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Biomedical subjects

M Adler

Publications and source records attributed to M Adler.

At least 235 records · Page 13Linked to original sources
PubMed1980

Pericanalicular hepatocytic and bile ductular microfilaments in cholestasis in man.

The cytoplasmic microfilaments of hepatocytes in the pericanalicular area and of bile ductular cells in various types of human cholestasis were examined and compared with those seen in the noncholestatic human liver. An increase in the number of hepatocytic microfilaments with an increase in the apparent density of the filamentous network and in the thickness of bundles of filaments was evident in the vicinity of the bile canaliculi, in the pericanalicular ectoplasm, and in the surrounding cytoplasm in all types of cholestasis but more so in intrahepatic cholestasis. This increase in the number of microfilaments was also seen around undilated canaliculi. Microfilaments were also increased in number beneath the surface of the bile ductular cells facing the cytoplasm but not beneath the rest of the plasma membrane. More microfilaments also were found around ductular cell nuclei. No striking differences were noted between intrahepatic and extrahepatic cholestasis. These findings suggest that microfilaments play a role that is not established in human cholestasis.

Bile Ducts, Intrahepatic↗
PubMed1979

Fatty liver hepatitis and cirrhosis in obese patients.

Liver function and liver biopsy findings were studied in a selected group of 29 overweight patients. Fatty liver, fatty hepatitis, fatty fibrosis and fatty cirrhosis were seen with equal frequency. Diabetes was also present with an equal incidence in each of these four pathologic groups. Lipoprotein abnormalities, particularly type IV hyperlipoproteinemia, were found mostly in the two groups with the lesions with less fibrosis (fatty liver and fatty hepatitis). The pathologic picture resembled that of alcohol and postjejunoileal bypass-induced liver diseases suggesting a common denominator in these three conditions.

Adolescent↗
PubMed1979

Tetraethylammonium: voltage-dependent action on endplate conductance and inhibition of ligand binding to postsynaptic proteins.

Tetraethylammonium (Et(4)N(+)) ions depressed the amplitude and accelerated the decay rate of spontaneously occurring and nerve-evoked endplate currents (EPCs) in frog sartorius muscle. The relationship between peak EPC amplitude and membrane potential became nonlinear in the presence of 100 muM Et(4)N(+), and with drug concentrations of 250 muM or greater the current-voltage relationship exhibited negative conductance in the hyperpolarized region. Et(4)N(+) modified the exponential dependence of the EPC decay on membrane potential such that the decays between -150 and -50 mV were abbreviated and voltage independent but remained near control levels at more positive membrane potentials. The minimal effective concentration of Et(4)N(+) for altering the EPC time course was 10, and maximal effects were attained with 100 muM. Little additional shortening in the EPC decay phase was detected on raising the drug concentration to 1000 muM. Acetylcholine noise analysis revealed a voltage-dependent reduction in the mean channel open time, which was comparable in magnitude to the shortening in the EPC decay, and a depression of single-channel conductance. In concomitant biochemical studies, Et(4)N(+) was found to inhibit the binding of both [(3)H]acetylcholine and [(3)H]perhydrohistrionicotoxin to receptor-rich membranes from the electric organ of Torpedo ocellata with K(i) values of 200 muM and 280 muM, respectively. These results suggest that Et(4)N(+) interacts with both the acetylcholine receptor and its associated ionic channel. The voltage-dependent actions of Et(4)N(+) are attributed to blockade of the ionic channel in closed as well as open conformation.

Acetylcholine↗
PubMed1979

Reaction of tetraethylammonium with the open and closed conformations of the acetylcholine receptor ionic channel complex.

