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Biomedical subjects

T C Mathew

Publications and source records attributed to T C Mathew.

At least 19 recordsLinked to original sources

Serum changes in trace elements during thyroid cancers.

The objective was to examine changes in trace elements due to thyroid cancer in humans. Serum levels and tissue contents of trace elements (Zn, Cu, Mn, Mg, Fe and Se) were measured in 43 patients with thyroid cancer before and 4 days after surgery were compared to normal values. The serum levels of zinc in cancer patients were lower than those of normal subjects. Surgical removal of the cancer resulted in the restoration of these levels. Although serum Cu levels in patients were not different from normal, but post-operatively these levels rose significantly (p < 0.001). Levels of Fe, Mg and Mn were significantly lower (p < 0.001) post-operatively. There was no significant change in Serum Se levels. The thyroid tissue contents of these trace elements did not show a difference between the normal (Juxta-tumor) thyroid tissue and the cancerous lesion. Out of the six trace elements examined, the decrease of serum levels of zinc in cancer patients may be linked to the disease condition. It is suggested that this change: (a) may be used to demonstrate successful cancer surgery and (b) may have implications for a long-term follow-up of thyroid cancer patients.

Adenocarcinoma, Follicular↗

Expression of CD44s in human colorectal cancer.

CD44s is a cell adhesion molecule, which belongs to the family of hyaluronan binding proteins. Anti-body to CD44s is used to establish the association of its expression with the clinicopathological characteristics of colorectal cancer using immunohistochemical methods. The aim of this study is to investigate the expression of the standard form of CD44 (CD44s) in colorectal cancer tissues as compared to adjacent normal colonic tissues. Furthermore, the level of expression of CD44s in colorectal cancer tissues was correlated with the degree of histological differentiation, Duke s classification, sex, size and site of the tumor. Immunohistochemical analysis for CD44s was carried out in 49 paraffin-fixed sections of neoplastic colorectal tissues and non-neoplastic ones adjacent to the lesion, by the standard peroxidase-antiperoxidase method. Expression of these antigens were compared in normal and malignant epithelium and stromal cells. The results show that the level of CD44s in the epithelial and stromal cells was significantly higher in the colorectal cancer tissues than the normal ones. However, there was no association between the percentages of expressions of CD44s and the degree of histological differentiation, Duke s classification, sex or size of the tumor. There was however, a significantly higher expression of CD44s in the epithelium of rectal cancer than that of colonic cancer. This study indicates that the expression of CD44s is significantly higher in colorectal cancer tissues. However, further studies are required to understand its role in tumor progression and metastasis of this disease.

Adult↗

Expression of E-cadherin in human colorectal cancer.

AIM: To investigate the expression of E-cadherin, a calcium-dependent cell-cell adhesion molecule in colorectal carcinoma. Antibodies to E-Cadherin were used to establish the association of their expression with the clinicopathological characteristics of this disease using immunohistochemical methods. METHODS: Immunohistochemical analysis for E-cadherin was carried out in formalin-fixed, paraffin-embedded sections of neoplastic colorectal tissues and non-neoplastic ones adjacent to the lesion from 49 patients who underwent surgery, by the standard peroxidase-antiperoxidase method. Expression of this antigen in normal and malignant epithelium and stromal cells was compared. RESULTS: Both neoplastic and normal tissues showed expression of E-cadherin. There was, however, higher expression of E-cadherin in epithelial cells in both tumour and normal tissues than stromal cells. The percentage of expression in epithelial cells of well-differentiated tumours was significantly higher than moderately differentiated tumours. Loss of normal membranous expression and the presence of cytoplasmic and mixed staining were found frequently in tumour tissues (p = 0.004). This loss of membranous expression, however, did not correlate with Duke's staging, tumour grade, sex, size or site of the tumour. CONCLUSION: This study suggests that the lower expression of E-cadherin in less differentiated tumours may explain their aggressive nature, although loss of membranous expression was not significantly correlated to Duke's staging, tumour grade, sex, size and site of tumour.

