alpha-L-fucosidase in cultured skin fibroblasts from normal subjects and fucosidosis patients. alpha-L-Fucosidase (EC 3.2.1.51) activity was studied in cultured skin fibroblasts obtained from 23 members of a family in which two cases of fucosidosis type 2 had occurred and in the fibroblasts of a patient with fucosidosis type 1. Both the 4-methylumbelliferyl glycoside and the p-nitrophenyl derivative were used as substrates. pH activity profiles showed two major peaks of activity. With the fluorogenic substrate pH optimum was at 4.5, whereas with the colorigenic substrate maximum activity was at pH 5.7. No activity was found in the fibroblasts of the three patients with the colorimetric assay. With the fluorometric assay the mean activity in the two patients with fucosidosis type 2 was 4.1 and 2.8 (range 1.3-9.9); activity in the patient with fucosidosis type 1 was 4.6 nmol 4-methylumbelliferone/mg protein/hr (range 1.0-8.6). The specific activity in the lysates of the patients' fibroblasts decreased as the amount of cellular protein used per assay increased. Fucosidosis fibroblasts cultured for 3 and 5 days in medium without fetal calf serum showed almost the same levels of apparent residual activity as fibroblasts cultured in medium containing fetal calf serum. Maximum activity in the deficient fibroblasts was at pH 4.5-4.75. Mixing experiments between lysates of both of fucosidosis and a normal fibroblast strain showed the expected enzymatic activities. The mean alpha-fucosidase activity in four heterozygotes for fucosidosis was 37.6 (range 24.1-48.7) and 30.3 (range 19.0-44.1) nmol final product split/mg protein/hr with the fluorogenic and the colorigenic substrate, respectively. In 12 normal fibroblast strains the mean activity +/- SD was 85.3 +/- 24.4 (range 50.8-129.3) and 67.6 +/- 21.1 (range 31.1-118.3). However, in four family members in which the alpha-L-fucosidase phenotype (by isoelectric focusing) was type 2-1, and who should therefore be carrying two normal alleles, the activity was within the heterozygote range. This indicates that occasional overlap between normal subjects and carriers may be present in cultured skin fibroblasts. Increased specific activity of alpha-L-fucosidase at pH 3.2-4.0 was observed after incubation of cell lysates with neuraminidase. The alpha-L-fucosidase activity did not show any increase after fusion between fucosidosis fibroblasts type 1 and 2.


[The detection of soluble bacterial antigens studied in various pathological substances using counterimmunoelectrophoresis. Contribution to diagnosis(151 cases)]. Examinations for soluble bacterial antigens using counter-immunoelectrophoresis (C.I.E.) was carried out in 151 patients suspected of suffering from various infectious syndrome were successful for S. pneumoniae, H. influenzae b, N. meningitis, sero-group B and D streptococcus. Thus meningitis and pneumonia represent those areas in which the technique is particularly useful. Apart from its rapidity--result in a hour--C.I.E., in association with bacteriology, makes possible an increase in aetiological diagnosis of 27% with H. influenzae b, 24% with S. pneumoniae and 6% with N. meningitidis (lower result by virtue of technical difficulties with sero-group B). Thus using this technique we were able to reach an aetiological diagnosis in 10 (23.8%) out of 42 cases of purulent meningitis where blind antibiotic therapy had already been given. These two advantages--rapidity and increase in aetiological diagnosis--justify the introduction of this simple technique in every medical microbiology laboratory.


An investigation of renal function in chronic bronchitis. An investigation has been made into various parameters of renal function in patients with chronic bronchitis and in a group of hypoxic controls. Abnormalities of glomerular filtration rate and of water handling have been demostrated in chronic bronchitic patients but not in hypoxic controls. The abnormalities are related to the arterial Pco2. A hypothesis is presented as to the role of CO2 in causing abnormalities of renal function in chronic bronchitis.


Polyarteritis nodosa of the liver: a report of two cases. Two patients with liver disease due to polyarteritis nodosa are described. They presented in a similar manner, with a swinging fever, a polymorphonuclear leucocytosis and high alkaline phosphatase levels, but the natural history of the illness was different, with revocery in one and death in the other.


[Assessment of the mental load of flight managers and of perforating machine operators by means of measuring the residual mental capacity via the subsidiary task method]. The purpose of the study is to evaluate mental loading due to working activities in two occupational groups--flight managers and punching machine operators. Changes in residual mental capacity are studied in relation to character of the specific work performed and working conditions. Residual capacity changes, measured with the method of double task assignment, disclose an essential difference in the nature of labour inherent of the two professions under study. The increased quantity of tasks performed under normal conditions of work exerts less influence on the level of residual mental capacity than work assignments fulfilled under complicated situations (such as bad weather conditions and the like). The level of residual mental capacity is likewise altered under the effect of fatigue in the course of the working day.


Non-equilibrium freezing behaviour of aqueous systems. The tendencies to non-equilibrium freezing behaviour commonly noted in representative aqueous systems derive from bulk and surface properties according to the circumstances. Supercooling and supersaturation are limited by heterogeneous nucleation in the presence of solid impurities. Homogeneous nucleation has been observed in aqueous systems freed from interfering solids. Once initiated, crystal growth is ofter slowed and, very frequently, terminated with increasing viscosity. Nor does ice first formed always succeed in assuming its most stable crystalline form. Many of the more significant measurements on a given systeatter permitting the simultaneous representation of thermodynamic and non-equilibrium properties. The diagram incorporated equilibrium melting points, heterogeneous nucleation temperatures, homogeneous nucleation temperatures, glass transition and devitrification temperatures, recrystallization temperatures, and, where appropriate, solute solubilities and eutectic temperatures. Taken together, the findings on modle systems aid the identification of the kinetic and thermodynamic factors responsible for the freezing-thawing survival of living cells.


Water transport and cell survival in cryobiological procedures. Living cells may be cooled to 77 K (liquid nitrogen) either to destroy them selectively or to store them for long periods. Water transport across the cell membranes during freezing and thawing is a primary factor determining whether the cells survive. These water movements are controlled by phase changes both intracellular and extracellular and by other factors such as the nature of any cryoprotective agent present, and the rates of cooling and thawing. The relation between cooling procedure, water transport and cell survival is discussed. In particular, the crucial rôle of dilution shock is emphasized: this is the damage to cells induced during the dilution that occurs both as ice melts during rewarming and when any cryoprotective additives are removed after thawing. Apart from the usefulness of understanding these processes for maximizing preservation or controlling selective destruction, the diverse responses of cells to different combinations of water transport and temperature changes appear likely to provide basic information on the properties of cell membranes.


The organization and function of water in protein crystals. Dry proteins are dead, or at best asleep. Substitution of D2O can drastically alter biological activity. Water is thus essential in maintaining the structural integrity of biologically active macromolecules, and is implicated in their functioning. Such water may occupy a range of dynamical states, from being strongly bound and localized, to more labile and 'liquid-like'. Spatially ordering the macromolecules aids the search for the more localized water molecules. For example, diffraction experiments on singly crystals can resolve 'bound' water molecules within a protein molecule--ofter at active sites, coordinated to metals or ions. Less precise information is obtained on the partially occupied external water sites, which are of importance to the folding and dynamics of the biomolecule. Orientation of fibrous molecules increases the information obtainable from n.m.r. experiments. Combination of other experimental results on disordered aggregates (e.g. in solution) with chemical and structural data on the macromolecule and water itself yields useful, if circumstantial, information. Statistical and computer techniques may help to elucidate the complex nature of water-protein interactions, and to interpret the results of more complex experiments.


Theoretical approaches to the intermolecular nature of water. A brief review is presented of recent advances in theoretical understanding of liquid water. These advances include detailed quantitative specification of water-molecule interaction potentials, and development of several techniques in statistical mechanics for predicting molecular order in the liquid. Specifically, computer simulation now plays a particularly important rôle. A labile, defective, random network picture for the liquid is the only consistently supported possibility. Implications of this picture for  an explanation of hydrophobic solvation and bonding are mentioned. Furthermore, the apparent cooperative restructuring of the random network near the supercolling limit suggests that a dielectric anomaly might exist in this régime. Several areas for future development of water theory are suggested, bearing specifically on phenomena of biological interest.


Stress-induced alterations of cyclic nucleotide levels in brain: effects of centrally acting drugs. Acute stressing procedures cause a shortlasting increase in the levels of guanosie 3',5'-monophosphate (cGMP) in mouse brain without significantly influencing the concentrations of adenosine 3'-5'-monophosphate (cAMP). Animals were pretreated with various centrally acting drugs before being stressed in order to study the involvement of specific neurotransmitters in the stress-induced rise of cGMP levels. Centrally depressant drugs affecting different synaptic mechanisms, such as chlorpromazine, reserpine, haloperidol, diazepam, and pentobarbital, inhibited the cCMP increase elicited by stress. Pretreatment with atropine, diphenhydramine, antazoline, cyproheptadine, phentolamine, bunitrolol, and indomethacin had no significant effect. Clonidine and both the (-)- and (+)-isomers of propranolol inhibited the stress-induced cGMP increase in a dose-related manner. Our results suggest that norepinephrine, serotonin, acetylcholine, or prostaglandins are not involved in the elevation of cGMP levels elicited by acute stress. Participation of other neurotransmitter(s), such as dopamine or GABA, cannot be excluded.


Physiological role of yeasts NAD(P)+ and NADP+-linked aldehyde dehydrogenases. The activity of NAD+ and NADP+-linked aldehyde dehydrogenases has been investigated in yeast cells grown under different conditions. As occurs in other dehydrogenase reactions the NAD(P)+-linked enzyme was strongly repressed in all hypoxic conditions; nervetheless, the NADP+-linked enzyme was active. The results suggest that the NAD(P)+ aldehyde dehydrogenase is involved in the oxidation of ethanol to acetyl-CoA, and that when the pyruvate dehydrogenase complex is repressed the NADP+-linked aldehyde dehydrogenase is operative as an alternative pathway from pyruvate to acetyl-CoA: pyruvate leads to acetaldehyde leads to acetate leads to acetyl-Coa. In these conditions the supply of NADPH is advantageous to the cellular economy for biosynthetic purposes. Short term adaptation experiments suggest that the regulation of the levels of the aldehyde dehydrogenase-NAD(P)+ takes place by the de novo synthesis of the enzyme.


