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Biomedical subjects

D M Goldberg

Publications and source records attributed to D M Goldberg.

At least 73 records · Page 4Linked to original sources
PubMed1987

Effect of phenobarbital upon serum cholesterol lipoprotein fractions of three rodent species.

Phenobarbital (PB) in doses previously shown to be optimal for induction of hepatic microsomal enzymes had no effect on the cholesterol content of whole serum or of serum lipoprotein fractions in the guinea pig, but reduced high density lipoprotein cholesterol (with increase in very low density lipoprotein cholesterol) in the rabbit, and increased high density lipoprotein cholesterol (as well as total and low density lipoprotein cholesterol) in the rat. These results, when taken together with previous data demonstrating that PB increases serum triglyceride in the rabbit but lowers it in the rat, suggest that the drug may be atherogenic in the rabbit but not in the rat which, in any case, is highly resistant to atheroma.

Animals↗
PubMed1986

Histoplasmosis in patients with the acquired immune deficiency syndrome.

Five patients with disseminated histoplasmosis are reviewed. Four of five had the acquired immune deficiency syndrome (AIDS) and one was receiving steroid therapy. All were immigrants to the United States from Puerto Rico, the Dominican Republic, or South America, and none had a history of travel to regions of the United States where Histoplasma is endemic. Histoplasma complement fixation titers to mycelial antigen were not demonstrable in three of three patients in whom they were measured. Of the four patients with AIDS, Histoplasma capsulatum was isolated from bone marrow aspirates in two patients and from lymph node and liver biopsy specimens in one patient each. One of the bone marrow specimens showed organisms on Gomori-methenamine silver stain. In the other three cases, results of staining were falsely negative and diagnosis awaited culture results weeks later. Amphotericin B therapy resulted in rapid clinical improvement in the three patients that were treated. Intravenous therapy was followed by treatment with oral ketoconazole. Follow-up has not been long enough to determine the ultimate efficacy of ketoconazole. Disseminated histoplasmosis should be considered in all patients from the Caribbean or South America with AIDS or who are receiving immunosuppressive therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Stool chymotrypsin activity measured by a spectrophotometric procedure to identify pancreatic disease in infants.

The aim of this study was to assess the analytical performance of the BMC stool chymotrypsin test and its accuracy in diagnosing pancreatic disease in infants. The test utilizes a detergent which solubilizes chymotrypsin bound to stool residues, and a tetrapeptide coupled to p-nitroaniline which is specifically cleaved by chymotrypsin. We employed the IL Multistat at 30 degrees C to monitor enzyme activity as an increase in absorbance at 405 nm. The reaction was linear to 600 U/g stool. Recovery of exogenous chymotrypsin with a single detergent extraction was 98-105%, and of endogenous chymotrypsin (as determined by multiple extractions) 80-97%. Imprecision (CV) was 2.2% within-day and 2.4% between-day for the BMC control, and 2.4-5.2% for stool chymotrypsin in the range 8.3-14.4 U/g. Since the test utilises only 100 mg of stool, inhomogeneity of enzyme distribution was assessed by multiple assays on a single stool, which revealed a range of activity from 4.2-150%. We therefore recommend sampling of each stool in triplicate. With this procedure, chymotrypsin was measured in 220 consecutive stool samples submitted for fat determination from children. Applying the manufacturer's lower reference limit of 4.1 U/g, the following results were obtained (number abnormal/total number): suspected intestinal disease with normal stool fat (5/127); proven intestinal disease and increased stool fat (1/26); untreated cystic fibrosis (CF) with (19/22), and without (0/3) steatorrhea; CF with pancreatic insufficiency on replacement therapy (4/42).(ABSTRACT TRUNCATED AT 250 WORDS)

Chymotrypsin↗
PubMed1986

Modulation by phenobarbital of the differentiation of 3T3 preadipocytes.

