Thiol-disulfide interchange in the binding of bence jones proteins to alpha-antitrypsin, prealbumin, and albumin. Native light Ig chains of kappa- but not of lambda-type form -S-S linked complexes with prealbumin, alpha1-AT and albumin in vivo. kappa-chains isolated from urines have cysteinyls which are more promptly reacting with dithionitrobenzoate (DTNB) than lambda-chains. Both are monomerized on this reaction. On addition to plasma mixed disulfides between both types of light chains and DTNB form larger amounts of complexes than the native chains. The lower reactivity of native lambda-chains to the plasma proteins can be explained by their higher dimer stability. From the light chain reactions obtained with isolated alpha1-AT and albumin it is concluded that alpha1-AT has a disulfide which efficiently interchanges with monomeric, light chain thiolate ions released from thionitrobenzoate derivates of light chains and that on interchange with the derivatized light chains albumin releases more free light chains into the solution than are bound to albumin. Addition of derivatized light chains to a mixture of alpha1-AT and albumin increases the yield of alpha1-AT complexes and decreases the amount of albumin complexes formed. The relative amount of the different complexes formed in the latter experiments corresponds to the findings in vivo in patients with Bence Jones proteinemia. Prealbumin and alpha1-AT in plasma have a roughly 10-fold stronger tendency to link the light chains than albumin. The complexes are formed through thiol-disulfide interchange though neither the disulfide of native alpha1-AT nor the thiols of prealbumin is available for reaction with DTNB. The three plasma proteins may together constitute a system for linkage and transport of peptides with reactive thiols or disulfides released into the extracellular fluids. The trypsin and elastase binding and inhibiting capacity of alpha1-AT remains after cleavage of the internal -S-S-bridge of alpha1-AT through interchange with a light chain thiol for which reason an intact internal -S-S-bridge of alpha1-AT is not necessary for inhibition and linkdage of the enzymes.


Gas transport and blood acid-base balance in diving sea snakes. The values of hemoglobin concentration, Hb-O2 affinity and buffering capacity of the blood of six sea snake species considerably overlap values from terrestrial squamates. Decreased blood pH had little effect on the P50 but increased the n-value of Hb-O2 equilibrium curves. The O2 saturation of blood in the dorsal aorta varied between about 30 and 70% during voluntary diving in Acalyptophis peronii and Lapemis hardwickii. Voluntary dives ended when the lung PP02 was about 50 mm Hg and the arterial PO2 about 30 mm Hg indicating that roughly half of the O2 reserves had been used. In conjunction with relatively stable blood lactate concentration and pH, this indicates that voluntary dives occurred largely aerobically. In contrast, forced dives resulted in depletion of O2 reserves and large changes in blood acid-base balance. Long recovery periods following forced dives are inconsistent with field observations and thus suggest that extensive anaerobic metabolism does not normally occur in sea snakes. Bradycardia was not evident during forced dives. Large differences in PO2 between the lung and dorsal aorta indicated considerable right to left shunting either in the heart or in the lung. Venous blood represented over 50% of the systemic flow when there was considerable O2 in the lung. Therefore blood PO2 may remain relatively low despite elevated lung PO2 resulting from diving. In view of substantial capability for extra-pulmonary gas exchange, high shunting reduces the possibility of losing O2 through the skin and also may help prevent decompression sickness following deep dives.


The effect of coenzyme leakage and replacement on the growth and metabolism of two fusobacteria. Suspensions in water of two species of Fusobacterium leaked several coenzymes when incubated at normal growth temperatures. Chromatography of filtrates from these suspensions revealed the presence of NAD, NADP, FMN, tetrahydrofolic acid and, in one of the two, pyridoxal phosphate. Analyses of some enzymic activities in whole organisms demonstrated deficiencies in coenzymes:glutamate dehydrogenase was virtually inactive in the absence of added NAD; tryptophanase activities were diminished by washing but the extent differed between strains; histidase activity was not decreased by washing or suspension in water or saline. Both lag phase and doubling time increased markedly in severely washed organisms inoculated into fresh medium. Addition of appropriate coenzymes shortened the lag phase for both strains and shortened the doubling time in one.


Extremely thermophilic acidophilic bacteria convergent with Sulfolobus acidocaldarius. A series of extremely thermophilic acidophilic bacteria has been characterized as closely resembling the species Sulfolobus acidocaldarius except for a totally different guanosine-cytosine content in the DNA; some conceptual consequences of this situation are discussed. Both organisms also share special features, including a very characteristic type of ether lipid, with other extreme acidophilic thermophiles.


Ammonia assimilation by rhizobium cultures and bacteroids. The enzymes involved in the assimilation of ammonia by free-living cultures of Rhizobium spp. are glutamine synthetase (EC. 6.o.I.2), glutamate synthase (L-glutamine:2-oxoglutarate amino transferase) and glutamate dehydrogenase (ED I.4.I.4). Under conditions of ammonia or nitrate limitation in a chemostat the assimilation of ammonia by cultures of R. leguminosarum, R. trifolii and R. japonicum proceeded via glutamine synthetase and glutamate synthase. Under glucose limitation and with an excess of inorganic nitrogen, ammonia was assimilated via glutamate dehydrogenase, neither glutamine synthetase nor glutamate synthase activities being detected in extracts. The coenzyme specificity of glutamate synthase varied according to species, being linked to NADP for the fast-growing R. leguminosarum, R. melitoti, R. phaseoli and R. trifolii but to NAD for the slow-growing R. japonicum and R. lupini. Glutamine synthetase, glutamate synthase and glutamate dehydrogenase activities were assayed in sonicated bacteroid preparations and in the nodule supernatants of Glycine max, Vicia faba, Pisum sativum, Lupinus luteus, Medicago sativa, Phaseolus coccineus and P. vulgaris nodules. All bacteroid preparations, except those from M. sativa and P. coccineus, contained glutamate synthase but substantial activities were found only in Glycine max and Lupinus luteus. The glutamine synthetase activities of bacteroids were low, although high activities were found in all the nodule supernatants. Glutamate dehydrogenase activity was present in all bacteroid samples examined. There was no evidence for the operation of the glutamine synthetase/glutamate synthase system in ammonia assimilation in root nodules, suggesting that ammonia produced by nitrogen fixation in the bacteroid is assimilated by enzymes of the plant system.


Glucose repression of enterotoxins A, B and C and other extracellular proteins in staphlyococci in batch and continuous culture. The production of enterotoxins, lipase and total extracellular protein by four strains of Staphylococcus aureus grown in batch culture at a controlled pH of 6.5 in a completely defined medium was markedly reduced by glucose or glycerol constantly maintained at 0.I M. A concomitant increase in the production of deoxyribonuclease, up to 13-fold, showed however that not all extracellular proteins are under the same control mechanism. The presence of glucose and glycerol in the medium also resulted in a rapid increase in the specific growth rate. However, growth of S. aureus s6 in Mgilimited continuous culture showed that glucose repression of enterotoxin B when the growth rate was held constant was more than twice that in batch culture. Therefore glucose repression can occur independently of an increase in growth rate. The specific rate of production of enterotoxin B, lipase, deoxyribonuclease, beta-haemolysin and total extracellular protein by S. aureus s6 increased as the growth rate increased from 0.07 to 0.24 h-1. Non-replicating cells grown in the absence of glucose produced considerable amounts of enterotoxin, and production was not repressed by the presence of glucose in the resuspension medium. In contrast, no enterotoxin B or C was obtained from nonreplicating cells grown in the presence of glucose. Chloramphenicol completely inhibited enterotoxin production by non-replicating cells, indicating that synthesis of new protein was required.


Enzyme electrophoretograms in the analysis of taxon relatedness of Micrococcus cryophilus, Branhamella catarrhalis and atypical Neisserias. Extracts were prepared from Micrococcus cryophilus, several strains of Branhamella catarrhalis and Neisseria spp. Esterases, NADP-dependent isocitrate dehydrogenase and malate dehydrogenase activities were assayed after electrophoresis of extracts of polyacrylamide gels. Except for Neisseria perflava and N. sicca which resolved activity bands for the acetate-esterase only, the remaining bacteria exhibited species-specific esterase patterns also for the propionate and butyrate substrates. The multiple esterase patterns from B. catarrhalis ATCC25238 were qualitatively and quantitatively different from those of B. catarrhalis ATCC23246. This finding and other evidence supports a taxonomic shift of the latter to a species level of that genus. The atypical neisserias N. caviae and N. ovis appeared to exhibit an intrageneric specificity in their esterase patterns with those from B. catarrhalis but not to the other Neisseria spp. tested. The malate dehydrogenase patterns from the atypical neisserias and B. catarrhalis ATCC23246 were qualitatively similar; however, the patterns of isocitrate dehydrogenase activity were variable for these species. Micrococcus cryophilus was distinct in its esterase and dehydrogenase bands, strongly suggesting its taxon unrelatedness to the genus Branhammella or the atypical neisserias. Of the enzymes assayed, esterase proved to be the most reliable for taxonomic identifications.


Microbial water relations. Effects of solute concentration on the respiratory activity of sugar-tolerant and non-tolerant yeasts. The respiratory activity of the sugar-tolerant (osmophilic) yeast, Saccharomyces rouxii, and the non-tolerant species, Sacchromyces cerevisiae, were compared after growth in a complex basal medium, the medium supplemented with polyethylene glycol (mol. wt 200) to give a water activity of 0-95, and the medium supplemented with glucose (24 and 36%, w/v). The properties compared were Qo2 (glucose), NADH oxidase activity of isolated mitochondrial fractions, and cytochrome content. When grown in the basal medium S. cerevisiae was somewhat more active than S. rouxii by all criteria. Growth in the media supplemented were high glucose concentrations produced catabolite repression of respiration in S. cerevisiae but not in S. rouxii. The implications of this difference for polyol biosynthesis and the water relations of the sugar-tolerant species are discussed.


The basis of the alkalophilic property of a species of bacillus. An alkalophilic bacterium belonging to the genus Bacillus was isolated from an indigo ball. The bacterium exhibited a maximum growth rate at pH 10-0 TO 10-5. The incorporation of 14C-labelled amino acids or [14C]uracil, uptake of 14C-labelled alpha-amino isobutyric acid into the bacterium and oxygen consumption of the bacterium with amino acids as substrates were all maximum at pH 9-0 to 10-5. The uptake of [U-14C]glucose into the organism and oxygen consumption with carbohydrates, on the other hand, showed little variation of rate in the pH 8 to 10 region. The oxygen consumption of intact bacteria or protoplasts in culture medium was maximum at pH 10. The membrane of the bacterium oxidized NADH maximally at pH 7-5, and ATPase bound to the membrane exhibited maximum activity at pH 7.L-Lactate, L-alanine and malate dehydrogenases in the soluble fraction exhibited maximum activities at pH 7-4 to 8-4. The alkalophilic property of the bacterium may be due to the behaviour of the membrane towards charged substances admitted into the organisms.


