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Biomedical subjects

B Tobin

Publications and source records attributed to B Tobin.

At least 19 recordsLinked to original sources

Comparison of therapeutic regimens in the amelioration of alterations in rat gastrointestinal mucosal DNA, RNA and protein induced by streptozotocin diabetes mellitus.

Type 1 diabetes mellitus is characterized by hyperglycemia, insulinopenia, and secondary neural, renal and vascular complications. Clinical manifestations in the gastrointestinal tract range from initial mild complications to more severe complications as the disease progresses, but as of yet, are poorly understood. The current study has two main foci 1) to monitor the alterations in gastrointestinal DNA, RNA and protein content induced by streptozotocin diabetes and 2) to use these parameters to monitor the efficacy of intensive insulin treatment versus pancreatic islet transplantation in the amelioration of the diabetes induced alterations. Female Wistar Furth rats were rendered diabetic by streptozotocin injection and measured for alterations in gastrointestinal DNA, RNA and protein content. Similarly, animals which had streptozotocin-induced diabetes were also treated by intensive insulin therapy or pancreatic islet transplant and monitored for alterations in gastrointestinal DNA, RNA and protein content. In general, diabetes induced increases in stomach, duodenal, jejunal and colonic macromolecular content. With few exceptions, treatment with either intensive insulin or pancreatic islet transplantation returned each variable measured back to control levels. In every case, pancreatic islet transplantation was comparable to intensive insulin therapy. In the short term the treatments are comparable, but long term analyses are needed to determine if the treatments offer any difference in their ability to prevent the long term complications related to diabetes mellitus.

Animals↗

Iron status and exercise.

The prevalence of iron deficiency anemia is likely to be higher in athletic populations and groups, especially in younger female athletes, than in healthy sedentary individuals. In anemic individuals, iron deficiency often not only decreases athletic performance but also impairs immune function and leads to other physiologic dysfunction. Although it is likely that dietary choices explain much of a negative iron balance, evidence also exists for increased rates of red cell iron and whole-body iron turnover. Other explanations of decreased absorption and increased sweat or urine losses are unlikely. The young female athlete may want to consider use of low-dose iron supplements under medical and dietary supervision to prevent a decline in iron status during training.

Adolescent↗

Reply to Savulescu: why we should maintain a prohibition on destructive research on human embryos.

Julian Savulescu argues that destructive experimentation on human embryos is ethically permissible. He attempts to refute objections to such experimentation, and offers an account of the status of the early human embryo according to which it is the kind of entity upon which it is perfectly permissible to experiment. However, his attempts to refute the objections to destructive experimentation on human embryos are unconvincing, and the consequences of his own view of the status of the embryo are counter-intuitive.

Cloning, Organism↗

Frequent loss of imprinting of PEG1/MEST in invasive breast cancer.

The human PEG1 gene is a newly identified imprinted gene on 7q32. Genetic aberrations of this chromosomal region are often detected in invasive breast carcinomas. In this study, we show monoallelic PEG1 expression in normal breast tissue, indicating the presence of a functional imprint, and more importantly, we demonstrate loss of imprinting (LOI) in all of seven informative invasive breast carcinomas. In contrast to this, in one case of atypical ductal hyperplasia (ADH) found in residual breast, imprinting was maintained. This raises the possibility that aberrant imprinting of PEG1 may be involved in the progression from hyperplasia to invasive breast cancer.

Alleles↗

Loss of heterozygosity of the Wilms' tumor suppressor gene (WT1) in in situ and invasive breast carcinoma.

The Wilms' tumor suppressor gene (WT1), a nuclear transcription factor, regulates the expression of the insulin-like growth factor (IGF) and transforming growth factor (TGF) systems, both of which are implicated in breast tumorigenesis. WT1 allelic integrity was examined by loss of heterozygosity (LOH) studies in formalin-fixed, paraffin-embedded (FFPE) ductal carcinoma in situ (DCIS, n = 20) and fresh frozen primary invasive breast carcinomas (n = 24). Loss of heterozygosity (LOH) at the WT1 locus (11p13) was examined by PCR evaluation of an Hinf1 restriction fragment length polymorphism (RFLP) and correlated to tumor stage (in situ and invasive). After identification of the heterozygous/informative breast lesions, 1 of 12 (8.3%) DCIS (high-grade micropapillary) and 3 of 14 (21.4%) of infiltrating carcinomas (high grade) showed loss of one allele, suggesting that LOH of the WT1 locus is a rare genetic event in early breast cancer, becoming more common in invasive and in high-grade lesions.

