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Biomedical subjects

J Griffith

Publications and source records attributed to J Griffith.

At least 37 records · Page 2Linked to original sources
PubMed2000

Alendronate prevents bone loss in Chinese women with osteoporosis.

The objectives of the Hong Kong study are to investigate the efficacy of 10 mg alendronate in preventing bone loss at the hip and spine in osteoporotic Chinese women. One hundred osteoporotic Chinese women, aged 60-79 years, were randomized to receive 10 mg of alendronate or placebo, with 500 mg elemental calcium. Bone mineral density (BMD) at the spine and hip were measured at baseline, 6 months, and 12 months. Seventy-eight subjects completed the study. The alendronate-treated group gained more bone at both the spine (p < 0.01) and femoral neck (p < 0.001), with a mean difference (+/-SE) of 2.4% (+/-0.86%) at the spine and 3.98% (+/-0.95%) at the femoral neck. Of the 100 patients, 6 subjects in the alendronate group and 5 subjects in the placebo group had mild gastrointestinal symptoms. We conclude that alendronate (10 mg) was effective in preventing bone loss in postmenopausal osteoporotic Chinese women.

Aged↗
PubMed2000

Intentional weight control and food choice habits in a national representative sample of adults in the UK.

OBJECTIVE: To establish the association between intentional weight control and specific eating behaviours. DESIGN: An interview-based survey of a representative sample of the UK population including questions about demographic characteristics, weight and height, intentional weight control and eating behaviours. Associations among the eating behaviours, and between weight control and eating behaviours, were examined. SUBJECTS: 1894 men and women completed the interview (70% response rate). RESULTS: Approximately equal proportions of the sample were 'not bothered about weight' (30%), 'watching their weight' (36%), or 'trying to lose weight' (28%). More men were 'not bothered' and more women were 'trying to lose'. People who were trying to lose or were watching their weight were more likely to report restricting fats, sugars, snacks, and the amount eaten at meals, than those who were not bothered, but there were no differences between weight watchers and weight losers. The overall level of restriction among weight losers was modest. There were no group differences in eating breakfast, fruits or vegetables, skipping meals or fasting. CONCLUSIONS: Around two-thirds of the adult population of the UK appear to be concerned about weight control, and this is reflected in somewhat higher than average adherence to recommended restrictive dietary habits.

Adolescent↗
PubMed2000

Carcinoembryonic antigens are targeted by diverse strains of typable and non-typable Haemophilus influenzae.

Haemophilus influenzae (Hi), a commensal of the human respiratory mucosa, is an important cause of localized and systemic infections. We show that distinct strains belonging to typable (THi) and non-typable (NTHi) H. influenzae target human carcinoembryonic antigens (the membrane associated CEA family of cell adhesion molecules, are now termed CEACAMs). All strains of H. influenzae biogroup aegyptius (Hi-aeg) and more than 70% of THi and NTHi strains tested specifically recognize CEACAMI-Fc soluble constructs. Furthermore, transfection of Chinese hamster ovary cells with human CEACAM1 cDNA alone was sufficient for promoting Hi interactions with the transfected cells. The majority of the Hi-aeg strains tested interacted with soluble constructs containing only the N-terminal domain. In contrast, several THi and NTHi strains reacted with soluble constructs only when additional extracellular A and B domains of the receptor were present. The use of monoclonal antibodies confirmed that THi and NTHi strains also interact primarily at the N-domain. We used site-directed mutants of CEACAM1 that contained substitutions at surface exposed amino acids and a molecular model of the N-domain to identify the residues involved in interactions with Hi ligands. The studies show that a common region exposed at the CFG face of the molecule is targeted by diverse Hi strains. However, mutation at distinct sites within this area affected the interactions of distinct strains signifying the potential for tissue tropism via this receptor. Analyses of the molecular basis of interaction with human cell lines and purified CEA show that Hi strains, especially those belonging to Hi-aeg, interact with multiple CEACAMs. Because Neisseria meningitidis (Nm) strains are also known to bind at the CFG face of the receptor, we used Nm and Hi strains in co-infection experiments and demonstrate competition between these mucosal pathogens in colonization of target cells via CEACAMs.

Amino Acid Sequence↗
PubMed1999

Clinical utility of blood cultures drawn from indwelling central venous catheters in hospitalized patients with cancer.

