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Biomedical subjects

T Thomas

Publications and source records attributed to T Thomas.

At least 19 recordsLinked to original sources
PubMed1996

beta-Amyloid-mediated vasoactivity and vascular endothelial damage.

Deposits of beta-amyloid are apparent in ageing and Alzheimer's disease, but the role of this peptide in neurodegeneration is unclear. The free-radical theory of ageing may also account for Alzheimer-type degeneration and consequently links between free-radical generation and beta-amyloid have been sought. We demonstrate here that beta-amyloid interacts with endothelial cells on blood vessels to produce and excess of superoxide radicals, with attendant alterations in endothelial structure and function. The superoxide radical can scavenge endothelium-derived relaxing factor and produce potent oxidizing agents, which can cause lipid peroxidation and other degenerative changes. The alterations in vascular tone and endothelial damage are prevented by the oxygen-radical-scavenging enzyme superoxide dismutase. These observations suggest a normal vasoactive role for beta-amyloid as well as a mechanism by which beta-amyloid may play a role in vascular abnormalities and neurodegeneration mediated by free radicals.

Acetylcholine↗
PubMed1996

Rapid and efficient selection of human hematopoietic cells expressing murine heat-stable antigen as an indicator of retroviral-mediated gene transfer.

Recombinant retroviruses offer many advantages for the genetic modification of human hematopoietic cells, although their use in clinical protocols has thus far given disappointing results. There is therefore an important need to develop new strategies that will allow effectively transduced primitive hematopoietic target populations to be both rapidly characterized and isolated free of residual nontransduced but biologically equivalent cells. To address this need, we constructed a murine stem cell virus (MSCV)-based retroviral vector containing the 228-bp coding sequence of the murine heat-stable antigen (HSA) and generated helper virus-free amphotropic MSCV-HSA producer cells by transfection of GP-env AM12 packaging cells. Light density and, in some cases, lineage marker-negative (lin-) normal human marrow or mobilized peripheral blood cells preactivated by exposure to interleukin-3 (IL-3), IL-6, and Steel factor in vitro for 48 hours were then infected by cocultivation with these MSCV-HSA producer cells for a further 48 hours in the presence of the same cytokines. Fluorescence-activated cell sorting (FACS) analysis of the cells 24 hours later showed 21% to 41% (mean, 27%) of those that were still CD34+ to have acquired the ability to express HSA. The extent of gene transfer to erythroid and granulopoietic progenitors (burst-forming unit-erythroid and colony-forming unit-granulocyte-macrophage), as assessed by the ability of these cells to form colonies of mature progeny in the presence of normally toxic concentrations of G418, averaged 11% and 12%, respectively, in 6 experiments. These values could be increased to 100% and 77%, respectively, by prior isolation of the CD34+HSA+ cell fraction and were correspondingly decreased to an average of 2% and 5%, respectively, in the CD34+HSA- cells. In addition, the extent of gene transfer to long-term culture-initiating cells (LTC-IC) was assessed by G418 resistance. The average gene transfer to LTC-IC-derived colony-forming cells in the unsorted population was < or = 7% in 4 experiments. FACS selection of the initially CD34+HSA+ cells increased this value to 86% and decreased it to 3% for the LTC-IC plated from the CD34+HSA- cells. Transfer of HSA gene expression to a phenotypically defined more primitive subpopulation of CD34+ cells, ie, those expressing little or no CD38, could also be shown by FACS analysis of infected populations 24 hours after infection. These findings underscore the potential use of retroviral vectors encoding HSA for the specific identification and non-toxic selection immediately after infection of retrovirally transduced populations of primitive human hematopoietic cells. In addition, such vectors should facilitate the subsequent tracking of their marked progeny using multiparameter flow cytometry.

Animals↗
PubMed1996

Psychosocial characteristics of psychiatric inpatients with reproductive losses.

Rising fertility rates among the severely and persistently mentally ill require a better understanding of the family planning needs of this population. In the present study, 82 women hospitalized for major psychiatric disorders were divided into three groups: abortion (n = 22), relinquishment (n = 28), and no children (n = 32). Statistical analyses of demographic, diagnostic, and birth control data showed that those who aborted or relinquished custody of their children were likely to come from ethnic minority populations and have a history of substance abuse. More than 70 percent of the women who had abortions reported sexual and/or physical assaults as either children or adults. Only 34 percent of all participants indicated that they used contraceptives. Increased awareness of reproductive histories and family planning needs of women with major psychiatric disorders is suggested.

Abortion, Induced↗
PubMed1996

Inhibin-related proteins in rat prostate.

