Biomedical subjects

S J Thompson

Publications and source records attributed to S J Thompson.

At least 19 recordsLinked to original sources

PubMed2001

Distinct Albino3-dependent and -independent pathways for thylakoid membrane protein insertion.

The homologous proteins Oxa1, YidC, and Alb3 mediate the insertion of membrane proteins in mitochondria, bacteria, and chloroplast thylakoids, respectively. Depletion of YidC in Escherichia coli affects the integration of every membrane protein studied, and Alb3 has been shown previously to be required for the insertion of a signal recognition particle (SRP)-dependent protein, Lhcb1, in thylakoids. In this study we have analyzed the "global" role of Alb3 in the insertion of thylakoid membrane proteins. We show that insertion of two chlorophyll-binding proteins, Lhcb4.1 and Lhcb5, is almost totally blocked by preincubation of thylakoids with anti-Alb3 antibodies, indicating a requirement for Alb3 in the insertion pathway. Insertion of the related PsbS protein, on the other hand, is unaffected by Alb3 antibodies, and insertion of a group of SRP-independent, signal peptide-bearing proteins, PsbX, PsbW, and PsbY, is likewise completely unaffected. Proteinase K is furthermore able to completely degrade Alb3, but this treatment does not affect the insertion of these proteins. Among the thylakoid proteins studied here, Alb3 requirement correlates strictly with a requirement for stromal factors and nucleoside triphosphates. However, the majority of proteins tested do not require Alb3 or any other known form of translocation apparatus.

Arabidopsis Proteins↗

PubMed2001

Bacillus cereus bacteremia and meningitis in immunocompromised children.

Two cases of Bacillus cereus meningitis in immunocompromised children at our hospital within a 2-month period prompted us to review B. cereus--related invasive disease. We identified 12 patients with B. cereus isolated in blood cultures from September 1988 through August 2000 at our institution. Three of these patients also had B. cereus isolated from CSF specimens; 1 additional patient had possible CNS involvement (33%, group A), whereas 8 patients had no evidence of CNS involvement (67%, group B). Patients in group A were more likely to have neutropenia at the onset of sepsis and were more likely to have an unfavorable outcome. They were also more likely to have received intrathecal chemotherapy in the week before the onset of their illness. Two patients from group A died. One survived with severe sequelae. The fourth patient had mild sequelae at follow-up. No sequelae or deaths occurred among patients in group B. In patients with unfavorable outcomes, the interval from the time of recognition of illness to irreversible damage or death was short, which demonstrates a need for increased awareness, early diagnosis, and more-effective therapy, particularly that which addresses B. cereus toxins.

Adolescent↗

PubMed2001

Immediate neurocognitive effects of methylphenidate on learning-impaired survivors of childhood cancer.

PURPOSE: To test if methylphenidate (MPH) has an objective beneficial effect on immediate performance on tests of neurocognitive functions among learning-impaired survivors of childhood acute lymphoblastic leukemia (ALL) and malignant brain tumors (BT). PATIENTS AND METHODS: From July 1, 1997 through December 31, 1998, 104 long-term survivors of childhood ALL or a malignant BT completed neurocognitive screening for learning impairments and concurrent problems with sustained attention. Eligibility criteria for the MPH trial included an estimated intelligence quotient greater than 50, academic achievement in the 16(th) percentile or lower for age in reading, math, or spelling, and an ability to sustain attention on a computerized version of the Conners' Continuous Performance Test (CPT) in the 16(th) percentile or lower for age and sex. Of the 104, 32 (BT, n = 25; ALL, n = 7) were eligible on the basis of these a priori criteria for a randomized, double-blinded, placebo-controlled trial of MPH. The patients ingested a placebo (lactose) or MPH (0.6 mg/kg; 20 mg maximum) and repeated selected portions of the screening battery 90 minutes later. RESULTS: Compared to the 17 patients randomized to the placebo group, the 15 patients randomized to the MPH group had a significantly greater improvement on the CPT for sustained attention (errors of omission, P =.015) and overall index (P =.008) but not for errors of commission (indicative of impulsiveness) nor reaction times. A trend for greater improvement in the MPH group on a measure of verbal memory failed to reach statistical significance. No trend was observed for MPH effectiveness in improving learning of a word association task. No significant side effects from MPH were observed. CONCLUSION: MPH resulted in a statistically significant improvement on measures of attention abilities that cannot be explained by placebo or practice effects.