BACKGROUND: Because of concern about low specificity, the American College of Physicians guidelines and expert opinion discourage the use of a central venous catheter when obtaining blood for culture for bacteremia or fungemia. However, data on the reliability of cultures done with blood obtained from a central venous catheter are conflicting. OBJECTIVE: To determine the sensitivity, specificity, and positive and negative predictive values of cultures done with blood obtained through a central venous catheter compared with peripheral venipuncture. DESIGN: Retrospective cohort study of hospitalized patients with cancer in whom samples for paired cultures were drawn through a central venous catheter and peripheral venipuncture. SETTING: Tertiary care, university-affiliated medical center. PATIENTS: 185 patients hospitalized on a hematology-oncology ward between August 1994 and June 1996. MEASUREMENTS: Blinded assessments of culture results done by infectious disease experts were used as the gold standard. Sensitivity, specificity, and positive and negative predictive values were compared for culture of blood from central catheters and culture of blood from peripheral venipuncture. RESULTS: Of 551 paired cultures, 469 (85%) were catheter-negative/venipuncture-negative, 32 (6%) were catheter-positive/venipuncture-positive, 17 (3%) were catheter-negative/venipuncture-positive, and 33 (6%) were catheter-positive/venipuncture-negative pairs. For the 82 paired cultures with at least one positive result, blinded determination of true bacteremia or fungemia was made by two infectious disease specialists. For catheter draw compared with peripheral venipuncture, sensitivity was 89% (95% CI, 79% to 98%) and 78% (CI, 65% to 90%) (difference, 11 percentage points [CI, -6 to 28 percentage points]), specificity was 95% (CI, 93% to 97%) and 97% (CI, 96% to 99%) (difference, -2 percentage points [CI, -5 to 0.2 percentage points]), positive predictive value was 63% (CI, 50% to 75%) and 73% (CI, 60% to 86%) (difference, -10 percentage points [CI, -26 to 5 percentage points]), and negative predictive value was 99% [CI, 97% to 100%]) and 98% (CI, 96% to 100%) (difference, 1 percentage point [CI, -0.5 to 3 percentage points]). CONCLUSIONS: In hospitalized hematology-oncology patients, culture of blood drawn through either the central catheter or peripheral vein shows excellent negative predictive value. Culture of blood drawn through an indwelling central venous catheter has low positive predictive value, apparently less than from a peripheral venipuncture. Therefore, a positive result from a catheter needs clinical interpretation and may require confirmation. However, the use of a catheter to obtain blood for culture may be an acceptable method for ruling out bloodstream infections.

Anti-Bacterial Agents↗
PubMed1999

Visualization of double-stranded RNAs from the myotonic dystrophy protein kinase gene and interactions with CUG-binding protein.

Myotonic dystrophy (DM) is associated with a (CTG) (n) triplet repeat expansion in the 3'-untranslated region of the myotonic dystrophy protein kinase (DMPK) gene. Using electron microscopy, we visualized large RNAs containing up to 130 CUG repeats and studied the binding of purified CUG-binding protein (CUG-BP) to these RNAs. Electron microscopic examination revealed perfect double-stranded (ds)RNA segments whose lengths were that expected for duplex RNA. The RNA dominant mutation model for DM pathogenesis predicts that the expansion mutation acts at the RNA level by forming long dsRNAs that sequester certain RNA-binding proteins. To test this model, we examined the subcellular distribution and RNA-binding properties of CUG-BP. While previous studies have demonstrated that mutant DMPK transcripts accumu-late in nuclear foci, the localization pattern of CUG-BP in both normal and DM cells was similar. Although CUG-BP in nuclear extracts preferentially photocrosslinked to DMPK transcripts, this binding was not proportional to (CUG) (n) repeat size. Moreover, CUG-BP localized to the base of the RNA hairpin and not along the stem, as visualized by electron micro-scopy. These results provide the first visual evidence that the DM expansion forms an RNA hairpin structure and suggest that CUG-BP is unlikely to be a sequestered factor.

3' Untranslated Regions↗
PubMed1999

Activity of recombinant HIV-1 integrase on mini-HIV DNA.

