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Biomedical subjects

S Thomas

Publications and source records attributed to S Thomas.

At least 613 records · Page 34Linked to original sources

Dissociation of cellular proliferation and c-myc expression by buttercup extract.

Buttercup extract (BE), an extract of the buttercup plant (Zanthoriza simplicissima), inhibits RNA and DNA synthesis by HL-60 promyelocytic leukemia cells. Exposure of these cells to 3% BE for 48 hours results in dramatic inhibition of RNA synthesis without loss of cell viability. The effect of BE is partially reversible over 12-24 hours with the level of RNA synthesis returning nearly to control levels during this time period. DNA synthesis is also reversibly inhibited by exposure to BE. Despite the inhibition of RNA synthesis in HL-60 cells, there is no decrease in the level of c-myc mRNA, even at high BE concentrations. The level of gene-specific mRNA for the c-Ha-ras, c-fms, and c-mos genes in these cells also remained constant during exposure to BE. Ribosomal RNA is not degraded during 24 hours of BE treatment in vitro, suggesting that BE does not maintain the relative mRNA level for these genes by selective degradation of other RNA species. The inhibition of RNA and DNA synthesis by BE without a corresponding alteration in the level of expression of the c-myc gene suggests that this agent dissociates c-myc expression and cellular proliferation in these cells.

Cell Division↗

Does 99Tcm human serum albumin alter the characteristics of nebulized pentamidine isethionate?

Nebulized pentamidine has been used as therapy for Pneumocystis carinii pneumonia. The lung dose delivered using different nebulizer systems and doses of pentamidine from 50-600 mg is unknown. To measure this a marker which does not alter the characteristics of the nebulized pentamidine solution must be found. We have assessed the aerosol characteristics of four jet nebulizers (System 22, System 22 Mizer, Optimist, Respigard II) and one ultrasonic device (Pulmosonic) using two concentrations of pentamidine isethionate (50 mg and 300 mg) in 3 ml of solution. The jet nebulizers were operated at a flow rate of 6 l min-1, a rate suitable for home use. These measurements were repeated with 99Tcm labelled human serum albumin (HSA) added to the solutions. A linear relationship between 99Tcm-HSA activity and pentamidine concentration was demonstrated by using a nine stage cascade impactor. The Respigard II and Optimist produced the best results in terms of particle size (96% less than 5 microns), but the addition of the tracer to the latter led to a smaller particle size range and a reduction in the amount of aerosol present at the mouthpiece. The Mizer system had 52% of particles less than 5 microns, the Pulmosonic 46%. The Respigard II had a total output of 8.7 mg for the 50 mg concentration and 30.9 mg for the 300 mg concentration. The System 22 produced corresponding outputs of 18.0 mg and 67.1 mg with 54% of the aerosol particles less than 5 microns.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗

Na+-H+ exchange and pH regulation in red blood cells: role of uncatalyzed H2CO3 dehydration.

Erythrocytes of rainbow trout respond to adrenergic stimulation by activation of a Na+-H+ exchange. When red blood cells are suspended in their own plasma and equilibrated with a convenient gas mixture in a tonometer, the extrusion of H+ induces a fast, very strong acidification of the blood (by 0.5-0.7 pH units), explained as follows. Excretion of H+ into a medium containing HCO3- causes the formation of H2CO3. The uncatalyzed dehydration of H2CO3 is slow so that H+ accumulates above the level that would prevail at equilibrium, promoting a strong acid disequilibrium pH. Then the blood pH progressively returns to a value close to its initial value because of the slow uncatalyzed dehydration of H2CO3 and washout of the CO2 so produced. The period of acid disequilibrium pH, however, is lengthened because part of the CO2 generated by the spontaneous dehydration is not washed out by tonometry but diffuses into the red cells where it is rapidly converted into HCO3- and H+ by carbonic anhydrase and then excreted by Na+-H+ and Cl-HCO3- exchangers. This recycling process "refuels" the ionic reaction, increasing the time needed to reach equilibrium. The anion exchanger does not sense this strong acid disequilibrium pH, since the external HCO3- concentration is practically unchanged at that time. During the extracellular pH (pHe) recovery period, simultaneously extracellular HCO3- content decreases and intracellular Cl- content increases. Thus intracellular pH and pHe appear to be uncoupled. This overall interpretation is confirmed by experiments using carbonic anhydrase and drugs such as propranolol and amiloride.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗

Mithramycin blocks protein binding and function of the SV40 early promoter.

