PubMed Health⌕ Search

Biomedical subjects

H Müller

Publications and source records attributed to H Müller.

At least 307 records · Page 17Linked to original sources
PubMed1994

Immunohistochemical analysis of cell composition and in situ cytokine expression in HIV- and non-HIV-associated tuberculous lymphadenitis.

Inflammatory cells in lymph nodes of eighteen patients suffering from culture-proven tuberculous lymphadenitis were examined by histological and immunohistochemical techniques. Ten patients suffered from symptomatic HIV-infection and eight patients were immunocompetent individuals without HIV-1 serology. Characteristic granulomas with or without caseation were observed in eight immunocompetent and four HIV-1-infected patients with less marked lymphopenia of CD4 positive peripheral blood lymphocytes. No epitheloid cell formation was present in lymph nodes of HIV1-infected patients with more severe depression of CD4 positive peripheral blood lymphocyte count. Foamy macrophages were found instead of these cells. While many cells--predominantly lymphocytes--express CD25 (IL-2 receptor) in cases with typical epitheloid granulomas there is no such CD25 expression in cases without any epitheloid cell formation. This result suggest that T cell function is necessary for epitheloid granuloma formation in human tuberculosis. The phenotype of macrophages underwent progressive changes parallel to decreasing numbers of CD4 positive peripheral blood lymphocytes. Foamy macrophages in Mycobacterium avium-intracellulare infection represented an end-stage phenotype. They were positive for S100 protein and they did not express lysozyme, alpha-1-anti-chymotrypsin, L1 antigen (Mac387) and CD4, whereas positivity for HLA-DR, CD68 and Ki-M8 was preserved. In situ immunohistochemical demonstration of IFN-alpha, IFN-beta, TNF-alpha, IL-1 and IL-6 revealed that foamy cells in M. tuberculosis infection were highly active effector cells. They contained higher concentrations of the examined cytokines than epitheloid cells in the lesions of HIV+ and HIV-patients. Corresponding to these findings the histological proof of acid-fast bacilli was generally not successful in typical HIV-associated tuberculosis. The foamy appearance may result from the lipid-rich cell membranes of destroyed acid-fast bacilli. In contrast acid-fast bacilli-packed foamy macrophages in AIDS patients with M. avium-intracellulare (MAI) infection did not produce any of the examined cytokines.

AIDS-Related Opportunistic Infections↗
PubMed1994

DNA tumor virus oncoproteins and retinoblastoma gene mutations share the ability to relieve the cell's requirement for cyclin D1 function in G1.

The retinoblastoma gene product (pRB) participates in the regulation of the cell division cycle through complex formation with numerous cellular regulatory proteins including the potentially oncogenic cyclin D1. Extending the current view of the emerging functional interplay between pRB and D-type cyclins, we now report that cyclin D1 expression is positively regulated by pRB. Cyclin D1 mRNA and protein is specifically downregulated in cells expressing SV40 large T antigen, adenovirus E1A, and papillomavirus E7/E6 oncogene products and this effect requires intact RB-binding, CR2 domain of E1A. Exceptionally low expression of cyclin D1 is also seen in genetically RB-deficient cell lines, in which ectopically expressed wild-type pRB results in specific induction of this G1 cyclin. At the functional level, antibody-mediated cyclin D1 knockout experiments demonstrate that the cyclin D1 protein, normally required for G1 progression, is dispensable for passage through the cell cycle in cell lines whose pRB is inactivated through complex formation with T antigen, E1A, or E7 oncoproteins as well as in cells which have suffered loss-of-function mutations of the RB gene. The requirement for cyclin D1 function is not regained upon experimental elevation of cyclin D1 expression in cells with mutant RB, while reintroduction of wild-type RB into RB-deficient cells leads to restoration of the cyclin D1 checkpoint. These results strongly suggest that pRB serves as a major target of cyclin D1 whose cell cycle regulatory function becomes dispensable in cells lacking functional RB. Based on available data including this study, we propose a model for an autoregulatory feedback loop mechanism that regulates both the expression of the cyclin D1 gene and the activity of pRB, thereby contributing to a G1 phase checkpoint control in cycling mammalian cells.

