PubMed Health⌕ Search

Biomedical subjects

M Frosch

Publications and source records attributed to M Frosch.

At least 55 records · Page 3Linked to original sources
PubMed2000

Molecular and phenotypic identification of the yeast pathogen Candida dubliniensis.

Candida dubliniensis is an emerging yeast pathogen generally misclassified as Candida albicans by standard diagnostic procedures. This study examined the efficiency of molecular identification, based on a discriminative PCR test, in a prospective study on the prevalence of C. dubliniensis among 103 oropharyngeal isolates from HIV-infected individuals or transplant recipients, and 30 vaginal isolates. All of the isolates had been classified as C. albicans by standard laboratory procedures. The PCR was evaluated in a blinded fashion against classification achieved by sequencing rDNA. Sequencing results corresponded 100% to the results of the discriminative PCR, indicating the validity of this rapid test. Twenty-one C. dubliniensis isolates were identified, all of them from HIV-infected individuals (prevalence 30%). The internal transcribed spacer regions of the C. dubliniensis isolates were sequenced. Phenotypic features of C. dubliniensis, namely abundant chlamydospore formation, atypical color on CHROMagar, growth defect at 45 degrees C, and colony morphology on Staib agar, were evaluated in a blinded fashion with respect to their discriminative potential, facilitating the design of further epidemiological studies. Carbohydrate assimilation patterns were determined for C. dubliniensis with a novel automated system showing that, in contrast to previous reports, C. dubliniensis is able to utilize D-xylose and trehalose. In evaluating these tests we present a rational approach to identification of the new species and characterization of C. dubliniensis isolates.

AIDS-Related Opportunistic Infections↗
PubMed2000

[Musculoskeletal pain].

BACKGROUND: In paediatrics, numerous diseases present with the leading symptom of muscular, articular, or bone-related pain. The pain as such is seldom diagnostic with regard to pain etiology. Regularly, the significance of inflammatory as well as non-inflammatory pain is underestimated. CLASSIFICATION OF MUSCULOSKELETAL DISEASES: We present 4 case reports, illustrating the classification of musculoskeletal diseases into 4 main groups, being the basis for the modelling of disease, and pain treatment. THERAPY: Pain therapy is either symptomatic or based on specific pathophysiology. Pain therapy consists of the moduls analgesics, antiphlogistics, physiotherapy, psychosocial support, and complementary therapies. We give advice on differential therapy. A transparent team-oriented concept comprising physicians, physiotherapists, ergotherapists, psychologists, and social workers is the basis for any successful long-term therapy. Regular outpatient visits in consent with the family doctor are mandatory as are education and treatment periods on ward. We encourage our patients to join formal self-supportive patient groups.

English Abstract↗
PubMed2000

Cloning and functional characterization of a 30 kb gene locus required for lipopolysaccharide biosynthesis in Legionella pneumophila.

The spontaneous Legionella pneumophila lipopolysaccharide (LPS) mutant 137, which did not bind the LPS-specific mAb 2625, was complemented with a genomic library from the parental wild-type strain. Transformants were screened for reconstitution of the wild-type LPS phenotype, able to bind mAb 2625. By this strategy, a 32,661 bp region comprising 30 open reading frames (Orfs) was identified. Orfs with significant homologies to genes encoding enzymes required for LPS or capsule biosynthesis of Gram-negative bacteria were located on the gene locus. The mutation of strain 137 could be assigned to a deletion of a cytosine residue in Orf 8. The protein encoded by Orf 8 exhibited homology to bacterial methyl-transferases. The L. pneumophila LPS gene locus included genes with deduced products likely to be involved in LPS core oligosaccharide biosynthesis (rmlA-D, rhamnosyl-transferases, acetyl-transferase) as well as LPS O-chain biosynthesis and translocation (mnaA, neuB, neuA, wecA, wzt, wzm). The neuA (Orf 25) and neuB (Orf 24) gene products were functionally characterized by complementation of the capsule negative E. coli K1 mutants EV5 and EV24, respectively. By introduction of the L. pneumophila neuA gene into E. coli EV5 and the neuB gene into EV24, expression of the K1 polysialic acid capsule could be restored. We, therefore, conclude that the biosynthesis pathway of legionaminic acid, the structural unit of the L. pneumophila Sg1 O-antigen, might be similar to the biosynthesis of sialic acid. Southern blot analysis indicated the entire gene locus to be present in L. pneumophila serogroup (Sg)1 strains, whereas only parts of the DNA stretch hybridized to DNA from Sg2 to Sg14 strains.

