2' (or 3')-O-(2, 4, 6-trinitrophenyl)adenosine 5'-triphosphate as a probe for the binding site of heavy meromyosin ATPase. 1. From NMR, IR and visible absorption studies of 2'(or 3')-O-(2, 4, 6-trinitrophenyl)-adenosine 5'-triphosphate (TNP-ATP), 2'(or 3')-O-(2, 4, 6-trinitrophenyl) adenosine (TNP-Ad(, and 1-(2'-hydroxyethoxy)-2, 4, 6-trinitrobenzene (TNP-EG), it was concluded that there is an intramolecular interaction between the base and 2, 4, 6-trinitrophenyl (TNP) moieties in the TNP-ATP molecule. 2. A broad new absorption band was observed in the 530-630 nm region when excess indole was added to reaction mixtures containing TNP-ATP dissolved in 50% methanol or dimethyl sulfoxide. On addition of aromatic amino acid derivatives, methanol or dimethyl sulfoxide. On addition of aromatic amino acid derivatives, TNP-ATP and TNP-Ad underwent spectral shifts in the 400-550 nm region. The formation of a 1:1 complex apparently occurred between TNP-ATP and aromatic amino acid derivatives, and the complex with N-acetyltryptophan was stable in 50% methanol. The difference spectrum of TNP-EG vs. TNP-ATP closely resembled that induced by the addition of N-acetyltryptophan to the TNP-ATP solution. 3. The binding of 2'(or 3')-O-(2, 4, 6-trinitrophenyl)adenosine 5'-diphosphate (TNP-ADP) to heavy meromyosin (HMM) was studied by the rapid gel equilibrium method using Sephadex G-25. A dissociation constant of 1.4 muM and a maximum binding number of 1.8 were obtained in 0.15 M KCl, 10 mM MgCl2, and 50 mM Tris-HCl (pH 8.0) at 25 degrees. TNP-ADP bound to the enzyme caused a characteristic spectral shift in the visible region. This spectral shift was explained in terms of an interaction between tryptophanyl residues and the adenine base of TNP-ADP bound to the enzyme. TNP-ADP quenched the tryptophanyl fluorescence, but TNP-EG and TNP-Ad did not. In the presence of 6 M guanidine hydrochloride, TNP-ADP scarcely quenched the tryptophanyl fluorescence, its effect being comparable to that of TNP-Ad.


Development of mitochondrial membranes in anaerobically grown yeast cells. Biochemical analyses of mitochondrial marker substances, especially cardiolipin and oligomycin-sensitive ATPase [EC 3.6.1.3], as well as electron microscopic observations were carried out to eludicate the process of mitochondrial development in annaerobic yeast cells. Cardiolipin was found to be localized in the mitochondria in anaerobic cells. Its cellular content was a little higher in the stationary phase than in the exponential phase in glucose-grown cells and increased further in galactose-grown cells. The lipid content of the mitochondrial preparation obtained from glucose-grown stationary cells was nearly as high as that from galactose-grown cells. It was also comparable to that of aerobic cells in the stationary phase, where mitochondria are fully developed. Both cellular and mitochondrial levels of oligomycin-sensitive ATPase activity were also found to rise markedly in galactose-grown anaerobic cells, although not in stationary phase cells grown anaerobically on glucose. These high levels of the mitochondrial markers indicate a developmental change in mitochondrial structure even in anaerobically grown cells, which lack mitochondrial cytochromes. In the process of aerobic adaptation, respiratory system formation was observed to occur much faster in galactose-grown cells than in glucose-grown cells, and not to be inhibited by chloramphenicol and high concentrations of glucose structure in anaerobic cells. The developmental change was also corroborated by electron microscopic observations, which revealed the occurrence of two types of mitochondria in anaerobic cells. One was found in glucose-repressed cells and was characterized by the presence of numerous electron-dense granules in the matrix. In contrast, the other type, found in glucose-derepressed cells, had an electron-lucent matrix. No crista membrane was seen in either type of mitochondria in anaerobic cells, although the infoldings of the inner membrane, which partition the matrix into two parts and therefore are called "septum membranes," appeared frequently in the stationary phase cells. On the basis of these results, the process of mitochondrial development in yeast cells is discussed.


Reaction mechanism of the Ca(2)+-dependent ATPase of sarcoplasmic reticulum from skeletal muscle. XI. Re-evaluation of the transition of ATPase activity during the initial phase. We previously reported (J. Biochem. 70,95--123 (1971) that the time course of Pi liberation in the reaction of Ca2+, Mg2+--dependent ATPase [EC 3.6.1.3.] of fragmented sarcoplasmic reticulum (SR) consists of a lag phase, a burst phase, and a steady phase. We also showed that the rate constant, kd, of decomposition of the phosphorylated intermediate (E approximately P) decreases during the initial phase, and suggested that the burst phase is due to transition of the kd value. Recently, Froehlich and Taylor (J. Biol. Chem. 250, 2013--2021 (1975)) claimed that the Pi burst is caused by the formation of an acid-labile intermediate containing phosphate (E.P) formed by rapid hydrolysis of E approximately P. In the present study, the transition of the kd value during the initial phase was measured precisely, and the results showed that the burst phase is due to a transition in the kd value, not to the existence of E-P. The main results obtained were as follows: 1. After the SR had been phosphorylated with [gamma-32P]ATP in the presence of Mg2+ and Ca2+ ions, further phosphorylated was stopped by the addition of EGTA. The concentration of E approximately 32P then decreased exponentially with time. 2. The first-order rate constants, kd, of decomposition of E aproximately 32P after adding EGTA decreased with increase in the interval, t, between the start of E approximately 32P formation and the time of adding EGTA...


Beta-glycosidases and diabetic microangiopathy. I. Decreases of beta-glycosidase activities in diabetic rat kidney. Deposition of PAS2-positive materials and thickening of the basement membrane in vascular lesions are characteristic findings in diabetes mellitus, suggesting altered metabolism of glycoprotein. Changes in the activities of the glycosidases, beta-N-acetylglucosaminidase [EC 3.2.1.30], beta-glucuronidase [EC 3.2.1.31], beta-galactosidase [EC 3.2.1.23], and beta-glucosidase [EC 3.2.1.21] were measured in various organs and the serum of diabetic rats. The activities of the first three enzymes listed above were found to be much reduced in the kidney but increased in the serum. The decreased activities of beta-glycosidases in the kidney may be one of the factors responsible for the pathogenesis of microangiopathy.


Separation of subfragment-1 of H-meromyosin into two equimolar fractions with and without formation of the reactive enzyme-phosphate-ADP complex. H-Meromyosin (HMM) was digested with insoluble papain [EC 3.4.22.2].  Neither the size of the initial burst of Pi liberation (0.5 mole/mole of myosin head) nor the Mg2+-ATPase [EC 3.6.1.3] activity of HMM in the steady state was affected by this treatment.  Acto-S-1 was obtained by mixing F-actin with HMM digested with insoluble papain (HMM-S-1).  The size of the initial burst of Pi liberation of acto-S-1 was 0.35 mole/mole of S-l at an ATP concentration of 0.5 mole/mole of S-1, and 0.5 mole/moleof S-1 at ATP concentrations above 1 mole/mole of S-1...


Assembly of the sarcoplasmic reticulum. Biosynthesis of the adenosine triphosphatase in rat skeletal muscle cell culture. Temporal patterns of biosynthesis of the Ca2+ + Mg2+-dependent adenosine triphosphatase of sarcomplasmic reticulum were obtained from studies with primary cultures of rat skeletal muscle cells. Rates of synthesis at various stages of differentiation were estimated from the incorporation of tritium-labeled leucine into the ATPase. Cells were solubilized with detergent, and newly synthesized ATPase was isolated from cells by antibody precipitation in the presence of carrier ATPase. Radioactivity incorporated into the ATPase was determined after gel electrophoresis of the precipitates and counting of gel slices containing the ATPase band. In Dulbecco's modified Eagle's medium containing 10% horse serum and 0.5% chick embryo extract, mononucleated myoblast cells began to form multinucleated myotubes after about 50 hours in culture. Prior to fusion little ATPase synthesis was detectable; during fusion the ATPase was synthesized at an accelerating rate for a period of about 30 hours. The rate of synthesis levelled off after about 90 hours coincident with termination of fusion. In Dulbecco's modified Eagle's medium containing 20% fetal calf serum and 8% embryo extract, the onset of fusion was delayed for 30 to 40 hours. In this medium biosynthesis of the ATPase was also delayed so that biosynthesis of the ATPase appeared to be correlated with fusion of muscle cells. Cells cultured in Culbecco's modified Eagle's medium containgin 10% horse serum, but only 60 muM Ca2+, proliferated but did not fuse. Under these conditions, synthesis of the ATPase was measurable at 50 to 60 hours, and the rate of synthesis accelerated until 120 hours when it declined. Under all conditions degradation of the ATPase occurred with a half-life of 20 hours whereas the half-life of total protein degradation was 40 hours. Synthesis of the sarcoplasmic reticulum ATPase, like that of a number of other muscle-specific proteins, is greatly accelerated as myoblasts fuse and differentiate into myotubes. Fusion is not essential for this phenomenon, however, although it is normally concomitant with it.


Analysis of the arrangement of protein components in the sarcomplasmic reticulum of rat skeletal muscle. The nature of the protein components and their location in the sarcoplasmic reticulum membrane were studied using sarcoplasmic reticulum vesicles isolated from rat skeletal muscle and purified by a density gradient centrifugation system. On the basis of analysis by means of sodium dodecyl sulfate gel electrophoresis, the protein components appear to be similar if not identical with those reported by others for rabbit sarcoplasmic reticulum, and the relative amount of each component is also similar to that found with rabbit sarcoplasmic reticulum. Evidence is presented that radioiodine-labeled diazotized diiodosulfanilic acid is a nonpermeant labeling agent of the protein components of sarcoplasmic reticulum vesicles; this agent minimally disturbs the functional activities of these membranes. By means of this labeling agent and perturbing agents, it is concluded that the protein components with molecular weights greater than 120,000 and the (Ca2+ + Mg2+)-adenosine triphosphatase partially or totally reside on or at the external surface of the sarcoplasmic reticulum vesicles. In the case of the adenosine triphosphatase, highly controlled trypsin treatment cleaves the molecule into two products, a 65,000 molecular weight fragment and a 56,000 molecular weight fragment. The evidence indicates that the 65,000 molecular weight component of the (Ca2+ + Mg2+)-adenosine triphosphatase is located in a more exposed fashion on the external surface of the vesicles than the 56,000 molecular weight compoenet and that some adenosine triphosphatase molecules have a more exposed position on the external surface of the vesicle than others. The protein components designated by MacLennan (MacLennan, D. H. (1975) Can. J. Biochem. 53, 251-261) as "calsequestrin" and "high affinity Ca2+ binding protein" are shown not to be on the external surface of the rat sarcoplasmic reticulum vesicle but rather to reside either within the core of the membrane or on the inside surface of the vesicle. The results of this study are in agreement with the model for the organization of the protein components of the sarcoplasmic reticulum membrene recently proposed by MacLennan (MacLennan, D. H. (1975) Can. J. Biochem. 53, 251-261).


