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Biomedical subjects

J E Hines

Publications and source records attributed to J E Hines.

8 recordsLinked to original sources
PubMed1992

Macrophage and perisinusoidal cell kinetics in acute liver injury.

Perisinusoidal cells (PSCs) are currently regarded as the major source of extracellular matrix proteins during hepatic fibrogenesis in response to liver injury. However, the cellular mechanisms underlying their response to injury are not fully understood. One hypothesis is that the PSCs are stimulated by peptide growth factors produced by hepatic macrophages (Kupffer cells) in response to parenchymal cell damage. In this study we have investigated the kinetics of the PSC and macrophage populations in acute carbon tetrachloride-induced hepatic injury in rats. PSCs were identified immunohistochemically by detection of cytoplasmic desmin; monocytes and macrophages were detected using the monoclonal antibodies ED1 and ED2; cells in S phase were identified by immunohistochemical detection of nuclear-incorporated bromodeoxyuridine. The results showed an expansion of the desmin-positive PSC population, predominantly within the damaged perivenular zones, which reached a peak on days 3 and 4 following administration of carbon tetrachloride; this was contributed to by local PSC proliferation. The PSC response was preceded by an expansion of the macrophage population resulting from both local macrophage proliferation and influx of blood monocytes. These results are in keeping with the hypothesis that the PSC response to acute liver injury is mediated, at least in part, by hepatic macrophages.

Animals↗
PubMed1992

Hepatic reinnervation following orthotopic liver transplantation in man.

We have studied changes in the pattern of intrinsic hepatic innervation in sequential liver biopsies from 16 patients who underwent orthotopic liver transplantation. Seventy-one needle biopsies were used, including specimens obtained at the time of transplantation (time zero) and up to 4 years post-transplantation; five transplant hepatectomy tissue blocks removed 3-32 months after transplantation were also assessed. Paraffin sections were immunostained with anti-PGP 9.5 and anti-S-100 to identify nerve fibres. All 'time zero' biopsies contained portal nerves and all but two showed staining of parenchymal fibres. After 1 week, no subsequent biopsies contained parenchymal fibres. The disappearance of portal fibres was less rapid and showed greater variability between patients, but they had all disappeared by 6 weeks and there was no positive staining between 6 and 60 weeks. Thereafter, a minority of biopsies showed innervation of a few small portal tracts. Samples from the porta hepatis, hepatectomy specimens, and needle biopsies containing large tracts showed persistence of major nerve trunks at all stages. Abnormally large nerve bundles were seen in some of these areas. The pattern of nerve staining showed no obvious relationship to the intensity of rejection changes. Our results suggest that there is a limited, delayed capacity for regeneration of portal, but not parenchymal, fibres in the transplanted human liver. The physiological significance of this long-term parenchymal denervation in transplanted livers remains to be determined.

Humans↗
PubMed1992

Immunolocalization of proliferating perisinusoidal cells in rat liver.

There is now substantial evidence that perisinusoidal (Ito or fat-storing) cells are the principal source of extracellular matrix proteins during hepatic fibrogenesis. In rat liver these cells express the intermediate filament protein desmin; this is now widely used as an immunohistochemical marker for these cells. It has been shown that in experimental models of acute and chronic liver injury there is an increase in the number of desmin-positive perisinusoidal cells prior to the deposition of matrix proteins; however, these studies have failed to establish whether local proliferation is involved in this expansion of the desmin-positive perisinusoidal cell population. In order to investigate the kinetics of the perisinusoidal cell response, we have developed a novel double-labelling immunohistochemical technique for the simultaneous demonstration of desmin and incorporated bromodeoxyuridine in proliferating perisinusoidal cells in sections of fixed paraffin-embedded rat liver. Application of this technique to a model of acute liver injury (single dose carbon tetrachloride by gavage) has shown that expansion of the perisinusoidal cell population is contributed to by local proliferation, with a labelling index of 18.7% 2 days following injury.

Animals↗
PubMed1992

Disappearance of hepatic parenchymal nerves in human liver cirrhosis.

