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Biomedical subjects

C L Smith

Publications and source records attributed to C L Smith.

At least 199 records · Page 11Linked to original sources
PubMed1992

Hypothyroidism producing reversible dementia. A challenge for medical rehabilitation.

The evaluation of dementia for reversible causes should not be overlooked. Hypothyroidism is a reversible cause for dementia. Mental status is one of the important factors to be assessed prospectively to determine whether a patient is likely to benefit from intensive inpatient rehabilitation. Because of the negative effect of dementia on the learning process during intensive inpatient medical rehabilitation, it alone may be a sufficient reason to consider alternatives to intensive inpatient rehabilitation. On our rehabilitation unit, hypothyroidism causing confusion was recognized and corrected in two patients. The thyroid-stimulating hormone test is suggested as a screening tool.

Aged↗
PubMed1992

Residues 20, 22, and 26 determine the subtype specificities of staphylococcal enterotoxins C1 and C2.

Nonconserved residues of staphylococcal enterotoxin C1 (SEC1) were converted to their counterparts in SEC2. The mutants that resulted were examined for reactivity with monoclonal antibodies (MAbs). Substitution at position 20, 22, or 26 interfered with binding of an SEC1-specific MAb. SEC1 mutants with substitutions at all three positions reacted only with an SEC2-specific MAb. Antibody-binding patterns were not associated with isoelectric point differences. All mutants retained biological activity.

Antibodies, Monoclonal↗
PubMed1992

Is there a role for fluconazole in the treatment of vulvovaginal candidiasis?

OBJECTIVE: To review the data describing the use of fluconazole in the treatment of vulvovaginal candidiasis (VVC). DATA IDENTIFICATION: A MEDLINE search of the English-language literature and a bibliographic review of pertinent articles examining the use of fluconazole in the treatment of VVC. STUDY SELECTION AND DATA EXTRACTION: Relevant open and controlled studies reporting on the efficacy, associated adverse effects, or both of fluconazole for the treatment of VVC are reviewed. Appropriate conclusions and/or data are extracted from each article and described. DATA SYNTHESIS: Studies comparing fluconazole with ketoconazole and topical antifungal agents such as clotrimazole and miconazole have shown fluconazole to be equally efficacious with minimal adverse effects. Most of these trials used single-dose fluconazole, which would theoretically lead to a high degree of medication compliance. Fluconazole also has shown promise at diminishing VVC relapse or recurrence, possibly because of more complete vaginal and rectal eradication of Candida species. Pharmacoeconomically, single-dose fluconazole therapy is cost-effective; however, the recent approval of miconazole and clotrimazole by the Food and Drug Administration for over-the-counter use may limit this potential advantage. CONCLUSIONS: Until additional data are available, fluconazole may be considered a treatment alternative for women with VVC who experience frequent relapses or recurrences, or for those who are noncompliant with standard therapy.

Candidiasis, Vulvovaginal↗
PubMed1992

Hormonal regulation of corticosteroid-binding globulin biosynthesis in the male rat.

Corticosteroid-binding globulin (CBG) is an acidic glycoprotein produced primarily by the liver and is the major glucocorticoid transport protein in rat blood. Various hormone treatments are known to modify plasma CBG levels and may thereby influence the bioavailability of glucocorticoids. We have, therefore, examined serum CBG and hepatic CBG mRNA levels in male rats after sc steroid (25 micrograms/100 g BW twice daily of dexamethasone, prednisolone, corticosterone, estrone, estradiol, ethinyl estradiol, progesterone, or 5 alpha-dihydrotestosterone) or T4 (10 micrograms/100 g BW twice daily) administration. After dexamethasone treatment, serum CBG levels decreased significantly (P less than 0.002) within 48 h and were 26% of those in vehicle-treated animals by 72 h. At this time, CBG mRNA was undetectable in liver RNA extracts by Northern blotting or solution hybridization, and nuclear run-off experiments indicated that dexamethasone reduces CBG gene transcription in the liver by at least 14-fold. Treatment with ethinyl estradiol also reduced serum CBG levels significantly (P less than 0.015) compared to pretreatment values. No other significant changes in serum CBG levels were observed after any other steroid hormone treatment, and alterations in hepatic CBG mRNA levels were only observed after dexamethasone treatment. T4 administration for 72 h increased serum CBG and hepatic CBG mRNA levels by 66% and 39%, respectively, but did not influence the rate of CBG gene transcription. Thus, increased CBG biosynthesis after thyroid hormone treatment appears to be due to an increase in CBG mRNA stability. No change in the Concanavalin-A-binding properties of CBG molecules was observed after treatment with either dexamethasone or T4, and this suggests that these hormones do not influence the type of oligosaccharide chains associated with this protein. We, therefore, conclude that dexamethasone and T4 regulate hepatic CBG biosynthesis in the rat by modulating CBG mRNA synthesis and stability, respectively.