Evidence for a new intermediate state in the mechanism of (Na+ + K+)-adenosine triphosphatase. A rapid mixing technique was used to follow the intermediate formation of phosphorylated enzyme and liberation of inorganic phosphate by a microsomal preparation of (Na+ + K+)-ATPase. In the presence of 100 mM Na+,but without added K+, phosphorylation reaches a constant level at a rate which is dependent on ATP concentration. Inorganic phosphate production lags during the inital phase of phosphorylation and then accumulates at a constant rate. These observations favor a scheme in which Pi is liberated as the result of turnover of the phosphorylated enzyme. In the presence of 100 mM Na+ and 2.5 mM K+ phosphate production was resolved into two phases consisting of an initial 'burst' and late steady state phase...


Thymidylate nucleotide supply for mitochondrial DNA synthesis in mouse L-cells. Effect of 5-fluorodeoxyuridine and methotrexate in thymidine kinase plus and thymidine kinase minus cells. The effects of 5-fluorodeoxyuridine and methotrexate on [3H]thymidine and 32P labeling of mtDNA were studied in two lines of mouse L-cells. LMTK- cells, which lack the major cellular thymidine kinase (EC 2.7.1.21) but contain a genetically distinct mitochondrial enzyme, were compared to LA9 cells, which contain both thymidine kinase activities. LMTK- cells were resistant to 5-flurodeoxyuridine by a factor of 200 in comparison to LA9 cells. In both cells lines appropriate drug treatment increased utilization of exogenous thymidine for mtDNA synthesis. The maximum enhancement was 10- to 12-fold for LA9 cells and approximately 20-fold for LMTK- cells when treated with 10 muM methotrexate. The rates of mtDNA and nuclear DNA synthesis during drug treatment were analyzed with 32P labeling and 5-bromo-2'-deoxyuridine density labeling experiments. Synthesis of both mtDNA and nuclear DNA were strongly inhibited by drug treatment of either LA9 or LMTK- cells in the absence of exogenous thymidine. The rate of mtDNA synthesis substantially exceeded that of nuclear DNA in LA9 cells treated with 4 muM 5-fluorodeoxyuridine and less than 5 muM thymidine. Both synthetic rates approached those of untreated LA9 control cultures if 20 muM thymidine was present during 5-fluorodeoxyuridine treatment. In contrast, in LMTK- cells treated with 10 muM methotrexate and 20 muM thymidine, mtDNA synthesis continued at 50 to 60% of the control rate for at least 10 hours while nuclear DNA synthesis was 96% inhibited. Synthesis of mtDNA mass-labeled in both strands with 5-bromouracil occurred when LMTK- cells were incubated for 30 hours with 10 muM methotrexate and 20 muM 5-bromodeoxyuridine. These results indicate that mtDNA synthesis is resistant to a limitation of the thymidine triphosphate supply and is not strictly dependent upon concomitant nuclear DNA synthesis in these cells.


The fructose 6-phosphate site of phosphofructokinase. Epimeric specificity. The epimeric specificity of the catalytic site of rabbit muscle phosphofructokinase was investigated by testing three ketose phosphates as alternate substrates. These (and their epimeric carbons) included: D-psicose-6-P (C-3), D-tagatose-6-P (C-4), and L-sorbose-6-P (C-5). The Michaelis constants (and relative maximal velocities) were: 3.0 mM (45%), 0.054 mM (104%), and 11 mM (15%), respectively. Under the same conditions, D-fructose-6-P had a Km of 0.043 mM and an arbitrary Vmax of 100%. The low affinity of the enzyme for D-psicose-6-P indicates that the L configuration at C-3 is required for effective binding, a specificity similar to several other fructose-metabolizing enzymes. The D configuration at C-5 is also important for tight binding and the proper orientation of the phosphate group of the substrate. The kinetic constants of D-tagatose-6-P were identical with those of D-fructose-6-P, within experimental error. Thus, the configuration at C-4 is not essential for activity; an indication that D-tagatose may be utilized in mammalian tissues. A novel method for the synthesis of D-psicose-6-P and an improved procedure for the synthesis of D-tagatose-6-P are described. All products and intermediates were characterized unequivocally by chemical and physical methods.


Reconstitution of an active calcium pump in sarcoplasmic reticulum. Recovery of calcium transport and calcium-activated ATPase activity was studied in relation to the retention of protein components in sarcoplasmic reticulum reconstituted after solubilization with deoxycholate and centrifugation, followed by removal of the detergent from the supernatant by dialysis. Control sarcoplasmic reticulum was similarly treated except for omission of deoxycholate. Maximum capacity for oxalate- and phosphate-supported calcium uptake was increased 2- to 3-fold in reconstituted sarcoplasmic reticulum compared to original and control. Calcium uptake velocity of the reconstituted sarcoplasmic reticulum was approximately 80% that of original and 90% of control sarcoplasmic reticulum. Calcium uptake/ATP hydrolysis ratio was approximately 2 in the original sarcoplasmic reticulum and decreased to approximately 1 in the control and reconstituted sarcoplasmic reticulum. Calcium storage in the absence of calcium-precipitating anion was approximately 85% in control and 70% in reconstituted sarcoplasmic reticulum, compared to the original sarcoplasmic reticulum. Ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid-induced calcium release after phosphate-supported calcium uptake was slower in reconstituted sarcoplasmic reticulum than in original or control sarcoplasmic reticulum. Polyacrylamide gel electrophoresis of original and control sarcoplasmic reticulum showed similar amounts of protein components of approximately 93,000, 59,000, 50,000, 30,000 to 37,000, and 20,000 to 26,000 daltons. Reconstituted sarcoplasmic reticulum, however, lost over 85% of the 50,000- and 20,000- to 26,000-dalton proteins while retaining most of its calcium transport functions.


Biochemical changes in the cartilage of the knee in experimental and natural osteoarthritis in the dog. Biochemical changes in the articular cartilage of the knees of mature dogs, one with natural and four with surgically induced osteoarthritis, have been investigated. The four dogs were killed three, six, nine and forty-eight weeks after division of the right anterior cruciate ligament, the left knees serving as controls. The cartilage of the joints operated on was thicker and more hydrated than the control cartilage; the proteoglycans were more easily extracted and had higher galactosamine/glucosamine molar ratios. The proportion of proteoglycans firmly associated with collagen, and hence not extractable, diminished before fibrillation was demonstrable by indian ink staining of the surface. These biochemical changes were present throughout the entire cartilage of the joints operated on of the dogs killed more than three weeks later, and of the dog with natural osteoarthritis. The results suggest that in response to altered mechanical stresses the chondrocytes synthesise proteoglycans that contain more chondroitin sulphate relative to keratin sulphate than normally, as in immature articular cartilage.


Long-range observations with external aortic grafts. The late results of aortic aneurysms treated by external grafting are presented. This procedure consists of completely dissecting the involved aortic segment and suturing it in a well-fitted tubular Dacron prosthesis. The operation was carried out under the following circumstances: (a) Small fusiform aneurysm of the abdominal aorta. (b) Small and medium-sized aneurysms of the thoracic aorta. (c) Aneurysms unfavorably located in the very old and very debilitated. (d) Aneurysms involving the origin of the renal arteries. (e) Aneurysmatic dilatation of the aortic arch. Sixty-two patients were operated upon with this method with the follow-up period ranging from three months to seven years. There were no deaths during this period which could be directly related to either the aneurysm or the procedure itself.


Ouabain-resistant human lymphoblastoid lines altered in the (Na+ + K+)-dependent ATPase membrane transport system. Diploid human lymphoblastoid cells with altered response to ouabain inhibition of the (Na+ + K+)-dependent ATPase transport system, manifest both in whole cells and in purified plasma membrane vesicles, were selected for their resistance to 0.1 muM ouabain. Ouabain-resistant (OUA(R)) cells with normal growth at 50 times this dose were recovered at a frequency 1 X 10(-6). This frequency was increased 9-fold after exposure to ethyl methane sulphonate but was decreased by the frameshift mutagen ICR-191, under conditions where both increased the frequency of 8-azaguanine-resistant colonies. The ouabain resistance phenotype was stable after 200 population doublings in the absence of ouabain. OUA(R) clones show showed 30-50% of the wild type amount of 3H-ouabain bound per cell, with the same dissociation constant for ouabain, 0.1 muM at 0.5 mM K+, as observed in wild-type cells. Both the initial rate of uptake of 86Rb+ in OUA(R) cells and the (Na+ + K+)-dependent ATPase activity of OUA(R) plasma membranes showed decreased sensitivity to ouabain inhibition. However, growth and transport properties of OUA(R) cells in the absence of ouabain were unchanged compared with wild type cells.


Early events during substrate adhesion of normal and virus-transformed mouse fibroblasts. The relationship between attachment of Balb/c3T3 cells and their SV40 transformants to glass or plastic substrates and deposition of substrate-attached material (SAM-proteoglycans implicated in substrate adhesion) has been examined very early after inoculation of cells subcultured with ethylenebis (oxyethylenenitrilo) tetra-acetic acid (EGTA). The metabolic inhibitors cycloheximide and colchicine minimally affected the kinetics or short-term stability of attachment of cells or deposition of SAM. SAM deposition on to the substrate began immediately after inoculation of cells and was maximal prior to the highest cell attachment level (30-40 min after inoculation). At 4 degrees C, there was no attachment of cells to the substrate and no deposition of leucine- or glucosamine-radiolabelled SAM on to the substrate. 3T3 cells deposited SAM to a maximal level earlier during the attachment process than SV40-transformed cells. SVT2 cells deposited much smaller amounts of SAM (measured on a per-cell basis) to 3T3 SAM-coated substrates during attachment processes, whereas 3T3 cells and concanavalin A (con A) revertant variants of SVT2 cells, which have regained density-dependent inhibition of growth, deposited identical amounts of SAM (per-cell) on untreated or SAM-coated substrates. Serial attachment experiments with SVT2 cells indicated that all SVT2 cells reduced their deposition amounts on SAM-coated substrates, rather than there being an ability of a small proportion of cells to attach preferentially to SAM-coated substrates while being unable to deposit SAM themselves. The data are consistent with the presence of a sizeable pool of SAM-like proteoglycans being present on the surface of EGTA-removed cells whose deposition may be a requirement for, but may not necessarily be sufficient for, stable adhesion of cells to the substrate.