The effect of tetraethylammonium (TEA) bromide on the neurally and iontophoretically evoked endplate current (EPC) of frog sartorius muscle was investigated using voltage-clamp and noise analysis techniques, and its binding to the acetylcholine (ACh) receptor ionic channel complex was determined on the electric organ of Torpedo ocellata. TEA (250-500 microM) produced an initial enhancement followed by a slow decline in the amplitude of the endplate potential and EPC, but caused only depression in the amplitude of the miniature endplate potential and current. In normal ringer's solution, the EPC current-voltage relationship was approximately linear, and the decay phase varied exponentially with membrane potential. Upon addition of 50-100 microM TEA, the current-voltage relationship became markedly nonlinear at hyperpolarized command potentials, and with 250-2000 microM TEA, there was an initial linear segment, an intermediate nonlinear segment, and a region of negative conductance. The onset of nonlinearity was dose-dependent, undergoing a 50 mV shift for a 10-fold increase in TEA concentration. The EPC decay phase was shortened by TEA at hyperpolarized but not depolarized potentials, and remained a single expotential function of time at all concentrations and membrane potentials examined. These actions of TEA were found to be independent of the sequence of polarizations, the length of the conditioning pulse, and the level of the initial holding potential. TEA shifted the power spectrum of ACh noise to higher frequencies and produced a significant depression of single channel conductance. The shortening in the mean channel lifetime agreed closely with the decrease in the EPC decay time constant. At the concentrations tested, TEA did not alter the EPC reversal potential, nor the resting membrane potential, and had little effect on the action potential duration. TEA inhibited the binding of both [3H] ACh (Ki = 200 microM) and [3H]perhydrohistrionicotoxin (Ki = 280 microM) to receptor-rich membranes from the electric organ of Torpedo ocellata, and inhibited the carbamylcholine-activated 22Na+ efflux from these microsacs. It is suggested that TEA reacts with the nicotinic ACh-receptor as well as its ion channel; the voltage-dependent actions are associated with blockade of the ion channel. The results are compatible with a kinetic model in which TEA first binds to the closed conformation of the receptor-ionicchannel complex to produce a voltage-depdndent depression of endplate conductance and sudsequently to its open conformation, giving rise to the shortening in the EPC decay and mean channel lifetime.

Acetylcholine↗
PubMed1978

Plasma cyclic AMP levels during a secretin-caerulein pancreatic function test in liver and pancreatic disease.

Plasma cyclic AMP levels were determined during a 40 minute secretin infusion (1 Cl.U kg-1h-1) followed by a 40 minute combined secretin (1 Cl.U kg-1h-1) caerulein (75 ng kg-1h-1) infusion. In nine healthy subjects, both secretin alone and secretin in combination with caerulein did not affect plasma cyclic AMP levels. The same was observed in six patients with chronic pancreatitis. By contrast, in patients suffering from liver disease (nine cases) or extrahepatic cholestasis (six cases), secretin elicited large increases in plasma cyclic AMP concentration; the mean values attained being, respectively, seven and four times higher than before the infusion. On the other hand, increases in plasma cyclic AMP 10 minutes after a bolus injection of glucagon (1 mg) were four times lower in the liver disease group as compared to the controls. The results reported here suggest that the liver plays a major role in the degradation of plasma cyclic AMP produced by target tissues responding to secretin, and in the release of cyclic AMP under glucagon. Liver disease reduce the capacity of the liver to clear cyclic AMP from the blood. The pancreas does not contribute significantly to the cyclic AMP in the blood.

Ceruletide↗
PubMed1978

The parotid and the pancreas. V. Effects of a synthetic prostaglandin analog on parotid gland secretion.

Effects of a synthetic prostaglandin analog--16,16-dimethyl prostaglandin E2 methyl ester (16-diMe-PGE2)--on parotid secretion were evaluated in eight dogs under anesthesia. Graded doses of 16-diMe-PGE2 (0.3, 0.5, 1.0 and 2.5 microgram./kg.) were administered intravenously with the parotid in the resting state or in response to urecholine (intravenous infusion or subcutaneous injections). Profound and prolonged inhibition of volume occurred. Amylase concentration was increased but output was unchanged. Bicarbonate concentration was increased but output was decreased. Nonsteroid inhibitors of endogenous prostaglandin synthesis did not alter these effects. Although these studies do not establish a physiologic role for prostaglandins in the regulation of salivary secretion, they do demonstrate a wide-ranging effect of prostaglandins on the gastrointestinal tract.

Amylases↗
PubMed1978

The pancreas: a correlation of function and structure.

Fifty-two patients with or without pancreatic disease were studied with both secretin test and endoscopic retrograde pancreatography. Pancreatic histopathology was obtained by exploratory laparotomy in half of these patients. The following conclusions were reached: 1. Secretory tests are the most sensitive indicators of chronic pancreatitis, although not all cases of chronic pancreatitis will be discovered by this test. 2. When secretory tests show low volume output, pancreatography is crucial in differentiating between malignant ductal obstruction or pancreatic replacement by fibrosis or atrophy. 3. Histologic correlation with ductular structure and/or secretin function is frequently discordant. 4. The secretin test and pancreatogram measure different parameters and the use of both these complementary studies will lead to increased diagnostic accuracy and better understanding of pancreatic pathophysiology.

Carcinoma↗
PubMed1978

The parotid and the pancreas.

