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J M Vierling

Publications and source records attributed to J M Vierling.

67 records · Page 4Linked to original sources
PubMed1978

Receptor specific clearance by the reticuloendothelial system in chronic liver diseases. Demonstration of defective C3b-specific clearance in primary biliary cirrhosis.

An approach to the assessment of reticuloendothelial function that quantitates clearance specifically mediated by membrane receptors for C3b and immunoglobulin (Ig)G has been applied in man. Clearance of isologous erythrocytes coated with IgM or C3b or coated with IgG were examined in patients with primary biliary cirrhosis (PBC), chronic hepatitis, or alcoholic cirrhosis and normal control subjects and compared with the clearance of aggregated human serum albumin. Clearance of these three types of particles varied independently. None of the patients studied had a defect in the clearance of aggregated albumin. No patient with PBC (0:6) had delayed clearance of IgG-coated erythrocytes; one of six patients with chronic hepatitis had delayed clearance of these cells. Indeed, four of six with PBC had increased rates of IgG-mediated clearance. In contrast, six out of six patients with PBC had an unequivocal defect in clearance mediated by C3b receptors. The patients with PBC varied widely in terms of duration of symptoms, degree of cholestasis, and histologic stage of disease. No defect of C3b-mediated erythrocyte clearance was found in the patients with chronic hepatitis or alcoholic cirrhosis. Furthermore, a patient with severe cholestasis secondary to large duct biliary obstruction exhibited normal C3b-mediated clearance. The defect in C3b-mediated clearance in PBC did not correlate with serum levels of individual complement components or inhibitors or with the presence of circulating immune complexes as measured by the Clq precipitation assay. Thus, measurements of receptor specific clearance, but not clearance of aggregated proteins, have revealed a highly specific defect in reticuloendothelial function in PBC.

Adolescent↗
PubMed1978

Cell-mediated cytotoxicity of desialylated human lymphocytes induced by a mitogenic mammalian liver protein.

The ability of a purified rabbit liver membrane protein that selectively binds desialylated glycoproteins to induce desialylated human peripheral blood lymphocytes to mediate mitogen-induced cellular cytotoxicity has been determined. After short term exposure to purified hepatic binding protein, desialylated, but not intact, lymphocytes exhibited mitogen-induced cellular cytotoxicity against Chang target cells, which do not have exposed hepatic binding protein on their surface membrane. Furthermore, desialylated lymphocytes, in the absence of purified hepatic binding protein, reduced the proportion of isolated rabbit hepatocytes that adhered to plastic to a significantly greater extent than did intact lymphocytes, suggesting that the exposed hepatic binding protein demonstrated on the surface membrane of these target cells is capable of inducing mitogen-induced cellular cytotoxicity. The specific inhibition of this effect by asialo-orosomucoid, but not by intact orosomucoid, indicates that the site involved in the binding of asialo-glycoproteins to hepatic binding protein is probably also responsible for the induction of mitogen-induced cellular cytoxocity. The demonstration that hepatic binding protein, a normal constituent of the surface, membrane of mammalian hepatocytes, can induce mitogen-induced cellular cytotoxicity, suggests that mitogen-induced cellular cytotoxicity may be a mechanism of cellular injury in vivo.

Animals↗
PubMed1977

In vitro cell-mediated cytotoxicity in primary biliary cirrhosis and chronic hepatitis. Dysfunction of spontaneous cell-mediated cytotoxicity in primary biliary cirrhosis.

