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Biomedical subjects

O Epstein

Publications and source records attributed to O Epstein.

At least 37 records · Page 2Linked to original sources
PubMed1991

In vivo insulin action in hepatocellular and cholestatic liver cirrhosis.

The in vivo dose response curve to insulin were studied, using an euglycemic insulin clamp technique, in 13 cirrhotic patients [8 with "hepatocellular" (HC) (nonalcoholics) and 5 with "cholestatic" (CHOL) cirrhosis] and 12 healthy controls (N). Subjects were studied in the basal state and during infusion of insulin at 3 different rates - 1, 3, 10 mU kg-1 min-1. Insulin responsiveness was similar in N and in HC, but it was 23% greater in CHOL (p less than 0.001). Insulin sensitivity was decreased in cirrhotics as compared with N but this difference was only significant (p less than 0.001) in HC. (ED50:62 + 5, 88 + 13 and 136 + 16 muu ml-1 in N, CHOL and HC respectively). Insulin clearance rate (ICR) was significantly (p less than 0.005) decreased in HC (1060 +/- 80, 996 +/- 95 and 776 +/- 128 ml sq m-1 ml-1 in N, CHOL and HC respectively. Basal hepatic glucose production (BHGP) was 39% lower in HC (p less than 0.005) and 24% lower in CHOL (p less than 0.05) than in N. Erythrocyte cholesterol phospholipid ratio was significantly elevated (p less than 0.001) in both groups of cirrhotic patients but was not correlated to specific metabolic changes described. In summary: i) intervariations in insulin dependent glucose metabolism were described in different cirrhotic groups; ii) basal hepatic glucose production and insulin clearance rate impaired in the different groups of cirrhotics; iii) the role of decreased cholesterol/phospholipid ratio on tissues glucose metabolism in cirrhotic patients should be further studied.

Adult↗
PubMed1991

Ontogeny of iron uptake across brush border membrane of guinea pig duodenum and its autoradiographic localisation.

Although the neonatal guinea pig has substantial body iron stores, the rate of duodenal iron absorption is greater than in the mature animal. Here we have used brush border membrane vesicles and biopsy tissue to examine the role of the brush border in changes in Fe2+ and Fe3+ uptake by the duodenum of newborn and adult guinea pigs. We conclude that the brush border membrane is unlikely to be an important site for developmental alterations in iron absorption. Autoradiographic analysis of Fe2+ uptake, however, implies that whilst only the upper villus cells of adult duodenal villi are involved in iron uptake, all enterocytes in the neonate display this function.

Absorption↗
PubMed1990

Developmental changes in hepatic copper proteins in the guinea pig.

We have suggested that Wilson's disease is caused by failure to adapt from the fetal to adult mode of copper metabolism and that the study of liver copper ontogeny might provide clues to the pathogenesis of Wilson's disease. This study traces the developmental changes in hepatic copper binding proteins in the guinea pig. During the last trimester, as fetal hepatic copper increases, metallothionein is the major copper binding peak in both the soluble and particulate supernatant fractions. After birth this peak decreases in parallel with the fall in liver copper. Metallothionein is absent from adult soluble supernatant and copper is associated with superoxide dismutase and a high molecular weight protein. A novel low molecular weight copper binding component is present in the particulate supernatant of neonatal liver, but is absent from the adult. Unlike many other animals, but similar to man, the switch from the fetal to adult mode of copper metabolism occurs at birth. Comparison of the copper protein profiles of the fetus and neonate with Wilson's disease are required to test the hypothesis that Wilson's disease is caused by developmental arrest of copper ontogeny.

Animals↗
PubMed1990

Immunological features of lung lavage cells from patients with primary biliary cirrhosis may reflect those seen in pulmonary sarcoidosis.

To investigate the basis of subclinical alveolitis in patients with primary biliary cirrhosis, 10 primary biliary cirrhosis patients were studied by bronchoalveolar lavage. Both bronchoalveolar lavage lymphoid and non-lymphoid cell populations were analysed using immunocytological methods to determine their proportions and phenotypic features in an attempt to gain information as to possible immune mechanisms active in the lung of these patients. Six of the 10 patients in our study showed evidence of an alveolitis (raised lymphocyte count: 27.6 (4.3)% of total count) on lavage. The results were compared with control groups of normal volunteers and patients with active pulmonary sarcoidosis. The six primary biliary cirrhosis patients with lymphocytosis had a raised CD4/CD8 T-cell ratio (4.13:1), similar to the sarcoid patients (5.60:1). A proportion of these T-lymphocytes expressed markers of activation (HLA-DR+ 7.5 (2.1)%); CD25 + 2.3 (0.9)%; CD7 + 5.8 (1.5)%. This increased T-cell activation was also seen in the sarcoid groups (HLA-DR+ 10.0 (1.9)%; CD25 + 3.0 (1.1)%; CD7 + 5.0 (0.2)%). This was not seen in the primary biliary cirrhosis patients without lymphocytosis and the normal volunteers. Within the non-lymphoid cell population, an increase in dendritic (RFD1+) cells was seen in primary biliary cirrhosis patients with lymphocytosis (31.2 (1.9)%) and sarcoid patients (46.3 (5.1)%) in contrast with the normal and primary biliary cirrhosis group without lymphocytosis. The primary biliary cirrhosis patients without lymphocytes had a relatively greater proportion of mature phagocytes (RFD7+). We postulate that these observations suggest the emergence in the lung of a granuloma producing mechanism similar to that occurring in the liver. By comparison, the alveolitis found in primary biliary cirrhosis is consistent with that observed in interstitial granulomatous lung disorders such as sarcoidosis.

