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Biomedical subjects

K Thomas

Publications and source records attributed to K Thomas.

At least 127 records · Page 7Linked to original sources
PubMed1998

An oligo-screening strategy to fill gaps found during shotgun sequencing projects.

During the course of projects to sequence human and nematode cosmids we encountered great difficulties generating contiguous sequence in regions with repetitive DNA (Alu repeats in humans and tandem or inverted repeats in the nematode). We have developed a simple and efficient strategy to fill gaps. By screening M13, plasmid or phagemid libraries with oligonucleotides flanking the gap, clones are identified that contiguate the cosmid sequence. Our method has been integrated into the GAP4 sequence assembly program. The strategy reduces both time and costs in large scale sequencing projects.

Animals↗
PubMed1998

Development and implementation of a breast and cervical cancer screening program in urban and rural Alaska.

Early detection of breast and cervical cancers represents the single best strategy to effect the reduction of associated morbidity and mortality. The State of Alaska identified a need to establish a service delivery system which would assure the availability of breast and cervical cancer screening services for women who are low income, under- and uninsured, and from racial/ethnic minorities. In March 1995 the Alaska Breast and Cervical Cancer Early Detection Program (AK-BCCEDP) began funding breast and cervical cancer screening services through the Centers for Disease Control and Prevention, National Breast and Cervical Cancer Early Detection Program. The purpose of AK-BCCEDP is to establish a comprehensive service delivery strategy which includes screening, tracking, referral, follow-up, public education, quality assurance, surveillance, coalition building/partnering, and evaluation. During the first year of services (March 1, 1995, to February 29, 1996) 651 women were screened for breast and cervical cancer. Higher than expected numbers of breast cancer were detected. Of the 651 women screened, four were diagnosed with invasive breast cancer and three were diagnosed with high-grade squamous intraepithelial lesions.

Adolescent↗
PubMed1998

Transient basophilia following the application of lymphatic pump techniques: a pilot study.

Lymphatic pump techniques (LPTs) consisting of pectoral traction and splenic pump were performed on seven male medical students following blood collection for baseline value determinations. Blood was collected from each subject at 15, 30, 60, 120, and 240 minutes post-LPT. The samples were analyzed for serum chemistry and complete blood cell count. All subjects showed an increase in the percentage of basophils. There was variation in the time points for the initial occurrence of basophilia among the subjects. A separate cohort of five male medical students served as control subjects. The control group did not receive LPTs. Blood samples collected at the same time points as the experimental group did not show the basophilia.

Adult↗
PubMed1998

Effect of aspirin and sodium salicylate on cataract development in diabetic rats.

The role of acetylation in the antiglycating and anticataract effects of aspirin (ASA) is explored by comparing ASA's effects with that of sodium salicylate (SS), a nonacetyl analog of ASA, on cataract development in diabetic rats. Streptozocin diabetic rats were provided with either ASA or SS, orally, for 24 weeks. Appropriate drug controls, normal controls and diabetic controls were run in parallel. Periodic estimations of blood glucose, glycated hemoglobin and assessments of cataract progression were done. After 24 weeks lenses were removed, homogenised and separated into water soluble fraction and urea soluble fraction. The glycated lens proteins in each fraction was quantified. Results were analysed statistically and interpreted in relation to serum salicylate levels. Both ASA and SS did not influence blood glucose levels. In the untreated diabetic groups the onset and progression of cataract was quicker and complete within 16 weeks. Both ASA and SS delayed the onset and progression in diabetic rats, but ASA's effect was more pronounced than that of SS. The levels of glycated Hb and lens proteins in diabetic rats were significantly reduced by ASA and not by SS for the same serum salicylate levels. ASA's anticataract potential far exceeds that of SS and it is ASA, and not SS, that inhibits protein glycation. Thus the results favour the hypothesis that acetylation plays a major role in ASA's anticataract effect via inhibition of glycation.

Animals↗
PubMed1997

Molecular and functional characterization of the promoter region of the mouse LDH/C gene: enhancer-assisted, Sp1-mediated transcriptional activation.

Molecular and functional studies of the LDH/C 5' upstream promoter elements were undertaken to elucidate the molecular mechanisms involved in temporal activation of LDH/C gene expression in differentiating germ cells. Ligation mediated-PCR (LM-PCR) gene walking techniques were exploited to isolate a 2.1 kb fragment of the mouse LDH/C 5' promoter region. DNA sequence analysis of this isolated genomic fragment indicated that the mouse LDH/C promoter contained TATA and CCAT boxes as well as a GC-box (Sp1-binding site) situated upstream from the transcription start site. PCR-based in vivo DNase I footprinting analysis of a 600 bp fragment of the proximal LDH/C promoter region (-524/+38) in isolated mouse pachytene spermatocytes identified a single footprint over the GC-box motif. Three DNase I hypersensitive sites were also detectable in vivo, in a region containing (CT)n(GA)n repeats upstream from the CCAT box domain. Functional characterization of the promoter region was carried out in a rat C6 glioma cell line and an SV40 transformed germ cell line (GC-1 spg) using wild-type and mutated LDH/C promoter CAT reporter constructs. These studies provide experimental evidence suggesting that transcriptional activation of the LDH/C promoter is regulated by enhancer-mediated coactivation of the Sp1 proteins bound to the GC-box motif footprinted in vivo in pachytene spermatocytes.

