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D Smith

Publications and source records attributed to D Smith.

At least 325 records · Page 18Linked to original sources
PubMed1999

The spindle checkpoint of budding yeast depends on a tight complex between the Mad1 and Mad2 proteins.

The spindle checkpoint arrests the cell cycle at metaphase in the presence of defects in the mitotic spindle or in the attachment of chromosomes to the spindle. When spindle assembly is disrupted, the budding yeast mad and bub mutants fail to arrest and rapidly lose viability. We have cloned the MAD2 gene, which encodes a protein of 196 amino acids that remains at a constant level during the cell cycle. Gel filtration and co-immunoprecipitation analyses reveal that Mad2p tightly associates with another spindle checkpoint component, Mad1p. This association is independent of cell cycle stage and the presence or absence of other known checkpoint proteins. In addition, Mad2p binds to all of the different phosphorylated isoforms of Mad1p that can be resolved on SDS-PAGE. Deletion and mutational analysis of both proteins indicate that association of Mad2p with Mad1p is critical for checkpoint function and for hyperphosphorylation of Mad1p.

Benomyl↗
PubMed1999

Worldwide trends in DDT levels in human breast milk.

BACKGROUND: Concern over human breast milk contamination with the pesticide DDT (1,1,1-trichloro-2,2-bis(chlorodiphenyl)ethane) has prompted numerous studies around the world during the last five decades. This article examines trends in reported DDT levels, and the apparent effect of restrictions on DDT use. METHODS: More than 130 published values for DDT in human milk since 1951 were compiled, and trend lines were fit for regions of the world. RESULTS: Population means have declined in much of the world, from 5000-10000 microg DDT/kg milk fat to around 1000 today in many areas. Although different regions have different means, the decline seen in various countries corresponds to their restricting DDT use. DISCUSSION: DDT concentrations in human milk have declined in most areas of the world, consistent with restrictions on its use. Nevertheless, levels can be high in areas still using DDT, even higher than the World Health Organization's recommended limit for infants. These results indicate that population averages can be reduced by a predictable amount as DDT use is restricted.

Asia↗
PubMed1999

Are HIV-infected patients with rapid CD4 cell decline a subgroup who benefit from early antiretroviral therapy?

We have developed a model to determine whether asymptomatic HIV-infected individuals who have a rapid CD4 cell decline are a subgroup who might benefit from early antiretroviral therapy. Data were obtained from a subgroup of participants in the Concorde and EACG020 trials, two randomized, double-blind, comparative trials of immediate (IMM) versus deferred (DEF) zidovudine therapy in asymptomatic HIV-infected individuals. The subgroup comprised 297 patients (IMM = 154, DEF = 143) who had at least one CD4 cell count before and after randomization. The median CD4 cell count at randomization was 491 x 10(6)/L, and the median follow-up was 61 months. The rate of CD4 decline before and after randomization was estimated using multi-level linear regression analysis, and patients were stratified into quartiles according to the rate of CD4 cell decline before randomization. Outcome measures were the development of AIDS, a 50% drop in CD4 count from the baseline, and death. A Cox proportional hazards model was used to examine whether the effect of zidovudine on disease progression varied according to the previous rate of CD4 decline. We found that a more rapid rate of CD4 decline before randomization was associated with a greater reduction in the rate of CD4 decline following IMM antiretroviral therapy (r = -0.5, P = 0.03). The greatest risk reduction in disease progression with IMM antiretroviral therapy was seen in the quartile of patients with the highest rate of CD4 decline (> or = 26 x 10(6) cells/L per 6 months) (hazards ratio (HR) = 0.61, 95% CI = 0.35-1.05). However, this effect was statistically significant in only the Concorde trial (HR = 0.48, 95% CI = 0.29-0.89). In contrast, we found no evidence in the EACG020 trial of any trend towards greater benefit in those with the most rapid CD4 cell decline. These findings suggest that asymptomatic patients with rapid CD4 cell decline are a subgroup likely to benefit from early antiretroviral therapy. This analytic approach should now be replicated in trials of combination therapy, and these should include viral load data.

Adult↗
PubMed1999

Decreasing ascorbate intake does not affect the levels of glutathione, tocopherol or retinol in the ascorbate-requiring osteogenic disorder shionogi rats.