Adenocarcinoma↗

Level of superoxide dismutase, glutathione peroxidase and uric acid in thioacetamide-induced cirrhotic rats.

Levels of superoxide dismutase and glutathione peroxidase were determined in blood and hepatic tissues of thioacetamide-induced cirrhotic rats and compared to levels in age-matched control animals. The plasma level of uric acid was also determined in these animals. A general decrease was noticed in the level of all the antioxidants examined as compared to the control. This decrease was statistically significant in the level of all the antioxidants studied, except for the level of superoxide dismutase in blood. A decrease in the antioxidant level may indicate an increase in free radical level and thereby an increase in cellular damage in cirrhotic rats. The changes in the level of antioxidants showed a direct correlation with the changes in the level of trace elements observed in our previous studies. These studies suggest that antioxidants alone or in combination with trace elements may have beneficial effects in treating liver cirrhosis.

Animals↗

Brain selenium accumulation in rat pups of selenium supplemented mothers.

Selenium is essential for normal mammalian development. Being a component of antioxidant enzyme, glutathione peroxidase, it plays a major role in protecting the cells from free radical damage. The level of glutathione peroxidase was directly related to the amount of selenium present in various tissues and organs. A decrease in selenium leads to various pathological changes in humans as well as in various laboratory animals. The aim of the present study was to understand whether there is an increase in the level of selenium in different brain regions of rat pups whose mothers were supplemented with selenium, either 2 or 4 mg/l of their drinking water throughout the period of their pregnancy. There was a significant increase in the level of selenium in the cerebellum, cortex and hypothalamic and hippocampal tissues of selenium supplemented mothers as compared with those of non-supplemented mothers. The brain stem of these animals did not show any significant difference in the level of selenium. Furthermore, the differences in the level of selenium between the rat pups of 2 mg/l selenium supplemented mothers and 4 mg/l selenium supplemented mothers were not statistically significant. These studies suggest that supplementation of selenium to mothers during the period of their pregnancy can selectively increase the level of this trace element in different brain regions. Further studies are necessary to understand the significance of selective accumulation of selenium in specific brain regions on brain development and function.

Animals↗

Levels of IL-8 and myeloperoxidase in the lungs of pneumonia patients.

Interleukin-8 (IL-8) is considered as the major polymorphonuclear neutrophils (PMNs) chemoattractant cytokine in lung diseases such as asthma and adult respiratory distress syndrome (ARDS). However, controversial results were obtained regarding the involvement of IL-8 in the pathogenesis of pneumonia. This study examines the role of IL-8 in the recruitment and activation of PMNs in the lung of pneumonia patients. The interesting aspect of this study is that it is a site- specific analysis of the infected and uninfected lungs of the same patient. The level of IL-8 mRNA, protein and myeloperoxidase present in the cells of the bronchioalveolar lavages (BALs) taken from the areas of known pneumonic consolidations on chest X-ray (infected lung) are compared with the BALs obtained from areas of no obvious infiltrate (non-infected lung). The results obtained from the infected and non-infected lungs of pneumonic patients were further compared with that of a control group of non-smoking patients. The level of IL-8 mRNA and protein were determined by RT-PCR and ELISA respectively. There was a significant increase in the level of IL-8 mRNA in the infected lung as compared to its level in the non-infected lung (p < 0.001). In correlation with the increase in mRNA, IL-8 protein concentrations in BAL fluids from the infected lung were 6 fold higher than those taken from the non-infected lung (p < 0.0001). This pattern was also consistent with MPO activity in the BALs (4.5 fold more MPO activity in the infected lung as compared to that of the non-infected lung), indicating that IL-8 is directly implicated in neutrophil accumulation that follows acute respiratory infection. The results of the present study, therefore, indicate the involvement of IL-8 in the pathogenesis of pneumonia.

Adult↗

Pre- and postnatal tissue selenium of the rat in the growing state.