Animals↗
PubMed1997

In vivo activation of the cystic fibrosis transmembrane conductance regulator mutant deltaF508 in murine nasal epithelium.

The gene causing cystic fibrosis (CF) encodes the CF transmembrane conductance regulator (CFTR), a cAMP-regulated chloride channel. Mutations in this gene result in reduced transepithelial chloride permeability across tissues affected in CF. Consequently, restoring chloride permeability to these tissues may prove therapeutic. Here we report that a combination of forskolin, an adenylate cyclase activator, and milrinone, an inhibitor of class III phosphodiesterases, increases the magnitude of the potential difference across nasal epithelium of mice homozygous for the most common CF mutation, delta F508, while neither drug alone has a significant effect on potential difference. Transgenic mice lacking CFTR do not respond to the milrinone/forskolin combination, indicating that the effect in delta F508 mice requires CFTR. These results suggest that, by pharmacological means, at least partial CFTR-mediated electrolyte transport can be restored in vivo to CF tissues expressing delta F508.

Amiloride↗
PubMed1997

The relationship between chromosome structure and function at a human telomeric region.

We have sequenced a contiguous 284,495-bp segment of DNA extending from the terminal (TTAGGG)n repeats of the short arm of chromosome 16, providing a full description of the transition from telomeric through subtelomeric DNA to sequences that are unique to the chromosome. To complement and extend analysis of the primary sequence, we have characterized mRNA transcripts, patterns of DNA methylation and DNase I sensitivity. Together with previous data these studies describe in detail the structural and functional organization of a human telomeric region.

Base Sequence↗
PubMed1997

Accumulation of glycosphingolipids in human atherosclerotic plaque and unaffected aorta tissues.

We have measured the levels of glycosphingolipids and the activity of glycosphingolipid glycosyltransferases in human aortic intima and media from patients who died of atherosclerosis. The effects of lactosylceramide (LacCer) and glucosylceramide (GlcCer) from plaque intima on smooth muscle cell proliferation were assessed. When the GlcCer data was expressed as (micrograms GlcCer/mg cholesterol and/mg total phospholipid, a 28-fold and 7-fold increase in plaque intima compared to normal intima was observed. Similarly, the level of LacCer was elevated 5-fold and 4-fold, respectively, compared to unaffected intima. The activity of UDP-GlcCer: ceramide beta 1-->4 glucosyltransferase (GlcT-1) was similar in unaffected tissue, fatty streaks, and plaques. However, the activity of UDP-galactose: GlcCer, beta 1-->4 galactosyltransferase (GalT-2) activity was moderately higher in plaque than in unaffected tissue. LacCer, but not GlcCer derived from plaque intima exerted a approximately 2.8-fold increase in the proliferation of human aortic smooth muscle cells grown in tissue culture compared to control presumably due to a marked increase in LacCer molecular species containing C16:0, C22:1, and C24:0 fatty acids in plaque intima compared to control. In sum, our findings provide an interesting and novel pathogenic mechanism of lactosylceramide mediated plaque formation via stimulation of aortic smooth muscle cell proliferation.

Adult↗
PubMed1997

Is prednisolone as good as flutamide in hormone refractory metastatic carcinoma of the prostate?

PURPOSE: There are no generally accepted rules for the second line treatment of prostate cancer and few prospective studies have attempted to compare 2 therapeutic strategies with different modes of action. MATERIALS AND METHODS: We describe a prospective, randomized study of 40 patients comparing the second line response of flutamide to prednisolone in patients with known hormone refractory stage M1 prostate cancer. RESULTS: The median survival of patients receiving either treatment was 32.9 weeks, with no difference between the 2 groups. In terms of biological response 11 of 20 patients (55%) receiving prednisolone and 10 of 20 (50%) receiving flutamide exhibited prostate specific antigen (PSA) suppression. Average minimum PSA was 54 and 52% of the initial PSA in patients receiving prednisolone and flutamide, respectively. There was no difference between the 2 treatment groups in terms of long-term survival, although 35% of all patients survived beyond 1 year and 3 survived beyond 2 years. CONCLUSIONS: More patients taking prednisolone described better pain relief, although both medications were well tolerated and there was no difference in terms of performance status or analgesic requirements.

