment significantly increased the activities of renal pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-diphosphatase and glucose 6-phosphatase. The observed enhancement of kidney gluconeogenic enzymes in chronically treated animals was associated with a stimulation of the adenylate cyclase-cyclic AMP system, a rise in blood blucose and urea as well as a depression in hepatic glycogen and serum immunoreactive insulin (IRI) levels. In contrast, subacute exposure to lead failed to significantly alter cyclic AMP metabolism and the concentrations of liver glycogen, blood glucose, serum urea or IRI. Whwereas the insulinogenic index (the ratio of serum IRI to blood glucose concentration) was markedly suppressed in chronically treated rats, this ratio remained within normal limits following subacute exposure to the heavy metal. However, a marked decrease in the insulinogenic index was observed in subacutely treated rats 15 min after the administration of a glucose load. The data provide evidence to show that increased glucose synthesis as well as suppressed pancreatic function may be responsible for lead-induced disturbances in glucose homeostasis.


Nodular renal blastema, nephroblastomatosis, and Wilms' tumor. Different points on the same disease spectrum? A case of nodular renal blastema developing into nephroblastomatosis is presented. Definitions and histopathology of these entities is given, and it is suggested that they represent a developmental spectrum with natural progression to Wilms' tumor.


[Hepatic tissue respiration in pathology of the biliary system and the effect of hyperbaric oxygenation on the course of hepatic insufficiency]. Under study was the effect of hyperbaric oxygenation in 46 patients on the course of bile tract diseases, complicated with hepatic insufficiency. Hyperbaric oxygenation was found to render a positive effect on the course of hepatic insufficiency.


Immunosuppressive effect of a naturally acquired subclinical bursal agent infection on vaccination against Newcastle disease. A naturally acquired subclinical infection of infectious bursal agent was shown to be the probable causative factor of marked immunosuppression of Newcastle disease vaccine in young chicks. Old hens maintained in the same contaminated environment did not exhibit immunosuppression.


[Concentration of different forms of RNA in the brain and ribonuclease activity of the nuclear, ribosomal and supernatant fractions of brain tissue following the action of cyclic adenosine-3',5'-monophosphate and S-adenosyl-L-methionine]. Quantitative changes of various forms of ribonucleic acids [nuclear (n-RNA), ribosomal (r-RNA), transport (t-RNA)] as well as ribonuclease activity have been studied in rat brain, in its nuclear, ribosomal and supernatant fractions following 3,5-cyclic AMP (c-AMP) and S-adenosyl-L-methionine. These substances were shown to raise the levels of r-RNA in brain and reduce the amount of n-RNA of GC type. c-AMP was also found to reduce the n-RNA of AU type and t-RNA in brain, while S-adenosyl-L-methionine does not affect n-RNA of AU type and raises considerably t-RNA. S-adenosyl-L-methionine has been found to raise the levels of all kinds of RNA while c-AMP has no effect. Ribonuclease activity of nuclear, ribosomal and supernatant fractions (105,000 g) of brain has been found to be enhanced by c-AMP while S-adenosyl-L-methionine raises ribonuclease activity of ribosomal fraction only at pH 7.9. The data obtained indicate that c-AMP and S-adenosyl-L-methionine are of importance in the mechanisms regulating the level of nucleic acids and activity of enzymes involved in their metabolism.