Inhibin and activin are members of the transforming growth factor beta (TGF beta) family which can regulate cell proliferation in a number of tissues. The presence of inhibins and the related proteins, activins, in the prostate has been implicated by the detection of activin type II receptors. The aim of this study was to determine whether or not immunoactive (ir) inhibin and ir-activin are present in the rat prostate and to study the acute regulation by androgens. The results showed that mRNAs for the alpha and beta inhibin subunits were detected in rat prostate by reverse transcription-PCR together with ir-inhibin and ir-activin in prostate cytosols. The levels of ir-activin in the prostate (223 +/- 44 ng/gland) were greater than the levels of ir-inhibin (6.89 ng/gland), and activin immunoreactivity was localised to the epithelial cells. The presence of these proteins and the subunit mRNAs suggests that these proteins are produced in the prostate and may have a role in prostate function. The study of the effect of androgen withdrawal on the levels of ir-activin and ir-inhibin in these tissues showed no change in the content of ir-inhibin or ir-activin (ng/g tissue) after 3 days of castration or following the administration of the cytotoxic drug ethane dimethane sulphonate (EDS), although there was a significant (P < 0.01) decline in prostate weight. Fourteen days after EDS treatment, as the prostate weight fell significantly lower, the amount of ir-inhibin and ir-activin per prostate gland was significantly (P < 0.01) reduced although the concentration was unaffected. These data demonstrate, for the first time, that inhibin alpha and beta subunit mRNA and ir-inhibin and ir-activin are present in the prostate; the role of these proteins in prostate function remains to be established.

Activins↗
PubMed1996

[Paracrine regulation of Leydig cells].

In addition to the endocrine control of Leydig cell functions by LH, paracrine control of Leydig cell functions has been suspected from the indirect stimulatory effect of FSH on Leydig cells. Coculture experiments of Leydig and Sertoli cells and the effect of Sertoli cell conditioned media on Leydig cells confirmed the production by Sertoli cells of acute steroideogenic factor(s) and factors involved in the positive or negative control of Leydig cell differenciated functions. Characterization and purification of these paracrine factors has been until recently unsuccessful. Another approach has been to investigate whether compounds of known biological activities in other systems, were produced within the testis and act on leydig cells. IGF-I is produced by Sertoli and Leydig cells under the control of their respective gonadotropin, LH and FSH. IGF-I enhanced hCG responsiveness of Leydig cells by increasing both LH receptor and steroidogenic enzymes. On the contrary TGF-beta which is also produced by Sertoli and Leydig cells is a potent inhibitor of Leydig cell functions. Its production by Sertoli cells is inhibited by FSH. Inhibin enhanced Leydig cell differentiated cell functions. Activin has, conversely to what has been published in the rat, a stimulatory effect on Leydig cell functions in the immature porcine Leydig cell model. The effects of these growth factors or related molecules mainly consist in positive (IGF-I, Inhibin, Activin) or negative (TGF-beta, TGF-alpha/EGF, bFGF) trophic effects regulating LH/hCG receptor number and mRNAs and steroidogenic enzyme mRNAs and activites, allowing regulation of the responsiveness of Leydig cells to LH. Thus both gonadotropins contribute, directly for LH and indirectly, through paracrine mecanisms, for FSH, to testosterone production.

Activins↗
PubMed1996

Arthritis, hypercalcemia, and lytic bone lesions after hepatitis B vaccination.

We report a case of arthritis, hypercalcemia, and lytic bone lesions that occurred shortly after repeated administration of recombinant hepatitis B virus (HBV) vaccine in a 44-year-old man who had had myasthenia gravis 20 years earlier. He presented with ankle and knee arthritis and hypercalcemia. Radiographs revealed small lytic lesions and densitometry showed severe osteopenia. Quantimetric bone biopsy confirmed major bone loss and showed dramatic increase in bone turnover, as well as an unusual periosteal apposition of woven bone. Short term treatment with prednisone and furosemide and longterm treatment with clodronate allowed rapid improvement. After one year, the patient remains clinically asymptomatic. Despite negative immunologic investigations to sustain the hypothesis of HBV vaccination as a causal factor, we believe the bone lesions could be attributed to unusual bone "hyperremodeling" triggered by an immune process in a predisposed individual.

Adult↗
PubMed1995

Defective signal-transduction pathways in T-cells from autoimmune MRL-lpr/lpr mice are associated with increased polyamine concentrations.