Animals↗
PubMed1992

Cloning of an ovine 11 beta-hydroxysteroid dehydrogenase complementary deoxyribonucleic acid: tissue and temporal distribution of its messenger ribonucleic acid during fetal and neonatal development.

Glucocorticoids promote the development of many organ systems vital for extrauterine survival, and fetal cortisol provides the trigger for birth in sheep. The activity of glucocorticoids may be influenced at a cellular level by 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), which is responsible for the interconversion of cortisol and cortisone. To examine 11 beta-HSD gene expression during fetal development, two overlapping clones which yield a 1.4 kilobase (kb) complementary DNA encoding sheep 11 beta-HSD from a liver library were isolated by using a rat 11 beta-HSD cDNA as the probe. This cDNA contains a 879 base pair open reading frame for a protein of 292 amino acids that has more than 70% sequence identity to rat and human 11 beta-HSDs. To define the tissue distribution of 11 beta-HSD messenger RNA in sheep, selected tissues were collected from one fetus at day 130 and term (approximately 145 days), and from a nonpregnant ewe. Cellular RNA was extracted and subjected to Northern blot analysis, and a single 1.8 kb transcript was detected in the fetal and adult liver, lung, hypothalamus, anterior pituitary, and placenta. This was undetectable in adrenals and kidneys, but a smaller (1.5 kb) transcript was present in fetal and adult kidney RNA. The relative abundance of 11 beta-HSD mRNA was greatest in fetal and adult livers, and it was much higher in adult liver, lung, and kidney than in the corresponding fetal tissues. To examine whether 11 beta-HSD gene expression is developmentally regulated in the fetal sheep, liver, lung, and kidney tissues were taken from fetuses at day 60-70, day 100-110, day 125-130, at term, and from newborn lambs (24-48 h old). In the lung and kidney, the relative abundance of 11 beta-HSD mRNA did not change from day 60 to term but increased in the lungs of newborn lambs. In contrast, 11 beta-HSD mRNA levels in the liver increased between day 125 and term and rose further in the newborn. Collectively, these results demonstrate that 11 beta-HSD gene expression in sheep is regulated in a tissue-specific and developmentally programmed manner.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1991

Alignment of Sfi I sites with the Not I restriction map of Schizosaccharomyces pombe genome.

A Sfi I restriction map of the fission yeast Schizosaccharomyces pombe genome was aligned with the Not I restriction map. There are 16 Sfi I sites in the S. pombe genome. Three Sfi I sites are on chromosome III which is devoid of Not I sites. The sizes of the entire genome and individual chromosomes, calculated from the Sfi I fragment sizes, are consistent with that calculated from the Not I fragment sizes. The Sfi I map provides greater physical characterization of the S. pombe genome and further validates the use of S. pombe chromosomal DNA as size standard. These maps have allowed detection of polymorphism on all three chromosomes.

Base Sequence↗
PubMed1991

D,L-(tetrazol-5-yl) glycine: a novel and highly potent NMDA receptor agonist.

This paper describes the pharmacological activity of D,L-(tetrazol-5-yl)glycine, a structurally novel and highly potent agonist at the N-methyl-D-aspartate (NMDA) subtype of excitatory amino acid receptor. D,L-(Tetrazol-5-yl)glycine potently displaced NMDA receptor binding to rat brain membranes as measured using [3H]CGS19755 (IC50 = 98 +/- 7 nM) and [3H]glutamate (IC50 = 36 +/- 18 nM) as ligands. D,L-(Tetrazol-5-yl)glycine did not appreciably inhibit the binding of D,L-alpha-[5-methyl-3H] amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), [3H]kainate, or [3H]glycine (IC50s greater than 30,000 nM). D,L-(Tetrazol-5-yl)glycine was more potent than NMDA or cis-methanoglutamate as a depolarizing agent in the rat cortical slice, and unlike these other agents induced rapid receptor-mediated neurotoxicity. Depolarization by D,L-(tetrazol-5-yl)glycine was antagonized by LY233053, a selective NMDA receptor antagonist. D,L-(Tetrazol-5-yl)glycine was a highly potent convulsant when given to neonatal rats (ED50 = 0.071 mg/kg i.p.). Convulsions in neonatal rats or lethality in mice induced by D,L-(tetrazol-5-yl)glycine were selectively antagonized by competitive and non-competitive NMDA receptor antagonists. D,L-(Tetrazol-5-yl)glycine is a structurally novel (tetrazole-substituted) compound that is a highly potent and selective NMDA receptor agonist. D,L-(Tetrazol-5-yl)glycine could be used to probe further NMDA receptor function in vitro and in vivo.