Bioenergetics in clinical medicine XV. Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors. Adrenergic blockers for beta-receptors were studied for inhibition of mitochrondrial CoQ10-enzymes. These enzymes are indispensable for the bioenegetics of the myocardium. Propranolol is frequently used to treat hypertension; in some patients, it depresses myocardial function as an adverse reaction. This side effect may be related to the inhibition by propranolol of CoQ10-enzymes of the myocardium. Timolol showed negligible inhibition of the CoQ10-enzyme, NADH-oxidase. Metoprolol was less inhibitory than propranolol. Five alprenolols showed inhibition which approached that of propranolol. The 1-isomer of alprenolol showed weak inhibition of another CoQ10-enzyme, succinoxidase, but the other beta-blockers were essentially non-inhibitory to this enzyme. The drug of choice is timolol, based on negligible inhibition of these bioenergetic enzymes of the heart, which correlates with its pharmacologically low cardiac depressant effects.


Ethanol-induced inhibition of guanylate cyclase in liver, pancreas, stomach and intestine. Ethanol decreases hepatic protein and albumin synthesis, and inhibits pancreatic water, bicarbonate, and protein secretion. Since these actions of ethanol are opposite to those reported for secretin, cholecystokinin-pancreozymin, and pentagastrin which may be mediated through increases in cyclic GMP, it appeared possible that the inhibitory actions of ethanol might be mediated through inhibition of guanylate cyclase, the enzyme that catalyzes the production of cyclic GMP. Ethanol inhibited soluble preparations of guanylate cyclase from rat liver, pancreas, stomach, and ileum. Maximal inhibition was observed at 5.0 and 2.5 percent ethanol. The inhibitory effects of ethanol on the guanylate cyclase-cyclic GMP system of these tissues provide a possible explanation for some of the diverse effects of ethanol on these tissues.


Procainamide pharmacokinetics in beagles: urinary pH dependency and comparison with n-acetylprocainamide. Male and female beagles received intravenous (i.v.) bolus injections of procainamide (PA) to study its pharmacokinetic behavior and to determine the effect of urinary pH upon renal excretion. Urinary alkalinization caused an increase in plasma disappearance half-life (t1/2) and decreases in renal clearance (ClR) and total body clearance (ClB), while the apparent volume of distribution remained unchanged. Acid hydrolysis of the urine collected caused a 17% increase in the amount of PA measured. This hydrolyzable substance was found not to be the N-acetylated metabolite of PA. When i.v. N-acetylprocainamide (NAPA) was administered in crossover fashion to some of the above animals, it exhibited a longer t1/2 than PA. Mean ClR and mean ClB values were smaller with NAPA while both compounds showed similar dependence upon renal and non-renal clearance mechanisms.


Brain gamma-glutamyl transpeptidase levels in mice genetically selected for sensitivity to ethanol. The present study describes the regional distribution of the enzyme gamma-glutamyl transpeptidase for two lines of mice (long-sleep and short-sleep) selectively bred for differences in sleep-time after the administration of ethanol. The long-sleep animals exhibited higher levels of the enzyme in all areas of brain.


Blood-gas properties and function in the fossorial mole rat under normal and hypoxic-hypercapnic atmospheric conditions. Blood and tissue gas exchange properties of mole rats in normoxic and hypoxic-hypercapnic conditions were compared to the common mammalian pattern. RBC count was 14.0 +/- 1.2-10(6)/microliter. Hb concentration was 15.0 +/- 0.4g/100 ml. P50 (at pH 7.4 and 37 degrees C) was 29.5 +/- 0.5 mm Hg. Oxygen capacity averaged 20.2 +/- 0.4 vol% and the Hill coefficient was 2.9 +/- 0.1. The Bohr effect was -0.53 +/- 0.02 (deltalog P/deltapH). The temperature coefficient was 0.0152 +/- 0.0014 (deltalog P/delta degrees C). The Haldane effect was 4.8 +/- 0.5 (deltaCCO2 vol%)at PCO2 =40 mm Hg. Steady-state partial pressures in gas pockets were PO2 = 15.1 +/- 1.4 mm Hg and PCO2 = 85.8 +/- 3.9 mm Hg in normoxia, and 11.5 +/- 3.0 and 101.8 +/- 3.5 repectively in hypoxia-hypercapnia (PIO2 congruent to 85 mm Hg). Under the same conditions 2,3-DPG dropped from 0.87 and 0.88 to 0.62 and 0.65 (mol/mol Hb) in the rat and in the white rat, respectively. Heart muscle myoglobin concentration of the mole rat (1.44 mg/g) did not differ significantly from that of the white rat (1.96 mg/g), whereas masseter myoglobin was 4.0 mg/g--significantly different from the rat (1.21 mg/g). Results indicate that the strategy used by the mole rat to maintain a normal metabolic rate under variable atmospheric conditions, besides having high oxygen affinity, is to expand the physiological range of the oxygen dissociation curve to very low oxygen tensions, at the expense of its acid-base regulation. The regulation of the shape of the oxygen dissociation curve is discussed.


Crayfish respiration as a function of water oxygenation. Crayfish, Astacus leptodactylus, for several hours breathed water equilibrated either with a hypoxic gas mixture, or air, or oxygen. The hydrostatic pressure in the right epibranchial cavity was recorded and the left epibranchial water sempled from time to time. The higher the water oxygenation, the less the duration of ventilation, the frequency of the scaphognathite beats which ensure water convection, the negative of the water hydrostatic pressure relative to ambient water pressure, and the respired water flow. The water convection per unit quantity of oxygen consumed decreased by a factor of about 20 when the animal passed from hypoxic water at PO2 of 72 torr to hyperoxic water at PO2 of 697 torr. Prolonged hyperoxia, up to 100 days, results in a hypercapnic acidosis of the prebranchial blood. pH decreased about 0.2 unit, PCO2 increased from 2.5 torr to a value of 6 torr, and [HCO-3] from 6 to a value of 9 meq-L-1. This hypercapnic acidosis remained uncompensated during several weeks exposure to hyperoxia. Observations on the fresh water crayfish, a marine crab, and several species of fish, suggest that in aquatic animals (1) the ventilatory activity depends greatly on the degree of water oxygenation: the higher the water oxygenation, the lower the ventilation; (2) the change of ventilation may be accompanied by a new equilibrium of the blood acid-base status, quite different from that observed in normoxia.


Pineal vasotocin: release into cat cerebrospinal fluid by melanocyte-stimulating hormone release-inhibiting factor. The intracarotid injection of both synthetic melanocyte-stimulating hormone release-inhibiting factor (MIF) and purified MIF prepared from bovine hypothalami induces arginine vasotocin release into cerebrospinal fluid of cats and significantly decreases the pineal arginine vasotocin content at 5 minutes after the injection. The present results demonstrate an extrapituitary endocrine effect of synthetic and purified bovine MIF.


Haloperidol: effect of long-term treatment on rat striatal dopamine synthesis and turnover. The short- and long-term effects of neuroleptic drugs differ both clinically and biochemically. Short-term treatment with such a drug causes a kinetic activation of striatal tyrosine hydroxylase. Long-term treatment causes a prompt activation of the enzyme which is followed by a delayed, compensatory deactivation below control levels. Tolerance also develops to the stimulating effect of haloperidol on striatal dopamine turnover.


Electrically coupled, photosensitive neurons control swimming in a jellyfish. Central neurons in Polyorchis (Hydromedusae) were impaled with microelectrodes, and conventional resting potentials were obtained. The waveform of action potentials recorded concurrently with swimming events shows evidence of electrotonic coupling between these neurons, which are also directly photosensitive and receive excitatory synaptic input from other conduction systems.


[Polyneuropathy due to "allergic vasculitis" possibly related to australia antigen. (author's transl)]. The authors describe a case of flaccid tetraplegia due to a polyneuropathy in a man aged 50 years, progressing rapidly to death from mesenteric infarction. As significant abnormalities, the hematologic examinations revealed a very high erythrocyte sedimentation rate, a marked leukocytosis and a positive Australia antigen in repeated controls. In spite of the clinical picture being that of a symmetrical polyneuropathy rather than that of mononeuritis multiplex, the diagnose of a collagenosis was suspected. Nevertheless steroid treatment was not given because the patient had a peptic ulcer. On histological investigation many focal infarctions were found in several internal organs but the brain was pratically normal. Instead the nerve trunks examined (the sciatic nerve and the lumbo-sacral plexus) showed gross changes in the vasa nervorum represented by abundant perivascular cuffing and marked evidence of axonal degeneration secondary to an ischaemic damage. In the kidneys there were definite signs of membranous glomerulitis. The pathological findings in this fatal case of diffuse peripheral involvement were not those of classical periarteritis nodosa, but showed the picture of so-called "allergic vasculitis". This type of blood vessels inflammation is now assumed to be part of an immune-complex disease, in which the Australia antigen could be one of the causative agents.


Stimulation of in vitro translation of messenger RNA by actinomycin D and cordycepin. Actinomycin D and cordycepin were tested for their effect on translation in the wheat germ embryo extract and reticulocyte lysate assays for in vitro protein synthesis. Both drugs were found to stimulate the incorporation of 35S-labeled methionine into protein up to threefold as compared to control assays. This was true for synthesis directed by murine myeloma polyadenylate-containing RNA, tobacco mosaic virus RNA, and endogenous reticulocyte messenger RNA.


Dihydrofolate reductase: x-ray structure of the binary complex with methotrexate. A central eight-stranded beta-pleated sheet is the main feature of the polypeptide backbone folding in dihydrofolate reductase. The innermost four strands and two bridging helices are geometrically similar to but are connected in a different way from those in the dinucleotide binding domains found in nicotinamide-adenine dinucleotide-linked dehydrogenases. Methotrexate is bound in a 15-angstrom-deep cavity with the pteridine ring buried in a primarily hydrophobic pocket, although a strong interaction occurs between the side chain of aspartic acid 27 and N(1), N(8), and the 2-amino group of methotrexate.


Calcium-dependent depression of a late outward current in snail neurons. Neuron cell bodies of Helix pomatia were voltage-clamped with a 300-millisecond depolarizing test pulse (pulse II) delivered I second after a depolarizing conditioning pulse (pulse I). The outward current, measured 200 milliseconds after the onset of pulse. II, exhibited a strong depression that was dependent on the presence of pulse. I. The maximum depression of the pulse II outward current occurred when pulse I voltages lay in the range over which calcium influx is inferred to be greatest; depression of the pulse II current subsided as pulse I potentials approached the putative calcium equilibrium potential. In the presence of extracellular [ethylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA) or D600, the intensity of the pulse II current became largely independent of pulse I, approaching the values of maximal depression seen in normal Ringer solution. On the other hand, lowering the intracellular pH with extracellular carbon dioxide-carbonate buffer had no measurable effect on the outward currents. Other experiments showed that it is primarily the calcium-dependent, outward-current hump of the N-shaped late current-voltage curve that is depressed by presentation of the conditioning pulse. It was concluded that distinct from an early potassium-activating role, calcium entering during a depolarization leads, during a subsequent depolarization, to a depression of the calcium-activated potassium system that persists for many seconds.