We previously reported that difluoromethylornithine (DFMO), an inhibitor of polyamine biosynthesis, exerted significant beneficial effects on the lifespan and disease expression of MRL-lpr/lpr mice, which spontaneously develop a lupus-like syndrome. Polyamine levels in splenic T-cells of MRL-lpr/lpr mice were significantly higher than those of Balb/c mice. In the present investigation, we examined the role of endogenous polyamines in transmembrane Ca2+ influx, generation of InsP3 and tyrosine phosphorylation of the p56lck protein in concanavalin A-stimulated splenic T-cells. Cytosolic free calcium concentrations ([Ca2+]i) in concanavalin A-stimulated T-cells of MRL-lpr/lpr and Balb/c mice were 250 +/- 25 and 450 +/- 42 nM respectively. Treatment of MRL-lpr/lpr mice with DFMO increased [Ca2+]i to 360 +/- 30 nM (P < 0.05). InsP3 levels of concanavalin A-stimulated MRL-lpr/lpr splenic T-cells were only 20% higher than those of unstimulated controls, whereas those of Balb/c T-cells were 90% higher. DFMO treatment increased InsP3 levels in concanavalin A-treated MRL-lpr/lpr T-cells to 67%. Western-blot analysis showed a 7-fold higher level of p56lck phosphorylation of MRL-lpr/lpr splenic T-cells than that of Balb/c mice. DFMO treatment reduced tyrosine phosphorylation of p56lck of MRL-lpr/lpr mice significantly (P < 0.001). Two-colour flow-cytometric analysis revealed no significant difference in the CD4+/CD8+ ratio in splenic T-cells of MRL-lpr/lpr mice after DFMO treatment. Polyamine levels in splenocytes were significantly reduced by DFMO treatment. These data show that DFMO treatment could alter signal-transduction pathways of splenic T-cells of MRL-lpr/lpr mice. Increased levels of polyamines in T-cells of untreated lpr mice contribute to defective signal-transduction pathways and the pathogenesis of lupus-like symptoms.

Animals↗
PubMed1995

Suppression of c-myc oncogene expression by a polyamine-complexed triplex forming oligonucleotide in MCF-7 breast cancer cells.

Polyamines are excellent stabilizers of triplex DNA. Recent studies in our laboratory revealed a remarkable structural specificity of polyamines in the induction and stabilization of triplex DNA. 1,3-Diaminopropane (DAP) showed optimum efficacy amongst a series of synthetic diamines in stabilizing triplex DNA. To utilize the potential of this finding in developing an anti-gene strategy for breast cancer, we treated MCF-7 cells with a 37mer oligonucleotide to form triplex DNA in the up-stream regulatory region of the c-myc oncogene in the presence of DAP. As individual agents, the oligonucleotide and DAP did not downregulate c-myc mRNA in the presence of estradiol. Complexation of the oligonucleotide with 2 mM DAP reduced c-myc mRNA signal by 65% at 10 microM oligonucleotide concentration. In contrast, a control oligonucleotide had no significant effect on c-myc mRNA. The expression of c-fos oncogene was not significantly altered by the triplex forming oligonucleotide (TFO). DAP was internalized within 1 h of treatment; however, it had no significant effect on the level of natural polyamines. These data indicate that selective utilization of synthetic polyamines and TFOs might be an important strategy to develop anti-gene-based therapeutic modalities for breast cancer.

Antineoplastic Agents↗
PubMed1995

A study on rats of the effects of chronic hypoxia from birth on respiratory and cardiovascular responses evoked by acute hypoxia.

1. Comparative studies were performed on eighteen rats 54 days old made chronically hypoxic from birth in an hypoxic chamber at 12% O2 (CHB), and in eight weight-matched control rats (NB, 42 days old); both CHB and NB rats were anaesthetized with Saffan. 2. In NB rats, breathing 12 or 8% O2 for 5 min induced a pattern of response comparable to that described in older rats (10-11 weeks old): an initial increase and secondary fall in minute volume (VE), a fall in arterial pressure (ABP), an increase in muscle vascular conductance, while cerebral blood flow (CBF) increased at the 1st minute in six animals and fell by the 5th minute in all animals. The adenosine receptor antagonist 8-phenyl-theophylline (8-PT, 10 mg kg-1) reduced the secondary fall in VE, the fall in ABP and muscle vasodilatation, indicating they were partly mediated by adenosine. 3. In CHB rats breathing 12% O2, VE was higher (277 +/- 12 vs. 204 +/- 18 ml min-1), arterial partial pressures of O2 (45 +/- 2 vs. 88 +/- 3 mmHg), CO2 (32 +/- 1 vs. 44 +/- 1 mmHg) and ABP (105 +/- 5 vs. 131 +/- 5 mmHg) were lower, while muscle vascular conductance was higher (0.08 +/- 0.01 vs. 0.03 +/- 0.01 ml min-1 mmHg-1) than in NB rats breathing air; these differences were reduced, but not abolished, when CHB rats acutely breathed air for 5 min. 4. In CHB rats, the smaller change from 12 to 8% O2 for 5 min evoked a similar pattern of response to that evoked by 8% O2 in NB rats, except that heart rate (HR) and CBF decreased progressively. However, 8-PT increased baseline VE and reduced ABP in 12% O2 and reduced the secondary decrease in VE and HR evoked by 8% O2, but had no effect on the fall in ABP, or change in muscle vascular conductance. 5. We propose that in CHB rats (i) there is accentuation of the components of the response to acute hypoxia (the fall in ABP, HR and CBF) that form a positive feedback loop which promotes central ventilatory depression and (ii) that adenosine exerts a tonic inhibitory influence on VE and vasodilator influence in muscle and mediates the secondary fall in VE, but not the muscle vasodilation induced by acute hypoxia.

