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Biomedical subjects

S Smith

Publications and source records attributed to S Smith.

At least 379 records · Page 21Linked to original sources
PubMed1997

Urinary excretion of 5-L-oxoproline (pyroglutamic acid) during early life in term and preterm infants.

Urinary 5-L-oxoproline was measured in term and preterm infants from shortly after birth until 6 weeks of postnatal age to determine their ability to synthesise glycine. In term infants the excretion was five to 10 times that seen in normal adults, increasing from 105 mumol/mmol creatinine in the first 72 hours after birth to 170 mumol/mmol creatinine at 6 weeks of age. There was a significant inverse linear correlation between the excretion of 5-L-oxoproline and length of gestation or birthweight. By 6 weeks of age there was no longer a significant difference in 5-L-oxoproline between term and preterm infants. There was no difference in the excretion of 5-L-oxoproline between boys and girls, or between infants fed on human milk or an artificial formula. If, in part, variability in the excretion of 5-L-oxoproline is determined by the extent to which the endogenous formation of glycine is adequate, then glycine formation may be marginal during early life, more so in preterm than in term infants, providing additional evidence that glycine is a conditionally essential amino acid in the neonate.

Birth Weight↗
PubMed1997

Perceived control of asthma: development and validation of a questionnaire.

Psychological factors can play a role in asthma symptoms and may play a role in how individuals manage asthma. Because poor self-management of asthma has been linked to poor outcomes, it is important to understand perceived control of asthma--the individual's perceived ability to deal with asthma and its exacerbations effectively. This study used data from an ongoing panel study of adults with asthma (n = 601). The 11-item Perceived Control of Asthma Questionnaire (PCAQ) demonstrated internal consistency (Cronbach's alpha = 0.74) and excellent construct validity, correlating strongly with asthma severity, quality of life, and Medical Outcomes Study Short Form (SF-36) measures of health status (p < 0.05). After controlling for demographics and asthma severity, each 6-point decrement in PCAQ score was significantly associated with increased risk of hospitalization (OR = 1.4 [95% CI: 1.1 to 1.8]), frequent activity restriction (OR = 1.5 [1.2 to 1.8]), and, among those with labor force participation (n = 551), asthma-related cessation of employment (OR = 1.7 [1.1 to 2.4]). The PCAQ is a short, easy to administer, reliable, and valid measure of perceived control of asthma. It is strongly associated with adverse asthma outcomes even taking into account demographic characteristics and asthma severity, suggesting that patient-centered interventions focusing on perceived control might improve asthma outcomes.

Adolescent↗
PubMed1997

Who is a heavy service user? Preliminary development of a screening instrument for prospective consumers of a mobile intensive treatment team.

OBJECTIVE: The mobile intensive treatment team (MITT) of the Valley Integrated Adult Mental Health Service in Brisbane, Australia, aims to provide services in the community to people with severe and persistent mental illness who have traditionally been heavily reliant on inpatient services (i.e. heavy service users). The MITT screening instrument (MITTSI) was developed to provide an objective measure to appropriately identify patients for referral to the service. METHOD: A literature review and a panel of multidisciplinary clinicians were consulted to identify a list of specific attributes that would assist in the detection of heavy service users. These attributes were then formulated into an easy-to-administer screening instrument entitled the MITTSI. The MITTSI was administered in an interview format to MITT case managers (intensive case management) and to case managers in standard case management with prospective MITT patients (prospective heavy service users). RESULTS: Analyses of the responses indicated support for the MITTSI as a valid screening instrument in identifying heavy service users and for determining appropriate patients for referral to the MITT. CONCLUSION: The MITTSI is an easy-to-administer screening instrument which provides clear guidelines for inclusion and exclusion, and is an objective measure regarding the patients' urgency for referral to the MITT. Follow-up of the MITTSI within a broader, longer-term project will attempt to further refine the MITTSI and to further determine its validity. Outcomes will be published at a later stage.

Adult↗
PubMed1997

Cardiac troponin T composition in normal and regenerating human skeletal muscle.

