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Biomedical subjects

D West

Publications and source records attributed to D West.

At least 55 records · Page 3Linked to original sources
PubMed1996

Induction of single and dual cytotoxic T-lymphocyte responses to viral proteins in mice using recombinant hybrid Ty-virus-like particles.

The induction of cytotoxic T-lymphocyte (CTL) responses to viral proteins is thought to be an essential component of protective immunity against viral infections. Methods for generating such responses in a reproducible manner would be of great value in vaccine development. We demonstrate here that the recombinant antigen-presentation system based on the yeast transposon (Ty) particle-forming p1 protein is a potent means of inducing CTL responses to a variety of viral CTL epitopes, including influenza virus nucleoprotein (two epitopes), Sendai virus and vesicular stomatitis virus nucleoproteins, and the V3 loop of human immunodeficiency virus type-1 (HIV-1) gp120. CTL were primed by hybrid Ty-virus-like particles (VLP) carrying the minimal epitope or as much as 19,000 MW of protein. Ty-VLP carrying two different epitopes (dual-epitope Ty-VLP) were capable of priming CTL responses in two different strains of mice or against two epitopes in the same individual. Furthermore, co-administration of a mixture of two different Ty-VLP carrying single epitopes could induce responses to both epitopes in the same individual. Ty-VLP appear to represent a reproducible and flexible system for inducing CTL responses in mice, and warrant further evaluation in primates.

Amino Acid Sequence↗
PubMed1996

Health care integration: the role of information technologies.

Information technologies are rapidly becoming the major process drivers of health care system integration. These integrated information systems will emanate from MCOs and pervade the entire health care system at each level of service delivery. Suggestions for facilitating the integration process and the role of pharmaceutical industry, wholesalers, service providers, and end users are discussed herein.

Computer Security↗
PubMed1995

Perioperative considerations of glaucoma.

Perioperative nurses need to have a basic understanding of the anatomy of the globe and the physiological effects of the intraocular pressure from glaucoma. Surgical procedures are implemented initially for closed-angle (acute) and congenital glaucoma because of the emergent status of the diagnosis. The patient with open-angle (chronic) glaucoma may have a prolonged medical treatment before the need for surgical procedures.

Glaucoma↗
PubMed1995

Calmodulin inhibitors and calcium channel blockers influence dideoxycytidine renal excretion.

Renal handling of 2',3'-dideoxycytidine (ddC), a new anti-HIV dideoxynucleoside which undergoes renal and non-renal clearance, was determined in CF-1 male mice. Since calmodulin inhibitors (CIs) and calcium channel blockers (CCBs) have been shown to influence the flux of pyrimidine nucleosides across mammalian membranes and since the plasma concentration (and hence the efficacy) of therapeutic nucleosides is usually affected by the rate of renal elimination, we decided to determine the impact of the CIs loperamide (LOP) and trifluoperazine (TFP) as well as the CCB verapamil (VER) on the renal excretion of ddC. The ratio of ddC clearance to inulin clearance suggests that ddC undergoes secretion into renal tubules. Pre-exposure of mice to the calmodulin inhibitors loperamide (LOP) and trifluoperazine (TFP) resulted in a decrease in ddC renal secretion while pre-treatment with the calcium channel blocker verapamil increased ddC secretion.

Animals↗
PubMed1994

Transcription activation by the Escherichia coli cyclic AMP receptor protein. Receptors bound in tandem at promoters can interact synergistically.