Adenosine↗
PubMed1995

Ceruloplasmin gene expression in the rat uterus.

In this paper we identify the uterine epithelial cells as the site of ceruloplasmin gene expression in the uterus. We show that during the estrous cycle ceruloplasmin RNA levels change substantially reaching a maximum at estrous. In the absence of endocrine control by the ovaries, ceruloplasmin RNA is still present suggesting that this gene is constitutively expressed by the uterine epithelial cells. However, the changes in RNA level immediately after ovariectomy and during pregnancy suggest that it is also the subject of a complex regulatory system.

Acute-Phase Reaction↗
PubMed1995

Cell membrane dynamics and insulin resistance in non-insulin-dependent diabetes mellitus.

Insulin resistance in non-insulin-dependent diabetes mellitus (NIDDM) could be related to changes in cell membrane properties. We measured insulin sensitivity and mononuclear leucocyte membrane fluidity by fluorescence polarisation in fifteen NIDDM patients and twenty-one normal subjects. Core-region anisotropy was significantly lower in leucocytes from diabetic subjects (mean 0.164 vs 0.174, p < 0.001). Insulin sensitivity was positively correlated with such anisotropy before and after acute in-vitro insulin treatment. There was no difference in superficial membrane anisotropy. This study suggests that altered membrane dynamics in NIDDM may contribute to insulin resistance.

Cell Membrane↗
PubMed1995

Ineffectiveness of calcitonin on a local-disuse osteoporosis in the sheep: a histomorphometric study.

Local immobilization is a good model for studying disuse-induced bone loss and to appreciate the effects of drugs, especially preventive action of antiresorptive therapy. In fact, increased osteoclastic activity is the main point of such a bone loss. The effect of salmon calcitonin was investigated on immobilization-induced osteoporosis in the sheep. Twenty-four nonovariectomized, adult, female, Welsh mountain sheep were submitted, by an external fixator procedure, to hock joint immobilization from the tibia to the the metatarsus for 12 weeks. The sheep were randomized into two groups receiving either an injection of placebo or salmon calcitonin (100 IU) three times per week, for 12 weeks. Histomorphometric analysis was performed on pre- and posttherapeutic transiliac bone biopsies, and on immobilized (left) and nonimmobilized calcanei removed after sacrifice. Results showed a 29% significant decrease of cancellous bone volume in the placebo group due to a significant reduced trabecular thickness when we compared immobilized versus nonimmobilized calcaneus. This structural adaptation appeared to be the consequence of an overall increased bone turnover. In the calcitonin group, same changes were observed, with a 23% reduction of bone mass in the immobilized calcaneus. By comparing calcitonin with placebo groups in both left and right calcanei, no difference was found. On the other hand, a significant increase of mineralization parameters in the iliac crest was only observed in the calcitonin group. In conclusion, salmon calcitonin, at a dose of 100 IU/day three times a week, was ineffective in preventing local disuse osteoporosis in this sheep model.

Animals↗
PubMed1995

Pitfall of stiff shoulder: inveterated posterior dislocation.

The authors relate the observation of an inveterated bilateral posterior dislocation, occurring during a generalized epileptic attack and mimicking a painful stiff shoulder. The clinical signs (i.e. aetiologic circumstances causing a forced internal rotation, limitation or absence of external rotation) and radiological data, especially the necessity of a profile X-ray, which lead to the diagnostic are reiterated. The interest of computerized tomography in the pre-operative assessment is underscored.