Cardiac troponin T (cTnT), measurement of which has been recommended for diagnosing myocardial infarction, was initially believed to be specific for the heart. However, recent publications have reported cTnT in sera of patients without cardiac disease; therefore, we investigated whether cTnT could be found in human skeletal muscle tissues. Using immunohistochemistry, Western blot, and quantitative cTnT ELISA, we assayed human heart (n = 3), normal human skeletal muscle (n = 6), and diseased skeletal muscle samples from patients with polymyositis (PM, n = 13) and Duchenne muscular dystrophy (DMD, n = 6). All heart specimens contained cTnT, but the expression of cTnT in normal skeletal muscle samples varied widely, ranging from no expression (quadriceps femoris) to expression by up to 20% of the muscle fibers (diaphragm). Immunohistochemistry detected cTnT in skeletal muscle of 8 of the PM patients and all of the DMD patients. Mean myofibrillar cTnT concentrations (mg/g myofibrillar protein) were: cardiac = 10.0, normal skeletal = 0.8, PM skeletal = 0.7, and DMD skeletal = 4.37, confirming the results of immunohistochemistry. Western blot analysis also confirmed the expression of cTnT in muscle from DMD patients. These findings provide evidence that cTnT is not 100% cardiac-specific but also is expressed in regenerating (PM and DMD) as well as in normal (nonregenerating) skeletal muscle.

Antibody Specificity↗
PubMed1997

Dysfibrinogenemia or afibrinogenemia in a Border Leicester lamb.

Hereditary fibrinogen deficiency is a rare condition in all species. Measurement of plasma fibrinogen should indicate low levels. Specific factor assays and pedigree analysis are essential in establishing a definitive diagnosis of the hereditary deficiency. Differentiation between afibrinogenemia, hypofibrinogenemia, and dysfibrinogenemia requires sophisticated techniques and assistance from a specialized laboratory.

Afibrinogenemia↗
PubMed1997

Use of advanced analytical techniques in assessing telemedicine.

Telemedicine is becoming increasingly prevalent in health care services. This article provides a general description of telemedicine and a detailed description of its use in Operation Joint Endeavor (Bosnia). Use of computer modeling for prospective analyses of telemedicine issues is focused on. Finally, this article describes the potential use of model-based analyses to address the impact of telemedicine on key nursing-related topics.

Bosnia and Herzegovina↗
PubMed1997

It's like a regular part of gay life: repeat HIV antibody testing among gay and bisexual men.

HIV antibody testing is a critical facet of national AIDS prevention strategies and increasing numbers of persons are tested each year. Research has shown that a significant number of men who have sex with men are repeatedly tested for HIV antibodies, and many are tested regularly every 6 months. This study investigated the prevalence of repeat testing (having been tested three or more time) and regular testing (having been tested three or more times and getting tested every 6 months), and their association to testing attitudes and sexual behaviors. We found that 66% of 253 HIV seronegative gay and bisexual men surveyed at a large gay pride festival had been repeatedly tested, and 47% were tested regularly. Repeat testing was associated with knowing people with HIV or AIDS, whereas regular testing was associated with younger age and not being in an exclusive sexual relationship. Both repeat and regular testers held more positive health-related attitudes about testing than nonrepeat and nonregularly tested men, respectively. Contrary to previous research, repeat testing was not associated with unprotected anal intercourse or unprotected oral sex. However, both repeat and regular testing were positively related to condom use during anal intercourse as well as having multiple protected anal intercourse partners. We therefore conclude that both repeat testing and higher rates of condom use reflect positive health attitudes and that repeat testing may function to meet the needs of some men who have sex with men.

AIDS Serodiagnosis↗
PubMed1997

Differential induction of cutaneous TNF-alpha and IL-6 by topically applied chemicals.

BACKGROUND: Increasing evidence shows that contact allergens and skin irritants can induce or upregulate the cutaneous expression of cytokines, including those that are required for the initiation of immune responses and which participate in inflammatory reactions. OBJECTIVE: The present investigation compared the ability of the skin allergens oxazolone and 2,4-dinitrochlorobenzene (DNCB) and the skin irritant benzalkonium chloride (BZC) to stimulate the cutaneous expression of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in mice. RESULTS: Each chemical tested induced the dose-dependent production of IL-6 with similar kinetic profiles. BZC was less effective at provoking increases in this cytokine; concentrations (1%) that caused marked edema failed to stimulate significant changes in IL-6 expression. Under conditions of topical exposure in which each of these chemicals caused a vigorous inflammatory response in the skin, as measured by induced edema and the increased production of IL-6, only oxazolone and DNCB stimulated expression of TNF-alpha. The failure of BZC to initiate TNF-alpha production in the skin was not attributable to inhibition of the bioassay used to measure this cytokine and was apparently independent of the stimulation by this chemical of TNF-alpha inhibitory factors. CONCLUSION: These data indicate that not all chemicals that have the ability to cause skin irritation and cutaneous inflammation will elicit detectable TNF-alpha responses and that characterization of cutaneous irritants and allergens on the basis of induced cytokine expression patterns in the skin must be approached with caution.

