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Biomedical subjects

H Müller

Publications and source records attributed to H Müller.

At least 271 records · Page 15Linked to original sources
PubMed1995

Identification of a novel viral protein in infectious bursal disease virus-infected cells.

Infectious bursal disease virus (IBDV), a member of the Birnaviridae, specifies two genomic double-stranded RNAs, segment A and segment B. Segment A encodes a 110 kDa polyprotein which is processed into virus proteins VP2, VP3 and VP4. A second open reading frame (ORF), designated ORF A-2, immediately preceding and partially overlapping the 110 kDa protein gene has also been described. After prokaryotic expression of this ORF and immunization of rabbits with the expressed protein we obtained reagents that allowed the identification of the ORF A-2 gene product in IBDV-infected cells. The ORF A-2 protein exhibits an apparent molecular mass of 21 kDa which is larger than the size of 16.5 kDa calculated from the deduced amino acid sequence. Immunofluorescence studies demonstrated the presence of the ORF A-2 protein in bursa samples from IBDV-infected chicken. In summary, the IBDV ORF A-2 product represents the fifth IBDV protein described. Therefore, we propose to designate it as IBDV VP5.

Animals↗
PubMed1995

A phase I/II trial of recombinant human interleukin-6 in patients with aplastic anaemia.

In a phase I/II study, 11 patients with marrow failure (10 with acquired aplastic anaemia and one with pancytopenic Fanconi anaemia) were treated with recombinant human interleukin-6 (rhIL-6) to assess the safety and tolerability of rhIL-6 and its effects on peripheral blood counts, bleeding complications and transfusion requirements. All patients with acquired aplastic anaemia were refractory to immunosuppressive treatment or had relapsed after immunosuppressive therapy and were not bone marrow transplantation candidates. Recombinant hIL-6 was to be given as a once-daily subcutaneous injection for 28 d at doses ranging from 0.5 to 5.0 micrograms/kg. After an observation period of 2 weeks, five patients received a second treatment course of 28 d. Only one patient had a sustained increase in platelet count from 18,000 to 72,000/microliters. Bleeding occurred in four patients and caused premature discontinuation of rhIL-6 therapy in three patients. A deterioration of pre-existing anaemia was observed in nine patients. No significant changes of leucocyte counts were observed during the first cycle. During the second cycle the peripheral blood monocyte counts decreased significantly. No significant changes in bone marrow cellularity were observed. Recombinant hIL-6 induced a dose-dependent increase in acute-phase reactants in all patients. Other adverse events included fever, headache, arthralgia, tachycardia and hypertension. In conclusion, rhIL-6 given alone at low doses does not increase platelet counts in the majority of patients with aplastic anaemia and can precipitate a sudden worsening of pre-existing anaemia and thrombocytopenia. This study was discontinued prematurely on account of the toxicity of rhIL-6 seen in patients with aplastic anaemia.

Acute-Phase Reaction↗
PubMed1995

Correlation of morphometry, nucleolar organizer regions, proliferating cell nuclear antigen and Ki67 antigen expression with grading and staging in urinary bladder carcinomas.

OBJECTIVE: To investigate the correlation of four different indicators of proliferation--mean nuclear area (MNA) morphometry, nucleolar organizer region (NOR) count, proliferating cell nuclear antigen (PCNA) and Ki67 antigen expression--in specimens of invasive and non-invasive urinary bladder carcinomas with the grading and staging of the tumour and to determine which indicator is most suitable for discriminating between non-invasive and invasive carcinomas. MATERIALS AND METHODS: Biopsies of 58 urinary bladder carcinomas of different grade and stage (38 invasive, 20 non-invasive) and 11 carcinomata in situ were included in the study. Ten specimens of normal bladder mucosa served as controls. Analysis of indicators was performed on sequential serial paraffin sections of the same tissue, applying each test once to one of four serial sections. RESULTS: In comparison to normal bladder mucosa the values of the four indicators were significantly greater (P < 0.001) in all carcinomata in situ and in carcinomas. Values also increased from grade 1 to grade 3 carcinomas, but indicator values were similar for carcinomata in situ and grade 2 carcinomas. All indicators correlated with each other and allowed a significant discrimination between grade 1 and 2 or grade 2 and 3 carcinomas. Non-invasive carcinomas (Ta) showed a significantly lower proliferative activity (P < 0.001) than invasive carcinomas but there were overlapping values within the invasive carcinomas (T1,T2 and T3/4). CONCLUSIONS: MNA, NOR count, PCNA index and Ki67 index could be correlated with tumour grade, but not with stage, of transitional bladder carcinoma. Of the indicators studied the Ki67 antigen was the most useful in differentiating between invasive and non-invasive carcinomas. This could be of prognostic relevance, especially for the heterogeneous group of grade 2 carcinomas.