Levels of glutathione in liver and kidney, and other nutrients in plasma were evaluated in male and female ascorbate-requiring osteogenic disorder Shionogi (ODS) rats fed semipurified diets in which the concentrations of ascorbate were gradually decreased from 1965 to 180 mg/kg. Plasma ascorbate levels in ODS rats were unaffected when ascorbate levels in the diet were decreased from 1965 to 768 mg/kg. However, plasma ascorbate levels decreased progressively when levels of ascorbate in the diet were decreased from 527 to 180 mg/kg. Plasma ascorbate levels decreased up to 77% when the dietary ascorbate concentration decreased from 1965 to 180 mg/kg. Ascorbate levels in liver and kidney fell as much as 60-70% when the dietary ascorbate levels were reduced from 1965 to 180 mg/kg. However, the glutathione levels in these tissues were not affected. Plasma retinol and vitamin E levels were not affected by decreasing dietary ascorbate intake. Total cholesterol levels increased significantly in female rats as dietary ascorbate intake declined. Levels of glycated hemoglobin decreased significantly when dietary ascorbate levels decreased from 1965 to 527 mg/kg. This study suggests that levels of vitamin E, retinol and glutathione are not affected by decreased dietary intake of ascorbate under nonscorbutic conditions, whereas elevated ascorbate intake is associated with a decrease in levels of plasma cholesterol in female ODS rats. However, excessive intake of ascorbate may be associated with elevated glycation of hemoglobin. To achieve the maximal health benefit of ascorbate supplementation, further studies are necessary to define optimal ascorbate intakes.

Administration, Oral↗
PubMed1999

The misdiagnosis of epilepsy and the management of refractory epilepsy in a specialist clinic.

We assessed the frequency, causes and consequences of erroneous diagnosis of epilepsy, and the outcome of patients referred with 'refractory epilepsy', by retrospective analysis of the case records of 324 patients. The sample was divided into those exposed to anti-epileptic drugs (n = 184), of whom 92 were said to have refractory seizures, and those who had not received treatment (n = 140). The latter group is reported elsewhere. The overall misdiagnosis rate was 26.1% (46/184), with incomplete history-taking and misinterpretation of the EEG equally responsible. Side-effects were reported by 19/40, while unnecessary driving restrictions and employment difficulties were encountered by 12/33 and 5/33, respectively. Of those labelled 'refractory epilepsy', 12 did not have epilepsy. Sixteen were rendered seizure-free and 25 significantly improved by the optimal use of anti-epileptic drugs or surgery. Diagnostic and management services for patients with suspected and established epilepsy are suboptimal, with psychological and socio-economic consequences for individual patients. The resulting economic burden on the health and welfare services is probably substantial.

Ambulatory Care↗
PubMed1999

Silicon assays in women with and without silicone gel breast implants--a review.

During the past 5 years, as the failure properties of silicone gel breast implants have emerged, there has been considerable interest in measuring the levels of silicone and silicon in blood, serum, breast milk, and body tissues. Assays have been done in control patients without implant exposure, and in patients with silicone gel implants in an attempt to predict implant failure. Nuclear magnetic resonance measurements of silicone compounds have not been helpful because of their low sensitivity of detection. However, all compounds containing the element silicon, which includes silicone, have been measured accurately. Modern techniques, such as electrothermal atomic absorption spectrometry, direct-current plasma emission spectrometry, and inductively coupled plasma emission spectroscopy have allowed precise measurement of silicon in body fluids and tissues. Using these techniques, recent studies have demonstrated consistent levels of silicon in the blood and plasma of control women without exposure to implants. In one study, plasma silicon was shown to be 140 +/- 10 ng per milliliter. In four other studies, serum silicon levels in control patients were the following: mean, 130 +/- 70 ng per milliliter; mean, 170 +/- 100 ng per milliliter; median, 100 ng per milliliter (range, 30-209 ng per milliliter); and 10 to 250 ng per milliliter. Three independent studies have shown that women with silicone gel implants have higher blood and serum silicon levels than control subjects, but their values were still within the range of control subjects. One study has shown that the mean silicon level in breast milk was not significantly different between 15 implant patients and 34 control patients. The measurement of silicon in control breast tissue has shown consistent results in three different studies, with most tests varying from <0.2 to 2.2 microg per gram dry weight. Three studies have shown that capsules from women with silicone gel breast implants had markedly elevated silicon levels compared with control breast tissue. Median silicon levels varied from 9,980 to 14,390 microg per gram dry weight. There was no significant difference in capsule silicon level between intact and ruptured implants or associated with implant duration in situ or year of implantation. Four studies have shown that capsules from saline implants had elevated levels of silicon compared with control tissue, but their silicon levels were much lower than those of gel implants. The median levels of silicon in the capsules of these studies were as follows: 7.7, 71.5, 198, and 1,100 microg per gram dry weight. Based on current knowledge, because of the large variability among patients, the use of silicon measurements in blood, serum, breast milk, or implant capsule tissue has no clinical role for the effective monitoring of implant leakage in women with silicone gel breast implants.