The normal human liver receives a substantial autonomic innervation that is thought to subserve motor, metabolic, and sensory functions. In this study an antibody to a neural axoplasmic protein (PGP 9.5) was used to visualise autonomic nerves in tissue from normal, precirrhotic, and cirrhotic livers. Nerve fibres were readily identified in the parenchyma and portal tracts of normal livers, and in those where the histological diagnosis was non-specific reactive hepatitis or acute liver injury. In precirrhotic and cirrhotic livers nerves in portal tracts and fibrous septae remained prominent, but the parenchymal innervation was reduced in precirrhotic livers and was absent from regenerating nodules in established cirrhosis. The causes and functional consequences of this parenchymal denervation in cirrhosis remain to be established.

Antibodies, Monoclonal↗
PubMed1992

Glutathione S-transferases in neonatal liver disease.

AIMS: To investigate the distribution of alpha and pi class glutathione S-transferases (GST) in normal fetal, neonatal, and adult liver; and to examine changes in GST expression in neonatal liver disease. METHODS: alpha and pi class GST were immunolocalised in sections of formalin fixed liver tissue obtained from human fetuses (n = 21), neonates (n = 8), young children (n = 9) and adults (n = 10), and from neonates with extrahepatic biliary atresia (n = 15) and neonatal hepatitis (n = 12). Monospecific rabbit polyclonal antibodies were used with a peroxidase-antiperoxidase method. RESULTS: Expression of pi GST was localised predominantly within biliary epithelial cells of developing and mature bile ducts of all sizes from 16 weeks' gestation until term and in neonatal and adult liver. Coexpression of pi and alpha GST was seen in hepatocytes of developing fetal liver between 16 and 34 weeks' gestation. Although pi GST was seen in occasional hepatocytes up to six months of life, this isoenzyme was not expressed by hepatocytes in adult liver. By contrast, alpha GST continued to be expressed by hepatocytes in adult liver; this isoenzyme was also seen in some epithelial cells of large bile ducts in adult liver. No change was observed in the distribution of alpha GST in either neonatal hepatitis or extrahepatic biliary atresia. However, aberrant expression of pi GST was identified in hepatocytes of all but one case of extrahepatic biliary atresia but in only two cases of neonatal hepatitis. CONCLUSIONS: The phenotypic alterations noted in extrahepatic biliary atresia may result from the effect of cholate stasis. Evaluation of the pattern of pi and alpha GST distribution by immunohistochemical staining may provide valuable information in distinguishing between these two forms of neonatal liver disease.

Adult↗
PubMed1992

Phenotypic modulation of perisinusoidal cells following acute liver injury: a quantitative analysis.

Expression of the alpha-(smooth muscle) isoform of actin (alpha-SMA) by non-parenchymal cells in rat liver was studied following induction of acute liver injury using a single sublethal dose of carbon tetrachloride (CCl4). In normal liver, alpha-SMA immunoreactivity was identified in the smooth muscle cells of hepatic arteries and in the walls of portal and hepatic vein branches. Occasional alpha-SMA-containing stellate shaped cells were found in acinar zone 3 but most perisinusoidal cells (PSCs) did not express this protein. In CCl4-treated animals, there was an increase in the number of immunoreactive cells in perivenular zones, reaching a peak at day 3 following exposure to the toxin. These cells were morphologically identical to desmin-positive PSCs and the kinetics of the responses of alpha-SMA-positive and desmin-positive cells were similar. In en face labelling experiments, evidence of co-expression of alpha-SMA and desmin by non-parenchymal cells was obtained, although some desmin-positive PSCs did not appear to express alpha-SMA. These results suggest that PSCs rapidly undergo phenotypic modulation in response to acute liver injury with acquisition of alpha-SMA expression. It is proposed that these phenotypic changes coincide with functional alterations, such activated 'myofibroblast-like' cells being responsible for the enhanced matrix protein synthesis necessary for tissue repair.

Actins↗
PubMed1986

Constant-parameter capture-recapture models.

Jolly (1982, Biometrics 38, 301-321) presented modifications of the Jolly-Seber model for capture-recapture data, which assume constant survival and/or capture rates. Where appropriate, because of the reduced number of parameters, these models lead to more efficient estimators than the Jolly-Seber model. The tests to compare models given by Jolly do not make complete use of the data, and we present here the appropriate modifications, and also indicate how to carry out goodness-of-fit tests which utilize individual capture history information. We also describe analogous models for the case where young and adult animals are tagged. The availability of computer programs to perform the analysis is noted, and examples are given using output from these programs.

Aging↗