Aged↗
PubMed1995

Expression of heat shock genes in Clostridium acetobutylicum.

Characterization of the heat shock response in Clostridium acetobutylicum has indicated that at least 15 proteins are induced by a temperature upshift from 30 to 42 degrees C. These so-called heat shock proteins include DnaK and GroEL, two highly conserved molecular chaperones. Several genes encoding heat shock proteins of C. acetobutylicum have been cloned and analysed. The dnaK operon includes the genes orfA (a heat shock gene with an unknown function), grpE, dnaK, and dnaJ; and the groE operon the genes groES and groEL. The hsp18 gene coding for a member of the small heat shock protein family constitutes a monocistronic operon. Interestingly, the heat shock response in this bacterium is regulated by a mechanism, which is obviously different from that found in Escherichia coli. So far, no evidence for a heat shock-specific sigma factor of the RNA polymerase in C. acetobutylicum has been found. In this bacterium, like in many Gram-positive and several Gram-negative bacteria, a conserved inverted repeat is located upstream of chaperone/chaperonin-encoding stress genes such as dnaK and groEL and may be implicated as a cis-acting regulatory site. The inverted repeat is not present in the promoter region of hsp18. Therefore, in C. acetobutylicum there are at least two classes of heat shock genes with respect to the type of regulation. Evidence has been found that a repressor is involved in the regulation of the heat shock response in C. acetobutylicum. However, this regulation seems to be independent of the inverted repeat motif, and the mechanism by which the inverted repeat motif mediates regulation remains to be elucidated.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1995

Fecal cholesterol excretion in preterm infants fed breast milk or formula with different cholesterol contents.

In 44 very low-birth-weight infants, fecal cholesterol excretion was measured and in 29 other infants serum total cholesterol concentrations in response to different cholesterol intakes were studied. The infants received fortified breast milk (mean cholesterol content 15.3 mg/dl) or were fed either a standard preterm formula (cholesterol content 5.5 mg/dl) or the same formula but with a modified lipid composition (long chain polyunsaturated fatty acid concentration closely related to breast milk fat) and 30 mg of cholesterol/dl. In the group fed the high cholesterol formula, fecal cholesterol excretion was significantly higher (35.5 mmol/kg/day) than in the groups fed breast milk or the standard formula (20.1 and 18.2 mmol/kg/day). Cholesterol balance in the group fed the high cholesterol formula (21.8 mg/kg/day) was significantly higher than in the group fed breast milk (+8.6 mg/kg/day). In the infants fed the low cholesterol formula the balance was negative (-7.7 mg/kg/day). Serum concentrations of total cholesterol were similar in the groups fed breast milk or the high cholesterol formula (3.47 and 3.51 mmol/l), but significantly higher than in the group fed the low cholesterol formula (3.15 mmol/l). The data suggest that preterm infants are able to regulate a higher cholesterol intake than during breast feeding by increasing fecal cholesterol excretion as well as decreasing endogenous synthesis.

Age Factors↗
PubMed1995

Novel germline APC gene mutation in a large familial adenomatous polyposis kindred displaying variable phenotypes.

