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Biomedical subjects

G Gerken

Publications and source records attributed to G Gerken.

At least 235 records · Page 13Linked to original sources
PubMed1987

Pre-S encoded surface proteins in relation to the major viral surface antigen in acute hepatitis B virus infection.

The role of pre-S encoded viral surface proteins in acute hepatitis B virus infection is still poorly understood. Binding sites for polymerized human serum albumin have been found to be encoded by the pre-s2 region of the hepatitis B virus genome. Recently, murine monoclonal antibodies against pre-s1 and pre-s2 encoded hepatitis B virus gene products were generated and used for their specific detection in serum. In sera from patients with acute hepatitis B, pre-s1 and pre-s2 antigen occurred in 16 of 20 and 15 of 20 patients, respectively. In the initial stage of the disease, pre-S gene products correlated with binding sites for polymerized human serum albumin, but not with hepatitis B surface antigen. Subsequently, pre-s1 and pre-s2 antigens were cleared from the serum of patients with acute hepatitis B before binding sites for polymerized human serum albumin and hepatitis B surface antigen. Possibly, the early clearance of pre-S markers can be of prognostic value in acute hepatitis B. The mechanisms of the early clearance of the pre-S antigens in acute hepatitis B remain to be elucidated. However, elimination by immunologic mechanisms appears likely.

Acute Disease↗
PubMed1987

Liver membrane autoantibodies in chronic active hepatitis. Studies on mechanically and enzymatically isolated rabbit hepatocytes.

Target antigens relevant for immune reactions in inflammatory liver diseases should be expressed on the hepatocellular membrane. Using mechanically or enzymatically isolated rabbit hepatocytes, we evaluated the influence of cell integrity on the detection of membrane-expressed antigens by sera from patients with chronic hepatitis and by murine monoclonal antibodies. Our results provide evidence that target antigens of liver membrane autoantibodies (LMA) as well as liver kidney microsomal antibodies (LKM) are not expressed on the hepatocellular membrane of viable and intact isolated rabbit hepatocytes. However, LMA were detected in the sera of 56% of patients with autoimmune chronic active hepatitis using mechanically isolated hepatocytes. These findings underline the diagnostic relevance of the autoantibodies. It is suggested that LMA are directed against constituents of the cytoskeleton. Therefore, it seems to be unlikely that this antibody is causally involved in the pathogenesis of autoimmune liver diseases.

Animals↗
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

Relationship of pre-S encoded antigens in liver and clinical manifestations of chronic hepatitis B infection.

Pre-S1 and pre-S2 encoded antigens of hepatitis B virus were localized in liver tissue using monoclonal antibodies. They were found to be exclusively expressed in the cytoplasm of liver cells. Cell bound pre-S1 encoded protein was often detected in patients with chronic liver disease and viremia. Only a small number of the HBsAg positive cells also contained pre-S1 antigen. There was no correlation with nuclear HBcAg. Livers of non-viremic HBsAg carriers contained many HBsAg expressing liver cells, that were frequently also positive for pre-S2 encoded protein but contained no detectable pre-S1 encoded protein at all. It remains open whether cell bound pre-S2 containing proteins of middle size have a significance for pathogenesis, as they are present in individuals with chronic liver disease as well as in healthy HBsAG carriers, and may be associated with both increased and normal liver enzymes. Cell bound pre-S1 antigen with viremia may, however, be involved in the maintenance of viremia and liver disease.

Biopsy↗
PubMed1987

Virus-associated receptors for polymerized human serum albumin (RpHSA) in patients with chronic active hepatitis B treated with recombinant leukocyte A interferon.

Hepatitis B surface antigen (HBsAg)-associated receptors for polymerized human serum albumin (RpHSA) are assumed to mediate viral attachment to hepatocytes in hepatitis B virus (HBV) infection. RpHSA was found to be coded by the pre-S region of HBV genome. Recently, the antiviral effect of recombinant leukocyte alpha-interferon was shown in patients with hepatitis B. Our study evaluated the detection and the clinical implications of RpHSA in patients with chronic active hepatitis B under treatment with recombinant alpha-interferon. Two out of nine patients eliminated all HBV markers including RpHSA. Four out of nine patients became negative for markers of viral replication but remained positive for HBsAg and in part for RpHSA. In three out of nine patients HBV markers including RpHSA remained unchanged. In summary, the titer for RpHSA is a reliable indirect marker for infectivity and of prognostic value in patients with chronic active hepatitis B during interferon treatment. Future studies should evaluate a putative immune response to RpHSA-containing viral surface proteins, which could be relevant for viral clearance in HBV infection.