Surgical treatment of annulo-aortic ectasia. Replacement of the aortic valve and the entire ascending aorta (modified Bentall's technique) was performed in 11 patients with annulo-aortic ectasia. Nine patients are alive and well postoperatively. In comparison with our previous surgical technique, by which the aortic root was left remaining without removal, the new technique required less bypass time, including less coronary perfusion time and less amount of intraoperative bleeding than the cases handled by the previous technique, whereas amount of postoperative bleeding in both groups was not significantly different. Details of the new technique were described and the advantages of this technique are security of intraoperative hemostasis as well as shortened operation time. The Björk-Shiley tilting disc prosthesis was really convenient for this surgical technique because of its low profil architecture, and also this prosthesis gives excellent postoperative results in combination with the new surgical technique.


Pyramidal cell abnormalities in the motor cortex of a child with Down's syndrome. A Golgi study. The neuronal organization of the motor cortex of a 19-month old child with Down's syndrome (mongolism) has been studied with the rapid Golgi method. This congenital syndrome, also known as 21 Trisomy is caused by a chromosomal abnormality consisting of the presence of an extra chromosome in the group 21. Various structural abnormalities have been found in the dendritic spines (postsynaptic structures) of the pyramidal neurons of the motor cortex of this child. The axo-spinous synapses of these neurons are considered to be altered by these spine abnormalities. In addition, a peculiar form of intrinsic vacuolar change affecting the dendrites and scattered neuronal fragmentation and necrosis have also been found. At least three different types of abnormality involving the spines--(the unusually long spine, the very short spine and a reduction in the number of spines)--are recognized among the pyramidal cells of the motor cortex. It is postulated herein: that a basic anomaly, possibly related to the genetic disorder affects primarily some cortical neurons which undergo progressive degenerative changes terminating in cell fragmentation and death. The different spine abnormalities are considered to represent various developmental stages of the common genetic anomaly. These changes might be structural correlates of the motor incoordination and mental retardation which are characteristic of this genetic disorder, but, final conclusions should await the investigation of other cases with this or similar methods capable of demonstrating the normal as well as the abnormal structural organization of the human cerebral cortex.


Effects of C-reactive protein on the lymphoid system. II. Inhibition of mixed lymphocyte reactivity and generation of cytotoxic lymphocytes. C-reactive protein (CRP), an acute phase reactant which increases in concentration during inflammation, has been found to bind to human T cells and to inhibit certain of their functions. In the present study CRP was found to display a binding specificity for theta-bearing cells from mouse peripheral lymphoid tissue but not for thymus cells. CRP inhibited the proliferative response in a similar manner in both murine and human mixed lymphocyte reactions. This inhibition was prevented by the addition of the CRP substrate, pneumococcal C-polysaccharide (CPS), and was not a result of toxicity of CRP for lymphocytes. By contrast the response of spleen lymphocytes to mitogenic Con A concentrations was not altered by CRP. CRP also exerted an inhibitory effect on the in vitro generation of cytolytic T lymphocytes (CL) in mixed lymphocyte reactions of mouse spleen cells. The expression of the cytolytic process by T cells sensitized either in vivo or in mixed lymphocyte cultures was not altered in the presence of CRP. Therefore, CRP appears to influence the inductive phase of the allograft response and perhaps exerts a regulatory effect on cellular immune responsiveness during inflammatory reactions.


Skin exfoliation and purulent conjunctivitis in a new mutant-the exfoliative mouse. A spontaneous autosomal recessive mutation has been named the exfoliative mouse (genotype ex/ex). Exfoliative mice suffer a transient purulent conjunctivitis in their 3rd week and an exfoliative skin disease in their 4th week. Gram-negative bacilli are present in blood and cerebrospinal fluid during the conjunctivitis stage, and in skin during the exfoliative period. The mutant can be differentiated from the ichthyotic mouse mutant.


Octadecadienoic acids in the skin surface lipids of acne patients and normal subjects. Measurements were made of the proportions of octadeca-5,8-dienoic acid and octadeca-9,12-dienoic acid in the scalp surface lipids of 6 normal subjects, 5 subjects with slight acne, and 9 subjects with severe acne. The group averages for the delta5,8 isomer were: 0.74,  0.85, and 0.61% and for the delta9,12 isomer were 0.56, 0.27, and 0.19%, respectively. The differences in the levels of the delta9,12 isomer between the normal subjects and the groups with slight and with severe acne were statistically significant (p less than 0.02 and 0.001), respectively) but there was no significant difference in the content of the delta5,8 compound. The ratio of the delta5,8/delta9,12 isomers showed no correlation with the rate of sebum production in 12 subjects.


Platelet antiplasmin: its extrusion during the release reaction, subcellular localization, characterization, and relationship to antiheparin in pig platelets. Antiplasmin activity was shown to be released from washed pig platelets by thrombin following a time course similar to that of 3H-serotonin. Antiheparin activity (platelet factor 4) appeared to be released by thrombin at a slower rate than 3H-serotonin or antiplasmin activity. Subcellular fractionation of pig platelets showed that the storage site for antiplasmin is probably the dense (amine storage) granules. Antiheparin was distributed among all of the subcellular particulate fractions except the fraction rich in dense granules. Material released from washed pig platelets and concentrated by ZnSO4 precipitation (crude antiheparin) was found to be rich in antiplasmin activity. Gel filtration on Sephadex G-150, DEAE cellulose column chromatography, and polyacrylamide gel electrophoresis showed that pig platelet antiplasmin is a low molecular weight (approximately 30,000 d) material of alpha1-globulin electrophoretic mobility. It was found to be heat labile and also inhibitory to the caseinolytic activity of trypsin but had no effect on the action of thrombin on fibrinogen. These data indicate that platelet antiplasmin is distinct from platelet antiheparin.


Differentiation of transient erythroblastopenia of childhood from congenital hypoplastic anemia. Erythrocyte properties of patients with congenital hypoplastic anemia were compared to those of patients with transient erythroblastopenia of childhood. The MCV was less than 85 in all nine TEC patients studied and greater than 90 in all 11 CHA patients. Hemoglobin F concentration was elevated beyond the normal level for age in eight CHA patients and almost always normal in TEC. The i antigen score was more likely to be elevated in CHA than in TEC. The activities of transaminase, aldolase, phosphofructokinase, and glutathione peroxidase were higher in CHA than in TEC (p less than  0.001). Some abnormal properties (namely, MCV and hemoglobi n F concentration) of CHA erythrocytes, present during remission but accentuated during relapse, seemed to vary with changes in serum erythropoietin. Early differentiation of TEC and CHA appears feasible, allowing prompt provision of a favorable prognosis and the avoidance of unnecessary corticosteroid therapy in TEC.


The histocompatibility system and human disease. The histocompatibility system and its associations with human diseases have been described. Although these associations remain unexplained, they represent an important step forward in the search for basic causes and mechanisms of diseases. Further studies may lead to better classifications of diseases and to an increased understanding of basic biologic processes, of etiologies of many important diseases, and of relationships between genetic and environmental susceptibility to disease. However, at the present time histocompatibility studied have little value as diagnostic or prognostic tests in clinical medicine, aside from their obvious usefulness in matching tissue donors to recipients.


The relation between stimulus frequency and the relative size of the components of the biphasic response of the vas deferens to electrical stimulation at different temperatures. 1. Electrical stimulation of the guinea-pig or rat vas deferens (pre- or post-ganglionically) at frequencies from 2-5 to 40 Hz with trains of stimuli of 30 sec duration induced a biphasic response. A rapid contraction (component A) was followed after a brief relaxation by a slower contraction (component B); the two phases were seen most clearly with stimulation frequencies of less than 10 Hz. 2. The responses to post-ganglionic stimulation were always larger than those to preganglionic stimulation. In general, at low frequencies component A exceeded component B whilst at high frequencies component B was the larger. Separation of the two components on the basis of their frequency response characteristics was better for rat than for guinea-pig vasa. 3. Log. frequency-response curves to transmural (post-ganglionic) electrical stimulation and log dose-response curves to noradrenaline were recorded for guinea-pig and rat vasa deferentia at 32 degrees, 22 degrees and 12 degrees C. For the guinea-pig reduction of bath temperature to 12 degrees C increased the amplitude of component A at 2-5 and 5 Hz; component B could not confidently be distinguished at this temperature. At 22 degrees C there was potentiation of B at lower frequencies and depression of B at higher frequencies. There was no response to noradrenaline at 12 degrees C. At 22 degrees C the response to noradrenaline was increased except to doses at or near the maximum to which the response was reduced. 4. For the rat was deferens component A was little changed by reduction of temperature. Component B at 12 degrees C was greatly depressed at higher frequencies. The response to noradreanaline was increased to lower doses and decreased to higher doses as the temperature was lowered. 5. The B component of the response of guinea-pig vasa at 22 degrees C and rat vasa at 32 degrees C was more sensitive than the A component to inhibition by thymoxamine. 6. Further analysis of the mechanisms underlying the A and B components of the biphasic response may be facilitated by relative isolation of each component by the appropriate selection of parameters of electrical stimulation and of temperature for the species being investigated. The contractions of the B component are similar to, if not identical with, those produced by exogenously applied noradrenaline.


The occurrence of C19 steroids in testicular tissue and submaxillary glands of intersex pigs in relation to morphological characteristics. Five true hermaphrodite pigs and two male pseudohermaphrodite pigs were studied. A 38XX sex chromosome constitution was found in peripheral leucocytes of three true hermaphrodites and in one male pseudohermaphrodite; XX/XY mixoploidy was present in the leucocytes of the remaining male pseudohermaphrodite. The occurrence of C19 steroids, including 16-androstenes, in the testicular tissue and submaxillary gland of intersex pigs was of a similar pattern to that found previously in mature boars, and masculinization of the genital tract was related to the amount of testicular tissue present. It is postulated that in the absence of germ cells in the testicular tissue of intersex pigs the Sertoli cells may be involved in the metabolism of dehydroepiandrosterone to 5-androstenediol, a possible testosterone precursor in the pig. The high levels of 16-androstenes found in the submaxillary gland of intersex pigs indicates that these steroids are responsible for 'boar taint' in these animals. In contrast to the boar, no consistent relationship was found between the occurrence of C19 steroids and the degree of masculinization of the submaxillary gland; it is postulated that the predominantly female genetic constitution may have affected the response of the salivary gland to androgen.


