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Biomedical subjects

J Thomas

Publications and source records attributed to J Thomas.

At least 1,099 records · Page 61Linked to original sources
PubMedDate not supplied

Interactions of merocyanine 540 with human brain tumor cells.

Merocyanine 540 (MC 540), a photosensitizing dye, has been used in preclinical studies and in a phase I clinical trial for the purging of leukemia, lymphoma, and neuroblastoma cells from bone marrow grafts. We evaluated MC 540 as an agent for the inactivation of brain tumor cell lines of medulloblastoma or glioma origin. The U373 glioma and 74SA medulloblastoma demonstrated significantly reduced survival as determined by in vitro clonogenic assay compared to normal glial cells when exposed to MC 540 and light. U87 glioma and Daoy medulloblastoma, however, were less sensitive than normal glial cells to MC 540 photoinactivation. In vivo injection of MC 540 into mice with malignant brain tumors disclosed greater dye incorporation into the malignant tissue compared with normal control mice brains or normal tissue surrounding the brain tumor. Increased uptake of MC 540 was observed in mice injected with either photosensitive (U373 and 74SA) or photoresistant (Daoy) cell lines. These data suggest that MC 540 may be an effective agent against certain brain tumors and that dye uptake in vivo does not reflect photosensitivity.

Animals↗
PubMedDate not supplied

LY339434, a GluR5 kainate receptor agonist.

The activity of a gamma-substituted glutamate analogue, (2S, 4R, 6E)-2-amino-4-carboxy-7-(2-naphthyl)hept-6-enoic acid (LY339434) and (2S,4R)-4-methylglutamic acid at ionotropic glutamate receptors has been examined. Ligand binding studies were performed using [3H] AMPA binding to membranes expressing either homomeric recombinant GluR1, GluR2, GluR4 receptors, and [3H] kainate binding to GluR5 and GluR6 kainate receptors. LY339434 and (2S,4R)-4-methylglutamic acid showed selectivity in ligand binding studies for kainate receptors over AMPA receptors. Within the kainate class of glutamate receptors, LY339434 showed selectivity for GluR5 over GluR6 whereas (2S,4R)-4-methylglutamic acid showed high affinity for both GluR5 and GluR6 kainate receptors. Examination of the functional activity of LY339434 and (2S,4R)-4-methylglutamic acid showed that both compounds evoked inward currents in dorsal root ganglion neurons (DRG) with estimated EC50 values of 0.8 +/- 0.2 microM and 0.17 +/- 0.04 microM, respectively. In GluR5 expressing HEK 293 cells, LY339434 evoked inward currents with an estimated EC50 value of 2.5 +/- 0.9 microM but had little effect on GluR6 expressing cells at concentrations less than 100 microM. LY339434 was a weak AMPA receptor agonist (EC50 values > 300 microM) as determined by activity in acutely isolated cerebellar Purkinje neurons. LY339434 and (2S,4R)-4-methylglutamic acid had agonist activity at NMDA receptors studied in cultured hippocampal neurons with EC50s of 2.5 microM and 11.7 microM, respectively. These results indicate that both LY339434 and (2S,4R)-4-methyl glutamic acid may be useful pharmacological tools for the examination of kainate receptors.

Amino Acids↗
PubMedDate not supplied

Reliability and validity of the Asthma Quality of Life Questionnaire--marks in a sample of adult asthmatic patients in the United States.

To render quality-of-life scores on an instrument acceptable for cross-national comparison, the instrument's reliability and validity must be established in all countries in question. The Asthma Quality of Life Questionnaire-Marks (AQLQ-M) was developed in Australia, where it was shown to have good reliability and validity. However, no attempt had been made to determine the psychometric properties of the AQLQ-M and its domains (i.e., Breathlessness, Mood, Social, and Concerns) in the United States. The objectives of the present study were to administer the AQLQ-M to a sample of adult asthmatic patients in the United States (N = 106) and assess (1) the acceptability of the AQLQ-M to respondents, (2) the internal consistency of the AQLQ-M and its domains, and (3) the construct validity of the AQLQ-M and its domains. Results indicated that respondents did not have difficulty answering the questions in the AQLQ-M. The Cronbach coefficient alpha value for the AQLQ-M was 0.94. The Cronbach coefficient alpha value for individual domains ranged from 0.84 to 0.91, providing evidence of good internal consistency reliability for the AQLQ-M and its domains. Pearson product-moment correlations between the domain scores ranged from 0.62 to 0.88, indicating that the domains were related but separate aspects of asthma-specific quality of life, as measured by the AQLQ-M. Spearman rank-order correlations of the AQLQ-M score and domain scores with an indicator of disease severity--number of different prescription medications taken for asthma in the preceding 3 months-were positive and significant. This indicated that subjects taking a greater number of prescription asthma medications had higher AQLQ-M and domain scores, or a greater negative impact of asthma on quality of life, a result consistent with previous findings and one that provides some evidence of convergent validity. Our findings support the use of the AQLQ-M as a decision-making tool in the United States and in cross-national comparisons between the United States and Australia.