Adjuvants, Immunologic↗
PubMed1997

Mutations, tissue accumulations, and serum levels of p53 in patients with occupational cancers from asbestos and silica exposure.

In order to determine the relationship between mutations, tissue accumulations, and serum levels of p53 in occupational cancers, we used denaturing gradient gel electrophoresis and DNA sequencing of exons 5-9 of the p53 gene, immunohistochemical analysis for tissue identification of mutant p53 protein, and enzyme-linked immunosorbent assay for serum levels of mutant p53 protein to examine for such alteration in a cohort of individuals with workplace exposure to asbestos or silica, and resultant lung cancers or mesotheliomas. DNA analysis detected mutations in 5 of 18 (28%) tumors, and tissue accumulations of protein were detected in 7 of 20 (35%) tumors; the agreement between mutational and immunohistochemical analyses was significant (kappa = 0.62, P = 0.002). Serum elevations of protein were detected in 4 of 11 (36%) cases with available serum samples; the agreement between tissue alterations and serum elevations was also significant (kappa = 0.71, P = 0.017). In addition, based on the analysis of banked samples, serum results tended to be consistent over time prior to the diagnosis of disease (positive predictive value = 0.67, negative predictive value = 0.83). These results suggest that serum levels of p53 are reasonably accurate in reflecting tissue alterations in p53 at the gene and/ or protein level and may be early biomarkers of disease risk.

Adult↗
PubMed1997

Histomorphological and immunohistochemical evaluation of joint changes in a model of osteoarthritis induced by lateral meniscectomy in sheep.

OBJECTIVE: To evaluate the histomorphological and immunohistochemical changes induced in cartilages of ovine stifle (knee) joints 6 months after unilateral lateral meniscectomy. METHODS: Osteochondral sections were obtained from 8 distinct regions of knee joints of 6 adult Merino wethers that 6 months earlier had undergone lateral meniscectomy. Joint regions of 6 age matched sheep housed under identical conditions were used for controls. Serial sections were stained with toluidine blue or immunolocalized with monoclonal antibodies (Mab) 3B3(-), 7D4, and 5B10, which recognize epitopes on proteoglycans. RESULTS: In control joints the cartilage from the region of the tibial plateau not protected by the meniscus had significantly (p < 0.005) more structural abnormalities than other joint regions. After meniscectomy, only cartilages in the lateral femorotibial compartment showed histomorphological changes consistent with osteoarthritis (OA). The nature and severity of the lesions differed between the topographical regions within the joint. The most severe were found on the lateral femoral condyles and tibial plateaus. Reactivity with Mab 3B3(-), 7D4, and 5B10 was increased only in the lateral compartment cartilages, and was stronger in mild rather than moderate OA. CONCLUSION: Six month lateral meniscectomy in sheep produces histomorphological and immunohistochemical cartilage changes analogous to those described for early human OA and in other animal models. The severity and type of lesions obtained were dependent on the topographical joint location, but were most evident in cartilages from the lateral compartment.

Animals↗
PubMed1997

Pulmonary and allergy subspecialty care in adults with asthma. Treatment, use of services, and health outcomes.