Adult↗
PubMed1987

Detection of hepatitis B virus markers in sera of asymptomatic hepatitis B surface antigen carriers with special emphasis to pre-S-encoded proteins.

Sera of asymptomatic hepatitis B surface antigen (HBsAg) carriers were analyzed for the presence of pre-S-encoded proteins. Four individuals with biopsy-proven chronic hepatitis uniformly expressed pre-S1- and pre-S2-encoded proteins. Individuals who had histologically normal or largely normal livers were heterogeneous with respect to expression of pre-S-encoded proteins. This heterogeneous expression of pre-S-encoded proteins occurred most likely due to difference in serum HBsAg concentration. Alternatively differences in pre-S gene expression need to be considered. Clinically the study indicates that expression of pre-S domains in serum is unrelated to viremia or chronic liver disease.

Carrier State↗
PubMed1987

Characterization of primary biliary cirrhosis (PBC) specific mitochondrial determinants by immunoblotting.

Antimitochondrial antibodies (AMA) are detected in up to 100% of patients with primary biliary cirrhosis (PBC); subtypes of AMA are disease specific. Sera from 21 patients with PBC and from 50 patients with various hepatic and non-hepatic diseases were tested for AMA by indirect immunofluorescence, radioimmunoassay for PBC-specific subtype anti M2 and characterized by western blot analysis and agarose-IEF-immunoblotting. Sera from patients with PBC reacted with up to 7 different mitochondrial polypeptides on western blots, mol. wt. 24,000-62,000 dalton. Sera from 50 patients with various hepatic and non-hepatic diseases did not react with these polypeptides. Sera with other AMA subtypes were included in this study (anti M1, anti M3, and anti M5). These mitochondrial polypeptides were associated with inner mitochondrial membranes (mitoplasts). Sonification led to a solubilization of several mitochondrial polypeptides (p 62, p 48, p 40, p 24). On agarose-IEF-immunoblotting sera from patients with PBC and 3 sera from patients with AMA positive cholestatic CAH but no other sera reacted with a protein band at pI 4.0; seven PBC sera reacted in addition with a protein band at pI 4.4. Western blot and agarose-IEF-immunoblotting are sensitive and specific tools to identify and characterize mitochondrial target antigens in PBC. Furthermore these techniques allow to study the clinical relevance of the heterogeneity of AMA in cholestatic liver disease.

Autoantibodies↗
PubMed1987

Distinction between natural and pathological autoantibodies by immunoblotting and densitometric subtraction: liver-kidney microsomal antibody (LKM) positive sera identify multiple antigens in human liver tissue.

Using one-dimensional and two-dimensional immunoblotting techniques the reactions of sera from 14 patients with liver-kidney microsomal (LKM) antibody positive chronic active hepatitis (CAH) with human liver microsomal preparations was compared with the reaction of sera from 12 healthy persons and from five patients with systemic lupus erythematosus (SLE). All sera displayed a multiplicity of reactions. This demonstrates the presence of many autoantibodies in normal human sera. It could be shown that all sera react with the cytoskeletal antigens cytokeratin, actin and actomyosin. These reactions were more marked in the autoimmune sera, i.e. LKM-positive CAH and SLE. Densitometric subtraction was found to be a reliable technique to distinguish the natural antigen/autoantibody reactions from pathological, disease-characteristic autoantibodies. It was shown that the pathological LKM autoantibodies recognize non species-specific microsomal proteins at 50 kD of pI 7.5-8.0 at high titres, which are only very weakly recognized by normal or SLE sera. We recommend sensitive immunoblotting techniques and densitometric subtraction as the currently most accurate method to distinguish natural from pathological autoantibodies.

