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R Thomas

Publications and source records attributed to R Thomas.

At least 271 records · Page 15Linked to original sources
PubMed1998

Qualitative analysis of gene networks.

In this paper, we review the qualitative tools developed by our group for the analysis of regulatory networks. Focusing on the dynamical and biological roles of feedback circuits, this method can be applied in the context of both logical and differential formalisms. This approach already led to several interesting results about the relation between the network structure and the corresponding dynamical properties. In particular, it could be shown that at least one positive regulatory circuit is necessary to generate multistationarity (i.e., alternative states of gene expression), whereas at least one negative circuit is necessary to generate a stable oscillatory behavior. Applications to the analysis of complex gene networks, as well as to the synthesis of regulatory models to account for global expression data are discussed.

Animals↗
PubMed1998

The role of artificial drainage devices in glaucoma surgery.

The use of artificial drainage devices (ADDs) or "setons" in glaucoma surgery is generally restricted to patients with refractory glaucoma at high risk for failure from conventional filtration surgery. ADDs, both valved and nonvalved are currently available in this country. Recently, some of these devices have been propogated as primary treatment even for primary glaucomas. This article examines the role of ADDs in the modern management of the glaucomas. Specific indications for ADDs and methods to reduce the complication of overfiltration are discussed. The use of antimitotics, such as 5-fluorouracil or mitomycin, with traditional filtration has decreased the indications for ADDs. The literature and our experience confirm that currently there is no role for use of ADDs as a primary procedure in most glaucomas.

Animals↗
PubMed1998

Prevalence of primary glaucoma in an urban south Indian population.

Glaucoma is fast emerging as a major cause of blindness in India. In order to estimate the prevalence of primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG) in an urban South Indian population, we examined 972 individuals aged 30-60 years, chosen using a cluster sampling technique from 12 census blocks of Vellore town. They underwent a complete ocular examination, including applanation tonometry and gonioscopy, at the Medical College Hospital. Characteristic field defects on automated perimetry was a diagnostic requisite for POAG. Prevalence (95% CI) of POAG, PACG, and ocular hypertension were 4.1 (0.08-8.1), 43.2 (30.14-56.3), and 30.8 (19.8-41.9) per 1,000, respectively. All the PACG cases detected were of the chronic type. Hitherto unavailable community-based information on primary glaucoma in our study population indicates that PACG is about five times as common as POAG.

Adult↗
PubMed1997

Prolonged allogeneic and xenogeneic microchimerism in unmatched primates without immunosuppression by intrathymic implantation of CD34+ donor marrow cells.

Engraftment of stem cell-enriched donor marrow implanted in the thymus of a foreign host might facilitate acceptance of donor-specific organ or tissue grafts. To test this hypothesis, allogeneic and xenogeneic CD34+ marrow cells from unrelated adult male baboons and humans were injected intrathymically in eight infant female baboons, both with and without standard cyclosporine-based immunosuppression. In allogeneic experiments, male (donor) cells, of both T- and B-cell lineages, were detected by PCR in the peripheral blood of all six recipients and persisted for at least 15 months in 2/4 recipients studied longtutudinally. Donor-derived skin grafts survived twice as long as third party grafts in unimmunosuppressed recipients. In xenogeneic protocols, human male (donor) cells were demonstrable for 7 and 15 months, respectively, in two baboon recipients with evidence that implanted human CD34+ cells had produced lymphoid progeny. Survival of donor-specific skin xenografts was prolonged in one of two recipients. These experiments demonstrate that the intrathymic injection of CD34+ marrow cells can result in long-lasting lymphohematopoietic microchimerism in unrelated primates even without immunosuppression and can alter donor-specific skin graft survival.

Animals↗
PubMed1997

Functional CD40 ligand is expressed by T cells in rheumatoid arthritis.