Physiological studies on the pneumococcal Forssman antigen: a choline-containing lipoteichoic acid. The cell concentration and possible biological activities of the pneumococcal Forssman (F) antigen (membrane lipoteichoic acid) were examined in a number of physiological situations. In test tube cultures of pneumococci the concentration of the Forssman antigen per bacterium showed no significant fluctuations within a typical culture cycle. Purified F antigen had no effect on the activation of pneumococci to competence for genetic transformation, DNA mediated genetic transformation or adsorption of the  pneumococcal phage Dp-1 to bacteria. Pneumococci grown in the presence of different amino alcohols (ethanolamine, N-monomethylethanolamine, or choline) exhibit differences with regard to both their ability to stimulate heterophile (haemolytic) antibody production in rabbits and in their ability to bind such antibodies. Choline-grown bacteria seem to cross-react with sheep red blood cells better than do the analogue-grown bacteria.


The structural gene for NADP L-glutamate dehydrogenase in Aspergillus nidulans. A total of 41 mutants lacking NADP L-glutamate dehydrogenase (NADP-GDH) activity have been studied. All the mutations were located at the gdhA locus within 0-1% recombination of gdhAI. Two mutants, gdhAI and gdhA2, out of five examined, produced cross-reacting material which neutralized NADP-GDH anti-serum. The mutant gdhA9 has altered Km values for all five substrates: ammonium, alpha-ketoglutarate, l-glutamate, NADPH and NADP. The mutant gdhA20 had temperature-sensitive growth, abnormal ammonium-regulation characteristics and thermolabile NADP-GDH activity. These results show that gdhA is the structural gene for NADP-GDH.


Enniatin production by Fusarium sambucinum: primary, secondary, and unitary metabolism. Fusarium sambucinum liquid surface cultures on semi-defined medium with glucose as carbon source passed through well-defined phases corresponding to trophophase, idiophase (enniatin production), and a degenerative phase. All the glucose was consumed by day 6, at which time the mycelial dry weight had reached only half its maximum. When glucose was replaced by lactose, there was no separation of trophophase and idiophase. Enniatin production, dry weight, and sugar and nitrogen consumption were in approximate balance throughout the growth period (25 days), after which slow degeneration began. The term 'unitary metabolism' is proposed for this type of unphased behaviour. Unitary metabolism may approximate more closely to that occurring under natural conditions than does the metabolic phase separation observed when rapidly utilized carbon sources are used in laboratory cultures.


Use of 6-hydroxydopamine to create lesions in catecholamine neurons in rats. The authors report experiments in rats with 6-hydroxydopamine (6-OHDA), a chemical agent used for creating lesions in catecholamine neurons. Stereotaxic injection of 6-OHDA into the compact zone of the substantia nigra induced degeneration of the nigrostriatal dopamine (DA) system, confirmed by histology and histochemistry of the substantia nigra and by dopamine determinations in the neostriatum. These observations closely mimic those found in Parkinson's disease. In the experimental model a rotatory behavior is induced by DA agonists; this response has been used to test drugs for potential therapeutic use and also in basic studies of the extrapyramidal system. This technique may be useful in developing other experimental models for neurosurgical problems involving catecholamine pathways.


Radionuclide detection of a pheochromocytoma. An area of increased radioactivity was visualized superior to the right kidney during the flow phase of a routine radionuclide renal angiography using 99mTc-Sn-DTPA. This same area failed to concentrate the radiopharmaceutical during delayed static images. This sequence suggested a highly vascular mass above the right kidney. The mass proved to be an adrenal pheochromocytoma as was suggested by the radionuclide study.


Cisternographic imaging patterns: effects of partial extra-arachnoid radiopharmaceutical injection and postinjection CSF leakage. A cisternographic pattern of subarachnoid block with transient or no ventricular radiopharmaceutical reflux was observed in 52% of 105 patients with partial extra-arachnoid injections or postinjection leakage of CSF or both at the lumbar puncture site. In several patients, adequate repeat studies demonstrated considerably different CSF flow patterns. This block pattern was seen in only 11% of 217 patients with adequate intrathecal injections. Lumbar CSF leakage may alter the pattern seen on a cisternographic study and, if present, the study should be interpreted with caution.


Steroid effect on the brain scan in a patient with cerebral metastases. A case of cerebral metastases is presented in which the initial brain scan did not demonstrate the lesion because steroid medication had been started 18 hr earlier. The lesion was seen after the patient had been off medication for several days. Therefore, brain scans should be performed prior to starting or following the removal of steroid medication for several days in order to avoid false-negative results secondary to steroid effects.


Alteration of porcine skin acid mucopolysaccharides in zinc deficiency. Zinc deficiency is overtly manifested as a dermatitis in swine; therefore, the purpose of this investigation was to determine possible zinc-related alterations in the metabolism of the skin acid mucopolysaccharides (AMPs). Eighteen 4-week-old Yorkshire pigs were randomly allocated to one of three dietary treatments. Six animals were fed a semipurified, zinc-deficient, basal diet containing 20 ppm zinc. Six animals served as pair-fed controls and were fed the basal diet supplemented with 90 ppm zinc as zinc carbonate. The remaining six animals were fed the zinc-supplemented diet on and ad libitum schedule. All animals were killed after 36 days when overt deficiency symptoms were apparent in those animals fed 20 ppm zinc. Skin AMPs were isolated. Total hexosamine and galactosamine indicated no alteration in total AMPs. Fractionation of total AMPs into consitituent sulfated and nonsulfated components revealed a significant increase in hyaluronic acid. No statistical difference in sulfated AMPs was found in skin from deficient and pair-fed animals, which was in accord with an in vitro sulfur-35 uptake study.


Inflammatory disease of the colon: ulcerative colitis and Crohn's colitis. Ulcerative colitis differs from Crohn's colitis in several ways. In ulcerative colitis the disease is limited to the mucosa and, occasionally, the submucosa; Crohn's colitis may involve all layers of the large intestine. Ulcerative colitis almost always begins in the rectum, is diffuse, and spreads proximally. Crohn's colitis may spare the rectum and has a patchy distribution. Perianal fistulas and ulcers are rare in ulcerative colitis but are common in Crohn's colitis. Granulomas and giant cells are not found in ulcerative colitis but are seen in the majority of patients with Crohn's colitis. Colonic and extraintestinal symptoms in the two illnesses may be indistinguishable but growth failure is far more severe in Crohn's colitis and may precede intestinal symptoms by months to years. Cancer of the colon is a risk in patients with either ulcerative or Crohn's colitis but is far more common in the former. It is important to distinguish between ulcerative colitis and Crohn's colitis because response to treatment and prognosis are different. Although neither condition can be cured by medical management, patients with ulcerative colitis may respond more frequently. Unfortunately, in the pediatric age range most cases of ulcerative and Crohn's colitis may be classified as moderate to severe. Fortunately for patients with ulcerative colitis, total colectomy with ileostomy will result in cure of illness. Patients with Crohn's colitis who require surgery may obtain remission of symptoms, but the disease is likely to recur in the small intestine.


A common factor in the MMPI scales of married couples. Using canonical analysis, a common factor in the MMPI scales of husbands and wives was found. The Sc, Pd, and Hs scales for both the husbands and the wives contributed heavily to the relationship. Other scales contributing to the correlation between the personality components of the pairs were F, Hy Pt, and Si for the husbands and Pa for the wives. The results were interpreted as indicating areas of homogeneity and heterogeneity in the personalities of married couples.


Immunologic induction of malignant lymphoma: identification of donor and host tumors in the graft-versus-host model. Primary lymphoid tumors were induced by inoculation of parental line spleen cells into H-2 incompatible F1 hybrid mice. The genotypes of lymphomas arising in 19 different parent yields F1 combinations were determined with cytotoxic antisera against H-2 specificities of donor and host. Additional chromosome marker studies established the reliability of tumor genotyping by the cytotoxicity test. According to H-2 typing, 12 primary lymphomas were of donor type, 66 of host type, and 14 of intermediate type. As a group, those parent yields F1 combinations in which donor-type lymphomas developed (group 1) showed a higher degree of histocompatibility between donor and host than those combinations in which donor-type lymphomas failed to appear (group 2). Allogeneic inhibition may have suppressed the development of donor-type tumors in the combinations of group 2. The development of malignant lymphomas of donor-type in the graft-versus-host reaction (GNHR) supports the concept of lymphomagenesis as a consequence of persistent stimulation by antigen.


Interaction between aromatic diamidines and nucleic acids: possible implications for chemotherapy. Interaction between aromatic diamidines (pentamidine, propamidine, and stilbamidine) and nucleic acids were studied to elucidate the mechanism underlying renal toxicity included by pentamidine in patients. Pentamidine, propamidine, and stilbamidine precipitated with RNA and DNA of all species and types. Furthermore, the diamidines interacted and precipitated with all nucleoside triphosphates and nucleoside diphosphates, but not with nucleoside monophosphates, nucleosides, or free bases. Nucleoside diphosphate is the minimum unit necessary for interaction with the diamidines. This interaction between diamidines and nucleotides or nucleic acids may be implicated in the etiology of renal damage and skin reactions associated with these drugs.


Stability of nitrosamines in samples of lake water, soil, and sewage. N-nitrosodimethylamine, N-nitrosodiethylamine, and N-nitrosodi-n-propylamine were resistant to degradation in soil, sewage, and lake water. No degradation of these nitrosamines was observed in lake water during a 3.5-month period. A lag of nearly 30 days occurred before their slow disappearance from soil; they disappeared slowly from sewage, but a minimum of 50% remained after 14 days. The results with sewage and soil suggesta a microbial involvement in the slow decomposition of these nitrosamines.


Suppression and regression of a transplanted tumor in the guinea pig colon mediated by Mycobacterium bovis, strain BCG. The growth in the colon wall of a diethylnitrosamine-induced hepatocarcinoma was suppressed by BCG. Injection of BCG into established colon-wall tumors caused tumor regression. Successful therapy required a limited tumor burden. Guinea pigs in which growth of the neoplasm was suppressed at the site of BCG infection developed systemic tumor transplantation immunity.