[Role of adenine mono- and dinucleotides in ammonia formation in brain tissue]. The investigations carried out have shown that not only AMP but ADP also undergoes direct deamination in both soluble and mitochondrial fractions of rat brain tissue. Deamination of AMP is stimulated by the addition of ATP and the activity of one of the isoenzymes of AMP-aminohydrolase is markedly enhanced by both yeast and brain hexokinase. Activation by hexokinase is mainly due to its SH groups, through which hexokinase reacts with AMP-aminohydrolase, forming, probably, a protein-protein complex in which AMP aminohydrolase activity is considerably increased. Hexokinase does not affect the deamination of ADP and NAD. Further experiments are needed to find out whether the activation of AMP-aminohydrolase is accomplished by hexokinase itself or by an other protein contaminating it. Deamination of NAD, in contrast to AMP and ADP, takes place only in mitochondria and does not occur in the soluble fraction. In mitochondria besides deamination, AMP and ADP undergo intensive dephosphorylation, while the deamination of NAD is not accompanied by an increase of phosphate, i. e. mitochondria lack enzymes which breakdown NAD to mono nucleotides. Our data indicate that the formation of deamino -NAD from NAD and reamination of deamino-NAD by aspartate to NAD by the formation of intermediary NAD-succinate is of greater importance. The formation of the latter and that of deamino-NAD from NAD as well as the presence of preformed deamino-NAD in mitochondria have been demonstrated by Movsessian. The occurrence of these processes in mitochondria and their role in the formation of ammonia from amino acids is of importance in as much as oxaloacetate formation and its conversion to aspartate, which is necessary for the reamination of deamino-NAD, are localized in mitochondria. The main source of the amino nitrogen of aspartate is known to be glutamate, which incorporates the amino nitrogen of most amino acids. alpha-Keto-glutarate, which is necessary  for the synthesis of glutamate, is also formed in mitochondria are the most favourable site for the formation of ammonia from amino acids with the participation of pyridine nucleotides. Of the purine mono and dinucleotides studied deamino-NAD is most effective in the formation of ammonia from amino acids in mitochondria since in contrast to purine mono nucleotides, deamino-NAD and NAD are not dephosphorylated in mitochondria. According to some authors the reamination of IMP by aspartate is of importance in the formation of ammonia from amino acids in brain tissue. In our studies, however, IMP was not effective in the formation of ammonia from aspartate in mitochondrial fractions. IDP was found to be more effective. IMP and IDP may probably participate in the formation of ammonia in the soluble fraction, where nucleotidase activity is considerably low.


[Soluble cerebral metalloproteins. 1. Purification and properties of cerebral cortex cytochrome c]. Cytochrome c from grey matter of brain has been obtained as a homogeneous preparation by electrophoresis on polyacrylamide gel and following electrofocusing in ampholine solutions. Its molecular weight, content of iron, redox potential and isoelectric point have been established. The absolute spectra of its oxidized and reduced forms are presented. Cytochrome c of brain cortex is similar in its properties to that obtained from other animal tissues as the heart and adrenal cortex.


[Coenzyme specificity and isoenzyme spectrum of lactate dehydrogenase from different regions of the brain]. The coenzyme affinity of lactate dehydrogenase of various parts of rat brain is different to deamino-NAD and NAD as well as to their reduced forms. In direct reactions NAD exhibits a higher activity than deamino-NAD. In the reverse reaction an opposite pattern is observed. The effect of deamino-NADH is much higher than that of NADH. Our studies have shown that the isoenzymes of LDH which are richer in H subunits have a higher affinity for deamino-NAD and deamino-NADH than for NAD and NADH. The isoenzymes of LDH that contain more M forms have opposite properties. LDH-3 does not show a pronounced selective affinity. The data obtained indicate that the activity of LDH and of its 5 isoenzymes varies greatly in different brain parts; crucial changes being observed in the relative percentage of molecular forms of LDH.


[Coenzyme specificity and isoenzyme spectrum of rat brain malate dehydrogenase]. Our studies have shown that malatedehydrogenase of rat brain mitochondrial fraction (M-MDH) and soluble fraction (S-MDH) differ in respect to their coenzyme specificity. Affinity of both M-MDH and S-MDH to deamino-NAD (direct reaction) is about two times lower than toward NAD. In the reverse reaction deamino-NADH and NADH enhance the activity of M-MDH to the same extent while in the presence of deamino-NADH the activity of S-MDH is somewhat higher. The isoenzyme composition of M-MDH and S-MDH have been studied as well as the relative affinity of each isoenzyme towards deamino-NAD and NAD. Both M-MDH and S-MDH have been shown to consist of 3 isoenzymes, the second isoenzyme being the most active. The percentage of the 3-rd isoenzyme is the lowest. The coenzyme affinity of isoenzymes M-MDH and S-MDH have been shown to differ very markedly.


[Course and outcome of treatment of synovial sarcoma]. The results of exploration of 126 patients with synovial sarcoma are reported; males -- 70, females -- 54, aged from 4 to 74 years old. The tumor was found to be localized as follows: the extremities -- 117 (upper -- 33, lower -- 84), and the body -- 9 patients. Seven structural variants of synovial sarcoma were differentiated: 1) alveolar -- 19, 2) adenomatous -- 10, 3) histioid -- 65, 4) perithelial --3, 5) fibrous -- 6, 6) gigantic-cell -- 3 and 7) mixed -- 20 patients. The patients were treated surgically (56 patients) and using the combined technics (70 patients). The most favourable results were noted in treatment of patients with adenomatous and fibrous types of synovial sarcoma, worse issues -- in patients with gigantic-cell and perithelial forms. Synovial sarcomas of histioid and mixed types occupy the intermediate place. The most malignant character of the neoplasm was observed in patients with alveolar tumor.