The aim of this study is to quantify the selenium (Se) content (in microg/g) during different gestational periods in rat fetal tissues, and to follow up the changes in the Se content of the placenta, fetal head, liver and lung during gestation and postpartum periods. Locally reared virgin female Wistar rats were mated. Pregnant rats were sacrificed on days 15, 18 and 21 of pregnancy. Newborn pups at the age of 3 days and rats at the age of 1 month were also investigated. There was a gradual increase in placental and whole head Se content as gestation proceeded compared to day 15; however, the differences between the groups were not statistically significant. The liver Se content at day 18 of gestation was significantly higher than at day 21 of gestation and in rats at 3 days of age, but lower than the Se content of the liver of rats at the age of 1 month and the differences were statistically significant. The lung Se content was higher at day 18 of gestation than at day 21 and in the 3-day-old rats, and all differences between all groups were statistically significant except when the lung Se content at day 18 is compared to that of 1-month-old animals. The continuous increase in the Se content of the placental tissues and the whole head, although not significant statistically, may indicate that the fetus relies heavily on its supply of Se from the maternal blood and in part on the supply of thyroid hormones which are important for brain development, as evidence exists that T(4) and T(3) are present in the fetal brain in early fetal life before the onset of fetal thyroid function. The higher content of Se on day 18 and its decline on day 21 of gestation in the liver may imply that it is stored and being utilized partly in other tissues for other functions and particularly for thyroid hormone synthesis, metabolism and functions.

Animals↗

Cholangiocarcinoma and liver cirrhosis in relation to changes due to thioacetamide.

Different doses of thioacetamide (0.05%, 0.1% and 0.15%) were used to induce liver cirrhosis in Wistar rats. Thioacetamide at 0.5% caused cirrhosis by the twelfth week of treatment. A severe bile duct proliferation and cholangiocarcinoma was seen at longer intervals. Animals treated with higher doses (0.1% and 0.15%) of thioacetamide developed more severe intense degenerative changes in the liver and died in the twelfth and eighth week respectively. The serum and tissue contents of Zn and Cu changed in a characteristic fashion that was consistent with the severity of the liver damage. Serum Zn and Cu concentrations were at their lowest in the animals that developed severe degenerative liver and died at higher dose (0.15%) of thioacetamide. This study indicates that treatment of rats with 0.05% thiocetamide is more effective and appropriate for the induction of liver cirrhosis. Continued administration of the drug at this dosage led to the development of further changes in the liver. This model may be suitable for studying these long term changes that occur in the liver and lead to cirrhosis. Events that precede the development of severe bile duct proliferation and cholangiocarcinoma may also be studied.

Animals↗

Thioacetamide toxicity and the spleen: histological and biochemical analysis.

Exposure to thioacetamide is associated with the development of liver cirrhosis in experimental animals. In addition to liver, thioacetamide toxicity has been observed in other organs. In this study, the toxic effect of thioacetamide on the spleen was investigated at 0, 4, 8 and 12 weeks post-treatment durations. The level of tissue copper and selenium increased until the eighth week when a significant drop was observed. The zinc level was also increased but returned back to normal by week 8, thereafter it showed further increase. Calculation of the copper/zinc ratio showed an increase, but, recovered and returned to normal value by week 12. The level of manganese fluctuated until the eighth week. It then increased rapidly. Histological studies of the spleen tissue showed a significant increase in extramedullary haematopoiesis in the red pulp region and marked hyperplasia in the marginal zone and follicles. The results of this study, demonstrate an intimate association between trace element levels and spleen pathology, as observed in studies of other organs.

Animals↗

Association between supraependymal nerve fibres and the ependymal cilia of the mammalian brain.

The ciliated ependymal cells that line the floor of the fourth ventricle in adult Wistar rats are overlaid by an immense network of supraependymal nerve fibres. This study presents morphological evidence of a characteristic association of supraependymal nerve fibres with the cilia of the ependymocytes of the ventricular surface. It is found that the supraependymal nerve fibres accumulate and/or terminate at the base of the clusters of ependymal cilia. These fibres are varicose in nature and consist of large-diameter fibres with numerous prominent varicosities and small-diameter fibres with less frequent and less prominent varicosities. The characteristic association of the supraependymal nerve fibres with the ciliated ependymocytes suggests that these nerve fibres may be involved in producing co-ordinated ciliary movements in the mammalian brain.