Interaction of Sindbis virus with liposomal model membranes. Radiolabeled Sindbis virus was found to bind to protein-free lipid model membranes (liposomes) derived from extracts of sheep erythrocytes. The virus interaction was dependent on initial pH, and the range of pH dependence (pH 6.0 to 6.8) was the same as the observed with virus-dependent hemagglutination. After the initial interaction, pH changes no longer influenced the virus binding to liposomes. Virus bound to liposomes prepared from a mixture of erythrocyte phospholipids, but the binding was greatly diminished when either cholesterol or phosphatidylethanolamine was omitted from the liposomal lipid mixture. It was concluded that phospholipids and cholesterol, in a bilayer configuration, may be sufficient for specific virus binding in the absence of membrane protein.


pH stability studies with avian infectious bronchitis virus (coronavirus) strains. A comparison of 17 infectious bronchitis virus strains, using the same test procedure and assay system, demonstrated that stability at an acid pH is a variable characteristic of the avian coronaviruses.


Electron microscopy of simian virus 40 DNA configuration under denaturation conditions. After isolation, the DNA of simian virus 40 appeared as a negative supertwist (form I) or as an open circle with at least one single-strand scission (form II). Under the denaturation conditions usually applied, such as heating in the presence of formaldehyde or application of alkali, form I molecules could appear as "relaxed" circles without single-strand scissions (form I') containing denatured sites not visible under the electron microscope. Form II molecules, under these denaturation conditions, showed partial or complete strand separations allowing the construction of denaturation maps. By using a modified denaturation procedure, i.e., heating of isolated SV40 DNA in the presence of dimethyl sulfoxide and formaldehyde followed by keeping the DNA in this denaturation solution at room temperature for periods up to 3 weeks, partially denatured relaxed circles without single-strand scissions were produced (form I'D) in addition to completely denatured form II molecules. The absence of single-strand scissions in form I'D molecules was demonstrated by a second heat treatment, which did not change the configuration of this molecular form. Form I'D molecules, in contrast to form I', contained denatured sites clearly discerible under the electron microscope. This combined application of two subsequent denaturation steps (denaturation by heating followed by denaturation at room temperature and neutral pH) showed that the molecular configuration I'D originated in two steps. The heating procedure produced molecules not distinquishable by electron microscopy from form I. In contrast to form I, these molecules were assumed to possess "preformed" denaturation sites (form I). Further treatment of form I molecules with denaturation solution at room temperature finally transformed them into convalently closed, relaxed, partially denatured circles exhibiting strand separations easily measurable on electron micrographs (form I'D). Denaturation maps of form I'D molecules were constructed by computer and compared with denaturation maps derived from partially denatured form II molecules. From these denaturation maps it can be concluded that the melting of base pairs occurring during the transition of simian virus 40 DNA form I into form I'D also preferentially happened at sites rich in the bases adenosine and thymine.


Left and right ventricular volumes in A-V block, and their changes induced by the infusion of isoproterenol. In mongrel dogs (14.5 to 26.3 Kg) during complete heart block and right ventricular pacing, the cardiovascular dynamics were observed with the effect of isoproterenol infusion (8 mug/min intravenously). During complete heart block, cardiac output 2.01 plus or minus 0.17 L/min, heart rate 57.6 plus or minus 3. 5 beats/min, and stroke volume 35.5 plus or minus 2%. Left ventricular (LV) residual fraction was 54 plus or minus 2%. LV end-diastolic volume (EDV) IN WHich almost complete filling is performed due to the long filling period was 4.01 plus orminus 0.35 ml/Kg by thermodilution method. Right ventricular (RV) residual fraction and EDV were 39 plus or minus 3% and 3.01 ml/Kg, which were significantly smaller than the left. Infusion of isoproterenol increased cardiac output (2.67 plus or minus 0.21 L/min), heart rate (66.9 plus or minus 3.5 beats/min), and stroke volume (40.4 plus or minus 3.1 ml), but both ventricular residual fractions and EDV's didnot change significantly, although mean blood pressure decreased remarkably. During right ventricular pacing the effects of isoproterenol were essentially the same as in complete heart block except no change of heart rate and relatively improved cardiac functions. The plots of derived force-velocity relationship expressed in normalized mean circumferential shortening rate (MCSR) and peak ventricular force (F) showed that isoproterenol increased the velocity of shortening of muscle contraction significantly without significant change of F, while increase of heart rate didnot. It is concluded that isoproterenol affects the myocardium mainly throughits direct action and the improvement of contractile state via positive chronotropic effect (Bowditch's effect) is relatively small.


Hyperreactive arterial endothelial cells in atherogenesis and cyclic AMP phosphodiesterase inhibitor in prevention and treatment of atherosclerotic disorders. The hyperreactive arterial endothelial cells have been introduced in this paper. They are characterized by their ability to transport particles too large for the small holes of the internal elastic lamina locating underneath the endothelial cells, such as carbon particles with the similar size of LDL, floating beta-lipoprotein, Lp(a) and especially of VLDL, into the subendothelial space from the blood stream by their abnormally strong contracting and phagocytosis-like activity. Large particles such as carbon particles with a size of 200 to 700 angstrom are too large to penetrate further through holes of the internal elastic lamina from the subendothelial space to muscular layers of the arterial wall, resulting in stagnating for a long time in the subendothelial space, thus showing the atherogenic property of the hyperreactive arterial endothelial cells. Such endothelial cells appear spotty and streaky in the localized endothelial lining of predominantly susceptible parts to atherosclerosis in susceptible animal species such as rabbit, chicken, and rhesus monkey especially densely in their atheromatous lesions, but do not generally appear in non-susceptible animals to atherosclerosis like rate and dog. They are extremely few in infant rabbit, but increase by age.They appear in hypertensive rat, showing a characteristic distribution even in small groups of arteriessuch as the circle of Willis. Cyclic AMP, and especially dibutyryl cyclic AMP, exhibited an inhibitory effect on the hyperreactivity of those cells. Cyclic AMP phosphodiesterase inhibitors, EG467 and eg626, exhibited a powerful inhibitory effect on the contracting and phagocytosis-like activity of those cells, as in the case of pyridinolcarbamate, which enhances enzymes to produce ATP and inhibits slightly cyclic AMP phosphodiesterase, although its inhibitory effect on cyclic AMP phosphodiesterase is weaker than that of EF467 and EG626. The usefulness of the inhibitors on cyclic AMP phospodiesterase of arterial endothelial cells and platelets and on that of brain, such as EG467 AND EG626, has been suggested in the treatment of atherosclerotic disorders, especially of cerebral atherosclerosis. Some of the hitherto desperate mental disability of the aged seem to be a promising target for treatment with cyclic AMP phosphodiesterase inhibitors.


[Equation of the helix for separating plants in a spiral-radial cultivator]. Highly effective and compact cultivators must pullapart plants during vegetation in order to save light energy and area under crops. Cultivators ensuring a helical method for pulling plants apart are already available. The present paper suggests the criteria of the efficiency of using the area under crops of the cultivator and deformation of the leaf crown of plants (sigma- and delta-spectra). With respect to these values the main task of calculating the helix has been formulated. Having Chinese cabbage as an illustration, an equation of the helix has been derived. With the aid of the equation an optimal helix can be marked along the circle in polar coordinates.


Mitochondrial changes in dog myocardium induced by lowered pH in vitro. The effects of increased acidity and of lactate at acid pH values on the ultrastruct of normal dog myocardium were investigated using a simple in vitro system. Thin tissue slices incubated in isotonic, phosphate-buffered sodium chloride at pH 6.5, 6.8, or 7.0 developed within 10 minutes electron-dense mitochondrial inclusions resembling those seen in dog heart muscle after 40 or more minutes of ischemia. Mitochondria of tissue incubated in a comparable medium incorporating 3000 mu g. of lactate per ml. showed similar electron-dense inclusions, together with marked swelling. These results indicate that lowered tissue pH alone is not responsible for the mitochondrial changes typical of ischemic heart muscle. Since an earlier study has shown that marked mitochondrial swelling without dense granule formation can be produced by incubation of tissue in lactate at physiologic pH, it seems likely that the swelling of mitochondria in ischemic myocardium is due to the accumulation of lactate anions, whereas the development of the mitochondrial inclusions is associated with decreased pH.


Landé-Edwards membrane oxygenator without pump as total lung prosthesis. Fourteen anesthetized dogs remained in apnea for 1 to 4 hours on total extracorporeal breathing through a Landé-Edwards membrane oxygenator (LEMO). The LEMO was directly perfused by the right heart in total pulmonary bypass, without a pump or reservoir, as an external artificial lung. A 2 sq. M. LEMO proved adequate for a dog weighing 10 kiolgrams. Pulmonary arterial pressure increased 60 per cent of the base-line value at the start of bypass because of transitory LEMO resistance, three times the normal pulmonary resistance; the pressure then returned to the initial value. Systemic arterial pressure dropped to 61 per cent on bypass. The heart did not fail. Cardiac output, central venous pressure, and the electrocardiogram remained unchanged. PO2 at the LEMO outlet was more than 200 mm. Hg. Oxygen transfer was less than 20 ml. per minute per square meter because of hemodilution and hypothermia. Dogs survived if bypass was arrested after 1 hour; if not, they died after an average of 3 hours, 20 minutes on bypass.


Experimental coronary artery fistula.

Experimental coronary artery fistula. Despite numerous clinical reports of coronary artery fistulas, there have been no laboratory models. A circumflex coronary-pulmonary artery fistula was constructed with a vein graft in 11 adult foxhounds. A temporary intravascular shunt obviated the need for cardiopulmonary bypass. Measurements of aortic flow, arterial pressure, left ventricular pressure and its derivative, heart rate, and flow in the proximal coronary, distal coronary, and fistula were made with the fistula open and closed in 9 animals. Mean fistula  flow was 89 c.c. per minute, representing a 1.1:1 left-to-right shunt. Mean proximal coronary flow increased 211 per cent, and there was a relative steal of 26 per cent of distal coronary flow with the fistula functioning. Phasic flow patterns showed continuous systolic and diastolic flow in the proximal coronary artery and fistula. Despite the striking changes in coronary flow patterns, there was no significant effect on measured left ventricular function. Futher uses for this model and variations of it aresuggested.


Dental health status of third grade children and their families within the context of a community's dental health care system. Utilizing structure, process, and outcomes as conceptual dimensions of appraisal of quality, data were analyzed to present an evaluation of the quality of a community's dental health care system as reflected in a population subgroups' dental health status. Data were collected from 838 Caucasian third-graders and their parents through interviews, mail questionnaires, and dental screening examinations. Indicators of structure were: status of community water fluoridation in the study community, dentist to population ratio, and dental care resources in the public sector available to eligible residents. Process indicators of quality were: 1) screening, case finding, examinations, and quality of restorations as measures of provider behaviors, and 2) complaints, compliance, conditioned behaviors, level of dental health knowledge, and utilization of dental services as measures of client behaviors. Outcomes, subjected to analysis included indices indicative of dental disease experience. Variables operationally defined as indicators of the subgroup's dental health status were subjected to a descriptive analysis and were then crosstabulated with the socioeconomic status of the child's family to identify socioeconomic differences in the process of obtaining care and in dental health outcomes. Findings indicate which elements in a community's prevailing dental health care system function well and which would need alteration to maximize dental health for the subgroup.