Adenovirus E1A Proteins↗
PubMed1994

Mitochondrial protein import: biochemical and genetic evidence for interaction of matrix hsp70 and the inner membrane protein MIM44.

The import of preproteins into mitochondria involves translocation of the polypeptide chains through putative channels in the outer and inner membranes. Preprotein-binding proteins are needed to drive the unidirectional translocation of the precursor polypeptides. Two of these preprotein-binding proteins are the peripheral inner membrane protein MIM44 and the matrix heat shock protein hsp70. We report here that MIM44 is mainly exposed on the matrix side, and a fraction of mt-hsp70 is reversibly bound to the inner membrane. Mt-hsp70 binds to MIM44 in a 1:1 ratio, suggesting that mt-hsp70 is localizing to the membrane via its interaction with MIM44. Formation of the complex requires a functional ATPase domain of mt-hsp70. Addition of Mg-ATP leads to dissociation of the complex. Overexpression of mt-hsp70 rescues the protein import defect of mutants in MIM44; conversely, overexpression of MIM44 rescues protein import defects of mt-hsp70 mutants. In addition, yeast strains with conditional mutations in both MIM44 and mt-hsp70 are barely viable, showing a synthetic growth defect compared to strains carrying single mutations. We propose that MIM44 and mt-hsp70 cooperate in translocation of preproteins. By binding to MIM44, mt-hsp70 is recruited at the protein import sites of the inner membrane, and preproteins arriving at MIM44 may be directly handed over to mt-hsp70.

Adenosine Triphosphate↗
PubMed1994

Expression and DNA binding of budgerigar fledgling disease virus large T antigen.

Budgerigar fledgling disease virus (BFDV) represents the first non-mammalian member of the polyomavirus genus and possesses uncommon structural and biological properties. Recombinant baculoviruses were constructed to express BFDV small t antigen, large T antigens, as well as a large T deletion mutant Td and beta-galactosidase-Td fusion proteins to high levels in infected insect cells. A recombinant virus containing a genomic copy of the BFDV early region was used for small t antigen expression, and corresponding intron-deleted cDNAs for production of large T antigen derivatives. Recombinant T as well as authentic T antigen proteins from infected chicken embryo fibroblasts were purified using both immunoaffinity and DNA affinity column chromatography. We present evidence that the large T antigen interacts specifically with DNA sequences present in the non-coding region of BFDV; by indirect DNA immunoprecipitation mapping and DNase I footprinting, four regions including 12 DNA-binding sites have been determined that cover most of the BFDV non-coding region. The T antigen binding pattern observed suggests a protein-DNA interaction system considerably different from those of simian virus 40 and other polyomaviruses.

Animals↗
PubMed1994

Host restriction in the productive cycle of avian polyomavirus budgerigar fledgling disease virus type 3 depends on a single amino acid change in the common region of structural proteins VP2/VP3.

The three avian polyomaviruses budgerigar fledgling disease virus types 1 to 3 (BFDV-1 to -3) contain genomes of identical size, 4981 bp. With differences of up to only 15 bp between the three genomes, these viruses show distinct tropism for cultured cells of various avian species: infection of chicken embryo (CE) cells with BFDV-1 and -2 results in virus propagation, whereas BFDV-3 is not replicated; all three viruses replicate, with different efficiencies, in infected Muscovy duck cells. Transfection of CE cells with BFDV-3 DNA results in a single productive cycle. As shown by construction of hybrid virus genomes and site-directed mutagenesis, a single amino acid difference (glycine instead of valine or alanine) within the common region of the minor structural proteins VP2/VP3 is responsible for this type of abortive infection of CE cells. Further experiments indicate a defect in one of the early steps during infection, at or prior to uncoating.