Epilepsy, Tonic-Clonic↗
PubMed1995

Polyamine-mediated conformational perturbations in DNA alter the binding of estrogen receptor to poly(dG-m5dC).poly(dG-m5dC) and a plasmid containing the estrogen response element.

The binding estrogen receptor (ER) to the upstream regions of estrogen-responsive genes, the estrogen response elements (ERE), is of fundamental importance in the regulation of gene expression by estradiol. Multiple cell-specific factors affect ER-ERE binding and modulate the responses of estradiol. We studied the role of polyamines in the recognition of ER, a ligand-activated transcription factor, with a left-handed Z-DNA forming polynucleotide as well as with a plasmid containing ERE. Polyamines are cellular organic cations with multiple functions in cell growth and differentiation. Polyamines induce Z-DNA conformation in alternating purine-pyrimidine sequences. To understand the role of polyamine-induced DNA conformational transition in ER-DNA interaction, we studied the binding of partially purified rabbit uterine ER to poly(dG-m5dC).poly(dG-m5dC). The induction of Z-DNA in the polynucleotide was monitored by circular dichroism and ultraviolet spectroscopic measurements. Binding of ER to poly(dG-m5dC).poly(dG-m5dC) increased from 15% to approx. 50-60% in the presence of 7.5 mM putrescine, 0.5 mM spermidine or 0.25 mM spermine. Maximal binding of ER to the polynucleotide was observed near the midpoint of the B-DNA to Z-DNA transition of the polynucleotide. N1-acetyl spermidine and N1-acetyl spermine facilitated the B-DNA to Z-DNA transition and the binding of ER although they were less effective than the unacetylated analog. Co(NH3)6(3+), a trivalent inorganic cation, also provoked the B-DNA to Z-DNA transition of the polynucleotide and increased its binding to ER. At higher polyamine concentrations, there was an inhibition of ER binding to the polynucleotide. In the presence of polyamines, the binding of ER to a plasmid containing ERE was 2-3-fold higher than that to a control plasmid devoid of ERE. Polyamine-induced facilitation of ER-ERE binding was also confirmed by gel mobility shift assay. Our data indicate that conformational perturbations, similar to that of the early stages of B-DNA to Z-DNA transition, are important in the recognition of ER and ERE.

Animals↗
PubMed1995

Corrugator supercilii muscle resection through blepharoplasty incision.

Corrugator supercilii muscle resection through an upper blepharoplasty incision, with or without concomitant blepharoplasty, is suitable for patients who have significant corrugator hyperactivity and deep frown lines without eyebrow or forehead ptosis. This procedure is also appropriate for patients who decline a forehead rhytidectomy. After infiltration of local anesthesia with intravenous sedation, skin and fat are excised when a concurrent blepharoplasty is planned. The plane between the orbicularis oculi muscle and the orbital septum is dissected until the corrugator supercilii muscle is exposed. This muscle is identified immediately cephalad to the medial half of the superior orbital rim. The muscle is resected carefully to prevent injury to the supratrochlear nerve medially and the supraorbital nerve laterally. The resultant depression is eliminated with fat removed during the blepharoplasty, or fat or dermis from other sites should the aesthetic plan not include eyelid surgery. Eight patients, seven females and one male, underwent this procedure. The follow-up period ranged from 11 to 19 months, with a mean of 14.5 months. Patients' ages ranged from 25 to 66 years, with a mean of 51.3 years. A scale of 1 to 5, with 5 being excellent, was used to rate postoperative appearance, producing a mean of 4.25. The advantages of fewer skin incisions, less tissue mobilization, and a direct approach to the origin of the problem make this procedure a valuable adjunct to the cosmetic surgery armamentarium.

Adult↗
PubMed1995

Considerations about a unique clinical pattern: flexion block of the shoulder.

Frozen shoulder is a well-defined nosologic entity characterized by retraction of the anterior portion of the glenohumeral joint capsule. When clinical findings are inconclusive, arthrography can differentiate a frozen shoulder from a stiff and painful shoulder. We report three cases of stiffness of the shoulder that we believe was due to a unique pathological process. Flexion was restricted to 120 degrees and a sensation suggestive of mechanical blockage was felt upon passive flexion. Medical rotation was restricted and painful, whereas lateral rotation with the elbow held against the torso was normal. Findings upon arthrography or magnetic resonance imaging were normal, with no evidence of capsulitis or chronic rotator cuff lesions. Our pathogenic hypotheses include a lesion of the proximal portion of the long head of the biceps brachii or a focal ligamentous lesion. Treatment should consist of specific physical therapy and, in refractory forms, gentle mobilization under general anesthesia.

Adult↗