The arthritic complaint in primary care: prevalence, related disability, and costs. Surveys conducted in five areas of Southern Ontario obtained clinical and service utilization data from 5,478 adults over 25 years of age. The two week period prevalence rates of arthritic and rheumatic (AR) complaints were 1.72 per cent and 2.14 per cent among two groups of users of primary care. In free-living general populations, the rates ranged from 6.23 per cent to 8.84 per cent. It was shown that only 25 per cent of complainants with AR symptoms sought health services. Of all adults seen by family physicians in one year, 28 per cent presented at least once with an AR complaint. While 20 per cent of all respondents reported some physical impairment, 43 per cent of those with AR complaints had impairment. The excess impairment was two per cent. Complaints with AR symptoms used health services at costs 78 per cent higher than the average expenditures in the same communities. The essential role of the primary care practitioner in the identification and control of AR disorders is strongly supported.


A probable case of mutation in Huntington's disease. A patient is described in whom Huntington's disease was diagnosed at the age of 34 years. No evidence of the disorder was found in either parent. Their parentage of the alleged mutant could not be excluded from a study of the inheritance of 25 genetic markers.


Vitamin A absorption and periodontal disease in trisomy G. Vitamin A tolerance tests were carried out on fourteen Trisomy G and fourteen non-Trisomy G subjects to determine whether vitamin A absorption in trisomics is associated with their high susceptibility to periodontal disease. Neither the vitamin tolerance levels nor the findings of medical examinations on these subjects indicated a vitamin A absorption problem or correlation with periodontal health.


Evidence for increased mental capacity with age in Down's Syndrome. In a previous study, the authors reported that Down's Syndrome children were deficient in short-term memory for colour compared with severely subnormal controls. The present study provides evidence that two-thirds of such children aged fifteen to seventeen years could perform tasks which no six-to-eight-year-old could, which suggests they might benefit from educational experiences which were of no value at a younger age.


The possibility of electron microscopic autoradiography of steroids after freeze drying of unfixed testes. A technique has been developed for the autoradiographic localization of steroids in testes at the light and possibly electron microscope level. During processing of the tissue there is no contact of tissue with water up to the moment of photographic development of the autoradiographs. Tritium labelled steroids have been introduced into the testis through perfusion of the isolated organ. Small tissue samples were rapidly frozen, freeze dried and fixed with osmium vapour. The fixed tissue was embedded in Epon and thin sections could be cut from this material on an ultra-cryotome without the aid of floatation liquids. Results with light microscopic autoradiography indicate the potential of this technique. This procedure which avoids any contact of the tissue with water offers good prospects for autoradiography of steroids and other soluble compounds at the electron microscope level. A comparison is made with other proposed techniques for steroid autoradiography.


Structural aberrations in group A Staphylococcus bacteriophages. Six related Staphylococcus phages spontaneously produced various abnormal head and tail structures: (i) giant capsids which were tailed and apparently contained nucleic acid; (ii) regular and irregular smooth polyheads; (iii) heads and polyheads with wavy outlines; (iv) mottled heads and polyheads; (v) abnormally long and short tails; and (vi) "double capsids" connected by a small bridge. Some of these structures are rare, or have not yet been reported. The frequency os specific aberrant particles varied from one phage to another. Length distribution of smooth irregular polyheads and of abnormal tails indicated that these structures assemble at random from protein synthesized in excess. These phages represent an interesting model for genetic and morphogentic studies.


Properties of the scrapie agent-endomembrane complex from hamster brain. Subcellular fractionation of scrapie-infected hamster brain indicated the association of the scrapie agent with a component of the endomembrane system. Characterization by equilibrium density gradient centrifugation, electron microscopy, and marker enzymes suggested a primary association with rough and smooth endoplasmic reticulum and a possible incorporation into the plasma membrane. DNA polymerase activity demonstrated a direct correlation with regions of scrapie activity from the gradient fractions. A scrapie-related product was detected after (3H)TMP incorporation and analysis on 2.2% polyacrylamide gels. Analysis of nucleic acid species extracted from subcellular fractions resulted in a greater quantity from healthy brain; however, no qualitative distinctions were detected.


Esophageal ulcers associated with tetracycline therapy. Esophageal ulceration has rarely been reported secondary to medicinal agents. we have treated three patients with esophageal ulceration associated with the ingestion of tetracycline or its derivative doxycycline. In light of the strong temporal relationship between taking the capsules and the onset of the esophageal ulceration, we believe that the capsules were the cause of the ulcers. We therefore recommend an alternative agent to tetracycline or doxycycline, if possible, for patients with any esophageal obstructive element. We also recommend that patients be cautioned not to take these drugs within one hour of going to bed.


[Further study on gentamicin in pediatrics (author's transl)]. Gentamicin (GM) was intramuscularly injected to 16 children with various infectious disease (1 septicemia, 1 purulent meningitis, 4 bronchopneumonia, 1 pyothorax, 3 pyelonephritis, 2 acute cystitis and 4 RITTER'S dermatitis). The results obtained are as follows: 1. The excellent and good clinical results were noted in all patients except for an indeterminate case with bronchopneumonia because of the concomitant therapy with CEZ. The effective rate was 100.0%. This was possibly because of quite high susceptibility (See Article) of all isolates to gentamicin. 2. Doses of GM were adjusted depending on the style of infectious diseases. The satisfactory clinical results were obtained in some cases by increasing its recommended dosage to about 5-8 mg per kg per day. 3. No kidney dysfunction, liver dysfunction, the 8th cranial nerve damage, etc. were observed by administering 5 to 8 mg per kg per day for at maximum 18 days, in this clinical trial. 4. It has been indicated in this clinical trial that GM is worthy to be used as a first-choice drug in chemotherapy of infectious diseases caused by Staphylococcus, gram-negative bacillus, etc., especially in patients who are hypersensitive to penicillin and cephalosporin derivatives. However, further study would be required for the safety of increase in its dosage and duration of administration.


Effect of dantrolene sodium on excitation-contraction coupling in frog skeletal muscle. The effect of dantrolene sodium, 1-(5-(p-nitrophenyl)furfuryli-deneamino)hydantoin sodium hydrate, on electrical and mechanical response in frog skeltal muscles (whole muscles or single fibers) and on the biochemical properties of contractile proteins and fragmented sarcoplasmic reticulum isolated from frog or rabbit skeletal muscle was investigated. The peak tensions of twitch, tetanus and potassium contracture were significantly inhibited by dantrolene, without affecting the magnitude of resting potential, the amplitude and duration of action potential and the negative afterpotential. On the other hand, ATP-INDUCED SHORTENING OF GLYCEROL-EXTRACTED RABBIT PSOAS MUSCLE FIBERS, ATPase activity of frog myofibrils and Ca release induced by caffeine, Ca uptake and ATPase activity of fragmented sarcoplasmic reticulum of frog or rabbit muscle were not affected by dantrolene. Caffeine contracture was partially inhibited by dantrolene and was almost unchanged by it in potassium-depolarized muscele fiber. Nitrate ions and low concentration of caffeine rapidly recovered the twitch inhibition induced by dantrolene. These results suggested that dantrolene acts on the membrane of transverse tubules and possibly the triadic junction and that it inhibits the inward movement of Ca and subsequently decreases the release of activator Ca from sarcoplasmic reticulum.


Bromide intoxication.

Bromide intoxication. Bromide intoxication is now an uncommon disease. This report reviews the experience with this disorder at the Johns Hopkins Hospital over the last 23 years and reemphasizes the variable neuropsychiatric symptoms which these patients present. Impaired sensorium, fever, skin rash, abnormal serum chloride, and a history of proprietary drug abuse are clinical features which may suggest the presence of bromide intoxication. Treatment consisting of saline administration often augmented with mercurial, thiazide or "loop" diuretics was uniformly effective. The declining incidence of this disorder is felt to be due to the decrease in physicians' use of prescription bromides and the declining availability of proprietary bromide containing compounds.


[The significance of the cytochemical adenosine triphosphatase reaction for the diagnosis of benign monoclonal gammopathy (author's transl)]. In 26 cases with benign monoclonal gammopathy the cytochemical activity of the adenosintriphosphatase (ATPase) in the plasmocytes of bone marrow smears was studied. 15 cases showed a decreased and 11 patients showed normal proportions of ATPase positive cells, indicating that the impairment of ATP-ase is non-specific for the diagnosis of multiple myeloma.


[Congenital centronuclear myopathy. Two morphological variants in one family (author's transl)]. This report deals with a family in which the mother and her two daughters suffer from a congenital, slowly progressive neuromuscular disease. Histological, histochemical and ultrastructural observations of the mother's muscle biopsy reveal the characteristics of the centronuclear myopathy. In this case central nuclei and pericentronuclear abnormalities of muscle fibers are found in almost all fibers. Biopsies obtained of the two daughters show alterations especially of type I-fibers, which often are smaller than normal. The presence of these two forms of centronuclear myopathy in one family indicates that these may be only different morphological types of states of one illness. Additionally, other structural findings (rod bodies, core like regions) emphasize the similarities with other congenital slowly progressive myopathies (nemaline myopathy, central core disease).


Use of Freund's adjuvant arthritis test in anti-flammatory drug screening in the rat: value of animal selection and preparation at the breeding center. The Freund's adjuvant technic, using killed Mycobacterium butyricum suspended in mineral oil, is a refined tool for anti-inflammatory drug evaluation. Its use has long been reserved for testing and not for screening due to technical problems in the preparation of valid animal models. After reviewing the methodology, the authors demonstrated that the availability of arthritic rats from a modern breeding center (Charles River France, SA, Elbeuf, France) make the procedure applicable to drug screening. This has both practical and economic advantages. The animals can be used as test organisms for drug evaluation 14 da after treatment. Three criteria for measuring the effectiveness of anti-arthritic drugs have been established: an arithritic index determined by examination of the 4 paws; changes in the erythrocyte sedimentation rate; and changes in levels of plasma fibrinogen. The curative activity of test substances can be evaluated by a single series of measurements of these 3 criteria after 14 da of treatment. This test was compared with 2 others; edema of the paw induced by the subcutaneous injection of kaolin or carrageenan, and was found to be superior.


Some data on establishing a specific-pathogen-free guinea pig colony. Detailed procedures for the germfree delivery of guinea pigs using a "dry hysterectomy" technic were given; 320 animals were alive after hysterectomy, but there was a subsequent loss of 37% of the animals, mainly during the first and second weeks. Their specific-pathogen-free maintenance, feeding, and association with an anerobic flora were described. Feeding 3 times a day vs twice a day decreased mortality from 48% to 20%.


The use of spontaneously hypertensive rats for the study of anti-hypertensive agents. Hypertension studies using laboratory animals have been conducted since 1930. These were not completely satisfactory because either surgery or pharmacologic induction were required to produce hypertensive animals. Many attempts have been made to breed spontaneously hypertensive rats, mainly from the Okamoto strain. The cause of hypertension in the rat, with specific reference to genetic aspects and pathogenicity, were reviewed. The hypertensive rat is an acceptable model for hypertension studies because of the stability of the hypertensive state and the reproducibility of experimental effects. It is a particularly useful model for screening antihypertensive agents. Development of mutant Okamato stran rats which have brain softening, cerebral hemorrhages, and myocardial infarctions would permit the screening of specific therapeutic agents with fewer side-effects. Mutants which develop obesity, hyperlipidism, and early atherosclerosis have been reported in Okamoto strain X Sprague-Dawley rat crosses.


