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Biomedical subjects

R Rubin

Publications and source records attributed to R Rubin.

At least 127 records · Page 7Linked to original sources
PubMed1991

Fatty liver. Chemical shift phase-difference and suppression magnetic resonance imaging techniques in animals, phantoms, and humans.

In vitro animal and human models were used to evaluate the potential of chemical shift magnetic resonance imaging (MRI) for assessing fatty liver. Phantoms of varying fat content were created from mayonnaise-agar preparations. Fatty liver was induced in eight rats by feeding them ethanol for three to six weeks (36% of total calories), whereas eight control rats were fed a normal diet. T1-weighted in-phase and opposed-phase MR images were obtained of the phantoms animals, and 28 human subjects. Additional images obtained in animals included long TR images with in-phase and opposed-phase technique, and hybrid chemical shift water and fat suppression. The rats were killed and histologic status was graded blindly by a hepatopathologist as normal, mild, moderate, or severe fatty change, for correlation with MR grading. Quantitative analysis of MR images included fat signal fraction for animals, and relative signal decrease between in-phase and opposed-phase images for phantom and human data. Phantom in-phase signal increased linearly with respect to fat content, whereas opposed-phase signal decreased linearly. MRI and histologic grading of rat livers were highly correlated, especially when based on water suppression images (r = 0.91, P = .0001). Opposed-phase images were also highly correlated, while fat suppression images were less effective. There was no overlap between MR-derived fat fractions for control (2.6%-5.7%) versus ethanol-fed rats (7.7%-17.9%, P = .0002). Human liver considered to be fatty by visual inspection (n = 8) had higher relative signal decrease than nonfatty liver (n = 22) (P less than .001). Phantom, animal, and human data demonstrate that comparison of T1-weighted in-phase and opposed-phase images is both practical and sensitive in the detection and grading of fatty liver.

Adult↗
PubMed1991

Recurrence of hepatitis C virus infection after orthotopic liver transplantation.

Identification of the hepatitis C virus--the main cause of posttransfusion and sporadic non-A, non-B hepatitis--and the development of a diagnostic serological test have allowed us to study possible recurrence of this type of hepatitis after liver transplantation. Six of 34 consecutive transplant recipients were found to have had antibodies to hepatitis C before transplantation. All six patients had possible exposure to hepatitis C through blood transfusion or intravenous drug use. Five of the six patients were positive for antibodies to hepatitis C after 1 yr of follow-up. Two of these patients had clinical and histological evidence of acute viral hepatitis in their allografts. In one patient this led to hepatic injury and dysfunction of two successive grafts. In contrast, none of the twenty-eight patients who were seronegative for hepatitis C virus antibodies before transplantation has converted to seropositivity after transplantation despite perioperative blood transfusions. These results suggest that hepatitis C diagnosed serologically recurs in a minority of transplant recipients and that de novo seroconversion must be uncommon.

Adult↗
PubMed1990

Effect of guanine nucleotides on polyphosphoinositide synthesis in rat liver plasma membranes.

The effect of guanosine 5'-[gamma-thio]triphosphate (GTP[S]) on PtdIns and PtdIns(4)P kinase activities was measured in rat liver plasma membranes. The addition of [32P]ATP resulted in the rapid incorporation of 32P into PtdIns(4)P and PtdIns(4,5)P2, with maximal levels reached within 30 s. GTP[S] (25-500 microM) increased the rate and magnitude of [32P]PtdIns(4)P and [32P]PtdIns(4,5)P2 formation by 50 and 120% respectively. Similar stimulatory effects were induced by guanosine 5'-[beta gamma-imido]triphosphate, GTP, GDP and guanosine 5'-[beta-thio]diphosphate. The stimulation of PtdIns phosphorylation by GTP[S] occurred in the presence of 2 mM-EGTA, a condition which fully inhibited phosphoinositide-specific phospholipase C. GTP[S] did not stimulate phosphomonoesterase activity, and its action was not due to the binding of magnesium. However, the overall ATP-hydrolysing activity of the membrane preparation was inhibited by GTP[S] and the other guanine nucleotides. There was a direct correlation between the extent of this inhibition and the stimulation of polyphosphoinositide formation. The results indicate that stimulation of polyphosphoinositide formation by guanine nucleotides in rat liver plasma membranes can be accounted for by an inhibition of ATP hydrolysis. These data are inconsistent with a specific GTP-binding protein (G-protein)-mediated stimulation of PtdIns or PtdIns(4)P kinase.

