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Biomedical subjects

T Thomas

Publications and source records attributed to T Thomas.

At least 217 records · Page 12Linked to original sources
PubMed1995

Hydrogen peroxide changes in ischemic and reperfused heart. Cytochemistry and biochemical and X-ray microanalysis.

Active oxygen species including hydrogen peroxide (H2O2) play a major role in ischemia-reperfusion injury. In the present study, changes in myocardial H2O2 content as well as its subcellular distribution were examined in rat hearts subjected to ischemia-reperfusion. Isolated perfused rat hearts were made globally ischemic for 20 or 30 minutes and were reperfused for different durations. H2O2 content in these hearts was studied biochemically and changes were correlated with the recovery of function. These hearts were also analyzed for subcellular distribution of H2O2. Optimal conditions of tissue processing as well as incubation medium were established for reacting cerium chloride with H2O2 to form cerium perhydroxide, an insoluble electron-dense product. The chemical composition of these deposits was confirmed by x-ray micro-analysis. Global ischemia caused complete contractile failure in minutes and after 30 minutes of ischemia, these was a > 250% increase in the myocardial H2O2 content. Depressed contractile function recovery in the early phase of reperfusion was accompanied by approximately a 600% increase in the myocardial H2O2 content. Brief pre-fixation with low concentrations of glutaraldehyde, inhibition of alkaline phosphatase, glutathione peroxidase, and catalase, post-fixation but no post-osmication, and no counterstaining yielded the best cytochemical definition of H2O2. In normal hearts, extremely small amounts of cerium hydroperoxide precipitates were located on the endothelial cells. X-ray microanalysis confirmed the presence of cerium in the reaction product. Ischemia resulted in a stronger reaction, particularly on the sarcolemma as well as abluminal side of the endothelial cells; and upon reperfusion, cerium precipitate reaction at these sites was more intense. In the reperfused hearts, the reaction product also appeared within mitochondria between the cristae as well as on the myofibrils, but Z-lines were devoid of any precipitate. The data support a significant increase in myocardial H2O2 during both the phase of ischemia and the first few minutes of reperfusion. A stronger reaction on the sarcolemma and abluminal side of endothelial cells may also indicate enhanced H2O2 accumulation as well as vulnerability of these sites to oxidative stress injury.

Animals↗
PubMed1995

Atypical osteomalacia after 2 year etidronate intermittent cyclic administration in osteoporosis.

A 68-year-old postmenopausal woman with osteoporosis received intermittent cyclic etidronate therapy (400 mg/day). No concomitant diseases were noted. A baseline transiliac bone biopsy showed a high bone turnover without impairment due to mineralization. After 2 years of treatment, she had increased osteoid volume, and mineralization lag time corresponded to a variant form of osteomalacia called atypical osteomalacia. No clinical consequence was observed. This is the first case report of such a mineralization defect due to 2 year intermittent cyclic etidronate therapy.

Aged↗
PubMed1994

Implicit memory.

Explore the source record for details and available documents.

Anesthesia, General↗
PubMed1994

Interdependence of respiratory and cardiovascular changes induced by systemic hypoxia in the rat: the roles of adenosine.

1. In ten spontaneously breathing, Saffan-anaesthetized rats (group I), respiratory and cardiovascular responses evoked by 10 min periods of hypoxia (arterial partial pressure of O2, Pa,O2, 33 mmHg) were recorded before and after the administration of the adenosine receptor antagonist 8-phenyltheophylline (8-PT, 10 mg kg-1 i.v.). Similar experiments were performed on nine constantly ventilated rats (group II; Pa,O2, 29 mmHg) with arterial partial pressure of CO2 (Pa,CO2) held constant. 2. In group I, hypoxia induced an initial increase and a secondary fall in ventilation (VE) with an accompanying secondary fall in heart rate (HR), arterial pressure (ABP) fell and cerebral vascular conductance (CVC) increased progressively. Cerebral blood flow (CBF) tended to fall with time during hypoxia. 8-PT abolished the secondary falls in VE and HR and reduced the fall in ABP and increase in CVC, while CBF was better maintained. 3. In group II, hypoxia induced a similar cardiovascular response to that in group I, but at the 1st minute of hypoxia, the HR was lower and the increase in CVC was greater. 8-PT did not affect the hypoxia-induced changes in HR, ABP, CVC or CBF. 4. These results indicate specific ways in which the ventilatory and cardiovascular responses induced by hypoxia in the spontaneously breathing rat are interdependent. They also indicate that the influences of 8-PT on the cardiovascular changes induced by hypoxia during spontaneous ventilation are mainly a consequence of its ability to block the centrally mediated contribution of adenosine to the secondary fall in ventilation.