Blotting, Western↗
PubMed2000

Molecular responses to changes in the environmental pH are conserved between the fungal pathogens Candida dubliniensis and Candida albicans.

In this work we cloned CdPHR1 and CdPHR2 from the human fungal pathogen Candida dubliniensis. The two genes are homologues to the pH-regulated genes PHR1 and PHR2 from Candida albicans. The pH-dependent pattern of expression of CdPHR1 and CdPHR2 was conserved in C. dubliniensis. CdPHR1 could be shown to be functionally equivalent to PHR1. The pH-regulated mode of expression was maintained when CdPHR1 was integrated in C. albicans. This indicates a fundamentally similar mode of expressional regulation in the two species. CdPHR1 was furthermore capable of reversing the aberrant phenotype of a Saccharomyces cerevisiae GAS1 deletion mutant. In this species, however, expression of CdPHR1 was no longer under control of the external pH. Expression of CdPHR1 was not detected when it was introduced into Aspergillus nidulans. In conclusion, C. dubliniensis and C. albicans respond to changes in the environmental pH with a change in cell shape and differential gene expression.

Apoenzymes↗
PubMed2000

Distribution of the meningococcal insertion sequence IS1301 in clonal lineages of Neisseria meningitidis.

The distribution of the meningococcal insertion sequence IS1301 was analysed in 496 strains of different serogroups and clonal lineages of Neisseria meningitidis, and in 64 neisserial strains other than N. meningitidis. IS1301 was found in meningococci, but not in apathogenic Neisseria sp. and Neisseria gonorrhoeae. The copy numbers of IS1301 varied between 2 and 17 per genome. IS1301 positive strains were mostly found among the serogroups 29E, W135, X, and Y. Clonal lineages of serogroup A, B, and C meningococci associated with epidemic meningococcal disease were rarely positive for IS1301.

Blotting, Southern↗
PubMed2000

Successful treatment of mycobacterium avium osteomyelitis and arthritis in a non-immunocompromised child.

In non-immunocompromised children, infections with mycobacterium avium complex (MAC) are rare, except for cervical lymphadenitis. We report here a 34-month-old boy who developed osteomyelitis and septic arthritis due to MAC. No findings could be revealed for immunodeficiency. He was treated successfully for 12 months with combined therapy consisting of clarithromycin, rifabutin and protionamid.

Anti-Bacterial Agents↗
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

Dominant active alleles of RIM101 (PRR2) bypass the pH restriction on filamentation of Candida albicans.

Morphological development of the fungal pathogen Candida albicans is profoundly affected by ambient pH. Acidic pH restricts growth to the yeast form, whereas neutral pH permits development of the filamentous form. Superimposed on the pH restriction is a temperature requirement of approximately 37 degrees C for filamentation. The role of pH in development was investigated by selecting revertants of phr2Delta mutants that had gained the ability to grow at acid pH. The extragenic suppressors in two independent revertants were identified as nonsense mutations in the pH response regulator RIM101 (PRR2) that resulted in a carboxy-terminal truncation of the open reading frame. These dominant active alleles conferred the ability to filament at acidic pH, to express PHR1, an alkaline-expressed gene, at acidic pH, and to repress the acid-expressed gene PHR2. It was also observed that both the wild-type and mutant alleles could act as multicopy suppressors of the temperature restriction on filamentation, allowing extensive filamentation at 29 degrees C. The ability of the activated alleles to promote filamentation was dependent upon the developmental regulator EFG1. The results suggest that RIM101 is responsible for the pH dependence of hyphal development.