Specific interactions between DNA and transcription factors are necessary for transcription initiation. These interactions provide a potential target for the selective inhibition of eukaryotic gene expression. Mithramycin is a DNA binding antibiotic which, in the presence of Mg2+, binds G-C containing sequences in the minor groove. The SV40 early promoter contains six G-C decanucleotide sequences, which are binding sites for the transcriptional activating factor, Sp1. Each of the six Sp1 binding sites of this promoter is protected from DNAse 1 digestion by mithramycin binding. Mithramycin binding to the G-C rich sequences in the SV40 early promoter prevents subsequent protein binding to these sequences. The gel retardation of the SV40 early promoter fragment incubated with a HeLa cell extract is completely abrogated by pretreatment of the DNA fragment with mithramycin. The functional significance of mithramycin binding is reflected in the ability of mithramycin to block promoter function. Mithramycin inhibits promoter dependent transcription in an in vitro runoff transcription system in a concentration dependent manner. This suggests that mithramycin prevents transcriptional activation of the SV40 early promoter by blocking binding of transcriptional activating proteins to G-C rich promoter regions.

Base Sequence↗

The effect of cyclosporin A administration and its withdrawal on bone mineral metabolism in the rat.

The in vivo administration of cyclosporin A (CsA) has been associated with significant bone loss and increased bone remodeling. To observe whether these changes are reversible, we have investigated the consequences of the administration and withdrawal of CsA immunotherapy on bone mineral metabolism. Three groups of Sprague-Dawley rats were studied for 28 days. Group A received vehicle, and group B received CsA (15 mg/kg BW) for 28 days, while group C received CsA (15 mg/kg BW) for 14 days and then vehicle from days 15-28 by daily gavage. Serum ionized calcium (Ca2+), PTH, bone gla protein, blood urea nitrogen, creatinine, magnesium, phosphorus, and 1.25-dihydroxyvitamin D were measured weekly. Bone histomorphometry was analyzed on days 14 and 28 in groups A and B and on day 28 in group C. CsA administration resulted in reversible hypomagnesemia and mild transient elevation in circulating 1,25-dihydroxyvitamin D levels with no change in Ca2+, PTH, blood urea nitrogen, or phosphorus. Serum bone gla protein levels were significantly increased (P less than 0.002) during CsA therapy, but tended to return to control values after CsA withdrawal. Enhanced bone remodeling and significant trabecular bone loss accompanied CsA administration. Withdrawal of CsA resulted in all of the histomorphometric parameters, except for bone volume, returning to control values within 2 weeks. Incomplete restoration of bone volume occurred 5 weeks after CsA withdrawal. This limited restoration of bone volume despite CsA withdrawal may have important clinical implications.

Animals↗

Frameworks of analysis for the neural representation of animate objects and actions.

A variety of cell types exist in the temporal cortex providing high-level visual descriptions of bodies and their movements. We have investigated the sensitivity of such cells to different viewing conditions to determine the frame(s) of reference utilized in processing. The responses of the majority of cells in the upper bank of the superior temporal sulcus (areas TPO and PGa) found to be sensitive to static and dynamic information about the body were selective for one perspective view (e.g. right profile, reaching right or walking left). These cells can be considered to provide viewer-centred descriptions because they depend on the observer's vantage point. Viewer-centred descriptions could be used in guiding behaviour. They could also be used as an intermediate step for establishing view-independent responses of other cell types which responded to many or all perspective views selectively of the same object (e.g. head) or movement. These cells have the properties of object-centred descriptions, where the object viewed provides the frame of reference for describing the disposition of object parts and movements (e.g. head on top of shoulders, reaching across the body, walking forward 'following the nose'). For some cells in the lower bank of the superior temporal sulcus (area TEa) the responses to body movements were related to the object or goal of the movements (e.g. reaching for or walking towards a specific place). This goal-centred sensitivity to interaction allowed the cells to be selectively activated in situations where human subjects would attribute causal and intentional relationships.