Animals↗

Regeneration of supraependymal nerve fibers in rat.

Factors intrinsic and extrinsic to the neurons regulate the regeneration of axons following axotomy. Elucidation of these mechanisms will provide fundamental information on the regulation of growth in mammalian neurons. To understand the role of environmental factors in nerve regeneration, this study focuses on the axotomy-induced regeneration of supraependymal nerve fibers that inhabit an environment different from other central nervous system neurons and the neurons of the peripheral nervous system. These fibers are ideally located to receive various neuroactive substances that are streaming in the cerebrospinal fluid. Transmission electron microscopic studies reveal the presence of three types of fibers on the ventricular surface. They are fibers with clear synaptic vesicles, those containing small dense core vesicles together with clear synaptic vesicles and fibers containing large dense core granules. To study the regenerative potential of supraependymal nerve fibers, they were axotomized by inflicting mechanical injury to the floor of the third ventricle. Following axotomy, the regenerative ability of the supraependymal nerve fibers was monitored between five and thirty days, by scanning electron microscopy. By the fifth day, there was a noticeable increase in the neuronal network that gradually increased throughout the experimental period. The regenerative ability of supraependymal neurons, as compared with other neurons in the central nervous system, could be due to the differences in their environment. These studies suggest that mammalian cerebral ventricles may be an adequate site for neural transplantation.

Animals↗

Electrocardiographic correlates of absent septal q waves.

Compared with 100 consecutive electrocardiograms with septal q waves, 100 consecutive electrocardiograms without septal Q waves were otherwise normal only 4 times (vs 28 times; p <0.001). The strongest electrocardiographic correlate was QS in lead V1 (68 vs 4; p <0.001).

Adult↗

Selenium and liver cirrhosis.

Effects of selenium deficiency, induced by thioacetamide, were investigated in rats. Thioacetamide (0.3 g/L) given in drinking water, as expected, caused a significant loss of selenium from the liver. It was accompanied by liver cirrhosis and a significant increase in the liver weight as well as liver to body weight ratio. A significant loss of selenium from spleen was also accompanied by an increase in its weight. Weights of lungs, testis and kidney, however, were not affected by thioacetamide and there was no change in their selenium content. Plasma levels of selenium were significantly reduced in the thioacetamide treated group. All these changes were confirmed to be due to selenium deficiency caused by thioacetamide, as supplementation with selenium reversed these changes. The mode of action of selenium is unknown but may involve anti-oxidant defense mechanisms.

Animals↗

Supraependymal neuronal elements of the floor of the fourth ventricle in adult rat: a scanning electron microscopic study.

Scanning electron microscopic studies of the floor of the fourth ventricle revealed the presence of a cluster of neuron-like structures and an extensive network of fibers on the ependymal surface. These supraependymal cell clusters are found on the sparsely ciliated regions of the fourth ventricle. The surface of these cells is richly covered with nerve ending-like structures of varying size and shape. Long cables of intertwined fibers are present all over the surface of the fourth ventricular floor. Majority of these fibers are varicose in nature. Some of these fibers end blindly as round or ellipsoid thickening in the ventricular cavity. The widespread occurrence of supraependymal structures of the third and fourth ventricles, which are presumed to be neurons, nerve fibers and free floating nerve endings in the cerebrospinal fluid (CSF), suggest that they potentially function as an additional of intraventricular communication.

Animals↗

Bacterial translocation in thioacetamide induced liver cirrhosis in rats.