Administration, Oral↗

PubMed2001

Associations between self-reported and objective physical environmental factors and use of a community rail-trail.

BACKGROUND: To effectively promote physical activIty, researchers and policy makers have advocated for greater use of environmental approaches, such as the construction of community paths and trails. However, research on the use of these facilities is limited. METHODS: In this cross-sectional community study, we examined associations between self-reported and objective physical environmental variables and use of the Minuteman Bikeway (Arlington, MA) in a random sample of 413 adults. Sociodemographic and perceived environmental variables were measured with a mail survey during September 1998. Geographic information system (GIS) data were used to geocode survey respondents' homes and create three objective environmental variables: distance to the Bikeway, steep hill barrier, and a busy street barrier. RESULTS: In logistic models, age and female gender showed statistically significant inverse associations with Bikeway use over the previous 4-week period. Increases in self-reported (OR = 0.65) and GIS distance (OR = 0.57) were associated with decreased likelihood of Bikeway use. Absence of self-reported busy street (OR = 2.01) and GIS steep hill barriers (OR = 1.84) were associated with Bikeway use. CONCLUSIONS: Environmental barriers such as travel distance and hilly terrain should be considered when planning community trails. A better understanding of such factors may lead to more effective promotion of trail use.

Adult↗

PubMed2001

Purification and characterization of hexahistidine-tagged cyclohexanone monooxygenase expressed in Saccharomyces cerevisiae and Escherichia coli.

Cyclohexanone monooxygenase (CMO) is a soluble flavoenzyme originally isolated from Acinetobacter spp. which carries out Baeyer-Villiger reactions with cyclic ketone substrates. In the present study we cloned the Acinetobacter CMO gene and modified it for facile purification from heterologous expression systems by incorporation of a His(6)-tag at its C-terminus. A single purification step employing metal (Ni(2+))-affinity column chromatography provided essentially homogeneous enzyme in yields of 69-72%. The properties of the purified, recombinant enzymes (rCMO) were compared with that of native CMO (nCMO) isolated from Acinetobacter cultures grown in the presence of cyclohexanone. The specific activities of His(6)-tagged rCMO and nCMO toward their index substrate, cyclohexanone, were similar and ranged from 14 to 20 micromol/min/mg. nCMO and rCMO from the Escherichia coli expression system exhibited molecular masses, determined by electrospray mass spectrometry, of 60,800 and 61,615 Da, respectively, an increase for the recombinant enzyme equivalent to the mass of the His(6)-tag. However, rCMO expressed in Saccharomyces cerevisiae consistently exhibited a mass some 50 Da larger than rCMO expressed in bacteria. Edman degradation confirmed that rCMO purified from the E. coli system and nCMO shared the same N-terminal sequence, whereas no sequence information could be obtained for rCMO expressed in yeast. Therefore, the yeast-expressed enzyme possesses an additional posttranslational modification(s), possibly acylation, at the N-terminus. Expression in E. coli is the preferred system for future site-directed mutagenesis studies and crystallization efforts.

Acinetobacter↗

PubMed2001

Human aromatase in high yield and purity by perfusion chromatography and its characterization by difference spectroscopy and mass spectrometry.