Adenosine↗
PubMed1994

Polyamine-induced Z-DNA conformation in plasmids containing (dA-dC)n.(dG-dT)n inserts and increased binding of lupus autoantibodies to the Z-DNA form of plasmids.

Blocks of potential Z-DNA-forming (dA-dC)n.(dG-dT)n sequences are ubiquitous in eukaryotic genomes. We examined whether naturally occurring polyamines, putrescine, spermidine and spermine, could provoke the Z-DNA conformation in plasmids pDHf2 and pDHf14 with 23 and 60 bp inserts respectively of (dA-dC)n.(dG-dT)n sequences using an e.l.i.s.a. Spermidine and spermine could provoke Z-DNA conformation in these plasmids, but putrescine was ineffective. For pDHf2 and pDHf14, the concentration of spermidine at the midpoint of B-DNA to Z-DNA transition was 25 microM, whereas that of spermine was 16 microM. Polyamine structural specificity was evident in the ability of spermidine homologues to induce Z-DNA. Inorganic cations, Co(NH3)6(3+) and Ru(NH3)6(3+), were ineffective. Our experiments also showed increased binding of anti-DNA autoantibodies from lupus patients as well as autoimmune MRL-lpr/lpr mice to pDHf2 and pDHf14 in the presence of polyamines. These data demonstrate that small blocks of (dA-dC)n.(dG-dT)n sequences could assume the Z-DNA conformation in the presence of natural polyamines. Increased concentrations of polyamines in the sera of lupus patients might facilitate immune complex-formation involving circulating DNA and anti-Z-DNA antibodies.

Animals↗
PubMed1994

Regulation of cyclin B1 by estradiol and polyamines in MCF-7 breast cancer cells.

Recent studies have identified a family of proteins called cyclins that control cell cycle. Among these proteins, cyclin B synthesis and degradation are necessary and sufficient to cause a Xenopus egg cell-free system to oscillate between S and M. To understand the link between hormonal regulation of cell growth and the expression of B-type cyclins, we studied the effect of estradiol on cyclin B1 mRNA in a hormone-responsive breast cancer cell line, MCF-7. Cells were synchronized at G1 by isoleucine starvation, and estradiol was added along with the removal of cell cycle block. Flow cytometric analysis showed 81 +/- 7% cells in G1 after 30 h of isoleucine starvation. Significant population of cells progressed to S by 16 h after the addition of estradiol, whereas a comparable transition occurred in control cells by 36 h only. In cells progressing from G1-->S-->G2-->M under the influence of estradiol, there was a significant increase in cyclin B1 mRNA at 30 and 36 h, consistent with the accumulation of this cyclin in G2/M. In addition, we found that cyclin B1 mRNA degradation occurred early in G1, and this process was accelerated by estradiol. At 2 h after removal of the isoleucine block, there was a 40% reduction in the level of cyclin B1 mRNA in estradiol-treated cells compared to untreated controls. Cyclin B1 protein degradation followed a similar pattern, as determined by Western blots using a monoclonal anti-cyclin B1 antibody. Since previous studies suggested a polyamine pathway in the mechanism of action of estradiol, we questioned whether polyamines are important in controlling the level of cyclin B1 mRNA. Treatment of synchronized cells with the polyamine biosynthetic inhibitor, difluoromethylornithine attenuated cyclin B1 mRNA degradation in the presence of estradiol. This process was mostly reversed by exogenous putrescine and spermidine but not by putrescine homologues. Collectively, these data suggest that the mechanism of cell growth regulation by estradiol in MCF-7 cells includes alterations in cyclin B1 mRNA. Our data also indicate molecular pathways for the action of polyamines in estrogenic control of cell cycle.

Biogenic Polyamines↗
PubMed1994

Membrane fluidity is different in intact erythrocytes and ghost membranes.

The fluorescence anisotropy of 1,6-diphenylhexatriene (DPH) and trimethylammonium-DPH in the membranes of intact human erythrocytes and ghost membranes was compared. The anisotropy of fluorophores is significantly higher in intact erythrocytes compared to that in ghost membranes. Perturbation of membranes by heating at 47 degrees C and use of a rotating stirrer affected the anisotropy of fluorophores in intact erythrocytes only. These results suggest that: (a) spectrin has a significant modulating effect on membrane fluidity, and (b) the physical properties of the cell membrane are different between intact erythrocytes and erythrocyte ghost membranes.

Erythrocyte Membrane↗
PubMed1994

Estradiol control of ornithine decarboxylase mRNA, enzyme activity, and polyamine levels in MCF-7 breast cancer cells: therapeutic implications.