[X-ray contrast and radioisotope angiography in tumors of the neck]. Comparative results of angiography and radioisotope scintigraphy with technetium (Tc 99 m) in 38 patients having different jugular tumors are reported. Both methods were found to correlate well with respect to the estimation of tutor blood supply. Radioisotope scintigraphy is a more simple, physiological and practically safe method of investigation, and the former should be recommended for estimating the degree of tumors vascularization, the state of brain circulation and also in cases when angiography proves to be unfeasible.


[Transport of heterologous DNA in normal and tumor cells and its modification by radiation]. The authors have studied in a comparative way the kinetics of incorporation of labelled heterologous DNA in tumor and nontumor cells of an identical histological type, obtained from non-irradiated and irradiated with 800 rad rats. It has been shown that the process of incorporation of heterologous high-polymer DNA in cells is somewhat undulatory, and its temporal characteristics and level -- tissue-specific. Difference between tumor cells and their normal prototype show a quantitative character, conditioned by a large surface area. 30 minutes following the irradiation qualitative changes opposite for both kinds of cells were observed in the kinetics of incorporation: an acceleration for lymphoyctes and retardation for Pliss lymphosarcoma and Zajdela hepatoma cells.


[Effect of alkylating chemical substances on the activity and molecular heterogeneity of mouse sarcoma 180 nucleoside phosphate kinases]. The fractionation of extracts from sarcoma 180 cells was carried out on DEAE-cellulose following the administration to tumor-bearing mice of one of chloroctyl amino-phenildioxan derivatives. The tumor regression was noted more than in 50 per cent. It was found that the tumor regression, caused by this alkylating agent, results in marked changes in the fractionation pattern of thymidilatkinases. The origin of these changes is being discussed.


[Heterogeneity of a population of the Kekaya strain of Marek disease virus]. While infecting VMD-Kekava chick fibroblasts cultures two plaque-forming variants of the virus were isolated. Both variants are cell-associated viruses; during a prolonged period these are circulating in the blood of infected chicks, including also healthy ones. The cultures infected contain a common precipitating antigen; sera from the infected chicks have antibodies to VMD feather antigen, both viruses produced, although in a different degree, in the infected chicks lymphoid infiltration of nerve trunks typical for Marek's disease. These variants differ one from the other in the type of plaques formed by them in the tissue culture, and in their pathogenicity for chicks. Variant 83 is likely to be naturally attenuated virus, and further on it may be investigated as a vaccine strain.


[Excretion of cyclic adenosine monophosphate in breast and lung cancer]. The examination of over 150 human subjects failed to reveal any differences in the basal excretion of CAMP between breast cancer and lung cancer patients and the corresponding control. But breast cancer patients show certain disorders in the diurnal rhythm of CAMP production and also in the response of CAMP to euphylline, especially insulin. Moreover, a peculiar impairment of the coordination was noted between the state of fat-carbohydrate metabolism and the character of SAMP excretion in breast and lung cancer. The authors stress the necessity to study not only CAMP basal production in oncological patients but also its synthesis against the background of different functional stimuli and in measures aimed at the correction of disorders in fat-carbohydrate metabolism.


[Extracellular nucleic acid in ascitic experimental tumors]. By using the phenol method, employed for obtaining RNA, the factor possessing electrophoretic mobility close to that of more rapidly migrating conformomer 5 S p-RNA and resistant to the action of pancreatic RNA-s was isolated from noncellular ascitic fluid, Ehrlich and NK/Ly tumors, hepatoma 22a, Zajdela hepatoma, ovarian ascites tumor in rats. This factor is suggested to participate in suppression of antitumor immunity in cancer.


[Effect of an additional whole-body irradiation on the induction of rat liver neoplasms by x-rays]. In direct single exposure of the rat liver to x-rays in the dosage to 4600 r cholangiocellular tumors were induced in 44.4% of animals. An additional total x-ray irradiation in rats in doses of 200 and 400 r increases the incidence of hepatic tumors up to 76.1 and 82.9% accordingly, shortens the latent period and contributes to the appearance of hepatic tumors of various genesis, including hepatocellular ones.