Required research a disservice?
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Biomedical subjects
Publications and source records attributed to S Kirsch.
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BACKGROUND: There is a paucity of knowledge about the effects of exposure to alcohol abuse in the household on women who do not abuse alcohol. The purpose of this study was to determine whether women who did not abuse alcohol demonstrated any health-related adverse effects because they lived with family members who did abuse alcohol. METHODS: This study was a historical prospective survey of female patients at five primary care practices. Survey instruments included the CAGE questionnaire, a five-item screening test for exposure to alcoholism, and the Medical Outcomes Study 36-item Short Form Health Survey (MOS SF-36). Patient records were examined for specific diagnoses. RESULTS: A total of 267 patients completed the questionnaires and had complete medical records available for analysis. Forty-two (15.7%) potential alcohol abusers were excluded from the sample leaving a working total of 225; 70 (31.1%) were potentially exposed to alcoholism in the household. Women exposed to alcohol abuse in the home did not experience an increased risk for the medical diagnoses studied, but they did demonstrate decreased health-related quality of life as measured by the MOS-SF-36 for the following scales: role physical (P = .025), role emotional (P = .038), social functioning (P = .001), bodily pain (P = .016), and mental health (P = .040). CONCLUSIONS: Women exposed to alcohol abuse in the household are more likely to perceive themselves as less healthy. Although they may not have received a clinical diagnosis of depression, they are more likely to feel depressed. The extent to which subjects' health-related quality of life is influenced by exposure to alcohol abuse suggests that the medical diagnosis may be insensitive as a description of health status in this population.
In a large collaborative screening project, 370 men with idiopathic azoospermia or severe oligozoospermia were analysed for deletions of 76 DNA loci in Yq11. In 12 individuals, we observed de novo microdeletions involving several DNA loci, while an additional patient had an inherited deletion. They were mapped to three different subregions in Yq11. One subregion coincides to the AZF region defined recently in distal Yq11. The second and third subregion were mapped proximal to it, in proximal and middle Yq11, respectively. The different deletions observed were not overlapping but the extension of the deleted Y DNA in each subregion was similar in each patient analysed. In testis tissue sections, disruption of spermatogenesis was shown to be at the same phase when the microdeletion occurred in the same Yq11 subregion but at a different phase when the microdeletion occurred in a different Yq11 subregion. Therefore, we propose the presence of not one but three spermatogenesis loci in Yq11 and that each locus is active during a different phase of male germ cell development. As the most severe phenotype after deletion of each locus is azoospermia, we designated them as: AZFa, AZFb and AZFc. Their probable phase of function in human spermatogenesis and candidate genes involved will be discussed.
Conventional methods of long range restriction mapping for analysis of the genomic DNA structure failed in Yq11, because single-copy DNA probes for blot hybridization analyses are rare and the rate of DNA methylation is high in this Y region. Numerous repetitive sequence blocks of unknown extensions are scattered throughout Yq11 and a patchwork of X-Y homologous DNA blocks were found by different investigators. Therefore, our approach towards a molecular analysis of this Y region reduced this complexity by performing first its molecular analysis in YAC clones mapping to Yq11. YACs contain only a part of the whole Yq11 DNA structure. In this paper, we present our first results of this approach based on quantitative blot analysis of 51 DNA loci in 67 YAC clones. The YACs were isolated from the three CEPH libraries and mapped to a contig of 13 Mb from proximal to distal Yq11 with aid of a detailed interval map. In distal Yq11, our analysis revealed the presence of local amplification events of different DNA domains. A model of their possible arrangement is presented.
We have used a series of 30 DNA probes previously mapped to the long arm of the human Y chromosome, to screen a panel of 21 patients with structural abnormalities in Yq, by genomic blot hybridisation. The results have allowed us to construct a detailed map of interval 6 of the Y chromosome, in which 28 of the probes could be assigned to 14 sub-intervals within interval 6. Some probes detect two or more loci within this region, each of which has been localised. The same set of probes has been used to screen a panel of 19 chromosomally normal azoospermic men, two of whom have been found to carry microdeletions within this region. With the completion of this map we have been able accurately to localise these microdeletions within interval 6 and show that they do not overlap. We believe these microdeletions may disrupt the azoospermia factor (AZF) involved in spermatogenesis, and which is known to lie in this region. These results are an important step towards the localisation of the AZF locus.
