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Biomedical subjects

F Vogel

Publications and source records attributed to F Vogel.

At least 55 records · Page 3Linked to original sources
PubMed1996

Programs, databases, and expert systems for human geneticists--a survey.

We present an overview of the variety of databases and programs that offer substantial aid to medical and molecular geneticists. Databases and expert systems for genetic diseases and birth defects, programs for segregation and linkage analysis, certain DNA and protein sequence databases, and information resources in general for molecular biology are addressed. These systems cannot be used effectively without the newly developed techniques of information exchange based on international computer networks. A short introduction is given to the Internet and to European institutions and organizations that offer help with the acquisition and use of bioinformatic resources.

Computer Communication Networks↗
PubMed1996

Age increases brain complexity.

This study investigated age-related changes in the human brain function using both traditional EEG analysis (power spectra) and the correlational dimension, a measure reflecting the complexity of EEG dynamics and, probably, the complexity of neurophysiological processes generating the EEG. Assuming that the accumulation of individual experience is determined by the formation of functionally related groups of neurons showing a repetitive synchronous activation (cell assemblies), an increase in the number of such independently oscillating cortical cell assemblies can be expected, despite a decline of some metabolic and memory functions with normal ageing. Thus, the "wisdom of old age' may find its neurophysiological basis in greater complexity of brain dynamics compared to young ages. The experimental hypothesis was that EEG dimension steadily increases with age. In order to test this hypothesis the resting EEGs of 5 age groups from 7 to 60 were analysed. The results confirm the hypothesis: after a jump in the brain dynamics complexity during puberty a linear increase with age is observed. During maturation (7-25 years), the maximum gain in complexity occurs over the frontal associative cortex.

Adolescent↗
PubMed1996

Targeted mutation of plakoglobin in mice reveals essential functions of desmosomes in the embryonic heart.

Plakoglobin (gamma-catenin), a member of the armadillo family of proteins, is a constituent of the cytoplasmic plaque of desmosomes as well as of other adhering cell junctions, and is involved in anchorage of cytoskeletal filaments to specific cadherins. We have generated a null mutation of the plakoglobin gene in mice. Homozygous -/- mutant animals die between days 12-16 of embryogenesis due to defects in heart function. Often, heart ventricles burst and blood floods the pericard. This tissue instability correlates with the absence of desmosomes in heart, but not in epithelia organs. Instead, extended adherens junctions are formed in the heart, which contain desmosomal proteins, i.e., desmoplakin. Thus, plakoglobin is an essential component of myocardiac desmosomes and seems to play a crucial role in the sorting out of desmosomal and adherens junction components, and consequently in the architecture of intercalated discs and the stabilization of heart tissue.

Animals↗
PubMed1995

Sequential therapy in the hospital management of lower respiratory infections.

Conventional treatment for patients hospitalized with lower respiratory infections, such as pneumonia or bronchitis, typically consists of parenteral antibiotic therapy for 7-10 days. The clinical evidence, however, shows that in most patients the objective and subjective indicators of infection are substantially improved within the first 2 days of treatment. Thus, many of these patients can be switched to oral antibiotics after 2-3 days of parenteral therapy, with no loss in efficacy of treatment and with substantial savings in terms of cost of care and length of hospital stay. beta-Lactam antibiotics are a frequent choice for the oral component following short-term intravenous therapy. The results of recent, large-scale comparative clinical trials support the usefulness of this treatment approach, known as sequential therapy.

Administration, Oral↗
PubMed1995

Distinct functions for the two importin subunits in nuclear protein import.

The import of nuclear proteins proceeds through the nuclear pore complex and requires nuclear localization signals (NLSs), energy and soluble factors, namely importin-alpha (M(r) 60K), importin-beta (90K) and Ran. Importin-alpha is primarily responsible for NLS recognition and is a member of a protein family that includes the essential yeast nuclear pore protein SRP1p (ref. 16). As the first event, the complex of importin-alpha and importin-beta binds the import substrate in the cytosol. Here we show that this nuclear pore targeting complex initially docks as a single entity to the nuclear pore via importin-beta. Then the energy-dependent, Ran-mediated translocation through the pore results in the accumulation of import substrate and importin-alpha in the nucleus. In contrast, importin-beta accumulates at the nuclear envelope, but not in the nucleoplasm. Immunoelectron microscopy detects importin-beta on both sides of the nuclear pore. This suggests that the nuclear pore targeting complex might move as a single entity from its initial docking site through the central part of the nuclear pore before it disassembles on the nucleoplasmic side.