Appetitive and replacement naps: EEG and behavior. Consistent subjective, behavioral, and electroencephalographic sleep-stage differences were found between afternoon naps of 11 habitual appetitive nappers (who nap lightly for psychological reasons apparently unrelated to reported sleep needs) and 10 replacement nappers (who apparently nap regularly in response to temporary sleep deficits). Both types of naps were compared with naps of 12 confirmed non-nappers.


The use of counter-immuno-electrophoresis to identify causative organisms in bacterial meningitis: experience in Cape Town. Crebrospinal fluid (CSF) from 142 patients was tested for the presence of Haemophilus influenzae, pneumococcal and meningococcal antigens by counter-immuno-electrophoresis with commercial antisera. Group- or type-specific antigen was detected in the CSF of 67% of 64 patients with meningitis proved by culture to be due to these organisms, and in 10 of 25 patients with purulent meningitis but negative cultures. No false positive results were obtained in 24 normal CSF specimens, or in the CSF of 29 patients with meningitis caused by other organisms. The diagnostic usefulness of this specific, relatively simple and rapid procedure is confirmed.


Studies on myocardial reperfusion injury. I. Favorable modification by adjusting reperfusate pH. This study tests the hypothesis that postischemic myocardial depression can be reduced by providing an initial reperfusate pH which is appropriate for myocardial temperature (i.e., metabolic systems function optimally when pH is kept slightly alkaline to the neutral point, which changes with temperature in concordance with the pK of water). Ten dogs underwent 1 hour of ischemic arrest with topical hypothermia (intramyocardial temperature 16+/-2 degrees C). The initial reperfusate (500 cc of blood from the extracorporeal circuit) was infused (100 cc/minute) into the proximal aorta just before removing the cross-clamp. Reperfusate pH was kept at 7.4 in five dogs (control) and raised to 7.8 with THAM [tris (hydroxymethyl) aminomethane] in five dogs. Measurements 30 minutes after reperfusion showed that raising reperfusate pH to 7.8 resulted in (1) higher subendocardial blood flows (109+/-20 vs 61 cc+/-8 cc/100 gm/minute), (2) redistribution of postischemic blood flow toward the subendocardium (endocardial/epicardial flow 1.25+/-0.1 vs 1.0+/-0.03), (3) higher left ventricular oxygen uptakes (0.046 vs 0.033 cc/100 gm/beat), (4) better postischemic left ventricular compliance (56+/-3% more compliant), and (5) improved left ventricular performance (88+/-7% recovery vs only 57+/-3% recovery at pH 7.4). Postischemic edema (2% water gain) was unchanged by pH modification. We conclude that initial reperfusion with the appropriate pH provides an optimal milieu for restoration of cellular metabolism, counteracts the acidosis of ischemia, and improves postischemic left ventricular blood flow, distribution, oxygen uptake, compliance, and performance.


Endogenous serotonin in the control of gastric acid secretion. In three dogs with Heidenhain pouches (HP), gastric fistulas (GF), and duodenal cannulas, acidification of the duodenum with 0.1N HC1 (5 ml/minute) resulted in significant inhibition of GF output (preacidification, 8.66+/-0.58 mEq/30 minutes; postacidification, 5.47+/-0.66 mEq/30 minutes) and elevated peripheral venous blood levels of serotonin (basal, 226+/-64 ng/ml; peak, 521+/-168 ng/ml). Infusion of exogenous serotonin to comparable blood levels (basal, 208+/-38 ng/ml; mean postacidification, 571+/-153 ng/ml) resulted in similar GF inhibition (preacidification, 9.17+/-0.92 mEq/30 minutes; postacidification, 6.49+/-0.56 mEq/30 minutes). Per increment in peripheral blood serotonin of 1 ng/ml, endogenous serotonin inhibited 54.59+/-12.99 muEq/hour and exogenous serotonin inhibited 46.54+/-10.39 muEq/hour, p greater than 0.05. Neither endogenously released nor exogenous serotonin inhibited HP acid output. Using mesenteric venous infusions of serotonin, significant amounts of immunoreactive serotonin were found to escape hepatic inactivation; basal peripheral venous levels of serotonin, 233+/-103 ng/ml, increased to 455+/-127 ng/ml at 10 minutes. During release of endogenous serotonin, 92+/-21% of portal venous serotonin was bound to platelets; in contrast, during intraportal serotonin infusion, only 59+/-18% of serotonin was platelet bound.


Sensitization against non-HLA antigens following bone marrow graft rejection. A patient with severe aplastic anemia rejected consecutive bone marrow transplants from two HLA-identical sibling donors. Following rejection, the patient developed antibodies that reacted strongly against donor lymphocytes in the complement-dependent cytotoxicity assay. Whereas the reactivity was initially directed specifically against the first marrow donor, cells of both donors and most unrelated individuals were killed by sera obtained after the second injection. These sera were also cytotoxic to the patient's own pre-transplant cells but not to her autologous post-transplant lymphocytes.


Enhanced solubility of 2,8 dihydroxyadenine (DOA) in human urine. Water solubility of the adenine catabolite 2,8 dihydroxyadenine (DOA) frequently forms the basis for predicting potential DOA crystal formation in human urine following infusion of adenine-fortified blood. Measurements relevant to solubility, ionic dissociation, and supersaturability of DOA in aqueous buffers and human urine at 37 C establish striking quantitative differences in the physico-chemical behavior of DOA in the two media. The basal solubility of DOA is 1.53 +/- 0.04 mg/1 (approximately 9 X 10(-6) M) in water (pH 6.5). DOA is an ampholyte characterized by aqueous thermodynamic macrodissociation constants of pKa1 = 2.6, pKa2 = 8.1, and pKa3 = 11.52. This compound displays pH-dependent solubility, although significant solubility increases beyond basal values do not occur within the physiologic pH range for human urine. Supersaturated aqueous solutions (three to sixteen times basal solubility) can be achieved but are unstable. In contrast, human urine at 37 C exhibits enhanced capacity for solubilizing DOA. In vitro basal solubility is 2.68 +/- 0.84 mg/1 at pH 5.0 and 4.97 +/- 1.49 mg/1 at pH 7.8. The apparent pK 2for DOA in urine of 7.9 to 8.1 is dependent upon urine osmolality. Urine can be supersaturated with Doa in vitro to approximately ten times its basal solubility by adding DOA solubilized in weak base, or by evaporation of a urine-DOA mixture. DOA remains supersaturated in urine for at least 16 hours despite gentle agitation. Little variation in in vitro DOA apparent supersaturation was found among urine samples from four normal individuals (40.38 +/- 3.33 mg/1). A patient receiving oral adenine exhibited urinary DOA solubility in considerable excess (96.0 mg/1) of that predicted from water and from in vitro urine solubility studies. Thus, water solubility of DOA is poorly predictive of in vitro and in vivo DOA solubility in human urine. On the basis of these data, estimates of the load of adenine-fortified blood expected to result in urinary DOA crystal formation may be revised upward.


Uropharmacology: v. choline esters and other parasympathomimetic drugs. Various parasympathomimetic drugs are discussed, including the choline esters, bethanechol, carbachol, methacholine chloride, and furtrethonium. Other cholinomimetic agents include muscarine, muscarone, arecholine, and pilocarpine. Anticholinesterase agents inhibit or inactivate acetylcholinesterase enzyme and thus result in a prolonged stimulation of cholinergic receptors by endogenous ACh. Bethanechol is the most widely used parasympathomimetic drug in the United States. Its action is mainly muscarinic with activity largely confined to the urinary bladder and to a lesser degree the gastrointestinal tract. It can be administered only subcutaneously or orally, and adequate dosage is necessary for a successful response.


The outbreak of equine influenza in England: January 1976. Equine influenza type 2 infections occurred in the Newmarket areas in January 1976. The disease did not spread to any extent and while this may have been due to recent vaccination it was found that not all vaccinated horses were fully protected. The virus involved showed some antigenic drift from the prototype strain A/equine/Miami/1/63 (Heq 2 Neq 2).


Aneurysms of the coronary arteries in infants and children. A review, and report of six cases. In recent years large numbers of the so-called "mucocutaneous lymph node syndrome" or "Kawasaki's disease" have been described by Japanese workers, but instances of this disorder are only now being reported as isolated cases by European or North American physicians. The disease has, therefore, been considered to be a new entity. One of its most striking features is the development of aneurysms of the coronary arteries in infants or children, which may lead to sudden death. Aneurysms of the coronary arteries in childhood are rare, and hence it was considered relevant to report six such cases, and to examine their possible relationship to Kawasaki's disease. The pathological changes underlying the latter disorder are not well known; they are considered to be indistinguishable from infantile polyarteritis nodosa. A diagnosis of polyarteritis nodosa was also thought to be most likely to apply in the cases presented here, particularly in view of the frequency with which aneurysms of the coronary arteries have been found in this disorder. In the absence of valid pathological distinctions between Kawasaki's disease and infantile polyarteritis nodosa, the question arises whether these entities are, in fact, different, and whether Kawasaki's disease is the new entity it is assumed to be.


[Cardiac output, blood gas analysis and the acid-base state of the blood in chronic cor pulmonale]. In 61 patients with chronic cor pulmonale with compensation and decompensation of circulation, the stroke and minute heart volume were studied as well as the indices, characterizing the blood-gas contents and acid-base blood state. The minute heart volume in the patients examined proved to be with normal values. Stroke heart volume is decreased in all patients examined with chronic cor pulmonale. The acceleration of heart activity enables the maintenance of normal minute volume. Hypoxemia has a cardiac depressive effect as regards minute volume and heart rate. The moderate hypercapnia has a certain stimulating effect on heart. A direct proportional correlation exists between the hypercapnia degree and the tendency of minute volume increase and especially of heart rate. The campaign against hypoxemia is an essential element in the prophylaxis and early treatment of chronic cor pulmonale.


A physician extender training program based on clinical algorithms. The ability of physician extenders to provide patient care in a variety of settings has been reported widely. Less attention has been paid to training programs, especially those of short duration, for physician extenders. A three-month training program for physician extenders at a large teaching hospital was based on teaching the skills needed to run 39 clinical algorithms. The course content and the methods used to test the students during the three months may prove of value to those preparing similar programs.


[Aspartate transfer across the blood-retina barrier (author's transl)]. Permeability of the blood-brain barrier is restricted with respect to amino acids involved in neurotransmission. This finding is well-documented in the case of gamma-amino-butyric acid (GABA) and glycine. Aspartic acid, which is also considered to be a transmitter, equally does not cross the blood-brain barrier in the rat with ease. This amino acid is also thought to be a transmitter in the retina. In order to examine the permeability of the blood-retina barrier with respect to aspartic acid, and investigation was undertaken of the effect of asparate on the light-induced sum potential of the retina in the isolated, perfused cat eyeball, a preparation which guarantees intact retinal circulation. The findings were compared with findings in the isolated retina where the substance was brought into direct contact with the retinal neurons. It was found that aspartate crossed the vascular barrier only to a limited extent and with delay. These results support the hypothesis that aspartic acid is involved in the retinal information processing.