Breast Neoplasms↗

Drugs and brain death.

IN THE EARLY HOURS of the morning, a fit young man leaves a party, where drugs are reported to have been consumed, to walk home. A short time later he is found unconscious by the roadside, with severe head injuries. En route to hospital by ambulance, he suffers a cardiac arrest and is successfully resuscitated. On arrival at the Emergency Department he has obvious head injuries and is deeply unconscious, but shows spontaneous ventilatory movements. Available history is that he is a 20-year-old student with well-controlled epilepsy for which he takes phenytoin. It is not known how he sustained his injuries. Pupils are equal, small and react sluggishly to light. There is generalised flaccidity and an extensor-plantar response to painful stimuli. Skull x-rays show no fractures and computed tomography shows early cerebral oedema and scattered cerebral contusions with evidence of subarachnoid haemorrhage. He is transferred to the intensive care unit and measures to inhibit cerebral oedema, including mannitol, are commenced. An N-methyl-D-aspartate (NMDA) inhibitor is administered for neuroprotection and ventilatory support is commenced. Over the next 24 hours haemodynamic support is needed with fluid loading and vasopressors. A urine drug screen by Toxilab (Toxilab Incorporated, Irvine, Calif.) shortly after arrival shows the presence of phenytoin and morphine. The report states that the presence of benzodiazepines is suspected. Plasma phenytoin concentration at the time of arrival was 78 mumol/L (optimal range, 40-80 mumol/L). Forty hours after admission his condition has deteriorated. His pupils are at midposition, no longer reactive to light and his lower limbs exhibit only spinal reflexes. His relatives begin to prepare themselves for the fact he may not survive and raise the issue that he would have been keen to donate organs under such circumstances. What is the opinion regarding withdrawal of life support at this time?

Adult↗

Comparison of oestrogen receptor assessment in frozen and paraffin sections.

Estimation of oestrogen receptors (ER) in breast carcinoma has important therapeutic and prognostic implications. The dextran-coated charcoal (DCC) biochemical technique is being replaced in many institutions by immunohistochemical techniques. The aim of this study was to assess the level of agreement between ER counts in frozen and paraffin sections. Ninety-seven infiltrating breast carcinomas were studied immunohistochemically, for ER in frozen and paraffin sections. Cases were classified as ER-positive if > or = 10% of the tumor cells were positive. Both techniques gave a high level of correlation and agreement. There was complete agreement in classifying cases as ER-positive or ER-negative. ER estimation on only one case was outside 2SD of complete agreement. Oestrogen-receptor content can be assayed satisfactorily in paraffin sections and offers many advantages over the frozen section technique.

Frozen Sections↗

Aberrant MT2 positivity distinguishes follicular lymphoma from reactive follicular hyperplasia in B5- and formalin-fixed paraffin sections.

Often, it is difficult to distinguish follicular lymphoma from reactive follicular hyperplasia histologically. Immunotypic evidence of monoclonality cannot be demonstrated routinely or reliably in routine paraffin-embedded sections. To determine whether a panel of monoclonal antibodies reactive with lymphoid cells in paraffin-embedded sections might be useful in distinguishing these confusing proliferations, the authors examined 45 follicular lymphomas and 30 follicular hyperplasia with the following antibodies; L26, B2, MT1, MT2, and UCHL-I. All sections were routine paraffin preparations from formalin- or B5-fixed tissue and were immunostained with the avidin-biotin immunoperoxidase technique. Ninety-two percent of the B5-fixed and 77% of the formalin-fixed lymphomas were MT2 positive. None of the reactive hyperplasias stained positively, and none of the other antibodies demonstrated consistent differences between these benign and malignant proliferations. MT2 marks interfollicular T cells and mantle-zone B cells in normal lymph nodes but does not mark normal germinal centers; this staining pattern is retained in reactive hyperplasia. However, paradoxically, in most follicular lymphomas the neoplastic germinal centers show aberrant MT2 positively. The authors conclude that MT2 may be useful in distinguishing follicular lymphoma from follicular hyperplasia in paraffin sections.

