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Biomedical subjects

A Friedrich

Publications and source records attributed to A Friedrich.

At least 37 records · Page 2Linked to original sources
PubMed2000

comB, a novel competence gene required for natural transformation of Acinetobacter sp. BD413: identification, characterization, and analysis of growth-phase-dependent regulation.

Here we describe five tandemly arranged and converging ORFs in Acinetobacter sp. BD413, namely lytB, orfY, orfX, comB, and orfZ, located upstream of the previously identified competence gene comC. The N-termini of the deduced proteins OrfY and ComB exhibit the conserved endopeptidase cleavage motifs of prepilin proteins; the deduced protein ComB is similar to type IV pilins. LytB is similar to the Escherichia coli LytB, which has been implicated in the stringent response. No homologues of OrfX, OrfY and OrfZ could be identified. A mutation in orfY or orfZ led to 100-fold reduced transformation frequencies and a mutation in comB resulted in a non-competent phenotype. Disruption of lytB did not affect the natural transformation phenotype. Complementation studies clearly demonstrated that comB is involved in natural transformation, whereas the transformation-deficient phenotypes of orfY and orfZ mutants were due to polar effects on comB and comC, respectively. Analyses of the twitching motility phenotype and of the ultrastructure of the noncompetent comB mutant suggested that the competence gene comB is not essential for the biogenesis of type IV pili and expression of the type IV pili-associated property of twitching motility. Transcriptional fusions between comB and a promoter-free lacZ gene were constructed, and analysis of growth-phase-dependent transcription revealed increased expression of comB during prolonged exponential and stationary phases.

ATP-Binding Cassette Transporters↗
PubMed2000

Functional expression of the serotonin transporter in immortalized rat brain microvessel endothelial cells.

There is evidence from recent studies that the brain endothelium (of capillaries and/or larger vessels) may serve as a specific target for serotonin [5-hydroxytryptamine (5-HT)]. This neurotransmitter is expected to be involved in the regulation of the blood-brain barrier (BBB) permeability and/or of the cerebral blood flow via receptor-mediated mechanisms. Effective control of these processes depends on a speedy uptake and metabolism of released 5-HT molecules. To realize this, a similar mechanism of 5-HT uptake as in brain may exist at the BBB. In this study, we have demonstrated using RT-PCR that 5-HT transporter mRNA is present in the brain endothelium and that a saturable transport system for 5-HT is functionally expressed in immortalized rat brain endothelial cells (RBE4 cells). These cells take up [3H]5-HT by an active saturable process with a Km value of 397 +/- 64 nmol/L and a transport capacity of 51.7 +/- 3.5 pmol x g(-1) x min(-1). The 5-HT uptake depends on Na+, as indicated by the replacement of NaCl by LiCl. The 5-HT uptake was sensitive to specific 5-HT transport inhibitors such as paroxetine, clomipramine, fluoxetine, and citalopram but not to inhibitors of the vesicular amine transporter such as reserpine or tetrabenazine. Our results demonstrate that cerebral endothelial cells are able to participate actively in the removal and metabolism of the released 5-HT, which supports the concept of direct serotoninergic regulation of the BBB function.

Animals↗
PubMed2000

Differential distribution of novel restriction-modification systems in clonal lineages of Neisseria meningitidis.

Using representational difference analysis, we isolated novel meningococcal restriction-modification (R-M) systems. NmeBI, which is a homologue of the R-M system HgaI of Pasteurella volantium, was present in meningococci of the ET-5 complex and of lineage III. NmeAI was found in serogroup A, ET-37 complex, and cluster A4 meningococci. NmeDI was harbored by meningococci of the ET-37 complex and of cluster A4, but not by serogroup A meningococci. Two of the R-M systems, NmeBI and NmeDI, were located at homologous positions between the phenylalanyl-tRNA synthetase genes pheS and pheT, which appeared to be a preferential target for the insertion of foreign DNA in meningococci. The distribution of the three R-M systems was tested with 103 meningococcal strains comprising 49 sequence types. The vast majority of the strains had either NmeBI, NmeAI, or both NmeAI and NmeDI. Using cocultivation experiments, we could demonstrate that NmeBI, which was present in ET-5 complex meningococci, was responsible for a partial restriction of DNA transfer from meningococci of the ET-37 complex to meningococci of the ET-5 complex.

