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Biomedical subjects

R N MacSween

Publications and source records attributed to R N MacSween.

At least 37 records · Page 2Linked to original sources
PubMed1992

Role of the adenylate cyclase, phosphoinositidase C and receptor tyrosyl kinase systems in the control of hepatocyte proliferation by hepatocyte growth factor.

Hepatocyte growth factor (HGF) is the most potent known mitogen for hepatocytes in primary culture. However, the mechanisms through which HGF induces hepatocyte proliferation have not been defined. Here we have investigated the role of the adenylate cyclase, phosphoinositidase C and tyrosine kinase signalling systems in the control of hepatocyte proliferation by HGF using freshly isolated or cultured adult rat hepatocytes. We show that human recombinant HGF caused a dose-dependent increase in hepatocyte DNA synthesis with a maximal effect at 10 ng/mL and an EC50 of 5.9 ng/mL. HGF had no effect on hepatocyte adenylate cyclase activity or intracellular cAMP levels. Elevation of hepatocyte cAMP levels resulted in inhibition of HGF-stimulated DNA synthesis. HGF stimulated inositol phospholipid hydrolysis with a maximal effect at 25 ng/mL and potentiated the effect of vasopressin (10(-8) and 10(-9)M). HGF (100 ng/mL) caused an increase in the phosphorylation on tyrosine of an unknown hepatocyte protein with a molecular mass of 36 kDa. Thus, we have shown that HGF, like epidermal growth factor (EGF), can activate the phosphoinositidase C and tyrosine kinase systems in rat hepatocytes. As with EGF, these intracellular signalling systems may underlie HGF-induced hepatocyte proliferation.

Adenylyl Cyclases↗
PubMed1992

The spectrum of chronic liver disease in renal transplant recipients.

Chronic liver disease has been reported to be an important cause of late morbidity and mortality in renal transplant recipients. We have examined the prevalence and nature of chronic liver disease among 538 patients with functioning renal allografts managed at the Western Infirmary, Glasgow, between 1980 and 1989. Thirty-seven patients (7 per cent) satisfied biochemical criteria for chronic liver dysfunction. Liver biopsies were obtained from 24 of these, and autopsy tissue was available from three other patients. Chronic hepatitis of variable severity was present in 15 patients, haemosiderosis in 12 patients and nodular regenerative hyperplasia in five patients. Nineteen patients (51 per cent) had serological evidence of infection with the hepatitis C virus, and one of these developed chronic hepatitis B and D infection as well. Although a variety of chronic liver diseases occurred in our transplant population, the frequency of serious sequelae from liver dysfunction was much lower than that reported from transplant centres in other countries.

Chronic Disease↗
PubMed1990

Isolation and characterization of a high molecular weight lymphocyte Fc gamma receptor-blocking factor associated with renal allograft survival.

We have confirmed our previous observation that improved human renal allograft survival is associated with the presence in pre-transplant serum of a high molecular weight lymphocyte Fc gamma receptor-blocking factor. Serum fractionation studies suggest that this factor is a complex protein consisting of IgG together with an IgG-binding protein which has an apparent molecular weight of approximately 60 kD.

Antigens, Differentiation↗
PubMed1990

Ultrastructural localization of extracellular matrix proteins in liver biopsies using ultracryomicrotomy and immuno-gold labelling.

We describe a technique for the localization of extracellular matrix proteins in wedge and needle biopsy specimens of human liver. Using ultra-thin (50-70 nm) sections of puncture perfusion fixed tissue, extracellular matrix proteins were localized using a protein A-gold labelling procedure. We obtained good preservation of ultrastructural detail and specific labelling for collagen types I, III and IV and fibronectin. The method represents a sensitive means of identifying the extracellular distribution and the cellular origin of these proteins in normal and diseased human liver.

Biopsy↗
PubMed1989

Regulation of hepatic synthesis of C3 and C4 during the acute-phase response in the rat.

Following the i.p. injection of casein, rats showed increased serum levels of C4 and C3. C4 levels peaked on day 2 and returned to normal by day 4, while C3 levels peaked on day 3 before returning to normal on day 4. These changes were paralleled by changes in the hepatocyte synthesis rates of these two proteins. Macrophages, isolated from the peritoneal cavities of rats on days 1 to 7 (day-1 to day-7 macrophages) following i.p. injection of casein, were cultured in vitro, and the peritoneal macrophage-conditioned media (PMCM) assayed for their abilities to stimulate synthesis of C4 and C3 by hepatocytes from control rats. Day-2 PMCM selectively stimulated synthesis of C4, while day-3 and day-4 PMCM selectively stimulated C3 synthesis. These activities were called C4-hepatocyte stimulating factor (C4-HSF) and C3-HSF, respectively. The addition of anti-interleukin (IL) 1, tumor necrosis factor (TNF)-alpha, TNF-beta, IL 6 or interferon (IFN)-gamma antibodies to day-2 PMCM did not affect C4-HSF activity, and none had any effect on C3-HSF activity in day-4 PMCM. However, the addition of anti-IL 1 to day-4 PMCM resulted in the re-expression of C4-HSF activity as well as loss of thymocyte proliferative activity. C4-HSF activity could also be detected in day-4 PMCM by separating it from IL 1 activity using gel filtration chromatography. Furthermore the addition of recombinant IL 1 beta to day-2 PMCM prevented the expression of C4-HSF activity. Thus IL 1 appears to play a regulatory role in the acute-phase response in the rat, by preventing the expression of C4-HSF activity. The identities of C4-HSF activity and C3-HSF are still unknown but we believe that C3-HSF activity could be IL 6 as it has a similar molecular weight (30 kDa) and purified human IL 6 was more effective than IL 1, TNF-alpha or TNF-beta in stimulating C3 synthesis by rat hepatocytes. C4-HSF activity appears to be a property of a previously undescribed cytokine. It is not IL 1 alpha or beta, TNF-alpha or -beta, IL 6 or IFN-gamma.