Apoenzymes↗
PubMed2000

Twenty-four hour intraesophageal pH monitoring in children and adolescents with scleroderma and mixed connective tissue disease.

OBJECTIVE: To investigate esophageal dysmotility and gastroesophageal reflux, which are important, but often occult features of gastrointestinal (GI) involvement in children and adolescents with mixed connective tissue disease (MCTD) and scleroderma. METHODS: We carried out intraesophageal 24 h pH monitoring of 14 patients with scleroderma and MCTD. RESULTS: We observed an elevated reflux index in 64% of the patients. An increased number of reflux events was found in 85%. Reflux events > 5 min were noted in 50% of the patients, which is indicative of possible development of esophagitis. Only 3 patients presented clinical symptoms. Four of 5 patients with localized scleroderma revealed a pathological reflux index. We found no relationship between gastroesophageal reflux, age of patients, duration of disease, and Raynaud's phenomenon. CONCLUSION: GI involvement in children with scleroderma or MCTD is more frequent than clinical symptoms indicate. An active diagnostic investigation for GI dysmotility and gastroesophageal reflux is necessary to detect these complications.

Adolescent↗
PubMed2000

A subgroup-specific evaluation of the efficacy of intraarticular triamcinolone hexacetonide in juvenile chronic arthritis.

OBJECTIVE: To determine the subgroup-specific differences of intraarticular triamcinolone hexacetonide (TH) in the treatment of joint inflammation in patients with juvenile chronic arthritis (JCA). METHODS: A retrospective review of 194 children of all subgroups of JCA, treated by a single or repeated TH injection between 1989 to 1994. Efficacy and duration of benefit were evaluated after a mean duration of 3, 15, 30, and 64 weeks. RESULTS: In all, 1439 TH injections were given to 194 patients; 368 of these were reinjections. The median duration of improvement of all injections was 74 weeks. Responses were significantly different among subgroups (p = 0.0001): there were 121 weeks of efficacy in early-onset pauciarticular JCA type I (223 injections), 47 weeks in late-onset pauciarticular JCA type II (190 injections), 105 weeks in rheumatoid factor negative polyarticular JCA (445 injections), 63 weeks in rheumatoid factor positive polyarticular JCA (127 injections), and 36 weeks in systemic JCA (413 injections). Forty-one injections were done in other rheumatic diseases. In relation to this result there were also differences with regard to joint groups, antinuclear antibody (ANA) and HLA-B27 status, and sex. Side effects were rare: infections of skin or joints were not noted; skin and lipoatrophy were seen after 15 injections, necrosis of the hip in one case, luxation of 2 shoulders of one patient, and periarticular calcification in 3 patients. CONCLUSION: Intraarticular TH is an effective therapy for inflammatory joint disease in all subgroups of JCA. The risk of major complications is low. The median duration of improvement depends on the subgroup of the disease.

Administration, Topical↗
PubMed1999

The Alzheimer-related gene presenilin 1 facilitates notch 1 in primary mammalian neurons.