Integration of the human immunodeficiency virus type 1 (HIV-1) cDNA into the genome of a human cell is an essential step in the viral replication cycle. Understanding of the integration process has been facilitated by the development of in vitro assays using specific oligonucleotides and recombinant integrase. However, understanding of the biology of retroviral integration will require in vitro and in vivo model systems using long DNA substrates that mimic the HIV cDNA. We have now studied the activity of recombinant HIV-1 integrase on a linear 4.7 kb double-stranded DNA, containing flanking regions of approximately 200 bp that represent the intact ends of the HIV-1 long terminal repeat (LTR) sequences (mini-HIV). The strand transfer products of the integration reaction can be directly visualized after separation in agarose gels by ethidium bromide staining. The most prominent reaction product resulted from integration of one LTR end into another LTR end (U5 into U5 and U5 into U3). Sequence analysis of the reaction products showed them to be products of legitimate integration preceded by correct processing of the viral LTR ends. Hotspots for integration were detected. Electron microscopy revealed the presence of a range of reaction products resulting from single or multiple integration events. The binding of HIV-1 integrase to mini-HIV DNA was visualized. Oligomers of integrase seem to induce DNA looping whereby the enzyme often appears to be bound to the DNA substrate that adopts the structure of a three-site synapsis that is reminiscent of the Mu phage transposase complex.

Base Sequence↗
PubMed1999

The dependence for leukocyte function-associated antigen-1/ICAM-1 interactions in T cell activation cannot be overcome by expression of high density TCR ligand.

The leukocyte-specific integrin, LFA-1, can enhance T cell activation. However, it is unclear whether the binding of LFA-1 to its ligand, ICAM-1, functions through intercellular adhesion alone, resulting in an augmentation of the TCR signal, or involves an additional LFA-1-mediated cellular signal transduction pathway. We have previously shown that naive CD4+ lymph node T cells, isolated from DO11.10 TCR transgenic mice, are activated by increasing doses of exogenous OVA peptide presented by transfectants expressing both class II and ICAM-1, but not by cells expressing class II alone. To determine whether LFA-1/ICAM-1 interactions were simply enhancing the presentation of low concentrations of specific MHC/peptide complexes generated from exogenously added peptide, we transfected cells with class II that is covalently coupled to peptide, alone or in combination with ICAM-1. These cells express 100-fold more specific class II/peptide complexes than can be loaded onto class II-positive cells at maximum concentrations of exogenous peptide. Despite this high density of TCR ligand, activation of naive CD4+ T cells still requires the coexpression of ICAM-1. LFA-1/ICAM-1 interactions are not required for effective conjugate formation and TCR engagement because presentation of class II/peptide complexes in the absence of ICAM-1 does induce up-regulation of CD25 and CD69. Thus, high numbers of engaged TCR cannot compensate for the lack of LFA-1/ICAM-1 interactions in the activation of naive CD4+ T cells.

Animals↗
PubMed1999

'Saccharomyces cerevisiae MSH2/6 complex interacts with Holliday junctions and facilitates their cleavage by phage resolution enzymes.

Genetic and biochemical studies have indicated that mismatch repair proteins can interact with recombination intermediates. In this study, gel shift assays and electron microscopic analysis were used to show that the Saccharomyces cerevisiae MSH2/6 complex binds to Holliday junctions and has an affinity and specificity for them that is at least as high as it has as for mispaired bases. Under equilibrium binding conditions, the MSH2/6 complex had a Kd of binding to Holliday junctions of 0.5 nM. The MSH2/6 complex enhanced the cleavage of Holliday junctions by T4 endonuclease VII and T7 endonuclease I. This is consistent with the view that the MSH2/6 complex can function in both mismatch repair and the resolution of recombination intermediates as predicted by genetic studies.

Base Sequence↗
PubMed1999

Classifying the location of osteosarcoma with reference to the epiphyseal plate helps determine the optimal skeletal resection in limb salvage procedures.

Between 1989 and 1996, 21 skeletally immature patients were treated for osteosarcoma of the extremity. Their average age was 12.6 years (range 9-16 years). We classified the location and extent of the lesion in bone on magnetic resonance imaging (MRI) with reference to the growth plate and joint margin into five subtypes. This classification served as a guide for the level of resection and the type of reconstruction required for a limb salvage procedure. All patients received neoadjuvant chemotherapy using a modified T10 protocol before the definitive operation. These patients were followed up for periods ranging from 11-86 months, with a mean of 35. 5 months. Patients were assessed for (1) local tumour recurrence, (2) metastatic disease, (3) allograft complications and (4) extremity function and joint stability. Excellent function was retained in 2, good in 13 and fair function in 6 patients. The MRI classification proved useful for the resection and provides an insight into the possible functional outcomes.