Clone Cells↗
PubMed2000

Transport of N-acetylaspartate by the Na(+)-dependent high-affinity dicarboxylate transporter NaDC3 and its relevance to the expression of the transporter in the brain.

N-Acetylaspartate is a highly specific marker for neurons and is present at high concentrations in the central nervous system. It is not present at detectable levels anywhere else in the body other than brain. Glial cells express a high-affinity transporter for N-acetylaspartate, but the molecular identity of the transporter has not been established. The transport of N-acetylaspartate into glial cells is obligatory for its intracellular hydrolysis, a process intimately involved in myelination. N-Acetylaspartate is a dicarboxylate structurally related to succinate. We investigated in the present study the ability of NaDC3, a Na(+)-coupled high-affinity dicarboxylate transporter, to transport N-acetylaspartate. The cloned rat and human NaDC3s were found to transport N-acetylaspartate in a Na(+)-coupled manner in two different heterologous expression systems. The Michaelis-Menten constant for N-acetylaspartate was approximately 60 microM for rat NaDC3 and approximately 250 microM for human NaDC3. The transport process was electrogenic and the Na(+):N-acetylaspartate stoichiometry was 3:1. The functional expression of NaDC3 in the brain was demonstrated by in situ hybridization and reverse transcription-polymerase chain reaction as well as by isolation of a full-length functional NaDC3 from a rat brain cDNA library. In addition, the expression of a Na(+)-coupled high-affinity dicarboxylate transporter and the interaction of the transporter with N-acetylaspartate were demonstrable in rat primary astrocyte cultures. These studies establish NaDC3 as the transporter responsible for the Na(+)-coupled transport of N-acetylaspartate in the brain. This transporter is likely to be an essential component in the metabolic role of N-acetylaspartate in the process of myelination.

Animals↗
PubMed1999

The Ground State Rotational Spectra of HDCO and D2CO.

The ground state rotational spectra of HDCO and D2CO have been measured from 5 to 2000 GHz. These new measurements together with older ones have been fitted to a standard A-reduced Watson-type Hamiltonian. The accuracy of the rotational and centrifugal distortion constants has been significantly improved. It has to be noted that it was necessary to include octic constants. The experimental constants are compared to ab initio predictions. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Long-term outcome in children with fractures of the proximal femur after high-energy trauma.

BACKGROUND: Fractures of the femoral head and neck in children have a risk of severe complications, especially femoral head necrosis. We performed a long-term follow-up study of patients treated at our institution. METHODS: Patients were reexamined at least 3 years after trauma and were included if they were younger than 17 years old at the time of injury, if there was no history of previous fracture, and if there was no history of underlying bone disease. Fractures were classified according to Delbet, and outcome was graded according to Ratliff. Anterior capsulotomy was not performed, and stabilization devices were placed short of the epiphysis except for type I fractures. RESULTS: Of 32 patients, 28 were reexamined. Among these patients, the mean age at the time of injury was 11.8 years and the mean follow-up time was 11.1 years (range, 3-21 years). There were 3 patients with type I fractures, 8 patients with type II fractures, 12 patients with type III fractures, and 5 patients with type IV fractures. Thirteen patients had Injury Severity Scores > 18. At last follow-up, 20 patients presented with good function, 5 with fair outcome, and 3 with poor results; all of the latter suffered type I fractures. Eighteen patients had no restrictions in activities of daily living or during sports activities. In six other patients, the inability to participate in sports was attributable to head trauma, amputation, or peripheral neurologic damage. CONCLUSION: We found favorable long-term outcome in type II to type IV fractures. In these patients, restrictions of function were usually caused by other associated injuries. All patients with type I fractures presented with poor outcome secondary to their proximal femoral fractures, and not because of other associated injuries. Type I fractures during childhood and adolescence represent an unsolved problem.

Accidents↗
PubMed1997

Development of the neonatal rabbit retina in organ culture. 1. Comparison with histogenesis in vivo, and the effect of a gliotoxin (alpha-aminoadipic acid).