CD40 ligand (CD40-L), a member of the tumor necrosis family of transmembrane glycoproteins, is rapidly and transiently expressed on the surface of recently activated CD4+ T cells. Interactions between CD40-L and CD40 induce B cell immunoglobulin production as well as monocyte activation and dendritic cell differentiation. Since these features characterize rheumatoid arthritis (RA), the expression and function of CD40-L in RA was examined. Freshly isolated RA peripheral blood (PB) and synovial fluid (SF) T cells expressed CD40-L mRNA as well as low level cell surface CD40-L. An additional subset of CD4+ RA SF T cells upregulated cell surface CD40-L expression within 15 min of in vitro activation even in the presence of cycloheximide, but soluble CD40-L was not found in SF. CD40-L expressed by RA T cells was functional, since RA PB and SF T cells but not normal PB T cells stimulated CD40-L-dependent B cell immunoglobulin production and dendritic cell IL-12 expression in the absence of prolonged in vitro T cell activation. In view of the diverse proinflammatory effects of CD40-L, this molecule is likely to play a central role in the perpetuation of rheumatoid synovitis. Of importance, blockade of CD40-L may prove highly effective as a disease modifying therapy for RA.

Arthritis, Rheumatoid↗
PubMed1997

Nuclear localization of RelB is associated with effective antigen-presenting cell function.

Dendritic cells (DC) are potent APCs that enter resting tissues as precursors and, after Ag exposure, differentiate and migrate to draining lymph nodes. The phenotype of RelB knockout mice implicates this member of the NF kappa B/Rel family in DC differentiation. To further elucidate the role of RelB in DC differentiation, mRNA, intracellular protein expression, and DNA binding activity of RelB were examined in immature and differentiated human DC, as well as other PB mononuclear cell populations. RelB protein and mRNA were detected constitutively in lymphocytes and in activated monocytes, differentiated DC, and monocyte-derived DC. Immunohistochemical staining demonstrated RelB within the differentiated lymph node interdigitating DC and follicular DC, but not undifferentiated DC in normal skin. Active nuclear RelB was detected by supershift assay only in differentiated DC derived from either PB precursors or monocytes and in activated B cells. These RelB+ APC were potent stimulators of the MLR. The data indicate that RelB expression is regulated both transcriptionally and post-translationally in myeloid cells. Within the nucleus, RelB may specifically transactivate genes that are critical for APC function.

Adult↗
PubMed1997

Logical analysis of timing-dependent receptor signalling specificity: application to the insulin receptor metabolic and mitogenic signalling pathways.

We present a method for logical analysis of signal-transduction networks, focusing on metabolic and mitogenic signalling by the insulin receptor, with specific emphasis on dependence of the signalling properties on the timing of binding events. We discuss a basic model which demonstrates this dependence (hormone binding leads to activation of the receptor which can lead to a commitment to mitogenic signalling), and show how residence time of the hormone on the receptor can determine the specificity of signalling between the alternative metabolic or mitogenic pathways. The method gives conditions for the selection of specific branches in the signalling pathway expressed in terms of inequalities among the characteristic activation or deactivation times of components of that pathway. In this way, the conditions for mitogenic signalling can be given in terms of a required range of values of the hormone residence time on the receptor, which is directly related to the kinetic dissociation rate.

Animals↗
PubMed1997

Caprine enterotoxaemia associated with cerebral microangiopathy.

Cerebral microangiopathy is described in naturally occurring clostridial enterotoxaemia in two goats. The two cases were selected from the files of two diagnostic laboratories in Australia, on the basis that the clinical syndrome and history were consistent with a diagnosis of enterotoxaemia, and that the diagnosis was confirmed by the identification of epsilon toxin in the intestinal contents. The lesions consisted of acute perivascular proteinaceous exudate in the brain and bilaterally symmetrical foci of encephalomalacia were observed in one of the goats. These brain lesions confirm that Clostridium perfringens type D enterotoxaemia may produce histologically detectable brain changes in goats.

Animals↗
PubMed1997

Efficacy of targeted supradose cisplatin and concomitant radiation therapy for advanced head and neck cancer: the Memphis experience.