Animals↗
PubMed1994

Colorectal cancer: lessons for genetic counselling and care for families.

Cancers of the colon and the rectum are the second leading cause of malignancy in European countries with similar incidence rates for men and women and, therefore, one of the major health concerns. Emphasis is placed on the early detection of a developing neoplasm in order to improve the life expectancy of patients and their quality of life. Colorectal cancer (CRC) is an excellent model for studying the etiology and pathogenesis of a common malignancy and the complex multistage process of carcinogenesis. Abundant clinical and pathological evidence suggests that CRC arises from benign adenomas that proceed through a series of steps to metastatic carcinomas. Following the discovery of oncogenes and, more importantly tumor suppressor genes, Fearon & Vogelstein (1990) proposed a scheme of genetic events which are associated with colorectal tumorigenesis. Genetic linkage studies have recently identified another type of gene for colon cancer susceptibility that seems to act by destabilising the genome.

Adult↗
PubMed1994

A major Pseudomonas aeruginosa clone common to patients and aquatic habitats.

The genomic relatedness of 573 Pseudomonas aeruginosa strains from environmental and clinical habitats was examined by digesting the genome with the rare-cutting enzyme SpeI. Thirty-nine strains were collected from environmental habitats mainly of aquatic origin, like rivers, lakes, or sanitary facilities. Four hundred fifty strains were collected from 76 patients with cystic fibrosis (CF) treated at four different centers, and 25 additional clinical isolates were collected from patients suffering from other diseases. Twenty-nine P. aeruginosa isolates were collected from the environment of one CF clinic. Thirty strains from culture collections were of environmental and clinic origin. A common macrorestriction fingerprint pattern was found in 13 of 46 CF patients, 5 of 29 environmental isolates from the same hospital, in a single ear infection isolate from another hospital, and 8 of 38 isolates from aquatic habitats about 300 km away from the CF clinic. The data indicate that closely related variants of one major clone (called clone C) persisted in various spatially and temporally separated habitats. Southern analysis of the clonal variants with six gene probes and two probes for genes coding for rRNA revealed almost the same hybridization patterns. With the exception of the phenotypically rapidly evolving CF isolates, the close relatedness of the strains of the clone was also shown by their identical responses in pyocin typing, phage typing, and serotyping. Besides clone C, three other P. aeruginosa clones were isolated from more than one clinical or environmental source.

Cystic Fibrosis↗
PubMed1994

Antibodies of symptomatic human immunodeficiency virus type 1-infected individuals are directed to the V3 domain of noninfectious and not of infectious virions present in autologous serum.

The present study was designed to determine the antibody specificity for the human immunodeficiency virus type 1 (HIV-1) V3 domains of infectious and noninfectious virions present in the serum of AIDS patients. To accomplish this, HIV-1 was isolated in the presence of autologous antibodies from the serum samples of six AIDS patients in HIV-1-negative donor peripheral blood mononuclear cells by short-term cultivation. The isolated virus, defined as the infectious cell-free virus (iCFV), was characterized by sequence analysis of the proviral DNA coding for the third hypervariable (V3) region of the external glycoprotein gp120. This was carried out by amplifying and cloning the V3 region. In all six cases studied, 20 randomly selected V3 clones derived from the proviral DNA of the iCFV, 20 clones from patient cell-free virus, and 20 clones from cell-integrated virus were sequenced to study the distribution and frequency of the intrapatient virus population. The number of major virus variants in the six patients ranged from three to nine. The various V3 sequences found in the AIDS patients showed the typical amino acid pattern of the syncytium-inducing and non-syncytium-inducing viral phenotypes characteristic for the late stage of infection. However, only one patient-specific iCFV variant was detected within the 20 V3 clones analyzed per virus isolation. For the six patients a total of 34 V3-loop variants, either iCFV or non-iCFV, was observed. All 34 V3-loop sequences were expressed as glutathione-S-transferase fusion proteins (V3-GST). The autologous antibody response to the V3-GST fusion proteins was studied by Western immunoblot analysis. A strong antibody response to almost all non-iCFV V3-GST proteins was found in the sera of the six patients. In contrast, the autologous antibody response to the six iCFV V3 loops was undetectable (in four patients) or very faint (in two patients) compared with that to the non-iCFV V3 loops. Five of the six iCFV loops showed positively charged amino acids at positions strongly associated with the syncytium-inducing phenotype. These findings suggest that our in vitro isolation system selects for virions which are not recognized by V3-specific antibodies and are infectious both in vitro and in vivo.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Orthostatic challenge during neuroleptic test dose: a possible predictor of short-term outcome.