Organ cultures from neonatal rabbit retinae grew well over periods of up to 2 weeks in vitro. Proliferation in vitro declined in parallel with the decline seen in vivo, although the rate of proliferation in the explants was slightly reduced. The proliferation of progenitor cells in vitro produced the same cell types produced postnatally in vivo. Postnatally generated cell clones, labeled by means of a retroviral vector, consisted mainly of rods and Müller cells. The layers of the retinae developed as in vivo; an outer plexiform layer occurred after the first 2 days in vitro. Ultrastructurally, ribbon synapses (outer and inner plexiform layer) and conventional synapses (inner plexiform layer) were observed. The photoreceptor cells grew well-developed inner segments and cilia but no mature outer segments. The cultured retinae contained a well-developed, regular lattice of Müller cells expressing vimentin as in vivo. The neuron-to-Müller cell-ratios were essentially the same as in vivo, viz. about 15 to 16 neurons, among them about 10 to 11 (rod) photoreceptor cells per Müller cell. When the glia cell-specific toxin alpha-aminoadipic acid (alpha AAA) was applied, the pattern of vimentin-positive Müller cells became irregular, or even locally missing. In such cases, the tissue became disorganized as indicated by a local disappearance of the regular layering, and development of many rosettes. It is concluded that an intact lattice of Müller cells is necessary for the migration of young neurons, and for correct formation of retinal layers.

2-Aminoadipic Acid↗
PubMed1997

Is endogenous erythropoietin a pathogenetic factor in the development of essential hypertension?

BACKGROUND: Recent experimental studies have found that erythropoietin elicits vasoconstriction and proliferation of endothelial cells. We conducted the following study to assess the possible interactions between endogenous erythropoietin, systemic and renal haemodynamics at different stages of essential hypertension. METHODS: We examined 47 patients with borderline essential hypertension (age 26 +/- 3 years) and 49 patients with established essential hypertension WHO stage I-II (age 52 +/- 10 years), and compared them to 42 normotensive individuals (age 26 +/- 3 years). The concentration of erythropoietin (radioimmunoassay), 24-h ambulatory blood pressure (Spacelab 90207), systemic haemodynamics (Doppler sonography) and renal haemodynamics (para-aminohippuric acid and inulin clearance) were determined. RESULTS: Erythropoietin was within normal range and similar among the three groups. In patients with established essential hypertension, a close correlation was found between erythropoietin and systolic (r = 0.45, P < 0.002) and diastolic (r = 0.51, P < 0.001) ambulatory blood pressure. In contrast, ambulatory blood pressure was not correlated with erythropoietin in subjects with borderline hypertension. Total peripheral resistance (r = 0.41, P < 0.02) was linked to erythropoietin in established but not in borderline hypertension. However, erythropoietin was inversely correlated with renal plasma flow in both established and borderline hypertension (r = -0.33, P < 0.05, and r = -0.34, P < 0.05 respectively). In normotensive subjects, in contrast, erythropoietin was not correlated with any of the determined variables. In neither group erythropoietin was linked to the haematocrit or hemoglobin concentration. CONCLUSION: The correlation between erythropoietin and renal vascular changes which is already present in borderline hypertension and is confirmed in established hypertension indicates an involvement of erythropoietin in the development of essential hypertension. The presence of normal concentrations of endogenous erythropoietin in all groups suggests a dysregulation of erythropoietin in patients with essential hypertension as the pathophysiological link between erythropoietin and vascular changes.

Adult↗
PubMed1997

The Pai-associated leuX specific tRNA5(Leu) affects type 1 fimbriation in pathogenic Escherichia coli by control of FimB recombinase expression.

The uropathogenic Escherichia coli strain 536 (06:K15:H31) carries two large chromosomal pathogenicity islands (Pais). Both Pais are flanked by tRNA genes. Spontaneous deletion of Pai II results in truncation of the leuX tRNA5Leu gene. This tRNA is required for the expression of type 1 fimbriae (Fim) and other virulence factors. Transcription of fimA, encoding the major type 1 fimbrial subunit is controlled by an invertable DNA switch. The inversion is catalysed by two recombinases, FimB and FimE. FimB is able to turn the switch on, FimE only off. The fimB gene of strain 536 contains five TTG codons recognized by tRNA5Leu, fimE contains only two. It was proposed that turning on the fim switch requires efficient translation of FimB, in turn requiring tRNA5Leu. Strains in which the TTG codons in fimB were replaced with CTG codons at the wild-type locus were able to produce type 1 fimbriae in the absence of leuX. fimB transcription was influenced by the presence of leuX, but only slightly affected by the presence or absence of leuX codons in fimB. FimB translation was significantly higher from codon-replaced fimB genes than that of wild-type fimB genes in various strain backgrounds. The fim switch was shown to be switched off in leuX-derivatives of E. coli 536, but could be found in the on position when the codon-altered fimB gene was exchanged into the chromosome of these strains. From these data, it is apparent that tRNA5Leu is required for efficient translation of FimB, in turn, leading to type 1 fimbrial expression.