Islet cell membrane alteration by diabetogenic drugs. Freeze-fracture of islets of Langerhans treated in vitro with diabetogenic agents alloxan and streptozotocin shows a decrease in the number of intramembranous particles of islet cell plasma membranes. This decrease is restricted to the membrane's A-fracture face and it can be prevented by experimental conditions which are known to counteract the toxic effect of both alloxan and streptozotocin.


Surgical "correction" of solitus-concordant, double-outlet left ventricle with L-malposition and tricuspid stenosis with hypoplastic right ventricle. This report concerns a 2-year-old boy who had situs solitus and atrioventricular concordance with double-outlet left ventricle, L-malposition of the aorta, pulmonary stenosis, tricuspid stenosis, hypoplastic right ventricle, ventricular septal defect, and secundum atrial septal defect. These lesions were correctly diagnosed preoperatively, and "correction" was achieved by closing the atrial septal defect and tricuspid valve and performing a Fontan procedure using an antibiotic-sterilized aortic homograft for the conduit. The patient initially did well postoperatively but, despite vigorous diuretic therapy, developed large bilateral pleural effusions necessitating frequent aspiration. He died unexpectedly one month after the operation. Postmortem examination showed the repair to be intact. Despite his death, we are encouraged to consider this operation in such cases in the future.


The postvalvulotomy propranolol test to determine reversibility of the residual gradient in pulmonary stenosis. We advocate the use of propranolol in very low dosage at the end of operation to determine a prognosis of the long-term results to be expected after valvulotomy in diverse types of pulmonary stenosis.


Surgical treatment of floppy mitral valve syndrome in children. Five children whose ages ranged from 9 to 14 years underwent operation for floppy mitral valve syndrome. The clinical course of this syndrome in young patients was characterized by exceptionally rapid deterioration in congestive heart failure after the onset of symptoms. The children responded poorly to medical treatment. Early surgical treatment should be recommended soon after the onset of congestive heart failure. Three out of 5 patients required an associated tricuspid valve replacement for a floppy tricuspid valve, whose structure showed marked myxomatous transformation. Because of the high incidence of myxomatous transformation of the tricuspid valve in children, significant tricuspid insufficiency in this syndrome should be managed by valve replacement.


Aortoventriculoplasty: a new technique for the treatment of left ventricular outflow tract obstruction. Aortoventriculoplasty is a new method of treatment for left ventricular outflow tract obstructions. The concept is based on creating a surgical defect which is patched in such a way as to provide the largest possible outflow to the left ventricle. The incision of the aorta continues down as far as necessary, with the right ventricular wall, the aortic ring, and the septum being cut. Reconstruction with an inner Dacron patch on the septum is completed by replacing the aortic valve with an adequate prosthesis, covering the aortic incision with the same patch, and patching the right venticular opening with an outer patch. This method was used in 4 children with tunnel-like subaortic stenosis, 3 of whom had had unsuccessful previous surgical attempts. Other associated lesions including parachute mitral valve were also corrected during aortoventriculoplasty. Hemodynamic results were excellent following this operation. Two patients died postoperatively, one from advanced myocardial damage and progressive failure and the other from cerebral ischemia caused by insufficient retrograde perfusion through an aortic coarctation that was not repaired earlier. No arrhythmias were observed following the procedure. The other 2 patients are well 7 and 5 months postoperatively with excellent hemodynamic function.


[Streptoverticillium krissii n. sp. forming teleocidins A and B]. The taxonomy of the actinomycete LIA-0371, regarded as a new species Streptoverticillium krissii n. sp., was studied. The culture has straight sporophores assembed into verticils, gray-cream-coloured aerial mycelium and brown colonial mycelium, and produces pentaene 0371, ichtiocide T-0371, and a soluble pigment. Physico-chemical analysis has shown that ichtiocide T-0371 is identical to teleocidins A and B.


Possible rejection of an HL-A identical sibling renal allograft. A case is described of possible rejection of a renal allograft between siblings who are HL-A identical and who had a negative mixed lymphocyte reaction.


[Intensity of bacterial methane formation in ooze deposits in lakes]. The rate of methane production of bacteria via the decomposition of acetate in ooze deposits of the Mari lakes was 0.0165 to 0.483 mg CH4/day/ litre wet ooze. From 32 to 98 per cent of methane in the ooze of studied reservoirs formed through microbiological reduction of carbon dioxide by hydrogen.


[Microflora of underground waters in oil and gas fields of Mangyshlak]. The distribution of various physiological bacterial groups with respect to the geological profile and area was studied in underground waters of the gas and oil bearing complexes of Mangyshlak. Metamorphism of the environment in the complexes, in the direction of flow of underground waters, from the oxidative to the reductive medium, is correlated with changes in the composition of the prevailing and accompanying bacterial groups for each of the zones.


[The diagnostic value of enzymes in cerebrospinal fluid (author's transl)]. The clinical value of enzyme activities in cerebrospinal fluid (CSF) should be proved by examination of GOT, GPT, LDH and CPK in blood and CSF of 115 unselected and 4 selected patients. Only the GOT showed a significant correlated increase in diffuse vascular diseases in both, serum and CSF. Discussing the literature the authors affirm, that only mechanical or functional lesion of the blood-brain-barrier will increase the enzyme activities in serum and CSF. The origin of these enzymes however is unknown till now.


[The pathogenesis of acne vulgaris (author's transl)]. Stickl's method of oral treatment of acne vulgaris with antigens has been carried out on 26 test persons. During the treatment the number of comedones increased significantly and the number of papules decreased significantly. Biochemically, a significant increase of the free fatty acids and a significant decrease of the triglycerides could be demonstrated in the skin surface lipids, the total amount remaining unchanged. The following important conclusions for the pathogenesis of acne may be drawn: 1. The living conditions for Corynebacterium acnes on the surface of the skin or in the ducts of sebaceous glands respectively are influenced by the immunological system of the host. 2. The free fatty acids have a comedogenic effect in vivo. 3. The free fatty acids are not responsible for the development of inflammatory acne efflorescences.


Deletions of ribosomal protein genes in Escherichia coli merodiploids heterozygous for resistance to streptomycin and spectinomycin. In a merodiploid strain of Escherichia coli heterozygous for the ribosomal protein genes spc and str, deletions were observed preventing the expression of either gene but permitting the expression of the other. This suggests that the spc and str genes are in separate transcriptional units.


Antibacterial and antitumor activity of some derivatives of ureidosuccinic acid. The effect of several derivatives of ureidosuccinic acid on the growth of Escherichia coli 387, Staphylococcus aureus strain 209 and its mutant UV-2, Sarcina lutea, Candida tropicalis and Neurospora crossa 9863 as pre-screening systems for antitumor activity was studied. It was found that dihydrazide of D,L-ureidosuccinic acid (DHUA) had a marked antibacterial activity. The inhibitory effect of DHUA on N. crassa could not be removed by aspartic acid, ureidosuccinic acid, dihydroorotic acid, orotic acid, uracil or cytosine. DHUA suppressed the growth of Myeloma P-8 by 38%, that of Sarcoma 180 by 12% and that of Yoshida sarcoma by 19%. No effect was found on the growth of Lymphosarcoma Pliss.


[Functional study of peripheral obstructive arteriopathies using an ultrasound flow detector]. An ultrasound flow detector was employed to measure pressure values at the ankle at rest and after physical exercise in 91 limbs belonging to 61 patients with various degree of arteriosclerotic occlusion, and in 10 healthy subjects. Basal values and percent falls after effort, and recovery times were compared with the symptomatologies and the different degrees of occlusion. Statistically significant correlations were observed.


[Influence of vitamin A on the distribution of glycosaminoglycans in rat tissues]. Glycosaminoglycans (GAG) from brains, intestines, livers and skin of rats were analyzed by electrophoretic and enzymatic methods. Variations in GAG distribution have been studied in rats fed on a vitamin-A-deficient diet and on a diet supplemented with an excessive quantity of vitamin A. Hypervitaminosis A resulted in a decrease in GAG isolated from connective and hepatic tissues. The incorporation of labeled sulfate into the GAG of these tissues has been studied. Hypervitaminosis A resulted in a decrease in sulfate incorporation into the GAG isolated from connective tissues. A large increase in sulfate incorporation into the GAC of the digestive tract is observed for vitamin-A-treated rats. A decrease is noted for vitamin-A-deficient rats. It was suggested that these variations in distribution and specific activity of GAG could be due to different effects of vitamin A. Vitamin A seems to be required either for the release of lysosomal enzymes or for the sulfatation and elongation of certain glucidic chains in the biosynthesis of sulfated GAG.


Combined therapy with tetrabenazine and pimozide in Huntington's chorea: pilot study. Current medication for Huntingtons chorea is based on compounds which affect the activity of acetylcholine and dopamine in the basal ganglia and is unsatisfactory. This report describes a small clinical trial of dopamine antagonists, tetrabenazine (Nitoman) and pimozide (Orap). Improvement was early and striking but was not maintained over the trial period of 83 weeks.


Glycosaminoglycans of EDTA soluble and insoluble dentin in dentinogenesis imperfecta type I. A study of glycoasminoglycans (GAGs) in dentinogenesis imperfecta Type I (DI I) revealed increased GAG in DI I EDTA soluble dentin as compared to controls. EDTA insoluble GAG contained less GAG than age-matched controls. The role of GAG in dentin pathosis is discussed.


Lipolysis as a function of cell numbers and fat content: comparison between isolated rat and dog adipocytes. The lipolytic responses to dihydroergotamine (5 mug/mi) of isolated rat adipocytes andto epinephrine (50 ng/m1 and 1 mug/m1) of both rat and dog adipocytes were measured over a period of two hours. Glycerol release was calculated as a function of either glycerol ester content or of cell number per incubation vial. The conventional calculation based on glyceride content gave the following results: a) epididymal fat cells from rats weighing less than 160 gm were more sensitive to dihydroergotamine and epinephrine than were fat cells from heavier animals weighing close to 200 gm; b) dog adipocytes from abdominal subcutaneous tissue were less sensitive to eipnephrine than were rat adipocytes. No such differences were noted when the same data were calculated on the basis of cell numbers per incubation vial: the lipolytic response was uniform with rat adipocytes obtained either from the lighter or the heavier weight groups, and so was the response of dog and rat cells. These results indicate that in the type of studies where receptor-dependent hormone and drug effects are measured, the number of cells per incubation vial is an important parameter to be considered in evaluating a lipolytic response.