Parallel studies in parotid and pancreatic function and histology were carried out in Thomas fistula dogs with irradiation-induced chronic pancreatitis. After completion of base line studies of parotid and pancreatic secretion, four dogs were subjected to 2,400 rads tumor dose over two weeks (with a nominal single dose of 1,175 rets); two additional dogs served as control. Sequential studies were performed on pancreatic secretion in response to secretin and on parotid secretion in response to urecholine. After a short-lived period of hypersecretion. There was a progressive reduction in pancreatic secretory rate, bicarbonate and enzyme outputs (greater than 90% after three months). Parotid secretion increased over this period but subsequently decreased, so that at eight months there was a marked reduction both in pancreatic and parotid function. Whereas pancreatic histology showed diffuse interstitial fibrosis and reduction of acinar tissue, no histologic changes were noted in the parotid glands. Although the mechanisms are unclear, alterations in parotid secretion may be of value in the diagnosis of chronic pancreatitis, in the evaluation of its severity, and may yield information on the duration of the disease.

Animals↗
PubMed1977

Perhydrohistrionicotoxin: a potential ligand for the ion conductance modulator of the acetylcholine receptor.

Histrionicotoxin from the Colombian frog Dendrobates histrionicus and its perhydro derivative reversibly block the acetylcholine-sensitive ion conductance system in frog neuromuscular preparations. The perhydro derivative and [3H]perhydrohistrionicotoxin, like histrionicotoxin, caused a significant decrease in the peak amplitude of the end-plate current and shortened its rise time and half-decay time. In membrane preparations from Torpedo electroplax, [3H]perhydrohistrionicotoxin bound reversibly to a limited number of high-affinity sites [dissociation constant, (KD) = 0.4 micronM]. The ratio of perhydrohistrionicotoxin to acetylcholine binding sites in these membrane preparations approached 2. Histrionicotoxins, local anesthetics, and certain cholinergic agonists inhibited binding of perhydrohistrionicotoxin. Binding of perhydrohistrionicotoxin to membranes was decreased by heat or treatment with proteases. Treatment of membranes with Triton X-100 solubilized acetylcholine binding proteins and apparently also perhydrohistrionicotoxin-binding proteins. However, the detergent Triton X-100 also bound [3H]perhydrohistrionicotoxin. This nonspecific binding was not saturable and complicated studies on the antagonism by drugs of binding of [3H]perhydrohistrionicotoxin. In solubilized preparations the binding protein for acetylcholine could be removed by affinity chromatography or immunoprecipitation without affecting binding of perhydrohistrionicotoxin. Sephadex chromatography also separated acetylcholine- from perhydrohistrionicotoxin-binding proteins. Perhydrohistrionicotoxin did not bind significantly to purified acetylcholine-receptor protein but presumably bound to an ion conductance modulator protein that was associated with the acetylcholine-receptor in intact membrane and readily separable from the receptor protein after solubilization.

Amphibian Venoms↗
PubMed1977

Effects of duodenal alkalinization on pancreatic secretion.

Effects of duodenal alkalinization on pancreatic secretion were evaluated in seven dogs including two antrectomized dogs with chronic duodenal fistulas. Continuous intravenous injection of secretin or secretin plus CCK PZ was administered as a stimulus for the pancreatic secretion. Intraduodenal infusion of alkaline solutions such as pancreatic juice (pH 8.6), bile (pH 8.1), bicarbonate solution (160 mEq./I., pH 8.6) and TRIS buffer solution (0.3 M, pH 9.5) caused a moderate increase in protein output and a modest or no increase in flow but no change in bicarbonate output. During infusion of pancreatic juice, varied doses of secretin (0, 0.015, 0.03, 0.06 u./kg./min.), or secretin (0.03 u./kg./min.) plus CCK-PZ (0.05 u./kg./min.) were administered intravenously. For example, under the stimulation of secretin (0.03), flow increased modestly (17.7%), an increase which was of statistical significance. Protein output also showed a significant increase of 35.7%. There was, however, no response of the pancreas to the infusion of pancreatic juice when the gland was stimulated by secretin plus CCK-PZ. Antrectomy did not alter the effect of alkaline intraduodenal infusions on pancreatic secretion.

Animals↗
PubMed1976

Effect of irradiation on the canine exocrine pancreas.

Effects of irradiation on the pancreas was studied in 6 dogs receiving a dose equivalent to the biologic effect of 4000 R/6 weeks (with a nominal stnadard dose of 1175 rets) given to patients with Hodgkins disease. After control secretory, histologic and pancreatographic studies, 6 Thomas fistula dogs were subjected to 2400 R tumor dose over two weeks. There was a biphasic response to secretin alone or secretin with cholecystokininpancreozymin. An initial hypersecretion occurred at 2 weeks --volume was increased, but bicarbonate and enzyme output remained unchanged. Thereafter there was a progressive reduction in volume, bicarbonate and enzyme outputs ( greater than 90% after 3 months). Histology showed early ductal reduplication but with progressive fibrosis, features compatible with chronic pancreatitis. Pancreatic insufficiency may contribute to post-irradiation gastrointestinal symptomatology. Close field irradiation of the pancreas results in actual destruction of the parenchyma.

Animals↗