[Use of electric stimulation to prevent the development of muscle changes during hypokinesia]. An attempt was made to use electric stimulation of antigravity muscles of hind limbs of rats exposed to a 15 and 30 day hypokinesia as a method for preventing structural and metabolic disorders that develop in the muscular tissue during a diminished motor activity. The electric stimulation was carried out using the Bion device with a frequency-amplitude modulation. The impulses of an amplitude of 0.7-1 msec and a frequency of 100 to 130 Hz were modulated with a frequency of 0.5 Hz. During the first experimental days the electric stimulation was 5 to 7 min and by the end of the first week it reached 30 min. Throughout the first week the voltage grew from 6-7 to 20 V. Electric stimulation was applied 5 times a week. The favourable effect of the electric stimulation was demonstrated in 4 out of 12 animals during every experimental run. It is suggested that a higher percentage of the protective effect of the method can be achieved with the stimulation ensuring a more intensive influence on the deeply located muscles.


Nondependence of cell pH on sodium transport in rat diaphragm muscle. Both sodium and hydrogen ions are in lower concentration in muscle cell water than would be predicted from thermodynamic considerations alone, indicating active transport of these two ions out of muscle cells, To determine whether their transport is coupled, intact rat diaphragms were incubated at an external pH of 7.40, and sodium efflux was altered by exposure to ouabain. Despite a sixfold increase in intracellular sodium concentration, cell pH measured simultaneously by the distribution of both a weak acid (pH DMO) and a weak base (pH nicotine) was unaffected. Similarly, when sodium influx was decreased by incubating intact diaphragms in low sodium isoosmolar buffer, pH DMO and pH nicotine were unaltered. In addition, a pH-sensitive reaction, the evolution of 14CO2 from 1, 4-14C citrate by rat hemidiaphragm, was not changed by exposure to ouabain or low sodium media. These experiments demonstrate that in diaphragm muscle sodium and hydrogen ion transport appear not to be coupled, since alterations in sodium transport are unaccompanied by a change in cell pH. Although changes in membrane potential may explain part of the results, the data are most consistent with the hypothesis that active hydrogen ion transport in skeletal muscle in directly coupled to metabolic energy-producing reactions.


A pharmacologic comparison of histamine receptors in isolated extracranial and intracranial arteries in vitro. Isolated segments of cat extracranial and intracranial arteries were tested simultaneously for circular motor activity in an aerated Krebs-Ringer organ bath at constant temperature and pH. Histamine produced a strong contraction (about 850 dyn) in the extracranial arteries but a considerably weaker contraction, with a high half maximum response, in the intracranial arteries. The mode of inhibition of the latter response by antihistaminic compounds (chlorpheniramine and mepyramine) showed the response to be nonspecific; the contraction in the extracranial arteries was inhibited in a competitive manner, demonstrating the presence of histamine H1 receptors. The dilatory response was studied after the vessels had been given a tonic contraction with serotonin. Histamine produced similar dilatory effects (about 200 dyn) in both types of arteries and competitive inhibitions were obtained with burimamide, showing that the dilation was mediated through histamine H2 receptors. Dissociation constants were calculated for the receptor-antagonist complex.


[Physiological basis of homeostasis of the extracellular fluid volume]. Renal, glomerular and tubular, factors responsible for the volume control of extracellular liquid were examined. The part played by angiotensin II in mediating the compensation of this liquid losses was studied in patients with spontaneous polyuria due to diencephalo-posthypophyseal diabetes insipidus or psychogenic polydipsia and healthy subjects with induced hypotonic polyuria. It was noted that: 1) acute expansion elicited a natriuretic response and increased distal sodium load, due to an increase in filtrate and relative inhibition of proximal reabsorption, or proximal inhibition if the filtrate was unchanged. The efficiency of distal sodium transport was often unchanged. 2) Return to sodium balance parity during prolonged expansion of volume, was accomplished by varying renal means, in accordance with the experimental model employed. Distal reabsorption was essentially depressed during prolonged saline load (secondary hypoaldosteronism). When protracted mineralcorticoid treatment was used, however, distal reabsorption was high, even in the escape stage, and its saturation required marked augmentation of the sodium load reaching the distal tubules. 3) Depletion of volume caused by protracted natriuretic treatment in spontaneous polyuria reduced both diuresis and sodium excretion. This resistance to the natriuretic effect of the drug followed intrarenal compensation that reduced the distal sodium load and encouraged reabsorption in some distal sites (secondary hyperaldosteronism). 4) Infusion of angiotensin II in sub- or pauci-pressor doses causes an isosmotic sodium saving, since it reduced the glomerular filtrate and increases the fraction of filtrate reabsorbed by the proximal tubules; the tubular effect is likely secondary to increased vascular, especially postglomerular resistance. In the healthy subject, angiotensin II leads to antidiuresis referable, on account of its intensity and longer time cycle, to ADH release angiotensin-dependent.


A study of fetal heart rate deceleration areas. II. Correlation between deceleration areas and fetal pH during labor. Three FHR deceleration areas of fixed durations related to the onset of the concomitant uterine contraction were evaluated automatically with a small digital computer during labor. The correlations between these areas and the fetal scalp blood pH values were studied. The deceleration occurring 80 to 140 seconds after the onset of each uterine contraction during the 20 minutes preceding the fetal blood sampling presented the best correlation (r equals minus 0.453) with fetal pH values. In addition to FHR deceleration area, baseline FHR variability should be considered in predicting fetal condition.


Dependence of 2,3-DPG and oxygen affinity of haemoglobin on sex and pregnancy in the guinea-pig. Oxygen half-saturation of blood (P50), 2,3-diphosphoglycerate concentration (2,3-DPG) and Bohr effect were determined in male, and nonpregnant and pregnant female guinea pigs, according to a randomized block design. P50 was significantly higher in the female group (26.3 Torr plus or minus 0.22 SEM) than in the male group (24.8 Torr plus or minus 0.26 SEM) and was significantly lower in both these groups than in the pregnant group (27 Torr plus or minus 0.35 SEM). This difference in oxygen affinity was explained by differences in 2,3-DPG: 1.08 plus or minus 0.02 SEM in males, 1.24 plus or minus 0.03 in non-pregnant females and 1.34 plus or minus 0.03 mol/mol HB in pregnant females P50, 2,3-DPG and haemoglobin concentrations were significantly correlated for the ensemble of the 3 groups. There was no significant difference in Bohr effect between the 3 groups.


The renal plasma flow and glomerular filtration rate as estimated through double radiocompound renography. In order to estimate the renal plasma flow and glomerular filtration rate during the course of renography, a method was developed using simultaneously 131I Hippuran and 169Yb DTPA. First results obtained in a survey of approximately 200 patients are encouraging. The method permits an accurate evaluation of the renal function. In addition, by comparing the clearance rate of the two radiocompounds one can also obtain some interesting diagnostic information which can contribute usefully to the interpretation of renographic tracings and/or gamma camera sequential images.


99mTc-DTPA(Sn) dry-kit preparation. Quality control and clearance studies. The preparation technique for 99m-Tc-DTPA(Sn)-complex has been studied in detail in order to find the optimal conditions for preparation. The concentration of DTPA should be at least 10 mM, and that of Sn(II) less than 1 mM, in order to obtain a reproducible high-labelling yield. A dry sterile kit was prepared of 39.3 mg H-5DTPA and 2.3 mg SnCl-2 with 2H-2O in a 10 ml vial. The 99m-Tc-DTPA(Sn) was prepared by adding the 99m-Tc-eluate to the vial. After 1 min the solution was sterile-filtered and was ready for use. The plasma clearance of 99m-Tc-DTPA(Sn) in man determined by blood-sampling up to 200 minutes after administration shows a good correlation to endogenous creatinine clearance (r plus 0.93). The plasma disappearance curve studied during 24 h is, however, a sum of three exponentials corresponding to biological half-times of 18 plus or minus 8 min, 105 plus or minus 9 min and 17 plus or minus 4 h. The slow third component representing about 2% is assumed to be due to binding of 99m-Tc to plasma proteins. The absorbed radiation dose calculated for whole body is 8 mrad/mCi, kidneys 50 mrad/mCi, bladder 300 mrad/mCi, ovaries 17 mrad/mCi and testes 11 mrad/mCi. This agent is a valuable radiopharmaceutical for renovascular clinical problems. Scintigraphic imaging of the aorta, kidneys, ureters and bladder (for residual urinary volume-determination) could be performed.


A physiological analysis of walking in the American lobster (Homarus americanus). The normal, unrestrained, forward walking of the lobster was studied with a closed-circuit television system and a video-tape recorder. A frame-by-frame analysis was undertaken and measurements made of unilateral stepping sequences, contralateral and ipsilateral phase relations between pairs of legs, the movements at the leg joints primarily involved in stepping and their differences in each of the four pereiopods. The order of stepping was expressed in terms of the probability of any leg following any other leg and it was found that while there is a preferred order, there is considerable variation from the dominant pattern. The commonest deviations from the dominant gait are those involving the simplest types of re-ordering of the sequence. Pairs of contralateral legs show a strong tendency to alternate but all phase relations can occur. Similarly, while the ipsilateral legs show preferred phase relations, all possible relations do occur. The four pereiopods from anterior to posterior were found to have respectively, a pulling action, a combined pulling and rowing action, a rowing action and a combined pushing and rowing action. The same parameters of stepping were recorded from animals walking on a transparent, driven treadmill and, as no significant differences were found in comparisons with results from freely moving animals, subsequent results were obtained from animals walking on the treadmill where more detailed study and manipulation could readily be made. The stepping action of the third pereiopod during forwards walking involves major movements about two joints whereas the other pereiopods move about three joints. Detailed study of the intra-leg activity was therefore confined to the third pereiopod where the simpler action considerably simplified the problems involved in collecting and analysing data. Measurements were made of the angles swept out by the joints of the third pereiopod during movement. Electromyograms were recorded from the six muscles primarily responsible for these movements and from movement transducers placed at the joints. The duration of the movements and of the bursts of acitivity in the muscles and the interrelation between different muscle bursts were measured and a computer-aided analysis made to determine the characteristic features of the inter-burst relations during stepping. While there is considerable variability from step to step, the overall activity is relatively phase-constant over a wide range of stepping frequencies. When some of the key parameters of normal walking had been characterized, changes designed to alter the sensory input to the system were imposed.