Antibodies, Monoclonal↗

Evidence for thyroid hormone deficiency in iron-deficient anemic rats.

Iron-deficient anemic rats have previously been shown to have low plasma levels of thyroid hormone and a poor plasma thyroid hormone response to acute cold exposure. As an initial exploration, we examined thyroid hormone metabolism during iron deficiency in age-matched rats from three aspects: 1) plasma TSH (thyrotropin, thyroid stimulating hormone), T4 (thyroxine) and T3 (triiodothyronine) responses to graded doses of exogenous TRH (thyrotropin releasing hormone), 2) plasma T3 kinetics, and 3) rates of hepatic T3 production. Iron-deficient anemic rats had lower basal TSH values and blunted TSH responses to intravenous TRH injection at three different doses (10, 25 and 50 ng TRH/100 g body wt). Iron-deficient anemic rats also had a significant decrease in plasma T3 turnover (42 vs. 88 ng/h in controls), and significantly lower hepatic T4-5'-deiodinase activities than controls [26 vs. 44.0 ng T3/(mg protein.20 min)]. Thus, decreased rates of T3 production in iron-deficient anemic rats, as documented by turnover studies, may be related to decreased deiodinase activity and reduced peripheral formation of T3. The dampened TSH responses to TRH further facilitate or perpetuate this T3 deficiency. We propose that this abnormal thyroid state is partially responsible for impaired thermogenesis in iron-deficiency anemia.

Anemia, Hypochromic↗

Norepinephrine turnover in iron deficiency at three environmental temperatures.

Iron-deficient anemic rats had a significant elevation in urinary norepinephrine (NE) after 7 days at 30 and 24 degrees C, but not at 10 degrees C, compared with control animals. NE turnover studies were performed to examine sympathetic nervous system activity in a tissue-specific fashion. NE content in myocardium decreased by nearly 50% in hypertrophied iron-deficient hearts at all three temperatures, whereas fractional turnover rates were compensatorily increased. In contrast, interscapular brown adipose tissue NE turnover was significantly reduced to 30% of normal in iron-deficient animals at both 30 and 10 degrees C. Serum triiodothyronine concentrations were similar to controls at 30 degrees C but were decreased at lower temperatures. Serum tetraiodothyronine concentrations were lower in iron-deficient animals at all three environmental temperatures. We conclude that increased sympathetic nervous system activity compensatory to temperatures below thermoneutrality is less well controlled in iron-deficient animals than in controls, and at a low environmental temperature this may possibly explain the poor thermoregulatory capacity of iron-deficient animals. A generalized hypernoradrenergic state is not supported by our NE turnover study and does not explain the elevated urine NE concentrations.

Adipose Tissue↗

Solitary (localized) fibrous mesothelioma: evidence against mesothelial cell origin.

Five cases of solitary (localized) fibrous mesothelioma were studied immunohistochemically, utilizing monoclonal antibodies against high and low molecular weight cytokeratin, vimentin, carcinoembryonic antigen, epithelial membrane antigen and factor VIII related antigen. In contrast to normal mesothelium and contrary to previous reports from malignant mesotheliomas all the tumours were negative for keratin. They were strongly positive for vimentin. Two cases were studied electron microscopically; no ultrastructural evidence of mesothelial cell differentiation was identified. Our immunohistochemical and ultrastructural findings argue against a mesothelial cell origin, whereas the presence of vimentin suggests a mesenchymal histogenesis. It is postulated that these tumours arise from sub-mesothelial mesenchymal connective tissue.

Adult↗

Neonatal eye infections due to Mycoplasma hominis.

In one year Mycoplasma hominis was isolated from 8 out of 250 clinically infected eyes of newborn infants. This infection occurred in only a small proportion of babies whose mothers carried the organism in the vagina. Probably mycoplasma infection of the eye in neonates is commoner than is realized.

Adolescent↗