[Recent concepts of respiratory regulation (author's transl)]. There are two functional aspects of the respiratory control system, the one being adaptation of ventilation to metabolic needs and the other acid-base homeostasis of the extracellular fluid of the brain. These two functions are perfectly compatible with one another under normal conditions. During hypoxia or hyperthermia, however, a compromise has to be reaches by the system between securing oxygen availability or homeothermy, respectively and acid-base homeostasis of the brain. The control system works with tonic chemosensitive and non-chemosensitive neural input of action potentials to the centres. The centres, either by indigenous mechanisms or by phasic reflex input from the stretch receptors of the lungs or phasic feedback mechanisms from the pontine pneumotaxic centre, modulate the tonic impulse input into the rhythmic output to the respiratory muscles. Recent observations on this "inspiratory off switch mechanism" are discussed. Chemosensitive sensors are found in the carotid and aortic glomera responding to low pO2 and, additionally, to pH and pCO2 and in central chemosensitive structures on the ventral side of the medulla oblongata, responding mainly to changes in local hydrogen ion concentration. The proprioceptive reflexes in the sense of a gamma loop improve the performance of the system if additional flow resistance must be overcome. In metabolic and respiratory acidosis-alkalosis the kidney either plays a compensatory role or serves to restore normal conditions. The maternal hormones in pregnancy effect air improvement in CO2 output of the fetus.


[Bistability in the activity of glutamine synthetase in ammonium-limiting chemostat cultures of Escherichia coli ML 30]. The approximative estimation of the function micron([NH+4]) in cultures of E. coli ML 30 had shown that bistability of the ammonium concentration in ammonium limited continuous cultures could be possible (BERGTER et al. 1977). This phenomenon suggested a bistability in the regulation of ammonia assimilation. Therefore, the activity of one key enzyme of the two ammonia assimilation systems was measured. The distribution of the activity of glutamine synthetase in ammonia limited continuous cultures after different transition states confirmed this suggestion.


[The problems of adverse effects to the liver of alpha-methyldopa]. In 20 patients who were treated with alpha-methyldopa since at least one year the bilirubin content, the activities of aspartate and alanine-aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase as well as the retention of bromsulphalein were determined. In altogether 10 patients pathological findings of laboratory examinations were the result. The gamma-glutamyl transpeptidase activity proved to be particularly sensitive. By means of biopsy in 3 of these patients a fatty degeneration of the liver in stage I and in 4 of them a fatty degeneration of the parenchyma cell of minor degree were proved. A connection between duration and dosage of the treatment with alpha-methyldopa and these hepatological findings could not be ascertained statistically.


[Relationship between thermal treatment of milk and hysteresis of the milk protein system. II. Studies on casein micelles (author's transl)]. The association of colloidal calcium phosphate with the casein micelles is the principal reason for hysteresis of the milk protein system. Because of this association the secondary calcium phosphate cannot be titrated at its pK = 7.2, but only at lower pH values depending on the previous thermal treatment of the milk. However after overcoming certain energy barriers it can be titrated (between pH 5.8 and 5.2), but then calcium phosphate is separated irreversibly from the micelles. Therefore in the subsequent base titration other molecular conditions are passed through than in acid titration. The consequence is a hysteresislike titration curve. By heating, the surface of the micelles are covered successively with serum proteins. Due to this coating additional diffusion barriers are constructed. The diffusion of the protons into the interior of the micelles is measurably retarded. The expansion of the hysteresis loop can be determined quantitatively.


Regulation and characterization of L-serine: pyruvate aminotransferase in rat liver cytosol and mitochondria. Distribution of rat liver serine: pyruvate aminotransferase between cytosol and mitochondria varies considerably with the dietary and hormonal state of animals. Feeding a high-protein diet or fasting the animals results in an increase in the enzyme activity of both fractions but more marked in the mitochondrial fraction. A low-protein diet exerts the reverse effect. A single administration of dibutyryl cyclic AMP causes a rapid elevation of the enzyme activity in both fractions, which is effectively prevented by cycloheximide, actinomycin D and cortisone. The activity in mitochondria increases with a lag of 2 h following injection of the nucleotide inducer, in contrast to the cytosol enzyme, which increases without any lag. Gel filtration and DEAE cellulose chromatography of the enzyme from both fractions revealed the similar pattern and some kinetic constants of these two types of the enzyme were not significantly different from each other. These results indicate that rat liver serine: pyruvate aminotransferase is synthesized in the extra-mitochondrial site and transfered to mitochondria.


Identification of essential histidine residues of aminoacylase by photooxidation and by reaction with diethylpyrocarbonate. State and function of the histidine residues of aminoacylase were investigated by photoxidation in the presence of methylene blue and by chemical modification with diethylpyrocarbonate. Complete inactivation of the enzyme was observed after oxidation of 4 histidine residues. From the pH dependence of the photooxidation it becomes evident that the inactivation of the enzyme is not a consequence of the simultaneous oxidation of tryptophan residues. The enzyme is also inactivated by chemical modification of histidine residues with diethylpyrocarbonate. Activity is restored by treatment with hydroxylamine. Zn2+-ions which are essential for the activity of aminoacylase protect the available histidine molecules against photooxidation and attack by diethylpyrocarbonate. It is suggested that histidine is involved in the binding of the essential Zn2+-ions.


[On the enzymatic breakdown of tripolyphosphate and diphosphate in comminuted meat. VII. Influence of sodium chloride on the tripolyphosphatase and diphosphatase activity in bovine muscle (author's transl)]. Sodium chloride activates the tripolyphosphatase of the muscle tissue. Optimum activity occurs at 4--5 percent NaC1. The increase in activity seems to be due to the effect of C1-ions. NaC1 inhibits the tripolyphosphatase activity of muscle press juice. NaC1 decreases the total diphosphatase activity of muscle tissue as well as the diphosphatase activity of muscle press juice. Addition of NaC1 to pre-rigor muscle increases the ultimate pH value (post-rigor-muscle) and, consequently, causes a lower tripolyphosphatase activity and a higher diphosphatase activity than is observed, when NaC1 is added to the post-rigor muscle.


[On the enzymatic breakdown of tripolyphosphate and diphosphate in comminuted meat. VIII. Influence of divalent cations on the tripolyphosphatase activity of muscle tissue (author's transl)]. The tripolyphosphatase of comminuted muscle tissue is activated by MgC1(2) and ethylenediamine tetraacetate and inhibited by CaC1(2) and diphosphate. These results are discussed with reference to the formation of an inactive enzyme-substrate complex.


Factors influencing L-asparaginase production by staphylococci. Cultural and nutritional requirements for a maximum synthesis of 1-asparaginase by staphylococci were determined. The best production of the enzyme was found in the stationary phase of growth of a batch culture. The highest 1-asparaginase yield was obtained when the culture were aerated during an exponential phase of growth and further incubated in the stationary phase. Optimum pH for the enzyme production was 7.5. Glucose inhibited the enzyme formation. Maximum yield of 1-asparaginase was obtained when casein hydrolysate and yeast extract were supplied as carbon and nitrogen sources. Repression by 1-asparagine and 1-aspartic acid was absent.


Subcellular distribution and properties of alkaline inorganic pyrophosphatase of maize leaves. 1. Studies on the distribution of alkaline inorganic pyrophosphatase (pyrophosphate phosphohydrolase, EC 3.6.1.1) in the subcellular fractions of maize leaves showed that the enzyme is present in cytoplasm, chloroplasts and mitochondria. The activity observed in nuclei and microsomes may result from contamination with the mitochondrial fraction. 2. Alkaline pyrophosphatases from three subcellular fractions were purified by fractionation with (NH4)2SO4, followed by ion-exchange and gel-filtration chromatography, and by isoelectric focusing. Highly purified enzyme preparations, with specific activities ranging from 55 to 188 micronmoles/min/mg protein, were obtained. 3. All the enzymes exhibited the maximum activity at pH 8.5 and the Mg2+/PPi ratio of 5. They differed in electrophoretic mobility, pI, and susceptibility to urea and thermal denaturation. This indicates that they represent isoenzymes compartmentized in particular subcellular fractions.


Acid phosphatase of the yeast Rhodotorula rubra. Purification and properties of the enzyme. 1. Acid phosphatase from the yeast Rhodotorula rubra was purified 44-fold. The purification procedure involved mechanical disruption of cells, precipitation with ethanol, chromatography on DEAE- and CM-cellulose. 2. The purified enzyme is homogeneous in polyacrylamide gels at pH 4.5, 9.5 and 8.4. Carbohydrate content accounts for 57% of the total weight. The optimum pH is at 4.0-4.6, and the enzyme is stable over pH range from 2.6 to 6.0. Full activity was retained on 60-min incubation at 50 degrees C, but it was reduced by half on 60-min incubation at 65 degrees C. 3. Specificity of the enzyme is fairly broad; monoesters of carbohydrates, and nucleosides and inorganic pyrophosphate can serve as substrates. Km was found to be 1 X 10(-4) M for p-nitrophenyl phosphate as a substrate. The enzyme is inhibited by molybdate, phosphate, arsenate and fluoride ions.


[Proof of guanylate cyclase activity in the coronary artery of cattle]. Guanylate cyclase activities were identified in a soluble fraction and a particular fraction obtained from the Arteria coronaria of cattle. The Km-value was 1.0 +/- 0.7 - 10(-4) M for the enzyme substrate complex of the guanylate cyclase of the soluble fraction and 9.2 +/- 1.5 - 10(-4) M for the particular fraction. For the enzyme activity of the soluble fraction Mn++ cannot be replaced by Ca++ or Mg++, whereas for the enzyme activity of the particulate fraction Mn++ can be replaced by Mg++ but not by Ca++. The guanylate cyclase of the particulate fraction can be activated by acetylcholine. This activation can be cancelled by atropine. Acetylcholine exerts no influence on the guanylate cyclase activity of the soluble fraction. ATP inhibits the enzyme activities of both fractions whereas cAMP shows no influence on the guanylate cyclase activity.


