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Biomedical subjects

S Gray

Publications and source records attributed to S Gray.

At least 37 records · Page 2Linked to original sources
PubMed2002

Characterization of humoral and cellular immune responses elicited by meningococcal carriage.

In order to study the immune response elicited by asymptomatic carriage of Neisseria meningitidis, samples of serum, peripheral blood mononuclear cells (PBMCs), and saliva were collected from a cohort of more than 200 undergraduate students in Nottingham, United Kingdom, who were subject to high rates of acquisition and carriage of meningococci. Serum immunoglobulin G levels were elevated following increases in the rate of carriage, and these responses were specific for the colonizing strains. In order to investigate T-cell responses, PBMCs from 15 individuals were stimulated with a whole-cell lysate of the H44/76 meningococcal strain (B:15:P1.7,16), stained to detect cell surface markers and intracellular cytokines, and examined by flow cytometry. The cells were analyzed for expression of CD69 (to indicate activation), gamma interferon (IFN-gamma) (a representative T-helper 1 subset [Th1]-associated cytokine), and interleukin-5 (IL-5) (a Th2-associated cytokine). Following a brief meningococcal stimulation, the numbers of CD69(+) IFN-gamma(+) CD56/16(+) NK cells were much higher than cytokine-positive CD4(+) events. Both IFN-gamma(+) and IL-5(+) events were detected among the CD69(+) CD4(+) population, leading to the conclusion that an unbiased T-helper subset response was elicited by meningococcal carriage.

Antibodies, Bacterial↗
PubMed2001

Tissue- and time-dependent effects of endothelin-1 on insulin-stimulated glucose uptake.

Hyperendothelinaemia is associated with various insulin-resistant states, e.g., diabetes, obesity and heart failure, but whether endothelin-1 (ET-1) has a direct effect on insulin-mediated glucose uptake is unclear because the interpretation of in vivo metabolic studies is complicated by ET-1 effects on muscle blood flow and insulin secretion. This study investigated the effects of ET-1 (1-10 nM) on basal and insulin-stimulated 2-deoxy-D-[3H]glucose (2-DOG) uptake in cultured L6 myoblasts and 3T3-adipocytes. RT-PCR analysis showed that both cell types express ET(A) but not ET(B) receptors. ET-1 had no effect on basal (non-insulin-mediated) glucose transport, but there was evidence of a tissue- and time-dependent inhibitory effect of ET-1 on insulin-stimulated glucose uptake. Specifically, ET-1 10 nM had a transient (0.5 h) inhibitory effect on glucose uptake in 3T3 cells (C(I-150) [dose of insulin required to increase glucose uptake by 50%, relative to control 100%] increased from 89 +/- 14 nM to 270 +/- 12 nM at 30 mins, P < 0.05) but no effect on insulin sensitivity in L6 myoblasts (C(I-150) was 56 +/- 14 nM [control], 43 +/- 14 [30 mins] and 26 +/- 16 [2 h]). In conclusion, the inhibitory effect of ET-1 on insulin-stimulated glucose uptake is transient and occurs in 3T3-L1 adipocytes but not skeletal muscle-derived cells, perhaps reflecting tissue differences in ET(A)-receptor signaling. It is therefore unlikely that chronic hyperendothelinaemia has a direct insulin-antagonist effect contributing to peripheral (ie muscle/fat) insulin resistance in vivo.

3T3 Cells↗
PubMed2001

Vitellogenin induction in painted turtle, Chrysemys picta, as a biomarker of exposure to environmental levels of estradiol.