Acute-Phase Reaction↗
PubMed1989

Localization of adrenergic and neuropeptide tyrosine-containing nerves in the mammalian liver.

The distribution of adrenergic nerves in guinea pig and rat liver was studied by the immunolocalization of fibers containing tyrosine hydroxylase and dopamine beta-hydroxylase, enzymes involved in the synthesis of catecholamines. In both species, adrenergic fibers were identified within portal tracts, often in close proximity to hepatic artery branches. In guinea pig liver, but not rat liver, abundant intraacinar fibers were identified; fibers were also seen within the walls of terminal hepatic vein radicles and larger hepatic veins. The presence of peptidergic nerves containing the regulatory peptide neuropeptide tyrosine and the C-flanking peptide CPON was investigated by indirect immunofluorescence. The distribution of these nerves was similar to that of tyrosine hydroxylase- and dopamine beta-hydroxylase-positive nerves and showed the same species difference. The effector sympathetic nature of tyrosine hydroxylase- and neuropeptide tyrosine-positive fibers in rat liver was confirmed by chemical denervation studies using 6-hydroxydopamine.

Adrenergic Fibers↗
PubMed1989

Intrasplenic hepatocyte transplantation in rats with experimental liver injury: morphological and morphometric studies.

Isolated rat hepatocytes were transplanted into the splenic parenchyma of syngeneic animals. The effects on the degree of colonization by the transplanted cells of three forms of experimental liver injury in recipient animals were studied. Significant colonization was observed in animals with carbon tetrachloride (CCl4)-induced injury combined with portacaval shunt (PCS) and in animals with common bile duct (CBD) ligation but not in control animals or in animals with CCl4-induced injury alone. Transplanted cells in the CCl4/PCS group resembled normal hepatocytes. In contrast, in the CBD group, the intrasplenic hepatocytes exhibited a pattern of 'ductular metaplasia' similar to that observed in the obstructed liver of the recipients. Transplanted syngeneic hepatocytes can thus proliferate in the spleen in response to liver injury in the recipient. The morphological appearances of the transplanted cells can be modified depending on the nature of the liver injury.

Animals↗
PubMed1989

Hepatobiliary complications in chronic pancreatitis.

Thirty nine patients undergoing surgery for chronic pancreatitis were investigated for evidence of hepatobiliary disease. In addition to pre-operative assessment by liver function tests, ultrasound, ERCP (in 33) and percutaneous transhepatic cholangiography (in five), all had peroperative liver biopsy. Common bile duct stenosis was diagnosed in 16 (62%) of the 26 patients with successful cholangiography. Features of extrahepatic biliary obstruction were found on biopsy in 11 patients, three of whom showed features of secondary sclerosing cholangitis. No patients had secondary biliary cirrhosis. Three had parenchymal liver disease (cirrhosis, resolving hepatitis and alcoholic hepatitis respectively) and two others had features suggestive of previous alcohol-induced injury. Five (83%) of the patients with clinical jaundice had biopsy features of extrahepatic biliary obstruction, as did eight (67%) with alkaline phosphatase above twice normal and seven (44%) with radiological common bile duct stenosis. Neither alkaline phosphatase rise, nor common bile duct stenosis alone or in combination, were a reliable indication of the need for biliary enteric bypass surgery. Pre-operative liver biopsy may be a valuable adjunct in the assessment of such patients.

Adult↗
PubMed1989

Risk factors and prognosis in primary biliary cirrhosis.

The relationship between survival and 25 clinical and histologic variables was studied in 195 patients (171 women, 24 men) who satisfied stringent criteria for the diagnosis of primary biliary cirrhosis. The mean duration of follow-up was 6 yr (range 0-17). One hundred and sixteen patients died, 84% as the result of liver disease and 16% from nonhepatic causes. Using the Kaplan-Meier estimate, we calculated the mortality from liver disease to be 40% after 5 yr and 60% after 10 yr. Ascites, serum bilirubin level, variceal hemorrhage, and age were identified as independent clinical risk factors, and extent of hepatic fibrosis, bilirubinostasis, and Mallory's hyalin were identified as independent histologic risk factors correlating with reduced survival.

Adult↗
PubMed1988

The diagnostic significance of periportal hepatic necrosis and inflammation.

In this review the several types of cell damage and cell death which may be found in liver biopsy specimens are defined. We describe the different processes which occur at the portal/parenchymal or septal/parenchymal interface, viz. periportal spillover, periportal hepatitis, classic or lymphocytic piecemeal necrosis and biliary piecemeal necrosis. The diagnostic implications of these lesions in relation to the clinicopathological diagnosis and prognosis in various liver diseases are discussed.

Diagnosis, Differential↗
PubMed1988

Histocompatibility antigens in patients with alcoholic liver disease in Scotland and northeastern England: failure to show an association.

A study of HLA-A and B antigens in 248 patients with biopsy diagnosed alcoholic liver disease was conducted to examine for a genetic predisposition to alcohol related liver injury. No statistically significant differences were established for 8 HLA-A and 16 HLA-B antigens between normal healthy controls (n = 342) and patients with alcoholic fatty liver (n = 86), alcoholic hepatitis (n = 63), active alcoholic cirrhosis (n = 64) and inactive alcoholic cirrhosis (n = 35). It is concluded that no HLA-A or B locus genetic susceptibility to alcoholic related injury could be shown.

England↗