[Demonstration of protein kinase activities in the coronary artery of cattle]. Protein kinase activities were identified in a soluble and a particulate fraction from the A. coronaria of cattle. For both protein kinase activities Mg++ is essential. Protamine was used as a substrate of the protein kinase activity of the soluble fraction. The pH optimum of the protein kinase activity of the soluble fraction is around 6.5. The Km-value of the protein kinase for ATP is 1.9 +/- 0.4 - 10(-5) M. cAMP stimulates the protein kinase activity more effectively than cGMP. Ca++ cannot replace Mg++; monovalent cations (Na+ and K+) show no influence. The protein kinase activity of the fraction was determined via endogenous phosphorylation. By means of the cAMP-dependent particulate protein kinase 72 to 80 percent of the serine residues are phosphorylated. The pH optimum of the protein kinase activity of the particulate fraction lies around 7.0. The Km-value of the enzyme for ATP is 6.6 +/- 0.8 - 10(-5) M. cGMP stimulates the protein kinase of the particulate fraction better than cAMP. For the protein kinase activity of this fraction Ca++ replaces Mg++ in the endogenous phosphorylation but not in the exogenous phosphorylation (protamine). In the presence of Mg++ and in the additional presence of Na+ or K+, the protein kinase activity is suppressed in the endogenous phosphorylation whereas it is stimulated in the exogenous phosphorylation.


Effect of tilorone hydrochloride on graft-versus-host (GvH) reaction in mice. The effects of tilorone hydrochloride (TH), a powerful interferonogenic agent exhibiting also immune modulatory properties, on GvH reaction was studied, using the popliteal lymph node assay in mice. Administration of TH at ten days 0 or +2 relative to cell transfer to recipient mice led to a significant dose-dependent reduction of GvH reaction, whereas treatment of prospective donor mice at day -4 or -2 induced an enhanced GvH re activity of donor spleen cells. This effect was found not to be due to an altered proportion in the spleen cell inoculum of B and T lymphocytes, which latter are responsible for induction for GvH reaction. However, since normal parental lymphocytes are prepared for an enhanced GvH reactivity by addition of TH-treated macrophages, a stimulatory effect of the latter cells via macrophage-derived mediators, induced by TH, is suggested.


[An ion exchange method to determine free metal concentrations, adapted for use in biological fluids: methods and determination of (Mg2+)]. An ion exchange method for measuring concentrations of free (ionized) metal ions and its application to the determination of [Mg2+] is described. A surface sulfonated polystyrene material is used as the "twodimensional" cation exchanger. The sample-volume is 1 ml. About 50 determinations can be performed within 1 hr having a standard error of +/- (2-4)% in the optimal range of measurement. Advantages and disadvantages of the method compared with other ones are demonstrated and discussed. Free Mg2+ ion concentrations were measured in solutions containing pyrophosphate as well as haemoglobin and compared with those which were determined by equilibrium calculation or ultrafiltration.


Pulmonary complications, ventilation and blood gases after upper abdominal surgery. Forty patients who underwent elective cholecystectomy were examined preoperatively and during the first postoperative week by physical examination, measurement of FVC and FEV1, arterial pH and blood gas analyses, and chest x-ray. Postoperative pulmonary complications (p.p.c.) were detected in 30 (75%) of the patients. Simple auscultation was the most sensitive tool in discovering p.p.c., but 18 of the 30 patients with complications also had a pathological chest x-ray. Obesity, smoking postoperative naso-gastric tube and postoperative wound infection were predisposing factors for p.p.c. Six patients with preoperative pulmonary disease all had a progress in their lung pathology. There was no definite relationship of duration of anaesthesia or drainage of the abdominal wound to development of p.p.c. The patients with p.p.c. showed a deeper and more prolonged fall in Pao2 postoperatively than the normal group. None of the normals showed an arterial Po2 below 70 mmHg in the postoperative course, while 63% of the p.p.c. group did. FVC and FEV1 showed marked reductions from preoperative values on the first postoperative day, and then gradually increased to near preoperative values after 1 week. Arterial pH and Pco2 showed no definite changes during the postoperative course.


The cerebrovascular CO2 reactivity during the acute phase of brain injury. Using the intra-arterial 133xenon (133Xe) method, the cerebrovascular response to acute Paco2 reduction was studied in 26 unconscious, brain-injured patients subjected to controlled ventilation. The CO2 reactivity was calculated as delta in CBF/delta Paco2. The perfusion pressure was defined as the difference between mean arterial pressure and mean intraventricular pressure. Although the CO2 reactivities did not differ significantly from that in awake, normocapnic subjects, it was low in the acute phase of injury, especially in those patients with severe outcome in whom the brain-stem reflexes were often affected. An increase of the CO2 reactivity with time was observed, indicating normal response after 1-2 weeks. Chronic hypocapnia in six unconscious patients resulted in sustained CSF pH adaptation. The question whether a delay in CSF pH adapation exerts an influence on the CO2 reactivity, and the influence of cerebral lactacidosis on the CO2 response are discussed.


The pressure-flow relations of the canine brain in acute mechanically induced arterial hypertension at different levels of cerebral blood flow. Cerebral pressure-flow relations were studied in anaesthetized dogs during acute arterial hypertension, induced by compression of the thoracic aorta. In one group of animals steady state measurements were made with the radioactive gas elimination method. In another group the immediate changes of blood flow at a blood pressure change, as indicated by variations in the cerebral venous oxygen saturation, were studied with continuous oximetric analyses of the superior sagittal sinus blood. The initial blood flow was varied by variations of the arterial carbon dioxide tension of injections of papaverine. At low or normal blood flows autoregulation was efficient up to pressures around 180-200 mmHg, while at higher flows the upper autoregulatory pressure limit was found at lower blood pressures. Above the autoregulatory limit-irrespective of the control flow level-there was a rise in blood flow and a decrease in cerebrovascular resistance.


Peroperative arterial blood pressure control in ophthalmological anaesthesia. The effects were studied of a standardised general anaesthesia on mean arterial blood pressure, central venous pressure, blood gas values and the course of cataract operations. The material consisted of 20 unselected senile cataract operations, the mean age of the patients being 71.3 years. The arterial blood pressure was continuously checked, using an intra-arterial cannula. In order to avoid vitreous loss, the blood pressure was successfully kept optimally low during the extraction of the lens. No vitreous problems were noted. The oxygenation and ventilation of the patients were sufficient during anaesthesia and immediately postoperatively.


Effects upon the fetus of oxygen administration to the mother. A study in monkey. Catheters were placed into assorted arteries and veins of 8 anaesthetized pregnant monkeys and their fetuses. Oxygen-sensitive electrodes were also inserted subcutaneously into 3 of the 8 fetuses. Periodic samples of maternal and fetal blood were analyzed for PO2, PCO2 and pH. Oxygen administration to the mothers reliably increased the PO2 of blood taken from the fetal carotid artery and less constantly augmented the PO2 of blood withdrawn from the femoral artery and vein. During 5-6 hours of study the oxygen tension of fetal blood samples of all animals progressively declined. However, the most marked declines in PO2 values at all fetal sites were regularly observed at those times as--or after--the mothers emerged from anaesthesia. At these times also the magnitudes of the increases in fetal blood PO2 brought about by administering oxygen to the mothers diminished markedly and in parallel at all sample sites. The closely similar magnitudes of these various reductions at all fetal sample sties indicate that the basic mechanisms leading to decreased oxygen delivery lie outside the fetuses and are most likely due to decreased maternal blood flow to the uterus because of increased maternal sympathetic stimulation. These reductions in oxygen delivery to the fetus are all regularly reversed by reanasthetizing the mothers. The studies carried out with oxygen-sensitive electrodes demonstrate that administering oxygen to the mothers regularly increases oxygen tension of fetal tissues but after a 50 sec delay.


The finding that secretory component is not associated with gamma-glutamyltranspeptidase activity. The gamma-glutamyltranspeptidase activity of human milk was concentrated by ammonium sulphate precipitation. On gel chromatography of the dissolved precipitate, the activity was eluted in the high-molecular-weight fraction containing secretory IgA, while no activity appeared in the eluate at the position of free secretory component. Various antisera were added to portions of the pool of active fractions. No change of gamma-glutamyltranspeptidase activity appearedse activity was obtained with antisera against either IgA, secretory IgA or secretory component, while a large reduction of activity was seen with anti-human colostrum. Finally, purified free secretory component, secretory IgA and in vitro complexes between secretory component and IgA dimers were shown to be inactive in the gamma-glutamltranspeptidase assay, both in the absence and presence of zinc ions. Thus secretory component, either when free or bound to IgA, does not exhibit gamma-glutamyltranspeptidase activity, and therefore cannot function as such an enzyme in the transport of IgA across mucous membranes, as has been suggested previously.


Atenolol in the treatment of angina pectoris. Nineteen men, aged 41-64 years, with stable angina pectoris have completed a random double-blind study of atenolol, 50 mg b.i.d., atenolol, 100 mg b.i.d., and placebo. Fifteen patients had subjective improvement on atenolol, two were unchanged and two felt worse (because of asthenia/leg fatigue). No significant placebo effect was found. On both atenolol dosages there were highly significant reductions in heart rate at rest and during exercise and in BP. Only the maximal heart rate decreased significantly more on 100 mg atenolol than on 50 mg (p less than 0.01). Fourteen patients had the same or a better physical performance on the 50 mg b.i.d. regimen than on the 100 mg b.i.d. regimen, although this difference was not significant. Sixteen patients had higher bicycle exercise performance on atenolol than on placebo. Disregarding the three non-responders, a mean increase of 44% in bicycle performance was found. No serious side-effects were seen. Most individuals reported an increased feeling of well-being on atenolol.


Acute myocardial infarction and ischemic injury during surgery for coronary artery disease. The incidence of myocardial infarction, acute ischemic injury, and associated serum enzyme abnormalities has been evaluated in four operations involving the coronary circulation. The highest incidence of infarction was associated with internal mammary implantation (Vineberg procedure). There was no significant difference in the incidence of infarction, ischemic injury, or abnormal enzyme levels between patients with stable angina and those with unstable angina who had vein bypass surgery. In operations involving combined vein bypass grafting and valve replacement surgery, the incidence of abnormal serum enzyme elevations was higher than in any other procedure. The incidence of infarction and acute ischemic injury in combined operations was similar to that in other procedures but this may have been due to the difficulty in the ECG diagnosis of infarction in this group of patients, most of whom had abnormal preoperative ECGs.


Isolated coronary periarteritis: report of a case of unexpected death in a young pregnant woman. A case of sudden unexpected death in a 23 year old woman in her 8th month of pregnancy is reported. Death occurred from isolated coronary periarteritis with thrombosis. It is believed that the thrombosis was secondary to the adventitial infiltrate, which was of a type suggesting a hypersensitivity factor. It is proposed that pathogenetically this case is identical to reported cases of dissecting hemorrhage or aneurysm of the coronary artery and represents an entity different from other forms of inflammatory coronary disease.


An isozyme of erythrocyte pyruvate kinase (PK-Los Angeles) with impaired kinetics corrected by fructose-1, 6-diphosphate. A mutant isozyme of erythrocyte pyruvate kinase was found in a family of French-Canadian ancestry in association with hemolytic anemia. The isozyme was characterized by normal maximal activity, pH optimum, heat stability, and fructosediphosphate activation constants, but had markedly reduced affinity for the substrate, phosphoenolpyruvate. This kinetic defect was corrected almost entirely in vitro by low concentrations of fructosediphosphate.