Ponds within cattle farms often support turtle and fish populations and are impacted by manure runoff. Cattle excrete metabolized (glucuronide-conjugated) hormones in feces and urine into these ponds, and bacteria cleave the glucuronide metabolites to active steroids, which can be stable for several weeks in wastewater. The objectives of this study were to (1) assess levels of xenoestrogens found in ponds near livestock pastures; and (2) assess whether these levels of xenoestrogens induce vitellogenin (VTG) in painted turtles in the laboratory and field. We collected water twice, 6 weeks apart, and placed turtle traps weekly into two ponds, which receive runoff from beef cattle pastures, and into one pond with no cattle farm effluents. Water E(2) levels were analyzed using C(18) solid phase extraction disks and detected in a radioimmunoassay (RIA). Plasma was collected from painted turtles (Chrysemys picta) captured from these ponds and VTG levels were measured via enzyme linked immunosorbent assay (ELISA). Nine additional turtles were collected from a pond at the South Carolina Botanical Gardens, which receives no farm runoff, and were exposed in the laboratory to nominal concentrations of 0.15, 1.5, and 15 ng/l estradiol (static renewal) over a 28-day period, followed by 14 days in clean water. Plasma samples were taken weekly for VTG measurement via ELISA. Levels of free estradiol in the water column of farm ponds range from 0.05 to 1.80 ng/l, as measured by RIA, and up to 7.4 ng/l as measured by ER-beta binding affinity. This is similar to what has been reported in streams receiving sewage treatment works (STW) effluents. In the laboratory, plasma VTG in male painted turtles could not be induced even at the high E(2) dose (9.45 ng/l) after 28 days. In the field, VTG levels were induced only in females when compared with animals from the SC Botanical Gardens. Adult male turtles need to be primed with high doses of E(2) prior to being able to respond to exogenous E(2). Given that males would not typically be sensitized in the wild, environmentally relevant levels of E(2) may not be sufficient to affect them. However, higher VTG levels in females could potentially change their reproductive fitness by altering egg size or by shifting energy allocations away from other survival needs. Long-term studies are needed to study potential impacts of VTG induction on female turtle reproductive success.

Animals↗
PubMed2001

Transition programs in cystic fibrosis centers: perceptions of pediatric and adult program directors.

There is a growing population of adults with cystic fibrosis (CF) and a need for development of adult CF programs. Recommendations for transfer of patients to an adult program include a transition program. Our goal was to assess the current status of transition programs in US CF centers. In addition, we sought to determine the problems related to the transfer of patients to adult programs as perceived by CF center program directors. A survey was sent in 1998 to 110 pediatric and 44 adult program directors at CF centers approved by the Cystic Fibrosis Foundation (CFF), with a response rate of 65.5% and 72.7%, respectively: 22.2% of pediatric centers reported having a non-CFF-approved adult program, and 38.9% had no specific adult program. About one fifth of pediatric centers cited lack of an adult CF physician as an impediment to establishing an adult program. Age (82% of programs; mean, 18.5 years), but not marriage (17.1%) or pregnancy (24.8%), was used as a criterion for transfer. Criteria precluding transfer included patient/family resistance (51.4%), disease severity (50.5%), and developmental delay (46.7%). The concept of transfer is introduced to the patient and family at the time of diagnosis in a minority (14%) of programs. Over one half of the patients did not meet the adult team until the time of transfer. Pediatricians reported higher perceived parent, patient, pediatric staff, and adult staff concerns about transition issues than did adult program directors. We conclude that there is a lack of standardized programs for transfer of CF patients from a pediatric to an adult care setting, and that there are differences between pediatric and adult program directors' perceptions of concerns that CF patients, their families, and the medical teams have about transfer. These differences may impede the successful transition of patients into an adult program.

Adolescent↗
PubMed2001

Protein kinase C activation: isozyme-specific effects on metabolism and cardiovascular complications in diabetes.