The effect of phenobarbital upon the differentiation of two preadipocyte cell lines, 3T3 F442A and 3T3 L-1, was examined by measuring the synthesis and secretion of lipoprotein lipase. Extracellular enzyme was measured by treating intact cells with heparin, and the intracellular enzyme was subsequently assayed in cell homogenates. When confluent cultures of 3T3 F442A cells were treated with insulin, the cells underwent differentiation as indicated by increased activity of lipoprotein lipase within 6 days, followed in turn by increased levels of protein and triglyceride. Addition of phenobarbital with insulin enhanced total lipoprotein lipase, protein, and triglyceride content. The activity of lipoprotein lipase accumulated in the heparin-releasable fraction during differentiation was increased 2- to 3-fold and the intracellular enzyme was enhanced 15- to 20-fold by the addition of phenobarbital. The ability of phenobarbital to modulate differentiation was dependent upon the time of addition. When added early in the postconfluent period, there was a greater increase in lipoprotein lipase activity than when the drug was added at later times. Phenobarbital also stimulated lipoprotein lipase in differentiating 3T3 L-1 cells in the presence of insulin, although lipoprotein lipase activity was moderately enhanced by phenobarbital alone in these cells. These results suggest that phenobarbital may affect the conversion of adipoblasts into preadipocytes and thereby increase the proportion of cells susceptible to the differentiating stimulus.

Adipose Tissue↗
PubMed1986

Secretion of triglyceride lipase from rat hepatocytes in culture: modulation by insulin and phenobarbital.

Hepatic triglyceride lipase (HTGL) was measured in primary rat hepatocytes maintained for 3 days under three different culture conditions: basal medium, basal medium plus insulin, and basal medium plus insulin and phenobarbital. The activity of HTGL secreted by these cells was measured by treating intact cells with heparin; intracellular enzyme was subsequently measured in cell homogenates. Insulin stimulated intracellular triglyceride lipase activity by 48% and extracellular lipase by 30%. Phenobarbital, an enzyme-inducing drug, caused a further 15% increase in extracellular hepatic triglyceride lipase; whereas, the intracellular activity was reduced. The presence of insulin greatly stimulated the rate of enzyme secretion, and this rate was not notably affected by the presence of phenobarbital. After 3 days in culture, the short term (2-8 h) synthesis and secretion of enzyme from cultures treated with insulin or insulin plus phenobarbital were equally inhibited by cycloheximide. Monensin also inhibited enzyme secretion in both cultures and caused a similar increase in intracellular lipase activities. Insulin did not significantly affect the proportion of intracellular enzyme (17.7% basal vs. 15.8% insulin). On the other hand phenobarbital produced a 20-30% reduction in the proportion of intracellular enzyme (12.5 vs. 17.7% basal or 15.8% insulin). These findings suggest a drug-induced redistribution of triglyceride lipase.

Animals↗
PubMed1986

Activities of gamma-glutamyl transferase, 5'-nucleotidase and alkaline phosphatase in human duodenal aspirate.

Duodenal aspirates were obtained before, during, and after stimulation with secretin-cholecystokinin in 26 patients whose pancreatic function was classified as normal, moderately reduced, or severely reduced. The activities of gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), and 5'-nucleotidase (5NT) in the aggregated duodenal aspirate collected 10-40 min after stimulation showed marked overlap between the functional groups and lacked diagnostic value. For all three enzymes, the peak response occurred later in the severely impaired group than in those with normal pancreatic function. The three enzymes showed significant positive correlations with each other, and were negatively correlated with the output of trypsin and chymotrypsin and, in contrast with these proteolytic enzymes which were reduced in pancreatic disease, GGT, ALP, and 5NT all tended to increase with pancreatic disease. Contrary to a previous report, GGT did not serve as a useful index of pancreatic cancer in this study.

5'-Nucleotidase↗
PubMed1986

Role of membranes in disease.

The membranes of mammalian cells are composed of an ordered array of lipids and proteins, the latter containing carbohydrate residues directed towards the exterior and important in the interaction of cells with each other and with external proteins. This external (plasma) membrane and other more simple membranes within the cell are damaged in all diseases which compromise the integrity of the cell. However, in many cases, chemical or functional changes in these membranes are central to the pathogenesis of the disease. These processes are illustrated, and a classification of membrane-related diseases is proposed. This includes: receptor-related diseases such as type II familial hypercholesterolaemia, Grave's disease, some lysosomal storage diseases and some forms of diabetes and obesity; structural instability as manifested by red cell abnormalities and multiple sclerosis; changes in lipid state as in muscular dystrophy and multiple sclerosis; altered permeability or transport as in cystic fibrosis, diseases associated with specific transport defects, and the action of many bacterial toxins, and abnormality of the cytoskeleton-membrane interface as in Chediak-Higashi disease and some diseases associated with red cell abnormalities. Different mechanisms can contribute to the membrane disorder in a single disease state and many of these are described to illustrate this diversity.

Bacterial Toxins↗
PubMed1984

The noninvasive biochemical diagnosis of gastrointestinal disease, with special reference to children.

