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Biomedical subjects

M Meyer

Publications and source records attributed to M Meyer.

At least 343 records · Page 19Linked to original sources
PubMed1995

Consequences of lack of beta 1 integrin gene expression in mice.

beta 1 integrins are cell-surface receptors that mediate cell-cell and cell-matrix interactions. We have generated a null mutation in the gene for the beta 1 integrin subunit in mice and embryonic stem (ES) cells. Heterozygous mice are indistinguishable from normal littermates. Homozygous null embryos develop normally to the blastocyst stage, implant, and invade the uterine basement membrane but die shortly thereafter. Using beta 1 integrin-deficient ES cells we have established chimeric embryos and adult mice. Analysis of the chimeric embryos demonstrated the presence of beta 1 integrin-deficient cells in all germ layers indicating that beta 1-null cells can differentiate and migrate in a context of normal tissue. When evaluated at embryonic day 9.5 (E9.5), embryos with a beta 1-null cell contribution below 25% were developing normally, whereas embryos with a contribution above this threshold were distorted and showed abnormal morphogenesis. In adult chimeric mice beta 1 integrin-deficient cells failed to colonize liver and spleen but were found in all other tissues analyzed at levels from 2%-25%. Immunostaining of chimeric mice showed that in cardiac muscle, there were small, scattered patches of myocytes that were beta 1-null. In contrast, many myotubes showed some beta 1-null contribution as a result of fusion between wild-type and mutant myoblasts to form mixed myotubes. The adult chimeric brain contained beta 1-null cells in all regions analyzed. Also, tissues derived from the neural crest contained beta 1 integrin-deficient cells indicating that migration of neuronal cells as well as neural crest cells can occur in the absence of beta 1 integrins.

Animals↗
PubMed1995

Developmental regulation of full-length trkC in the rat sciatic nerve.

In order to gain insight into potential roles of neurotrophins in Schwann cell biology, the expression of neurotrophin receptors of the trk gene family was investigated in rat sciatic nerve development. This analysis revealed differential regulation of truncated and full-length receptors. TrkA was undetectable even when analysed with a sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) method. TrkB was present at the mRNA as well as protein level only in its truncated form. Surprisingly, multiple isoforms of trkC, including full-length forms, were detected in early postnatal nerve. Specific antibodies detected truncated and full-length trkC proteins in Western blotting, and RT-PCR revealed the presence of two full-length isoforms, one of them containing the 14 amino acid kinase insert. In situ hybridisation localized the expression of trkC to a subpopulation of Schwann cells. TrkC receptors are expressed already in nerves from day-16 embryos. In contrast to early postnatal stages, full-length trkC receptors are no longer expressed in adult nerves, which, however, maintain expression of truncated trkC transcripts. The presence of trkC kinases in peripheral nerve suggests a role for neurotrophin-3, the only known trkC ligand, in peripheral nerve development.

Animals↗
PubMed1995

Femtosecond infrared spectroscopy of reaction centers from Rhodobacter sphaeroides between 1000 and 1800 cm-1.

Time-resolved pump-and-probe experiments of reaction centers of the purple bacterium Rhodobacter sphaeroides (R26) in the mid-IR region between 1000 and 1800 cm-1 are recorded with a time resolution of 300-400 fs. The difference spectra of the states P*, P+HA-, and P+QA- with respect to the ground state P predominantly reflect changes of the special pair. They show positive and negative bands due to changes of distinct vibrational modes superimposed on a broad background of enhanced absorption. A number of certain bands can be assigned to the special pair P, to the bacteriopheophytin HA, and to the quinone QA. The temporal evolution of the IR absorbance changes is well described by the time constants known from femtosecond spectroscopy of the electronic states. Differences occur only at very early times, which are indicative of fast vibrational relaxation with a time constant of a few hundred femtoseconds.

Kinetics↗
PubMed1995

Positron emission tomography measures of benzodiazepine binding in Alzheimer's disease.