Bronchoalveolar Lavage Fluid↗
PubMed1990

Delayed stomach to caecum transit time in the diabetic rat. Possible role of hyperglucagonaemia.

Disturbances of gastrointestinal motility are a common feature of diabetes mellitus and are usually ascribed to autonomic neuropathy. In order to assess the role of other factors on changes in motility in diabetes we have studied the stomach to caecum transit time (SCTT) during the progression of streptozotocin induced diabetes in the rat. Rats were used one, two, four, and eight weeks after a single injection of streptozotocin and age matched animals were used as controls. In further experiments non-diabetic rats received a bolus injection of pancreatic glucagon (50 or 75 micrograms intraperitoneally) or its diluent. SCTT was estimated using the non-invasive hydrogen excretion method. SCTT was unaffected by the age of the animal (mean (SEM) value: 101 (5) min), but was significantly delayed at one week (139 (11) min, p less than 0.01), two weeks (163 (16) min, p less than 0.01), four weeks (148 (9) min, p less than 0.01), and eight weeks (171 (13) min, p less than 0.01) after streptozotocin. SCTT was also slower during hyperglucagonaemia (control 96 (6) min; glucagon treated 50 micrograms: 120 (7) min, p less than 0.05 and 75 micrograms: 127 (8), p less than 0.05). Since autonomic neuropathy is not a recognised feature of the initial stages of diabetes hyperglucagonaemia may be responsible, at least in part, for diabetes induced changes in gastrointestinal motility.

Animals↗
PubMed1989

Copper overload in the developing guinea pig liver: a histological, histochemical and biochemical study.

The copper profile in Wilson's disease resembles that of human and guinea pig neonates. Microvesicular steatosis is characteristic of early histological damage in Wilson's disease. The aim of this study was to relate the histological, histochemical and ultrastructural changes seen in developing guinea pig liver to the developmental pattern of liver copper in these animals. Copper-stressed and control guinea pigs were studied. Liver biopsies were stained with haematoxylin and eosin, rhodanine (for copper), orcein (for copper-associated protein) and oil Red 0 (for fat). Selected specimens were examined by electron microscopy. Liver and serum copper levels and copper oxidase activity were also determined. Fetal liver copper increased during the last trimester of pregnancy, reaching five times the adult level in the perinatal period and falling rapidly in the 4 days after birth. Marked steatosis developed in both control and copper-stressed guinea pig liver. The fat score correlated strongly with liver copper concentration (r: 0.60; p less than 0.001). Orcein and rhodanine staining correlated with liver copper concentration (r: 0.52 and r: 0.40 respectively, p less than 0.01). Marked prenatal hepatic steatosis and its postnatal clearance correlates with changes in liver copper concentration. This experimental model provides an opportunity to study the pathogenesis of hepatic steatosis and the relationship between copper retention and steatosis.

Animals↗
PubMed1988

The heme biosynthetic pathway in lymphocytes of patients with malignant lymphoproliferative disorders.

The metabolism of heme is impaired in lymphocytes of patients with malignant lymphoproliferative disorders (MLPO). Two of the enzymes of the heme biosynthetic pathway, delta-aminolevulinic acid dehydrase (ALAD) (EC 4.2.1.24) and ferrochelatase (FC) (EC 4.99.1.1) are markedly reduced. The activity of porphobilinogen deaminase (PBGD) (EC 4.3.1.8) is increased. The rate-limiting enzyme of heme biosynthesis in the liver, aminolevulinate synthase (ALAS) (EC 2.3.1.37) remains unchanged although the concentration of total heme in the lymphocytes is markedly reduced. This might reflect a lack of negative feedback inhibition by heme on ALAS activity in this system.

5-Aminolevulinate Synthetase↗
PubMed1988

Growth rate determines activity of porphobilinogen deaminase both in nonmalignant and malignant cell lines.

