Search PubMed⌕ Search

Biomedical subjects

D M Goldberg

Publications and source records attributed to D M Goldberg.

At least 55 records · Page 3Linked to original sources
PubMed1991

The biological significance of lipoprotein lipase modulation by phenobarbital and heparin.

When confluent cultures of 3T3 F442A cells were treated with insulin, differentiation occurred within 6 days as indicated by LPL secretion followed by increased intracellular levels of protein and triacylglycerol. PB increased LPL secretion 2- to 3-fold and intracellular LPL 3- to 10-fold in a time-dependent manner; these increments were less in proportion to the length of the time interval between confluence and initiation of PB treatment. These results are consistent with the notion that PB promotes conversion of adipocyte precursors to mature adipocytes by increasing the proportion of the former that become susceptible to the differentiating stimulus. Human subjects treated with heparin by continuous i.v. infusion over 4 days showed an initial decrease in serum triacylglycerol concentration in response to the initial bolus injection, accompanied by sharp increases in circulating LPL and HTGL, but the triacylglycerol concentration returned to normal within 24 hr. Rats infused with heparin by means of peritoneal implantation of osmotic minipumps demonstrated dose-dependent increases in circulating LPL, accompanied by reduction in heart muscle LPL but inconsistent changes in other tissues examined. Heparin had no effect on the clearance of circulating LPL but did reduce the total body pool of endothelial-bound enzyme. No changes in fasting triacylglycerol and free glycerol were observed, but exogenous VLDL were cleared at a faster rate in heparinized animals. Since the latter also manifested a decrease in de novo fatty acid synthesis, it seems that the heparinized rat is able to maintain circulating levels of triacylglycerol by efficient re-esterification of preformed fatty acids despite the enhanced lipolysis consequent upon higher plasma LPL activity.

Adipose Tissue↗
PubMed1991

Aminoaciduria as a marker of acute renal transplant rejection--a patient study.

Over 12 months, urine samples were systematically collected from 40 children who underwent renal transplantation for the treatment of end-stage renal disease. Sequential determinations of the excretion of individual amino acids relative to that of creatinine were carried out on 15 subjects. Nine of these (including three who sustained episodes of acute rejection) retained a native kidney in-situ, while in six patients (including three who underwent an episode of acute rejection) both native kidneys had been removed. In both subgroups, the amino acid/creatinine ratios of early morning urine samples were higher shortly before clinical manifestations of acute rejection became evident than in patients who, following renal transplantation, had stable kidney function, chronic graft rejection, or acute tubular necrosis, with one exception: a patient with one native kidney in-situ in whom acute tubular necrosis developed immediately after transplantation. The amino acids showing the greatest increase included Thr, Ser, Gly, and Ala. These values fell dramatically immediately prior to the clinical episode of acute rejection, with Thr, Ala, and Phe showing the most consistent changes. These alterations in urinary amino acid excretion occurred several days before changes in urinary protein excretion or the serum concentrations of urea and creatinine, and may have a role to play in the monitoring of renal transplant recipients.

Adolescent↗
PubMed1991

Aminoaciduria is an earlier index of renal tubular damage than conventional renal disease markers in the gentamicin-rat model of acute renal failure.

There are currently no reliable early markers of renal tubular damage. Since aminoaciduria is an accompanying feature of this condition, the usefulness of increased urinary amino acid excretion as a marker was investigated by inducing renal tubular necrosis in male Wistar rats by the administration of gentamicin (40 mg/kg/d) for 14 d. Plasma amino acids, urea, creatinine, protein and electrolytes, and urine amino acids, protein and N-acetylglucosaminidase (a lysosomal enzyme) were measured over a 20 d period. Amino acid excretion increased dramatically within 24 h of the initial dose for 14 of the 16 amino acids measured. The conventional renal disease markers listed above did not increase until after day 7. Glomerular damage caused by puromycin aminonucleoside did not induce aminoaciduria until marked proteinuria occurred (day 9), and even then amino acid excretion was much less than that caused by gentamicin. To distinguish whether the gentamicin-induced aminoaciduria was a consequence of tubular damage or inhibition of amino acid transport, isolated rat kidneys were perfused with a Krebs-Henseleit albumin buffer with and without gentamicin for 20 min, during which time urinary amino acids were quantitated. Gentamicin did not inhibit amino acid reabsorption. Thus, it appears that in the rat-gentamicin model of acute renal failure, urinary amino acids are early markers of renal tubular damage.

Acetylglucosaminidase↗
PubMed1990

Effect of chronic heparin administration on serum lipolytic activity and some aspects of lipid metabolism.

