Biomedical subjects

S Mohsin

Publications and source records attributed to S Mohsin.

14 recordsLinked to original sources

PubMed2003

Detecting microdamage in bone.

Fatigue-induced microdamage in bone contributes to stress and fragility fractures and acts as a stimulus for bone remodelling. Detecting such microdamage is difficult as pre-existing microdamage sustained in vivo must be differentiated from artefactual damage incurred during specimen preparation. This was addressed by bulk staining specimens in alcohol-soluble basic fuchsin dye, but cutting and grinding them in an aqueous medium. Nonetheless, some artefactual cracks are partially stained and careful observation under transmitted light, or epifluorescence microscopy, is required. Fuchsin lodges in cracks, but is not site-specific. Cracks are discontinuities in the calcium-rich bone matrix and chelating agents, which bind calcium, can selectively label them. Oxytetracycline, alizarin complexone, calcein, calcein blue and xylenol orange all selectively bind microcracks and, as they fluoresce at different wavelengths and colours, can be used in sequence to label microcrack growth. New agents that only fluoresce when involved in a chelate are currently being developed--fluorescent photoinduced electron transfer (PET) sensors. Such agents enable microdamage to be quantified and crack growth to be measured and are useful histological tools in providing data for modelling the material behaviour of bone. However, a non-invasive method is needed to measure microdamage in patients. Micro-CT is being studied and initial work with iodine dyes linked to a chelating group has shown some promise. In the long term, it is hoped that repeated measurements can be made at critical sites and microdamage accumulation monitored. Quantification of microdamage, together with bone mass measurements, will help in predicting and preventing bone fracture failure in patients with osteoporosis.

Animals↗

PubMed2003

Developmental and hormonal signals dramatically alter the localization and abundance of insulin receptor substrate proteins in the mammary gland.

Insulin receptor substrates (IRS) are central integrators of hormone, cytokine, and growth factor signaling. IRS proteins can be phosphorylated by a number of signaling pathways critical to normal mammary gland development. Studies in transgenic mice that overexpress IGF-I in the mammary gland suggested that IRS expression is important in the regulation of normal postlactational mammary involution. The goal of these studies was to examine IRS expression in the mouse mammary gland and determine the importance of IRS-1 to mammary development in the virgin mouse. IRS-1 and -2 show distinct patterns of protein expression in the virgin mouse mammary gland, and protein abundance is dramatically increased during pregnancy and lactation, but rapidly lost during involution. Consistent with hormone regulation, IRS-1 protein levels are reduced by ovariectomy, induced by combined treatment with estrogen and progesterone, and vary considerably throughout the estrous cycle. These changes occur without similar changes in mRNA levels, suggesting posttranscriptional control. Mammary glands from IRS-1 null mice have smaller fat pads than wild-type controls, but this reduction is proportional to the overall reduction in body size. Development of the mammary duct (terminal endbuds and branch points) is not altered by the loss of IRS-1, and pregnancy-induced proliferation is not changed. These data indicate that IRS undergo complex developmental and hormonal regulation in the mammary gland, and that IRS-1 is more likely to regulate mammary function in lactating mice than in virgin or pregnant mice.

Adipose Tissue↗

PubMed2000

A hypersensitive estrogen receptor-alpha mutation in premalignant breast lesions.

The best current model of breast cancer evolution suggests that most cancers arise from certain premalignant lesions. We have identified a common (34%) somatic mutation in the estrogen receptor (ER)-alpha gene in a series of 59 typical hyperplasias, a type of early premalignant breast lesion. The mutation, which affects the border of the hinge and hormone binding domains of ER-alpha, showed increased sensitivity to estrogen as compared with wild-type ER-alpha in stably transfected breast cancer cells, including markedly increased proliferation at subphysiological levels of estrogen. The mutated ER-alpha exhibits enhanced binding to the TIF-2 coactivator at low levels of hormone, which may partially explain its increased estrogen responsiveness. These data suggest that this mutation may promote or accelerate the development of cancer from premalignant breast lesions.

Breast↗

PubMed1994

Hyperthyroidism increases covalent binding and biliary excretion of 1,1-dichloroethylene in rats.

Distribution, covalent binding, and biliary excretion of 1,1-dichloroethylene (DCE) were examined in euthyroid (EuT) and hyperthyroid (HyperT) rats, which are more vulnerable to DCE hepatotoxicity. Male Sprague-Dawley rats were made hyperthyroid by 3 sc injections of thyroxine at 48-h intervals prior to experiments; euthyroid controls received vehicle injections. A time course study monitored the circulation and excretion of 14C-DCE label for 24 h after administration of 14C-labeled DCE (50 mg/kg in mineral oil) in serial blood and urine samples. At 24 h, total and covalently bound 14C-label were measured in liver, kidney, and lung. Hepatotoxicity of DCE was enhanced in the HyperT rats, as evidenced by elevated serum activities of aminotransferase and histopathology, and was associated with increases in circulating metabolite, and in metabolite bound to red blood cells and liver but not to kidney or lung. Hyperthyroidism had little effect on in vitro capacity of hepatic microsomes to convert DCE to reactive intermediates as reflected by covalent binding. A biliary excretion study in pentobarbital-anesthetized rats showed a striking, but transient, increase in toxicant metabolite excretion in bile of HyperT rats during the first 2 h after toxicant administration (14C-DCE, 100 mg/kg). During the next 2 h, biliary metabolite excretion by HyperT rats decreased while there was a rise in circulating amounts of total and bound 14C-label. Thus, although hyperthyroidism had little effect on the total extent of DCE metabolized, this hormonal disturbance may have transiently enhanced metabolite formation and definitely was associated with a lesser ability to detoxify reactive DCE metabolites capable of injuring hepatic cell constituents by covalent binding reactions.

Animals↗

PubMed1993

Serum level of iron and transferrin in normal and anaemic pregnant women.

Serum levels of iron and transferrin, and percent saturation of total iron binding capacity (TIBC) and latent iron binding capacity were estimated in 89 women in their I, II and IIIrd trimester of pregnancy. Associated infective, metabolic or degenerative diseases were excluded after clinical examination. The women were divided into three groups of normal, mildly anaemic and severely anaemic. In the normal group serum iron levels were within normal range irrespective of period of gestation, whereas in the anaemic groups, these were lower. Serum transferrin levels were significantly low in II and III trimester of pregnancy of anaemic women. Percent saturation of TIBC was even lower than normal in Ist trimester of pregnancy in normal pregnancy (27.12%). However in mild anaemic there was significant fall and in severe anaemia, it was very low, leaving a vast latent iron binding capacity. The decrease of % saturation of TIBC even in normal pregnant women is indicative of inherent poor stores, which may be due to defective diet.

Adolescent↗

PubMed1989

Significance of serum leucine aminopeptidase in tumours of female genital tract.

Serum leucine aminopeptidase (LAP) was estimated in 57 female patients with tumours of the genital tract and compared with 50 age-matched controls. Serum LAP was increased in leiomyomas (p less than 0.01) but significant rise was seen in leiomyosarcomas and endometrial carcinoma of the uterus (p less than 0.001). No increase in serum LAP level, above mean control value was observed in carcinoma of cervix. LAP levels were also increased in cystadenomas of the ovary (p less than 0.01) and highly significant increase, noted in cystadenocarcinomas and dysgerminoma stage III (p less than 0.001). However, no increase of enzyme activity was observed in poorly differentiated papillary carcinoma of the ovary. The serum enzyme level was higher in cystadenocarcinomas as compared to solid ovarian carcinomas in the same clinical stage.

Adult↗

PubMed1980