Previous studies have shown that natural polyamines-putrescine, spermidine, and spermine-play a key role in the mechanism of action of estrogens in breast cancer. Ornithine decarboxylase (ODC) is the first enzyme of the polyamine biosynthetic pathway. To examine estrogenic regulation of polyamine biosynthesis in breast cancer, we measured ODC mRNA, ODC activity, and polyamine levels in G1 synchronized MCF-7 cells. ODC mRNA and activity increased four-fold over that of cells in G1 phase between 8 to 16 h after the addition of estradiol. Polyamine levels showed a sharp increase by 8 h after the addition of estradiol and decreased by 12 h. We further examined whether synthetic homologs of putrescine or spermidine could replace natural polyamines in supporting MCF-7 cell growth. Treatment of MCF-7 cells with 1 mM difluoromethylornithine (DFMO), an inhibitor of ODC, suppressed putrescine, spermidine, and spermine levels by 74, 78, and 10%, respectively, within 48 h. Cells treated with DFMO for 48 h were supplemented with either putrescine or its homologs or spermidine or its homologs. Diaminopropane, diaminobutane (putrescine), and diaminopentane were capable of fully or partially reversing the growth inhibitory effects of DFMO, whereas diaminoethane had no significant effect. Among a series of triamines, H2N(CH2)nNH(CH2)3NH2 (where n = 2 to 8; abbreviated as APn n = 4 for spermidine, or AP4), spermidine was most effective in reversing the effects of DFMO, whereas compounds with shorter or longer methylene bridging regions were less effective. AP8 was ineffective in reversing the growth inhibitory effects of DFMO. At 10 microM concentration, AP8 also inhibited DNA synthesis by 66%, as measured by [3H]-thymidine incorporation. These data show that MCF-7 cells have a strong requirement for polyamines for their growth and that estradiol stimulates the polyamine cascade by inducing the ODC mRNA level. Our results also suggest that polyamine homologs such as AP8 might be potentially useful in breast cancer therapy.

Breast Neoplasms↗
PubMed1994

Polyamine-induced changes in the sedimentation profile and DNA binding of aryl hydrocarbon receptor.

Aryl hydrocarbon (Ah) receptor mediates the toxic action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We studied the effects of polyamines--putrescine, spermidine and spermine--on the physical chemical properties of Ah receptor from A431 cells. Spermidine and spermine caused the precipitation of 9S oligomeric receptor with a gradual decrease in the receptor peak during density gradient sedimentation. RNase A treatment transformed the 9S Ah receptor to a 6S form and DNA binding increased by 2-fold. Following partial purification of transformed Ah receptor by preparative sucrose gradient centrifugation, it lost the ability to bind to DNA, but addition of spermidine increased DNA binding in a concentration-dependent manner. These data show that polyamines modulate the structure and DNA binding of Ah receptor and suggest that cellular polyamine levels might be important in the tissue specific toxicity of TCDD.

Binding Sites↗
PubMed1994

Expression of collagen alpha 1(IV), laminin and nidogen genes in the embryonic mouse lung: implications for branching morphogenesis.

The patterns of laminin A, B1, B2, nidogen and collagen alpha 1(IV) gene expression in the embryonic mouse lung were determined using in situ hybridization histochemistry at a stage when branching morphogenesis is taking place. Collagen alpha 1(IV), laminin B1 and B2 genes were expressed throughout the mesenchyme and epithelium. Nidogen gene expression was uniform throughout the mesenchyme but was not detected in epithelial cells. Laminin A mRNA was localized to cells closely associated with a basement membrane at the epithelial-mesenchymal interface. However, expression of the laminin A gene was limited to the mesenchymal cells in bronchial regions and to epithelial cells in distal terminal lobules. We propose that the pattern of laminin A gene expression in different regions of the developing lung will influence the structure of the basement membrane at the epithelial-mesenchymal interface and thus have a role in branching morphogenesis.

Animals↗
PubMed1994

Oculonasal synkinesis.

A phenomenon the authors have termed oculonasal synkinesis has been observed in 13 individuals in two independent practices. This complex presents as simultaneous contraction of the orbicularis oculi and the compressor narium minor muscles. When the patient blinks, the compressor narium minor muscle contracts, causing depression of the ala. Its etiology is postulated as the formation of anomalous connections between the temporal and zygomatic branches of the facial nerve, innervating the orbicularis oculi muscle, and the buccal branches of the facial nerve, innervating the compressor narium minor muscle. All 13 individuals who exhibited this phenomenon are female. This anomaly was displayed bilaterally in 7 patients, on the right side in 2 patients, and on the left side in 4 patients. A 2-month-old daughter of one of the patients who had bilateral presentation, also displayed the phenomenon. In 6 patients who underwent rhinoplasty, resection of the compressor narium minor muscle resulted in complete elimination of the abnormal muscle movement. The plastic surgeon who performs rhinoplasty should be cognizant of the synkinesis and discuss its presence with the patient, since a patient may consider this a surgical sequela upon discovering the condition postoperatively. Furthermore, this unintentional muscle function is aesthetically displeasing.