Protein kinase C (PKC) is a family of multifunctional isoenzymes, activated by diacylglycerols (DAGs), which play a central role in signal transduction and intracellular crosstalk by phosphorylating at serine/threonine residues an array of substrates, including cell-surface receptors, enzymes, contractile proteins, transcription factors and other kinases. Individual isozymes vary in their pattern of tissue and subcellular distribution, function and Ca2+/phospholipid cofactor requirements, and in diabetes there is widespread activation of the DAG-PKC pathway in metabolic, cardiovascular and renal tissues. In liver, muscle and adipose tissue, PKC isozymes have been implicated both as mediators and inhibitors of insulin action. Activation of DAG-sensitive PKC isoforms, such as PKC-theta and PKC-epsilon, down-regulates insulin receptor signalling and could be an important biochemical mechanism linking dysregulated lipid metabolism and insulin resistance in muscle. On the other hand, atypical PKC isozymes, such as PKC-zeta and PKC-lambda, have been identified as downstream targets of PI-3-kinase involved in insulin-stimulated glucose uptake, especially in adipocytes. Glucose-induced de novo synthesis of (palmitate-rich) DAG and sustained isozyme-selective PKC activation (especially but not exclusively PKC-beta) has been strongly implicated in the pathogenesis of diabetic microangiopathy and macroangiopathy through a host of undesirable effects on endothelial function, VSM contractility and growth, angiogenesis, gene transcription (in part by MAP-kinase activation) and vascular permeability. Interventions that increase DAG metabolism (e. g. vitamin E) and/or inhibit PKC isozymes (e. g. the beta-selective inhibitor LY333531) ameliorate the biochemical and functional consequences of DAG-PKC activation in experimental diabetes, for example improving retinal blood flow and albuminuria in parallel with reductions in membrane-associated PKC isozyme activities. Thus, a greater understanding of the functional diversity and pathophysiological regulation of PKC isozymes is likely to have important clinical and therapeutic benefits.

Animals↗
PubMed2001

Are routine chest X-rays for students entering university worthwhile?

Mass radiographic screening for tuberculosis has lost favour in many countries. The aim of this study was to determine whether the continued practice of such screening of prospective students at the University of the West Indies was warranted by assessing the yield and the cost of the programme in our setting. In a cross- sectional retrospective study, 12,662 chest X-ray reports collected over the period 1989-1997 were studied. No active case of tuberculosis was detected. Three students reported a previous history of tuberculosis and 10 students had a positive family history of tuberculosis. Three hundred and ninety-nine clinically insignificant abnormalities were reported, such as mild scoliosis and calcified foci. Routine radiological screening of prospective students at the University of the West Indies for tuberculosis has an extremely low yield, places the students at unnecessary risk of radiation exposure and should be discontinued.

Cost-Benefit Analysis↗
PubMed2001

Are there still effects on Indian Subcontinent ethnic tuberculosis of return visits?: a longitudinal study 1978-97.

OBJECTIVE: To assess whether return visits to the Indian Subcontinent (ISC) are associated with increased risks of developing clinical tuberculosis. METHODS: Descriptive analysis of epidemiological records over a period of 1978-97 inclusive in Blackburn, Hyndburn and Ribble Valley for individuals of ISC ethnic origin notified with tuberculosis. Those cases diagnosed through local contact tracing exercises were excluded. RESULTS: Of 1032 eligible individuals notified with tuberculosis, 228 (22.1%) reported prior visits to the ISC. Of these 151 (66%) reported having visits within 3 years of that notification, including 60% of the United Kingdom (U.K.) born without prior exposure to the ISC. CONCLUSION: The clinical observations are consistent with the hypothesis that return visits to the ISC carry a risk of acquiring tuberculosis. This cannot be confirmed, however, without information about the return visits in the ISC population as a whole. A case-control study may be required to confirm the hypothesis.

Adult↗
PubMed2001

Effects of active, passive or no warm-up on metabolism and performance during high-intensity exercise.

The aim of this study was to determine the influence of type of warm-up on metabolism and performance during high-intensity exercise. Eight males performed 30 s of intense exercise at 120% of their maximal power output followed, 1 min later, by a performance cycle to exhaustion, again at 120% of maximal power output. Exercise was preceded by active, passive or no warm-up (control). Muscle temperature, immediately before exercise, was significantly elevated after active and passive warm-ups compared to the control condition (36.9 +/- 0.18 degrees C, 36.8 +/- 0.18 degrees C and 33.6 +/- 0.25 degrees C respectively; mean +/- sx) (P< 0.05). Total oxygen consumption during the 30 s exercise bout was significantly greater in the active and passive warm-up trials than in the control trial (1017 +/- 22, 943 +/- 53 and 838 +/- 45 ml O2 respectively). Active warm-up resulted in a blunted blood lactate response during high-intensity exercise compared to the passive and control trials (change = 5.53 +/- 0.52, 8.09 +/- 0.57 and 7.90 +/- 0.38 mmol x l(-1) respectively) (P < 0.05). There was no difference in exercise time to exhaustion between the active, passive and control trials (43.9 +/- 4.1, 48.3 +/- 2.7 and 46.9 +/- 6.2 s respectively) (P= 0.69). These results indicate that, although the mechanism by which muscle temperature is elevated influences certain metabolic responses during subsequent high-intensity exercise, cycling performance is not significantly affected.