Bacterial Proteins↗
PubMed1996

Angiotensin II related to sodium excretion modulates left ventricular structure in human essential hypertension.

BACKGROUND: Urinary sodium excretion and angiotensin II (Ang II), which are linked in a physiological feedback mechanism, have both been described to be blood pressure-independent determinants of left ventricular hypertrophy in essential hypertension. We conducted a study to investigate the interaction of sodium excretion with Ang II and its potential impact on myocardial hypertrophy. METHODS AND RESULTS: Sixty-eight patients (46 men and 22 women; mean age, 52 +/- 10 years) with untreated World Health Organization stage I to II essential hypertension were examined in a cross-sectional study. Left ventricular structure and function (two-dimensionally guided M-mode echocardiography), dietary sodium intake (as estimated by 24-hour urinary sodium excretion), and noninvasive ambulatory blood pressure over 24 hours (Spacelab 90207) were determined in parallel with plasma renin activity and plasma Ang II and serum aldosterone concentrations (radioimmunoassay). Twenty-four-hour urinary sodium excretion emerged as a strong correlate of relative wall thickness independent of 24-hour ambulatory blood pressure (partial r = .49, P < .001). Ang II concentrations were weakly correlated with septal wall thickness (r = .27, P < .05) and left ventricular mass (r = .25, P < .05). Patients with high Ang II concentrations in relation to sodium excretion had a greater left ventricular mass (318 +/- 77 versus 257 +/- 54 g, P < .02), posterior wall thickness (11.8 +/- 1.9 versus 10.5 +/- 0.8 mm, P < .02), and septal wall thickness (13.6 +/- 1.8 versus 11.9 +/- 1.3 mm, P < .01) than those with "relatively low" Ang II levels in relation to sodium excretion. CONCLUSIONS: Impaired suppression of the renin-Ang II system appeared to act as a stimulus for myocardial hypertrophy in hypertensive patients.

Adult↗
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

[Detection of mixed lymphoid chimerism after allogeneic bone marrow transplantation: demonstration by interphase cytogenetics in paraffin-embedded tissue].

In bone marrow transplantation (BMT) the detection of residual host lymphoid or haematopoietic cells surviving conditioning therapy is because of its association to graft-versus-host disease, graft-versus-leukemia reaction, and relapse of leukemia a matter of great interest. We studied the occurrence of this mixed lymphoid chimerism (MC) in the formol-fixed lymphatic tissue of lymph nodes and spleen from 21 autopsies after allogeneic sex-mismatched BMT (5 females, 16 males, survival 5 to 1140 days after BMT). In situ hybridisation with biotinylated centromer-specific anti-X- and anti-Y-chromosome probes was performed on pepsin-digested paraffin sections. The number of double X-, single X-, and Y-chromosome bearing cells was analysed microscopically. Because of artefacts only 14 cases remained for valid investigation. MC was detected in 6 cases (5 out of 11 males 5 days to 840 days and 1 out of 3 females 76 days after BMT). MC occurred after whole body irradiation with 10 Gy (n = 5) and 7 Gy (n = 1). In 1 autopsy relapse of leukemia caused host cell infiltration. Cases with MC did not express histological signs of acute or chronic graft-versus-host disease, but 5 out of 8 with complete lymphoid chimerism did. The sensitivity of interphase cytogenetics on paraffin embedded tissue is low.

Autopsy↗
PubMed1993

Detection of anticoagulant rodenticides (4-hydroxycoumarins) by thin-layer chromatography and reversed-phase high-performance liquid chromatography with fluorescence detection.

The detection of 4-hydroxycoumarin rodenticides in poisoned domestic animals requires a highly sensitive method as tissue and serum levels of anticoagulants may be very low owing to rapid elimination, metabolism or post-mortem degradation. Thin-layer chromatography (TLC) and reversed-phase high-performance liquid chromatography (RP-HPLC) with fluorescence detection were used to identify the anticoagulants in spiked tissues and in suspicious samples. The analysis of ten suspicious samples highlighted the limitations of both methods. Only the three samples of baits were found positive by TLC whereas one of the five anticoagulants was detected in eight samples by RP-HPLC with fluorescence detection. Therefore, RP-HPLC with fluorescence detection proved to be the more sensitive method for detecting low levels of 4-hydroxycoumarins in blood serum, liver and ingesta, whereas TLC is usually sufficient for analysing baits.