Cirrhotic liver is predisposed to bacterial infections. Different species of bacteria including Escherichia coli, Enterobacter and Bacteroides fragilis were found to colonize thioacetamide-induced cirrhotic rat liver. Zinc treatment of the cirrhotic rats significantly corrected the histological and histochemical changes in the liver. However, this reversal with zinc treatment was not accompanied by any change in the bacterial colonies in the liver. The study shows that cirrhosis predisposes liver to bacterial colonization and the process is not reversible despite the partial reversal of the cirrhotic changes.

Animals↗

Coronary artery bypass grafting in immune thrombocytopenic purpura.

BACKGROUND: Reports of patients with idiopathic thrombocytopenic purpura undergoing cardiac operations are scarce and no recommendations exist regarding their management. We report 3 patients with idiopathic thrombocytopenic purpura and severe coronary artery disease who underwent uncomplicated coronary bypass grafting. METHODS: The case history of each patient with idiopathic thrombocytopenic purpura who underwent coronary artery bypass grafting and the literature were reviewed. RESULTS: All 3 patients underwent uncomplicated coronary artery bypass grafting after preoperative treatment with intravenous immunoglobulin and intraoperative platelet transfusions if needed. Prophylactic splenectomy was not performed. There was no increased incidence of bleeding complications. CONCLUSIONS: Coronary artery bypass grafting can be safely performed in patients with idiopathic thrombocytopenic purpura using conventional conduits after pretreating with immunoglobulin G and avoiding splenectomy.

Aged↗

Zinc and liver cirrhosis: biochemical and histopathologic assessment.

Experimental liver cirrhosis was produced by administration of thioacetamide. Cirrhotic animals were divided into two groups: one group was given zinc sulphate and the second kept as cirrhotic control. Zinc-treated animals showed a restoration of normal hepatic and plasma zinc and copper levels. Similarly, plasma levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl aminotransferase, and total bilirubin decreased significantly. Light microscopic studies showed that most of the hepatocytes appeared normal in zinc-treated as compared with untreated cirrhotic animals. The amount of fibrin, reticulin, and collagen, which was high in the cirrhotic livers, decreased following zinc treatment. Staining with periodic acid Schiff's reagent showed the ability of hepatocytes to store glycogen after zinc treatment. These results revealed that zinc may have some beneficial effect in the treatment of liver cirrhosis.

Alanine Transaminase↗

Subpopulations of stromal cells from long-term human bone marrow cultures: ontogeny of progenitor cells and expression of growth hormone receptors.

Long-term culture of bone marrow derived stromal colony forming cells (S-CFC) in matrix and nutrient defined agar medium resulted in stromal cell colonies that pass sequentially through three distinct morphological stages: firstly, aggregated loose syncytium of round to avoid cells (stage I), a second developmental stage of large branching colonies in which the cells become enlarged, elongated with cytoplasmic projections forming a loosely anastomized network with adjacent cells (stage II), and finally cells become dissociated, loosing their long, thin cytoplasmic filaments and breaking their contacts with one another, but remain large and retain a bi-polar nature (stage III). Cells were also grown in liquid medium in a culture microenvironment closely resembling conditions of haemopoiesis in vitro. Using a panel of well defined monoclonal antibodies reactive against the rat, rabbit and human growth hormone receptors, this study found immunochemical evidence of the presence and localization of binding sites of growth hormone (GH) in the cell membrane and extra-nuclear Golgi area of long-term bone marrow derived human stromal cells in liquid and semi-solid nutrient agar mediums. GH-receptor immunoreactivity was present in small proliferating progenitor cells, myofibroblast-like cells, large reticular fibroblast cells, adipocytes and endothelial cells. Only MAb known to be reactive against human tissue resulted in strong immunoreactivity. The expression of GH-receptors not only on small proliferating, but also on the well differentiated cells, indicates a role for growth hormone on non-progenitor cells. GH-receptor immunoreactivity on differentiating and/or differentiated cells suggests that GH is also necessary for, or has a trophic function in differentiation. We propose that direct GH action is necessary not only for differentiation of progenitor cells as implied by the dual effector hypothesis, but also their subsequent clonal expansion, differentiation and maintenance.

Animals↗