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Biomedical subjects

T H Hütteroth

Publications and source records attributed to T H Hütteroth.

At least 19 recordsLinked to original sources
PubMed1987

Liver cell damage caused by monoclonal antibody against an organ-specific membrane antigen in vivo and in vitro.

Monoclonal antibodies have been raised against different antigenic determinants of normal rabbit hepatocytes. One antibody (2D3) recognized a liver-specific 43 kDa protein displayed exclusively on the basolateral portion of the hepatocellular membrane. Purified monoclonal antibodies were injected intravenously into rabbits. Following the injection of antibody 2D3, a dose-dependent increase of liver enzyme activities in sera was observed. Within 8 h, marked morphological alterations of the hepatocytes, including multiple cell necroses, could be demonstrated by light and electron microscopy. When isolated vital rabbit hepatocytes in culture were used as targets, cytotoxic effects of this antibody could also be observed. This indicates that liver cell damage was not due to antibody-dependent cellular cytotoxicity, but was mediated by the antibody itself. Control antibodies did not show these effects. Thus, our results clearly demonstrate that humoral immune reactions against particular liver membrane antigens may play a role in the development of liver diseases, and provide a useful experimental approach for the investigation of their specificity.

Animals↗
PubMed1987

Analysis of liver-specific protein LSP using murine monoclonal antibodies.

We describe twenty murine monoclonal antibodies directed against different antigenic determinants of human and rabbit liver-specific protein LSP. Among them, nine were directed against liver-specific epitopes as judged from immunohistological studies. Immunoelectronmicroscopy revealed that seven of these monoclonals recognized membrane determinants differing in staining of distinct areas of the hepatocellular surface. Eleven antibodies were directed against intracellular structures. Western blot analysis showed that the epitopes detected were displayed on either single or multiple protein bands with apparent molecular weights between 24,000 and 60,000. Further differences were observed with respect to the species specificity and (among the non-organ-specific antibodies) pattern of tissue cross-reactivity. Our results demonstrate the presence of several liver-specific determinants and membrane components within LSP. There are, however, a very much greater number of non-organ-specific epitopes and numerous determinants displayed on intracellular structures. This emphasizes the remarkable heterogeneity of the antigen preparation named LSP and warrants the use of clearly defined antigens in further studies dealing with auto-immune phenomena in liver diseases.

Animals↗
PubMed1987

Spontaneous and antibody-dependent cellular immune reactions to ethanol-altered hepatoma cells.

Spontaneous cell-mediated cytotoxicity (SCMC), antibody-dependent cellular cytotoxicity (ADCC) and proliferative lymphocyte stimulation in alcoholic liver disease (ALD) were investigated. Peripheral blood lymphocytes (PBL) from eight patients with advanced ALD and nine normal controls were tested against hepatoma cells (PLC/PRF/5) as targets. Target cells were grown in either normal culture medium or medium supplemented with 1 and 5% ethanol, respectively, for 24 to 48 h. Ethanol-exposed hepatoma cells exhibited profound and characteristic morphological alterations. Ethanol preincubation, however, proved to be without effect on immune reactions. Provided that hepatoma cells are an appropriate model, we assume that the proposed immune reactions in ALD are based on metabolic interactions operative only in vivo but do not parallel morphological alterations of liver cells directly induced by ethanol.

Adult↗
PubMed1987

Discontinuation of immunosuppressive therapy in hepatitis B surface antigen-positive chronic hepatitis: effect on viral replication and on liver cell damage.

Immunosuppressive therapy was stopped in 12 individuals positive for hepatitis Be antigen (HBeAg) and hepatitis B surface antigen (HBsAg) and in 4 individuals positive for HBsAg but negative for HBeAg. Discontinuation of immunosuppressive therapy in HBeAg-positive patients was always associated with a bout of hepatitis and elimination of HBeAg in 8/12 patients. One patient died from liver failure and 2 patients experienced a decompensation of their liver disease indicating that this approach might be harmful if used therapeutically. A bout of hepatitis was not noted in any of the individuals negative for HBeAg when the immunosuppressive therapy was stopped, implying that this event is not potentially harmful to the patient.