Human muscle fiber types in power lifters, distance runners and untrained subjects. Muscle biopsies were taken from the vastus lateralis of 12 males: 5 control subjects, 4 power lifters and 3 distance runners. Three fiber "types" were distinguished by comparing serial sections for alkaline myofibrillar adenosine triphosphatase (ATPase) and succinic dehydrogenase (SDH) activities: 1. high ATPase and low SDH; fast-twitch-glycolytic (FG). 2. High ATPase and high SDH; fast-twitch-oxidative-glycolytic (FOG). 3. Low ATPase and high SDH; slow-twitch-oxidative (SO). In some cases the distinction between the FOG and FG classess was not clear and a group termed "transitional" was employed. A variation in percentage of fiber types and fiber area was found among individuals. The percentage of SO fibers varied from 19.6-60.1% within all 3 groups, with a mean of 40.5%. In the control group approximately 75% of the fibers were oxidative (FOG + SO). The major characteristics of the lifters were a decrease in the percentage of FOG fibers and a hypertrophy of FOG and FG fibers. The distance runners had a high percentage of oxidative fibers with few FG fibers. It is suggested that the fast-twitch fibers are mainly involved in the adaptation of muscle to exercise since the percentage of SO fibers varies greatly among individuals within and between the 3 groups studied.


Inhibition of extensor gamma motoneurons by anatagonistic primary and secondary spindle afferents. About 2/3 of the gamma efferents isolated from the medial gastrocnemius nerve were inhibited by longitudinal high-frequency vibration applied to the tendons of the non-contracting pretibial flexors (decerebrate cats). The inhibition appeared at 15-25 mum amplitude of vibration and increased up to maximum at nearly 100 mum. Increasing the frequency of vibration from 100 to 300 Hz increased the inhibition. The reflex effects elicited by muscle vibration corresponded well in incidence and magnitude with those evoked by tetanization of the deep peroneal nerve at group I stimulus strength. The reflex disappeared when the nerve supply of the vibrated muscles was cut. The sensitivity of some pretibial proprioceptors to vibration was also tested. It is concluded that primary spindle endings of the pretibial flexors inhibit the extensor gamma motoneurons. Some findings hint at a spinal pathway involving Ia inhibitory interneurons. In addition, an inhibitory action of pretibial group II afferents, probably secondary spindle endings, on extensor gamma efferents was demonstrated. The described fusimotor inhibition by antagonistic muscle spindle afferents is a further example of alpha-gamma-linkage.


DNA methylase: purification from ascites cells and the effect of various DNA substrates on its activity. DNA methylase has been purified 405-fold from Krebs II ascites cells. The purified enzyme is homogeneous on SDS-poly acrylamide gel electrophoresis (molecular weight about 80,000) and the only product of the reaction with DNA is 5-methyl cytosine. Both native and denatured DNA are methylated by the enzyme; with calf thymus DNA the double stranded form is the better substrate but the enzyme preferentially methylates single stranded E.coli DNA even in "native" preparations. Our results do not support a mechanism whereby the enzyme methylates DNA by binding irreversibly and "walking" along it. By measuring maximum levels of methylation of DNAs from different sources we have estimated the proportion of unmethylated sites present in them. Homologous ascites DNA can be methylated, but only to about 5% of the level of the best substrate, undermethylated mouse L929 cell DNA. DNA isolated from growing cells or tissues is a better substrate than DNA from normal liver or pancreas, or from stationary cells.


[Study of diabetes mellitus morbidity].

[Study of diabetes mellitus morbidity]. The incidence of diabetes mellitus was studied among the population of Dushanbe. TTH test was used to examine 8768 persons. Morbidity index proved to constitute 15.46 per 1000 residents. This index increased with age from 0.36 in the age group from 15 to 29 years to 81.06 per 1000 residents in the age group of 60 years and older. The ratio of morbidity index of the manifest and latent forms of diabetes mellitus constitutes 1.13: 1 (8.68 and 6.78 per 1000 residents, respectively). By the results of study with the use of TTH test the total morbidity index was 3.1 times greater than that according to the application for medical aid to the therapeutic-prophylactic institutions of the town.


[Ways to lower temporary work disability in diseases of the endocrine system and disorders of metabolism]. The level of temporary incapacitation was studied with the aid of analytical prognostication (on the example of the town of Chimkent). Diseases of the endocrine system and metabolic disturbances were of significance among the causes of temporary incapacitation (1% of all the cases and 1.4% of total duration of temporary incapacitation) of the urban population. The indices studied were greatest in diseases of the thyroid gland and diabetes mellitus. Incapacitation indices depended on the patients' age and sex. The main routes for reduction of temporary incapacitation in diseases of the endocrine system were early detection, improvement of dispensary observation, and also complex treatment of the patients.


[Activity of the hypophyseal-adrenal system under the influence of substances of mediator type action]. The paper treats of the results indicating the activation of the hypophysioadrenal system following the stimulation of the central adreno-, cholino-, serotonino- and histamino-sensitive receptors in case of administration of the mediators or their precursors into the third ventricle of the rat brain. At the same time it was shown that depression of catecholamine and serotonin synthesis in the brain after the administration of alpha-methylparatyrosine or parachlorphenylalanine, respectively, and also an exhaustion of the tissue stores of the monoamines in administration of reserpine failed to influence significantly the reaction of the hypophysio-adrenal system to the immobilization of the animals. The data obtained led to the conclusion that the reactions of the hypothalamus-hypophysis-adrenal cortex system to the stimuli were not strictly determined by any one monoaminergic mechanism of the brain.


The neurospora plasma membrane ATPase is an electrogenic pump. Biochemicalical evidence is presented which demonstrates that the Neurospora crassa plasma membrane ATPase (ATP phosphohydrolase, EC 3.6.1.3) is an electrogenic pump. The electrical potential across the Neurospora plasma membrane, as monitored by [14C]SCN- uptake by isolated Neurospora plasma membrane vesicles, is markedly increased interior positive under conditions of ATP hydrolysis catalyzed by plasma membrane ATPase. [14C]SCN- uptake by the vesicles is minimal in the presence of Tris phosphate, Tris phosphate plus Mg+2, Tris ADP plus Mg+2, and Tris ATP, but is markedly stimulated in the presence of Tris ATP plus Mg+2.


An experiment eliminating the rotating carrier mechanism for the active transport of Ca ion in sarcoplasmic reticulum membranes. An experiment has been carried out to test the rotating carrier mechanism of the translocation event in membrane transport. To the Ca-ATPase in intact sarcoplasmic reticulum membranes, 2,4-[3H]dinitrophenyl-cadaverine has been covalently attached by the action of the enzyme, transglutaminase. The binding of anti-2,4-dinitrophenyl antibodies to the 2,4-dinitrophenyl-modified membranes was found to have no effect on either the Ca-ATPase activity or the Ca ion transport rate of the membranes. These results rule out the rotating carrier mechanism in this system. A different scheme for the translocation process, the aggregate rearrangement mechanism, is discussed.


Introduction of breast implants through the abdominal route. We present our technique of doing an abdominal lipectomy and augmentation mammaplasty in the same operation, through the same incision, in selected patients. We introduce the breast implants through tunnels made from the top of the abdominal pocket into the breast areas. We have had no complications in 12 patients in whom we have done this operation.


[Exogenous psychosis in a patient with carcinoid syndrome following treatment with p-chlorophenylalanine (PCPA)]. A case is reported of a patient with carcinoid syndrome who developed a exogenous psychosis while under treatment with the serotonin-inhibitor p-chlorophenylalanine (PCPA). Partial symptoms similar to delirium and schizophrenia were exhibited. The attached literature survey focuses on the psychological side effects of PCPA treatment. A discussion follows concerning noteworthy phenomenological similarities between the case reported and certain forms of amphetamine psychosis. Common biochemical mechanisms are hypothetically stated.


[Blind nailing with reaming in fractures of the femoral shaft. Technique, indications, and results in 399 cases]. The authors have treated 399 fractures of the femoral shaft by blind nailing with reaming following Kuntscher's technique. They fully describe the necessary technical details for a safe operation. They emphasize the importance of an adequate instrumentation and report peroperative complications and the way for avoiding them (poor reduction of the fractures, difficulty for bridging the fracture site, creating of additional fragments, blockage of reamers or nails in the medullary canal). Indications and results are described. I non-union, 15 malunions and 4 sepsis were reported.


[Chairi pelvic osteotomy in adults. Technique, biomechanical study and early results in 21 cases]. The authors have reviewed 14 cases of Chiari pelvic osteotomy performed in adults and followed up during more than one year. They describe the bio-mechanical properties of this procedure, and a surgical technique with some original modifications. They conclude that this operation may be contra-indicated in young women for obstetrical reasons. It is indicated in degenerative arthritis of the hip at an early stage when acetabulum is dysplasic or the femoral head subluxated.


[Osteoarthrosis of the first metatarso-phalangeal joint. Surgical treatment; 92 cases]. The study of 92 cases of osteoarthrosis of the first metatarso-phalangeal joint (or hallux rigidus) shows the importance of two aetiological factors : excessive length of the first metatarsal in the so-called primitive osteoarthrosis, and traumatism for the secondary forms. The results of arthrodesis are rather better than these of arthroplasty and exostosectomy, mainly in men after 50 years.


[Treatment of comminuted fractures of the distal end of the radius by traction using transfixing Kirschner's wires and plaster cast]. Based on the analysis of 45 cases of comminuted fractures of the lower extremity of the radius, this study points out the insufficiency of conventional treatments. The authors advocate a technique using a Kirschner's wire passed through the metacarpal bones and another one through the ulna, both beind embeded in plaster cast. This method was tested on 19 cases with encouraging results. The technique was precisely described and the authors think that it should be used in fractures incorrectly reduced by conventional methods.


A diurnal rhythm of incorporation of L-[3H] leucine in myocardium of the rat. The influence of the time of day on myocardial protein synthesis and hypertrophy was examined in rats entrained to a 12-12 hr light-dark cycle. Analysis of ventricular weight to body weight ratio indicates that isoproterenol was a more effective stimulus of hypertrophy if given during the dark period, when the rat is most active, than when administered during the light hours. The difference was not attributed to alterations in percent water of the myocardium or nutritional status of the animal. Differential incorporation of labeled leucine into protein throughout the day indicated that myocardial protein may be synthesized at the greatest rate late in the light period with least synthesis occurring during the late hours of the dark period. The implications of these results are discussed.


Estimated glycolytic flux in infarcting heart. Regional ischemia results in infarction even in the presence of residual oxidative metabolism. Although glycolytic flux is relatively inhibited at the level of phosphofructokinase, glucose competes more effectively than does free fatty acid for the residual oxygen supply. Glycogen is not the major energy source until effective collateral flow is virtually zero.