Tryptoline formation by a preparation from brain with 5-methyltetrahydrofolic acid and tryptamine. An enzymatic preparation from human brain converts tryptamine to tryptoline (9H-1,2,3,4-tetrahydropyrido[3,4-b]indole) in the presence of 5-methyltetrahydrofolic acid. Similarly, N-methyltryptamine and 5-hydroxytryptamine yield 1-methyltryptoline and 5-hydroxytryptoline, respectively. Neither in vitro nor in vivo formation of these compounds by human tissues has been described.


The influence of body position on pulmonary function in low birthweight babies. The influence of the prone and supine body positions on the respiratory rate, arterial pH, pO2, pCO2 and serum bicarbonate level; on alveolar pO2 and pCO2; and on alveolar/arterial gradients for carbon dioxide and oxygen, were compared in 10 low birthweight infants. THE ALveolar pCO2 was higher in the prone, while pO2 was higher in the supine position, possibly as a result of ventilation/perfusion imbalance with increased physiological dead space in the supine position. There were no significant differences between the other parameters studied. Since aspiration of feed by the low birthweight infant is a major cause of morbidity and mortality, evidence is presented in favour of the prone nursing position.


[Fibrin (ogen) Split products of nephropathies]. On healthy individuals fibrin(ogen) split products cannot be demonstrated in the blood. Catabolic products of fibrin and fibrinogen appear in the blood in case of general fibrinolysis, consumption coagulopathy with secondary fibrinolysis as well as local fibrin films with secondary fibrinolysis. The regular routine determination of fibrin(ogen) split products in serum or urine may indicate starting complications of many diseases. The appearance of these split products in case of renal affections indicates acute and active processes on the kidneys themselves; fibrin films appear in case of acute and chronic glomerulonephritis, casting-off crises on renal transplants, EPH gestosis, renal phlebothrombosis, hemolytic-uremic syndrom and occasionally urinary tract infections. The demonstration of fibrin(ogen) split products in serum or urine allows the following conclusions: a) acute and active process on the kidneys themselves; b) HMWS in urine indicate a fibrin film in the kidneys; c) an immediate beginning of an anticoagulation therapy; d) good possibilities to judge the therapeutic effect and by this the further progress of disease.


[Continuous irrigation of the bladder with acetic acid solution and its therapeutic effect on candida-infection]. Our clinical experience with acetic acid solution in the treatment of candida infection of the bladder was confirmed by in vitro experiments. We apply continuous bladder irrigation with increasing concentrations of acetic acid solution up to pH 5.0. The majority of patients had received antibiotics or cytostatic drugs and suffered from chronic and malignant diseases. A case report is given with endoscopic documentation of the influence of acetic acid solution on the bladder.


Renal calculi and biochemical abnormalities. In children with myelomeningocele and heoconduit diversion. Of 38 pediatric cases of ileoconduit urinary diversion of myelomeningocele, 4 with renal calculi are presented. An increased risk of renal calculus formation may be imposed on children with myelomeningocele with ileoconduit urinary diversion especially so in functionally and anatomically abnormal kidneys and in chronic renal infection with urea-splitting bacteria. It is not clear why the ileoconduit procedure should increase the incidence of renal calculi in such children.


Response of rat testis to localized induced hyperthermia. A method is presented in which the rat testis is extensively mobilized through a low abdominal incision, but in which its blood supply is carefully preserved. Localized hyperthermia is induced in this mobilized testis by water bath immersion. The tissue temperature is measured during and after immersion by means of a thermocouple inserted into the tissue. The relative sensitivity of spermatogenic tissue to increased temperature is confirmed and the relative resistance of Sertoli and Leydig cells is noted. Minimal or absent inflammatory reaction to thermal destruction of testicular cells is found as long as the tubule is intact. A marked peritesticular inflammatory response is noted when the total testicular tissue is destroyed at the highest temperature tested.


In vitro hatching of the tapeworm Moniezia expansa (Cestoda: Anoplocephalidae) and some properties of the egg membranes. In vitro studies revealed that the hatching of oncospheres of Moniezia expansa requires the mechanical breakage of the eggshell and subshell membrane and enzymic digestion of the pyriform apparatus. Removal of the outer two egg membranes elicits the activation of most oncospheres. Between pH 5.0-7.8, there is no significant difference in numbers of oncospheres activated by eggshell removal and the addition of sodium bicarbonate has no effect. Solutions of more extreme pH values (2.0 and 10.0) are harmful and render oncospheres immobile. The subshell membrane forms a barrier to the passage of water in an osmotic gradient and to several molecular and ionic substances. Between the eggshell and subshell membrane is a layer of droplets which have a strong affinity for Sudan stains and which are partially removed by lipase. The eggshell is resistant to a variety of proteolytic enzymes, amylases and lipase. The pyriform apparatus is digested by chymotrypsin and pepsin, though not by trypsin. Both eggshell and pyriform apparatus are dissolved by solutions of sodium sulphide and sodium hypochlorite, indicating that their structures are stabilized by disulphide bonds and other covalent linkages.


Follicular and luteal function in the puberal rat: gonadotrophic hormone stimulation and enzymic-nucleotide interactions. Using the puberal rat and the PMS-treated rat as animal systems, ovarian events associated with follicular and luteal development have been characterized by measuring gonadotrophic hormone (LH, FSH and prolactin) and progesterone concentrations in peripheral serum; and selected enzymic (NAD-kinase:NAD-K and glucose-6-phosphate dehydrogenase: G6PD) activities and nucleotide (NAD, NADH, NADP, NADPH, ATP) concentrations in ovarian tissue. In the puberal rat, the period of follicular development was characterized by increased ovarian NAD-K SA, NAD and NADH concentrations and decreased ATP and NADP concentrations. The first pro-oestrus was characterized by greatly elevated LH, FSH, prolactin and progesterone concentrations, significant decreases in ovarian NAD-K SA, NAD, NADP and ATP concentrations, and an increase in NADPH concentrations. The development of new corpora lutea was associated with striking increases in ovarian NAD-K SA and G6PD SA. Increased activity of both enzymes exhibited a significant positive coefficient of correlation with the number of corpora lutea contained within the ovarian tissue. PMS (4 IU) stimulation of follicular activity resulted in events leading to the induction of an endogenous LH surge and ovulation. Associated with increased follicular activity was increased ovarian NAD-K SA. In contrast to the puberal rat, no rise in progesterone concentrations was associated with the LH surge or the formation of corpora lutea.


Hormone and enzyme assays in pregnancy. V. A rapid method for measuring the placental cystine-aminopeptidase using 1-cystine-bis-1-cystine-bis-p-nitroanilide-nitroanilide as substrate. A rapid and simple method for determination of the placental cystine-aminopeptidase (P-CAP) activity in plasma is presented. The enzyme-catalysed hydrolysis of the substrate, 1-cystine-bis-p-nitroanilide, is followed in a spectrophotometer by reading the absorbance of the product p-nitroaniline at 380 nm. The absorbance increases linearily with time after a lag-period of 30 seconds to 5 min. The reaction is followed for about 10 min and the increase in absorbtion per min is calculated from the linear part of the absorbtion curve. The test could also be performed by taking 2 readings at about 5 min intervals. In the studies of the enzyme kinetics a competitive inhibitor of the reaction was found in plasma. The amount of the inhibitory substances seemed to be nearly constant in the plasma samples studied from normal pregnant women as well as in plasma samples with high enzyme activity (twin-pregnancy) and low enzyme activity (severe pre-eclampsia). The normal enzyme activity pattern showed an increase from about 210 days of pregnancy and towards the term. A coefficient of correlation of plus 0.83 with the more time consuming method using 1-cystine-di-beta-naphtylamide as substrate was found. It was concluded that the present method could replace the method described by Babuna & Yenen (1966) at least from about 210 days of pregnancy and where a rapid answer is necessary.


Glycosidases in human skin fibroblast cultures. Alpha-fucosidase, alpha-galactosidase, alpha-glucosidase, beta-mannosidase, and N-acetyl-alpha-glucosaminidase. Five glycosidases, alpha-fucosidase, alpha-galactosidase, alpha-glucosidase, beta-mannosidase and N-acetyl-alpha-glucosaminidase were studied in human skin fibroblast cultures. The pH-dependency, kinetic properties of the enzymes and results of isoelectric focusing and ion exchange chromatography are presented. Techniques suitable for diagnosing inborn lysosomal diseases in skin fibroblast cultures are defined.


Arrhythmias following cardiac surgery: relation to serum digoxin levels. Arrhythmias were analyzed in 50 patients undergoing cardiac surgery: 27 with valve surgery, 15 with coronary artery bypass (CAB), 5 with CAB and valve surgery, and 3 with miscellaneous procedures. The role of electrolyte abnormalities, pericarditis, serum osmolarity, digoxin level, and the type of surgery performed was evaluated. Thirty-seven out of 50 patients (74 per cent) had a postoperative arrhythmia, and a total of 78 different arrhythmias were noted. Twenty-six out of 27 patients with valve surgery had an arrhythmia vs. six out of 15 patients with CAB (p less than 0.001). Atrial fibrillation was the most common arrhythmia in all groups. Although postoperative hypocalcemia, hypomagnesemia, pericarditis, and wide shifts in osmolarity were common, they did not correlate with arrhythmias. Seventeen patients developed postoperative arrhythmias compatible with digitalis toxicity, including junctional rhythm, atrioventricular dissociation, or atrial tachycardia with block. However, the range of serum digoxin levels in these patients was zero to 2.80 ng. per milliliter. This suggests increased sensitivity to digitalis glycosides or the effects of surgical trauma as the etiology of arrhythmia in many patients. The distinction between digitalis-induced arrhythmia and spontaneously occurring arrhythmia cannot be made with certainty in most postoperative patients. Therapy should reflect an awareness of the potential for postoperative digitoxicity.