Breast Implants↗
PubMed1999

Use of rifampin for severe pruritus in children with chronic cholestasis.

BACKGROUND: Rifampin has been proposed to reduce pruritus in children and adults with chronic cholestasis; however, there is a paucity of published data regarding the use of rifampin in children. METHODS: In an open trial, 24 children were evaluated during a 6-year period. Diagnoses included 13 patients with extrahepatic biliary atresia (54%), six with Alagille's syndrome, three with Byler's disease, and one each with primary sclerosing cholangitis and alpha1-antitrypsin deficiency. All patients had severe pruritus that had not responded adequately to at least 2 months of therapy with ursodeoxycholic acid, diphenhydramine, or phenobarbital and local skin care measures. Treatment was initiated with rifampin, 10 mg/kg per day in two divided doses for 18+/-20 months, and the effect on the severity of pruritus was assessed by a clinical scoring system. RESULTS: Ten patients showed a complete response, 12 a partial response, and 2 no response. Complete response was more common in extrahepatic cholestasis (64% vs. 10%), whereas partial response was more common in intrahepatic cholestasis (80% vs. 29%). Treatment was associated with reduction of gamma-glutamyl transpeptidase. No clinical or biochemical toxicity of rifampin was observed. CONCLUSIONS: We conclude that for more than 90% of children with chronic cholestasis and severe pruritus unresponsive to other treatments, rifampin appears to be a safe and effective therapy.

Adolescent↗
PubMed1999

Evaluation of a Treadmill with Vibration Isolation and Stabilization (TVIS) for use on the International Space Station.

A treadmill with vibration isolation and stabilization designed for the International Space Station (ISS) was evaluated during Shuttle mission STS-81. Three crew members ran and walked on the device, which floats freely in zero gravity. For the majority of the more than 2 hours of locomotion studied, the treadmill showed peak to peak linear and angular displacements of less than 2.5 cm and 2.5 degrees, respectively. Vibration transmitted to the vehicle was within the microgravity allocation limits that are defined for the ISS. Refinements to the treadmill and harness system are discussed. This approach to treadmill design offers the possibility of generating 1G-like loads on the lower extremities while preserving the microgravity environment of the ISS for structural safety and vibration free experimental conditions.

Equipment Design↗
PubMed1999

Control of acid resistance in Escherichia coli.

Acid resistance (AR) in Escherichia coli is defined as the ability to withstand an acid challenge of pH 2.5 or less and is a trait generally restricted to stationary-phase cells. Earlier reports described three AR systems in E. coli. In the present study, the genetics and control of these three systems have been more clearly defined. Expression of the first AR system (designated the oxidative or glucose-repressed AR system) was previously shown to require the alternative sigma factor RpoS. Consistent with glucose repression, this system also proved to be dependent in many situations on the cyclic AMP receptor protein. The second AR system required the addition of arginine during pH 2.5 acid challenge, the structural gene for arginine decarboxylase (adiA), and the regulator cysB, confirming earlier reports. The third AR system required glutamate for protection at pH 2.5, one of two genes encoding glutamate decarboxylase (gadA or gadB), and the gene encoding the putative glutamate:gamma-aminobutyric acid antiporter (gadC). Only one of the two glutamate decarboxylases was needed for protection at pH 2.5. However, survival at pH 2 required both glutamate decarboxylase isozymes. Stationary phase and acid pH regulation of the gad genes proved separable. Stationary-phase induction of gadA and gadB required the alternative sigma factor sigmaS encoded by rpoS. However, acid induction of these enzymes, which was demonstrated to occur in exponential- and stationary-phase cells, proved to be sigmaS independent. Neither gad gene required the presence of volatile fatty acids for induction. The data also indicate that AR via the amino acid decarboxylase systems requires more than an inducible decarboxylase and antiporter. Another surprising finding was that the sigmaS-dependent oxidative system, originally thought to be acid induced, actually proved to be induced following entry into stationary phase regardless of the pH. However, an inhibitor produced at pH 8 somehow interferes with the activity of this system, giving the illusion of acid induction. The results also revealed that the AR system affording the most effective protection at pH 2 in complex medium (either Luria-Bertani broth or brain heart infusion broth plus 0.4% glucose) is the glutamate-dependent GAD system. Thus, E. coli possesses three overlapping acid survival systems whose various levels of control and differing requirements for activity ensure that at least one system will be available to protect the stationary-phase cell under naturally occurring acidic environments.