Expression of human cytochrome P450 aromatase (CYP19A1, aromatase) was accomplished at a high level using a baculovirus expression system in an insect cell suspension culture. Using the relatively new chromatographic technique of perfusion chromatography, a very rapid procedure for purification of the protein from solubilized cells was developed. At extraordinary flow rates of between 3 and 9 column volumes per minute, all chromatographic procedures could be performed, including setup, equilibration, and column regeneration steps, in less than 2 h, not including brief dialysis periods. Total yields were 40-52% and resulted in preparations with specific content values of 17.1 nmol aromatase/mg protein. Final purified preparations showed virtually no typical P450 spectra under standard conditions, but displayed full activity with typical enzyme kinetic parameters. These unusual results suggest that standard methods of P450 measurement are inappropriate when applied to aromatase. The findings are fully consistent with those encountered previously for purified preparations from a human placental source and led us to a new aromatase quantification method based on ligand-induced difference spectroscopy. A new HPLC assay is described which rapidly separates heme and apoprotein while measuring total heme content. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry was employed with both glycosylated and deglycosylated forms of the final purified product to confirm its identity as a glycosylated cytochrome P450.

Animals↗

PubMed2001

Assessment of a two-generation reproductive and fertility study of mercuric chloride in rats.

Effects of mercuric chloride (MC) on the reproductive performance of two successive generations of rats was evaluated. F(0) rats were exposed to 0.0:0.0 (males:females), 0.50:0.75 (males:females), 1.00:1.50 (males:females) and 1.50:2.50 (males:females) mg/kg/day MC. Selected parental F(1) males and females were exposed to the same doses received by their parents (F(0)). Significant differences resulting from exposure of the F(0) generation to MC were found in implantation efficiency, fertility, live births and day 4 survival indices, litter size, and the body weight of F(1) pups. However, the continued exposure of the F(1) generation to MC did not affect fertility index or litter size, but did significantly affect implantation efficiency, live births and day 4 survival indices. In F(0) males, body weight and weights of the kidneys, testes, epididymides, prostate and seminal vesicles were significantly different, while in F(1) males, body weight, kidney weight, brain weight, liver weight and the weights of the testes, prostate and seminal vesicles were significantly different. In F(0) females, body weight and the weights of the kidneys, brain and liver were significantly different, while in F(1,) females, body weight, as well as the weights of the kidneys, liver, adrenals, uterus and ovaries were significantly different. These data showed that exposure to MC resulted in more adverse reproductive effects in the first generation and that these effects moderated in the second generation.

Animals↗

PubMed2001

Multiple pathways used for the targeting of thylakoid proteins in chloroplasts.

The assembly of the chloroplast thylakoid membrane requires the import of numerous proteins from the cytosol and their targeting into or across the thylakoid membrane. It is now clear that multiple pathways are involved in the thylakoid-targeting stages, depending on the type of protein substrate. Two very different pathways are used by thylakoid lumen proteins; one is the Sec pathway which has been well-characterised in bacteria, and which involves the threading of the substrate through a narrow channel. In contrast, the more recently characterised twin-arginine translocation (Tat) system is able to translocate fully folded proteins across this membrane. Recent advances on bacterial Tat systems shed further light on the structure and function of this system. Membrane proteins, on the other hand, use two further pathways. One is the signal recognition particle-dependent pathway, involving a complex interplay between many different factors, whereas other proteins insert without the assistance of any known apparatus. This article reviews advances in the study of these pathways and considers the rationale behind the surprising complexity.

Amino Acid Sequence↗

PubMed2001

Influence of family structure on health among youths with diabetes.

Type 1 diabetes mellitus is a chronic metabolic disorder and is one of the most common chronic diseases in childhood. The study discussed in this article examined the extent to which family structure is significantly associated with health in youths with Type 1 diabetes. A convenience sample of 155 children with diabetes and their mothers completed face-to-face interviews; multiple regression analyses were conducted. Findings demonstrated that family structure remains a significant predictor of youths' health when statistically controlling for race, child's age, family socioeconomic status, and adherence. Social workers in outpatient medical settings are in a unique position to develop family-oriented strategies targeting this neglected area of primary care.

Adolescent↗

PubMed2001

Dietary methionine is involved in the etiology of neural tube defect-affected pregnancies in humans.