Angiotensin- and norepinephrine-induced myocardial lesions: experimental and clinical studies in rabbits and man. The ability of large doses of exogenous angiotensin II to cause widespread multifocal microscopic myocardial necrosis in the rabbit has been confirmed. Angiotensin II also consistently produced acute renal failure with, less consistently, renal tubular necrosis. Norepinephrine infusions caused histologically indistinguishable myocardial lesions, but did not detectably affect renal function or histology. Severe renal failure, induced by bilateral nephrectomy (with or without concurrent glycerol administration) was not associated with similar cardiac lesions. Acute renal failure of comparable or greater severity to that induced by angiotensin II was produced by intramuscular cephaloridine, and was not associated with cardiac lesions. Rabbits infused with saline intravenously or "sham"-operated by simply opening and closing the peritoneal cavity did not develop renal failure and showed no cardiac or renal lesions histologically. Myocardial lesions, apparently identical to those seen in the rabbits, were observed postmortem in three patients known to have had high circulating levels of angiotensin II before death, although in all three cases alternative explanations are possible. Unexplained arrhythmia, cardiac arrest, and central chest pain without clear cardiographic or serum enzyme evidence of myocardial infarction occurred in two other subjects with very high plasma levels of angiotensin II. These attacks ceased after bilateral nephrectomy and a consequent fall in plasma angiotensin II. The cardiac attacks in these five patients all occurred during or shortly after procedures, such as sodium-depleting dialysis, renal artery surgery, or diazoxide administration, known to cause increase in plasma concentrations of renin and angiotensin II.


The long Q-T syndrome.

The long Q-T syndrome. Recent clinical and experimental data on the long Q-T syndrome (LQTS) are presented and discussed. The pathogenesis of LQTS is dependent on an imbalance between various components of the cardiac sympathetic innervation. A congenital decreased activity through the right cardiac sympathetic nerves seems to be the more likely pathogenetic mechanism for the majority of cases. Other forms of sympathetic imbalance, including left or even right hyperactivity, are, however, possible in isolated cases. Beta-blockers, at full blocking dose, represent the therapy of choice and are greatly effective in reducing the mortality (from 73 per cent to 6 per cent). If syncopal attacks are not eliminated by the medical therapy, the the ablation of the left stellate ganglion along with the first thoracic ganglia is the most rational and specific therapy. The possiblity for the correctly diagnosed and treated patients to escape an otherwise impending death calls urgently for diffusion of the knowledge about the long Q-T syndrome.


A comparison of timolol and propranolol in essential hypertension. The antihypertensive efficacy of a new beta-adrenergic receptor inhibiting compound, timolol (MK-950), was evaluated using two treatment protocols: double-blind timolol vs. placebo treatment and double-blind timolol vs. propranolol (10 and 12 patients, respectively). These studies indicate that timolol significantly and safely reduced arterial pressure in mild to moderately severe essential hypertensive patients. The reduction in mean arterial pressure with timolol was equivalent to the pressure reduction with propranolol when the doses of 30 and 120 mg. per day, respectively, were used.


Effects of aminophylline on the threshold for initiating ventricular fibrillation during respiratory failure. Cardiac arrhythmias have frequently been reported in association with respiratory failure. The possible additive role of pharmacologic agents in precipitating cardiac disturbances in patients with respiratory failure has only recently been emphasized. The effects of aminophylline on the ventricular fibrillation threshold during normal acid-base conditions and during respiratory failure were studied in anesthetized open chest dogs. The ventricular fibrillation threshold was measured by passing a gated train of 12 constant current pulses through the ventricular myocardium during the vulnerable period of the cardiac cycle. During the infusion of aminophylline, the ventricular fibrillation threshold was reduced by 30 to 40 percent of the control when pH and partial pressures of oxygen (PO2) and carbon dioxide (CO2) were kept within normal limits. When respiratory failure was produced by hypoventilation (pH 7.05 to 7.25; PC02 70 to 100 mm Hg: P02 20 to 40 mm Hg), infusion of aminophylline resulted in an even greater decrease in ventricular fibrillation threshold to 60 percent of the control level. These experiments suggest that although many factors may contribute to the increased incidence of ventricular arrhythmias in respiratory failure, pharmacologic agents, particularly aminophylline, may play a significant role.


Serum gamma-glutamyl transpeptidase activity in normal children. Serum gamma-glutamyl transpeptidase (GGT) activities of 82 healthy neonates (aged 9 hours to 11 days) and 106 healthy children (aged 2 months to 15 years) were determined. Serum GGT activity of 47 neonates (51%) was higher than the accepted upper limit of normal for adults. By three months of age, all of the children had serum GGT activities that were within the accepted normal range for adults. Thereafter there was only minimal variation in serum GGT activities of older children. Although mean serum GGT activity was higher in male children than in female children, there was no significant difference between the values for male and female neonates. That after the neonatal period serum GGT activity is constant in the adult range and is not affected by bone growth as is alkaline phosphatase suggests that GGT may be of value in the evaluation of hepatobiliary disease in children.


Redesigned apparatus for anaerobic measurement of blood pH at low temperatures. A newly designed apparatus for anaerobic measurement of blood pH at low temperatures is presented. This apparatus features a larger glass electrode surface area, which is necessary to overcome the increased resistance of the glass as blood pH determinations at 0-15 C. are undertaken. Utilization of this equipment has confirmed the deltapH per degree C. of whole blood to be 0.0156, while intracellular pH of blood has a deltapH per degree C. of 0.0165.


Mucosal-cell counts in ulcerative and granulomatous colitis. Epithelial and connective-tissue cells were counted in rectal mucosal biopsies from 215 patients with ulcerative colitis, 98 patients with granulomatous colitis, and 50 controls. The results were analyzed statistically. Significantly decreased mucous goblet cells were found both in sigmoidoscopically abnormal ulcerative colitis and in granulomatous colitis, and they increased during the healing process. More pyknotic and karyorrhectic epithelial cells occurred in active ulcerative colitis than in granulomatous colitis. Inactive ulcerative colitis still manifested histologic evidence of acute and chronic inflammation, while sigmoidoscopically normal granulomatous colitis biopsies after previous gross rectal disease showed significantly increased macrophages in the lamina propria. Cell counts were valuable for differential diagnosis after the sigmoidoscopic appearance became normal. The acute inflammation of ulcerative colitis, as indicated by neutrophils, was decreased most notably following therapy with prednisone or 6-mercaptopurine. Chronic inflammation associated with fewer plasma cells was decreased after salicylazosulfapyridine as well as either of the other two drugs; macrophages, indicators of healing, increased most after 6-mercaptopurine combined with another anti-inflammatory agent.


Control factors in the release of gastrin by direct electrical stimulation of the vagus. The release of gastrin by direct electrical stimulation of the vagus was studied together with the relative effects on the response of antral and duodenal acidification. As expected, gastrin levels increased to three times the normal simulated response following antral neutralization. In contrast, duodenal acidification failed to influence the vagal release of gastrin when the antrum was neutralized although it had a minor effect when the antrum was acidified. Thus the antral pH dominates over duodenal pH as a factor in controlling gastrin release. Surprisingly, atropine in doses which blocked acid release and produced marked cardiac effects failed to inhibit the release of gastrin from the antrum on vagal stimulation. This suggests that, using this model, vagal release of gastrin, if cholinergic, is highly resistant to atropine.


Renal prostaglandins.

Renal prostaglandins. Relative renal ischemia, produced by a variety of interventions, is modulated or buffered by prostaglandins synthesized within the kidney. These prostaglandins, however, do not account for renal autoregulation in its classic sense. They can facilitate salt and water excretion, largely through effects on physical forces in proximal peritubular capillaries, as evidenced by augmented renal blood flow. Renal prostaglandins may play a role in chronic water balance, but they probably are not important in chronic electrolyte homeostasis. There are several potential mechanisms by which renal prostaglandins could exert antihypertensive efects. Establishment of the importance of these agents, however, as antihypertensive hormones remains a challenge for future investigation.


The renin axis and vasoconstriction volume analysis for understanding and treating renovascular and renal hypertension. Information defining the renin-angiotension-aldosterone axis as a control system concurrently regulating salt balance and blood pressure has been applied to reexamine the role of renin in experimental and clinical forms of renovascular and renal hypertension, and thence to develop criteria for differentiating these entities. Experimentally, there are two models of renovascular hypertension; one is characterized by excess renin with reduced sodium (vasoconstrictor form) and the other by excess sodium with reduced renin (volume form). But with sodium depletion, the volume form converts to a vasoconstrictor form illustrating how the two factors coordinate to maintain blood pressure. In man, renovascular and renal hypertensions appear to be sustained by the same two mechanisms. Studies in man show that, in the absence of unilateral disease, the supine renal venous renin level in each kidney is consistently 24 percent higher than the peripheral level. Because of this constant relationship, the peripheral renin level is a measure of the renal secretion rate. Our studies indicate the curable unilateral renovascular hypertension is, in fact, renin-dependent vasoconstrictor hypertension. Three criteria, derived from four renin measurements, identify this situation: (1) Hypersecretion of renin is reflected by a high peripheral level when indexed against sodium excretion. (2) Lateralization of renin secretion with contralateral suppression rules out occult bilateral disease. It is indicated by V-A equal 0 from the uninvolved kidney. (3) (V-A)/A greater than 48 per cent from the ipsilateral kidney  supports unilateralization. With data derived from patients with essential hypertension as a reference, the degree to which (V-A)/A is greater than 0.48 can be used to estimate the degree of renal ischemia, using Fick's principle. Corroborative evidence to support these three criteria can be developed from the blood pressure response to angiotensin blocking drugs or to antirenin therapy with propranolol. Clinical analysis validates these criteria to identify curable hypertension from unilateral renovascular or parenchymal disease. In patients with either occult or overt bilateral renal disease, the volume factor often predominates and is expressed by some suppression of plasma renin levels. Continued


Role of anaerobic bacteria in subdural empyema. Report of four cases and review of 327 cases from the English literature. Anaerobic bacteria were isolated from the subdural space in all four cases of subdural empyema encountered over a 2 and a half year period. Only one aerobe was isolated in these cases. The bacteriology of subdural empyema was further analyzed from a review of 327 cases reported in the English literature. Anaerobes accounted for 12 per cent of 234 cases; In addition, 27 per cent of cases were reportedly "sterile." These data support our finding that anaerobic bacteria may play a far more important role in subdural empyema than was previously appreciated.


Gram-negative bacillary endocarditis. Interpretation of the serum bactericial test. Although the serum bactericidal test is commonly used in the management of infective endocarditis, little has been written about its validity or limitations. We report three cases of gram-negative bacillary endocarditis (Pseudomonas aeruginosa, Vibrio fetus and Serratia marcescens) encountered in 1 year at a Veterans Administration hospital. Serum bactericidal titers were considered necessary to identify inadequate antibiotic regimens or to avoid unnecessary drug toxicity. The limitations of the test, particularly those pertaining to gram-negative infections, are reviewed. Misleading results during treatment with aminoglycoside antibiotics could be due to the tendency of serum to become alkaline on standing. A detailed study of the interaction of the complement-dependent bactericidal system of serum with eight antibiotics is presented. In the context of the serum bactericidal test, the interaction was additive or synergistic in 15 of 16 determinations, indicating the need to include a control study of serum sensitivity of the infecting microorganism in each case.


