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Biomedical subjects

M Hamacher

Publications and source records attributed to M Hamacher.

At least 19 recordsLinked to original sources
PubMed2006

The HUPO Brain Proteome Project--no need to hurry?

The HUPO Brain Proteome Project (HUPO BPP) is dedicated to the analysis of the brain proteome and has initiated two pilot studies in order to elaborate a standardised system for data collection and reprocessing. Samples of mouse brains (different developmental stages) and human brain tissue (biopsy and post-mortem samples) were shipped to different laboratories in Europe, Asia and the US that were invited to identify as many proteins as possible using their own approaches. In addition, a centralised data reprocessing strategy has been elaborated in an iterative way to generate highly reliable lists of identified proteins. This consortium could be a good example for a standardized proteomics workflow.

Animals↗
PubMed2006

Proteomics in neurodegeneration--disease driven approaches.

Proteins as a product from genetic information execute and determine how development, growth, aging and disease factors are orchestrated within the lifetime of an organism. Differential protein expression and/or modification are always context dependent i.e. they happen within a specific context of a tissue, organ, environmental situation and individual fate. Consequently, the function/dysfunction (in a certain disease) of a specific gene cannot be predicted comprehensively by its sequence only. Genetic information can only be understood when genes and proteins are analyzed in the context of the biological system and specific networks they are involved in. In regard to neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's disease (PD) many proteins are known for long years to be the cause or the consequence of the pathomechanism of the respective disease. The treatment of these neurodegenerative diseases represents a major challenge for the pharmaceutical industry, whereas the understanding of their pathogenesis is still in its infancy. With the development of several powerful techniques for proteome analysis it is now possible to investigate the expression of thousands of proteins in single cells, tissues or whole organisms at the same time. These developments opened new doors in medical sciences, and identification of cellular alterations associated with e.g. neurodegeneration will result in the identification of novel diagnostic as well as therapeutic targets. In this review, general considerations and strategies of proteomics technologies, the advantages and challenges as well as the special needs for analyzing brain tissue in the context of AD and AD are described and summarized.

Animals↗
PubMed2001

Plasmolipin: genomic structure, chromosomal localization, protein expression pattern, and putative association with Bardet-Biedl syndrome.

Plasmolipin is a membrane protein and belongs to the tetraspan molecule (4TM) family, an expanding group of myelin proteins many of which could be linked to human hereditary demyelinating neuropathies. We have cloned and sequenced the mouse plasmolipin gene, revealing the common organization of the 4TM gene group with four exons and a large first intron. Western blot analysis with an antibody raised against the C-terminal intracellular part of the protein showed that plasmolipin is expressed not only in the nervous system and kidney, but also in a number of other tissues such as thymus, testis, lung, and thyroid gland. By means of radiation hybrid mapping and FISH analysis, we could localize the human plasmolipin gene to Chromosome 16q13 within the putative region of the Bardet-Biedl syndrome type 2 (BBS2) gene locus. BBS2 is a clinically and genetically heterogeneous group of disorders resulting in rod-cone dystrophy, obesity, postaxial polydactyly, renal dysfunction, and mental retardation, which were very recently associated with a novel gene designated BBS2. With respect to intrafamiliar variations in the manifestation of BBS, we suggest that plasmolipin might be either another candidate gene or a modifier of the BBS2 phenotype.

Animals↗
PubMed2001

Multistate outbreak of Salmonella serovar Muenchen infections associated with alfalfa sprouts grown from seeds pretreated with calcium hypochlorite.

During September 1999, a multistate outbreak of Salmonella serovar Muenchen infection associated with eating raw alfalfa sprouts was identified in Wisconsin. Despite use of a calcium hypochlorite sanitizing procedure to pretreat seeds before sprouting, at least 157 outbreak-related illnesses were identified in seven states having sprouters who received alfalfa seed from a specific lot. The continued occurrence of sprout-related outbreaks despite presprouting disinfection supports the concern that no available treatment will eliminate pathogens from seeds before sprouting and reinforces the need for additional safeguards to protect the public. A lack of consumer knowledge regarding exposure to sprouts documented in this investigation suggests that more-targeted outreach to high-risk individuals may be needed to reduce their risk.

Adolescent↗
PubMed2000

ENL, the MLL fusion partner in t(11;19), binds to the c-Abl interactor protein 1 (ABI1) that is fused to MLL in t(10;11)+.

Translocations of the chromosomal locus 11q23 that disrupt the MLL gene (alternatively ALL-1 or HRX) are frequently found in children's leukemias. These events fuse the MLL amino terminus in frame with a variety of unrelated proteins. Up to date, 16 different fusion partners have been characterized and more are likely to exist. No general unifying property could yet be detected amongst these proteins. We show here that the frequent MLL fusion partner ENL at 19p13.1 interacts with the human homologue of the mouse Abl-Interactor 1 (ABI1) protein. ABI1 in turn, is fused to MLL in the t(10;11)(p11.2;q23) translocation. ABI1 was identified as an ENL binding protein by a yeast two-hybrid screen. The interaction of ENL and ABI1 could be verified in vitro by far-Western blot assays and GST-pulldown studies as well as in vivo by co-immunoprecipitation experiments. A structure-function analysis identified an internal region of ENL and a composite motif of ABI1 including an SH3 domain as mutual binding partners. These data introduce novel aspects that might contribute to the understanding of the process of leukemogenesis by MLL fusion proteins.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Activity of human immunodeficiency virus type 1 promoter/TAR regions and tat1 genes derived from individuals with different rates of disease progression.