The APC gene is mutated in the germline of people from families where there is a predisposition to develop polyposis coli. Many mutations have been described but the relation between their site and the phenotypic expression of the disease remains unclear. The most commonly seen mutation occurs at codon 1309. Many other mutations have been described towards the 5' end of exon 15 of the APC gene but comparatively few have been seen towards the 3' end. Recent reports have indicated the possibility of a functional boundary with respect to severity and age of onset of disease, which lies towards the 5' end of the gene. This report describes a large family whose affected members present with a very variable phenotype ranging from an early onset and severe form to a comparatively mild later onset one. The mutation that predisposes to disease in this family is at a previously undescribed site that lies towards the 3' end of exon 15 of the APC gene, which results in a stop codon. Interestingly, the stop codon is 63 codons downstream of the mutation and therefore may affect the expression of the disease. The addition of this mutation to the growing list of mutations described in the APC gene may provide some insight into the genotype/phenotype relation of the disease thus contributing to the understanding and significance of mutations at specific sites in the APC gene.

Adenomatous Polyposis Coli↗
PubMed1995

Detection of new mutations in six out of 10 Swiss HNPCC families by genomic sequencing of the hMSH2 and hMLH1 genes.

The cancer predisposition in most HNPCC families is believed to be associated with mutations in the human mismatch repair gene homologues hMSH2 and hMLH1. We searched for mutations in our collection of 10 Swiss HNPCC families by sequencing the exons and exon/intron boundaries of the hMSH2 and hMLH1 genes. In four families we found different mutations which are expected to lead to protein truncations of either the hMSH2 or the hMLH1 proteins owing to premature in frame stop codons or splice defects. In two more families we detected mutations leading to an amino acid deletion and an amino acid substitution in an evolutionary conserved residues respectively. None of these mutations has been reported in other families, which is consistent with the notion that HNPCC associated hMSH2 and hMLH1 mutations are heterogeneous and there is no striking founder effect in the Swiss population. Whenever this could be investigated, the presence of the mutations was confirmed in other family members who showed manifestations of HNPCC. Interestingly, an obligate carrier in one of the families developed a brain tumour at the age of 29, histologically verified as a glioblastoma multiforme, which was recently linked to HNPCC in the context of Turcot's syndrome.

Adenocarcinoma, Mucinous↗
PubMed1995

Are there any differences in the safety and efficacy of brofaromine and imipramine between non-elderly and elderly patients with major depression?

There is a rather limited database of controlled clinical trials on the comparative effects of antidepressants in elderly and non-elderly depressed patients. A common finding is reduced efficacy and an increased incidence of side effects. To further examine the question of efficacy and safety of antidepressant drugs in elderly versus non-elderly patients, the differential effects of a new selective type A monoamine oxidase inhibitor brofaromine, and the classical tricyclic imipramine were investigated using the data of two recently published trials. We found no major difference between non-elderly and elderly depressed patients as concerns efficacy, total incidence of adverse findings or safety parameters such as laboratory values and heart rate. These results are discussed in the light of some methodological questions and previous reports.

Adolescent↗
PubMed1995

Anticoagulant-induced pseudothrombocytopenia and pseudoleucocytosis.

Pseudothrombocytopenia (PTP) is the phenomenon of falsely low platelet counts due to in vitro platelet clumping in the presence of platelet autoantibodies and anticoagulants. We assessed anticoagulant-dependence, time course of platelet counts and impact of different counter devices on the phenomenon. Blood of 10 persons with previously recognized pronounced EDTA-dependent PTP was collected into 7 different anticoagulants and counted after different intervals in parallel in a Coulter T540 and a Coulter STKS counter and by phase contrast microscopy. With the Coulter T540 model PTP was most pronounced in blood samples anticoagulated with EDTA, Na-oxalate or Na-citrate. In the STKS counter EDTA, heparin and oxalate presented as the worst anticoagulants. The time course of platelet counts was significantly different between the two counters. Our results demonstrate that PTP is not restricted to EDTA, but is also present with other anticoagulants. In contrast, pseudoleucocytosis was observed only in EDTA-anticoagulated blood in the Coulter T540 device. We investigated the expression of platelet integrins and activation antigens on platelets of persons with anticoagulant-dependent PTP and in healthy controls without PTP. In the presence of EDTA the expression of GpIIb/IIIa was significantly reduced in the PTP subjects compared to control. Activation antigens CD62, CD63 and thrombospondin-antigen were upregulated in the presence of EDTA. These alterations in the expression of platelet antigens could also be induced on platelets of normal donors by incubation with sera of PTP subjects and EDTA.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticoagulants↗
PubMed1995

[Cholesterol, HDL-cholesterol, triglycerides and beta-lipoprotein in diabetic pregnancy].