Animals↗

Extracorporeal shock wave lithotripsy in paediatric patients.

24 children with urolithiasis of the upper urinary tract were treated by extracorporeal shock wave lithotripsy (ESWL). In all patients sufficient stone disintegration could be achieved by an average of 950 shock waves. Percutaneous nephrostomy was required for "Steinstrasse" ureteral obstruction in 2 cases. At discharge from hospital 16 children were considered stone-free. Follow-up showed 90% of the children to be stone-free without recurrence (mean 20 months). The necessary precautions considered, ESWL is the method of choice for treatment of urolithiasis of the upper urinary tract in children. The long term effects of ESWL on the juvenile kidney have yet to be observed.

Child↗

[Administration of intracorporeal, laser-induced shock waves for the destruction of urinary calculi].

In spite of rapid developments in modern endourologic methods of urinary tract stone management, a definitive solution regarding the energy source for intracorporeal lithotripsy has not yet been found. Laser-induced shock wave lithotripsy is one of the most promising approaches. The evolution of this treatment modality within the last 4 years gives rise to the hope that a commonly accepted standard method will soon become available. General acceptance depends on increasing reliability and effectivity of current systems, especially in the case of problem stones. The advantages of intracorporeal shock wave lithotripsy can be summarized in the following points. (1) The shock wave is applied directly to the intended object, i.e., the stone, so that adverse side effects are virtually excluded. (2) Laser-induced shock wave lithotripsy leads to a precise and extremely fine fragmentation of stones, avoiding urinary tract obstruction with consecutive tract infection. (3) Cost and treatment handling are further points in favour of intracorporeal lithotripsy. (4) Perspectives are widened by the possibility of treating, of biliary, pancreatic and salivary gland duct stones.

Animals↗

Mouse fibroblasts transformed with the human c-myc gene express a high level of mRNA but a low level of c-myc protein and are non-tumorigenic in nude mice.

Overexpression of a transfected c-myc gene under the control of a strong promoter causes the phenotypic changes of malignant transformation. We have investigated the effect of exogenous c-myc gene expression in NIH3T3 cells transfected with an intact human c-myc gene which is expressed under the control of its own promoter. The presence of the exogenous c-myc gene in the transfected cells was documented by Southern blot analysis. The transfected clones contained 20-40 copies of the human c-myc gene and demonstrated a proportional elevation in the level of c-myc mRNA which had a normal half life of 20-30 min. Despite the high level of c-myc mRNA, the transfected cells contained a relatively low level of c-myc protein and expression appears to be regulated at a post-transcriptional level. The transfected cells exhibited a decreased serum requirement for growth and formed colonies in soft agar, but were non-tumorigenic in Balb/c athymic nude mice. The morphologic evidence of transformation in the absence of tumorigenesis suggests that transfection of murine fibroblasts with multiple copies of the c-myc gene expressed under the control of its own promoter may cause partial transformation.

Animals↗

Developmental regulation of erythropoiesis by hematopoietic growth factors: analysis on populations of BFU-E from bone marrow, peripheral blood, and fetal liver.

Fetal hematopoiesis is characterized by expanding erythropoiesis to support a continuously increasing RBC mass. To explore the basis for this anabolic, nonhomeostatic erythropoiesis, the proliferative effect of recombinant hematopoietic growth factors on highly enriched hematopoietic progenitor cells from fetal and adult tissues were compared. Fetal hepatic BFU-E, unlike adult bone marrow (BM) or peripheral blood (PB) BFU-E, were capable of proliferating in response to erythropoietin in the absence of added GM colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3), and erythropoietin (Epo) directly stimulated the expansion of the fetal BFU-E pool in suspension culture. A murine monoclonal antibody (MoAb), Ep 3, was raised against enriched fetal liver progenitor cells, which detected all fetal BFU-E and which reacted with the erythropoietin-responsive, GM-CSF/IL-3-independent fraction of adult BM BFU-E and CFU-E. All adult PB BFU-E were Ep 3- but became Ep 3+ after stimulation with GM-CSF or IL-3. These data indicate that Epo plays a unique role in fetal hepatic erythropoiesis, stimulating proliferation of immature BFU-E in addition to promoting terminal differentiation of later erythroid progenitor cells. In addition, these results demonstrate a MoAb which detects all erythropoietin-responsive progenitor cells and distinguishes the BFU-E compartments in adult BM and PB.