Adolescent↗
PubMed1994

Gustatory rhinorrhea--a complication of septoplasty.

A previously unreported complication of septoplasty, which is the profuse flow of thin clear nasal drainage on mastication, is described. Of a combined group of 1332 patients with septoplasty and septorhinoplasty, 6 females and 1 male presented with gustatory rhinorrhea after surgery. The average age of the patients who experienced this complication was 44.43 years. Three patients tested the efficacy of antihistamines, which proved helpful in reducing the severity of this condition. The cause of gustatory rhinorrhea is postulated as inadvertent injury to the nasopalatine nerve within the septal layers after removal of the deviated portion of the vomer and the perpendicular plate of the ethmoid bone during septoplasty. It is the authors' supposition that regenerating nerve sprouts are inappropriately directed toward nasal, rather than palatal, target receptors. Consequently, rhinorrhea results while eating. The pathophysiology of this new finding is not dissimilar to gustatory sweating after parotidectomy. Although this complication is not life-threatening, it is socially disturbing to patients. The authors believe that awareness of this sequela will lead to the discovery of a larger patient population and a potential treatment or prevention.

Adult↗
PubMed1994

Differentiation of the peripherally mediated from the centrally mediated influences of adenosine in the rat during systemic hypoxia.

In two groups of Saffan-anaesthetized, spontaneously breathing rats we have attempted to identify the peripheral influences of adenosine in mediating the responses evoked by hypoxia by using an adenosine receptor antagonist, 8-sulphophenyltheophylline (8-SPT, 20 mg kg-1 i.v., Group 1) and adenosine deaminase (ADA, 500 units in 0.04 ml infused into the tail artery for 10 min, Group 2); neither of these drugs crosses the blood-brain barrier. Recordings were made of respiration, heart rate, arterial pressure, blood flow and vascular conductance in the femoral artery, with ankle ligated (FBF and FVC, respectively) and in the carotid artery with all branches except the internal carotid ligated (CBF and CVC, respectively, Group 1 only) in order to indicate responses in skeletal muscle and cerebral vasculature. Hypoxia (breathing 8 or 10% O2 for 10 min) evoked an increase followed by a secondary decrease in respiration, tachycardia followed by secondary bradycardia, a fall in arterial pressure, an increase in FVC and CVC and an increase, followed by a decrease, in CBF. Neither 8-SPT nor ADA had any significant effect on the secondary decrease in respiration. The secondary bradycardia was unaffected by 8-SPT, but abolished by ADA. Both drugs reduced the fall in arterial pressure and the increase in FVC; 8-SPT had no significant effect on the increase in CVC, but CBF no longer fell with arterial pressure. We propose that adenosine contributes to the hypoxia-induced fall in arterial pressure by causing vasodilatation in skeletal muscle and possibly by causing bradycardia by a direct action on the heart; other evidence suggests that adenosine contributes to the secondary decrease in respiration by acting on central respiratory neurones. The possibility that the fall in arterial pressure and the secondary falls in CBF, respiration and heart rate, can become interdependent in a positive feedback manner is discussed.

2-Chloroadenosine↗
PubMed1994

Why do levels of human welfare vary among nations?

This article investigates what factors explain the wide differences in human welfare among nations. Applying the theory of human need developed by Doyal and Gough, the authors construct a series of indicators of need satisfaction and use these to map contemporary national levels of welfare. They criticize past cross-national studies of welfare outcomes for using a single index of welfare, usually the Physical Quality of Life Index. A comprehensive model of national differences in need satisfaction is then developed. Seven theories are deployed and are tested against the evidence using path analysis, which permits different causal patterns to be simultaneously considered. The authors conclude that per capita incomes are only one of several factors explaining cross-national variations in need satisfaction: the degree of economic and political independence, the extent of democracy and human rights, the capacity and dispositions of the state, and relative gender equality all positively and independently affect a nation's level of welfare. Economic development alone cannot guarantee social development.

Cross-Cultural Comparison↗
PubMed1994

Periodontal complications following orthognathic surgery and genioplasty in a 19-year-old: a case report.

Bimaxillary osteotomies and a sliding genioplasty were performed to correct mandibular micrognathia and maxillary vertical hyperplasia in a 19-year-old white male with a Class II, division 1 malocclusion and anterior open bite. At a follow-up appointment with the orthodontist 4 weeks after the surgical procedure, the mandibular anterior teeth showed severe gingival recession, exposing labial root surfaces on the mandibular central incisors. Grafting procedures were able to restore labial soft tissue on the affected teeth. It is suggested that wound healing contraction of gingival tissue in the area of the incision for the genioplasty caused this complication.

Adult↗