PURPOSE/OBJECTIVE: To evaluate the feasibility, response rates, and toxicity of a Phase II study using targeted supradose cisplatin and concurrent radiation therapy in unresectable Stage III-IV head and neck squamous cell carcinoma. METHODS AND MATERIALS: Sixty patients presenting between 6/93-9/94 were enrolled, 44 (73%) of whom had T4 and/or N2-N3 nodal disease. All patients were treated with rapid targeted superselective intraarterial infusions of cisplatin (150 mg/m2 weekly x 4) and simultaneous sodium thiosulfate intravenously (9 g/m2) for systemic neutralization of cisplatin. Concurrent (day 1) daily radiation therapy was delivered to the primary tumor and overt nodal disease to 66-74 Gy while the uninvolved lower neck received 50 Gy, at 2.0 Gy/fraction. RESULTS: Fifty-one (85%) patients completed the full RADPLAT protocol as planned. Fifty-seven of 60 patients were evaluable for response. Histological (n = 50) or clinical (n = 7) assessment of primary site revealed a complete response (CR) in 52 patients, partial response (PR) in 4, and stable disease (SD) in 1. Of the 40 patients presenting with nodal metastases, pathological (n = 31) or clinical (n = 6) assessment revealed a CR in 25, PR in 11, and SD in 1, while 3 were unevaluable. Overall, for both primary site and nodal disease, CR was attained in 44 (75%), PR in 12 (23%), and SD in 1 (2%) of the 57 evaluable patients. Only 2 (4%) of 57 evaluable patients have recurred above the clavicle, 1 in the primary site and 1 in the regional lymph nodes. Twelve patients (23%) have failed in distant sites. Grade III/VI toxicity has included gastrointestinal in 6, hematologic in 6, mucosal in 12, vascular in 4, and neurological in 4 patients. CONCLUSION: Concurrent radiation therapy and targeted supradose cisplatin (i.e., RADPLAT) can be safely delivered with high response rates and excellent loco-regional control in advanced Stage III/IV head and neck squamous cell carcinoma.

Adult↗
PubMed1997

Peripheral blood chimerism following human liver transplantation.

The aim of this study was to prospectively investigate the peak levels and kinetics of donor leucocyte chimerism in human recipients following liver transplantation. The peak levels of chimerism were observed within the first 48 hours following transplantation and ranged from 0.15% to 20% of total peripheral blood mononuclear cells. In all but one patient, who developed graft versus host disease, there was an early peak level of chimerism that declined over time such that donor leukocytes were only intermittently detectable after 3 to 4 weeks. In 8 patients who had no episodes of graft rejection, the peak level of donor leukocyte chimerism ranged from 1.3% to 20% (mean +/- SEM; 5.5% +/- 2.1%). In 3 patients who were treated for episodes of acute graft rejection during the first four postoperative weeks, the peak level of donor leukocyte chimerism ranged from 0.15% to 0.2% (0.18 +/- 0.02, P = .012). The results demonstrate a marked variation in the total number of donor leukocytes detectable in the peripheral blood early after liver transplantation and also, that lower levels of chimerism may be associated with lower rates of initial graft acceptance and a higher incidence of acute rejection.

Adult↗
PubMed1997

Comparison of attitudes and behaviors related to nutrition, body size, dieting, and hunger in Russian, black-American, and white-American adolescents.

Attitudes and behaviors related to nutrition are known to differ between white-American and black-American adolescents, however, little is known about teenagers from Russia. We hypothesized that, compared with white-American or black-American teenagers, Russian teenagers would prefer a larger body size, be less likely to diet, and be less concerned about being overweight. Self-administered questionnaires were completed by 196 students in Moscow, 326 white-American, and 239 black-American adolescents who attended school in North Carolina (mean age = 16). Ideal body mass index (BMI) was calculated from measured height and the response to the question, "What do you consider to be your ideal weight?" Mean ideal BMI was higher in black-American boys (25.1) and girls (21.4) than in white-American boys (22.1) and girls (19.2), and Russian boys (21.8) and girls (19.1). After controlling for BMI, black-American girls were less than half as likely to report dieting compared with white-American girls. There were no significant differences among white-American girls and Russian girls, and there were no ethnic differences between boys in the prevalence of dieting. White-American girls and black-American girls were much more likely to identify being overweight as an important nutritional concern than were Russian girls (odds ratios > 10), and there were no ethnic differences among boys. We conclude that preferences for body size, the prevalence of dieting, and concerns about being overweight were similar in Russian and white-American teens, with the exception of Russian teenaged girls who were less likely than American girls to identify being overweight as an important concern. Overall, weight-related attitudes and behaviors in Russian teenagers were more similar to those of white-American teenagers than those of black-American teenagers.