Adolescent↗
PubMed1999

Electron microscopy of DNA-protein complexes and chromatin.

This article focused on a number of aspects of the preparation of chromatin and other DNA-protein complexes for conventional transmission EM that are critical for success but may not have been addressed in a single chapter before. These include the importance of optimizing fixation, the generation of active supporting supports, and the use of negative staining as a means of obtaining higher resolution detail than can be garnered from shadow casting methods.

Animals↗
PubMed1999

Ten years after: examination of adolescent screening questions that predict future violence-related injury.

PURPOSE: To determine which screening questions used in routine adolescent health care maintenance visits correlate with subsequent violence-related injury. METHODS: A prospective cohort study was undertaken of adolescents initially seen at the East Boston Neighborhood Health Center (EBNHC) in 1986. Risk factor data were collected based on the adolescent health intake form in the medical records. The primary outcome measure, time until first violence-related injury was determined through identification on chart review of the treatment of any such injuries at the urgent care center at EBNHC in the subsequent 10 years. Kaplan-Meier survival statistics and Cox proportional hazards models were used to account for loss of patients to follow-up. RESULTS: Median follow-up for this sample was >5 five years. Male gender, cigarette smoking, alcohol use, other drug use, poor relationships with parents, not being in school or failing school, and history of fighting in the past year, predicted violence-related injury within the follow-up period. The number of fights in the past year appeared to have a dose-response effect on risk of subsequent violence-related injury. A simple screening instrument consisting of items concerning school status, drug use, and fighting history was used to stratify youth into low, moderate, and high risk of violence-related injury during the follow-up period. CONCLUSIONS: These results suggest that a simple three-item screening instrument may be used to stratify the risk of future injury at the time of adolescent health maintenance visits. Further research is indicated to validate this finding in other populations. Interventions designed to assist adolescents who are not in school or who have drug use problems should also incorporate violence prevention strategies.

Adolescent↗
PubMed1999

hMSH2-hMSH6 forms a hydrolysis-independent sliding clamp on mismatched DNA.

Mismatch recognition by the human MutS homologs hMSH2-hMSH6 is regulated by adenosine nucleotide binding, supporting the hypothesis that it functions as a molecular switch. Here we show that ATP-induced release of hMSH2-hMSH6 from mismatched DNA is prevented if the ends are blocked or if the DNA is circular. We demonstrate that mismmatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts hMSH2-hMSH6 into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. Our results support a model for bidirectional mismatch repair in which stochastic loading of multiple ATP-bound hMSH2-hMSH6 sliding clamps onto mismatch-containing DNA leads to activation of the repair machinery and/or other signaling effectors similar to G protein switches.

Adenosine Triphosphatases↗
PubMed1999

The influence of abdominal obesity and chronic work stress on ambulatory blood pressure in men and women.

OBJECTIVE: To assess the influence of abdominal obesity and work stress (operationalised as low control over work) on ambulatory blood pressure on a working day and evening. PARTICIPANTS AND METHODS: 156 school teachers (58 men and 98 women) carried out ambulatory blood pressure and heart rate monitoring on a work day and evening. Cardiovascular activity was also measured under baseline conditions on another occasion, when body weight, height, waist and hip circumference were assessed. Perceived control over work was assessed by questionnaire, along with mental health, anger expression and social support. 126 participants repeated the protocol after 12 months. Waist/hip ratio was used as the index of abdominal obesity. RESULTS: Baseline blood pressure was positively associated with waist/hip ratio in men, but ambulatory blood pressure and heart rate were not independently related to waist/hip ratio or job control. However, blood pressure and heart rate recorded during the working day and evening were elevated in men with high waist/hip ratio who experienced low job control, independently of age and body weight. Effects for diastolic blood pressure and heart rate were replicated after 12 months. Body mass index was not related to blood pressure or heart rate during the day or evening after adjustment for age and waist circumference. Low job control was associated with poor psychological well-being, negative mood and lack of social support. CONCLUSIONS: The results are consistent with the hypothesis that abdominal obesity in men is characterised by a tendency towards heightened stress-induced physiological activation, but that this tendency will only be manifest in the presence of appropriate environmental challenges such as chronic work stress.

Adult↗
PubMed1999

Clinical presentation, radiographic findings, and diagnostic methods of pulmonary blastomycosis: a review of 100 consecutive cases.