Adult↗
PubMed1986

[Neurocysticercosis. Diagnostic and therapeutic advances].

A 42-year-old man of Croatian birth, with long-standing neurological symptoms, was found to have neurocysticercosis (a rare disease in Central Europe), as proven by positive antibody titres in serum and CSF and typical foci by computed tomography (CT). Ventriculo-cisternal drainage (after Torkildsen) controlled the acute symptoms of raised intracranial pressure. Postoperatively the CT revealed new low-density intracerebral foci, which responded to praziquantel.

Adult↗
PubMed1986

A case of Sjögren's syndrome with severe anemia due to myelitis.

An unusual case of Sjögren's syndrome presenting with severe anemia as the predominant clinical feature is described. Histological examination of a bone marrow biopsy specimen demonstrated that the patient's anemia was caused by myelitis and vasculitis of the small intraosseous vessels. Our report might stimulate a more thorough investigation of bone marrow in patients with connective tissue diseases and anemia.

Anemia↗
PubMed1986

Treatment of hepatitis B surface antigen (HBsAg)-positive chronic hepatitis with recombinant leucocyte alpha-A interferon.

A total of 32 individuals with HBsAg-positive and anti-delta-negative chronic hepatitis were treated with recombinant alpha-A interferon in phase I and phase II studies. In 5/32 patients HBsAg could be eliminated and in 19/32 individuals HBeAg became negative including all those who also eliminated HBsAg. Side-effects were tolerable in most patients and were readily reversible upon discontinuation of interferon therapy. In conclusion, treatment of HBsAg-positive chronic hepatitis with interferon seems to be a promising therapeutic approach. Future studies will have to establish the optimal dose, duration of treatment and factors predicting a favourable outcome of the treatment.

Drug Evaluation↗
PubMed1986

HBsAg clearance in patients with long-standing chronic active hepatitis B and hepatitis B virus-induced liver cirrhosis.

During a period of 3 years we observed 5 patients with chronic active hepatitis B and 2 with hepatitis B virus-induced liver cirrhosis who cleared HBsAg from their sera after 2-14 years of HBsAg carriership. 4 of them developed anti-HBs. After HBsAg clearance there was no evidence of persisting inflammatory activity within their livers. 5 of the 7 patients had been treated for 1-39 months with prednisolone, sometimes in combination with azathioprine. This therapy, however, had been stopped more than 3 years before these patients terminated their HBsAg carriership. Our observations indicate that even after long-standing chronic active hepatitis B or hepatitis B virus-induced liver cirrhosis HBsAg may be eliminated in a considerable number of patients.

Adult↗
PubMed1985

Cellular cytotoxicity against autologous hepatocytes in chronic hepatitis B--its relationship to the HBeAg/anti-HBe status.

Cellular cytotoxicity of peripheral blood lymphocytes against autologous hepatocytes was studied in 9 patients with HBeAg positive and 8 patients with anti-HBe positive chronic hepatitis B. In the HBeAg positive group a greatly increased cytotoxicity of 41 +/- 7% (mean +/- SEM) was found, in contrast the moderately increased cytotoxicity in anti-HBe positive cases of 15 +/- 5% was clearly different (p = 0.005). The different cytotoxicity values could not be explained on the basis of the histological classification, but seemed to correlate at least to some degree to the aminotransferase levels. The cytotoxic activity resided in both T cell and non-T cell enriched lymphocyte compartments. Our findings may provide an explanation for the poor prognosis of HBeAg positive patients with chronic hepatitis B in contrast to their anti-HBe positive counterparts.

Alanine Transaminase↗
PubMed1984

[Polycythemia in kidney cysts. A report on an unusual case].

A 43-year-old woman with a solitary renal cyst developed polycythaemia. 21 well documented cases of this type have been previously published. In the majority of them a causal connection could be assumed between the renal cyst and polycythaemia: in 13 of the 15 cases (as in the reported one), the polycythaemia disappeared after surgical removal of the cyst. Measurement of serum erythropoietin can help in the differential diagnosis, but exclusion of polycythaemia vera may be difficult in the individual case.