Invasive tests to diagnose patients with gastrointestinal disease are rapidly being replaced by procedures which enable organ function to be assessed by monitoring the product of a metabolic reaction in readily available materials such as breath, blood, and urine. Examples of these approaches that will be assessed in this review include the hydrogen breath test for lactase deficiency, radioactive carbon dioxide breath measurements to test for fat digestion and absorption, and tests of pancreatic function based upon synthetic substrates from which fluorescein or para-aminobenzoic acid can be liberated by pancreas-specific enzymes. Significant advances have been made in improving the organ sensitivity of enzyme determinations. The determination of amylase isoenzymes has been less useful than the measurement of immunoreactive trypsin; this latter enzyme is greatly elevated in the blood of neonates with cystic fibrosis, whereas serum levels are greatly depressed in cystic fibrosis patients with pancreatic insufficiency as well as in most patients with steatorrhea due to chronic pancreatitis. Many of these tests are now becoming standard procedures in the investigation of infants with gastrointestinal disease.

Amylases↗
PubMed1983

Age-related changes in hepatic triacylglycerol content and phosphatidate phosphohydrolase activities in fasting male and female rats.

Hepatic microsomal phosphatidate phosphohydrolase (PPH) showed minor fluctuations with age in male and female rats. In males, hepatic cytosolic PPH rose to a peak at day 58 and then declined. In female rats, the activities of this enzyme were much lower than those of the male to day 35, but then increased fivefold by day 50 to values approximating those of males, and thereafter gradually declined. The hepatic triacylglycerol (TG) content of male rats was fairly constant, but in females the values rose to a peak on day 50 and then declined in parallel with the cytosolic PPH activity, but remained substantially higher than values for male rats. A significant correlation between cytosolic PPH and hepatic TG was obtained. The microsomal PPH did not correlate with hepatic TG. These results suggest that in the rat cytosolic PPH may play a role in modulating age-related changes in hepatic TG metabolism, and that it is functionally more important than the microsomal enzyme in this species.

Aging↗
PubMed1983

Behavioral effects of clozapine: comparison with thioridazine, chlorpromazine, haloperidol and chlordiazepoxide in squirrel monkeys.

The behavioral effects of the antipsychotic drug, clozapine, were compared with those of thioridazine, chlorpromazine, haloperidol and chlordiazepoxide. Behavior of squirrel monkeys was controlled by different consequences of a lever-pressing response (presentation of food, presentation of electric shock or termination of a stimulus associated with electric shock) under different schedules of reinforcement (a fixed-interval schedule or a multiple schedule with alternating fixed-ratio and fixed-interval components). The effects of thioridazine (0.2-24.6 mumol/kg), chlorpromazine (0.03-2.8 mumol/kg) and haloperidol (0.001-0.08 mumol/kg) were largely independent of the type of schedule or the type of consequent event that maintained responding: each drug produced dose-related decreases in responding under all conditions in which they were studied. Clozapine (0.1-9.2 mumol/kg) and chlordiazepoxide (0.9-167.4 mumol/kg) also only decreased responding under most schedule conditions; however, intermediate doses of either drug markedly increased responding maintained by presentation of food under the fixed-interval schedule (whether programmed singly or as a component of the multiple schedule). Only clozapine increased responding maintained by presentation of electric shock under the fixed-interval schedule. Thus, the behavioral effects of clozapine differed qualitatively from those of representative antipsychotic and antianxiety drugs.

Animals↗
PubMed1982

Models of illusory pausing and sticking.

When identical dots moving at equal velocities but in opposite directions become coincident, a striking illusion occurs. The dots appear to pause momentarily, despite no objective change in velocity. Three models for the illusion were examined: A vector averaging model best accounts for the data. According to this model a motion system maps visual space and assigns motion vectors to each position on the map. When identical objects traveling at equal velocities but in opposite directions become coincident, they lose their phenomenal identity and a form system detects a single object. The motion system, however, has two vectors mapped onto the same position occupied by a now-single object. Since an object cannot move in two directions at the same time, the motion system averages the vector and assigns the resultant to the object, thus resolving the ambiguity. With equal but opposite vectors, averaging yields a zero resultant (null vector), and thus pausing is perceived. With unequal vectors, averaging yields a nonzero resultant and something other than pausing is perceived. Velocity and number of collisions strongly affect the magnitude of the illusion, but in all cases in which the illusion is perceived, the objects appear to stick together and move at a velocity near the average of the component velocities.