Age Factors↗

New approaches in the treatment of urinary tract infections.

Our increased understanding of the pathophysiology of urinary tract infections (UTIs) have not only challenged our past approaches to the management of UTIs but also have enhanced our skills to diagnose and control the great majority of UTIs simply, quickly, and cost-effectively. Single-dose treatment is increasingly replacing traditional 10 to 14 days treatment for UTIs. Recurrent UTIs are better understood and becoming more manageable. Newer antibiotics are proving to be very promising and effective with minimal risk of development of resistant strains.

Anti-Bacterial Agents↗

The latent factor structure of the WAIS-R: a factor analysis of individual item responses.

Factor analytic examination of a 166 x 166 intercorrelational matrix that represents individual item scores from the 11 subtests of the WAIS-R provided evidence of five interpretable factors (N = 409). Two of these were identified as the Verbal and Performance factors previously encountered in traditional WAIS-R subtest-based factor analyses. The other three factors were characterized readily as involving (1) Advanced Vocabulary skills; (2) Basic Responsivity and (3) Advanced Computational ability. All three of these "new" factors accounted for at least 10% of the total variance, and comments are made with regard to the possible significance of their discovery to such topics as subtest variation and profile psychodiagnostics, theories that pertain to the nature and structure of human intellectual functioning, and subtest-based personality measurement theories.

Adult↗

Informational needs of patients who undergo excision of an acoustic neuroma.

Individuals who undergo removal of an acoustic neuroma are usually apprehensive in spite of the intrinsically benign nature of the disease. Fears surrounding the experience are related to the real risks involved in surgery near the brain and the complications which can ensue. The intensity of the patients' feelings of anxiety and uncertainty might be decreased if nurses were aware of and attended to the informational needs of these patients. In order to describe the informational needs of acoustic neuroma patients, a retrospective survey of 21 subjects who had had removal of such a tumor six to eighteen months previously was carried out. The survey determined: (1) the type of information patients received preoperatively and postoperatively (2) the type of information patients wanted (3) the type of problems experienced postoperatively and (4) the length and severity of the problems if they occurred. Content analysis indicated that the majority of subjects experienced tiredness, depression, headache, and dryness of eyes and mouth in the postoperative and convalescent phases. The actual illness experience persisted much longer than the subjects had expected. Subjects expressed explicit informational needs related to self-management after the surgery. The implications for nursing care will be discussed and the recommendations for an interdisciplinary patient education programme will be outlined.

Female↗

Differences in relative efficiency of nebulisers for pentamidine administration.

The study compared the pulmonary deposition of nebulised pentamidine when inhaled by way of different nebuliser systems by nine human-immunodeficiency-virus-positive patients with a history of previous Pneumocystis carinii pneumonia. Pentamidine, 50 mg or 300 mg, mixed with technetium-99m-labelled human serum albumin in a total volume of 3 ml, was administered by way of three jet nebulisers (System 22', 'System 22 Mizer', and 'Respigard II') operated with a gas flow of 6 l/min, and one ultrasound nebuliser ('Pulmosonic'). Pulmonary and non-pulmonary isotope deposition was measured for each apparatus and adverse effects and lung function tests were recorded. For both doses of pentamidine, the system 22 mizer produced the largest pulmonary isotope deposition and it was completed in the shortest time. Oropharyngeal and gastric deposition were least with the respigard II, which also caused the fewest adverse effects. The adverse effects were greatest with the system 22 mizer and pulmosonic and the higher pentamidine dose, which also caused significant reductions in measurements of pulmonary function. It is concluded that either the system 22 mizer or the respigard II should be used to administer nebulised pentamidine.

Amidines↗