BACKGROUND: We sought to determine the relationship among radiographic findings, clinical presentation, and diagnostic testing of pulmonary blastomycosis. METHODS: We reviewed the medical records of 100 consecutive patients with pulmonary blastomycosis. RESULTS: Air-space infiltrates were the usual radiographic finding of pulmonary blastomycosis. Mass-like infiltrates were associated more with chronic than acute presentations. Air-space and mass-like infiltrate were predominately involved in the upper lobes. Sputum analysis made the initial diagnosis of blastomycosis most often. Acute and chronic presentations were not different between immunosuppressed patients and the remainder of the patients. In addition, infiltrates on chest radiographs in immunosuppressed patients were similar to the other patients. CONCLUSIONS: In an endemic area, pulmonary blastomycosis should be considered for any pulmonary infiltrate, especially in the upper lobes. Sputum analysis in most cases aids in the diagnosis, but bronchoscopy and/or tissue biopsy should be considered if the suspicion of blastomycosis is high and sputum analysis is inconclusive, negative, or not possible. Follow-up with chest radiographs after antifungal therapy is reasonable until complete resolution or fibrotic changes in patients with pulmonary blastomycosis.

Acute Disease↗
PubMed1999

A nursing home outbreak of Clostridium perfringens associated with pureed food.

OBJECTIVE: To investigate and ascertain the source of a nursing home outbreak of gastroenteritis in Melbourne in 1997. METHOD: A retrospective cohort study. We obtained fecal and food samples and environmental swabs, and reviewed food handling. RESULTS: There were 25 cases, and 21 of these had their meals pureed (liquidised). The relative risk for eating pureed food and becoming ill was 5.8 (95% CI 2.2-15.4). Clostridium perfringens and its enterotoxin was detected in nine fecal samples. Samples of pureed food tested positive for coliforms. CONCLUSIONS: This outbreak was caused by C. perfringens contaminating pureed food. Food liquidising provides opportunities for re-contamination of cooked food through the use of contaminated equipment and deficiencies in food handling practices. Pureed foods should be reheated to 70 degrees C after liquidising to inactivate pathogens. IMPLICATIONS: Health care facilities need to take specific precautions to manage the special hazards involved in preparing pureed food.

Aged↗
PubMed1999

Auditory P50 in schizophrenics on clozapine: improved gating parallels clinical improvement and changes in plasma 3-methoxy-4-hydroxyphenylglycol.

Schizophrenic patients have decreased inhibition of the P50 auditory evoked potential response to the second of two paired click stimuli delivered 500 ms apart. This deficit in inhibitory gating does not change during treatment with typical neuroleptics. We recently reported that neuroleptic-resistant schizophrenics had enhanced P50 gating after 1 month of clozapine treatment, if they responded with decreased clinical symptoms. This study reports the outcome of more prolonged treatment. Ten treatment-refractory schizophrenic patients were studied at baseline, after 1 month on clozapine, and again after 15 +/- 6.1 (SD) months of clozapine treatment. Eight subjects reached a clinically stable improved state, at which time they had significantly improved P50 auditory gating. One patient had a return of impaired gating after stopping clozapine, as did another during a clinical relapse. Decreasing plasma 3-methoxy-4-hydroxyphenylglycol levels with clozapine treatment were correlated with improved P50 gating and improved Brief Bsychiatric Rating Scale-positive scores. This study provides further evidence that improved P50 gating in schizophrenic patients treated with clozapine coincides with clinical improvement and that this improvement can be sustained for at least 1 year.

Adult↗
PubMed1999

An investigation of coping strategies associated with job stress in teachers.

BACKGROUND: School teaching is regarded as a stressful occupation, but the perception of the job as stressful may be influenced by coping responses and social support. AIMS: To assess the associations between teacher stress, psychological coping responses and social support, taking into account the plaintive set engendered by negative affectivity. METHOD: Questionnaire survey of 780 primary and secondary school teachers (53.5% response rate). RESULTS: In stepwise multiple regression, social support at work and the coping responses behavioural disengagement and suppression of competing activities predicted job stress independently of age, gender, class size, occupational grade and negative affectivity. High job stress was associated with low social support at work and greater use of coping by disengagement and suppression of competing activities. CONCLUSIONS: It is suggested that behavioural disengagement and suppression of competing activities are maladaptive responses in a teaching environment and may actually contribute to job stress. Coping and social support not only moderate the impact of stressors on well-being but influence the appraisal of environmental demands as stressful.

Adaptation, Psychological↗