Adult↗
PubMed1984

Cellular cytotoxicity against autologous hepatocytes in alcoholic liver disease.

We tested lymphocyte cytotoxicity against autologous hepatocytes in patients with alcoholic liver disease (ALD). The following cytotoxicity values were found (mean +/- SEM): alcohol-induced steatosis with or without fibrosis 16.5 +/- 2% (n = 29), alcoholic cirrhosis 28 +/- 4% (n = 13), controls with normal liver histology or minimal changes 6 +/- 2% (n = 11). The differences were statistically significant (both forms of ALD versus controls p less than 0.005). T-cell as well as non-T-cell-enriched lymphocyte fractions showed increased cytotoxicity in ALD. We did not observe a correlation between cellular cytotoxicity and the degree of biochemical or histological alterations within the groups tested. Thus, our study demonstrating enhanced cellular cytotoxicity against autologous hepatocytes in ALD further supports the hypothesis that cellular immune reactions are involved in the pathogenesis of ALD, especially of alcoholic cirrhosis.

Cytotoxicity, Immunologic↗
PubMed1984

Cellular cytotoxicity against autologous hepatocytes in acute and chronic non-A, non-B hepatitis.

In a microcytotoxicity assay we tested lymphocyte cytotoxicity against autologous hepatocytes. The following cytotoxicity values were found (given mean +/- SEM): acute non-A, non-B (NANB) hepatitis 45.7 +/- 4.3% (n = 7), chronic NANB hepatitis 32.8 +/- 5.1% (n = 11), chronic active hepatitis B (CAH-B) 27.7 +/- 6.7% (n = 10), toxic lesions 18.1 +/- 4.2% (n = 18), controls with normal liver histology or minimal changes 4.9 +/- 2.5% (n = 8). Thus our study shows enhanced cellular cytotoxicity in acute and chronic NANB hepatitis and indicates that T cells as well as non-T cells have cytotoxic effector functions. These findings are similar to those obtained in CAH-B and suggest that cellular immune reactions play an important role in the course of NANB hepatitis. For comparison we tested cytotoxic reactions in toxic lesions. They were only moderate and well distinguishable from those observed in NANB hepatitis and CAH-B; they even may be unspecific. No correlation was seen between cytotoxicity and aminotransferase concentrations.

Acute Disease↗
PubMed1983

Characterization of circulating immune complexes in chronic non-A, non-B hepatitis.

We studied the frequency and composition of circulating immune complexes (CIC) in patients with chronic persistent non-A, non-B (NANB) hepatitis and in convalescent persons after an apparently normal recovery from acute NANB hepatitis. 10 of 16 patients with chronic NANB hepatitis and 5 of 11 convalescent persons after acute NANB hepatitis had CIC as detected by the Raji cell technique. CIC in chronic NANB hepatitis were composed of IgG, C3, and in 7 of 10 cases also IgM, while in CIC from convalescent persons IgG and C3 were present, too, but IgM was detected in only 1 case. Viral antigens within the CIC were not detectable in any case while 14 of 16 chronic NANB hepatitis patients were found to have free virus-associated antigen in serum.

Antigen-Antibody Complex↗
PubMed1981

Spontaneous cell-mediated (SCMC) and antibody-dependent cellular cytotoxicity (ADCC) in patients with acute and chronic active hepatitis.

spontaneous (SCMC) and antibody-dependent (ADCC) cellular cytotoxicity was studied in patients with aucte viral hepatitis B and chronic active hepatitis (CAH) B and non-A, non-B. Chang cells displaying the liver-specific protein LSP on the plasma membrane were used as target cells. SCMC and ADCC in acute hepatitis B were not different from normal controls. SCMC and ADCC in chronic active hepatitis B as well as in non-A, non-B were significantly elevated in comparison to normal controls. In additional experiments, the influence of patients sera on SCMC and ADCC was studied. Autologous serum from CAH patients significantly reduced cytotoxicity in SCMC and ADCC assays. This inhibitory capacity of patients sera was attributable to immune complexes, as ultracentrifugation studies and determination of immune complexes of fractionated sera demonstrated.

Acute Disease↗