OBJECTIVE: To evaluate the integrity of neurons and neuropil in metabolically affected association cortices of patients with Alzheimer's disease by measuring central benzodiazepine binding sites with the use of positron emission tomography. DESIGN: In patients with Alzheimer's disease, we determined the cerebral distribution of flumazenil tagged with carbon 11 ([11C]flumazenil), a ligand that binds to the gamma-aminobutyric acid A (GABAA) receptor complex, and the distribution of fludeoxyglucose tagged with fluorine 18 fludeoxyglucose F 18), a measure of local cerebral glucose metabolism. Tracer kinetic analysis was applied to quantify data in regions of interest. These data were compared with those of normal control subjects. SUBJECTS: Patients with probable Alzheimer's disease ([11C]flumazenil, n = 13; fludeoxyglucose F 18, n = 11) and normal elderly control subjects ([11C]flumazenil, n = 6; fludeoxyglucose F 18, n = 10). RESULTS: Significant decreases of the [11C]flumazenil transport rate were found in hypometabolic parietal and temporal association cortices, but [11C]flumazenil binding was not significantly decreased. CONCLUSIONS: When measured in living patients, association cortical benzodiazepine binding sites are relatively preserved, suggesting structurally intact cortical neuropil underlying the glucose hypometabolism identified in Alzheimer's disease.

Aged↗
PubMed1995

The nickel resistance determinant cloned from the enterobacterium Klebsiella oxytoca: conjugational transfer, expression, regulation and DNA homologies to various nickel-resistant bacteria.

Klebsiella oxytoca strain CCUG 15788, isolated from a mineral oil emulsion tank in Göteborg, Sweden, was found to be nickel-resistant (tolerating 10 mM NiCl2 in non-complexing mineral-gluconate media; inducible resistance). The nickel resistance determinants were transferred by helper-assisted conjugation to various strains of Escherichia coli and Citrobacter freundii and expressed to between 5 and 10 mM NiCl2. A 4.3 kb HindIII fragment was cloned from the genomic DNA of K. oxytoca. Ligated into the vector pSUP202, the fragment caused constitutive nickel resistance (of up to 3 or 10 mM Ni2+) in various E. coli strains. After cloning into the broad host range vector pVDZ'2 the fragment even expressed low nickel resistance in the transconjugant of Alcaligenes eutrophus AE104. With the 4.3 kb HindIII fragment as a biotinylated DNA probe it was shown by DNA-DNA hybridization that the nickel resistance determinant resides on the chromosome of K. oxytoca and not on its circular plasmid pKO1 (160 kb) or linear plasmid pKO2 (50 kb). Nickel resistance strongly correlated with the presence of the 4.3 kb HindIII fragment in the transconjugants. No homologies were detected when the nickel resistance determinants of other well-known nickel-resistant bacteria, such as A. eutrophus CH34 or A. denitrificans 4a-2, were used as target DNA. Among the 60 strains examined, positive signals only appeared with the 3.1 kb DNA fragment from A. xylosoxydans 31A and the genomic DNA of two enterobacterial strains (5-1 and 5-5) isolated from nickel-rich soil in New Caledonia.

Cloning, Molecular↗
PubMed1995

The role of pulmonary CO2 flow in the control of the phase I ventilatory response to exercise in humans.