To study the relationship between physician subspecialty practice type and health measures in patients with adult asthma, we prospectively studied 601 adults with asthma. The subjects were recruited from a random sample of board-certified pulmonary or allergy internal medicine subspecialists practicing in northern California; 539 patients (90%) were restudied after 18 months. Structured telephone interviews were used to elicit demographics, clinical variables, and measures of asthma severity, asthma-specific quality of life, and physical function status. At baseline and follow-up, 283 subjects (53%) reported their principal asthma care provider type as a pulmonary specialist throughout and 150 (28%) as an allergy specialist throughout, 53 (10%) switched provider type during follow-up, and 53 (10%) reported that their principal asthma care physician was from neither subspecialist group. Taking into account illness severity and other demographic and clinical covariates, the group whose principal asthma care came from an allergy subspecialist was more likely than the pulmonary specialist-care group to report possessing a peak expiratory flow rate meter (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.8 to 4.6) and less likely to be receiving high-dose inhaled steroids (OR, 0.3; 95% CI, 0.1 to 0.6). Taking into account demographic and clinical covariates, allergists' care was related to worse subject-reported asthma-specific quality of life (P = 0.02), but not to statistically increased risk of hospitalization, decreased physical function, or an increased number of reported health-related restricted-activity days. We observed subject-reported specialist variation in management and health outcomes among adults with asthma not accounted for by differing disease severity or other clinical and demographic variables.

Adult↗
PubMed1997

Parameters of protein delivery using hydroxyapatite in simulated body fluid.

Various studies have been conducted using hydroxyapatite (HA) to deliver therapeutic drugs over a long period of time. However, the rate of drug release from ceramics varies tremendously. Thus a study was designed to observe the effect of particle size, pressure, drug ratio, and the addition of a zinc stearate binder on the release of BSA from ceramics. Samples were collected every two hours for a 12 hour period. Three particle sizes were used in the study (< 38, 45-63, and 63-75 microns). Variations in particle size did not influence the release of BSA. Ceramics compressed at a pressure of 150 Mpa delivered more protein than pressures of 300 MPa, 450 MPa, and 900 MPa. Drug to ceramic ratio had the most significant effect. A ratio of 1:25 BSA to HA delivered the protein quickly whereas the 1:100 BSA to HA delivered BSA to HA delivered BSA slowly and in zero order kinetics. The addition of the zinc binder improved the quality of the composite and decreased the release rate of protein delivery when present in 5% or less of the total ceramic weight. HA ceramics can be used to deliver proteins at different rates by varying compression pressure and drug to HA ratio.

Biocompatible Materials↗
PubMed1996

Expression in Escherichia coli and refolding of the malonyl-/acetyltransferase domain of the multifunctional animal fatty acid synthase.

A cDNA encoding residues 429-815 of the multifunctional rat fatty acid synthase has been expressed in Escherichia coli and the recombinant protein refolded in vitro as a catalytically active malonyl-/acetyltransferase. Kinetic properties of the refolded recombinant enzyme were indistinguishable from those of a transferase preparation derived from the natural fatty acid synthase by limited proteolysis, indicating that the transferase domain is capable of folding correctly as an independent protein. Replacement of the active site Ser-581 (full-length fatty acid synthase numbering) with alanine completely eliminated catalytic activity, whereas replacement with cysteine resulted in retention of about 1% activity. The wild type transferase was extremely susceptible to inhibition by diethyl pyrocarbonate, and protection against inhibition was afforded by both malonyl- and acetyl-CoA. Replacement of the highly conserved residue His-683 with Ala reduced activity by 99.95%, and the residual activity was relatively unaffected by diethyl pyrocarbonate. The rate of acylation of the active site serine residue was also reduced by several orders of magnitude in the His-683 --> Ala mutant. These results indicate that His-683 plays an essential role in catalysis, likely by accepting a proton from the active site serine, thus increasing its nucleophilicity.

Acetyl Coenzyme A↗
PubMed1996

Reconstitution of T cell receptor signaling in ZAP-70-deficient cells by retroviral transduction of the ZAP-70 gene.

A variant of severe combined immunodeficiency syndrome (SCID) with a selective inability to produce CD8 single positive T cells and a signal transduction defect in peripheral CD4+ cells has recently been shown to be the result of mutations in the ZAP-70 gene. T cell receptor (TCR) signaling requires the association of the ZAP-70 protein tyrosine kinase with the TCR complex. Human T cell leukemia virus type I-transformed CD4+ T cell lines were established from ZAP-70-deficient patients and normal controls. ZAP-70 was expressed and appropriately phosphorylated in normal T cell lines after TCR engagement, but was not detected in T cell lines from ZAP-70-deficient patients. To determine whether signaling could be reconstituted, wild-type ZAP-70 was introduced into deficient cells with a ZAP-70 retroviral vector. High titer producer clones expressing ZAP-70 were generated in the Gibbon ape leukemia virus packaging line PG13. After transduction, ZAP-70 was detected at levels equivalent to those observed in normal cells, and was appropriately phosphorylated on tyrosine after receptor engagement. The kinase activity of ZAP-70 in the reconstituted cells was also appropriately upregulated by receptor aggregation. Moreover, normal and transduced cells, but not ZAP-70-deficient cells, were able to mobilize calcium after receptor ligation, indicating that proximal TCR signaling was reconstituted. These results indicate that this form of SCID may be corrected by gene therapy.