Bacteremia in hospitalized children.

Bacteremia in hospitalized children. The results of 6,951 blood cultures taken from hospitalized children are reviewed. One or more organisms grew from 6% (399) of the cultures, of which 189 (two thirds) were considered to represent confirmed bacteremia. The most common organisms associated with bacteremia were Haemophilus influenzae, Streptococcus pneumoniae, enterobacteriaceae, and Staphylococcus aureus. Patients with deficient host defenses (newborns, oncology patients) with bacteremia had a higher mortality than normal children. Laboratory techniques allowing more rapid detection of positive blood cultures resulted in major alterations in therapy in almost one half of all bacteremic patients.


Effects of cimetidine, a histamine H2-receptor antagonist, on various experimental gastric and duodenal ulcers. The effects of cimetidine, a new histamine H2-receptor antagonist, on the development of experimental gastric and duodenal ulcers were studied. It was found that either by the oral, intraduodenal, or intraperitoneal route this agent had a marked inhibitory activity on stress-, aspirin-, indomethacin-, or histamine-induced gastric ulcers in rats and guinea pigs. The effects of cimetidine on stress-, aspirin-, and indomethacin-induced gastric ulcers were dose-dependent in many cases. Pylorus-ligation uclers, reserpine- or serotonin-induced gastric ulcers were little influenced by cimetidine. Duodenal ulcers induced by continuous infusion of carbachol-histamine were significantly inhibited by a simultaneous infusion of cimetidine. An analysis of gastric contents in pylorus-ligated rats after stressing indicated a decreased volume and acid output as the result of intraduodenal cimetidine treatment. In contrast, cimetidine exerted little influence on gastric secretion in rats treated with aspirin or in guinea pigs treated with histamine. Thus, the mechanism of action of cimetidine in preventing gastric or duodenal ulcers is likely to occur by suppression of gastric secretory function in a duodenal ulcer model but by suppression of other unknown ulcerogenic factors in gastric ulcer models.


Quantitative determination of four antihistamines in combination by high-pressure liquid chromatography. A procedure used to assay four antihistamines--brompheniramine maleate, chlorpheniramine maleate, pheniramine maleate and pyrilamine maleate in combination--is discussed. The method requires a high-pressure liquid chromatograph and an intermediate polarity column. The method is accurate and appears to be stability-indicating. The four antihistamines can be separated and assayed accurately. There is no interference from the two commonly used decongestants, phenylephrine hydrochloride and phenylpropanolamine hydrochloride, from the expectorant potassium guaiacolsulfonate, from the preservative propyl paraben or from two other antihistamines, diphenhydramine hydrochloride and bromdiphenhydramine hydrochloride. Guaifenesin, methylparaben and sodium benzoate interfere only with pheniramine maleate. Methapyrilene hydrochloride interferes only with pyrilamine maleate.


Bladder dysfunction after radical abdominal hysterectomy. Bladder dysfunction is a common occurrence following radical hysterectomy. We studied bladder function prospectively in 10 patients before and after radical hysterectomy. Results suggest that the hypertonic phase observed immediately postoperatively is the result of an increase in myogenic tonicity of the detrusor muscle secondary to the trauma of operation and prolonged catheter drainage. The inability of patients to urinate effectively is due to partial detrusor denervation. Combined cystometry and electromyography confirmed the presence of normal sphincter function and the absence of detrusor sphincter dyssynergia. Prevention of postoperative bladder atony includes a careful preoperative urologic evaluation, including cystometry. Postoperative bladder care should emphasize the prevention of overdistention. Inability to empty the bladder after operation may be managed effectively by intermittent self-catheterization, Urecholine, or prolonged catheter drainage. Patients should be evaluated periodically to uncover delayed bladder decompensation.


Effects of prolonged infusion of beta-adrenergic agonists on uterine and umbilical blood flow in pregnant sheep. We have extended our evaluation of the effects of three beta-adrenergic agents in near-term pregnant sheep to include a period of infusion three times longer than previously studied. This extension has provided the following information: (1) Initial depression of uterine blood flow and mean arterial pressure associated with administration of ritodrine or salbutamol abate with time despite continued drug infusion; (2) the uterine hyperemia associated with salbutamol and fenoterol are drug-related rather than postinfusion-related phenomena; (3) increased uterine vascular resistance is found with ritodrine, and decreased uterine vascular resistance occurs with salbutamol and fenoterol.


Thymic involution in murine graft-versus-host reaction. Epithelial injury mimicking human thymic dysplasia. Mild, moderate, and severe graft-versus-host (GVH) reactions were induced in four series of experiments in 71 CBA X A and C57BL/6 X A F1 hybrid mice. At regular intervals post-GVH reaction induction (Days 4-42), the animals were sacrificed, autopsied, and histologically studied. Visceral alterations of GVH reaction were recorded in the spleen, lymph nodes, liver, kidney, gut, and thymus. A spectrum of thymic changes was documented, ranging from obliteration of a definable cortex and medulla with loss of Hassall's corpuscles to marked involution with complete disappearance of the gland. Ultrastructural studies revealed damage to both lymphocytes and epithelial cells along with lymphocyte emperipolesis of epithelial cells, lymphocytolysis within epithelial cells, and accumulation of numerous autophagic vacuoles containing fragments of cellular debris within epithelial cells and histiocytes. The resemblance of these alterations to human thymic dysplasia as observed in primary immunodeficient conditions was striking. The theoretical implications of these studies for the pathogenesis of human congenital immunodeficiency states are considered.


Thyroid cold acclimation influences on norepinephrine metabolism in brown fat. Norepinephrine turnover rates and tyrosine hydroxylase activities were determined in the interscapular brown fat pad of the rat during cold acclimation, hyperthyroxinism, and after thyroidectomy. Rats were cold acclimated by placement in a cold room, one rat to a cage, for a period of 6 wk. Hyperthyroxinism was induced by daily subcutaneous injections of L-thyroxine (1 mg/kg) for 6 days. Norepinephrine turnover rate and enzyme activity were determined at the end of each experimental period and at 8 wk after thyroidectomy. The rate of norepinephrine turnover increased during cold acclimation and hyperthyroxinism and decreased after thyroidectomy. Cold acclimation resulted in a significant increase in tyrosine hydroxylase activity, whereas no significant effect on enzyme activity was observed in hyperthyroxinism or after thyroidectomy. None of the conditions produced a change compared to controls in the apparent Km of tyrosine hydroxylase for L-tyrosine. Cold acclimation resulted in a significant decrease in the apparent Km of tyrosine hydroxylase for pterin cofactor, whereas thyroxine treatment and thyroidectomy had no effect.


Hexose monophosphate shunt in isolated cardiac myocytes from normal rats. The activity of the hexose monophosphate shunt was studied in myocytes obtained from the ventricles of normal, adult, male rats. When myocytes were incubated in buffer containing either 1-14C- or 6-14C-labeled glucose the ratio of C-1/C-6 14CO2 evolved was essentially unity. The addition of plasma levels of amino acids did not alter this finding. If, however, a competitive substrate (pyruvate, octanoate, acetate, or lactate) was present, in sufficient quantity to lower the oxidation of glucose to approximately 20% of the control, the C-1/C-6 14CO2 ratio rose to values between 1.3 and 2.1. This ratio was dependent on the concentration of the competitive substrate, which was dependent on the buffer system. The data indicates that the hexose monophosphate shunt is active in the heart because it can be demonstrated when a substrate, which competes with glucose for oxidation, is present. The presence of competing substrates parallels the situation occuring in vivo.


HCO3- and H+ secretion in rat ileum in vivo. Replacing Cl- in the perfusion fluids decreased the luminal pH of rat ileum perfused in vivo. Varying the initial pH in Cl- depletion studies indicated an equilibrium pH near 6.6. Na+ depletion in Cl- deleted fluids partially inhibited luminal acidification. Addition of HCO3- accelerated Na+ absorption and decreased Cl- absorption. Luminal PCO2 was increased using fluids buffered to initial pH 6.6, suggesting secretion of HCO3- rather than OH-. The decreased HCO3- secretion using Cl- depleted fluids was not due to an acclerated rate of H+ secretion. Reaffirmed and expanded in this study is an ileal H+ secretory process that is partially related to Na+ absorption and direct HCO3- secretion that is related to Cl- and Na+ absorption.


Neural control of glycogen content and its diurnal rhythm in mouse pineal cell. In adult male dd mice, possible mechanisms regulating the glycogen content in the pineal cell were investigated by a semiquantitative histochemical method, with particular reference to the role of the sympathetic innervation. Reserpine, superior cervical ganglionectomy (SCGX), or decentralization of the ganglia (DC), as well as continuous light, prevented the nocturnal decrease in the glycogen content, causing a marked increase, and caused a gradual decrease in the size of the pineal cell. In the SCGX or DC group, the glycogen content reached a peak at 2 days and then decreased gradually. The nocturnal decrease was also prevented by propranolol. Noradrenaline caused a marked decrease in the glycogen content. These findings support the hypothesis that the glycogen metabolism and its diurnal rhythm in the pineal cell are regulated by the sympathetic nerve terminals innervating the pineal gland, presumably by the release of noradrenaline. In addition, the nature of the internal mechanism in the organism generating the pineal glycogen rhythm was examined. Light was considered to induce a phase shift in such a mechanism, but reserpine was not.


Function of human platelets during extracorporeal circulation. The interaction between human platelets and nonbiologic surfaces was studied during in vitro recirculation of 500 ml of fresh, heparinized human blood in four different perfusion circuits. Circuits differed in surface area (0.1 m2 or 0.9 m2) and in surface composition. No important differences were observed between standard silicone-rubber and filler-free, silicone-rubber surfaces. Platelet counts decreased to 85% of control in 0.1- m2 circuits, but retained normal sensitivity to aggregating agents and released only small amounts of platelet factor 4 (PF4). In contrast, platelet counts in 0.9-m2 circuits decreased to 20% of control within 2 min and platelet sensitivity was depressed out of proportion to the fall in platelet count. Plasma PF4 progressively increased and platelet PF4 content progressively decreased during 6 h of recirculation. The results indicate that human platelets may exist in three conditions during extracorporeal circulation. Some platelets are unaltered, some are less sensitive to aggregating agents, and others have undergone extensive release. The ratio of blood volume to surface area appears to be an important determinant of platelet-surface interaction.