Cues↗
PubMed1982

Modulation by phenobarbital of lipolytic activity in postheparin plasma and tissues of the rat.

Male rats injected with phenobarbital at a dose of 100 mg/kg for 5 days manifested increased postheparin lipolytic activity of fasting plasma. Inhibition studies with protamine sulphate, 1 M NaCl, and sodium dodecyl sulphate revealed that the activities of both lipoprotein lipase and hepatic triacylglycerol lipase were increased in the postheparin plasma of the drug-treated rats. Adipose tissue lipoprotein lipase activity was also increased in the phenobarbital-treated rats. The triacylglycerol lipase activity elutable by heparin from liver slices and the residual activity of liver microsomes increased significantly in the drug-treated rats. Lipoprotein lipase of cardiac muscle and red skeletal muscle was unaltered by phenobarbital treatment. The increased postheparin lipolytic activity of fasting phenobarbital-treated rats seems to be accountable through increased lipoprotein lipase activity of adipose tissue and increased triacylglycerol lipase activity of liver, both of which may contribute to the lowered fasting concentrations of serum triacylglycerol mediated by the drug, as previously reported.

Adipose Tissue↗
PubMed1981

Persistent behavior at high rates maintained by intravenous self-administration of nicotine.

Squirrel monkeys pressed a level at high rates under a second-order schedule of reinforcement in which level pressing produced a brief visual stimulus that was occasionally contiguous with an intravenous injection of nicotine. The rate of lever pressing could be markedly reduced either by substituting saline for nicotine injections or by blocking the effects of nicotine with mecamylamine. The rate of level pressing could be reduced by eliminating the brief visual stimulus. These results show that nicotine can function as an effective reinforcer under a second-order schedule of drug self-administration and that an environmental stimulus associated with nicotine intake can contribute to the maintenance of persistent drug-seeking behavior.

Animals↗
PubMed1981

Triacylglycerol metabolism in the phenobarbital-treated rat.

1. Various aspects of triacylglycerol metabolism were compared in rats given phenobarbital at a dose of 100mg/kg body wt. per day by intraperitoneal injection; controls were injected with an equal volume of 0.15m-NaCl by the same route. Animals were killed after 5 days of treatment. 2. Rats injected with phenobarbital demonstrated increased liver weight, and increased microsomal protein per g of liver. Other evidence of microsomal enzyme induction was provided by increased activity of aminopyrine N-demethylase and cytochrome P-450 content. Increased hepatic activity of gamma-glutamyltransferase (EC 2.3.2.2) occurred in male rats, but not in females, and was not accompanied by any detectable change in the activity of this enzyme in serum. 3. Phenobarbital treatment increased the hepatic content of triacylglycerol after 5 days in starved male and female rats, as well as in non-starved male rats; non-starved females were not tested in this regard. At 5 days after withdrawal of the drug, there was no difference in hepatic triacylglycerol content or in hepatic functions of microsomal enzyme induction between the treated and control rats. 4. After 5 days, phenobarbital increased the synthesis in vitro of glycerolipids in cell-free liver fractions fortified with optimal concentrations of substrates and co-substrates when results were expressed per whole liver. The drug caused a significant increment in the activity of hepatic diacylglycerol acyltransferase (EC 2.3.1.20), but did not affect the activity per liver of phosphatidate phosphohydrolase (EC 3.1.3.4) in cytosolic or washed microsomal fractions. A remarkable sex-dependent difference was observed for this latter enzyme. In female rats, the activity of the microsomal enzyme per liver was 10-fold greater than that of the cytosolic enzyme, whereas in males, the activities of phosphohydrolases per liver from both subcellular fractions were similar. 5. The phenobarbital-mediated increase in hepatic triacylglycerol content could not be explained by a decrease in the hepatic triacylglycerol secretion rate as measured by the Triton WR1339 technique. Since the hepatic triacylglycerol showed significant correlation with microsomal enzyme induction functions, with hepatic glycerolipid synthesis in vitro and with diacylglycerol acyltransferase activity, it is likely to be due to enhanced triacylglycerol synthesis consequent on hepatic microsomal enzyme induction. 6. In contrast with rabbits and guinea pigs, rats injected with phenobarbital showed a decrease in serum triacylglycerol concentration in the starved state; this decrease persisted for up to 5 days after drug administration stopped, and did not occur in non-starved animals. It seems to be independent of the microsomal enzyme-inducing properties of the drug, and may be due to the action of phenobarbital at an extrahepatic site.

Animals↗