CD4-Positive T-Lymphocytes↗
PubMed1996

Improvement in human health risk assessment utilizing site- and chemical-specific information: a case study.

This paper provides results of an effort to use site- and chemical-specific data and other factors to characterize and refine risk estimates to a community. The refined assessment illustrated the influence of additional key variables on the risk estimates. Influence of variables associated with meteorological data and decay was relatively low. Influence of exposure assumptions was somewhat higher, approaching an order of magnitude. Of the variables examined, the butadiene slope factor assumption had the greatest impact, contributing nearly three orders of magnitude to the risk estimates separating the Best and Worst Case scenarios. Monte Carlo analysis indicated a high level of uncertainty in the risk estimates. Risk estimates in this paper should be considered in comparison to the approximate 1 in 4 background fatal cancer risk in the US population. In all cases the risk would be zero if butadiene is not carcinogenic in humans at prevailing exposure levels.

Humans↗
PubMed1996

Enhancement of thymopoiesis after bone marrow transplant by in vivo interleukin-7.

Bone marrow transplantation (BMT) is followed by a period of profound immune deficiency, during which new T lymphocytes are generated from either stem cells or immature thymic progenitors. Interleukin-7 (IL-7) induces proliferation and differentiation of immature thymocytes. We examined whether the in vivo administration of IL-7 to mice receiving BMT would alter thymic reconstitution. Lethally irradiated C57BL/6 mice received syngeneic BMT, followed by either IL-7 or placebo from days 5 to 18 post-BMT. At day 28, BMT recipients that had not received IL-7 had profound thymic hypoplasia (< 5% of normal), with relative increases in the numbers of immature thymocytes, decreased numbers of mature peripheral (splenic) T lymphocytes, and severely impaired T- and B-cell function. In contrast, transplanted mice treated with IL-7 had normalization of thymic cellularity, with normal proportions of thymic subsets and T-cell receptor beta variable gene (TCRV beta) usage, normal numbers of peripheral CD4+ T lymphocytes, and improved antigen-specific T- and B-cell function. In the BMT-IL-7 mice, there was an eightfold increase in the number of immature CD3-CD4-CD8- thymocytes in G2-M of the cell cycle, indicating that restoration of thymic cellularity was due to enhanced proliferation of immature thymic progenitors. Similar effects following IL-7 administration were also observed when donor bone marrow was depleted of mature T lymphocytes, indicating that IL-7 administration affected immature hematopoietic progenitors. IL-7 promotes thymic reconstitution after BMT, and may be useful in preventing post-BMT immune deficiency.

Animals↗
PubMed1996

Somatic mutations in human Ig variable genes correlate with a partially functional CD40-ligand in the X-linked hyper-IgM syndrome.

X-linked hyper-IgM (HIGM-1) syndrome is a rare disorder resulting from mutations in the CD40-ligand (CD40L) gene. This defect is associated with normal or elevated serum levels of IgM, and with low to undetectable levels of serum IgG, IgA, and IgE. We analyzed the somatic mutation status in Ig V genes from three unrelated HIGM-1 patients by reverse-transcription PCR and sequence analysis. Two patients (B.S. and P.S.) expressed unmutated VH6 genes. In contrast, one patient (A.T.) was found to express mutated VH6 genes. Whether the presence of somatic mutations in this patient was related to a functional CD40L was assessed by deriving T cell clones from his peripheral blood cells. Upon activation, these T cell clones expressed weakly and transiently surface CD40L, and were able to induce limited isotype switch of normal native B cells, indicating residual CD40L function. Altogether, our results 1) confirm the central role played by CD40L in the generation of somatic mutation (patients B.S. and P.S.), 2) provide an unusual illustration of the relative dissociation between somatic mutation and isotype switching (patient A.T.), and 3) demonstrate a further complexity of the X-linked HIGM syndrome that may occur despite a partially functional CD40L.

B-Lymphocytes↗