The in vitro cytotoxic function and target cell specificity of peripheral blood lymphocytes from selected patients with primary biliary cirrhosis and hepatitis B surface antigen-negative chronic hepatitis were investigated using 51Cr-labeled human Chang and EL-4 mouse sarcoma cell targets in assays of spontaneous cell-mediated cytotoxicity (SCMC) and mitogen-induced cellular cytotoxicity (MICC). In addition, antibody-dependent cellular cytotoxicity (ADCC) against Chang cells was assessed. At an effector-to-target cell ration of 100:1, the mean SCMC against Chang cells was much less in patients with primary biliary cirrhosis than that in either the controls (P less than 0.001) or the patients with chronic hepatitis (P less than 0.005) whereas the value for patients with chronic hepatitis did not differ significantly from that of the controls. The mean SCMC against EL-4 mouse sarcoma cells was also less in patients with primary biliary cirrhosis than in controls (P less than 0.005) whereas the value for chronic hepatitis was not significantly different from that of the controls or patients with primary biliary cirrhosis. In contrast, MICC against both targets and ADCC against Chang cells were similar for each group. Comparison of SCMC and MICC against both target cells, measured simultaneously, showed similar cytotoxic potenital against both target cells for each group. Effector cells capable of mediating cytotoxicity in each assay were defined by testing the cytotoxic function of lymphocyte subpopulations isolated from two representative patients with each disease using techniques of immunoabsorbent affinity chromatography and Fc receptor binding to antigen-antibody complexes. In both primary biliary cirrhosis and chronic hepatitis SCMC and ADCC were mediated by a subpopulation of lymphocytes which lack surface immunoglobulin (sIg-) and bear Fc receptors (Fc+). In contrast, MICC was mediated by sIg- cells which lack Fc receptors. Lymphocytes bearing sIg- were not cytotoxic in any assay. These results establish a difference in cytotoxic function in primary biliary cirrhosis and chronic hepatitis by defining the presence of a defect in spontaneous cytotoxic function of sIg-, Fc+ lymphocytes against Chang cells in primary biliary cirrhosis.

Adult↗
PubMed1976

Abnormal hepatic transport of indocyanine green in Gilbert's syndrome.

The plasma fractional disappearance rate of indocyanine green (kICG, min-1) and the absolute hepatic ICG removal rate (VICG, mg per kg per min) were determined in 26 patients with Gilbert's syndrome (GS) and 19 normal control volunteers following intravenous administration of doses of 0.5, 2.0, 3.5, and 5.0 mg per kg of dye. The diagnosis of GS was based on studies of radiobilirubin kinetics in all cases and liver biopsy in 22 cases. The patients were further classified into 3 subgroups, based on patterns of sulfobromophthalein (BSP) kinetics, as follows: GS I (15 patients) had normal BSP metabolism; GS II (5 patients) had a defect in BSP metabolism beyond the stage of initial hepatic uptake; and GS III (6 patients) had a defect in the initial hepatic uptake of BSP (Gastroenterology 63:472-481, 1972). Both kICG and VICG were significantly reduced, compared to normal controls, in the GS III group with defective BSP uptake, but did not differ significantly from normal in the GS I and GS II groups. Michaelis-Menten analysis of the data indicated that VMAX for ICG uptake in the GS III group (1.2 +/- 0.6 mg per min per kg) was significantly reduced compared to the previously established normal value of 3.6 +/- 0.6 mg per min per kg; (P less than 0.01). For the total population of 26 patients with Gilbets' syndrome, there was a highly significant correlation (r= 0.77, P less than 0.01) between kICG and lambda21BSP, the fractional hepatic uptake rate for BSP. These studies confirm previous work indicating that patients with Gilbert's syndrome constitute a heterogeneous population with regard to defects in hepatic organic anion transport, some of the defects not being attributable to glucuronyl transferese deficiency. Future studies of Gilbert's syndrome must take into account the existence of these subgroups, since they may have different underlying pathogenetic mechanisms.

Adolescent↗
PubMedDate not supplied

Normal fasting-state levels of serum cholyl-conjugated bile acids in Gilbert's syndrome: an aid to the diagnosis.

Fasting levels of cholic acid conjugates were determined by radioimmunoassay in the serum of 24 patients with extensively documented Gilbert's syndrome and in 98 healthy controls without unconjugated hyperbilirubinemia. The Gilbert's syndrome patients studied included all three subtypes, as determined from studies of the plasma disappearance kinetics of sulfobromophthalein and indocyanine green. Although patients with structural liver disease severe enough to produce hyperbilirubinemia almost invariably have elevated fasting serum levels of cholic acid conjugates, values were normal in each of the Gilbert's syndrome patients, including patients with metabolic abnormalities in sulfobromophthalein and indocyanine green transport. It is concluded that the measurement of fasting serum levels of cholic acid conjugates is a useful adjunct to the diagnosis of Gilbert's syndrome.

Cholic Acids↗
PubMedDate not supplied

Relationship of pretransplant hepatobiliary disease to bile duct damage occurring in the liver allograft.