To gain an insight into the origin of the phase I ventilatory response to exercise (ph I) in humans, pulmonary ventilation (VE) and end-tidal partial pressures of oxygen and carbon dioxide (PETO2 and PETCO2, respectively) were measured breath-by-breath in six male subjects during constant-intensity exercise on the cycle ergometer at 50, 100 and 150 W, with eupnoeic normocapnia (N) or hyperpnoeic hypocapnia (H) established prior to the exercise test. Cardiac output (Qc) was also determined beat-by-beat by impedance cardiography on eight subjects during moderate exercise (50 W), and the CO2 flow to the lungs (Qc.Cv-CO2 where Cv-CO2 is concentration of CO2 in mixed veneous blood) was estimated with a time resolution of one breathing cycle. In N, the initial abrupt increase of VE during ph I (delta VE approximately 18 1.min-1 above rest) was followed by a transient fall. When PETCO2 started to increase (and PETO2 decreased) VE increased again (phase II ventilatory response, ph II). In H, during ph I delta VE was similar to that of N. By contrast, during ph II delta VE kept gradually decreasing and started to increase only when PETCO2 had returned to approximately 40 mmHg (5.3 kPa). Thus, as a result of the prevailing initial conditions (N or H) a temporal shift of the time-course of VE during ph II became apparent. No correlation was found between CO2 flow to the lungs and VE during ph I. These results are interpreted as suggesting that an increased CO2 flow to the lungs does not constitute an important factor for the initial hyperventilatory response to exercise. They are rather compatible with a neural origin of ph I, and would support the "neurohumoral" theory of ventilatory control during exercise.

Adult↗
PubMed1995

Primary structure and sequence analysis of RNA2 of a mechanically transmitted barley mild mosaic virus isolate: an evolutionary relationship between bymo- and furoviruses.

The RNA2 nucleotide sequence of a mechanically transmitted isolate of barley mild mosaic virus (BaMMV) has been determined. A combination of Northern blot and sequence analysis indicates that this RNA2 lacks approximately 1000 nucleotides of its C-terminal protein (P2) gene, with respect to Polymyxa graminis transmitted BaMMV. This is confirmed by sequence comparison with RNA2 of a fungus transmitted BaMMV isolate, which reveals the presence of a single deletion located in the 3'-terminal part of the P2 gene. As a consequence, this RNA2 codes for a P2 protein of only 34 K. Sequence homology between the bymovirus P2 protein and the capsid readthrough protein of beet necrotic yellow vein virus and soil-borne wheat mosaic virus suggests an evolutionary relationship between bymo- and furoviruses.

Amino Acid Sequence↗
PubMed1995

[Urodilatin. Use of a new peptide in intensive care].

On the subject of natriuretic peptides there is a great deal of controversy, and intensive research efforts have been made studying their effects on electrolyte homeostasis. In the early 1980s, a peptide that caused diuresis, natriuresis, and had a relaxant effect on vascular smooth muscle was discovered independently by several groups. This was the breakthrough for the identification of natriuretic peptides, followed by the characterisation of the amino-acid sequences of several species. Synthesis of the peptide, cloning of the encoding gene, identification and characterisation of specific receptors, as well as the development of antibodies and radioimmuno-assays were rapidly accomplished. Research on the immunohistochemistry of cardiodilatin/atrial natriuretic peptide (CDD/ANP) and the regulation of CDD/ANP gene expression led to detection of the peptide in extra-atrial tissues. Later on, two new peptides were discovered brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP). These peptides share structural features with CDD/ANP with regard to their 17-amino-acid-exhibiting loop bridged by a disulfide bond. Another recently discovered peptide is urodilatin (URO), a renal-borne new member of A-type natriuretic peptide. URO was isolated from human urine and consists of the same sequence as CDD/ANP, containing the 17-amino-acid residue loop of the circulating hormone with 4 additional amino acids located at the NH2-terminus of the peptide. Regarding physiological actions, data strongly support a close association between URO and urinary sodium excretion. The application of URO in animals revealed a stronger diuresis and natriuresis with a lower influence on arterial blood pressure compared to CDD/ANP-99-126. These results were encouraging for the use of URO in clinical trials as a tool to prevent acute renal failure (ARF) in patients following heart transplantation and for treatment of incipient ARF in patients following liver transplantation. Summarising the results of these two studies, URO represents a new approach for not only prevention, but also for treatment of ARF following organ transplantation. This opens up new possibilities for the treatment of ARF of other origins in intensive care medicine.