Adult↗
PubMed2001

Effect of cruciferous vegetable consumption on heterocyclic aromatic amine metabolism in man.

The consumption of cooked meat appears to predispose individuals to colonic cancer and heterocyclic aromatic amines (HA), formed during the cooking of meat, have been suggested as aetiological agents. Consumption of cruciferous vegetables is thought to protect against cancer. To study the effect of cruciferous vegetables on heterocyclic aromatic amine metabolism in man, a three-period, dietary intervention study has been carried out with 20 non-smoking Caucasian male subjects consuming cooked meat meals containing known amounts of these carcinogens. A high cruciferous vegetable diet (250 g each of Brussels sprouts and broccoli per day) was maintained during period 2 but such vegetables were excluded from periods 1 and 3. At the end of each period, subjects consumed a cooked meat meal and urinary excretion of the HA 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) was measured. Following a 12 day period of cruciferous vegetable consumption (period 2), induction of hepatic CYP1A2 activity was apparent from changes in the kinetics of caffeine metabolism. Excretion of MeIQx and PhIP in urine at the end of this period of the study was reduced by 23 and 21%, respectively, compared with period 1. This reduction in excretion is probably due to an increase in amine metabolism that might be expected given the observed increase in CYP1A2 activity, since this enzyme has been shown to be primarily responsible for the oxidative activation of MeIQx and PhIP in man. In period 2, urinary mutagenicity was increased relative to period 1 by 52 and 64% in the absence and presence, respectively, of a human liver microsomal activation system, yet no evidence was found of PhIP adduction to lymphocyte DNA, a potential biomarker of the activation process. After another 12 days without cruciferous vegetables (period 3 of the study), the kinetics of caffeine metabolism had returned to original values but excretion of MeIQx and PhIP was still reduced by 17 and 30%, respectively, and urinary mutagenicity (with metabolic activation) was still elevated compared with period 1. This prolonged response of amine metabolism to the cruciferous vegetable diet, shown especially with PhIP, suggests that enzyme systems other than CYP1A2 are involved and affected by a cruciferous vegetable diet.

Adult↗
PubMed2001

Hyperbilirubinemia during quinupristin-dalfopristin therapy in liver transplant recipients: correlation with available liver biopsy results.

STUDY OBJECTIVE: To review the liver histopathology in transplant recipients who developed hyperbilirubinemia during therapy with quinupristin-dalfopristin, a new streptogramin antibiotic, and to ascertain whether objective histologic evidence of adverse drug effect could be correlated to serum bilirubin levels. DESIGN: Retrospective analysis. SETTING: University of Pittsburgh Medical Center. PATIENTS: From a database of 34 liver recipients who received quinupristin-dalfopristin for vancomycin-resistant Enterococcus faecium infection who were prospectively enrolled in a multicenter, open-label, emergency-use protocol, the data for a subset of 25 patients who underwent one or more liver biopsies during therapy were reviewed for this study. INTERVENTIONS: Quinupristin-dalfopristin was administered intravenously at 7.5 mg/kg every 8 hours. Available serum bilirubin levels from before, during, and 1 week after therapy were tabulated. Liver biopsy results obtained within 1 week before and during therapy were retrospectively reviewed. Histopathologic results were characterized and correlated to bilirubin level. MEASUREMENTS AND MAIN RESULTS: Cholestatic changes were already present in 15 of 17 patients who underwent biopsy before therapy. During therapy, the most common findings from 40 biopsies (25 patients) were cholestasis (33 biopsies), acute rejection (10), and periportal inflammation (8). There was no evidence of drug-specific histopathologic injury. CONCLUSION: Hyperbilirubinemia in these patients was likely multifactorial and most frequently due to sepsis and prior graft injury.

Adult↗
PubMed2001

Epidemiology of over-the-counter drug use in community dwelling elderly: United States perspective.

