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Biomedical subjects

Michael Weissel

Publications and source records attributed to Michael Weissel.

11 recordsLinked to original sources
PubMed2006

Disturbances of thyroid function in the elderly.

Disturbances of thyroid function occur more often in the elderly than in the young. This short review gives an up-to-date overview of this topic. After discussing the difference in epidemiology of thyroid dysfunction in elderly persons in areas with different iodine nutrient status, the physiologic age-induced changes of the hypothalamic-pituitary-thyroid axis are discussed, especially with regard to their consequences on normal ranges of thyroid hormones. Although slight decreases in thyrotropin (TSH) and free triiodothyronine (T3) have been described as occurring in healthy elderly persons, it is concluded from the available data that abnormal values of thyroid hormones in serum of old people should be further investigated, since none of the described changes lead to values outside the normal range. Special emphasis is given to the fact that disturbances of thyroid function are oligosymptomatic or may even be asymptomatic in old persons. Therefore, laboratory screening for thyroid dysfunction in patients over 65 years of age seems to be justified. Lastly, differences of treatment in comparison with younger patients with hyper- or hypothyroidism are presented. The impact of subclinical disturbances of thyroid function in the elderly and their possible therapeutic consequences are also included in this discussion.

Aged↗
PubMed2005

A newly identified RET proto-oncogene polymorphism is found in a high number of endocrine tumor patients.

Multiple RET proto-oncogene transcripts, due to genomic variations and alternate splicing, have been described. To investigate endocrine tumor tissue characteristic RET proto-oncogene expression, we performed quantitative RT-PCR, Northern blot and Southern blot analyses of benign and malignant endocrine-derived tissues. We newly describe RET proto-oncogene expression in carcinoid-, gastrinoma- and insulinoma-derived tissue samples. In addition, the presence of a 3'-terminally truncated RET proto-oncogene mRNA variant in benign and malignant thyroid neoplasias, as well as in a pheochromocytoma, an ovarian carcinoma and a medullary thyroid carcinoma, is demonstrated. Southern blot analysis revealed no evidence of gross RET proto-oncogene rearrangements or deletions. As the underlying cause for a bi-allelic TaqI restriction fragment length polymorphism (RFLP), a C (allele 1)/T (allele 2) transition within intron 19, was characterized. This polymorphism is close to a recently described polyadenylation site and lies within a binding site for the nucleic acid binding protein Pbx-1. Screening of healthy subjects and of patients suffering from various endocrine malignancies revealed exclusively allele 1 homozygous and allele 1/allele 2 heterozygous genotypes. Heterozygous genotypes were found in a significantly higher percentage in samples derived from endocrine tumor patients when compared with those from healthy control subjects. Homozygosity for allele 2 was found exclusively in somatic DNA derived from endocrine tumors with high malignant potential. Analysis of DNA derived from varying regions within individual anaplastic thyroid carcinomas revealed an allele 1/allele 2 switch of the RFLP banding pattern, indicating loss of heterozygosity at the RET proto-oncogene locus. In conclusion, our data demonstrate presence of a 5'-terminal RET proto-oncogene transcript in endocrine tissues and reveal a bi-allelic RET proto-oncogene polymorphism. A heterozygous genotype for this polymorphism is found in a considerable number of endocrine tumor patients.

3' Untranslated Regions↗
PubMed2005

[Thyroid dysfunction in aged persons].

This is a short review about thyroid dysfunction in the elderly. Screening investigations from the United States have shown that nearly every 4th woman above the age of 65 is affected. Therefore a state-of-the-art article about this phenomenon seems justified. Epidemiologic studies show that the pattern of thyroid dysfunction depends on the iodine-nutrient status, thyrotoxicosis being more common in countries with iodine deficiency, overt and subclinical hypothyroidism occurring very frequently in areas with sufficient iodine supplementation. After discussing the state of the art of what is known about physiologic changes induced by age in the hypothalamic-pituitary-thyroid axis, it is pointed out that abnormal values of thyroid function parameters in serum should be further investigated. Symptoms of thyroid dysfunction are very rare and often unspecific. Therefore, laboratory screening in women above the age of 65 seems to be justified. Finally, the differences of treating elderly patients with thyroid dysfunction in comparison to treating young patients is discussed. In this discussion the impact of subclinical disturbances of thyroid dysfunction is included.

Adult↗
PubMed2005

Differential expression of alphaB-crystallin and Hsp27-1 in anaplastic thyroid carcinomas because of tumor-specific alphaB-crystallin gene (CRYAB) silencing.

Expression of the small heat shock protein alphaB-crystallin in differentiated thyroid tumors has been described recently. In this study, we investigated the molecular mechanisms that affect the expression of alphaB-crystallin in benign goiters (n = 7) and highly malignant anaplastic thyroid carcinomas (ATCs) (n = 3). AlphaB-crystallin expression was compared with that of Hsp27-1. Immunoblot and quantitative real-time (RT) polymerase chain reaction revealed marked downregulation of alphaB-crystallin in all the tested ATCs and the ATC-derived cell line C-643 . In contrast, considerable expression of Hsp27-1 in benign and malignant thyroid tissue was demonstrated. Immunofluorescence analysis revealed no relevant topological differences between benign and malignant thyrocytes in the cytoplasmic staining of both proteins. Consistent and marked downregulation of TFCP2L1 was identified as one of the main mechanisms contributing to CRYAB gene silencing in ATCs. In addition, CRYAB gene promoter methylation seems to occur in distinct ATCs. In silico analysis revealed that the differential expression of alphaB-crystallin and Hsp27-1 results from differences between the alphaB-crystallin and Hsp27-1 promoter fragments (712 bp upstream from the transcriptional start site). Biological activity of the analyzed promoter element is confirmed by its heat shock inducibility. In conclusion, we demonstrate downregulation of alphaB-crystallin expression in highly dedifferentiated ATCs because of a tumor-specific transcription factor pattern. The differential expression of alphaB-crystallin and Hsp27-1 indicates functional differences between both proteins.