Acids↗
PubMed1999

Trace gases in breath of healthy volunteers when fasting and after a protein-calorie meal: a preliminary study.

The selected ion flow tube technique was used to quantify in breath the trace gases acetone, ammonia, ethanol, isoprene, and methanol during single exhalations while fasting and in response to feeding. Six normal volunteers were fasted for 12 h, and, after baseline breath samples were obtained, were fed a liquid protein-calorie meal to provide 0.47 g/kg of protein (Fortisip). Further breath samples were obtained at 20, 40, and 60 min, and then hourly for a further 5 h. Breath acetone concentrations fell from a maximum during fasting, reaching their nadir between 4 and 5 h. Breath ammonia concentrations fell immediately to one-half their fasting levels before a steady increase to two or three times baseline values at 5 h. There was a brief increase in breath ethanol concentrations after feeding, reflecting detectable ethanol contamination of the food. Subsequently, breath ethanol levels remained low throughout the experimental protocol. Isoprene concentrations did not change significantly, whereas changes in methanol concentrations reflected those in the ambient air. This preliminary study indicates that the selected ion flow tube technique may be used to detect changes in the trace gases present in breath and define their concentrations in the fasting and replete state. Of particular interest is the biphasic response of the breath ammonia concentration after feeding.

Adult↗
PubMed1999

Transmission rates of hepatitis C virus by different batches of a contaminated anti-D immunoglobulin preparation.

BACKGROUND AND OBJECTIVES: The aim of this study was to determine the hepatitis C virus (HCV) infection rate of recipients of different batches of anti-D immunoglobulin associated with an outbreak of HCV infection which occurred in 1977 and its relationship to the polymerase chain reaction (PCR) status of the implicated batches. This study was undertaken to determine the predictive value of HCV genome detection and quantification for subsequent infection in recipients of an HCV-contaminated anti-D immunoglobulin product for intravenous use. MATERIALS AND METHODS: Sera from recipients of anti-D were tested by HCV enzyme immunoassay and if found positive were subsequently tested by recombinant immunoblot assay and HCV PCR in a national HCV anti-D screening programme set up in 1994. The HCV status of 1,342 known recipients of infectious or potentially infectious batches has been compared to the amount of HCV RNA in the anti-D batch they received so as to determine the value of PCR in the prediction of infectivity in immunoglobulin preparations. RESULTS: It has been demonstrated that HCV-infected plasma derived from batches of anti-D showing levels of viral genome in excess of 10(4) genomes per millilitre led to infection of up to 60% of recipients. In contrast, batches with undetectable levels of HCV genome very rarely transmitted infection. CONCLUSIONS: The presence of HCV RNA in intravenous immunoglobulin preparations which have not undergone a specific viral inactivation step is a predictor of HCV infection in recipients.

Disease Outbreaks↗
PubMed1999

Novel polyisobutylene/polydimethylsiloxane bicomponent networks: III. Tissue compatibility.

The tissue biocompatibility of a series of novel rubbery polyisobutylene (PIB)/polydimethylsiloxane (PDMS) bicomponent networks was investigated by in vivo implantation into rats. Bicomponent networks of varying composition (PIB wt%/PDMS wt% = 70/30, 50/50, 35/65) as well as a standard polyethylene control were implanted intraperitoneally. After eight weeks the implants and surrounding tissue were removed for histological evaluation. In all scoring categories (i.e. collagen thickness, fibrous tissue orientation, collagen deposition in muscle tissue, lymphocyte infiltration, angiogenesis) the PIB/PDMS bicomponent network implants elicited either less or similar tissue and cellular response than polyethylene. To determine which implant elicited the least tissue and cellular response overall, a weighted score including collagen thickness, lymphocyte infiltration, and angiogenesis was calculated for each implant. According to these preliminary investigations, PIB/PDMS bicomponent networks are suitable for implant applications.