Adenosine Triphosphate↗
PubMed1995

Proliferation of intracellular membrane structures upon homologous overproduction of cytochrome P-450 in Candida maltosa.

In an alkane-assimilating yeast, Candida maltosa, a cultivation on alkane causes both induction of endoplasmic reticulum (ER)-resident membrane proteins, such as cytochrome P-450, and proliferation of ER. In this study, individual genes for alkane-inducible forms of cytochrome P-450 (P-450alk) were homologously overexpressed in C. maltosa using a galactose-inducible expression system developed in this yeast. Immunoelectron microscopy revealed that, upon the overexpression, a dramatic proliferation of ER occurred, in which overproduced P-450alk protein accumulated. The proliferated membranes were mainly tubular forms and stacks of paired membranes were also observed after prolonged expression. The tubular forms were morphologically very similar to the proliferated ER in alkane-induced C. maltosa cells. The observed proliferation of ER membranes by homologous overproduction of P-450alk, here depicted, will provide a unique opportunity for investigating the mechanisms by which cells regulate ER biogenesis, in comparison with the intrinsic form of ER proliferation.

Candida↗
PubMed1995

In vivo reconstitution of highly active Candida maltosa cytochrome P450 monooxygenase systems in inducible membranes of Saccharomyces cerevisiae.

To establish a system for functional characterization of individual Candida maltosa cytochrome P450 monooxygenases, the NADPH-cytochrome P450 reductase from this yeast species was co-expressed in Saccharomyces cerevisiae with each of the following cytochrome P450 forms; P450Cm1 (CYP52 A3), P450Cm2 (CYP52 A4), and P450AlK2A (CYP52 A5). For this purpose, a multicopy plasmid was constructed that contained two independent expression units controlled by the galactose-inducible GAL10 promoter. As shown by spectral and immunological methods, large amounts of the desired monooxygenase components could be simultaneously produced in the respective S. cerevisiae transformants. It was important, however, to adjust semi-anaerobic cultivation conditions during induction by galactose to minimize a mutual impairment of cytochrome P450 and NADPH-cytochrome P450 reductase formation. Compared to the specific cellular content of the host-own enzyme, a 75- to 100-fold overproduction of the reductase component was obtained resulting in P450/reductase molar ratios of about 1:3 in the microsomal fractions prepared from the co-expression strains. At the same time, the rates of cytochrome P450-dependent lauric acid hydroxylation increased more than 10-fold, showing a proper reconstitution of the C. maltosa monooxygenase systems in S. cerevisiae. Using intact cells, an efficient biotransformation of lauric acid to omega-hydroxylauric acid and dodecanedioic acid was found. S. cerevisiae cells coexpressing cytochrome P450 and NADPH-cytochrome P450 reductase were characterized by a marked proliferation of the endoplasmic reticulum. Immunoelectron microscopy revealed a colocalization of the monooxygenase components produced to these newly formed membrane structures.

Base Sequence↗
PubMed1995

VIP21-caveolin, a membrane protein constituent of the caveolar coat, oligomerizes in vivo and in vitro.