Research has provided evidence of the role of multivitamin supplementation in the prevention of neural tube defects (NTD). Failure of the neural tube to close is one of the most frequent and severe human developmental defects. The etiology of NTD is complex, encompassing genetic, dietary and environmental factors. The purpose of this study was to explore the relationship between maternal dietary intake of methionine and the risk of having a NTD-affected pregnancy. We hypothesized that women with high maternal dietary methionine intake were at a decreased risk for a NTD. Combinations of methionine, folate and vitamin B-12 intakes and NTD risk were also examined. Data from a 5-y, population-based, case-control study of 170 NTD-affected pregnancies and 269 controls were provided by the South Carolina NTD Surveillance, Prevention, and Research Project. There was a 30-55% lower NTD risk among women whose average daily dietary intake of methionine was greater than the lowest quartile of intake (>1580 mg/d). The odds ratios associated with the three quartiles of methionine intake > 1580 mg/d after adjusting for energy, race and body mass index were 0.72 (P < 0.07), 0.68 (P < 0.07) and 0.45 (P < 0.06), respectively. These findings indicate that a reduction in the risk of having a NTD-affected pregnancy is associated with maternal dietary intake of methionine (3 mo pre- to 3 mo postconception). This finding is consistent with the hypothesis that methionine plays a role in the etiology of NTD and suggests the need for further research in the area of maternal diet and pregnancy.

Adult↗

PubMed2001

Comparison of single-mother and two-parent families on metabolic control of children with diabetes.

OBJECTIVE: To understand the impact of family structure on the metabolic control of children with diabetes, we posed two research questions: 1) what are the differences in sociodemographic, family, and community factors between single-mother and two-parent families of diabetic children? and 2) to what extent do these psychosocial factors predict metabolic control among diabetic children from single-mother and two-parent families? RESEARCH DESIGN AND METHODS: This cross-sectional study included 155 diabetic children and their mothers or other female caregivers. The children were recruited if they had been diagnosed with diabetes for at least 1 year, had no other comorbid chronic illnesses, and were younger than 18 years of age. Interviews and self-report questionnaires were used to assess individual, family, and community variables. RESULTS: The findings indicate that diabetic children from single-mother families have poorer metabolic control than do children from two-parent families. Regression models of children's metabolic control from single-mother families indicate that age and missed clinic appointments predicted HbA1c levels; however, among two-parent families, children's ethnicity and adherence to their medication regimen significantly predicted metabolic control. CONCLUSIONS: This study suggests that children from single-mother families are at risk of poorer metabolic control and that these families have more challenges to face when raising a child with a chronic illness. Implications point to a need for developing strategies sensitive to the challenges of single mothers.

Adolescent↗

PubMed2000

CNS germinoma: disease control and long-term functional outcome for 12 children treated with craniospinal irradiation.

PURPOSE: To provide evidence that radiation therapy alone in the form of craniospinal irradiation (CSI) and a boost to the primary site of disease provides effective disease control and limited additional morbidity for patients with CNS germinoma. METHODS AND MATERIALS: Twelve patients with a median age of 12 years (range 9-16 years) with CNS germinoma were treated with CSI (median 25.6 Gy, range 23.4-32 Gy) and a boost to the primary site of disease (50.4 Gy, range 45-54 Gy) between January 1987 and June 1998. All patients were biopsied prior to radiation therapy and none received chemotherapy. No patients were lost to follow-up and the majority had long-term (> 45 month) pre- and postirradiation endocrine and psychology assessment. RESULTS: All 12 patients are alive and no failures have occurred with a median follow-up of 69 months (range 14-143 months). Preirradiation endocrine deficiencies were present in 6 of 6 suprasellar tumors and 1 of 6 pineal tumors; with follow-up there was no substantial difference between age and gender adjusted pre- and postirradiation stature and weight. With long-term follow-up, there were no significant differences between pre- and postirradiation full-scale, verbal, and performance IQ scores. CONCLUSIONS: This study confirms the ability of radiation therapy alone to achieve disease control with a high rate of success in pediatric patients and demonstrates that the treatment toxicity faced by these patients may be less than anticipated. Because these patients present with substantial preexisting morbidity at diagnosis and may be of an age where the potential for radiation-related side effects is relatively small, the superiority of treatment alternatives may be difficult to prove.