Autoantibodies↗
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

[Detection and significance of HBsAg associated receptors for polymerized human serum albumin in acute hepatitis B virus infection].

Receptors for polymerized human serum albumin (R-pHSA) may play a role in the attachment of hepatitis B virus (HBV) to hepatocytes. Therefore, we evaluated the incidence and prognostic value of R-pHSA in acute hepatitis B virus infection. High titers of R-pHSA were found in 12/12 patients with HBeAg positive acute hepatitis B (log2-Titer: 8.5 +/- 1.5). Titers for R-pHSA and HBsAg correlated closely. Furthermore, R-pHSA occurred (log2-titer: 6.5 +/- 1.5) in 10/10 patients with HBeAg positive chronic active hepatitis B (CAH-B). In the course of HBV infection, R-pHSA were eliminated earlier than HBsAg. 4/20 patients which were asymptomatic HBsAg carriers had high titers of R-pHSA in correlation to the histological findings of CAH-B. Asymptomatic HBsAg carriers which were R-pHSA negative had a normal liver histology. R-pHSA were found to be an early prognostic marker in acute hepatitis B infection.

Carrier State↗
PubMed1986

[Acute fatty liver of pregnancy. A case report of the differential diagnosis of pregnancy-associated liver diseases].

Acute fatty liver of pregnancy (AFLP) is a rare, but often fatal disorder in the third trimester of pregnancy. We report on a patient with AFLP complicated by acute hemorrhagic diathesis, who survived after early diagnosis and adequate treatment. On electronmicroscopy, the characteristic microvesicular fatty deposits in the centrolobular hepatocytes could be demonstrated.

Acute Disease↗
PubMed1985

Rare association of herpes simplex virus IgM-specific antibodies and Guillain-Barré syndrome successfully treated with plasma exchange and immunosuppression.

Herpes simplex virus (HSV) has been associated with various neurological disorders. In contrast, HSV infection is very rarely found in acute polyneuroradiculitis. In this report, a patient is described with a severe course of Guillain-Barr¿ syndrome (GBS). HSV IgM-specific antibodies and a rise of complement-fixation antibodies were detected. During the acute phase of neurologic syndrome, a nerve biopsy showed myelin damage and IgM deposits on the inner layer of the perineurium. Plasma exchange, in combination with immunosuppression, was successfully applied as a treatment in the relapsing course of GBS. Finally, after recovery, HSV-specific IgM antibodies disappeared.

Aged↗
PubMedDate not supplied

The effect of recombinant alpha-interferon treatment on serum levels of hepatitis B virus-encoded proteins in man.

The effect of alpha-interferon treatment on serum levels of hepatitis B virus-encoded proteins was analyzed in eight patients with chronic type B hepatitis who participated in a pilot study of interferon therapy. Three individuals became HBsAg-negative, 4 lost HBeAg but remained HBsAg-positive and 1 remained positive for both HBsAg and HBeAg. Initiation of interferon treatment was rapidly followed by reduction or loss of hepatitis B virus DNA in the serum but by little immediate change in hepatitis B virus antigen levels. Changes in hepatitis B virus antigens were usually delayed. Loss of HBsAg from the serum was preceded by the sequential disappearance of pre-S-encoded proteins (pre-S1 and polymerized human serum albumin) and HBeAg. In patients who lost HBeAg but remained HBsAg-positive, serum levels of pre-S1 and polymerized human serum albumin usually, but did not always, decrease. The individual who remained HBsAg- and HBeAg-positive had unchanged serum levels of pre-S1, polymerized human serum albumin and HBsAg. These results suggest that alpha-interferon inhibits hepatitis B virus DNA replication but has little direct effect on synthesis of hepatitis B virus gene products.

Adult↗
PubMedDate not supplied

Two different subtypes of antimitochondrial antibodies are associated with primary biliary cirrhosis: identification and characterization by radioimmunoassay and immunoblotting.