Current concepts on physiological control of gastric acid secretion. Clinical applications. Gastric acid secretion by the parietal cell is a single digestive process involving a continuous interplay between nervous and hormonal stimuli. Gastric acid hypersecretion and hypergastrinemia may represent pathologic disturbance of the normal "gastric phase" of acid secretion (excluded antrum syndrome) or abnormal gastrin secretion from a nongastric source as in the Zollinger-Ellison syndrome. Diagnosis of these two syndromes preoperatively is dependent on immunoassay for serum gastrin. A fall in serum gastrin level after the injection of secretin will distinguish the excluded antrum syndrome from the Zollinger-Ellison syndrome. Which hormone or hormones cause the acid hyposecretion of the watery diarrhea hypokalemia achlorhydria syndrome is still uncertain. Potential candidates include secretin, glucagon (alone or combined with gastrin), vasoactive intestinal peptide and gastric inhibitory polypeptide. Secretin has undergone trials as therapy in peptic ulcer whereas glucagon is under investigation for the treatment of acute pancreatitis because of its dual actions as (1) an enterogastrone and (2) an inhibitor of pancreatic secretion.


Enzymes of glucose and fatty acid metabolism in early and term human placenta. The activity of enzymes involved in glycolysis, gluconeogenesis, and lipoenesis in early and term human placenta was determined. A high activity of pyruvate kinase was found, indicating high glycolytic potential. The activity of this enzyme tended to decrease with gestation. The presence of phosphoenolpyruvate carboxylase activity was detected, suggesting the possibility of gluconeogenesis in the placenta. Very low activity of enzymes involved in fatty acid synthesis was found, whereas the activity of the pentose shunt pathway enzymes, glucose-6-phosphogluconate dehydrogenases, was relatively high. This suggested a role of this pathway in the synthesis of lipids other than fatty acids in the placenta. The activities of enzymes in the human placenta and their changes during gestation where compared to previous observations on enzymes in rat placenta.


Lumbar epidural analgesia with bupivacaine in labor. Determination of drug concentration and pH in fetal scalp blood, and continuous fetal heart rate monitoring. Lumbar epiduval analgesia with bupivacaine was given to 37 women for uncomplicated labor. After the blcokade serial determinations of pH and bupivacaine concentration were made in fetal scalp blood and maternal venous blood and there was continuous monitoring of the fetal heart rate. Fetal scalp blood pH was within normal limits and no pathologic FHR tracings were elicited by the blockade, although a temporary decrease of the baseline fetal heart rate irregularity was seen in about one-fifth of the cases. Fetal drug concentrations were low and about one-fourth of corresponding maternal values. After reinjection of bupivacaine the degree of drug accumulation was fairly similar in fetal and maternal blood.


The effect of berotec (Th 1165a) on spontaneous and induced uterine activity in the pregnant baboon. Berotec (Th 1165a), a specific beta-adrenergic agent, has been found to be a more potent agent than metaproterenol in the inhibition of uterine activity in animals and human beings. The effect of berotec on spontaneous (postinduced) and induced uterine activity in the pregnant baboon near term was investigated. Berotec administered intravenously in a dose of 5 mug per minute consistently and significantly reduced spontaneous uterine activity as well as uterine activity by either oxytocin or prostaglandin F2-alpha. The frequency of contractions was consistently reduced whereas the effect on the amplitude of contractions was less marked. There was no reduction of the baseline muscle tonus. Berotec infusion produced a marked increase in the maternal heart rate, averaging 40 beats per minute. Berotec appears to be a potent inhibitor of spontaneous, oxytocin-induced, and prostaglandin-induced uterine activity in the pregnant baboon, but it has considerable cardiovascular side effects.


Delay in seeking induced abortion: a review and theoretical analysis. Second-trimester abortion is known to be associated with increased morbidity and mortality rates. In this paper, possible reasons for delayed abortion are examined by: (1) reviewing the available literature to seek a synthesis of current findings, (2) discussing the findings within the theoretical context of decision-making under conflict which offers a conceptual framework for further understanding delay in seeking abortion, and (3) pointing to some methodologic problems in studies of delay in seeking abortion.


Effect of osmolarity on intracellular pH of rat diaphragm muscle.?22. To investigate the effect of altered extracellular osmolarity on cell pH, intact rat diaphragms were incubated in a Krebs-Ringer bicarbonate solution. Cell pH was measured simultaneously by weak-acid (pH DMO) or weak-base (ph nicotine) distribution. When osmolarity was raised by mannitol addition, cell water decreased 5-10% (P smaller than .01) while both pH DMO and pH nicotine increased (P smaller than .01) under acid, normal, and alkaline external pH conditions. Hyperosmolarity of identical degree caused by urea resulted in no changes in either cell water or cell pH. Identical amounts of mannitol added to the bath in the absence of external osmolar changes resulted in no changes in either cell water or cell pH. When extracellular osmolarity was lowered by decreasing sodium chloride concentration, cell water increased 10-12% (P smaller than .01). Despite this large change in cell water, no changes in pH DMO or pH nicotine occurred. These data indicate that osmolar induced alterations in cell water only partially explain cell pH changes found in abnormal osmolar states. Alterations in passive and active hydrogen ion transport must also play significant roles.


Fate of labeled angiotensin II microinfused into individual nephrons in the rat. 14C-labeled angiotensin II ([14C]AII) and tritiated inulin ([3H]In) were infused into individual nephrons in Inactin-anesthetized rats and urinary excretion was measured. Site of infusion was identified by neoprene injection and microdissection. In other experiments with higher doses of [14C]AII, microperfused at 10-4-10-5 M (concentrations 10-5-10-6 higher than contained in plasma), [14C]AII and its urinary metabolites were identified and quantified by two-dimensional peptide mapping. Recovery of 14C was 10.9% when proximal tubules were infused and 94.8% when distal tubules were infused. There was no correlation with tubular length in either case. For proximal tubules, two-thirds of the 11% recovered from urine appeared as peptide fragments of AII. With distal tubules almost all 14C activity appeared as intact AII. The principal metabolic product recovered from urine after proximal injection was the chymotryptic peptide, and its recovery was inversely related to tubular length. It is suggested that rapid removal of [14C]AII by proximal tubular cells occurs by enzymatic cleavage at the luminal surface with reabsorption of most of the products and excretion of the remainder


Lung vascular smooth muscle as a determinant of pulmonary hypertension at high altitude. The pulmonary hypertensive response to chronic hypoxia varies markedly among mammalian species. An explanation for this variability was sought by exposing seven species to hypobaric hypoxia (PB equal to 435 mmHg) for 19-48 days. Control animals were studied at 1,600 m (PB equal to 630 mmHg). The pulmonary hypertension that developed varied in the following order of decreasing severity: calf and pig (severe); rat and rabbit (moderate); sheep, guinea pig, and dog (mild). Right ventricular hypertrophy developed in proportion to the elevation in right ventricular systolic pressure. These interspecies variations in response were not correlated with the degree of arterial hypoxemia, degree of polycythemia, elevation in heart rate, or postnatal age. However, the medial thickness of the small pulmonary arteries in control animals was highly correlated with the development of pulmonary hypertension and right ventricular hypertrophy in hypoxic animals. Thus, the amount of lung vascular smooth muscle inherent within each species is a major determinant of the pulmonary hypertensive response to high altitude and contributes to the interspecies variability in this response.


ATPase activity of kidney mitochondria stimulated by sodium. ATPase activity of intact mitochondria may be induced by the presence of sodium. Mitochondria obtained from kidney cortex or medulla demonstrate a higher sodium-stimulated ATPase than mitochondria prepared from liver. This difference is not due to a greater capacity of kidney mitochondria for ATP hydrolysis. Sodium-stimulated ATPase activity of mitochondria is not further enhanced by magnesium or potassium, nor is it inhibited by ouabain. Furthermore, the ATPase of submitochondrial particles is not enhanced by the presence of sodium. These results indicate that the ATPase activity of mitochondria which is stimulated by sodium is unrelated to the microsomal Na-K-ATPase. mitochondrial sodium-stimulated ATPase is affected by pH, anionic composition, furosemide, and ethacrynic acid. The demonstration that mitochondrial ATP hydrolysis can be activated by sodium suggests that intracellular sodium may directly influence intracellular energy metabolism.


In vivo Na+- and Cl minus-independent transport across the skin of Rana esculenta. The relationship between the trans-epithelial Na+ and Cl minus absorptions from dilute external solutions and the H+ and base excretions were studied in Rana esculenta in vivo. The following results relate to transport from Na2SO4 solutions: 1) The Na+ absorbed is exchanged against endogenous H+. 2) Diamox injection (1.10-4 M-kg-1) simultaneously inhibits both Na+ absorption and H+ excretion. 3) The addition of amiloride to the external medium (final concn: 5-10-5 M) inhibits Na+ absorption and H+ excretion. Measurements of chloride movements from choline chloride solutions give the following results: 1) The chloride absorbed is exchanged against a base, probably HCO3-. 2) Diamox injection (1-10-4 M-kg-1)inhibits the net fluxes of both ions. When transport is measured in NaCl solutions, it is impossible to measure the HCO3-excreted when H+ is also being excreted (HCO3- plus H+ in equilibrium CO2 plus H2O). In these solutions, therefore, only the action of Diamox on the sodium and chloride fluxes was followed and was found to have similar effects on these fluxes as those described for choline chloride and sodium sulphate solutions. The results are discussed in relation to other studies on the action of inhibitors on sodium and chloride transport in the in vitro skin.


Effect of infusion of pharmacologic amounts of vasopressin on renal electrolyte excretion. Aqueous vasopressin was infused to bicarbonate- and glucose-loaded dogs and to nonloaded antidiuretic dogs in doses of 50 mU/kg per min or 50 mU/kg per h. Both doses caused a marked increase in sodium, chloride, and water excretion. The larger dose raised the fractional excretion (sodium clearance (C-Na)/glomerular filtration rate (GFR) times 100) of these ions from 2% or less to in excess of 20%. Blocking the pressor effects of these doses of vasopressin with sodium nitroprusside did not alter the marked natriuretic and chloriuretic effect.  The maximal rate of bicarbonate and glucose reabsorption was not depressed by vasopressin infusion; fractional phosphate excretion, however, was markedly increased. Inhibiting distal hydrogen ion secretion by inducing selective aldosterone deficiency failed to uncover a vasopressin-induced inhibition of proximal bicarbonate reabsorption that might have been masked by increased distal bicarbonate reabsorption. There was no significant change in GFR, renal plasma flow, or filtration fraction. The distribution of cortical renal blood flow (measured by the radioactive microsphere technique) shifted toward the inner cortex after vasopressin administration. Vasopressin, in pharmacologic doses, is a potent diuretic that most likely exerts this effect by directly inhibiting sodium reabsorption at a point in the nephron distal to the proximal tubule.