Attenuation of beta-adrenergic cardiac responses in chronically hypoxic rats with right ventricular hypertrophy. Rats were kept for 30 days in an O2-N2-mixture of gradually reduced O2 (18 leads to 6 Vol%) and constant CO2 (0.5 Vol percent). This induces a selective hypertrophy of the right ventricle and the ratio ventricular/body weight (g/kg) increased from 0.6 to 1.4 while it remained constant in the left heart. In the right and left ventricles of control animals the contents of myocardial ATP (4.0 muM/g) and of phosphocreatine (CP) (5.8 muM/g) were the same. These values were not significantly changed by hypertrophy. In the control animals, a single test-dose of isoproterenol (30 mg/kg), subcutaneously administered 2 hr before the heart was removed, caused a diminution of the ATP-content by 15 percent in the right ventricle and by 40 percent in the left. The CP-content was reduced by 40 percent on the right and by 50 percent on the left side. In the hypertrophied right ventricle, however, there was no major decrease in ATP and CP following the isoproterenol injection. In the nonhypertrophied left heart the response to isoproterenol was still detectable but much less than normal. As the chronotropic and hypotensive effects of isoproterenol were also lessened in the hypoxic animals it is concluded that a general reduction in the responsiveness to beta-adrenergic stimulation has occurred.


Restriction of beta-adrenergic responsiveness in hypertrophied hearts of chronically isoproterenol-treated rats. A single subcutaneous dose (1 mg/kg) of isoproterenol (ISO) increases the net calcium-45 uptake into the ventricular myocardium of normal rats by a factor of 3 to 4 within 6 hr. When the same dose of ISO was administered to rats previously treated with 1 mg ISO/kg per day for 1--3 weeks, this rise in labeled Ca-uptake was greatly reduced. Consequently the stimulatory effect of ISO on the Ca-dependent high-energy phosphate consumption was considerably diminished. Furthermore the chronic application of ISO produced a hypertrophy of both ventricles. When this treatment was discontinued for 7 days the ventricular weights returned to normal, whereas the restriction of beta-adrenergic reactivity persisted for more than 3 weeks. The results indicate that the decrease in responsiveness to beta-adrenergic agents is not due to the hypertrophy itself but must be considered to be an independent phenomenon-possibly resulting from adaptation to chronic beta-adrenergic overstimulation.


The mechanism of chlorpromazine and quinidine inhibition of cardiac sarcotubular ATPase. Although chlorpromazine and quinidine have dissimilar chemical properties, both are negative inotropic agents and both depress the ATPase activity of cardiac sarcotubular fractions. With the aid of gamma-AT32 P we have identified the step in ATP hydrolysis which is inhibited by each of these agents. By optimizing the conditions for formation of a phosphorylated intermediate (EP) by addition of 5 mM calcium to the incubation medium we found that chlorpromazine (0.25--1 mM) severely depressed EP formation, whereas quinidine (0.25--1 mM) had no effect. After the isolation of EP we showed that chlorpromazine had no effect on the magnesium-facilitated hydrolysis of EP, whereas quinidine was a potent inhibitor of this hydrolytic step. The effects of both quinidine and chlorpromazine on the E + ATP equilibrium EP + ADP reaction were studied. Quinidine had no effect on this reaction, whereas chlorpromazine, at 1 mM, shifted the reaction toward ATP formation.


The effects of hypoxia, hypertrophy, and diet on rat myocardial ornithine decarboxylase activity. We have shown that there is a highly significant difference between right and left ventricular ornithine decarboxylase activity. The left ventricle had a much higher activity compared with the right ventricle. A restricted diet caused a decrease in ornithine decarboxylase activity after 24 hr. Hypoxia caused a depression of the ornithine decarboxylase activity during the first 2 days of the experiment. In the hypertrophied right ventricle there was an initial decrease in ornithine decarboxylase after 24 hr and then a gradual increase in ornithine decarboxylase activity during the 7 days of the experiment. The increase in ornithine decarboxylase activity became significant when an increase in tissue weight became apparent.


Polyamine and nucleoprotein correlations in hypertrophied and perfused heart. A close relationship has been observed between polyamine, as spermine and spermidine, and nucleic acid synthesis during heart hypertrophy, induced in the rats experimentally, by physical exericse (swimming). The role of spermine on RNA synthesis has been studied by perfusion experiments of the heart. Spermine is able to stimulate myocardial RNA synthesis of all subcellular fractions. The biochemical mechanism of this phenomenon may be explained by the results of histone acetylation under the action of spermine, showing an increased radioactivity of F 2aI and F 2a2 arginine-rich histone fractions. This suggests that spermine may act modulating histone acetylation, with a consequence on the gene transcription mechanism.


Studies on fluoride distribution in infants and small children. The fluoride (F) concentrations in hard tissues and blood plasma were determined in biopsy and autopsy specimens from fetuses, infants, and children on varying F intake. In newborn autopsy cases specimens consisting of rib, jawbone with teeth, and blood plasma the F concentrations of bone and dentin were of the same order, those of the enamel lower. Correlations between individual F values in different tissues were all positive, highest for enamel/dentin. Low birth weight entailed only slightly reduced F contents, high water F significantly increased F contents. In the biopsy material (rib and blood plasma) the maximal rib/ash concentration was about 400 parts/10(6) F. A negative correlation between rib F and plasma F is specially commented on. The possible influence of F on bone development as expressed by blood plasma F and phosphatase activity was investigated in three groups of infants aged 2-6 months, either breast-fed or fed dry-milk formulas diluted with drinking waters of different F content. The children of these groups were calculated to ingest F in the ratio of about 1:10:50. The highest F group had higher plasma F values than the two other groups, whereas its alkaline phosphatase was significantly higher than that of the lowest F group only. The influence of disturbances in the skeletal development on F retention studied in physically handicapped children aged 4-15 years living in a city with about 1 part/10(6) F in the drinking water. The severely handicapped showed a higher urinary F excretion than the controls.


Effect of granulocyte chalone on acute and chronic granulocytic leukaemia in man. Report of seven cases. This study reports results from the first clinical tests in which 7 patients with myeloid leukaemia (5 acute and 2 chronic leukaemias in metamorphosis) were treated from 4 to 45 days with granulocyte chalone, the tissue-specific endogenous inhibitor of granulopoiesis. It was observed that i.v. injection of partially purified chalone inhibits proliferation of leukaemic, and presumably also normal granulocytic cells, leaving all other cell types unaffected. Inhibition of leukaemic growth was distinct in 6 of the 7 patients; in 5 cases the inhibition was followed by acutal regression of the leukaemia, lasting up to several months in the absence of any maintenance therapy, and in one case the treatment led to a complete remission. Chalone treatment also resulted in an enhancement of erythropoiesis and megakaryopoiesis, and in phenomena some of which were totally unexpected, such as immunostimulation and a remarkable resistance to bacterial infections in the presence of extreme granulocytopenia. This study shows that granulocyte chalone is biologically active against myeloid leukaemia in man, but not that the therapeutic value of the impure chalone is superior to modern cytostatic drugs. Long-term therapeutic trials were not possible with the partially purified preparations available, mainly because of side-effects which prevented adequate dosing.


Tropomyosin binding to F-actin induced by myosin heads. Tropomyosin is a regulatory protein associated with F-actin in many actomyosin contractile systems. If in vitro conditions are such that tropomyosin binds only slightly to F-actin, then the addition of myosin heads can induce stoichiometric binding between them. This suggests that formation of rigor bonds between actin and myosin heads may cause some change in the actin, stabilizing the appropriate binding site for tropomyosin.


Carbon dioxide homeostasis during laparoscopy. Arterial blood gases were monitored in ten patients undergoing laparoscopy for diagnostic or sterilization procedure. During constant volume of ventilation, mean arterial co2 tension rose approximately 5 torr following insufflation of the peritoneal cavity with carbon dioxide. Arterial pH changes correlated well with arterial Pco2 changes. There was no significant change of oxygen tension in these patients.


Insecticide susceptibility of some vector fleas and mosquitoes in Burma. Rat fleas and mosquitoes are insect vectors of public health importance in Burma. Plague is endemic in Central Burma and DDT has been the principal insecticide used for its control to date. Dengue haemorrhagic fever, recently introduced and transmitted by Aedes aegypti, has been spreading to major towns since 1971. The rodents, Rattus rattus, R. exulans, Bandicota bengalensis, Mus musculus, as well as shrews were commonly caught during routine trapping in the country. Rattus norvegicus, prevalent in Rangoon City, is not found in Central Burma. The rat fleas, Xenopsylla cheopis and X. astia, were found to be infesting these rodents, the former being the principal vector of plague. Insecticide susceptibility tests have been carried out periodically in plague endemic areas and Rangoon since 1966 and it is now observed that rat fleas in most of these endemic towns and Rangoon Port are no longer susceptible to DDT. Subsequent rechecks in towns where fleas became resistance to DDT show that fleas are persistently resistant to the insecticide. Aedes aegypti is found to be highly prevalent both in rural and urban areas of almost every major town and townships below 900 meters. Insecticide susceptible tests on this mosquito in limited areas show that the mosquito is generally resistant to DDT but susceptible to other insecticides. With the development of DDT resistance in fleas, it is now necessary to change to an effective insecticide in the control of plague in Burma.


Hydrocortisone in the management of dengue shock syndrome. A total of 98 patients with dengue shock syndrome admitted into Children's Hospital from February 1973 to February 1974 were randomly selected into 2 groups. A double blind controlled trial of the efficacy of pharmacologic doses of hydrocortisone hemisuccinate was carried out. The 2 groups were confirmed to be completely matched by age, sex and severity of the disease. Nine deaths occurred out of 48 cases in the steroid group (Case Fatality Rate 18.75%) and 22 deaths out of 50 cases in the non-steroid group (Case Fatality Rate 44%), the difference being statistically significant. No significant difference was detected in fluid requirements and other morbidity pattern.


Dengue haemorrhagic fever in Burma.

Dengue haemorrhagic fever in Burma. Although sporadic from 1965 to 1969, a major outbreak of dengue haemorrhagic fever (DHF) occurred for the first time in Rangoon in 1970. Since then the disease has occurred every year in Rangoon and is now observed to be expanding to other urban areas in the country. The clinical diagnosis of DHF was confused by concurrent outbreaks of influenza A in 1971 and influenza A and B in 1972. A laboratory study of 3,447 clinically diagnosed haemorrhagic fever cases showed that 1643 cases (47.8%) were due to dengue and chikungunya, 296 (8.6%) to influenza A, 85(2.5%) to influenza B, 12(0.3%) to measles and 1411(40.8%) were of unknown aetiology during the 5 year period 1970-1974. Ae. aegypti mosquitoes are widely distributed in the country up to and including 900 meters above sea level but breeding is not found above that altitude. The absolute larval population which is highest in July as well as landing rate correlated with the peak incidence of DHF cases.