Abdominal Muscles↗
PubMed1999

Asthma hospitalization trends in California, 1983-1996.

Annual asthma hospitalization rates were calculated for California's ethnically diverse population from 1983 through 1996. Trends were examined for four race/ethnicity groups: Hispanics, African-Americans, non-Hispanic Caucasians, and Asians/Pacific Islanders. The overall rate decreased by 30% during the time period. African-Americans had the highest rate, more that three times greater than the rate for Caucasians. Among children, the rates for Caucasians decreased by one-third, while rates increased for Hispanics and Asians. The rate for African-American children remained generally constant and was four times higher than the rate for Caucasians. Data from 1996 were assessed for repeat admissions, age and sex differences in rates, costs, and progress toward national goals.

Adolescent↗
PubMed1999

[Assessment of quality of life of patients with gastroesophageal reflux. Elaboration and validation of a specific questionnaire].

UNLABELLED: Quality of life is frequently impaired in patients with gastro-esophageal reflux. The aim of this study was the validation of a new specific quality of life questionnaire in patients with gastro-esophageal reflux. METHODS: A questionnaire was generated as follows: a) item generation with patients, b) item reduction, c) psychometric validation and comparison to a reference questionnaire (SF36) in patients with symptomatic gastro-esophageal reflux, d) assessment of reproducibility, and e) responsiveness over time. RESULTS: The primary questionnaire was made of 104 items. Two hundred twenty three patients were enrolled, 38 items were selected in 7 dimensions. One item was deleted following a new analysis conducted in 349 patients. Cronbach coefficient ranged from 0.84 to 0.91 for the specific questionnaire and from 0.78 to 0.90 for the SF36 questionnaire. Dimensions of specific questionnaire and SF36 were correlated. Quality of life was more impaired in patients with more frequent symptoms. Severity of endoscopic lesions was partly correlated with impaired quality-of-life. Reproducibility and responsiveness over time were correct. The final valid questionnaire was made of 37 items in 7 dimensions. CONCLUSION: This work is the first validation of a specific questionnaire in French which has the ability to measure quality of life in patients with gastro-esophageal reflux. The use of this questionnaire during therapeutic trials might allow to be more accurate in assessment of treatment efficacy.

Adult↗
PubMed1999

The effect of immunodeficiency on cutaneous delayed-type hypersensitivity testing in HIV-infected women without anergy: implications for tuberculin testing. HER Study Group. HIV Epidemiology Research.

SETTING: A collaborative study in four urban medical centers in the United States. OBJECTIVE: To determine the effect of human immunodeficiency virus (HIV) infection and immunodeficiency on delayed type hypersensitivity (DTH) responses and the implications for interpretation of tuberculin reactions in non-anergic women with or at risk for HIV infection. DESIGN: Demographic and behavioral information, HIV antibody testing, CD4+ lymphocyte counts, and cutaneous responses to DTH testing with mumps, Candida, tetanus toxoid, and tuberculin (purified protein derivative-PPD) antigens were obtained in 1184 women. RESULTS: Reactions to one or more of the four antigens occurred in 436 HIV-seropositive and 356 high-risk seronegative women. Among non-anergic women, HIV-seropositives were less likely (P < or = 0.05) to react to mumps (62% vs 81%), tetanus (72% vs 84%), and PPD (13% vs 19%). Induration in HIV-seropositive reactors was associated with CD4+ cell level for mumps (P = 0.004) and tetanus (P < 0.001), but not for Candida or PPD. HIV-seropositive reactors with CD4+ cell counts >500/mm3 did not have significantly smaller reactions than HIV-seronegatives for any antigen tested. PPD sizes were similar among HIV-seropositive reactors with CD4+ cell counts >500/mm3 (12.4 +/- 7.4 mm) and HIV-seronegative reactors (12.0 +/- 8.3 mm); induration > or =10 mm was seen in 16/173 (9.2%) seropositive women with CD4+ cell counts >500/mm3 and 41/356 (11.5%) seronegative women, respectively (P = 0.5). CONCLUSION: Among HIV-infected women able to react to a DTH antigen, induration in response to that antigen was relatively intact at CD4+ counts >500/mm3. This suggests that degree of immunodeficiency should be considered when interpreting PPD reactions in HIV-infected persons.

Adolescent↗