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A Erhardt

Publications and source records attributed to A Erhardt.

33 records · Page 2Linked to original sources
PubMed1999

[Demonstration of HFE polymorphism in German patients with hereditary hemochromatosis].

BACKGROUND AND OBJECTIVE: Hereditary haemochromatosis (HH) is the most common genetically determined disease of the white population which by iron overload causes multiorgan functional impairment. Recently the gene for HH (HFE gene) has been located on chromosome 6. The development of HH is thought to be caused by two point mutations that lead to an amino acid exchange of tyrosine for cysteine on codon 282 (Cys282Tyr) and of histidine by aspargic acid on codon 63 (His63Asp). PATIENTS AND METHODS: 75 patients with phenotypically confirmed HH were examined genetically. The analysis of the HFE-gene mutation was done on genomic DNA by restriction digestion with the restriction enzymes Rsal and Mbol. RESULTS: Homozygosity for the Cys282Tyr mutation was found in 66 (88%) of the patients, while two were heterozygous. Of seven patients with wild-type sequence of the amino acid position 282, three (43%) had a His63Asp exchange. Overall only four patients had neither of the two mutations. CONCLUSIONS: Because of different geographical distributions, a knowledge of the mutation rate is important for patients with HH. to assess the diagnostic value of the gene test. For the first time gene analysis makes it possible to diagnose HH before clinically significant iron overload occurs. It may further improve prognosis of the disease by early application of therapeutic blood-letting.

Amino Acid Sequence↗
PubMed1999

[Sheep, chills and "doughnut granuloma"--an atypical course of Coxiella infection].

Q fever usually presents with high fever, headache and an atypical pneumonia. A case report of a 47-year-old patient with an atypical course of a coxiella infection is described. The dominant clinical symptoms were a liver and bone marrow involvement, whereas pulmonary manifestations were absent. The diagnosis of Q fever in this patient was based on the detection of cytoplasmatic inclusion bodies in macrophages and granulocytes. Furthermore fibrin-ring granulomas ("doughnut lesions") were found in liver tissue specimen and epitheloid-cell granulomas were detected in bone marrow specimen. Complement-fixation antibody titers and PCR resulted unspecific or negative on different occasions during the course of the disease. A confirmation of the diagnosis by complement-fixation antibody test was possible only after recovery from the disease. In Q fever with atypical clinical and serological presentation the screening of blood cells for inclusion bodies and liver or bone marrow tissue for granulomas may be important for establishing the diagnosis.

Animals↗
PubMed1999

[Hereditary hemochromatosis--new developments after discovery of the HFE gene].

Hereditary hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism, resulting in an increased iron deposition and multiorgan failure. Recently a candidate gene of HH, termed HFE, has been identified on chromosome 6, coding for a protein homologous to major histocompatibility complex (MHC) class I molecules. Two mutations of the hemochromatosis gene leading to an exchange of cysteine to tyrosine at aminoacid 282 and histidine to asparagine at aminoacid 63, are retained responsible for the development of hereditary hemochromatosis. The Cys282Tyr-mutation disrupts a disulfid bond and thus abrogates binding of the mutant HFE-protein to beta 2-microglobulin and its presentation on the cell surface. The His63Asp-mutation seems to play a role in pH-regulated dissociation of the transferrin receptor/transferrin complex in the lysosome. Mutations of the HFE-protein alter the affinity of the transferrin receptor for its ligand transferrin and may thus cause an intracellular accumulation of iron. Knowledge of the responsible gene allows a molecular diagnosis of HH. The new genetic marker can be used for screening and confirmation of HH reducing the need for confirmatory liver biopsies. Compared to standard screening parameters like ferritin and transferrin saturation genetic testing will allow the diagnosis of HH in an early, asymptomatic state before iron accumulation has occurred. As a normal life expectancy of patients with HH can be achieved if iron reduction is initiated early, genetic testing may thus be of great benefit for patients with HH.

Algorithms↗
PubMed1998

Prognosis of chronic hepatitis C: results of a large, prospective cohort study.