Development of SHR hypertension and cardiac hypertrophy during prolonged beta blockade. Spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were treated with beta-adrenergic receptor inhibiting drugs (either propranolol or timolol) from conception until 12 weeks of age to determine if this therapy would alter the development of systemic hypertension or left ventricular hypertrophy. Therapy (propranolol or timolol, 500 mg/liter drinking water) was initiated with breeding parents and continued throughout the pregnancy, nursing, and postweaning periods. Although the heart rates of beta-adrenergic receptor inhibited WKY and SHR rats were consistently reduced with respect to their respective tap-water controls, this therapy did not alter body growth. Hemodynamic studies demonstrated reduced central venous pressure, cardiac index, and maximum acceleration of aortic flow in the beta-adrenergic inhibited rats. In spite of these findings, the arterial pressure of the treated rats and the degree of left ventricular hypertrophy of the SHR were unaltered by treatment. Thus, administration of the beta-adrenergic receptor blocking agents, propranolol or timolol, from conception through the developmental stage of SHR hypertension, failed to alter either the progressive rise in arterial pressure or the development of hypertensive vascular disease and left ventricular hypertrophy.


Effects of increased intracranial pressure on pulmonary vascular resistance of fetal and neonatal goats. The effects of increased intracranial pressure on the pulmonary circulation were investigated in fetal and neonatal goats. Pulmonary vascular resistance and systemic arterial pressure increased with elevation of intracranial pressure in neonatal animals. Alpha-adrenergic blockade completely eliminated both of these responses. The response of the fetal pulmonary circulation was unlike that seen in the postnatal animal. Although there was a slight elevation of pulmonary vascular resistance initially, the predominant response was a decrease in resistance. The decrease in fetal pulmonary vascular resistance was unaffected by phenoxybenzamine, but reversed by propranolol. After the beta-adrenergic blockade, increased intracranial pressure produced an increase in pulmonary vascular resistance. Similarly, ventilation of fetal lungs resulted in an increase in pulmonary vascular resistance after increased intracranial pressure. These results demonstrate for the first time that pulmonary vascular resistance may be altered in fetal and neonatal animals by increasing intracranial pressure. The elevation of pulmonary vascular resistance after elevated intracranial pressure must be due to an active pulmonary vascular constriction.


Active alkalinization by amphibian gastric fundic mucosa in vitro. Gastric fundic mucosae in vitro from four species of frog and Necturus secrete HCO-3 at a steady-state rate of 0.25-0.55  microneq-cm-2-h-1 which corresponds to 5-10% of maximal H+ secretion. Net alkalinization was quantitated in mucosae with spontaneously resting H+ secretion or in mucosae inhibited by histamine H2-receptor antagonists or SNC-. HCO-3 secretion was inhibited by DNP (10(-4) M), CN- (10(-2) M), or anoxia. Acetazolamide inhibited alkalinization at 10(-2) M when added to the nutrient side and at 10(-4) M on the luminal side. Carbachol (10(-4) M) and DBcGMP (10(-4) M) stimulated alkalinization and caused a transient rise in the transmucosal PD; DBcAMP (10(-3) M) was without effect. An almost identical secretion occurred spontaneously in antral mucosae and was insensitive to histamine (10(-5) M). Occurrence in both antral and fundic mucosa suggests that active alkalinization is a property of gastric surface epithelial cells. Gastric alkalinization may protect the luminal surface of the mucosa from the damaging effects of acid and contribute to the continuous removal of H+ ions from gastric contents.


Pancreatic bicarbonate, serum gastrin, and secretin responses to meals varying in pH. The role of secretin in the postprandial bicarbonate response by the pancreas is not clear. This study reports secretin and bicarbonate secretion after exogenous and endogenous acidification of meal. In dogs with gastric and pancreatic fistulas, a liver extract meal at various pH levels was introduced into the stomach and kept at the preselected pH by intragastric titration. Gastric acid, pancreatic bicarbonate, serum gastrin, and plasma secretin were measured. The meal at pH 7 produced an increase of gastrin levels of 230% above basal and a gastric acid output from a basal of 0.8-16.9 meq/30 min. Acidification of the meal evoked a pH-dependent reduction of gastrin and gastric acid secretion, a pH-dependent elevation of pancreatic bicarbonate, and significant elevation of secretin at pH 3 (43% above basal) and at pH 2 (80% above basal). Postprandial endogenous acidification of a meal, without intragastric titration, also provoked significant release of secretin. Maximal pancreatic bicarbonate secretion in response to exogenous secretin was augmented 30% by the addition of a liver extract meal at pH7. It is concluded that in dogs with pancreatic fistulas, a meal exogenously or endogenously (postprandial) acidified is capable of the release of secretin in immunoassayable amounts. The normal pancreatic bicarbonate response to food may depend partially upon potentiation of the secretin effect by other neurohumoral stimuli.


Influence of aldosterone on renal ammonia production. Administering D-aldosterone, 7 microgram 100 g-1, to rats results in a marked rise in ammonium excretion and metabolic alkalosis. Increased ammonium excretion is not related to either a significant elevation in potassium excretion nor to hypokalemia. Consequently, potassium depletion does not appear to be the causative factor in the aldosterone-stimulated ammonium excretion. Isolated kidneys from aldosterone-treated rats, perfused with 1 mM L-glutamine, produced twice as much ammonia from glutamine as did controls. Ammonia production per glutamine extracted increased from 1.33 +/- 0.07 in control to 1.79 +/- 0.08 in kidneys from hormone-treated rats, suggesting stimulation of the mitochondrial glutaminase I-glutamate dehydrogenase pathway; this was supported by a proportional rise in production of glucose and CO2, end products of glutamine's carbon skeleton. Consequently, aldosterone-stimulated renal ammonia production, by specifically activating the mitochondrial pathway, leads to the elimination of hydrogen ions in the form of urinary ammonium excretion and an ensuing metabolic alkalosis.


Solute permeability of the alveolar epithelium in acute hemodynamic pulmonary edema in dogs. Ten anesthetized dogs, 48 h postintravenous 131I-albumin injection, had a segment of lung airspace isolated by a balloon-tipped catheter lodged in a bronchus. An isotonic saline solution containing trace amounts of Blue Dextran, 125I-albumin, and 57Co-cyanocobalamin was instilled into the lung segment. During control periods, lung saline was absorbed at a rate of 0.133% per minute as measured by indicator dilution of Blue Dextran. Only 57Co-cyanocobalamin crossed the epithelium. Acute hemodynamic pulmonary edema was produced by aortic constriction plus saline overload. In pulmonary edema the fluid volume in the airspace increased at the rate of 0.96% per minute, and there was a significant influx of 131I-albumin into the lung saline from the blood in all animals. However, neither 125I-albumin nor Blue Dextran diffused from the airspace into blood during edema; both were merely diluted by fluid influx. The rate of diffusion of 57Co-cyanocobalamin increased fivefold during edema. A small number of discrete breaks in the lung epithelium allowing bulk flow of interstitial fluid is proposed to account for the one-way movement of albumin in hemodynamic alveolar edema.


Prostaglandin metabolism in the kidneys of spontaneously hypertensive rats. Renal prostaglandins have been implicated in the regulation of blood pressure. We have therefore compared prostaglandin metabolism in the kidneys of spontaneously hypertensive rats (SHR's) of the Aoki-Okamoto strain and normotensive Wistar-Kyoto (WKY) controls. The microsomal fraction of the renal medulla contained most of the prostaglandin synthetase activity in both groups; SHR's had significantly higher enzymatic activity than their normotensive controls at age 10 wk and thereafter; furthermore, synthetase activity in SHR's increased with age. Two forms of 15-hydroxyprostaglandin dehydrogenases were demonstrated: an NAD+-dependent form which was localized mainly in the cortex and an NADP+-dependent form, higher in the medulla. The activities of these enzymes were lower in the hypertensive animals at all ages studied; this depression was more pronounced for the NAD+-dependent dehydrogenase. The results indicate that, in hypertension, renal prostaglandin metabolism is altered so that enhanced synthesis is accompanied by decreased degradation rate.


Properties of the laryngeal chemoreflex in neonatal piglets. Cardiorespiratory reflex responses to laryngeal chemoreceptor stimulation were studied in 62 piglets of both sexes varying in age from 1 to 79 days. The distal trachea was cannulated to provide a free airway and the proximal end used to introduce fluids into the laryngeal area. Introduction of either water or milk produced apnea, bradycardia, and hypertension. Swab application of test fluids to the laryngeal epithelium produced similar responses. The reflex could be interrupted by flushing the laryngeal region with saline, by cutting the superior laryngeal nerves (SLN) or by anesthetizing the laryngeal epithelium with lidocaine. Electrical stimulation of SLN elicited identical responses. Respiratory inhibition by the reflex was enhanced following central depression with chloralose and overridden by administration of the respiratory stimulant, aminophylline. The relative potency of the laryngeal reflex was estimated to be equivalent to about 40% of the dose of chloralose which produced permanent respiratory arrest. It is concluded that in circumstances where respiratory drive is reduced the laryngeal inhibitory reflex is capable of caused persistent apnea and asphyxial death in the young piglet.


[The aging alimentary tract (author's transl)]. The physiological process of aging causes changes in volumen and composition of saliva, gastric and pancreatic juice and bile flow, a diminished absorption and an altered bacterial flora. However, these changes are compensated and do not cause symptoms. Besides of an increased disposition to develop carcinoma of the gut the alimentary tract in contrast to the cardiovascular system has no specific symptomatology as signs of wear. In old age, too, functional disorders rank first in clinical symptomatology.


[Differentiation of the aging intestinal epithelium by morphology, histochemistry and discelectrophoresis (author's transl)]. The intestinal epithelium of the small and large intestine of fetal rats (19th, 20th and 21st day of pregnancy) newborn and juvenile rats (1st to 50th day of life) adult rats (3rd to 4th month) and senile rats (18th to 30th month) was investigated by means of morphology, enzyme histochemistry and discelectrophoresis. The results obtained permit division of the development and aging of the rat intestinal epithelium into five periods: 1. The period of prenatal development. 2. The period of postnatal development. 3. The period of adaptation. 4. The stage of adult maturity. 5. The senile atrophy of the intestinal mucosa.


[Gastroscopic findings in aged patients (author's transl)]. Endoscopic findings in a group of 169 aged patients are shown to be concentrated in the stomach, whereas pathologic findings in the duodenal bulb are less frequent. In comparison to a group of young patients gastric mucosal atrophy, gastric ulcer, carcinoma of the operated and unoperated stomach, polyps are predominant in the aged patients. Approximately one half of carcinomas were seen in patients operated by the Billroth II technique. On behalf of this fact it is necessary to review patients endoscopically from the fifteenth year after operation on with regularity in order to detect growth of carcinoma in the early stage.