Spontaneously active tyrosine-specific protein kinases I and II (designated TyrK I and TyrK II) have been purified to electrophoretic homogeneity from a particulate fraction of porcine spleen based on an assay that used poly(4Tyr, Glu) as a substrate. SDS/polyacrylamide gels revealed a doublet of bands of about Mr 51,000 for TyrK I and two protein bands of Mr 55,000 and 54,000 for TyrK II. After incubation in the presence of [gamma-32P]ATP, the bands corresponding to both protein kinases contained phosphotyrosine. The two tyrosine protein kinases showed high activities with poly(Tyr, 4Glu) and poly(Tyr, 3Ala, 6Glu) as substrates and lower activity with angiotensin II. Neither histone, phosvitin, casein nor bovine serum albumin were phosphorylated. Both protein tyrosine kinases were activated by millimolar concentrations of Mg2+ whereas Mn2+ was less effective. The effects of various polyanionic and polycationic substances depended on the nature of the peptide substrate. With poly(Tyr, 4Glu) as a substrate, the substances either inhibited the activities of TyrK I and TyrK II or had no effect. However, activation was observed with angiotensin II as substrate in the presence of polylysine, polyornithine, protamine sulfate, and heparin as effectors. When angiotensin II was used as substrate, activation also occurred by autophosphorylation, in parallel to the phosphate incorporation into the protein kinases. Activation by autophosphorylation was not observed with the synthetic peptide substrates, poly(Tyr, 4Glu) and poly(Tyr, 3Ala, 6Glu).
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Post-transfusion hepatitis developed in 2% of 842 cardiac-surgery patients surveyed in Sydney (4 cases per 1000 units of transfused blood). 3 of the 18 cases were caused by hepatitis B virus even though all units of blood which contained hepatitis B surface antigen (HBsAg) had been rejected. 1 case was caused by cytomegalovirus, and there were 14 (78%) cases of non-A, non-B hepatitis. A significantly higher proportion of the units of blood given to the patients in whom non-A, non-B hepatitis developed contained antibodies against both hepatitis B core antigen and HBsAg than the units of blood given to the other patients. Rejection of blood with these markers of past exposure to hepatitis B may reduce the incidence of post-transfusion non-A, non-B hepatitis by up to a half.
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The Göttingen mini swine is a good experimental animal. The electrolytes and the bone healing rate is comparable to human. The weight of the animals should be 30-45 kg. All surgery is performed under endotracheal general anaesthesia without any complication. There is minimal blood loss because blood pressure is only 40/80 mmHg. We used the anterolateral approach. The feature peculiarity of this animal model are: 1. Skin incision should start 10 cm cranial to the tail and should be curved. 2. The osteotomy of the head is V-shaped in maximal external rotation. 3. The acetabulum is prepared with a 23.5 mm reamer. 4. The stem should be implanted first. After completion of the preliminary test operations, 10 animals were operated in the described standard manner. During one year follow-up there was only one radiological cup-loosening.
The shoulder joint does not represent a simple ball-and-socket joint with three degrees of freedom unlike widely believed. Series of X-ray pictures show that in abduction the momentary rotational axis does not meet the center of the humerus. Morphological measurements yield the result that the radius of curvature of the cavitas is slightly greater (2 mm) than the humeral one. This physiological incongruity of the articulating surfaces is functionally necessary. Thus, the shoulder joint represents a force-locked dimeric ball-and-socket joint. In abduction e.g. the humerus simultaneously rotates around the humeral center and around the cavitas center in opposite direction. The resultant momentary rotational axis is therefore shifted towards the scapula as in vivo measurements confirm. Fundamental kinematical and statical properties of the joint are derived which explain substantial experimental finding in literature.
A rapid molecular screening programme has been established for the long arm of the human Y chromosome in Yq11 in order to quickly detect small interstitial deletions in this chromosome region. They have been observed in idiopathic sterile males with azoospermia and a severe oligozoospermia and are therefore indicative for deletion of AZF gene sequences. AZF (i.e. azoospermia factor) is a genetic factor located in Yq11 which controls human spermatogenesis. The screening programme is based mainly on a multiplex PCR approach using a series of Y-specific primers amplifying single DNA loci in Yq11. The order of all Y-DNA loci can be unequivocally arranged along the whole long Y arm. Therefore, any detected deletion can be quickly mapped in relation to the proposed position of AZF. Benefits and pitfalls of this new diagnostic Y screening method will be discussed.
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