Aged↗
PubMed1997

E test as an alternative to conventional MIC determination for surveillance of drug resistant Streptococcus pneumoniae.

A commercial E test was compared with the standard agar dilution method for the determination of minimum inhibitory concentration (MIC) of penicillin, erythromycin, chloramphenicol and cefotaxime for 36 strains of Streptococcus pneumoniae from patients with invasive diseases. Additional strains were tested for MIC values for penicillin (6), erythromycin (14) and cefotaxime (13) for a better statistical evaluation. Besides, 5 reference standards with predetermined MIC values obtained from WHO pneumococcal reference center at Copenhagen, Denmark were tested for penicillin and erythromycin, for quality assessment using both agar dilution as well as E test methods. An overall agreement within +/- 2 dilutions was noted for 97 per cent of the strains tested for all the antimicrobials. A high degree of correlation was noted for erythromycin (r = 1), penicillin (r = 0.99), chloramphenicol (r = 0.95) and cefotaxime (r = 0.9). In MIC determination of a single antimicrobial for diagnostic purpose, E test was found to be more cost effective than conventional agar dilution method. E test was simple to perform, easy to interpret and a valid method for MIC determination of antimicrobials for S. pneumoniae in our center.

Drug Resistance, Microbial↗
PubMed1996

Yeasties and beasties: 7 years of genome sequencing.

The Saccharomyces cerevisiae genome sequencing project was the first of many projects aimed at sequencing the entire genomes of model organisms. Since its initiation in 1989, there have been numerous debates about the validity of genome sequencing, especially with reference to the model organisms. Seven years on, I hope to satisfy some of the critics by demonstrating that, as a consequence of the mass of data now becoming available from such projects, and the beginning of the major collaborative effort to sequence the human genome, we are now entering an exciting and dynamic time for those involved not only in genome sequencing, but also in all areas of the biological sciences.

Animals↗
PubMed1996

Molecular cloning of tissue-specific transcripts of a transketolase-related gene: implications for the evolution of new vertebrate genes.

As part of a systematic search for differentially expressed genes, we have isolated a novel transketolase-related gene (TKR) (HGMW-approved symbol TKT), located between the green color vision pigment gene (GCP) and the ABP-280 filamin gene (FLN1) in Xq28. Transcripts encoding tissue-specific protein isoforms could be isolated. Comparison with known transketolases (TK) demonstrated a TKR-specific deletion mutating one thiamine binding site. Genomic sequencing of the TKR gene revealed the presence of a pseudoexon as well as the acquisition of a tissue-specific spliced exon compared to TK. Since it has been postulated that the vertebrate genome arose by two cycles of tetraploidization from a cephalochordate genome, this could represent an example of the modulation of the function of a preexisting transketolase gene by gene duplication. Thiamine defiency is closely involved with two neurological disorders, Beriberi and Wernicke-Korsakoff syndromes, and in both of these conditions TK with altered activity are found. We discuss the possible involvement of TKR in explaining the observed variant transketolase forms.

Alternative Splicing↗
PubMed1996

Modified latex agglutination test for rapid detection of Streptococcus pneumoniae and haemophilus influenzae in cerebrospinal fluid and direct serotyping of Streptococcus pneumoniae.

A modified latex agglutination test was designed and evaluated for the rapid detection of Streptococcus pneumoniae and haemophilus influenzae type b capsular antigens, and for direct serotyping of Streptococcus pneumoniae in the cerebrospinal fluid. Reagents were prepared by sensitizing latex particles with Omniserum (against 83 capsular serotypes of pneumococci) and Haemophilus influenzae type b burro antiserum. For serotyping reagents, latex particles were similarly coated with nine pneumococcal pool (a to I) antisera and 46 individual pneumococcal serogroup/serotype specific antisera. The test was performed on cerebrospinal fluid from 298 patients with suspected meningitis. Serotyping was done directly on untreated cerebrospinal fluid samples showing positive reactions with the Omniserum reagent. Pneumococcal or Haemophilus influenzae type b antigens were detected in 41 patients; in 32 of these the etiology was established by culture and in 2 by smear examination. Five of the remaining seven cases were judged clinically and by cytological examination of cerebrospinal fluid to have partially treated bacterial meningitis. In two cases the test was false positive. The overall sensitivity and specificity of the latex agglutination test for the detection of Streptococcus pneumoniae and Haemophilus influenzae type b antigens was 100% and 96.8% respectively. The commonest pneumococcal serotypes were type 1 (30%), types 6 and 19 (10% each). The latex agglutination test is rapid and simple to perform, yielding serotype data directly by testing of cerebrospinal fluid.

Adult↗