[Gastroduodenal ulcers in patients of a geriatric hospital (author's transl)]. Among 3646 patients of a geriatric hospital we we found 7,82% = 285 patients who suffered once in their life from a gastroduodenal ulcer. We noted: 1. gastroduodenal scars in 3,3% = 121 cases, 2. anamnestic proved gastroduodenal ulcer disease in 1,5% = 57 cases, 3. clinical and/or pathological proved gastroduodenal ulcers in 3% = 107 cases. Additional findings were put down as there are aortal arteriosclerosis, pulmonary heart and complications like perforation, penetration, bleeding and death.


[Ischemic bowel disease (author's transl)]. Geriatric patients are preferentially involved in ischemic bowel disease. The sudden occlusion of the large mesenteric arteries (a. mesenterica superior (more frequently) and inferior) is followed by intestinal gangrene and peritonitis with a poor prognosis and a high letality (greater than 90%). In chronic intestinal ischemia the leading clinical symptom is postprandial pain ('claudicatio intestinalis'). In some cases of acute mesenteric artery occlusion no embolus or thrombus will be found. In these cases the circulation in the arteriosclerotic vessels falls below a critical value due to cardiac insufficiency, shock, digitalis overdose and others. In less severe ischemia the mucosa is involved being most sensitive to O2 deprivation. It usually regenerates within a few days. This form is found more frequently in the colon than in other parts of the gut (about 40%): ischemic colitis. The therapy - if possible in acute, fulminant ischemia or if necessary in chronic intestinal ischemia - is surgical consisting in reconstructive procedures of the mesenteric circulation.


[Dependence of diverticulosis on age (author's transl)]. The diverticulosis of the gastrointestinal tract is a widespread senile disease. The dependence of the diverticulosis on age is investigated on the basis of 1 000 proven cases of this disease. The importance of the anatomicomorphological lesions of the organs at old age as its cause is pointed out. The males seem to be affected by the diverticulosis somewhat more than the females, whereas its percental manifestation in the different organs is about equal for both sexes. It prevails in the colon with 48.4% and in the duodenum with 35.4% of all cases of organ diverticulosis. The existence of constitutional associations with other diseases, such as diabetes mellitus, is discussed. Finally, the therapeutic problems of the diverticulitis and their dependence on age are examined.


[Functional digestive troubles in old age (author's transl)]. Functional disorders are frequent in elderly patients. However the high incidence of organic lesions in advanced age demands a most careful examination. Each diagnosis of functional disorders made by exclusion of organic lesions has to be revised, if symptoms persist or symptomatic treatment remains inefficient. Gastroenterological diagnostic should not be restricted to an endoscopic or radiologic glance to the gastrointestinal tract. It includes the less spectacular but more human trial to get an insight to the soul of the patient. This may be more helpful than any treatment with the newest double blind tested medication.


Age-dependent alterations of the rate of RNA synthesis in rat brain cell nuclei. Endogenous Mn2+ and Mg2+ activated RNA polymerase activity was measured in isolated cell nuclei of brain from rats of different age-groups. It was established that the activity of the nucleoplasmic RNA polymerase is maintained at the level of young animals up to an age of 16 months but is decreased after 24 months. The nucleolar RNA polymerase activity decreases already at 16 months and a higher ratio of the Mn2+:Mg2+ activated RNA polymerase activities has been found to be characteristic for the older animals. By means of stepwise sucrose density gradient centrifugation fractions were obtained from the nuclear preparations highly enriched in cell nuclei of neuronal and glial origin respectively. By measuring the activity of the nucleoplasmic and nucleolar RNA polymerases in these fractions it was found that the elevated ratio of the nucleoplasmic to nucleolar RNA polymerase activity at 16 months of age is a characteristic of the neuronal nuclei while the glial nuclei behave by the opposite manner. A parallelism existing between the age-dependent change of the endogenous RNA polymerase activity and that of perichromatic granules of rat brain cortical cells is discussed.


[Nutritional problems in old age (author's transl)]. While age is increasing involutiones specific to age can be proofed at the gastrointestinal tract, which lead to a deceleration but quantitative unchanged adsorption. Wrong nutrition concerning to the take up of fat, carbohydrates, proteins and trace elements can be found in greater age very often.  By watching a collective of healthy persons beyond the age of 90 years however it turns out that this group keeps a nearly faultless nutrition. The requirements of lysin, methionin and calcium is a little higher in old age than in younger. By intermitting starvation or addition of antioxidants life can be prolonged in experiments on animals, when this therapy starts already in younger age. Starvation in higher age, however, leads to a shortening of life in experiments on animals.


[In vitro-phosphorylation of histones in chromatin of various tissues in relation to age (author's transl)]. The influence of age on the structure of chromatin of various mammalian cells with modest or terminated mitotic activity has been examined. For this purpose chromatin from dog skeletal muscle, and human neuronal and glial cells, has been incubated together with an exogenous histone phosphokinase and ATP-gamma32P, and the phosphate incorporated into the histones determined. For comparison, also free histone has been phosphorylated. The amount of phosphate incorporated into total histone is 16-18 nmol Pi per mg histone in the case of free histone, and about equal for all cell types and ages. Into chromatin-bound histones only 5.5-8.2 nmol Pi per mg histone are incorporated. The differences between the various cell types and age groups are not significant. The relative phosphate incorporation into the single histone fractions depends on the histone as being free or chromatin-bound. In addition, relative phosphate incorporation into the single fractions of chromatin-bound histones is also cell type- and age-specific. The results permit the conclusion that the chromatin is subject to structural changes in the course of aging.


[RNA metabolism and ageing (author's transl)]. The labelling behaviour of RNA fractions in rat liver after application of 32P-orthophosphate and 14C-orotate in vivo in young (3-5 months) and old animals (20 months) was presented. Whereas the tracer incorporation in old animals 60 minutes after 32P-application seems to be decreased we observed increased specific activities of nuclear RNA 30 and 60 minutes after application of 14C-orotate i.p. - Measuring of RNA synthesis in isolated cell nuclei after in vivo stimulation by cortisol (2 mg/100 g body weight) showed a stronger and longer continued stimulation in young animals as in old both in the Mn++ system and in the Mg++ system. When we compared the young with the old controls the rate of synthesis was increased in the old controls. The results support observations on changed regulations of the transcription of genetic informations in the age.


[The vascularisation of the granulation tissue in different ages. - Its importance for wound healing (author's transl)]. The part of capillaries of a plastic sponge granuloma was determined in rats of different ages. It was found that granulation tissue of older rats contains significantly fewer capillaries than that of young animals. The diminished vascularisation of granulation tissue may be responsible for the deterioration of wound healing in aged individuals.


[Histone phosphorylation of human lymphocytes after PHA stimulation in relation to age (author's transl)]. Lymphocytes of young and old donors are stimulated by phytohemagglutinin (PHA). The 32P-incorporation into the histones which occurs in the early phase after PHA-stimulation is determined. In lymphocytes of old persons the 32P-incorporation in the histones is diminished by about 50% with respect to the cells of young donors. Furthermore, it could be shown that in the histones prepared from old cells the amount of H1 is much increased. It is postulated that, in old age, the other 4 histones are poorly extractable.


[Hydroxylation of skin collagen in relation to age: analyses of the human skin]. The results of human skin analysis are demonstrated. It has been pointed out, that the content of hydroxyproline and hydroxylysine, in addition to the usual variation as the other aminoacids varies extensively. The extent of hydroxylation was estimated from the relation of OH-aminoacids to (not hydroxylated) each other. The determined variation of the results is most probably due to a different collagen hydroxylation within the biological dispersion. An age-related degree of hydroxylation could not be detected.


[Investigations about the effect of run-training and run-stress on glucose tolerance and insulin secretion with ageing streptozotocin-diabetic rats (author's transl)]. Untrained grown-up and old rats with a mild Streptozotocin-diabetes show in i.v. glucose tolerance test a pathological glucose assimilation and diminished insulin secretion in comparison to control rats of the same age after a maximal run-stress. Trained rats show a different behaviour in glucose tolerance test depending on their age and seriousness of diabetes: Glucose tolerance is improved in grown-up rats with a mild diabetes and unchanged in old rats. Six-week run-training causes a significant deterioration of glucose tolerance in rats with a medium seriously Streptozotocin-diabetes and even leads to death of old rats because of decompensated metabolism. Grown-up rats with a mild diabetes stand run-stress after run-training better than the old ones. No animal with a medium seriously diabetes survives maximal run-stress, old rats don't even survive the slowly increasing run-training. - These results confirm the dualistic effect of muscular work. Metabolism of mild diabetes becomes better through muscular exertion the one of medium diabetes gets worse. Therefore a good effect of run-training is measurable only in grown-up rats not in old ones.


[Determination of neurophysiological parameters of the aging CNS. I. Evoked potentials (author's transl)]. Somatosensory (SEP) and visual (VEP) evoked potentials were studied in 65 healthy subjects who ranged in age from 62-91 years and in 48 normal persons aged 18-38 years. The amplitudes and latencies of the different components of the evoked potentials were measured. The transmission of evoked potentials from the specific response area into different regions of the ipsi- and contralateral hemisphere were studied. The findings can be summarized as follows: The latencies of the SEP and VEP of aged subjects are significantly prolonged. The increase in latency is relatively slight for the first components, progressively higher for the following components. The amplitudes of the different components of the SEP and VEP are significantly increased in aged subjects. The modifications of the SEP-latencies and of the VEP-amplitudes are more important over the dominant hemisphere. In young subjects the SE are confirmed to the centro-parietal region. In aged persons the SEP spreads over the whole hemisphere. The hypothesis that the aging process involves the synaptic transmitter mechanisms at the cortical level is discussed in relation to the involvement of the latencies. The increase in amplitude of the evoked potentials could be explained by assuming that the inhibition - an essential property of the cortex - decreases during the aging process.


[Lens changes occuring as a result of lowered pH (acidosis) (author's transl)]. In the lens, disorders of the metabolism occur, and, with them, active permeability (the cation pump with uptake of K and release of Na) changes to passive permeability and consequently Na ions enter with water. As a result, the lens increases in weight and a subcapsular (permeability) cataract develops. It is shown that the cattle lens in vitro increases in weight the lower the pH (6.5 greater than 7.5 greater than 8.5) of the surrounding fluid becomes. In a further experiment, 1 ml of buffered liquids with different pH were injected into the anterior chamber of the eyes of freshly slaughtered cattle. Here, too, the mechanically undamaged, untouched lens increased in weight more greatly as the pH (5.5 greater than 6.5 greater than 7.5 greater than 8.5) of the injected fluid was lowered. The significance of the lowering of the pH, e.g., in local inflammation (iritis, cyclitis, retinitis, etc.) or general acidoses (diabetes mellitus, galactosemia, hunger, extracorporeal circulation for atrophic kidney. Albright-, Love-, Fanconi-syndrome) for the appearance of incipient subcapsular clouding of the lens is pointed out.