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Biomedical subjects

M German

Publications and source records attributed to M German.

15 recordsLinked to original sources
PubMed2005

The production of hydrogen peroxide during early-stage protein aggregation: a common pathological mechanism in different neurodegenerative diseases?

By means of an ESR spin-trapping method, we have shown that Abeta (amyloid beta), alpha-synuclein and various toxic forms of the prion protein all appear to generate H2O2 in vitro. A fundamental molecular mechanism underlying the pathogenesis of cell death in several different neurodegenerative diseases could be the direct production of H2O2 during the early stages of protein aggregation.

Amyloid↗
PubMed2005

Genotyping of Toxoplasma gondii strains from immunocompromised patients reveals high prevalence of type I strains.

Toxoplasma gondii is an important food- and waterborne opportunistic pathogen that causes severe disease in immunocompromised patients. T. gondii has an unusual clonal population structure consisting of three widespread lineages known as I, II, and III. To establish the genotypes of strains of T. gondii associated with human toxoplasmosis, we have developed a set of four highly sensitive and polymorphic nested PCR markers. Multiplex nested PCR analysis was used to genotype parasites in cerebral spinal fluid samples from 8 of 10 human immunodeficiency virus-positive patients. Remarkably, a majority of these patients had infections with type I strains or strains containing type I alleles, despite the fact that this lineage is normally uncommon in humans and animals. Multiplex analysis of these four unlinked makers was able to distinguish all three common genotypes and also detected two strains with mixed genotypes. Further analysis based on sequencing of a polymorphic intron revealed that one of these recombinant strains was an exotic lineage distinct from the archetypal clonal lineages. The multiplex nested PCR analysis described here will be useful for analyzing the contribution of parasite genotype to toxoplasmosis.

AIDS-Related Opportunistic Infections↗
PubMed2004

Progress in near-field photothermal infra-red microspectroscopy.

Near-field photothermal Fourier transform infra-red microspectroscopy, which utilizes atomic force microscopy (AFM)-type temperature sensors, is being developed with the aim of achieving a spatial resolution higher than the diffraction limit. Here we report on a new implementation of the technique. Sensitivity of the technique is assessed by recording infra-red spectra from small quantities of analytes and thin films. A photothermomechanical approach, which utilizes conventional AFM probes as temperature sensors, is also discussed based on preliminary results. Early indication suggests that the photothermal approach is more sensitive than the thermomechanical one.

Journal Article↗
PubMed2000

Ventral neural patterning by Nkx homeobox genes: Nkx6.1 controls somatic motor neuron and ventral interneuron fates.

There is growing evidence that sonic hedgehog (Shh) signaling regulates ventral neuronal fate in the vertebrate central nervous system through Nkx-class homeodomain proteins. We have examined the patterns of neurogenesis in mice carrying a targeted mutation in Nkx6.1. These mutants show a dorsal-to-ventral switch in the identity of progenitors and in the fate of postmitotic neurons. At many axial levels there is a complete block in the generation of V2 interneurons and motor neurons and a compensatory ventral expansion in the domain of generation of V1 neurons, demonstrating the essential functions of Nkx6.1 in regional patterning and neuronal fate determination.

Animals↗
PubMed2000

Regulation of insulin gene transcription.

Recent studies of the insulin gene promoter and the transcription factors that regulate it have expanded our understanding of both how the production of insulin is restricted to the pancreatic beta -cell, and how that production is regulated by physiologic signals such as glucose. A picture is emerging in which an elaborate set of transcription factors binds to specific sequences along the promoter and recruits additional transcriptional co-activators to build a functional transcriptional activation complex that is unique to beta -cells. Surprisingly, however, genetic experiments in mice have demonstrated an unexpected degree of redundancy in the factors that control insulin gene expression, and have revealed the presence of a network of transcription factors that coordinate the expression of factors forming the insulin gene activation complex.

Animals↗
PubMed2000

Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of beta-cell formation in the pancreas.

Most insulin-producing beta-cells in the fetal mouse pancreas arise during the secondary transition, a wave of differentiation starting at embryonic day 13. Here, we show that disruption of homeobox gene Nkx6.1 in mice leads to loss of beta-cell precursors and blocks beta-cell neogenesis specifically during the secondary transition. In contrast, islet development in Nkx6. 1/Nkx2.2 double mutant embryos is identical to Nkx2.2 single mutant islet development: beta-cell precursors survive but fail to differentiate into beta-cells throughout development. Together, these experiments reveal two independently controlled pathways for beta-cell differentiation, and place Nkx6.1 downstream of Nkx2.2 in the major pathway of beta-cell differentiation.