PBGD activity and growth rate were determined in cultures of rat embryo fibroblasts, nontransformed and MLV/MS transformed fibroblastic cell lines; NIH-3T3 cells, and in a mouse lymphosarcoma cell line [L-929]. The two parameters examined correlate positively (P less than 0.001). The results of this investigation would seem to indicate clearly that porphobilinogen deaminase activity is related to growth. However, these experiments do not rule out the possibility that malignant transformation per se also causes changes in porphobilinogen deaminase activity.

Ammonia-Lyases↗
PubMed1988

Platelet aggregation and thromboxane A2 release in primary biliary cirrhosis and effect of D-penicillamine treatment.

Platelet function was assessed in 28 patients with primary biliary cirrhosis (PBC), of whom 10 were receiving D-penicillamine. Patients not on D-penicillamine treatment had platelet aggregation similar to that in the healthy control group; the group treated with D-penicillamine showed significantly enhanced platelet aggregation in response to threshold doses of adrenaline and collagen but not ADP. Median thromboxane B2 production was also higher in D-penicillamine treated patients than in controls or untreated patients; this difference did not reach statistical significance. The addition of D-penicillamine in vitro to platelet rich plasma from normal subjects was shown to enhance adrenaline- and collagen-induced platelet aggregation. Abnormalities of platelet function in PBC patients did not correlate with serum cholesterol concentration or with liver function tests but were related to the stage of disease. The present study emphasises the need to consider the aetiology, disease stage and type of treatment when assessing platelet function and prostanoid release in liver disease.

Aged↗
PubMed1988

Review: the treatment of primary biliary cirrhosis.

Considerable improvement in quality of life can be achieved by treating the complications of primary biliary cirrhosis. However, once fibrosis, cirrhosis, portal hypertension and hyperbilirubinaemia occur, it is unlikely that 'medical' treatment will cure the disorder. Trials of medical therapy should aim to delay or halt the progression of the early phase of the disease and clinicians should refer patients to centres conducting clinical trials. If the disease progresses, and the quality of life is seriously impaired, liver transplantation offers the realistic chance of a new life.

Humans↗
PubMed1988

Age-related changes in the kinetics of iron absorption across the guinea pig proximal intestine in vivo.

In the healthy human adult, body iron content is regulated by intestinal iron absorption. However in neonates who are iron replete, iron absorption is inappropriately increased. In this study we have compared the kinetics of iron absorption in the proximal small intestine of the newborn and adult guinea pig in order to gain insight into the cellular mechanisms underlying this difference. Iron uptake was studied in vivo over the concentration range 20-2,000 microM. Total iron uptake could be resolved into saturable and linear components. The kinetic constants for the saturable component in the adult were similar to the neonate. In contrast, the rate of uptake via the linear pathway was 4 times greater in the neonate compared to the adult. It is concluded that the increased absorption of iron by the neonatal guinea pig is due to an enhanced uptake via the linear pathway. In contrast to total iron uptake, we were unable to detect developmental changes in iron transfer into the carcass.

Aging↗
PubMed1988

Neonatal and adult copper-64 metabolism in the pig and the possible relationship between the ontogeny of copper metabolism and Wilson's disease.

The copper profiles of neonatal mammals differ from those of the adult; in man they are similar to those found in people with Wilson's disease (WD). WD patients handle an intravenous bolus of radioactive copper in a characteristic manner which aids diagnosis. In view of the similarity between neonatal mammals and WD patients, we have studied the fate of an intravenous bolus of 64Cu injected into neonatal and adult pigs. In adult pigs, plasma 64Cu activity fell for 10 h and then slowly increased over the next 14 h as newly synthesised caeruloplasmin was secreted. In the neonate a secondary rise in 64Cu activity was not observed. Gel filtration of the soluble supernatant revealed significant differences in the association of 64Cu with hepatic copper proteins. In adults 64Cu associated predominantly with superoxide dismutase whilst in the neonate the 64Cu associated with metallothionein and a protein of high molecular weight. This study indicates that 64Cu export from the neonatal pig liver is in many ways similar to that found in WD. Additionally, there are similarities in the profile of hepatic 64Cu-binding proteins.

Animals↗
PubMed1987

The heme biosynthetic pathway in the regenerating rat liver. The relation between enzymes of heme synthesis and growth.

Enzymes of heme synthesis, porphyrins and heme content of regenerating rat livers were examined. During the first three days of regeneration the weights of livers of one-third and two-third hepatectomized rats increased 1.5-fold and 2.7-fold and the activity of porphobilinogen deaminase increased 2-fold and 4-fold and was inversely correlated with ferrochelatase activity. delta-Aminolevulinic acid synthase and delta-aminolevulinic acid dehydratase activities were reduced. Concomitantly an increase in the concentration of porphyrins and a decrease in that of heme were observed. The changes in the biosynthetic pathway of heme during rapid growth of the liver are discussed.

Ammonia-Lyases↗