Adolescent↗
PubMed1997

In vivo detection of multidrug-resistant (MDR1) phenotype by technetium-99m sestamibi scan in untreated breast cancer patients.

Technetium-99m sestamibi is a transport substrate recognised by the multidrug-resistant P-glycoprotein (Pgp). To test whether 99mTc-sestamibi efflux is enhanced in breast carcinomas overexpressing Pgp, we determined the efflux rates of 99mTc-sestamibi and Pgp levels in tumours from 30 patients with untreated breast carcinoma. Patients were intravenously injected with 740 MBq of 99mTc-sestamibi and underwent a 15-min dynamic study followed by the acquisition of static planar images at 0.5, 1, 2 and 4 h. Tumour specimens were obtained from each patient 24 h after 99mTc-sestamibi scan and Pgp levels were determined using 125I-MRK16 monoclonal antibody and in vitro quantitative autoradiography. All breast carcinomas showed high uptake of 99mTc-sestamibi and data from region of interest analysis on sequential images were fitted with a monoexponential function. The efflux rates of 99mTc-sestamibi, calculated from decay-corrected time-activity curves, ranged between 0.00121 and 0.01690 min-1 and were directly correlated with Pgp levels measured in the same tumours (r=0.62; P<0.001). Ten out of 30 breast carcinomas (33%) contained 5 times more Pgp than benign breast lesions and showed a mean concentration of 5.73+/- 1.63 pmol/g of tumour (group A). The remaining 20 breast carcinomas had a mean Pgp concentration of 1.29+/-0.64 pmol/g (group B), equivalent to that found in benign breast lesions. 99mTc-sestamibi efflux from tumours of group A was 2.7 times higher than that observed in tumours of group B (0.00686+/-0.00390 min-1 vs 0.00250+/-0.00090 min-1, P<0.001). The in vivo functional test with 99mTc-sestamibi showed a sensitivity and a specificity of 80% and 95%, respectively. In conclusion, the efflux rate of 99mTc-sestamibi may be used for the in vivo identification of the multidrug resistant (MDR1) phenotype in untreated breast cancer patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Effects of epinephrine on right ventricular function in patients with severe septic shock and right ventricular failure: a preliminary descriptive study.