4-Hydroxycoumarins↗
PubMed1993

Multiple restricted lineages in the embryonic rat cerebral cortex.

We have labelled precursor cells in the embryonic rat cerebral cortex using BAG, a retroviral vector that expresses beta-galactosidase. We had previously reported that labelled precursor cells generate clusters of labelled cells that could be classified into four types by their morphological appearance and anatomical distribution (Price and Thurlow, 1988). In this study, we have used immunohistochemistry and intracellular dye labelling to identify the cell types that make up these clusters. We discovered that clusters are almost always composed of a single cell type. In addition to clusters composed entirely of neurones, we found four different types of glial cell clusters. In the grey matter, glial clusters are composed either of protoplasmic astrocytes, or of cells that have an astrocyte morphology, but no glial filaments. In the white matter, clusters are composed of either fibrous astrocytes or oligodendocytes. Our results indicate that each of these different cortical cell types is generated from a separate population of precursor cells.

Animals↗
PubMed1992

Detection of methandienone (methandrostenolone) and metabolites in horse urine by gas chromatography-mass spectrometry.

The metabolic transformation of methandienone (I) in the horse was investigated. After administration of a commercial drug preparation to a female horse (0.5 mg/kg), urine samples were collected up to 96 h and processed without enzymic hydrolysis. Extraction was performed by a series of solid-liquid and liquid-liquid extractions, thus avoiding laborious purification techniques. For analysis by gas chromatography-mass spectrometry, the extracts were trimethylsilylated. Besides the parent compound I and its C-17 epimer II, three monohydroxylated metabolites were identified: 6 beta-hydroxymethandienone (III), its C-17 epimer (IV) and 16 beta-hydroxymethandienone (V). In addition, three isomers of 6 beta,16-dihydroxymethandienone (VIa-c) were discovered. Apparently, reduction of the delta 4 double bond of 16 beta-hydroxymethandienone (V) in the horse yields 16 beta,17 beta-dihydroxy-17 alpha-methyl-5 beta-androst-1-en-3-one (VII). Reduction of the isomers VIa-c results in the corresponding 6 beta,16,17-trihydroxy-17-methyl-5 beta-androst-1-en-3-ones (VIIIa-c). The data presented here suggest that screening for the isomers of VI and VIII, applying the selected-ion monitoring technique, will be the most successful way of proving methandienone administration to a horse.

Animals↗
PubMed1992

[Esthesioneuroblastoma with orbital invasion].

The authors report on an 83-years-old woman with esthesioneuroblastoma (ENB). The first clinical manifestation was an invasion of the suborbital and orbital region. ENB are local destructive tumours which seldom metastasize. Complete surgical excision, supplemented by irradiation therapy offers the highest cure rate. Relapses should be treated with individualized afterloading radiotherapy.

Aged↗
PubMed1992

Herpes simplex virus-specific hybridoma cells cannot be persistently infected with this virus.

Mouse hybridoma clones were examined for their ability to support replication of herpes simplex virus (HSV). Infection of hybridoma clone 1 cells producing an antibody not specific for HSV resulted in a persistent infection with a continuous production of infectious virus, whereas infection of the parental myeloma cells X63-Ag8.653 led to an abundant virus production and extinction of the culture. In contrast, infection of hybridoma cells producing HSV-specific antibodies was restricted to a few weeks. Infectious virus was isolated for a maximum of 10 days and, afterwards, viral antigens were detected by immunofluorescence for a maximum of 18 days. The neutralizing capacity of the antibodies was not essential since the pattern of infection in clone III E8 cells, producing a non-neutralizing antibody, did not differ from that observed in clones 2c and VI A6, which produced highly and weakly neutralizing antibodies, respectively. After loss of viral antigen, HSV DNA was no longer detected by Southern blot hybridization in hybridoma clone 2c cells. Since no difference other than the specificity of the produced antibodies is suspected between the hybridoma clones, the results suggest that the presence of HSV-specific antibodies in the B-lymphoid cell cultures is responsible for virus elimination from the cells.

Animals↗