Among US community dwelling individuals aged > or = 65 years, about as many persons take nonprescription drugs as take prescription drugs. A review of US data from the last 2 decades indicates that the average number of over-the-counter (OTC) drugs taken daily is around 1.8, but varies with geographical area (highest in the Midwest) and race/ethnicity (lowest use among Hispanics, followed by African Americans. and highest use among Whites). Use has consistently been found to be higher in women than in men. While OTC use appears to be increasing over time, it also decreases with increase in age. The most common OTC classes used are analgesics, laxatives and nutritional supplements. Our ability to explain or to predict OTC use and change in use is poor, and further studies, particularly on use by elderly individuals of minority races, are needed.

Aged↗
PubMed2000

The value of informant versus individual's complaints of memory impairment in early dementia.

Self-reported versus informant-reported memory problems in nondemented elderly adults and in individuals with very mild and mild dementia of the Alzheimer type (DAT) were correlated with cognitive outcomes. No significant correlations were found between self-reported memory complaints and cognitive performance or (in controls) later development of dementia. In contrast, informant-reported memory loss distinguished nondemented from demented individuals and predicted future diagnosis of DAT.

Aged↗
PubMed2000

Temporal association between hospitalization and rate of falls after discharge.

BACKGROUND: Evidence suggests that acute illness and hospitalization may increase the risk for falls. OBJECTIVE: To evaluate the rate of falls, and associated risk factors, for 90 days following hospital discharge. METHODS: We consecutively enrolled 311 patients, aged 65 years and older, discharged from the hospital after an acute medical illness and receiving home-nursing services. Patients were assessed within 5 days of discharge for prehospital and current functioning by self-report, and balance, vision, cognition, and delirium by objective measures. Patients were followed up weekly for 13 weeks for falls, injuries, and health care use. RESULTS: The rate of falls was significantly higher in the first 2 weeks after hospitalization (8.0 per 1000 person-days) compared with 3 months later (1.7 per 1000 person-days) (P =.002). Fall-related injuries accounted for 15% of all hospitalizations in the first month after discharge. Independent prehospital risk factors significantly associated with falls included dependency in activities of daily living, use of a standard walker, 2 or more falls, and more hospitalizations in the year prior. Posthospital risk factors included use of a tertiary amine tricyclic antidepressant, probable delirium, and poorer balance, while use of a cane was protective. CONCLUSIONS: The rate of falls is substantially increased in the first month after medical hospitalization, and is an important cause of injury and morbidity. Posthospital risk factors may be potentially modifiable. Efforts to assess and modify risk factors should be integral to the hospital and posthospital care of older adults (those aged >/=65 years).

Accidental Falls↗
PubMed2000

Age-specific incidence rates of Alzheimer's disease: the Baltimore Longitudinal Study of Aging.

OBJECTIVE: To estimate age-specific incidence rates of AD in the Baltimore Longitudinal Study of Aging (BLSA). BACKGROUND: The BLSA is a volunteer cohort of normal subjects followed longitudinally with biennial evaluations at the Gerontology Research Center of the National Institute on Aging. METHODS: Subjects are 1236 participants (802 men, 434 women) in the BLSA with longitudinal follow-up between January 1985 and May 1998. The average length of follow-up was 7.5 years, with participants evaluated every 2 years by physical, neurologic, and neuropsychological examinations. Using Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria, the authors diagnosed dementia and AD. RESULTS: The authors diagnosed 155 cases of dementia, of which 114 (74%) were AD. Incidence rates of AD increased with age from an estimated 0.08% per year (95% CI 0.00 to 0.43) in the 60 to 65 age group to an estimated 6.48% per year (95% CI 5.01 to 8.38) in the 85+ age group for men and women combined. The doubling time of incidence rates was estimated to be approximately 4.4 years and the median time of conversion from mild cognitive impairment to diagnosis of AD was estimated to be 4.4 years. There was a trend for women to have higher incidence rates than men and for fewer years of education to be associated with higher incidence rates; however, these effects were not significant. CONCLUSION: Incidence rates for AD in the BLSA are consistent with published rates in other studies. The longitudinally followed subjects of the BLSA offer a unique opportunity to prospectively investigate the antecedents of AD.

Age Factors↗