Adolescent↗
PubMedDate not supplied

Effect of PDI overexpression on recombinant protein secretion in CHO cells.

In eukaryotic cells, protein disulfide isomerase (PDI) found in the endoplasmic reticulum (ER) catalyzes disulfide bond exchange and assists in protein folding of newly synthesized proteins. PDI also functions as a molecular chaperone and has been found associated with proteins in the ER. In addition, PDI functions as a subunit of two more complex enzyme systems: the prolyl-4-hydroxylase and the triacylglycerol transfer proteins. Increasing PDI activity in bacterial, yeast, and insect cell expression systems can lead to increased secretion of heterologous proteins containing disulfide bridges. Since Chinese hamster ovary (CHO) cells are widely used for the expression of recombinant proteins, we expressed recombinant human PDI (rhu PDI) in CHO cells to increase cellular PDI levels and examined its effect on the secretion of two different recombinant proteins: interleukin 15 (IL-15) and a tumor necrosis factor receptor:Fc fusion protein (TNFR:Fc). Secretion of TNFR:Fc (a disulfide-rich protein) is decreased in cells overexpressing PDI; the TNFR:Fc protein is retained inside these cells and colocalizes with the overexpressed rhu PDI protein in the endoplasmic reticulum. PDI overexpression did not result in intracellular retention of IL15. The nature of the interaction between PDI and TNFR:Fc was further investigated by expressing a disulfide isomerase mutant PDI in CHO cells to determine if the functional activity of PDI is involved in the cellular retention of TNFR:Fc protein.

Animals↗
PubMedDate not supplied

Initiation of capnography in a rural EMS system.

OBJECTIVE: Capnography is an effective means of monitoring cardiopulmonary resuscitation and managing endotracheal intubation. Numerous studies have validated its use in urban settings, but none have described its integration into a rural EMS system. The authors describe the process of integrating capnography training and use in Jackson County, West Virginia. METHODS: Two CO2SMOS capnography/ pulse oximeters were placed on the lead ambulances in Jackson County, West Virginia. Training in the operation and application of the equipment was provided, and providers used the monitors for a period of six months. A questionnaire was administered to assess their understanding of the equipment and its utility in prehospital care. Results were compiled and summarized. RESULTS: Ninety percent of the EMS providers subjectively felt that they understood capnography and its clinical application. They answered questions designed to test their understanding with 65% accuracy. CONCLUSION: In this model, capnography was successfully integrated into a rural EMS system. Reasonable proficiency in the use of the CO2SMOS monitor and an understanding of the information obtained were demonstrated, although the EMS providers tended to overestimate their actual understanding of the clinical application of capnography. This supports the need for ongoing, targeted education. The authors feel that capnography provides information that is uniquely relevant in rural EMS systems.

Allied Health Personnel↗
PubMedDate not supplied

Bacterial pathogens in rural water supplies in Southern Alberta, Canada.

Raw river and irrigation water in the Oldman River Basin in southern Alberta was tested for the presence of two bacterial pathogens, Escherichia coli O157:H7 and Salmonella spp., over the last 2 yr (2000-2001). The number of E. coli O157:H7 and Salmonella spp. isolated from raw water peaked during the summer months. While E. coli O157:H7 was only isolated from 11/802 (1.35%) of raw water samples over the entire sampling season in 2000 and from 16/806 (2.05%) of the samples in 2001, the pathogen was isolated one or more times from 10/35 (28.55%) sampling sites in 2000 and from 13/40 (32.55%) sampling sites in 2001. Salmonella was isolated from 44/802 (5.55%) of raw water samples in 2000 and from 122/822 (14.95%) of the samples in 2001; the pathogen was isolated one or more times from 25/35 (71.45%) sampling sites in 2000 and from 29/40 (72.55%) sampling sites in 2001. Certain sites had multiple pathogen isolations in the same year and from year to year. Salmonella Rublislaw was the most common Salmonella serovar isolated in both years, accounting for 52.45% of isolates.

Alberta↗
PubMedDate not supplied

Hodgkin's disease in a patient with Von Hippel-Lindau disease. A case report.

Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited disorder with a predisposition to develop a wide variety of lesions: retinal, cerebellar, spinal and medullar hemangioblastomas, renal cell carcinomas, phaeochromocytomas, and renal, pancreatic and epididymal cysts are the most frequent manifestations of the disease. The prevalence of VHL disease has been estimated to be 1 per 36,000 persons. We report the case of a 68-year-old woman with Von Hipple-Lindau disease who developed high fever with pulmonary and hepatic lesions proven to be Hodgkin's disease on biopsy. To our knowledge, this is the first report of Hodgkin's disease in a patient with Von Hippel-Lindau.

Aged↗