The normal functional neurobiology of the Alzheimer's disease (AD) related gene presenilin 1 (PS1) is unknown. One clue comes from a genetic screen of Caenorhabditis elegans, which reveals that the presenilin homologue sel-12 facilitates lin-12 function [D. Levitan, I. Greenwald, Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis elegans S182 Alzheimer's disease gene, Nature 377 (1995) 351-355]. The mammalian homologue of lin-12, Notch1, is a transmembrane receptor that plays an important role in cell fate decisions during development, including neurogenesis, but does not have a known function in fully differentiated cells. To better understand the potential role of Notch1 in mammalian postmitotic neurons and to test the hypothesis that Notch and PS 1 interact, we studied the effect of Notch1 transfection on neurite outgrowth in primary cultures of hippocampal/cortical neurons. We demonstrate that Notch1 inhibits neurite extension, and thus has a function in postmitotic mature neurons in the mammalian CNS. Furthermore, we present evidence demonstrating that there is a functional interaction between PS1 and Notch1 in mammalian neurons, analogous to the sel-12/lin-12 interaction in vulval development in C. elegans [D. Levitan, T. Doyle, D. Brousseau, M. Lee, G. Thinakaran, H. Slunt, S. Sisodia, I. Greenwald, Assessment of normal and mutant human presenilin function in Caenorhabditis elegans, Proc. Natl. Acad. Sci. U.S.A. 93 (1996) 14940-14944; D. Levitan, I. Greenwald, Effect of Sel-12 presenilin on Lin-12 localization and function in Caenorhabditis elegans, Development, 125 (1998) 3599-3606]. The inhibitory effect of Notch1 on neurite outgrowth is markedly attenuated in neurons from PS1 knockout mice, and enhanced in neurons from transgenic mice overexpressing wild type PS1, but not mutant PS1. These data suggest that PS1 facilitates Notch1 function in mammalian neurons, and support the hypothesis that a functional interaction exists between PS1 and Notch1 in postmitotic mammalian neurons.

Alzheimer Disease↗
PubMed1999

Activities of the EM10 protein from Echinococcus multilocularis in cultured mammalian cells demonstrate functional relationships to ERM family members.

The ezrin-radixin-moesin (ERM) homolog EM10 is expressed by the larval stage of the parasite E. multilocularis and shows 46.9% overall identity in the primary structure with human ezrin. To determine whether EM10 has similar activities to ERM proteins, we investigated properties of the protein expressed in mammalian cells. In particular, we transiently expressed haemagglutinin-tagged (HA-tagged) versions of the full-length EM10 as well as the amino- and the carboxy-terminal halves of EM10 in HtTA-1 cells. In addition we stably transfected NIH-3T3 cells with untagged full-length EM10. The data demonstrate that EM10 polypeptides behave like their corresponding portions of radixin when transiently expressed in mammalian cells. The full-length and amino-terminal EM10 polypeptides were localized to cortical structures. Cells expressing the carboxy-terminal polypeptide of EM10 showed long actin-filled protrusions. Cells expressing full-length EM10 showed a reduction in endogenous moesin-staining at cortical structures. In stably transfected NIH-3T3 cells EM10 was not crisply localized but rather was diffuse throughout the cytoplasm. These cells showed a conspicuous loss of stress-fibers, a phenotype that was not seen in analogous experiments with ERM proteins. The results demonstrate both similarities and differences between the functional properties of EM10 and ERM proteins expressed in vertebrate cells.

3T3 Cells↗
PubMed1999

Eye-hand coordination in uni- and bimanual goal-oriented tasks.

Two different drawer tasks were investigated with the aim of assessing the role of eye movements in well-coordinated hand movements. In an unimanual step-tracking task, which had a predictive and an unpredictive movement, a two-way repeated-measures ANOVA showed a significant effect of prediction on the onset of grip-force (GF) rate (300+/-39 ms for the predictive condition versus 394+/-53 ms for the non-predictive condition, P<0.0001). Correlation coefficients, computed from the eye and the hand movements were low for the right and the left hand. The saccade was more coupled with the visual step change than with the action of the hand per se. In a second bimanual pull-and-pick task, the instruction was to pull a drawer with the left hand from a closed position to a LED-cued open position and then to grasp and reinsert a small peg in the drawer with the right hand. Correlation coefficients, computed from the latencies of saccades and of the leading left hand or of the right hand, were significant in four of five subjects. Intermanual correlations were significant in all five subjects. In conclusion, we found that the initial saccade in the unimanual task was best related with the visual step change, but was poorly correlated with the pulling/pushing hand. In the bimanual task, a moderate, but significant temporal coupling between the eyes and hand events was observed. This coupling was, however, less tight than that between both hands.

Acoustic Stimulation↗