Acute Kidney Injury↗
PubMed1995

Prenylated isoflavanone from Erythrina eriotricha.

Bioassay-directed fractionation of a methylene chloride extract of the root bark of Erythrina eriotricha resulted in the isolation of a novel isoflavanone, named eriotrichin B, and the five known pterocarpans, isonorautenol, erybraedin A, erybraedin C, erybraedin D and erybraedin E. The structure of the new compound has been investigated by extensive spectroscopic studies, including 2D NMR and chemical evidence. The in vitro antimicrobial spectrum and potencies of the isolated compounds are also reported.

Anti-Bacterial Agents↗
PubMed1995

Technique for the digital imaging of histopathologic preparations of eyes for research and publication.

BACKGROUND: Although there are excellent techniques to photograph gross ocular pathology specimens, it is difficult to view or photograph the entire eye from a glass slide using equipment designed for photomicrography. This investigation was initiated to develop a technique to image the entire eye from a glass slide. METHODS: The glass histopathologic slide, placed in a carrier intended for 35-mm film transparencies, is inserted into a 35-mm slide scanner. The glass slide is scanned, creating a digital color image which may be converted to black and white with enhancement of certain histologic features. One may use a digital film recorder to produce 35-mm photographic transparencies or a dye sublimation printer to produce high-resolution color or black and white prints. RESULTS: More than 400 ocular whole-mount preparations have been digitized in the authors' laboratory to generate illustrations suitable for publication or for analysis in morphologic research. CONCLUSION: Digital techniques provide easier control over density and contrast than conventional photographic methods. Digitized images are well-suited for morphologic analyses in research. These techniques allow one to publish black and white photographs for books or journals while retaining the original color image for potential CD-ROM editions.

Eye↗
PubMed1995

A preliminary comparison of two perennially ice-covered lakes in Antarctica: analogs of past Martian lacustrine environments.

Perennially ice-covered lakes in the Antarctic have been suggested as analogs to lakes which may have existed on the surface of Mars 3.5 billion years ago. During the 1991-1992 austral summer, a joint Russian/American research effort was directed at studies of ice-covered lakes in the Bunger Hills Oasis, Antarctica (66 degrees S, 100 degrees E). The primary objective of the expedition was to investigate this ice-free area for features analogous to ancient martian environments that may have been capable of supporting life and to compare the ice-covered lakes of the Bunger Hills with those in the McMurdo Dry Valleys of southern Victoria Land (77 degrees S, 166 degrees E) as part of the continuing studies of Antarctic-Mars analogs.

Antarctic Regions↗
PubMed1995

[Age specific and age corrected mortality in gynecological carcinoma--including breast carcinoma].

Quality of life and life span are parameters which characterise a successful tumour diagnosis and therapy. We found out that the age-specific death rate and standardised death rate concerning gynaecological cancers and carcinoma of the breast in Bavaria increased and we compared different years. The standardized mortality ratio increased between 1977 and 1990 from 91 to about 108% Neither diagnostics using update equipment nor an individualised therapy improved the situation. The slightly increasing incidence rate does not explain the present rate of deaths in cancer. An important factor is the younger age and the endocrine situation of women at the time of the primary disease. 50% of our patients are less than 55 years old and pre- or perimenopausal. Estrogen-gestagen combinations used in contraceptives and hormone replacement therapy (HRS) seem to have a stimulating effect (Henderson). The significant decrease in cervical cancer is encouraging, but does not compensate the increase in breast cancer. No significant change is seen in ovarian cancer.

Aged↗
PubMed1995

Regulation of anaerobic citrate metabolism in Klebsiella pneumoniae.