OBJECTIVE: To recognize patients with unresponsive septic shock and right ventricular (RV) failure and to evaluate the effects of epinephrine on RV performance in these patients. DESIGN: Prospective descriptive study. SETTING: Medical intensive care unit. SUBJECTS: 14 consecutive patients in septic shock unresponsive to fluid loading, dopamine, and dobutamine. INTERVENTIONS: Evaluation of RV function by thermodilution with a pulmonary artery catheter equipped with a rapid-response thermistor. Measurements were obtained before and during epinephrine infusion to achieve a systolic arterial pressure > or = 90 mmHg or a mean arterial pressure (MAP) > or = 70 mmHg. RESULTS: At the time of inclusion in the study the hemodynamic pattern in the 14 patients was as follows: (MAP) 58 +/- 14 mmHg, systemic vascular resistance (SVR) 1046 +/- 437 dyne.s.cm-5.m-2, pulmonary artery occlusion pressure (PAOP) 14 +/- 4 mmHg, mean pulmonary artery pressure (MPAP) 24 +/- 4 mmHg, right arterial pressure (RAP) 11 +/- 4 mmHg, cardiac index (CI) 4 +/- 1.7 l/min per m2. During epinephrine infusion, MAP, CI and stroke volume index (SVI) were increased (27%, p < 0.01; 20%, p < 0.01; 15%, p < 0.05, respectively). There was no change in PAOP, SVR or heart rate. Seven patients (group A) had marked RV failure defined by both RV dilation [RV end-diastolic volume index (RVEDVI) > 92 ml/m2] and low RV ejection factor (RVEF) (< 52%) and 7 did not (group B). Group A had a lower baseline RVEF than group B (24 +/- 7 vs 45 +/- 9%, p < 0.05), a higher RVEDVI (134 +/- 28 vs 79 +/- 17 ml/ m2, p < 0.01), and a higher RVES (systolic) VI (103 +/- 30 vs 43 +/- 11 ml/ m2, p < 0.01). The other hemodynamics, especially RAP and RV stroke work index (RVSWI) were no different in the two groups and did not predict RV dysfunction. In group A, epinephrine infusion improved RVEF (25%, p < 0.05) by a reduction in RVESVI (-8%, p < 0.05) without any change in RVEDVI or in RAP, in spite of a rise in MPAP (11%, p < 0.05). A rise in RVSWI (76%, p < 0.05), SVI (23%, p < 0.05), and CI (24%, p < 0.05) was also achieved. An upward vertical shift of the Frank-Starling relationship RVSWI/ RVEDVI and an upward shift to the left of the pressure volume relationship pulmonary artery peak pressure/RVESVI was observed only in the group with RV failure following treatment with epinephrine. In group B (without RV failure), RV parameters were not modified by epinephrine. CONCLUSION: In patients with severe septic shock, RV dysfunction was identified by the use of an RVEF pulmonary artery catheter and was improved by epinephrine by means of an improvement in RV contractility.

Adult↗
PubMed1997

Perfluorocarbon emulsion in the cardiopulmonary bypass prime reduces neurologic injury.

BACKGROUND: Perfluorocarbon emulsion has proved beneficial in the prevention and amelioration of experimental air embolism. We examined whether the addition of perfluorocarbon to the prime solution could lead to a reduction in the incidence and severity of neurologic injury after the formation of a massive air embolism during cardiopulmonary bypass. METHODS: Fourteen pigs underwent bypass in which either a crystalloid prime solution or a perfluorocarbon prime solution (10 mL/kg) was used. Ten minutes into bypass a bolus (5 mL/kg) of air or saline (control) was delivered via the carotid artery. The resulting cerebral infarcts were graded on the basis of the findings in triphenyltetrazolium chloride-stained cerebral sections. Colored microspheres were used to measure cerebral blood flow. Bitemporal electroencephalography was used to evaluate cerebral function. RESULTS: Cerebral infarction was not found in the perfluorocarbon-air group (0 to 5 animals), as compared with its occurrence in 3 of the 5 animals in the crystalloid-air group. Cerebral blood flow was also maintained or increased in the perfluorocarbon-air group (p < 0.05), and the electroencephalogram total power showed less of a decrease and recovered more completely (p < 0.05) than it did in the crystalloid-air group. CONCLUSIONS: The addition of perfluorocarbon emulsion to the cardiopulmonary bypass prime solution leads to a reduction in the incidence and severity of neurologic injury after the formation of a massive air embolism during bypass.

Animals↗
PubMed1997

Combined percutaneous antegrade and cystoscopic retrograde ureteral stent placement: an alternative technique in cases of ureteral discontinuity.

We describe an alternative method of double J stent placement for ureteral transection following the failure of traditional antegrade and retrograde approaches. Cystoscopically, a guidewire was placed across the distal ureteral segment and was advanced into a urinoma cavity at the level of the transected ureter. Subsequently, an antegrade approach was used to place a gooseneck snare through the proximal ureteral segment into the urinoma cavity. The guidewire was grasped with the snare and pulled through the percutaneous access site. A double J ureteral stent was then placed using the typical antegrade method.

Adult↗