Animals↗
PubMed1991

An amino acid substitution in biobreeding rat corticosteroid binding globulin results in reduced steroid binding affinity.

BioBreeding (BB) rats are derived from an outbred colony of Wistar rats and are used as a model of autoimmune diabetes mellitus. A corticosteroid binding globulin (CBG) variant with reduced affinity for glucocorticoids has now been found in the blood of these animals. The dissociation rate constants of BB CBG for cortisol (4.42 nM) and corticosterone (1.43 nM) are both about 50% higher than those associated with Wistar CBG, but no obvious difference in the steroid binding specificity of BB and Wistar CBGs was detected. Purified BB and Wistar CBGs exhibit the same size heterogeneity when examined by polyacrylamide gel electrophoresis under denaturing conditions, and the sizes of their respective hepatic mRNAs are identical. The genetic basis for this abnormality was therefore determined by comparing the cDNA sequences for BB and Wistar CBG, and this revealed a point mutation that results in a single amino acid substitution at residue 276 (Ile in BB CBG and Met in Wistar CBG). To confirm that this mutation is responsible for the reduced steroid binding affinity associated with BB CBG, the cDNAs for rat CBG-Ile276 and CBG-Met276 were expressed in Chinese hamster ovary cells. The steroid binding affinities of the CBGs secreted by these cells were essentially identical with those observed in the corresponding serum samples from these two rat strains. The amino acid substitution identified in BB rat CBG therefore clearly accounts for the reduction in its steroid binding affinity, and further analysis of this and other natural CBG variants may reveal important information about the CBG steroid binding site. It is also possible that this mutation may contribute to the etiology of pathological abnormalities that are characteristic of the BB rat.

Amino Acids↗
PubMed1991

Giardia lamblia: haploid genome size determined by pulsed field gel electrophoresis is less than 12 Mb.

Previous estimates of the size of the Giardia lamblia genome have ranged from 30 to 80 million base pairs (Mb), based on DNA renaturation kinetics. This is much larger than the sum of the sizes of the 4 to 5 chromosomal DNAs seen in typical pulsed field gel electrophoretic analyses. One possible explanation is that each visible chromosomal DNA consists of several unresolved DNA species. To examine this we have performed quantitative densitometry of ethidium stained chromosomal DNAs and Notl genomic digests. We have also examined the distribution of rDNA on Notl genomic fragments. All of our results suggests that the true genome size is 10.6 to 11.9 Mb. It is conceivable that the previous larger estimates may be distorted by impurities in the DNA preparations used.

Animals↗
PubMed1991

Secondary pulsed field gel electrophoresis: a new method for faster separation of larger DNA molecules.

A novel technique, which we call secondary pulsed field gel electrophoresis (SPFG) has been developed. In SPFG, short pulses are applied in the direction of net migration of the DNA in addition to the reorienting pulses used in conventional pulsed field electrophoresis (PFG). Experimental results show that SPFG extends and improves the electrophoretic resolution of DNA for molecules from 0.5 megabase pairs to over 10 megabase pairs in size. This improved resolution is obtained with dramatically shorter run times. Thus SPFG appears to circumvent a number of the key limitations in previous PFG protocols.

Chromosomes↗
PubMed1991

Structural and transcriptional analysis of a human subtelomeric repeat.

A human subtelomeric repeat (designated as the HST repeat) has been isolated and characterized from a yeast artificial chromosome containing one human telomere. This repeat is located immediately adjacent to the telomeric T2AG3 repeats at the extreme termini of the human chromosomes. The DNA sequence of 3.6 kb of the HST repeat has been determined. The HST repeat spans over 3.6 kb in length, and contains one evolutionarily conserved CpG-rich region. The copy number of the HST repeat varies among telomeres. Genomic hybridization experiments suggest that the HST repeat consists of two distinct segments, and the distal portions of the HST repeat are also distributed elsewhere in the genome. In HeLa cells, the HST repeat sequence appears to be transcribed into a 6 kb polyadenylated RNA and a variety of non-polyadenylated RNA species.

Base Sequence↗
PubMed1991

Construction and characterization of a NotI linking library of human chromosome 21.