The prognosis of chronic hepatitis C virus (HCV) infection is still ill-defined. The present study prospectively evaluated mortality and complications in a large cohort of patients with chronic hepatitis C. The study included 838 anti-HCV and HCV-RNA-positive patients who were followed for 50.2 +/- 26.9 months (mean +/- SD; range, 6-122 months) in a prospective protocol. During follow-up, 62 patients died (31 from liver disease and 31 from other causes), and 12 patients needed liver transplantation. When compared with a matched general population, hepatitis C increased mortality mainly when cirrhosis was present and in patients who were less than 50 years old at study entry. During follow-up, a further 30 patients developed nonlethal complications of cirrhosis. By multivariate regression, survival was decreased by cirrhosis, long disease duration, history of intravenous drug abuse, and excessive alcohol consumption, whereas interferon therapy improved survival. Alanine transaminase (ALT), bilirubin, sex, and genotype had no effect on survival. The risk of hepatocellular carcinoma (HCC) (n = 17) was increased by cirrhosis and to a lesser degree by long disease duration and high bilirubin, whereas interferon therapy, genotype, and other factors had no effect. Chronic hepatitis C is a disease with considerable mortality and morbidity when cirrhosis is present at diagnosis. Patients who acquire the infection early in life have a markedly increased mortality even when cirrhosis is absent at diagnosis. The age at diagnosis therefore should play a major role in therapeutic considerations. The present data also suggest that interferon therapy has a long-term clinical benefit, although it did not reduce the risk of liver cancer.

Adult↗
PubMed1997

[Hepatocellular carcinoma in Germany. Epidemiology, etiology, clinical aspects and prognosis in 100 consecutive patients of a university clinic].

Chronic hepatitis C and B are the main causes of hepatocellular carcinoma (HCC) worldwide. Little is known about the etiology of HCC in Germany which is regarded as a low-prevalence area for viral hepatitis C (HCV) and B (HBV). To assess the etiologic factors of HCC in Germany we have retrospectively analyzed the records of 100 consecutive patients with hepatocellular carcinoma in our clinic. HCC-patients with documented status on HCV/HBV-infection and daily alcohol intake (n = 55) had HCV antibodies in 53%, HBs-Ag in 20%, isolated chronic alcohol abuse in 11% and genetic hemochromatosis in 2%. In 13% of the HCC-patients no risk factor could be identified. Coinfections with HCV and HBV were not observed. Liver cirrhosis was present in 90% of the HCC-patients. In histologically confirmed HCC (n = 71) serum alpha-fetoprotein level was normal (< 8.5 ng/ml) in 20%, moderately elevated (8.5-300 ng/ml) in 48% and considerably elevated (> 300 ng/ml) in 32% of the patients. Only 31% of all patients presented with small single lesions (< or = 5 cm) without evidence for extrahepatic metastases or portal vein thrombosis. Only 30% of the HCC-patients could be treated with a curative intention (28 hepatic resections, one orthotopic liver transplantation). Patients who underwent resection had cumulative 6-month, 1-year, 2-year and 3-year survival rates of 83.8%, 65.9%, 54.3% and 24.8% respectively. Median survival time after resection was 24.8 months compared with 5.8 months in symptomatically treated patients with unresectable HCC (n = 39). Patients with hepatitis C-associated HCC were significantly older than patients with hepatitis B-associated HCC (mean values: 63.2 vs. 54.2 years). Frequency of cirrhosis, tumor stage, alpha-fetoprotein level and prognosis did not differ between groups. In conclusion hepatocellular carcinoma was predominantly associated with chronic HCV-infection. Most patients presented with normal or moderately elevated serum AFP-levels. Prognosis was poor even after hepatic resection.

Adolescent↗
PubMed1996

Quantitative assay of PCR-amplified hepatitis B virus DNA using a peroxidase-labelled DNA probe and enhanced chemiluminescence.