Ocular reaction to oxprenolol. A case report. A case is presented of a patient who developed ocular symptoms and a skin rash after treatment with oxprenolol (Trasicor) for 2 months. The lesions improved on withdrawal of the drug and her eye symptoms became worse when she was again treated with oxprenolol. Patients who receive beta-adrenergic blocking drugs must be watched carefully for side-effects.


The role of technology in modern nutrition. The three basic nutritional problems facing the world today are the over-intake of foods by individuals or population segments, nutrient deficiencies in the diet of population groups, and food shortages. In all three cases the food scientist has a role to play but it is stressed that close co-operation between the nutritionist, the agricultural scientist and the food technologist is essential. To alleviate the problem of food shortages, consideration should be given to unconventional food resources. The shortage of trained food scientists in South Africa detrimentally affects research and development and could also affect quality control.


Interposition mesocaval H shunt associated with a left inferior vena cava. Variations in the anatomy of the inferior vena cava are important in abdominal surgery. A patient with recurrent bleeding from esophageal varices was noted to have a single left inferior vena cava at the time of panangiography. An interposition mesocaval H shunt subsequently was performed successfully. This represents the first reported case in which a mesocaval H shunt has been performed in a patient with a single left inferior vena cava.


Fibrodysplasia with dissecting aneurysm of the hepatic artery. The presentation and management of a patient with a symptomatic hepatic artery aneurysm is detailed. The aneurysm occurred secondary to fibromuscular hyperplasia of the hepatic artery and was associated with a limited area of dissection. This patient represents the second reported case of this type of aneurysm of the hepatic artery,


Use of high dose X-irradiation to block back stimulation in the MLC reaction. Paradoxical stimulation, "back stimulation" was observed in MLR (mixed lymphocyte culture reaction) in both family and population studies. This is one of the major problems in obtaining clear cut-off points for stimulation and non-stimulation in MLR using LD (lymphocyte defined) homozygous typing cells. The ability to provoke back stimulation was found to be different among LD homozygous typing cells. The presence of nonspecific blastogenic factors in supernatant from mixed culture of LD homozygous cells and heterozygous cells, which might be responsible for back stimulation, was confirmed. It was clearly shown that irradiation of LD homozygous typing cells with 6,000 rads instead of the widely used 3,000 rads can greatly reduce or eliminate this back stimulation without introducing any false non-stimulation.


[Use of immunochemical methods for characterization and purification of tissue-specific inhibitors of mitotic activity (chalones)]. The 81% ethanol-precipitable fraction of water-soluble proteins from skin inhibiting the proliferation of epidermal tissues was shown to contain 9 protein components according to acrylamide gel disk-electrophoresis. Seven of these were identical to homologous serum proteins and could be adsorbed on the corresponding immunosorbents. Two proteins remained in the solution after immunoadsorption. Their electrophoretic properties were the same as those in the total 81% ethanol fractions. These proteins like the 81% ethanol fraction inhibited the entering of cells into mitosis and DNA synthesis phase.


[Binding of Rb86 by a microsomal fraction of bovine cerebral cortex cells]. The maximal binding of 86Rb was noted when ions of Mg, ATP and Na were present simultaneously. The availability of olytoriside (1-10(-4)M), CaCl2 (1-10(-3)M) and phospholipase A (1-10(-5)M) in the medium and the removal of Na and substitution of ATP for ADP decreased to a different extent the binding of 86Rb.


Evaluation of a short term in vitro test for granulocyte chalone activity. A short term in vitro test for granulocyte chalone activity eas examined for its specificity and reliability. The test used the inhibition, by granulocyte extracts, of 3H-thymidine (3H-Tdr) uptake in to the acid-insoluble material by rat bone marrow cells in vitro to measure possible chalone activity. Among the many possible 3H-Tdr artifacts pool size dilution by Tdr contained in the extracts was excluded using an E. coli mutant requiring thymine. Several amino acids and biogenic amines do not affect the test. However, continuous and pulse labelling of bone marrow cells with 3H-Tdr, viability tests and micro flow fluorometric measurements of the cell cycle distribution following colcemid treatment strongly suggests that the cells do not proliferate in vitro during short term incubation, since practically no cells enter the S-phase, cells in the S-phase die and few if any cells proceed through G2 and mitosis. Moreover, the test cannot exclude cytotoxicity. Thus, the in vitro test may only sceem for an unspecific S-phase inhibitor and must hence be supplemented by another assay to prove the chalone nature of an extract or fraction. The test per se fails to meet most of the requirements of a valid granulocyte chalone assay.


[Remote and immediate results of treatment of cancer of the body of the stomach and the cardia from 1959-1973 (according to the data of the Pskov District Oncological Dispensary)]. In Pskov Province oncological dispensary during 1959-1973 156 patients were operated upon for cancer of the stomach and cardia. The postoperative mortality after gastrectomy was 18.5%, after proximal resection of the stomach - 30.7%, after combined gastrectomy - 31%. A 5-year survival in relation to patients operated upon was noted in 28.8%, to those discharged from the hospital - in 36.2%, to those followed up - in 50%.


Hypothermic effect of cocaine in rats.

Hypothermic effect of cocaine in rats. Cocaine injected intraperitoneally into rats resulted in a dose-dependent hypothermia. Intracerebral injection of smaller doses also produced a fall in body temperature. In rabbits and guinea-pigs, cocaine produced hyperthermia, in mice and chicks it produced hypothermia while inconsistent changes were produced in goats. Pre-treatment of rats with 6-hydroxydopamine, alpha-methyl-m-tyrosine or haloperidol significantly antagonized the cocaine hypothermia. Pre-treatment of the rats with either hyoscine or methscopolamine resulted in some but non-significant attenuation of the cocaineinduced hypothermia. Pre-treatment with p-chlorophenylalanine, however, did not modify the cocaine hypothermia. Pargyline pre-treatment significantly antagonized the hypothermic action of cocaine. It is suggested that cocaine may cause the release of noradrenaline centrally or it may potentiate its action by interfering with the uptake mechanism. It is also possible that cocaine may have a direct effect on the heat regulating centre in the hypothalamus.


A system for evaluating and treating chronic back disability. Five methods of personality assessment are evaluated to provide guidance for the psychological treatment of patients with chronic back pain. Patient pain drawings, pentothal pain studies, stress score index, psychological testing with the Minnesota Multiphasic Personality Inventory (MMPI) and response to treatment challenge are used as measurements for evaluation. This evaluation gives the treating staff guidelines for individual treatment programs utilizing operant conditioning techniques. Using this approach, three fourths of the severely disabled patients seen have been successfully treated.


[Combined administration of ipratropium bromide (sch 1000) and fenoterol in patients with chronic obstructive airway disease (author's transl)]. 40 outpatients with chronic obstructive airway disease received the parasympatholytic bronchodilator ipratropium bromide (Sch 1000) and the sympathomimetic bronchodilator fenoterol from a metered dose inhaler. After evaluation of the initial values, first Sch 1000 was administered and 20 min. later airway resistance was measured, then fenoterol was given and a measurement was taken again 20 min. later. On the following day the aerosol inhalants were given in the reverse sequence. After the first inhalation 0.08 mg Sch 1000 proved to be an equally strong bronchodilator as 0.4 mg fenoterol and airway resistance was decreased to 52% and 55%, respectively of the initial value (p less than 0.001). The additional inhalation of the other bronchodilator caused a further slight decrease in airway resistance to a minimum of 47%, but was statistically significant (p less than 0.001) only in the case of the fenoterol/Sch 1000 sequence. The importance of bronchiolar tonus in regard to fluctuation of airway resistance and the possibility of a specific additive bronchodilatory effect of adrenergics and vagolytics is discussed.


[A study on glycosaminoglycans in a case of pulmonary emphysema (author's transl)]. The fraction of crude glycosaminoglycans was prepared from an emphysematous lung by means of proteolytic digestion, precipitation with ethanol and fractionation with CPC (cetylpyridinium chloride). The above fraction of crude glycosaminoglycans was then subjected to chromatography with a column of Dowex-1. Individual glycosaminoglycan species was identified based on the results of electrophoresis and on those of incubation with specific mucopolysaccharide-lyases. As a result, hyaluronic acid, chondroitin sulfate A (C), dermatan sulfate and heparan sulfate were detected. Quantitation of individual glycosaminoglycan species revealed that the ratio to total glycosaminoglycan of hyaluronic acid was smaller in the emphysematous than in the normal lung. The significance which can be attributed to the change in quantity of glycosaminoglycan of the lung was discussed in relation to pathogenesis of pulmonary emphysema.


[Therapeutic effect of vitamin A acid (retinoic acid) in various forms of palmar/plantar hyperkeratoses: experimental studies on 68 patients]. Up to date, the treatment of palmar/plantar hyperkeratoses presents a therapeutic problem. The known therapeutic procedures result in short-term improvement only, if any at all. In these investigations involving 68 patients suffering from palmar/plantar hyperkeratoses of different etiology, small doses of vitamin A acid (retinoic acid) topically applied, produced a striking improvement in hypertrophic lichen planus of palms or soles: the regression was complete and in most cases permanent. The skin texture of patients with genetic keratoses and callosities became normal within a few weeks: but this condition remained free of symptoms only as long as vitamin A acid was used as a maintenance dose once or twice weekly. In hyperkeratotic exzema, pityriasis rubra pilaris, and in verrucae plantaris vitamin A acid topically applied was found to be unsuitable for treatment. The possible side effects of this treatment are mentioned. Several possibilities regarding the way of action of vitamin A acid are discussed.


Chemotherapy in stage II testicular tumours: preliminary communication. Twenty-six patients with stage II testicular teratomas (metastatic spread to the retroperitoneal lymph nodes only) were treated after retroperitoneal lymph node dissection (RLD) by cytostatic chemotherapy with or without radiotherapy. So far, eight patients (30.5%) have recurrent disease, with a median interval of 21 months from time of diagnosis to relapse. The 3-year survival rate for the total group (relapse-free and relapsed patients) was 85.7%. The median survival is not yet reached after 36 months. The own results and reports of the literature show an advantage of early cytostatic treatment over its institution in widespread disease only. It remains to be clarified whether chemotherapy in stage II disease prevents or only delays metastatic spread.


Platelet turnover in metastatic cancer and the effect of platelet aggregation inhibitors. Patients with metastatic cancer have a permanent shortening of platelet survival and increased platelet consumption. Acetylsalicylic acid or dipyridamole in doses known to inhibit platelet aggregation, had no effect on platelet consumption.