Adenosine Triphosphate↗
PubMed1990

Ethanol inhibits thrombin-induced secretion by human platelets at a site distinct from phospholipase C or protein kinase C.

Ethanol is known to inhibit the activation of platelets in response to several physiological agonists, but the mechanism of this action is unclear. The addition of physiologically relevant concentrations of ethanol (25-150 mM) to suspensions of washed human platelets resulted in the inhibition of thrombin-induced secretion of 5-hydroxy[14C]tryptamine. Indomethacin was included in the incubation buffer to prevent feedback amplification by arachidonic acid metabolites. Ethanol had no effect on the activation of phospholipase C by thrombin, as determined by the formation of inositol phosphates and the mobilization of intracellular Ca2+. Moreover, ethanol did not interfere with the thrombin-induced formation of diacylglycerol or phosphatidic acid. Stimulation of platelets with phorbol ester (5-50 nM) resulted in 5-hydroxy[14C]tryptamine release comparable with those with threshold doses of thrombin. However, ethanol did not inhibit phorbol-ester-induced secretion. Ethanol also did not interfere with thrombin- or phorbol-ester-induced phosphorylation of myosin light chain (20 kDa) or a 47 kDa protein, a known substrate for protein kinase C. By electron microscopy, ethanol had no effect on thrombin-induced shape change and pseudopod formation, but prevented granule centralization and fusion. The results indicate that ethanol does not inhibit platelet secretion by interfering with the activation of phosphoinositide-specific phospholipase C or protein kinase C by thrombin. Rather, the data demonstrate an inhibition of a Ca2(+)-mediated event such as granule centralization.

Adenosine Diphosphate↗
PubMed1990

Inhibition of ethanol-induced platelet activation by agents that elevate cAMP.

Ethanol activates phosphoinositide-specific phospholipase C in human platelets resulting in the mobilization of intracellular calcium and shape change (Arch. Biochem. Biophys. 260, 480-492, 1988). Preincubation of platelets with agents that increase levels of cAMP (i.e., forskolin, prostacyclin) inhibited these responses to ethanol in a concentration- and time-dependent manner. The inhibitory effect was potentiated by the phosphodiesterase inhibitor, isomethybutylxanthine. When added after ethanol, these agents also reversed platelet shape change and lowered cytosolic free calcium to basal levels. The results demonstrate a direct inhibitory effect of cAMP on the ethanol-induced activation of phospholipase C.

Adult↗
PubMed1990

Heterotopic liver transplantation for fulminant Wilson's disease.

Wilson's disease may present with severe acute hepatocellular failure. The only effective treatment for fulminant Wilson's disease is liver transplantation, which may lead to reversal of the underlying disease. Some patients with cirrhosis who are too ill to undergo orthotopic liver transplantation have been treated with heterotopic liver transplantation. However, use of heterotopic liver transplantation for fulminant hepatocellular failure has not been successful. This case study involves a patient in whom a heterotopic liver transplant was successfully used for treatment of Wilson's disease presenting with fulminant hepatocellular failure.

Adolescent↗
PubMed1990

Quantitation of venous clot lysis with the D-dimer immunoassay during fibrinolytic therapy requires correction for soluble fibrin degradation.