Histopathological features of nonsuppurative destructive cholangitis have been described in primary biliary cirrhosis, chronic graft-vs-host disease, and chronic rejection of human liver allografts. To determine whether or not susceptibility to injury of interlobular bile ducts was related to the original hepatobiliary disease requiring transplantation, we compared the histopathology of allografts transplanted into two groups of patients. The first group consisted of patients whose original hepatobiliary diseases primarily affect bile ducts: primary biliary cirrhosis, sclerosing cholangitis, and biliary atresia. The second group consisted of patients whose original hepatobiliary diseases do not result in injury to interlobular bile ducts. In 32 liver allografts studied histopathologically, the original disease did not recur. Interlobular bile duct damage occurred, however, in 17 of the 32 and resembled that seen in primary biliary cirrhosis. The spectrum of bile duct injury included mononuclear inflammation of the bile duct epithelium, destruction of the bile duct epithelium, and dissolution of the bile duct. There was no relationship between the frequency or severity of bile duct damage and original hepatobiliary disease, age, sex, duration of allograft survival, or cause of death. We conclude that nonsuppurative destructive cholangitis occurs frequently in liver allografts and represents one component of allograft rejection. This lesion resembles, in many respects, that seen in primary biliary cirrhosis so that histopathological differentiation may be difficult.

Adolescent↗
PubMedDate not supplied

Epidemiology and clinical course of liver diseases: identification of candidates for hepatic transplantation.

Among a variety of liver diseases that have been treated by hepatic transplantation, several were chosen for evaluation because of their frequency or high rate of fatality. Information regarding the incidence and prevalence in the United States, the natural history with conventional therapy, and prognostic indicators of a terminal phase is reviewed. Based on this information, specific candidates for hepatic transplantation are identified.

Adolescent↗
PubMedDate not supplied

Histopathology of early and late human hepatic allograft rejection: evidence of progressive destruction of interlobular bile ducts.

Cholestasis and injury of interlobular bile ducts occur during rejection of human hepatic allografts. However, knowledge of the nature and progression of bile duct injury during rejection remains incomplete. To define the role of inflammation in bile duct damage, we assessed the light microscopic appearance of hepatic tissue from selected patients in whom allograft failure was solely due to rejection. Nine patients with rejection were easily separated into two groups based on the duration of the allograft survival. The first group (early rejection) consisted of five patients in whom rejection occurred between 13 and 36 days. The second group (late rejection) consisted of four patients in whom rejection occurred between 170 and 912 days. Early rejection was characterized by distortion of bile ducts by adjacent inflammatory cell infiltrates, cytological changes of bile duct epithelial cells and occasionally by frank mononuclear cell inflammation of the epithelium with destruction of the duct. Late rejection was characterized by nonsuppurative destructive cholangitis culminating in the disappearance of interlobular bile ducts. Both groups exhibited histological cholestasis, intact limiting plates, preservation of hepatocytes and positive orcein stains for copper-binding protein. We conclude that the dominant histopathological feature of hepatic allograft rejection is progressive, nonsuppurative destructive cholangitis.

Adolescent↗
PubMedDate not supplied

Electron microscopy of rejected human liver allografts.

Recognition by biopsy of liver allograft rejection has been less successful than diagnosis of rejection of cardiac and kidney allografts. In a study of 138 failed liver allografts, we recognized damage to small interlobular bile ducts by lymphocytes as the most useful indicator of the presence of rejection. This is a report of the electron microscopic features of three patients with unequivocal allograft rejection. Lymphocytes and occasional granulocytes penetrated the epithelia of interlobular bile ducts. Ducts with diameters of 30 to 60 microM were preferentially affected but ducts up to 120 microM were also occasionally involved. Point contacts between infiltrating inflammatory cells and bile duct epithelial cells were observed occasionally. Degenerative changes of bile duct epithelial cells were conspicuous and involved nuclei and cellular organelles. Degeneration was often accompanied by aggregation of dense bundles of filaments in the cytoplasm. In severely affected ducts, epithelial cell disintegration was noted. In all involved bile ducts, the basement membrane was markedly thickened. Hepatocytes were well-preserved but contained lipid vacuoles, pigment granules, and blunted canalicular microvilli. The similarity between these observations and those seen in primary biliary cirrhosis and chronic graft-versus-host disease is striking.

Adolescent↗