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Biomedical subjects

K H zum Büschenfelde

Publications and source records attributed to K H zum Büschenfelde.

9 recordsLinked to original sources
PubMed2001

Autoimmune hepatitis in the elderly.

OBJECTIVES: Autoimmune hepatitis (AIH) is widely believed to be a disease of young women and menopause. Little is known about the frequency and clinical characteristics in patients aged > or =65 yr. METHODS: We reviewed charts of 120 consecutive outpatients with known AIH to identify patients who were diagnosed at the age of 65 or older. These 20 patients (median age, 69 yr) were compared to the same number of younger patients (median age, 24 yr) with well-documented AIH from the same cohort. RESULTS: Seventeen percent (20/120) of our patients were > or =65 yr at the time of diagnosis. In the older patients median time to diagnosis was significantly longer than in the younger patients (8.5 vs 3.5 months). Patients most commonly presented with an acute icteric hepatitis. Complete remission was achieved to a similar extent (18/20 and 17/20 patients). Fewer older patients expressed human leukocyte antigen A1-B8 (p = 0.005). CONCLUSIONS: Diagnosis of AIH often seems to be delayed in the elderly, presumably because AIH is erroneously considered to be a disease of young age. Presentation with acute icteric hepatitis is similar to that of younger patients, supporting the assumption that beneficial effects of hormonal changes associated with menopause are not as pronounced in AIH as in other autoimmune diseases. Human leukocyte antigen type seems to have an influence on the age of onset of AIH. Prognosis is excellent, and AIH should be considered in the older patient to avoid delayed initiation of immunosuppressive therapy.

Aged↗
PubMed1999

Combined therapy with azathioprine, prednisolone, and ursodiol in patients with primary sclerosing cholangitis. A case series.

BACKGROUND: No established medical therapy alters the progressive course of primary sclerosing cholangitis. OBJECTIVE: To explore the potential usefulness of combined therapy with azathioprine, steroids and ursodeoxycholic acid (UDCA) in primary sclerosing cholangitis. DESIGN: Case series. SETTING: University hospital in Mainz, Germany. PATIENTS: 15 patients with primary sclerosing cholangitis. INTERVENTION: Azathioprine (1 to 1.5 mg/kg of body weight per day), prednisolone (1 mg/kg per day initially, tapering to 5 to 10 mg per day) and UDCA (500 to 750 mg per day). MEASUREMENTS: Clinical and laboratory evaluation, liver biopsy, and endoscopic retrograde cholangiography (a >30% change in stenosis was considered significant). RESULTS: After a median observation period of 41 months (range, 3 to 81 months), liver enzyme levels declined significantly in all patients. Six of 10 patients with follow-up liver biopsies showed histologic improvement. Significant radiographic deterioration was seen in only 1 of 10 patients who had endoscopic retrograde cholangiography. In 7 patients previously treated with UDCA alone, liver enzyme levels declined significantly only after immunosuppressive therapy was added. Adverse drug reactions led to the withdrawal of study medications in 2 patients. CONCLUSIONS: Combined immunosuppressive therapy may alter the progression of primary sclerosing cholangitis. Our observations suggest a benefit from adding immunosuppressive drugs to UDCA therapy. A randomized trial is warranted.

Adult↗
PubMed1999

Characterization of the overlap syndrome of primary biliary cirrhosis (PBC) and autoimmune hepatitis: evidence for it being a hepatitic form of PBC in genetically susceptible individuals.

Some patients with autoimmune liver disease present with a clinical and/or histological picture showing characteristic findings of both autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC). Various names, mostly overlap syndrome, have been used to describe these cases, which have thus far not been more closely characterized. The aim of this study was the comparison of 20 patients with overlapping features to representative patients considered suffering from typical AIH or typical PBC (20 patients in each group). We found these patients to indeed show a very mixed picture of both conditions biochemically, serologically, and histologically. However, closer analysis suggested that all of these patients were primarily suffering from PBC as all of them had at least either bile duct destruction on histology or anti-M2 positive antimitochondrial antibodies (AMA). We suggest that these PBC patients because of their genetic susceptibility, evidenced by the AIH-characteristic histocompatibility leukocyte antigen (HLA) type B8, DR3, or DR4, developed a more hepatitic picture. Response to immunosuppressive therapy was excellent. We propose that the name "overlap syndrome" be abandoned for "PBC, hepatitic form." These observations not only have pathophysiological implications, but also suggest that therapy of PBC should be guided by the degree of biochemical and histological hepatic involvement.

Adolescent↗
PubMed1999

TGF-beta1 in liver fibrosis: an inducible transgenic mouse model to study liver fibrogenesis.