VIP21-caveolin is a membrane protein, proposed to be a component of the striated coat covering the cytoplasmic surface of caveolae. To investigate the biochemical composition of the caveolar coat, we used our previous observation that VIP21-caveolin is present in large complexes and insoluble in the detergents CHAPS or Triton X-114. The mild treatment of these insoluble structures with sodium dodecyl sulfate leads to the detection of high molecular mass complexes of approximately 200, 400, and 600 kDa. The 400-kDa complex purified to homogeneity from dog lung is shown to consist exclusive of the two isoforms of VIP21-caveolin. Pulse-chase experiments indicate that the oligomers form early after the protein is synthesized in the endoplasmic reticulum (ER). VIP21-caveolin does indeed insert into the ER membrane through the classical translocation machinery. Its hydrophobic domain adopts an unusual loop configuration exposing the N- and C-flanking regions to the cytoplasm. Similar high molecular mass complexes can be produced from the in vitro-synthesized VIP21-caveolin. The complex formation occurs only if VIP21-caveolin isoforms are properly inserted into the membrane; formation is cytosol-dependent and does not involve a vesicle fusion step. We propose that high molecular mass oligomers of VIP21-caveolin represent the basic units forming the caveolar coat. They are formed in the ER and later, between the ER and the plasma membrane, these oligomers could associate into larger detergent-insoluble structures.

Animals↗
PubMed1995

Treatment of acute bacterial exacerbations of chronic obstructive pulmonary disease in hospitalised patients--a comparison of meropenem and imipenem/cilastatin. COPD Study Group.

Meropenem and imipenem/cilastatin were compared in an open, randomised prospective multicentre study in the treatment of acute exacerbations of severe chronic obstructive pulmonary disease in hospitalised patients. One-hundred-and-seventy-three patients were enrolled; 164 were evaluable for clinical efficacy and 98 for bacteriological efficacy, with 144 pathogens isolated. The predominant pathogens were Haemophilus influenzae (n = 30), Streptococcus pneumoniae (18), Staphylococcus aureus (12), Pseudomonas aeruginosa (11), Moraxella catarrhalis (8), other Gram-negative bacteria (Neisseria, Klebsiella, Proteus, and Enterobacter spp.) (53) and other Gram-positive bacteria (12). A single bacterial pathogen was identified in 61 patients, whereas two bacterial pathogens were isolated in 31 patients and three in six patients. The clinical response at the end of treatment was very high in both groups with a satisfactory outcome (cured or improved) in 97.6% of the meropenem patients and in 96.3% of the imipenem/cilastatin patients; at follow-up the rates were 89.1% and 89.8%, respectively. The bacterial success (eradication or presumed eradication) was 88.2% in the meropenem group and 89.4% in the comparator group. Nausea or vomiting were reported more frequently in patients treated with imipenem/cilastatin, whereas in the meropenem group an increase in aminotransferases was reported. One patient treated with imipenem/cilastatin was withdrawn from the study due to seizures. Meropenem and imipenem/cilastatin were highly effective for the treatment of severe bacterial exacerbations of chronic bronchitis but meropenem was better tolerated.

Bacterial Infections↗
PubMed1995

A guide to the treatment of lower respiratory tract infections.

Acute bronchitis is usually a viral infection which, unless there is a special disposition, does not require antibiotic therapy. For the initial oral chemotherapy of bacterial infections of the lower respiratory tract (chronic bronchitis, pneumonia) the effective and well tolerated cephalosporins, macrolides and amoxicillin plus beta-lactamase-inhibitor are recommended. In complicated cases with severe underlying disease, longer history or frequent exacerbations, quinolones should be given if Gram-negative infections are suspected or if initial therapy with other substances has failed. If Legionella, Mycoplasma or Chlamydia spp., so-called 'atypical' pathogens, are involved, macrolide antibiotics are the therapy of first choice. Special attention should be given to the increase in resistance against cotrimoxazole (trimethoprim-sulfamethoxazole) and tetracyclines. In hospitals where primary pneumonias are treated preferentially by intravenous medication, therapy should be switched to oral antibiotics as soon as feasible (follow-up therapy). For severely ill patients with secondary pneumonia and underlying disease, second generation cephalosporins with aminoglycosides, or monotherapy with third generation cephalosporins are recommended. In very severe, high-risk cases, third generation cephalosporins, combinations with high-dosage quinolones or ureidopenicillins plus beta-lactamase-inhibitors are suitable. Future development in the antibiotic treatment of respiratory infections will follow the current trend of lower dosages, with the clear objective of shortening treatment periods and achieving earlier discharge from hospital.