Chronic heparin administration to rats for periods up to 8 days by i.p. implantation of mini pumps, increased serum total lipolytic activity in a dose-dependent manner up to infusion rates of 10 U/h per 100 g body weight. This augmentation was predominantly due to lipoprotein lipase (LPL). Synchronously, heart muscle demonstrated a dose-dependent reduction in LPL activity and adipose tissue showed a biphasic response, LPL activity decreasing at low doses and rising towards control levels at higher doses. Lipolytic activities of skeletal muscle and liver were unaffected. Increased serum LPL could not be attributed to altered enzyme clearance from the circulation in chronically heparinised rats, but was accompanied by a reduced response to i.v. high-dose heparin indicating reduction in the pool of endothelial-bound enzyme. Fasting serum concentrations of triacylglycerol and glycerol were unaffected in chronically heparinised animals although accelerated clearance of exogenous 14C-labelled VLDL was demonstrated, together with enhanced uptake of the isotope by liver and heart. Since de novo synthesis of fatty acids and triacylglycerol from 3H2O was not increased by heparin, we suggest that serum triacylglycerol concentrations were maintained by enhanced re-esterification of preformed fatty acids taken up by the liver. Hepatic cholesterol synthesis from 3H2O was augmented by heparin; this observation is consistent with reported increases in serum total and HDL-cholesterol mediated by chronic heparin administration in man and dog.

Adipose Tissue↗
PubMed1990

Effect of alcohol on lipoprotein metabolism. II. Lipolytic activities and mixed function oxidases.

The mechanism by which alcohol increases plasma total high density lipoproteins (HDLs) and HDL-cholesterol is unknown, but it may involve modulation of the lipolytic enzymes, hepatic triglyceride lipase (HTGL) and/or lipoprotein lipase (LPL) in hepatic and extrahepatic tissues. The modulation of HDL metabolism by alcohol may also be related to its potential to induce mixed function oxidases in liver microsomes. These possibilities were examined by a pair-feeding protocol in which rats were fed diets with 35% of the caloric content as ethanol; control groups received a diet with an isocaloric amount of sucrose or were fed chow ad libitum. Alcohol caused a significant decrease in HTGL activity of liver microsomes, but there was no significant effect of alcohol upon the activities of LPL in adipose tissue and heart muscle. The relative rates of mixed function oxidases, assayed in control liver microsomes using ethoxy-,pentoxy- and benzyloxy-resorufin as substrates, were benzyloxy greater than ethoxy greater than pentoxy. This order was not affected by alcohol, but the oxidation of ethoxy- and pentoxyresorufin was reduced in liver microsomes from the ethanol-fed group. HTGL synthesis and secretion were also measured using primary rat hepatocyte cultures isolated from animals on the above dietary regimes and maintained for up to 3 days in basal medium alone or supplemented with 10 mmol/l ethanol. In basal media the order of activity of extracellular HTGL, released by the addition of heparin, was sucrose-fed greater than chow-fed greater than ethanol-fed. The rate of HTGL secretion from hepatocytes was stimulated in ethanol-containing medium, and was greater in hepatocytes from the sucrose-fed controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism↗
PubMed1989

Microsomal induction, alcohol, and lipoprotein metabolism: is there a three-way relationship?

The role of ethanol as a microsomal enzyme-inducing agent and as a modulator of lipid metabolism is reviewed. In an attempt to ascertain the mechanisms underlying the latter effects we examined the changes in hepatic triglyceride lipase (HTGL), hepatic high density lipoprotein (HDL) binding, and apolipoprotein secretion mediated by ethanol in a variety of experimental situations. Chronic administration of ethanol to rats decreased the ability of the liver to secrete HTGL, but primary liver cultures prepared from both ethanol and sucrose-fed rats secreted more HTGL when acutely exposed to ethanol over a 3-day period than when grown in a control medium. Hep G2 cells when grown in ethanol-containing medium for 14-28 days manifested increased HDL-binding capacity; apolipoprotein-A1 secretion was increased by ethanol but apolipoprotein B secretion was not affected. These findings suggest that increased plasma HDL concentrations which follow chronic ethanol ingestion may be due, at least in part, to increased hepatic secretion and reduced intravascular conversion of the lipoprotein despite enhanced reuptake by the liver; they are not consistent with an ethanol-mediated alteration in very low density lipoprotein secretion by the liver.

Animals↗
PubMed1989

Effect of alcohol on lipoprotein metabolism. I. High density lipoprotein binding.