Starting with a semi-synthetic Escherichia coli promoter with a binding site for the cyclic AMP receptor protein (CRP) centred between base-pairs 41 and 42 upstream from the transcription start site, a second upstream CRP-binding site, centred between base-pairs 90 and 91, was introduced. CRP binding to this second upstream site results in a several-fold greater stimulation of CRP-dependent transcription initiation, compared to activation at the starting promoter with just one CRP-binding site. Activation of transcription by the upstream CRP molecule is blocked by the HL159 substitution, suggesting that the upstream-bound CRP makes a direct contact with RNA polymerase. Footprinting experiments suggest that RNA polymerase contacts the promoter DNA between the two CRP-binding sites, most likely due to interactions involving the C-terminal part of the alpha subunit. Synergy between tandem bound CRP molecules in transcription activation requires that the two CRP-binding sites be separated by around 40 or 50 base-pairs, but is not found at intermediate spacings. An experiment in which the upstream CRP-binding site is replaced by a site for the related transcription factor, FNR, shows that heterologous synergistic interactions between FNR and CRP are possible.

Bacterial Proteins↗
PubMed1994

Effect of age on the immunogenicity of yeast recombinant hepatitis B vaccines containing surface antigen (S) or PreS2 + S antigens.

A single-blind, multicenter, phase II trial of yeast recombinant hepatitis B virus (HBV) vaccines containing surface antigen (S) alone or with PreS2 (PreS2 + S) was conducted in 282 healthy HBV-seronegative adults aged 20-59 years. Each volunteer was randomly assigned to receive HBV vaccine containing 10 micrograms of S or one of three doses of PreS2 plus S: 2 + 10 micrograms, 4 + 20 micrograms, or 8 + 40 micrograms. The level of antibody to HBV surface antigen reached depended on the dose of S, not PreS2, received. In each vaccine group, volunteers 20-39 years old had higher titers of anti-PreS2 and antibody to S than those 40-59 years old. The age-related effect on immune response to HBV vaccination suggests that adults should be immunized against hepatitis B at as early an age as possible and that older persons may need a higher dose or booster immunizations to achieve durable immunity.

Adult↗
PubMed1994

Stimulation of phospholipase C in cultured microvascular endothelial cells from human frontal lobe by histamine, endothelin and purinoceptor agonists.

1. Cultures of endothelial cells derived from the microvasculature of human frontal lobe have been investigated for phospholipase C (PLC) responses to histamine, endothelins and purinoceptor agonists. 2. Using cells prelabelled with [3H]-inositol and measuring total [3H]-inositol (poly)phosphates, histamine acting at H1 receptors stimulated a substantial response with an EC50 of about 10 microM. 3. Endothelin-1 also gave a clear stimulation of phosphoinositide-specific phospholipase C. Both concentration-response curves and binding curves showed effective responses and binding in the rank order of endothelin-1 > sarafotoxin S6b > endothelin-3, suggesting an ETA receptor. 4. Assay of total [3H]-inositol (poly)phosphates showed no response to the purinoceptor agonists, 2-methylthioadenosine 5'-trisphosphate (2MeSATP), adenosine 5'-O-(3-thiotrisphosphate) (ATP gamma S) or beta,gamma-methylene ATP. Both ATP and UTP gave a small PLC response. 5. Similarly, when formation of [32P]-phosphatidic acid from cells prelabelled with 32Pi was used as an index of both PLC and phospholipase D, a small response to ATP and UTP was seen but there was no response to the other purinoceptor agonists tested. 6. Study by mass assay of stimulation by ATP of inositol (1,4,5) trisphosphate accumulation revealed a transient response in the first few seconds, a decline to basal, followed by a small sustained response. 7. These results show that human brain endothelial cells in culture are responsive to histamine and endothelins in a manner which may regulate brain capillary permeability. Purines exert a lesser influence.

Adenosine Triphosphate↗
PubMed1994

Abnormal pressure natriuresis in the dog model of obesity-induced hypertension.