Plasma cross-linked fibrin-degradation products were analyzed using a D-dimer (DD) immunoassay in patients with deep vein thrombosis (DVT) or acute myocardial infarction (MI) treated with fibrinolytic therapy, and the results were correlated with clot lysis documented angiographically. In 13 patients with DVT, the mean DD concentration increased 10-fold (1,074 +/- 252 to 10,333 +/- 1,004 ng/ml) during therapy, but neither the peak level nor the DD concentration integrated over the course of therapy correlated with clot lysis. Since plasma DD can derive from degradation of soluble plasma fibrin as well as from thrombi, the contribution of the former was estimated by in vitro incubation of the pretreatment plasma with plasminogen activator. Subtraction of this value from the measured posttreatment DD concentration provided a "corrected" level that represented DD originating from lysis of thrombi. This modification resulted in improved correlation of DD levels with clot lysis. The mean corrected peak DD was higher in patients with successful thrombolysis (8,780 +/- 1,352 ng/ml) compared with patients without lysis (3,075 +/- 589 ng/ml, p less than 0.001). There was a moderate correlation between the volume of clot lysed and the corrected peak DD (r = 0.62) and a higher correlation with the corrected DD integrated over the course of treatment (r = 0.97). By contrast, the corrected DD concentrations were near zero in patients treated for MI with or without thrombolytic reperfusion, suggesting that fibrin in small coronary thrombi did not contribute significantly to total plasma DD during therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

A modified apparatus for dual, sterilized, isolated perfusion of the rat liver.

The isolated perfused rat liver (IPRL) has proven to be a useful model for the study of physiology and pathology of the liver. For research in nonparenchymal cell (NPC) function that includes measurement of cytokine production (eg, TNF), it is necessary to have a sterilized perfusion system. We have modified the IPRL apparatus so as to be able to perform sterile perfusions of two livers simultaneously. The perfusion apparatus is a recirculating closed system in which the oxygenator is a plastic container separated into two chambers by a fenestrated plastic wall. A disposable macropore filter functions as both a bubble trap and perfusate filter. The sterilization process is done by immersing the various components in Benz-All solution. The tubing is disinfected by irrigation with 10% Clorox followed by 0.9% sodium chloride solution. The perfusate used is filter-sterilized Krebs buffer solution containing 0.5 g Mandol/250 mL perfusate. Not only can two organs be conveniently perfused simultaneously, but the entire system can be reliably sterilized for up to 20 consecutive perfusions. Bile production is higher and more stable with less leakage of intracellular enzymes. Many of the components are disposable and can be altered to suit the needs of a particular experiment.

Animals↗
PubMed1989

Hepatotoxicity associated with amiodarone therapy.

Amiodarone has been reported to cause asymptomatic increases in liver function tests in 15-55% of patients. Clinically apparent, symptomatic hepatic disease occurs less frequently, but patients have been reported to have hepatomegaly, jaundice, cirrhosis, or chronic active hepatitis. Less well recognized is the fact that amiodarone has been attributed to six deaths. We cared for a patient with amiodarone hepatotoxicity, which led us to review the literature associated with this serious condition.

Aged↗
PubMed1989

Ethanol interferes with collagen-induced platelet activation by inhibition of arachidonic acid mobilization.

The effect of ethanol on signal generation in collagen-stimulated human platelets was evaluated. Incubation of washed human platelets with physiologically relevant concentrations of ethanol (25-150 mM) resulted in a dose-dependent inhibition of aggregation and secretion in response to collagen (0.5-10 micrograms/ml), but did not inhibit shape change. In platelets labeled with [3H]arachidonic acid, ethanol significantly inhibited the release of arachidonic acid from phospholipids, in both the presence and the absence of indomethacin. Thromboxane B2 formation was also inhibited in proportion to the reduction in free arachidonic acid. There was a close correlation between the extent of inhibition of arachidonic acid release and secretion. The inhibition of platelet aggregation and secretion by ethanol was partially overcome by the addition of exogenous arachidonic acid. In the presence of indomethacin, ethanol had no effect on the activation of phospholipase C by collagen as determined by the formation of inositol phosphates and phosphatidic acid. Moreover, ethanol had no effect on the mobilization of intracellular calcium by collagen and only minimally inhibited the early phases of the phosphorylation of myosin light chain (20 kDa) and a 47-kDa protein, a known substrate for protein kinase C. Arachidonic acid formation was also inhibited by ethanol in response to ionomycin under conditions where phospholipase C activation was prevented. The results suggest that the functional effects of ethanol on collagen-stimulated platelets are due, at least in part, to an inhibition of phospholipase A2.

Adenosine Triphosphate↗