Adolescent↗

PubMed2000

Association of very low birth weight with exposures to environmental sulfur dioxide and total suspended particulates.

This paper presents results of a population-based case-control study of the association between maternal exposures to environmental sulfur dioxide and total suspended particulates (TSP) and risk for having a very low birth weight (VLBW) baby, i.e., one weighing less than 1,500 g at birth. The study, which took place between April 1, 1986 and March 30, 1988, comprised 143 mothers of VLBW babies and 202 mothers of babies weighing 2,500 g or more living in Georgia Health Care District 9. Environmental exposure estimates (microg/m3) were obtained through environmental transport modeling that allowed us to assign environmental sulfur dioxide and TSP exposure estimates at the birth home of each study subject. Exposures less than or equal to 9.94 microg/m3, the median of TSP and sulfur dioxide exposures for the controls, were considered as referent exposures. Exposures to atmospheric TSP and sulfur dioxide above the 95th percentile (56.75 microg/m3) yielded an adjusted odds ratio of 2.88 (95% confidence interval (CI): 1.16, 7.13), that from above the 75th to the 95th percentile (25.18-56.75 microg/m3) yielded an adjusted odds ratio of 1.27 (95% CI: 0.68, 2.37), and that from above the median (9.94 microg/m3) to the 75th percentile, an adjusted odds ratio of 0.99 (95% CI: 0.51, 1.72). The trend demonstrated in these adjusted estimates suggests an association between VLBW and maternal exposures to high levels of air pollution.

Adult↗

PubMed2000

Imaging aspects of neurologic emergencies in children treated for non-CNS malignancies.

There is a paucity of radiologic literature addressing neurologic emergencies in children receiving therapy for non-CNS primary malignancies. In the acute setting, many of these children present to local community hospitals. This pictorial is from a single institutional experience describing the spectrum of neurologic emergencies seen in children with non-CNS cancers. We hope to familiarize pediatric radiologists with these entities in order to expedite diagnosis, facilitate treatment, and minimize morbidity and mortality that may be associated with these complications.

Adolescent↗

PubMed2000

Trying to keep a balance: the meaning of health and diabetes in an urban aboriginal community.

Although the predominant paradigm of epidemiological investigation continues to focus narrowly on the individual and on individual risk factors, there is a growing body of work that calls for a rethinking of the current epidemiological models. In this paper we illustrate the need for a more comprehensive epidemiological approach towards understanding the risks for diabetes, by exploring the lived experiences of diabetes and lay meanings of risk among Aborigines living in Melbourne, Australia. Ethnographic fieldwork was conducted within the Melbourne Aboriginal community in the state of Victoria over a 22-month period (1994-1996). Melbourne Aborigines see non-insulin dependent diabetes mellitus (NIDDM) as the result of living a life out of balance, a life of lost or severed connections with land and kin and a life with little control over past, present or future. The lay model regarding diabetes that is derived from the narratives of Melbourne Aborigines, consists of three levels of connectedness important in determining an individual's susceptibility not only to diabetes but to all disease--(1) family, (2) community and (3) society. This structure of interactive systems at successive levels from the individual to the population fits within the framework of an ecological paradigm. The strength of ethnography as applied to epidemiology is that it has the capacity to discover previously unknown components of a system at several different levels, and to build models to explain how these components interact. This framework, developed using an ethno-epidemiological approach, has application in other indigenous populations who have been dispossessed of their land, their pasts and their future. There is great potential to apply this approach to the major public health challenges presented by rapid global socio-cultural and environmental change that are impacting negatively on population health.

Anthropology, Cultural↗

PubMed2000

Agency-based tracking of difficult-to-follow populations: runaway and homeless youth programs in St. Louis, Missouri.

