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Biomedical subjects

J Graf

Publications and source records attributed to J Graf.

At least 145 records · Page 8Linked to original sources

Ionic currents across pancreatic acinar cell membranes and their role in fluid secretion.

Fluid and enzyme secretion from a number of mammalian exocrine glands is controlled by the action of neurotransmitters and hormones on acinar cell membranes. Sustained stimulation evoking sustained fluid and enzyme secretion also evokes sustained membrane depolarization and increase in conductance. Mouse and rat pancreatic fluid and enzyme secretion, as well as membrane depolarization and conductance increase evoked by sustained stimulation with acetylcholine or cholecystokinin-gastrin peptides, are acutely dependent on extracellular calcium. However, the initial stimulant-evoked conductance increase and secretion appear to be triggered by calcium released from inside the cells. Direct measurement of membrane current during sustained stimulation in voltage-clamp experiments with resolution of the total current into its Na, Cl and K components has allowed calculations of stimulant-evoked Na and Cl uptake into the acinar cells. The NaCl uptake is quantitatively sufficient to account for the stimulant-evoked fluid secretion. The role of the stimulant-evoked transmembrane ionic current appears to be the supply of salt for the fluid secretion. Calcium derived from intracellular sources in the initial phase of secretion, and from the extracellular fluid in the sustained phase, couples fluid and enzyme secretion to hormone-receptor interaction.

Bicarbonates↗

Phase II study of dibromodulcitol in colorectal, kidney, and other carcinomas.

In a phase II study dibromodulcitol (DBD), an alpha-omega dibrominated hexitol, was used to treat 99 previously treated patients with colon, rectal, kidney, and other tumors. Six patients were ineligible and 10 patients were nonevaluable for response. Aside from thrombocytopenia toxicity was moderate. Twenty-three patients had platelet nadirs of less than 50,000/mm3 and there were three thrombocytopenic-associated drug deaths. One of 21 rectal and 1 of 13 kidney cancer patients entered a remission. All but seven patients had received previous treatment with one or more cytotoxic agents. Previously treated patients with colorectal and kidney cancer appear to be resistant to DBD.

Aged↗

[Campylobacter jejuni enteritis in Switzerland].

In a two-center study (Zurich and Berne) covering a 5-month period (September 1979 to January 1980) 665 faeces from patients with diarrhoea and 800 faeces from people without diarrhoea were examined for Campylobacter jejuni. By selective culture Campylobacter jejuni was isolated from 28 faeces of 35 patients with diarrhoea (5,7%) while none of the normal faeces yielded a positive culture. Isolation rates for Salmonellae and Shigellae from the same material (patients with diarrhoea) were 12.6% and 0.9% respectively. Infection with Campylobacter usually causes unspecific enteritis with spontaneous remission after 2--10 days. Occasionally, however, a more severe course initially simulating acute abdominal illness can lead to hospital admission and even to surgical procedures. Symptomatic treatment is suggested for mild cases. In more severe cases, antibiotic therapy is recommended, erythromycin being the drug of choice.

Campylobacter Infections↗

Influence of fibrinogen levels in dogs on mortality from hemorrhagic and traumatic shock.

1) Fibrinogen levels appear related to the outcome of hemorrhagic shock in dogs. 2) Fibrinogen levels can vary with different animals based on location, disease, stress, nutrition, or other factors. 3) Any experiments in hemorrhagic shock (or anything else) should utilize simultaneous and paired controls of animals from the same source or they may be subject to major error.

Animals↗

The danger of hemolysis in shock.

Intravascular hemolysis is sometimes harmful and often fatal. Other times it is harmless. Dogs were paired and subjected to hemorrhagic shock. One of the pair was given 2 ml/kg of autologous hemolyzed blood before bleeding. The other of the pair was given 2 ml/kg of heparinized autologous blood. All of the animals given heparinized blood survived, whereas, all of the animals given hemolyzed blood died. The animals given hemolyzed blood developed coagulation changes indicative of Disseminated Intravascular Coagulation (DIC), whereas, the dogs given nonhemolyzed blood did not. It is concluded that hemolysis in the presence of shock (slow capillary flow) causes DIC and death. Hemorrhagic shock alone or hemolysis alone was harmless.

Animals↗

Cell membrane potential and resistance in liver.