Cardiovascular measurements were used as indicators of autonomic arousal during an orthostatic challenge test without medication and after a test dose of 150 mg perazine in 20 acute schizophrenic patients. Unmedicated schizophrenics showed elevated heart rates and elevated systolic and diastolic blood pressure in comparison to healthy volunteers. After a test dose of 150 mg perazine, responders (using BPRS outcome criteria after 23 days) showed a pronounced orthostatic heart rate reaction in comparison to nonresponders. Results are discussed in relation to arousal theories and central dopaminergic activity in schizophrenia.

Adult↗
PubMed1994

[Fetal outcome after local prostaglandin E2 administration in a risk patient group--comparison of morbidity with a normal patient sample].

Intracervical application of prostaglandin E2 gel is considered to be effective in the induction of cervical ripening (priming). Within an 2-years period 244 perinatal risk patients primed with PGE2 were compared with matched paired controls retrospectively. These 244 controls were matched for age, gestational age, parity, birth weight and maternal body mass index and delivered spontaneously. PGE2 gel (Prepidil) was administered intracervically. Basis criteria of perinatal quality, such as neonatal umbilical cord pH and APGAR-score were significantly (p < 0.01) worse in the patients treated with PGE2 gel. In the priming group cord pH was 7.28 (+/- 0.085) and 7.30 (+/- 0.070) in the control group. APGAR 1 min. was found to be 7.56 +/- 1.86 (priming) and 8.18 +/- 1.23 (control); APGAR 5 min. 8.56 +/- 0.90 (priming) and 8.78 +/- 0.54 (control). Contraction disorders, such as hyperactivity and dyscoordination, combined with cardiotocographic pathology was found in 42% (priming) and 19% (control) resp. Severe bradycardia occurred significantly more often in the priming group, whereas no differences were found concerning fever under labor and in puerperium.

Acid-Base Equilibrium↗
PubMed1994

[Expectant management of premature rupture of fetal membranes before completion of the 35th week of pregnancy--retrospective analysis of 44 cases].

44 cases of preterm premature rupture of fetal membranes (PPROM) before 35 completed weeks of gestation were analyzed retrospectively. Expectative management was based on infection diagnosis, vaginal disinfection and in case of signs of infection on systemic antibiotic therapy. Glucocorticoids for induction of lung maturity were generally administered. Perinatal mortality was 11.4%, after exclusion of one congenital anomaly 9.3% respectively. Lung immaturity was the main cause of neonatal death. Only 5 neonates developed clinical infection, with 4 of these showing prepartal maternal signs of infection. Maternal signs of infection are not a specific signal for later neonatal infection. Cerebral bleeding complications and pathological neurologic status occurred in 10/39 and 8/39 cases respectively. Cesarean section rate amounted to 15/44 (34%).

Adolescent↗
PubMed1994

[Results of serological studies of Leptospira antibodies in foxes].

1253 serum samples of foxes were checked for the presence of Leptospira antibodies. 24 serum samples (1.92%) were positive. Leptospira grippotyphosa (10 samples) was the most common serotype, which ist also widespread in other wild and domestic animals. The possibility of distribution of Leptospira in fox populations are discussed. Leptospira antibodies were found in only 0.20% of the examined serum samples of domestic animals of the same territory (South-Thuringia).

Animals↗