OBJECTIVES: This study explored agency-based tracking methods for one of the most difficult-to-follow populations: runaway and homeless youth. METHODS: A total of 118 program discharges from three federally funded agencies serving runaway/ homeless youth in St. Louis, Missouri were tracked for a follow-up study of this population. Agency staff attempted to locate and interview program participants three months post-discharge using a protocol that systematically varied times and location of contact attempts. Separate analyses were conducted to compare the group of subjects whose locations were ascertained with those who were not, and who were successfully interviewed with those who were not. Variables related to the tracking protocol and individual descriptive and service use variables were examined in these analyses. RESULTS: Sixty-nine percent of the sample was successfully located and fifty-nine percent interviewed. Significant findings included: fewer contact attempts over fewer days were made for individuals successfully interviewed, individuals tracked through Division of Family Services were less likely to be both located and interviewed, and individuals successfully located were significantly younger. CONCLUSIONS: This report provides encouraging evidence that even relatively unsophisticated protocols for tracking agency clients developed in collaboration with community agencies can--with consistent implementation--yield follow-up samples that are acceptably representative of program participants.

Adolescent↗

PubMed2000

Relationship between disease severity and responses by blood mononuclear cells from patients with rheumatoid arthritis to human heat-shock protein 60.

The hypothesis that T-cell responses to the 60 000 MW family of heat-shock proteins (hsp) may be related to the severity of rheumatoid arthritis (RA) was examined. Peripheral blood mononuclear cells (PBMC) from most normal individuals and both early and established RA patients proliferated in vitro in response to human hsp 60 and mycobacterial hsp 65 as well as tetanus toxoid (TT) and mycobacterial purified protein derivative (PPD). PBMC from some patients with established RA gave responses to hsp 60 that were above the normal range and/or peaked earlier than PBMC from normal individuals. The responses of PBMC from established RA to hsp 65, but not PPD or TT, were also higher than those from normal individuals, but the peak responses to all three antigens appeared delayed. Thus a selective increase in responsiveness to hsp 60 develops with disease duration in many RA patients. Six assessments of disease activity and severity were made but apart from rheumatoid factor titre, they were unrelated to the proliferative response. Similarly, disease activity and severity did not differ between those RA patients whose hsp 60 stimulated cells produced interferon-gamma and those who did not, although patients whose hsp 60-stimulated T cells produced interleukin-4 (IL-4) and/or IL-10, appeared to have less disease activity and severity than those who did not. Significant negative correlations were found between IL-10 production by hsp 60-stimulated cells and disease assessments. It is considered that RA is less severe in those patients whose hsp 60-stimulated cells produce T-helper 2 type cytokines.

Adult↗

PubMed2000

The route of administration of an immunodominant peptide derived from heat-shock protein 65 dramatically affects disease outcome in pristane-induced arthritis.

Previous studies have shown that immunization of mice with an immunodominant epitope from heat-shock protein 65 (hsp 65) (amino acids 261-271) can protect from the development of pristane-induced arthritis (PIA) and this protection is mediated by an antigen-specific T helper type 2 (Th2) cytokine response. Here we confirm these findings and show that frequent intranasal administration of this peptide exacerbates disease. In naive mice given peptide intranasally an antigen-specific T-cell population is systemically activated similar to that induced by peptide immunization in incomplete Freund's adjuvant. Thus, a paradox exists whereby apparently similar peptide-specific populations are either associated with protection from, or exacerbation of, PIA. However, comparison of cytokine profiles reveals differences between these two cell populations. Peptide inhalation induces the production of Th1-type cytokines (interferon-gamma) whereas intraperitoneal immunization leads to the production of Th2-type cytokines (interleukin-4, interleukin-5 and interleukin-10) by splenic T cells upon stimulation with peptide. Thus, for the application of nasal 'tolerance' in clinical medicine, it is important to identify antigens and dosing regimes that counteract but do not activate adverse immune responses.

Animals↗