The effects of ethanol upon the binding of [125I]-labelled human high density lipoprotein 3 (HDL3) was examined in rat liver microsomes and monolayer cultures of human hepatoma (Hep G2) cells. Alcohol feeding to rats (35% caloric content) caused a significant (p less than 0.05) increase in serum cholesterol concentrations relative to pair-fed controls, but HDL3 binding to rat liver microsomes was unaffected by alcohol consumption. By contrast, addition of 10 mM ethanol to Hep G2 cells increased HDL3 binding, and this increase was observed after 14, 28 and 40 days of exposure. This alcohol-dependent rise in HDL3 binding was associated with a 2.3- to 5-fold rise in receptor number (Bmax), and a 2- to 6-fold increase in the dissociation constant (Kd). The data suggest that the net effect of increased receptor number and lower receptor affinity is to increase the capacity of hepatocytes to metabolize circulating high density lipoproteins, and that this increase in the face of elevated plasma high density lipoprotein cholesterol consequent upon alcohol consumption would facilitate greater mobilization of cholesterol from peripheral tissues to the liver.

Animals↗
PubMed1988

Evaluation of commercially formulated aspartate aminotransferase and alanine aminotransferase activity determinations by the Scandinavian Committee on Enzymes and IFCC methods as modified for use with automated enzyme analysers.

The performance characteristics of the Scandinavian Committee on Enzymes (SCE) methods for the assay of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined using six automated enzyme analysers. The reagent formulation did not include pyridoxal phosphate (PLP). An optimal operating mode was defined for each instrument and precision was assessed in greater detail on four instruments. A points rating system was devised to place the instruments in the following order of proficiency: IL Multistat III, LKB-8600, Gilford 3500, ABA 100. In contrast to AST, the ALT activity of patient samples was unstable at -20 degrees C over periods as short as seven days. The performance characteristics of the IFCC methods for assay of AST and ALT activities were determined by using three automated enzyme analyzers in order to assess the effect of PLP upon precision and activity of four quality control sera, and to compare the SCE and IFCC methods. Precision of AST assays did not alter on omission of PLP from the IFCC formulation, while that of ALT assays showed slight deterioration. The decrease in activity on omitting PLP was variable with each instrument. A points-rating system was devised to place the methods in the following order of precision: AST: IFCC (-PLP) 118, IFCC 109, SCE 61; ALT: IFCC 125, IFCC (-PLP) 97, SCE 66. The IFCC methods offer better precision, and the overall change on omitting PLP is minimal.

Alanine Transaminase↗
PubMed1988

The diagnostic accuracy of three recommended methods for serum aspartate aminotransferase assays in patients suspected of myocardial infarction and hepatobiliary diseases.

Serum aspartate aminotransferase (AST) activity was measured by the methods recommended by the Scandinavian Committee on Enzymes (SCE) and by the International Federation of Clinical Chemistry (IFCC) with pyridoxal phosphate (PLP) and without (-PLP) in one laboratory at 37 degrees C with the Abbott ABA-100 and in another at 30 degrees C with the IL Multistat III. Reference ranges were determined on 195 healthy hospital staff. Sera from 102 patients with suspected hepatobiliary disease (HBD) and 104 with suspected myocardial infarction (MI) were assayed at both laboratories by all three methods. Based on the above reference ranges, all assays with each method at both hospitals were abnormal in 59 of 67 cases with HBD and 53 of 55 with MI. In aggregate, all three methods yielded comparable rates of misclassification (20-23). The SCE method gave highest false negatives (18) and lowest false positives (5); the IFCC method gave lowest false negatives (1) and highest false positives (20); intermediate values of 8 false positives and 12 false negatives were given by the IFCC (-PLP) method. Using receiver operating characteristic (ROC) curves, the SCE method was clearly superior at 30 degrees C, and the IFCC (-PLP) method was marginally superior at 37 degrees C. However, when the decision threshold corresponded with a 2.5% false positive rate in the non-HBD, non-MI patients, the SCE method gave the lowest false negatives at both temperatures and, on the basis of the present data, must be considered to be the method of choice for AST activity determinations.

Aspartate Aminotransferases↗
PubMed1988

Is chymotrypsin output a better diagnostic index than the measurement of chymotrypsin in random stool?