1. Isolated segments of mouse liver were placed in a Perspex bath through which physiological saline solutions of varying composition were circulated. Two microelectrodes were inserted in different liver cells under microscopic control allowing measurement of distance between the two micro-electrode tips. Current pulses were injected through one of these electrodes, causing electrotonic potential changes in nearby cells by current spread through intercellular junctions. These electrotonic potential changes were recorded with the second micro-electrode. The spatial decrement of the amplitude of the electrotonzpotential changes and their dependence on extracellular ion concentrations were analysed by three-dimensional cable analysis, modified to account for the geometry of the tissue. 2. During exposure to control solution the mean resting cell membrane potential was -37 mV, the space constant for intracellular current spread (lambda3 = square root of Rm/chrRi) was 390 micron and Ri, a measure which includes the intracellular resistivity and the junctional resistances, was 1.4 komegacm. From these values, and an estimate of tissue cell membrane density (chi) obtained by others, the specific membrane resistance (Rm) was calculated to be 5.1 komegacm2. 3. Replacement of extracellular Na+ by K+ resulted in a large depolarization and a large decrease in the membrane resistance. Replacement of extracellular Na+ by choline resulted in a small transient hyperpolarization and a small increase in the membrane resistance. Replacement of extracellular Cl- by methylsulphate or sulphate or of NaCl by sucrose resulted in a small transient depolarization and a large increase in the membrane resistance. 4. Glucagon (10(-7) M) and adrenaline (10(-5) M) evoked membrane hyperpolarization and reduction of membrane resistance (Rm). 5. The resting membrane ion conductance can be considered to consist of three components, Cl conductance (GCl), GK and GNa. The results suggest that GCl greater than GK greater than GNa. Changes in extracellular ion concentrations specifically alter the permeability properties of the cell membrane. The glucagon action can be explained in part by an increase in GK.

Animals↗

Investigations on the sodium dependence of bile acid fluxes in the isolated perfused rat liver.

At [Na+]o = 118 mM the concentrative transfer of cholic and taurocholic acid from the perfusate into the isolated rat liver displays saturation kinetics (taurocholate: V = 299 nmol-min-1-g-1, Km = 61 muM; Cholate: V=327 nmol-min-1-g-1, Km = 436 muM). Perfusion with an isotonic sodium-free medium did not change the feature of a carrier-mediated transport but did markedly reduce V without affecting Km (taurocholate: V = 65 nmol-min-1-g-1, Km = 78 muM; cholate: V = 104 nmol-min-1-g-1, Km = 354 muM). It was experimentally assured that the observed reduction of bile salt uptake was not a consequence of regurgitation of bile salts or due to an excessive intracellular accumulation during cholestasis in the sodium-free state. The rate of taurocholate efflux is very low when compared with the rapid rate of the uptake. A stimulatory action of extracellular sodium on this pathway was also observed. Inhibition of the (Na+ + K+)-ATPase by 1 mM ouabain resulted in a decrease of bile salt uptake. Activation of the enzyme by potassium readmission to a K+-deprived liver enhanced bile salt uptake. The immediate response to alteration of the enzyme activity suggests a close association of a fraction of bile acid active transport with the sodium pump.

Adenosine Triphosphatases↗

Ouabain-mediated sodium uptake and bile formation by isolated perfused rat liver.

Ouabain exhibits a dose-dependent choleretic effect in the isolated perfused rat liver. Its uptake from the perfusate into the liver is maintained against a concentration gradient and becomes clearly saturated at higher perfusate concentrations. A low extracellular sodium concentration inhibits the rate of ouabain transfer into liver cells, resulting in a marked decrease of the maximal transport rate. Dibucaine completely abolishes the uptake of the glycoside by the isolated liver. Determination of Na-22 tracer fluxes suggests that ouabain uptake is accompanied by a net flux of sodium into the cell, which seems to be due to a cotransport of sodium with ouabain rather than to the inhibition of the sinusoidal Na+ -K+ -ATPase. Sodium introduced into the cell in this way apparently is extruded into the bile canaliculi. The increase of isotonic bile flow, which is simultaneously observed, points to a dilution of the canalicular sodium gradient by water and electrolytes through an intercellular pathway. Our results present further evidence that bile secretion is controlled by transcellular sodium movements.

Anesthetics, Local↗