Animals↗
PubMed2004

Do iodine-containing contrast media induce clinically relevant changes in thyroid function parameters of euthyroid patients within the first week?

Little is known about the reaction of normal thyroid glands to the iodine load given by x-ray dyes. We have therefore investigated the short-term effects of high doses of iodine on thyroid parameters in euthyroid patients. We measured free triiodothyronine (FT3), free thyroxine (FT4), and thyrotropin (TSH) serum concentrations before and daily for 1 week after parenteral application of x-ray dyes (coronary angiography: n = 16; computed tomography [CT] of either thorax or abdomen: n = 6; iodine dose range from 300-1221 mg of iodine per kilogram). Inclusion criteria were as follows: normal FT4, normal TSH, negative thyroid antibodies, urinary iodine excretion below 30 microg/dL, no palpable goiter and no euthyroid sick syndrome. All but one patient reacted with a TSH increase. Mean TSH values increased significantly 3-5 days after the iodine load within the normal range. Four patients (18%) had a TSH increase above normal, the maximal observed value being 6.4 microU/mL. Basal TSH values of these four patients were above 2 microU/mL. The day peak TSH concentrations were reached varied from day 1 to day 7, the majority (32%) having the peak on day 3. Peak TSH was significantly correlated with basal TSH values (r = 0.794, p < 0.0001). FT4 and FT3 remained unchanged and there was no significant correlation between the dose of iodine and the TSH reaction. In conclusion, iodine-containing contrast media can induce transiently subclinical hypothyroidism even in euthyroid patients. The TSH reaction seems to depend on the preexisting state of thyroid function.

Adult↗
PubMed2004

How you slice it: smarter segmentation for your sales force.

Three years ago, 70-year-old Hill-Rom Incorporated was in a position familiar to many mature businesses: The company was strong but needed to be stronger. It was a top producer of hospital beds and specialty mattresses, its core product lines. It also had competitive complementary lines of stretchers, furniture, and architectural equipment. It had an extensive customer base, a respected sales force, and solid profit margins. But by the time Ernest Waaser took over as chief executive in early 2001, revenue growth had been slowing, and competition was on the rise. To secure Hill-Rom's place in the market, Waaser decided to focus first on the sales organization--partly because the cost of sales had risen gradually over the past five years and partly because acquisitions and other initiatives had made the sales organization more complex. The CEO took several steps to restructure the sales force. First, the company changed its customer segments to better reflect customers' demands and financial status, ultimately targeting two main groups: key and prime customers. It then changed the overall structure of the sales organization so it could tailor its approach to these two segments; key customers received more specialized service than prime customers. Finally, Hill-Rom adjusted the sales force after the company took an in-depth look at historical data on products and services and sales completed. Reasons for staffing changes were carefully communicated to the sales force. Because of Hill-Rom's initiatives, the cost of sales is down, short-term revenue growth is up, the outlook for long-term revenue growth looks bright, sales and profit margins are up, and customer satisfaction has increased. Best practice, indeed.

Commerce↗
PubMed2003

The ATP-dependent helicase RUVBL1/TIP49a associates with tubulin during mitosis.

RUVBL1/TIP49a/Pontin52 is a recently identified multi-functional protein with 2 ATP binding (WALKER) sites, which is essential for cell proliferation. We recovered and identified RUVBL1/TIP49a as a tubulin-binding protein from Triton X-100 lysates of U937 promonocytic cells by protein affinity chromatography and tryptic peptide microsequencing. Performing co-immunoprecipitation using newly generated RUVBL1/TIP49a-specific antibodies (mAb and rabbit polyclonal Ab) and RUVBL1/TIP49a-GST fusion protein-pull down assays we demonstrate co-precipitation of alpha- and gamma tubulin with RUVBL1/TIP49a. Confocal immunoflourescence microscopy reveals that RUVBL1/TIP49a was present not only in the nucleus, as expected, but was also concentrated at the centrosome and at the mitotic spindle in colocalization with tubulin. The topology of RUVBL1/TIP49a at the mitotic spindle varied, depending on the mitotic stage. The protein was localized at the centrosome and at the polar and astral microtubules in metaphase, and was detectable at the zone of polar tubule interdigitation in anaphase B and telophase. During cytokinesis the protein reappeared at the area of decondensing chromosomes. Whereas preincubation of U937 cells with colcemid resulted in inhibition of mitotic spindle formation with subsequent loss of RUVBL1/TIP49a mitotic spindle staining, no relevant influence of colcemid on RUVBL1/TIP49a-tubulin binding was observed. An agonistic effect of RUVBL1/TIP49a on in vitro tubulin assembly is demonstrated. Our results reveal a new functional aspect of RUVBL1/TIP49a.

ATPases Associated with Diverse Cellular Activitie↗