This study compares the diagnostic utility of fecal chymotrypsin (CT) output in timed stool collections and random stools using a new photometric enzyme assay. The CT output (mean +/- SD, U/24 h) was 1,487 +/- 1,980 in 127 children with normal fat absorption and negative sweat-chloride test (mean age 45 months), and 1,804 +/- 1,452 in 27 cases with fat malabsorption due to nonpancreatic disease (mean age 41 months). 66 cases of cystic fibrosis (CF) were examined (mean age 119 months). Stool output in 19 newly diagnosed patients before therapy was 85 +/- 94, in 42 patients receiving enzyme replacement therapy was 3,462 +/- 2,841, and in 5 patients with pancreatic sufficiency 1,754 +/- 1,482. Using nonparametric statistics, 120 U/24 h was defined as the lower limit of the 95-percentile for stool CT output. Only 5 of the 127 patients with normal fat absorption had output below that limit. None of the patients with nonpancreatic malabsorption and only 1 treated CF patient had lower values. Sixteen of the newly diagnosed CF patients had stool CT less than 120 U/24 h. The sensitivity of the test is therefore 84% and its specificity 97% at this decision threshold. However, no diagnostic advantage is gained from measuring CT output in timed stool collections as compared to random stools.

Age Factors↗
PubMed1987

Lipolytic enzymes as markers of induction and differentiation.

Factors leading to microsomal enzyme induction are associated with hypertriglyceridemia in man. Phenobarbital (PB) increases hepatic synthesis of triglyceride but lowers its serum concentration in rats due to increased postheparin plasma activities of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL); these changes are accompanied by increased activity of these lipolytic enzymes in adipose tissue and liver. The present work explores the cellular mechanisms whereby PB increases the tissue content of these enzymes, using primary cultures of rat liver hepatocytes and a continuous cell line of mouse fibroblasts (preadipocytes) that undergo differentiation into mature fat cells. Secretion and synthesis of HTGL in primary rat hepatocytes increased 50% with insulin; when PB was added with insulin, activity was enhanced an additional 50%. By contrast, insulin inhibited HTGL secretion from the well differentiated rat hepatoma cell line, FU-5-5, C8, and this inhibition was partly overcome by PB. These results suggest that different control mechanisms govern the synthesis and secretion of HTGL in normal rat liver cells and hepatoma. In cultured pre-adipocytes (3T3-F442A) insulin promoted differentiation when added to confluent cultures. PB (0.5 mM) resulted in marked enhancement of conversion of adipocytes characterized by a two- to threefold increase in extracellular LPL and a 10-fold increase in intracellular enzyme. These results suggest that PB promotes conversion of uncommitted cells into pre-adipocytes at an early stage in the differentiation of adipose tissue.

Animals↗
PubMed1987

The enzymology of intestinal disease.

The role of enzyme estimations is reviewed. Serum levels of most enzymes do not alter significantly in intestinal diseases because dying mucosal cells slough off into the lumen. Similarly, biopsy material may provide misleading results because of lack of homogeneity between diseased and normal segments of bowel, whether in inflammatory or neoplastic conditions. Lactase deficiency is the most common intestinal enzyme deficiency. The once popular lactose tolerance test is lately giving way to the breath hydrogen test, which generally reflects unabsorbed carbohydrate reaching the colon. This test and its clinical usefulness are reviewed in some detail, and the use of lactulose as an indicator of intestinal transit is also discussed.

Breath Tests↗
PubMed1987

Advances in the application of biochemical tests to diseases of the liver and biliary tract: their role in diagnosis, prognosis, and the elucidation of pathogenetic mechanisms.

Despite the biochemical complexity of the liver, few laboratory tests provide discriminatory diagnostic information in patients with hepatobiliary disease. Recent efforts have concentrated upon tests which assess the function of the liver, the severity of the disease state, and underlying pathological processes. Bile Acids: The emergence of facile technology and widespread application has brought the realization that these assays are not as sensitive in detecting liver disease as previously believed, although the cholate/chenate ratio may be useful in distinguishing cholestasis from chronic liver disease. The presence of unusual bile acids in serum or urine may be helpful in some cases. Drug Metabolism: A number of tests provide good evidence about liver function, hepatic blood flow and portal shunting, but the aminopyrine breath tests is the most useful, giving prognostic information in acetaminophen overdose and alcoholic liver disease. The antipyrine half-life identifies surgical cases at risk from poor hepatic function. Proteins and Immunochemical Tests: Interest has developed in plasma proteins such as prealbumin and retinol-binding protein to monitor hepatic protein synthetic function. Secretory IgA is more elevated in biliary tract disease, unlike the native protein which is increased principally in cirrhosis. Type III procollagen can be measured in serum, and correlates with the activity of collagen synthesis and the degree of fibrosis in biopsy samples. Reye's Syndrome: Biochemical tests play an essential role in diagnosis of this recently discovered disease. These will be presented and discussed.

Bile Acids and Salts↗
PubMed1987

The cephalosporins.

Structural modification of cephalosporin antibiotics has produced a broad array of new compounds, notable chiefly for greatly extended gram negative activity with minor toxicity. An understanding of basic principles will enable most clinicians to use these drugs appropriately and effectively.

Bacterial Infections↗