Obesity is considered to be a major factor in the pathogenesis of hypertension in industrialized countries. Recent studies have suggested that the kidneys may play an important role in the development of obesity-induced hypertension. The purpose of this study was to determine whether obesity-induced hypertension is associated with abnormalities in the pressure-natriuresis relation. Renal function studies were performed in anesthetized control dogs (body weight, 20.2 +/- 0.8 kg) and obese dogs (body weight, 26.4 +/- 0.7 kg) that were maintained on a high-fat diet for 5 to 6 weeks. Mean arterial pressure averaged 122 +/- 5 mm Hg in the control group (n = 6) and 148 +/- 7 mm Hg in the obese group (n = 8). The effects of renal perfusion pressure on renal hemodynamics as well as sodium and water excretions were examined at five levels of renal perfusion pressure ranging from 75 to 165 mm Hg. Pressure-natriuretic and diuretic responses were reduced in the obese dogs by 40% to 50%. The renal blood flow and glomerular filtration rate autoregulatory responses and fractional lithium excretion responses to changes in renal perfusion pressure were similar in the control and obese dog groups. Associated with the attenuated natriuretic response to renal perfusion pressure in the obese dogs were significant elevations in plasma renin activity (4.3 +/- 1.6 versus 1.6 +/- 0.5 ng angiotensin I/mL per hour), plasma aldosterone concentration (34.4 +/- 6.4 versus 15.3 +/- 3.2 ng/dL), and plasma insulin concentration (30.5 +/- 6.8 versus 20.9 +/- 2.9 IU/mL).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Parental smoking and risk of childhood brain tumors.

Data from a large, population-based, case-control study were analyzed to assess the role of parental smoking in childhood brain tumors. Parents of 361 cases, newly diagnosed between January 1, 1977 and December 31, 1981 and ascertained from eight Surveillance, Epidemiology, and End Results (SEER) program registries, and 1,083 controls had been interviewed. No significant differences in risks were found to be associated with maternal or paternal smoking at any time (odds ratio (OR) = 0.92 for mothers and 1.06 for fathers), during the year of birth of the child (which included both the prenatal and postnatal periods) (ORs = 0.84 for < 1 pack/day and 1.0 for > or = 1 pack/day for mothers, and 0.68 for < 1 pack/day and 1.07 for > or = 1 pack/day for fathers), or 2 years before the child was born, i.e., the pre-conception period (ORs = 0.75 for < 1 pack/day and 1.01 for > or = 1 pack/day for mothers, and 0.90 for < 1 pack/day and 1.15 for > or = 1 pack/day for fathers). Mothers were also specifically asked if they smoked during the pregnancy, and no association was found compared with never smokers (OR = 1.08, 95% confidence interval (CI) 0.80-1.45) or for ever-smokers who continued to smoke during pregnancy compared with those who stopped smoking during pregnancy (OR = 1.15, 95% CI 0.75-1.78). Finally, no significant increase in risk of brain tumors was found for the child's passive exposure to parental smoking during the period from birth to diagnosis of the brain tumor in the case. The lack of an effect of parental smoking was observed for both the major histologic types and locations of brain tumors. These findings and those from earlier studies provide no support for the hypothesis that parental cigarette smoking influences the risk of brain tumors in children.

Adult↗
PubMed1993

HIV-1 envelope gp120 alters astrocytes in human brain cultures.

The majority of AIDS patients will experience some degree of dementia induced by human immunodeficiency virus (HIV-1). In this study, we report that treatment of human brain tissue with envelope gp120 of HIV-1 did not cause neuronal death but did cause astrocyte alterations and/or death. Human astrocyte cultures showed decreased expression of glial fibrillary acidic protein (GFAP), as well as the diminution of a major protein of 66 kDa. These findings are similar to the in vitro changes observed when astrocytes are exposed to ammonia and in vivo changes observed in experimental hepatic encephalopathy. We hypothesize that AIDS dementia may partially involve a perturbation of astrocyte function by gp120 that could indirectly impair neuronal function.

AIDS Dementia Complex↗
PubMed1993

Interactions between the Escherichia coli cyclic AMP receptor protein and RNA polymerase at class II promoters.