Transforming growth factor-beta1 (TGF-beta1) is a powerful stimulus for collagen formation in vitro. To determine the in vivo effects of TGF-beta1 on liver fibrogenesis, we generated transgenic mice overexpressing a fusion gene [C-reactive protein (CRP)/TGF-beta1] consisting of the cDNA coding for an activated form of TGF-beta1 under the control of the regulatory elements of the inducible human CRP gene promoter. Two transgenic lines were generated with liver-specific overexpression of mature TGF-beta1. After induction of the acute phase response (15 h) with lipopolysaccharide (100 microgram ip), plasma TGF-beta1 levels reached >600 ng/ml in transgenic animals, which is >100 times above normal plasma levels. Basal plasma levels of uninduced transgenic animals were about two to five times above normal. As a consequence of hepatic TGF-beta1 expression, we could demonstrate marked transient upregulation of procollagen I and procollagen III mRNA in the liver 15 h after the peak of TGF-beta1 expression. Liver histology after repeated induction of transgene expression showed an activation of hepatic stellate cells in both transgenic lines. The fibrotic process was characterized by perisinusoidal deposition of collagen in a linear pattern. This transgenic mouse model gives in vivo evidence for the important role of TGF-beta1 in stellate cell activation and liver fibrogenesis. Due to the ability to control the level of TGF-beta1 expression, this model allows the study of the regulation and kinetics of collagen synthesis and fibrolysis as well as the degree of reversibility of liver fibrosis. The CRP/TGF-beta1 transgenic mouse model may finally serve as a model for the testing of antifibrogenic agents.

Animals↗
PubMed1997

Regulation of endotoxin-induced IL-6 production in liver sinusoidal endothelial cells and Kupffer cells by IL-10.

Sinusoidal endothelial cells and Kupffer cells are the first cell populations in the liver that come into contact with gut-derived endotoxin in portal blood. Although endotoxin concentrations as high as 1 ng/ml are physiologically present in portal blood, no local inflammation is seen. We show that the proinflammatory cytokine IL-6, which is central to the development of inflammatory reactions in the liver, is produced by sinusoidal endothelial cells and Kupffer cells in response to low concentrations of endotoxin (100 pg/ml to 1 ng/ml). The anti-inflammatory cytokine IL-10 down-regulated endotoxin-induced IL-6 release in endothelial and Kupffer cells. Importantly, Kupffer cells secreted IL-10 after endotoxin stimulation and may therefore participate in the local regulation of inflammation. We have found that IL-6 secretion in Kupffer cells is tightly regulated by endogenous IL-10, because increased IL-6 secretion resulted when neutralizing antibodies to IL- 10 were added to resting and endotoxin-challenged Kupffer cells. Furthermore, repeated exposure of endothelial cells to endotoxin induced a state of tolerance which resulted in decreased release of IL-6 in response to a second endotoxin challenge. Our results support the notion that inflammatory reactions in the liver in response to endotoxin are down-regulated by local release of the anti-inflammatory cytokine IL-10 that is produced by Kupffer cells.

Animals↗
PubMed1997

The therapeutic potential of interleukin-6 hyperagonists and antagonists.

Interleukin-6 (IL-6) is a 4-helical protein that binds to a specific IL-6 receptor on target cells and to two molecules of the promiscuous signal transducing protein, glycoprotein 130 (gp130). Structure-function analysis has led to the definition of molecular contacts between IL-6 and its receptor subunits. This knowledge has led to the design of competitive antagonistic proteins that retain their receptor binding capability, but fail to stimulate one or both gp130 proteins; the properties of such recombinant antagonistic proteins are compared with traditional neutralising monoclonal antibodies targeted at IL-6 or receptor subunits. Furthermore, several strategies have been employed to construct molecules with increased bioactivity. Possible therapeutic applications in putative IL-6 dependent haematologic disorders, e.g., Castleman's disease (CD), POEMS syndrome, multiple myeloma, and bone diseases, e.g., Paget's disease, osteoporosis, are outlined. IL-6 antagonists could also, in theory, suppress inflammatory activity in rheumatic and autoimmune diseases and could prevent secondary amyloidosis. This principle may prove advantageous in myocardial infarction (MI) and unstable angina pectoris. More generally, IL-6 antagonists could improve the wasting and microcytic anaemia of chronic diseases. IL-6 antagonists might slow down development of mesangio-proliferative glomerulonephritis (MPGN). Hyperagonistic variants of IL-6 have a potential use in the ex vivo expansion of haematopoietic progenitor cells and as thrombopoietic agents. They might well be the first drugs to aid liver regeneration in vivo.

Journal Article↗
PubMed1979

Demonstration and partial characterization of 22-nm HBsAg and Dane particles of subtype HBsAg/ady.

The present paper describes the demonstration of d, y, w, and r HBsAg determinants in one serum. It was shown that there are two populations of HBsAg particles: HBsAg/ad and HBsAg/ady. All complete Dane particles were of subtype HBsAg/ady. Further characterization of HBsAg/ady particles did not reveal morphologic differences when they were compared with HBsAg/ad and HBsAg/ay particles. An HBsAg/ady phenotype may be the result of a double infection with hepatitis B viruses or exchanges of DNA sequences that determine HBsAg/ay and HBsAg/ad to form a new genotype.

Adult↗
PubMed1977

Simultaneous presence of HBsAg and anti-HBs in the serum of different subtypes (serological and immunofluorescent studies).

Serological and immunofluorescent studies were performed in 3 patients with the simultaneous presence of HBsAg and anti-HBs in the serum. Our investigations revealed the following results: HBsAg and anti-HBs in the serum were of different subtypes. HBsAg in the serum and in the liver had the same subtype. HBsAg in the liver did not react with the circulating anti-HBs in the patient's own serum. HBsAg-anti-HBs immune complexes could not be detected in the serum or in the liver tissue. These phenomena can most readily be explained by at least 2 contacts with hepatitis-B-viruses of different subtypes, one leading to immune tolerance and the other to an immune response. In a follow-up study there was no evidence for a short-term change in HBsAg subtype. Unexplained remains the cause why one contact with HBV did lead to immune tolerance and a second to an immune response.

Adult↗