UNLABELLED: Follow up studies regarding lipid metabolism in diabetic pregnancy are important in maternal and fetal morbidity. OBJECTIVE: With this background it is particularly opportune to consider the difference of cholesterol, triglycerides and HDL-cholesterol of diabetics and nondiabetics in pregnancy. In addition the correlation of lipids to the glycosylated hemoglobin (HbA1), White groups and other clinical parameters is of interest. Attention is given to the comparison of insulin dependent diabetics (IDDM) and gestational diabetes (GDM) in the 3rd trimester. PATIENTS: A diabetic group of 84 patients (IDDM, GDM) was used for the prospective study over a two years period. The lipid metabolism was estimated preconceptionally, during pregnancy and on 7th day after delivery. 36 pregnant healthy women served as controls. The information obtained from each patient was entered into an SPSS data base. Statistical analysis were done by Mann-Whitney U and Kruskall-Wallis test and by means of Pearson's correlation coefficient to correlate with age, parity, body mass index, creatinin, albumiuria, HbA1, blood pressure. RESULTS: There were no any correlations between lipid parameters cholesterol, triglycerides, HDL-C, beta-lipoprotein and HbA1 as well as White groups (Pearson's coefficient). The triglyceride levels were significant lower in diabetic pregnants compared with healthy controls (p = 0.0095; Wilcoxon Test); diabetes: mean = 1,831 mmol/l; min 0.35; max 5.99 and control group mean = 2,133 mmol/l; min 0.36; max 4.70. Cholesterol levels were higher in the 3rd trimester of GDM patients than values of IDDM's (p = 0.0017; Wilcoxon Test). The longitudinal study during diabetic pregnancy resulted in significantly progressive increase in cholesterol and triglyceride levels (p = 0.0035 bzw. p = 0.0099; Kruskal-Wallis Test). CONCLUSIONS: Significant lower triglyceride levels had been found in diabetic pregnants than in healthy controls. There was no any correlation between lipid parameters cholesterol, triglycerides, HDL-cholesterol, beta-lipoprotein on the one side and HbA1 and White groups on the other side. Increased cholesterol levels were noted in the 3rd trimester of pregnancy in the gestational diabetes in comparison of insulin dependent pregnant diabetics.

Adolescent↗
PubMed1995

[Diagnosis and therapy of toxoplasmosis infections in pregnancy at the Rostock University Gynecologic Clinic 1986-1994].

Over a period of eight years, 61 patients with toxoplasmosis infection in pregnancy were examined retrospectively at women's hospital. Diagnosis of maternal infection was based on seroconversion, positive IgM, raising IgG--titers above twofold, and very high primary titers in SFT. In 20 patients (32.8%) diagnosis was found with seroconversion. In 15 patients (24.6%) the first examination revealed very high titers (SFT > or = 1:2000, KBR > or + 1:40)> Using a score, time of infection was grouped into: periconceptional (24.59%), 1st Trimester (34.43%) 2nd Trimester (31.14%), 3rd Trimester (4.92%), not specified (4.92%). The latency phase between first suspect titer and treatment did vary markedly. Duration of latency phase was longer than 6 weeks only in 10% and 20% of cases identified via seroconversion or very high titers respectively. Of all cases with different diagnostic attempts 73.9% were treated later than 6 weeks after the first suspect titer. Therapy was performed with either a combination of pyrimethamine-sulfadiacine or spiramycin monotherapy. In 18/53 newborns (33.9%) fetal infections were proven with IgM-detection post partum. Clinical evaluation was normal in 48 children (77.5%). 6 newborns (9.7%) had dilated cerebral ventricles; 3 (4.8%) had irregularly dense intracerebral structures, one newborn (1.6%) had intracerebral calcifications. Primary neurological check-up of the newborn was normal in 91.9%. 2 children (3.2%) had facial paralysis or reduced muscle tonus. In 2 newborns (3.2%) opthalmological examination of the fundus revealed signs of retino-chorioditis.

Adult↗