Three enzymes are specifically required for uptake and catabolism of citrate by Klebsiella pneumoniae under anaerobic conditions: a Na+ -dependent citrate carrier (CitS), citrate lyase (CitDEF), and the Na+ pump oxaloacetate decarboxylase (OadGAB). The corresponding genes are clustered on the chromosome, with the citCDEFG genes located upstream and divergent to the citS-oadGAB genes. We found that expression of citS from its native promoter in Escherichia coli requires the DNA region downstream of oadB. Nucleotide sequence analysis of this region revealed the presence of two adjacent genes, citA and citB. By sequence similarity, the predicted CitA and CitB proteins were identified as members of the two-component regulatory systems. The sensor kinase CitA contained, in the N-terminal half, two putative transmembrane helices which enclosed a presumably periplasmic domain of about 130 amino acids. The C-terminal half of the response regulator CitB harboured a helix-turn-helix motif typical of DNA-binding proteins. K. pneumoniae citB null mutants were unable to grow anaerobically with citrate as the sole carbon and energy source (Cit- phenotype). When cultivated anaerobically with citrate plus glycerol, all of the citrate-specific fermentation enzymes were synthesized in the wild type, but not in the citB mutants. This showed that citS, oadGAB and citDEF required the CitB protein for expression and therefore are part of a regulon. In the wild type, synthesis of CitS, oxaloacetate decarboxylase and citrate lyase was dependent on the presence of citrate, sodium ions and a low oxygen tension. In a citA null mutant which expressed citB constitutively at high levels, none of these signals was required for the formation of the citrate fermentation enzymes. This result suggested that citrate, Na+, and oxygen exerted their regulatory effects via the CitA/CitB system. In the presence of these signals, the citAB gene products induced their own synthesis. The positive autoregulation occurred via co-transcription of citAB with citS and oadGAB.

Aconitate Hydratase↗
PubMed1995

Retrospective case-control study of diffusely adhering Escherichia coli and clinical features in children with diarrhea.

A retrospective case-control study with a small population group revealed that, among clinical signs, vomiting but not diarrhea was significantly associated with the presence of diffusely adhering Escherichia coli (DAEC) in children suffering from gastroenteritidis (P < 0.05). Of the children carrying DAEC strains, those who were F1845 DNA probe positive had a significantly longer hospital stay than those who were F1845 DNA probe negative. We believe that the heterogeneity of DAEC strains is responsible for the discrepant results concerning their involvement in disease and that only some of these strains are really pathogenic for children.

Adolescent↗
PubMed1995

Phosphodiesterase isoenzymes in human ureteral smooth muscle: identification, characterization, and functional effects of various phosphodiesterase inhibitors in vitro.

Phosphodiesterases (PDE) are key enzymes regulating intracellular cyclic nucleotide metabolism and, thus, contraction and relaxation of the muscle. At present, five different families of isoenzymes of PDE exist that show a distinct species-specific and organ-specific distribution. The aim of the present study was to analyze the PDE isoenzymes present in the human ureter and to evaluate the functional effects of isoenzyme-specific inhibitors in this tissue. Normal ureteral tissue was obtained during radical nephrectomies, homogenized, centrifuged, and the supernatant fraction was separated using DEAE-Sephacel anion-exchange chromatography. PDE assay was then performed and the isoenzymes characterized on the basis of their kinetic characteristics and their sensitivity to allosteric modulators and inhibitors. In vitro, longitudinal ureteral strips as well as ureteral rings were precontracted, and different selective and nonselective PDE inhibitors were added incrementally. Three different PDE isoenzymes were identified: PDE I (Ca/calmodulin-stimulated), PDE II (cyclic guanosine monophosphate-stimulated), and PDE IV (cyclic adenosine monophosphate-specific). All PDE inhibitors relaxed the strips dose-dependently with an EC50 of 30 microM for papaverine, 40 microM for zaprinast, 25 microM for quazinone, and 0.1 microM for rolipram. The existence of three different PDE isoenzymes was shown in this study. The ureter-relaxing effect of the PDE IV inhibitor at low concentrations, combined with its low effect on the systemic circulatory parameters, may open a possibility of using selective PDE IV inhibitors in the treatment of ureteral colics or ureteral stones.

Chromatography, Ion Exchange↗