Electrophysiology of the frog gastric mucosa with sufficient CO2. Changing from 5% CO2 in the serosal solution only to 10% CO2 on both sides doubles the acid secretory rate of the bullfrog stomach (as shown previously) and raises the transmural potential difference, although the short-circuit current is not changed. The secretory overshoot on reoxygenation after anaerobiosis, observed in 5% CO2, is virtually eliminated in 10% CO2, as predicted by the diffusion model which explains the secretory rate increase. It was found that the rate of rise of the secretory rate during anoxia was identical in the 2 conditions, which explains the increased secretory lag in 10% CO2 and suggests an interesting limitation on the rate with which acid secretion can be activated. During anoxia in 10% CO2, but not in 5% CO2, there occurs a sudden drop in PD to a slightly negative value associated with a fall in tissue resistance. This effect occurs under SCN-inhibition and thus seems unrelated to H+ transport per se. A working model is presented which can explain some of the events surrounding the sudden potential drop.


Characteristics of in vitro ammonia and glucose production by dog kidney cortex. Renal cortex slices from acidotic dogs incubated with L-glutamine 1 mM at pH 7.05 produced more ammonia and glucose than slices from nonacidotic animals but no significant difference could be demonstrated at pH 7.48. At a phosphate concentration of 20-30 mM in the medium, a 20-30% increase in ammonia and a 25-40% decrease in glucose production were observed. At L-glutamine concentrations from 0 to 8 mM, a curvilinear increase in both ammonia and glucose production was noted, the effect being greater in slices from acidotic animals. D-Glutamine had little effect on ammoniagenesis. Ammonia production (1 mM L-glutamine) in vitro was 50% lower in acidotic dogs than in vivo. Slices from the remnant left kidney (4-6 wk after right nephrectomy) did not behave differently during acidosis than those from the right kidney with regard to ammonia or glucose production. In vitro ammonia and glucose production was higher in the rat than in the dog in acidotic and nonacidotic conditions when comparable concentrations of L-glutamine substrate were used.


Personality and behavior patterns of heroin-dependent American servicemen in Thailand. The authors compared a groups of heroin-dependent American servicemen stationed in Thailand with a matched control groups of men not dependent on heroin. The data gathered regarding social history, attitudes, work record, previous drug use, personality, and intelligence show significant differences between the heroin-dependent men and the control group in four areas: intelligence, work record, number of years of schooling and number of drug used before using heroin. The data suggest that many of the heroin-dependent men had difficulties related to a distant or negative relationship to their fathers; however, in contrast to previous studies of heroin addicts, they do not confirm a relationship between heroin dependence and any particular personality pattern.


Renal clearance and excretion of endogenous substances in the small pony. Renal clearance and excretion of endogenous substances were studied in 13 small adult ponies (152 plus or minus 93 (standard deviation (SD)) kg). Normal data of serum and urinary concentrations, clearance, and excretion of creatinine, osmolality, free water, sodium, potassium, and chloride during a 12-hour period are presented. Significant linear regressions on body weight (BW) were obtained for creatinine clearance (Ccr (ml/hr) = 127.2 times BW (kg) - 1553), osmolar clearance (Cosm(ml/hr) = 1.81 times BW (kg) m0.3), and free water (CH2O(ml/hr) = - 1.43 BW (kg) - 25.0). Compared with renal excretion of man, kidneys of ponies seem to conserve more sodium and chloride and excrete more potassium.


Hypoxic pulmonary hypertension in the pony. Hemodynamic measurements were made in 6 ponies at low altitude (Madison, WI, altitude, 250 m) and after 1, 2, 4, and 6 weeks at high altitude (Climax, CO, altitude, 3,400 m). The salient findings were that ponies maintain an increased heart rate and cardiac output and develop significant pulmonary hypertension at high altitude. The average control resting mean pulmonary artery pressure (BPpul) was 25.1 mm of Hg at 250 m; this value increased to 56.3 mm of Hg after 6 weeks at 3,400 m. An additional finding was that the pulmonary vascular response to acute hypoxia seemed to increase with time at high altitude.


Intermittent mandatory ventilation: an alternative weaning technic. A case report. Many variations of measurement have been proposed for determining when a patient may be weaned from artificial ventilation. The present case report describes successful use of intermittent mandatory ventilation for weaning a patient when measurements had indicated weaning would not be possible.


Immunity to leptospirosis: antiserums in dogs and hamsters. Resistance to clinical and renal leptospirosis in dogs injected with antiserum to Leptospira interrogans serotype canicola and Leptospira interrogans serotype icterohaemorrhagiae was demonstrated. The relationship between resistance induced in serum-injected hamsters was also demonstrated, using criteria of leptospiremia, renal infection, leptospiruria, and clinical signs of disease in dogs and death in hamsters.


Immunity to leptospirosis: bacterins in dogs and hamsters. Resistance to clinical and renal leptospirosis in dogs vaccinated with a bacterin containing Leptospira interrogans serotype canicola and Leptospira interrogans serotype icterohaemorrhagiae was demonstrated. The relationship between resistance induced in vaccinated dogs and that induced in vaccinated hamsters was also demonstrated, using criteria of leptospiremia, renal infection, leptospiruria, and clinical signs of disease in dogs and death in hamsters.


The influence of chronic administration of hypnotics and analgesics on rate of recovery from inhalation anesthesia in rats. A series of groups of Sprague-Dawley rats were given either secobarbital, phenobarbital, morphine, pentazocine, diazepam, methotrimeprazine, or saline (control) intraperitoneally on 4 consecutive days and then, on day 5, anesthetized with chloroform, trichlorethylene, fluroxene, halothane, methoxyflurane, enflurane, isoflurane, bromotrifluorocyclobutane, or chlorotrifluorocyclobutane. One control group received neither pretreatment nor anesthetics and another was given pretreatment but no anesthetics. The factor of "enzyme induction" is also evaluated, as are SGPT elevation and liver and kidney lesions. If enzyme induction occurred with the drugs used for pretreatment, the anesthetics suppressed the expected response. SGPT levels were generally within normal range. The combinations of all pretreatments with enflurane, halothane, or methoxyflurane had the fastest recovery; recovery was slower with the other anesthetic agents, but none of the prior chemotherapeutic drugs accelerated recovery from the inhalation anesthetics.


Isolation and characterization of an adenovirus and isolation of its adenovirus-associated virus in cell culture from foals with respiratory tract disease. An adenovirus was isolated from a foal with respiratory tract disease. The virus produced cytopathic effects (CPE) in equine embryo kidney (EEK) cell culture, contained deoxyribonucleic acid (DNA), was resistant to chloroform and pH 3, and was moderately resistant to heat. The virus caused hemagglutination of human (type O) erythrocytes. Viral density was 1.34 g/cm,3 and diameter was 75 nm. An adenovirus-associated virus (AAV) isolated from the infected cell culture was 22 nm in diameter. These viruses are classified as equine adenovirus and equine AAV.


Comparative evaluation of a new inhalation anesthetic, BAX-3224, and halothane in Macaca speciosa. Two groups of 8 monkeys were anesthetized with either BAX-3224, a new fluorinated methyl-propyl ether, or with halothane, 3 hours daily for a total of 30 hours. Vomiting incidence was 12.5 percent with BAX-3224 during both induction and recovery, compared with 3.7 percent for halothane during induction and 7 percent for halothane during recovery. Induction time did not change during the course of study with either agent. Respiration was spontaneous and cardiopulmonary function was stable. Electroretinographic (ERG) responses were consistent, flicker-light responses similar, but visual evoked responses (VER) were not present during BAX-3224 anesthesia. A 33 percent incidence of electroencephalographic (EEG) silence occurred with BAX-3224, which was consistent with absence of VER. Hematologic and serum chemistry values were similar for both agents. Serum fluoride ion concentrations, measured before exposure and 4 times during the 10-day study, did not change after administration of either agent. This finding was significant for BAX-3224, a fluorinated ether. No cardiac arrhythmias were observed during BAX-3224 anesthesia, compared with a 17 percent incidence during halothane induction. Recovery time was 32 minutes following BAX-3224 and 14 minutes after halothane. BAX-3224 produced anesthesia similar to that of halothane, did not induce changes incompatible with recovery from anesthesia, and showed great potential as a new volatile liquid anesthetic agent with excellent biologic stability.


Cytomegalovirus pneumonia after human marrow transplantation. Thirty-three of 85 patients undergoing marrow transplantation between 1969 and 1973 developed interstitial pneumonia; 23 died. The clinical syndrome consisted of tachypnea, cough, fever, rales, and hypoxemia; the radiologic findings were variable. The development of interstitial pneumonia was significantly associated with graft-versus-host disease and allogenic grafting; patients with isogenic grafts were relatively spared. The increased attack rate between 1969-71 (20%) and 1972-73 (49%) was not fully explained by improved long-term survival, by an increased proportion of allogenic transplants, or by an increased incidence of graft-versus-host disease. Intranuclear inclusions typical of cytomegalovirus were identified in 9 of 17 autopsy-confirmed cases, and patients whose marrow donors had positive cytomegalovirus antibody titers developed interstitial pneumonia more often than patients whose donor had negative titers. Interstitial pneumonia is an important cause of morbidity and mortality after human marrow transplantation. No effective treatment is presently available.


The effect of electromagnetic radiation on the hematopoietic stem cells of mice. An increase in the leukocyte number in blood and a decrease in the total cell volume of the bone marrow and spleen were observed in mice after wholebody microwave irradiation (2450 MHz, lambda equals 12.5 cm, 100 mW/cm-2). The number of hematopoietic stem cells increased early after microwave irradiation (1626 plus or minus 53 CFU in bone marrow, 689 plus or minus 86 CFU in the spleen), as compared with that or control (598 plus or minus 92 and 349 plus or minus 79 CFU, respectively). Incorporation of 59Fe in the spleen decreased to 78% of the control value 24 hr after irradiation, which was followed by an increase to 250% on Day 14 after irradiation. After heat exposure, CFUs showed an early decrease in number, whereas the percentage of 59Fe incorporation increased. The different effects of microwaves and externally applied heat on the hematopoietic stem cells suggested that alterations in tissues caused by high-intensity microwave radiation need not be related only to increased internal temperature.