Antimitochondrial antibodies from patients with primary biliary cirrhosis react with different mitochondrial polypeptides as demonstrated by Western blots. The IgG fractions of a patient with primary biliary cirrhosis Stage I reacting exclusively with a pair of polypeptides at 48,000 daltons (p 48) on Western blot and from a patient with Stage III primary biliary cirrhosis reacting exclusively with a single 62,000 dalton polypeptide (p 62) were labeled with 125I; two radioimmunoassays were established detecting antimitochondrial antibodies against p 62 and p 48, respectively. Autologous sera blocked the assay, but the two reference sera did not block each other. Fourteen of 40 patients with primary biliary cirrhosis reacted with p 62, 6/40 with p 48 and 20 sera with both antigens. Sera from 200 patients with various hepatic and nonhepatic diseases were negative for anti-p 62 and anti-p 48. This collection of sera included 5 patients with nonhepatic autoimmune disorders, 3 with drug-induced pseudolupus syndrome and 2 with syphilis II, which were positive for antimitochondrial antibodies by immunofluorescence. Mitochondrial autoantigens p 62 and p 48 were both localized on mitoplasts, presumably inner mitochondrial membranes; they were thermolabile, trypsin- and chymotrypsin-sensitive, but resistant to DNAase, RNAase and neuraminidase treatments. In cesium chloride density gradients, p 62 floated at 1.28 gm per cm3 and p 48 at 1.30 gm per cm3. Thus, radioimmunoassays have been developed that specifically detect two distinct primary biliary cirrhosis-specific subtypes of antimitochondrial antibodies: anti-p 62 and anti-p 48. All primary biliary cirrhosis sera were positive for at least one of these antimitochondrial antibodies subtypes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Prokinetics in patients with gastroparesis: a systematic analysis.

BACKGROUND: The relative potency of prokinetics in patients with gastroparesis has not been systematically studied. This study, therefore, aimed to assess the available data and to compare the effects of different prokinetics on symptoms and gastric emptying rates in patients with gastroparesis. METHODS: A systematic search of the literature was performed, covering the period 1980 to March 1998. All identified studies were reviewed and the following data elements assessed: characteristics of study populations; sample sizes; treatment regimes; drug doses; study design; main outcome variables, and the validity of measurements. RESULTS: In 36 studies, 514 patients were treated with prokinetics p.o. Most studies had methodological limitations (i.e. nonvalidated measurement of symptoms or unblinded treatment). The mean improvement in gastric emptying and the reduction in the symptom score was higher in the open trial group than in patients treated double-blind. Overall, erythromycin seems to have had the strongest effect on gastric emptying as compared to domperidone, cisapride or metoclopramide. Concerning gastrointestinal symptoms, the symptom scores appeared to improve more during treatment with erythromycin than with domperidone, metoclopramide or cisapride. CONCLUSIONS: Most of the available trials have methodological limitations; this limits the conclusions. However, the data suggest that the motilin-agonist erythromycin is superior with regard to the acceleration of gastric emptying, while both erythromycin and domperidone appear to be the most effective with regard to improvements in the symptom score. Additionally, there is a lack of association between changes in gastric emptying times and improvements in symptoms.

Analysis of Variance↗
PubMedDate not supplied

Long-term follow-up of patients with chronic hepatitis C after interferon-alpha treatment.

In this study, 72 patients with chronic hepatitis C virus (HCV) were followed prospectively for a mean period of 27 months after interferon treatment. Fifty-seven percent (20/35) of the patients with complete response, 18/20 with HCV-RNA-negative serum, had a sustained biochemical remission. Reactivation was seen in 43% of these patients after a mean follow-up of 7.3 months. A late relapse after more than 12 months of follow-up occurred in only 2/15 patients. Patients with a long-term complete response had significantly lower pretreatment serum HCV RNA levels than complete responders with relapse (106,239 vs. 345,649 mEq/ml, p = 0.0213). A delayed sustained biochemical remission was seen in 3/37 patients with partial or no response. Thus, long-term response is achieved in 32% of the patients treated with interferon, clearly associated with a suppression of serum HCV RNA. Patients with normal ALT values and undetectable levels of HCV RNA for more than 12 months of follow-up may usually be considered as sustained responders. Thus, for the first time, the pretreatment HCV RNA level in serum was identified as predictive of long-term response.

Adult↗