Animals↗
PubMed1999

A pilot study of the management of uncomplicated candidemia with a standardized protocol of amphotericin B.

We evaluated an amphotericin treatment strategy on the basis of duration of candidemia and clinical findings. Patients without neutropenia who had uncomplicated candidemia received 200 mg of amphotericin B over 5-7 days if they had had </=1 day of documented positive blood cultures (SC group) or a total of 500 mg of amphotericin B over 14-20 days if they had had >1 day of positive cultures (PC group). The clinical cure rate was 93% (95% confidence interval [CI], 77%-99%; n=29 episodes) in the SC group, with no relapses (median follow-up, 272 days). The clinical cure rate was 83% (95% CI, 64%-94%; n=29 episodes) in the PC group, with 1 relapse (4.2%). The results of this pilot study suggest that patients with candidemia may be stratified into risk groups on the basis of the duration of positive blood cultures and other clinical findings. Decisions about the duration of therapy can be made 4-7 days after initiation of treatment. Carefully selected patients with transient uncomplicated candidemia may be safely treated with a short course of amphotericin B. Further prospective validation of this concept should be undertaken particularly to evaluate the impact on low-frequency late complications (e.g., endophthalmitis).

Adult↗
PubMed1997

Regulation of insulin preRNA splicing by glucose.

Glucose tightly regulates the synthesis and secretion of insulin by beta cells in the pancreatic islets of Langerhans. To investigate whether glucose regulates insulin synthesis at the level of insulin RNA splicing, we developed a method to detect and quantify a small amount of RNA by using the branched DNA (bDNA) signal-amplification technique. This assay is both sensitive and highly specific: mouse insulin II mRNA can be detected from a single beta cell (betaTC3 cells or mouse islets), whereas 1 million non-insulin-producing alpha cells (alphaTC1.6 cells) give no signal. By using intron and exon sequences, oligonucleotide probes were designed to distinguish the various unspliced and partially spliced insulin preRNAs from mature insulin mRNA. Insulin RNA splicing rates were estimated from the rate of disappearance of insulin preRNA signal from beta cells treated with actinomycin D to block transcription. We found that the two introns in mouse insulin II are not spliced with the same efficiency. Intron 2 is spliced out more efficiently than intron 1. As a result, some mRNA retaining intron 1 enters the cytoplasm, making up approximately 2-10% of insulin mRNA in the cell. This partially spliced cytoplasmic mRNA is quite stable, with a half-life similar to the completely spliced form. When islets grown in high glucose are shifted to low glucose medium, the level of insulin preRNA and the rate of splicing fall significantly. We conclude that glucose stimulates insulin gene transcription and insulin preRNA splicing. Previous estimates of insulin transcription rates based on insulin preRNA levels that did not consider the rate of splicing may have underestimated the effect of glucose on insulin gene transcription.

Animals↗
PubMed1994

Effective case management in managed mental health care: conditions, methods and outcomes.

Case management methods were utilized after changing from a "provider network" to a "staff model" mental health center serving approximately 30,000 HMO enrollees. This change allowed for tighter systems and case management, interdisciplinary coordination, longitudinal evaluation of clients and measures of quality assurance, staff productivity and cost savings. Effective case management conditions and methods were implemented that ensured immediate accessibility, broad-ranging evaluation and triage, use of both psychiatric and operational diagnosis, proper matching of client with therapist, group, and setting; coordination of the roles of various support systems and use of proven treatment and case management methods. The change to this staff model case management system resulted in 38.8% cost savings while delivering high-quality, accessible service.

Cost Savings↗
PubMed1977

[Relationship between ultrastructure of various phages and protein-phage conjugates with their specific neutralization].

Back to our technique of phage sensitization by protein fixation with the aid of coupling reagents, and of their inactivation by the specific anti-protein antibodies, comparative studies were made on phages having a morphologically different tail. Here we report the results concerning the ultramicorscopic observation of four phages, the efficiency and the rate of their sensitization, and the possibility of their respective neutralization.

Bacteriophages↗