Effective procedures have been developed for constructing NotI linking libraries starting from chromosome-specific genomic libraries. Fifteen different single copy and two rDNA NotI linking clones from human chromosome 21 were identified in two libraries. Their chromosomal origin was confirmed, and regional location established using hybrid cell panels. Hybridization experiments with these probes revealed pairs of genomic NotI fragments, each ranging in size from less than 0.05 to 4.0 Mb. Many fragments displayed cell type variation. The total size of the NotI fragments detected in a human fibroblast cell line (GM6167) and mouse hybrid cell containing chromosome 21 as its only human component (WAV17) were approximately 32 and 34 Mb, respectively. If these fragments were all non-overlapping, this would correspond to about 70% of the 50-Mb content estimated for the whole chromosome. The linking clones will be enormously useful in the subsequent construction of a NotI restriction map of this chromosome. Characterization of these clones indicates the presence of numerous additional sites for other enzymes that recognize sequences containing CpG. Thus most NotI linking clones appear to derive from CpG islands and probably identify the 5' end of genes.

Cell Line↗
PubMed1991

Separation and analysis of DNA by electrophoresis.

Pulsed-field gel electrophoresis, the polymerase chain reaction and capillary electrophoresis represent major technical advances in DNA electrophoresis in the last few years. This has lead to a number of new applications, including the cloning of large DNA fragments, multiplex analysis of DNA samples, and the detection of single base changes in DNA. New fluorescent and chemiluminescent techniques promise to simplify detection methods.

Animals↗
PubMed1991

Molecular studies of corticosteroid binding globulin structure, biosynthesis and function.

Phylogenetic comparisons of the primary structure of corticosteroid binding globulin (CBG) have revealed several conserved domains that include sites for N-glycosylation and a region which probably represents a portion of the steroid binding site. The major site of CBG biosynthesis in adults is clearly the liver, and the human CBG gene promoter contains sequence elements that interact with liver-specific transcription factors. Low levels of CBG gene expression have been detected in other tissues, and these may be important for fetal development during late gestation when hepatic CBG mRNA levels are low. Studies of the ontogeny of CBG biosynthesis in the rat have also indicated that plasma CBG levels may be influenced by a more rapid clearance of the protein during pubertal development. Analyses of the structural organization and chromosomal location of the human CBG gene have further confirmed its close relationship with the serine proteinase inhibitors, and suggests that CBG, alpha 1-proteinase inhibitor and alpha 1-antichymotrypsin evolved relatively recently by gene duplication. The functional significance of this relationship has been examined and our studies suggest that a specific interaction between CBG and elastase on the surface of neutrophils may represent a physiologically important event that promotes the delivery of glucocorticoids to these cells at sites of inflammation.

Amino Acid Sequence↗
PubMed1991

New techniques for physical mapping of the human genome.

We describe improvements in techniques and strategies used for making maps of the human genome. The methods currently used are changing and evolving rapidly. Today's techniques can produce ordered arrays of DNA fragments and overlapping sets of DNA clones covering extensive genomic regions, but they are relatively slow and tedious. Methods under development will speed the process considerably. New developments include a range of applications of the polymerase chain reaction, enhanced procedures for high resolution in situ hybridization, and improved methods for generating, manipulating, and cloning large DNA fragments. More detailed genetic and physical maps will be useful for finding genes, including those associated with human diseases, long before the complete DNA sequence of the human genome is available.

Base Sequence↗
PubMed1991

Incorporation of fatty acids from fish oil and olive oil into colonic mucosal lipids and effects upon eicosanoid synthesis in inflammatory bowel disease.

The incorporation of the fatty acids in fish and olive oil into the colonic mucosa of patients with inflammatory bowel disease was examined during 12 weeks' dietary supplementation with the oils, and the influence on colonic mucosal prostaglandin and thromboxane generation was measured. With a dietary supplement of 18 g fish oil daily, concentrations of the major polyunsaturated fatty acids in fish oil, eicosapentaenoic acid and docosahexaenoic acid, were significantly raised in mucosal lipids. The first time these were measured, after three weeks' supplementation, the mean increases in eicosapentaenoic and docosahexaenoic acid were seven fold and 1.5 fold respectively, and these increases were maintained during the 12 week study. Arachidonic acid values fell throughout the study and this reduction was significant at 12 weeks. Mucosal prostaglandin E2 (PGE2), thromboxane B2, and 6-keto prostaglandin F1 alpha synthesis were suppressed, and this reached significance (p less than 0.05) at three and 12 weeks for PGE2 and at 12 weeks for thromboxane B2. The predominant fatty acid in olive oil is oleic acid. Supplementation with 18 g/day resulted in a significant increase in oleic acid in colonic mucosa at 12 weeks (p less than 0.05) and a fall in stearic acid and docosahexaenoic acid; there was no significant change in eicosanoid synthesis. It is concluded that colonic lipids and prostaglandin and thromboxane synthesis can be readily altered by dietary supplementation with fish oil. The extent of incorporation of the fatty acids present in oils is dependent upon the individual fatty acid.

Adult↗