We have developed a sensitive and quantitative assay for hepatitis B virus (HBV) DNA in serum or plasma in which PCR and then microtiter hybridization analysis are used. Assay of HBV DNA in serum or plasma is important for demonstrating viral replication, indicating and monitoring antiviral therapy, determining the infectivities of virus carriers, and ensuring the safety of blood products. Under optimum conditions PCR can amplify one HBV DNA molecule to 10(8) copies, but detection of this amount of DNA still requires hybridization with labelled probes or a nested PCR. We labelled one strand of the PCR product with a biotinylated primer. The double-stranded amplicon was incubated in streptavidin-coated microplate wells. The nonlabelled strand was removed after denaturation of the double-stranded DNA with alkali, and the bound strand was hybridized with a peroxidase-coupled single-stranded probe. The amount of bound peroxidase was measured in a luminometer. Four picograms of amplicon was detectable in this system, whereas conventional ethidium bromide staining requires a 1,000 times higher amplicon concentration. The performance of the new assay was compared with those of nested PCR and a PCR system that uses a digoxigenin label, hybridization to a solid-phase adsorbed probe, and colorimetric detection. The chemiluminescence assay was found to be almost as sensitive as nested PCR and approximately five times more sensitive than the colorimetric test.

Bacterial Proteins↗
PubMed1990

In vitro synthesis and transbilayer movement of phosphatidylethanolamine molecules labelled with different fatty acids in chick brain microsomes.

The transbilayer fatty acid distribution of diacylglycerophosphoethanolamine and the translocation of newly synthesized phosphatidylethanolamine molecules labelled with different fatty acids has been investigated in chick brain microsomes using trinitrobenzensulfonic acid. The determination of the fatty acid composition of diacylglycerophosphoethanolamine in both the outer and the inner leaflet of the microsomal vesicles revealed a similar distribution indicating that both leaflets share the same molecular species. The in vitro incorporation of radioactive fatty acids (16:0, 18:1 and 20:4(n-6] into ethanolamine phospholipids, known to be catalyzed by the lyosphosphatidylethanolamine acyl transferase, showed that the radioactive diacylglycerophosphoethanolamine molecules appeared first in the outer leaflet and were thereafter transferred to the inner leaflet. The apparent rate of translocation of the newly synthesized ethanolamine phospholipid molecules was the highest for those labelled with 16:0 and the lowest for those labelled with 20:4(n-6). The results indicate that the active site of the acyl-CoA:lysophosphatidylethanolamine acyltransferases is located on the outer leaflet of the microsomal vesicles and that the different newly synthesized molecular species of diacylglycerophosphoethanolamine may be translocated from the outer to the inner leaflet at different rates.

Animals↗
PubMed1989

Mobilizable lead in patients with chronic renal failure.

Blood lead (Pb) and urinary Pb before and after i.v. infusion of 1 g of Na2Ca EDTA were determined (atomic absorption) in 46 control subjects and 91 patients with various stages of renal failure (median serum creatinine 2.5 mg dl-1). Under baseline conditions, patients with renal failure had higher blood Pb levels (112 ng ml-1, range 44-272 vs. 76; 36-187 in controls; P less than 0.001) and lower urinary Pb (16.2 nmol 24 h-1 1.73 m-2, 4.86-66.8 vs. 33; 11-91 in controls; P = 0.001). The increment in urinary Pb after EDTA infusion (mobilizable Pb) was higher (795 nmol 4 days-1 1.73 m-2, range 155-5611 vs. 307; 131-1587 in controls; P = 0.001). In 12 patients with renal failure (13%) mobilizable Pb was above the highest value in controls. Mobilizable urinary Pb correlated (r = 0.68) significantly (P = 0.001) with blood Pb, but only marginally with serum creatinine (r = 0.32; P less than 0.007). Mobilizable Pb was higher in patients with renal failure and a history of smoking or occupational Pb exposure and tended to be higher in patients with alcoholism. Ten of 91 patients had gout; increased mobilizable Pb was present in three of the 10. The data confirm relatively high prevalence of elevated body Pb burden in European patients with chronic renal failure. The question is unresolved whether Pb plays a role in the progression of renal failure.

Adolescent↗
PubMedDate not supplied

Pituitary response to LHRH during the puerperium in women.

Five breast-feeding women received 100 mug synthetic LHRH at between 19 and 58 days post-partum. One subject was treated twice. LH and FSH responses were monitored using radioimmunoassay. In four women treated at 19,21,29 and 51 days post-partum, the FSH response was greater than the LH response which was absent altogether in three of these women. In two women who were treated at 52 and 58 days both LH and FSH levels was elevated with the LH response being greater than the FSH response. This change in the pattern of pituitary response is considered in relation to the post-partum anovulatory condition.

Female↗