4-Quinolones↗
PubMed1994

[Treatment of lower respiratory tract infections including pneumonia. Comparative study with i.vl cefotaxime/oral cefixime versus parenteral cefotaxime].

METHOD: In this open, randomized and controlled multicenter study involving a total of 100 hospitalized patients with infections of the lower respiratory tract, including pneumonia, the efficacy and tolerability of sequential treatment with cefotaxime i.v./cefixime oral were compared with those of exclusively parenteral treatment with cefotaxime. The patients received either 2 x 2 g cefotaxime i.v. over a period of 7 to 10 days, or 2 x 2 g cefotaxime over a period of 48 to 72 hours followed by oral cefixime treatment (1 x 400 mg/day) for a further 5 to 8 days. RESULTS: A total of 94 patients were evaluated for efficacy; in 93.6% of the evaluable patients in each treatment group, either a cure or improvement was obtained. In four patients in the cefotaxime group and five patients treated first with cefotaxime and then with cefixime, adverse reactions were observed. For three of these adverse reactions (diarrhea, nausea, aggravation of an pre-existing genital mycosis) an association with the respective test substance was considered to be at least possible.

Administration, Oral↗
PubMed1994

Production of monoclonal antibodies against epitopes of the main coat protein of filamentous fd phages.

Three monoclonal antibodies (MAbs) were produced which react with epitopes of the main structural coat protein (pVIII) of filamentous fd phages as demonstrated by solid-phase fluorometric enzyme immunoassays and by immunoelectron microscopy. The antibodies are of the IgG1, IgG2a and IgG2b immunoglobulin subclasses. Since they also react with recombinant phages expressing antigen fragments in their pIII region they may be suitable reagents for the demonstration and isolation of filamentous phages used in recombinant protein technology.

Animals↗
PubMed1994

Hyperventilation-induced changes of blood cell counts depend on hypocapnia.

Voluntary hyperventilation for 20 min causes haemoconcentration and an increase of white blood cell and thrombocyte numbers. In this study, we investigated whether these changes depend on the changes of blood gases or on the muscle work of breathing. A group of 12 healthy medical students breathed 36 l.min-1 of air, or air with 5% CO2 for a period of 20 min. The partial pressure of CO2 decreased by 21.4 mmHg (2.85 kPa; P < 0.001) with air and by 4.1 mmHg (0.55 kPa; P < 0.005) with CO2 enriched air. This was accompanied by haemoconcentration of 8.9% with air (P < 0.01) and of 1.6% with CO2 enriched air (P < 0.05), an increase in the lymphocyte count of 42% with air (P < 0.001) and no change with CO2 enriched air, and an increase of the platelet number of 8.4% with air (P < 0.01) and no change with CO2 enriched air. The number of neutrophil granulocytes did not change during the experiments, but 75 min after deep breathing of air, band-formed neutrophils had increased by 82% (P < 0.025), whereas they were unchanged 75 min after the experiment with CO2 enriched air. Adrenaline and noradrenaline increased by 360% and 151% during the experiment with air, but remained unchanged with CO2 enriched air. It was concluded that the changes in the white blood cell and platelet counts and of the plasma catecholamine concentrations during and after voluntary hyperventilation for 20 min were consequences of marked hypocapnic alkalosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Congenital renal arteriovenous malformation in pregnancy presenting with hypertension.

Congenital renal arteriovenous malformations (AVMs) are rare, with approximately 50 cases reported in the literature. Typically, they are small (1 to 2 cm) and the majority present with hematuria and symptoms and signs of congestive heart failure. Review of the literature revealed only 4 cases reported in pregnant patients and their presentation was with hematuria and rupture of the AVM. We present a case of a young female patient with a 6 cm congenital renal AVM who was otherwise asymptomatic until her first pregnancy, when she developed and presented with symptoms of hypertension and an abdominal bruit. Her symptoms persisted postpartum. Hematuria and rupture of the AVMs were not part of her clinical course. A partial nephrectomy was curative.

Adult↗