Different rates of disease progression may be associated with different human immunodeficiency virus type 1 (HIV-1) promoter and/or transactivator activities. We therefore analyzed the sequences and activities of the first exon of Tat, tat1, and the promoter/trans-acting responsive (TAR) regions amplified directly from peripheral blood mononuclear cells obtained from five long-term nonprogressors and eight progressing HIV-1-infected individuals. The majority of tat1 alleles and promoter/TAR regions from all patients were intact and showed comparable activities in transient reporter assays. A substantial number of point mutations and some length variations were observed in the promoter/TAR region. In a single nonprogressor, the Sp1 binding site 3 was consistently altered and the transcriptional activity in the presence of Tat was diminished. Some LTR clones from a rapid progressor contained a fourth Sp1 binding site, which was associated with an elevated basal promoter activity. These data suggest that defects in the promoter/TAR region or tat1 are rare and that different promoter/transactivator activities are not commonly associated with different progression rates.

Alleles↗
PubMed1997

Simian immunodeficiency virus variants with differential T-cell and macrophage tropism use CCR5 and an unidentified cofactor expressed in CEMx174 cells for efficient entry.

The recent identification of coreceptors that mediate efficient entry of human immunodeficiency virus type 1 (HIV-1) suggests new therapeutic and preventive strategies. We analyzed simian immunodeficiency virus (SIV) entry cofactors to investigate whether the macaque SIV model can be used as an experimental model to evaluate these strategies. Similar to primary HIV-1 isolates, a well-characterized molecular clone, SIVmac239, which replicates poorly but efficiently enters into rhesus alveolar macrophages and an envelope variant, SIVmac239/316Env, with an approximately 1,000-fold-higher replicative capacity in macrophages used the beta-chemokine receptor CCR5 for efficient entry. The transmembrane portion of 316Env allowed low-level entry into cells expressing CCR1, CCR2B, and CCR3. A single amino acid substitution in the V3 loop of SIVmac239/316Env, 321P-->S, impaired the ability to enter into the T-B hybrid cell line CEMx174 but had relatively little effect on entry into primary cells and HOS.CD4 cells expressing CCR5. Although CEMx174 cells do not express CCR5, most SIVmac variants entered this hybrid cell line efficiently but did not enter the parental T-cell line CEM. It seems likely that CEMx174 cells express an as-yet-unidentified, perhaps B-cell-derived cofactor which allows efficient entry of SIVmac.

Animals↗
PubMed1995

[Clinical screening after thyroid gland diseases: contribution of orienting ultrasound examination].

AIM: Of this study was to define the significance of approximate ultrasound explorations of the thyroid gland for the clinical screening for thyroid diseases. METHOD: 918 patients in the medical service of a general hospital were screened for thyroid diseases by means of clinical, functional and sonomorphological methods. A sonographic screening scan with a 5 MHz probe provided data concerning structure and dimension of thyroid gland. Maximal sagittal diameter (SDm, normal range < 18 mm) was taken as a measure for thyroid size. RESULTS: Echogenicity has no essential meaning for thyroid dysfunction screening, but is indispensable for the detection of circumscript or general echo deficiency. SDm has proved to be a simple and well reproducible measure for thyroid size. Among 41 patients with thyrotoxicosis 40 had enlarged SDm, which means a sensitivity of 97.6%. However, a high rate of false positives makes TSH-screening of all enlarged thyroid glands obligatory. Moreover, SDm allows the estimation of a lack of thyroid mass as the most common cause of hypothyroidism. CONCLUSION: We recommend that an approximate ultrasound exploration of the thyroid gland including measuring of SDm should be part of every diagnostic procedure for thyroid disease, as it is precise and not time consuming.

Adult↗
PubMed1975

[Complications of pregnancy in female anesthesiologists (author's transl)].

A questionnaire was sent out to the members of the German Society of Anesthesiology and Reanimation with the purpose to clarify whether there is an increased incidence of certain complications during pregnancy among anesthesiologists. The results obtained allow the tentative conclusion that there is a higher abortion rate. There was also an increase of premature deliveries and congenital malformations. Surprisingly, a significant increase in births of females was observed among female anesthesiologists (with or without exposure) and among the offspring of male anesthesiologists (with or without exposure). Therefore this observation cannot be related to the exposure in operating rooms. On the basis of these results and reports from literature it is not permissible to relate the incidence of these complications exclusively to the chronic inhalation of narcotic gases. Other covariables which might cause the complications were not considered in this study. Nevertheless in spite of these limitations narcotic gases should be removed from the atmosphere of operating theatres as completely as possible.

Abortion, Spontaneous↗