The effects of a number of mutations in crp have been measured at different cyclic AMP receptor protein (CRP)-dependent Class II promoters, where the CRP-binding site is centred around 41 1/2 base pairs upstream from the transcription start point. The amino acid substitutions HL159 and TA158 result in reduced CRP-dependent activation, but the reduction varies from one Class II promoter to another. Deletions in the C-terminus of the RNA polymerase alpha subunit suppress the effects of HL159 and TA158. The role of the C-terminus of alpha at these promoters is assessed. Other changes at E58, K52 and E96 affect CRP activity specifically at Class II promoters and their role is discussed.

Amino Acid Sequence↗
PubMed1992

Cutaneous melanoma at Lawrence Livermore National Laboratory: comparison with rates in two San Francisco bay area counties.

During the period 1974 through 1985, employees at Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States) were diagnosed with cutaneous malignant melanoma at approximately three times the rate of the surrounding community. We investigated two explanations for this excess: the first explanation examined was that the recorded incidence of the neighboring community underestimates actual incidence. We estimated the amount of excess attributable to underreporting by using data from a survey conducted among San Francisco Bay Area clinicians and pathologists to determine previously unrecorded occurrences. We found that underreporting has negligible impact on melanoma incidence. The second explanation examined was that heightened medical awareness of the disease among LLNL employees and their physicians has led to greater detection. We found that LLNL melanomas are thinner than those from the surrounding community and that no excess was observed if we limited our attention to thicker, more invasive melanomas.

Adult↗
PubMed1992

Smoking, alcohol, dentition and diet in the epidemiology of oral cancer.

This matched case-control study was conducted in Western New York. The smoking, alcohol consumption, dental hygiene and diet of 290 cases were compared with those of 290 sex-, age-, and neighbourhood-matched controls. The results confirm earlier findings that cigarette smoking and alcohol consumption impart substantial risk of oral cancer. The results also confirm that poor oral hygiene increases the risk of oral cancer, although this effect is much smaller than those of cigarette smoking and alcohol consumption. The results suggest that, of macronutrients, intake of fat is more likely than those of protein or carbohydrate to be related to risk. Of micronutrients, calcium, sodium, riboflavin and retinol are associated with risk, while thiamin, niacin, and dietary fibre are associated with decreased risk. Although patterns of dietary effects are discernable, these effects are in general much weaker than are those of smoking and alcohol consumption.

Aged↗
PubMed1992

A mask to modify inspired air temperature and humidity and its effect on exercise induced asthma.

BACKGROUND: Heat and moisture loss from the respiratory tract during exercise are important triggers of exercise induced asthma. METHODS: A new heat and moisture exchange mask has been developed which both recovers exhaled heat and water and has a sufficiently low resistance for use during exercise. The effect of the mask on inspired air temperature was studied in four normal subjects. Eight asthmatic subjects performed identical exercise protocols on three separate days, breathing room air through a conventional mouthpiece, a dummy mask, and the new heat and moisture exchange mask. Seven different asthmatic subjects exercised while breathing cold air at -13 degrees C through a dummy or active mask. RESULTS: All subjects found the new mask comfortable to wear. The mean inspired temperature when the mask was used rose to 32.5 (1.4) degrees C when normal subjects breathed room air at 24 degrees C and to 19.1 (2.7) degrees C when they inhaled subfreezing air at -13 degrees C. The heat and moisture exchange mask significantly reduced the median fall in forced expiratory volume in one second (FEV1) after exercise to 13% (range 0-49%) when asthmatic subjects breathed room air compared with 33% (10-65%) with the dummy mask and 28% (21-70%) with the mouthpiece. The fall in FEV1 when the asthmatic subjects breathed cold air was 10% (0-26%) with the heat and moisture exchange mask compared with 22% (13-51%) with the dummy mask. CONCLUSION: Use of a heat and moisture exchange mask can raise the inspired temperature and humidity and ameliorate the severity of exercise induced asthma. The mask may be of practical value in non-contact sport or for people working in subzero temperatures.

Adolescent↗