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Biomedical subjects

J White

Publications and source records attributed to J White.

At least 271 records · Page 15Linked to original sources
PubMed1996

Cloning, characterization and disruption of a (p)ppGpp synthetase gene (relA) of Streptomyces coelicolor A3(2).

An internal segment of the (p)ppGpp synthetase gene, relA, of Streptomyces coelicolor A3(2) was amplified from genomic DNA using the polymerase chain reaction and used as a hybridization probe to isolate the complete gene from a cosmid library. relA lies downstream of a gene (apt) that apparently encodes adenine phosphoribosyltransferase and is transcribed from two promoters, relAp1 and relAp2, and by transcriptional readthrough from apt. While the level of relAp2 transcripts remained relatively constant, relAp1 activity apparently peaked during transition phase, following a decline in readthrough transcription from apt. Disruption of relA using an att- derivative of the temperate phage phi C31 abolished ppGpp synthesis on amino acid depletion. When grown on agar, the disruptants grew more slowly than a control lysogen made with an att+ phage vector and gave smaller colonies that sporulated normally. The relA mutation had no consistent or marked effect on actinorhodin production in either liquid- or agar-grown cultures, indicating that elevated levels of (p)ppGpp are not essential for triggering the onset of antibiotic production.

Amino Acid Sequence↗
PubMed1996

Partial night sleep deprivation reduces natural killer and cellular immune responses in humans.

Prolonged and severe sleep deprivation is associated with alterations of natural and cellular immune function. To determine whether alterations of immune function also occur after even a modest loss of sleep, the effects of early-night partial sleep deprivation on circulating numbers of white blood cells, natural killer (NK) cell number and cytotoxicity, lymphokine-activated killer (LAK) cell number and activity, and stimulated interleukin-2 (IL-2) production were studied in 42 medically and psychiatrically healthy male volunteers. After a night of sleep deprivation between 10 P.M. and 3 A.M., a reduction of natural immune responses as measured by NK cell activity, NK activity per number of NK cells, LAK activity, and LAK activity per number of LAK precursors (CD16,56, CD25) was found. In addition, concanavalin A-stimulated IL-2 production was suppressed after sleep deprivation due to changes in both adherent and nonadherent cell populations. After a night of recovery sleep, NK activity returned to baseline levels and IL-2 production remained suppressed. These data implicate sleep in the modulation of immunity and demonstrate that even a modest disturbance of sleep produces a reduction of natural immune responses and T cell cytokine production.

Cell Adhesion↗
PubMed1996

Delay of gratification, psychopathology, and personality: is low self-control specific to externalizing problems?

We assessed the delay of gratification behavior of 428 twelve- and thirteen-year-old boys, half of whom were known to manifest symptoms of behavioral disturbance. Consistent with the hypothesis that low self-control is a risk factor specific to externalizing (aggressive and delinquent) disorders, boys who showed signs of externalizing disorders tended to seek immediate gratification in a laboratory task more often than both nondisordered boys and boys who showed signs of internalizing (anxious and depressed) disorders. In addition, children who were able to delay immediate gratification were described by their mothers as ego controlled, ego resilient, conscientious, open to experience, and agreeable. These results suggest that poor delay of gratification may be one of a select number of specific risk factors for externalizing disorder, and that good delay of gratification is linked to multiple adaptive tendencies in early adolescence.

Adolescent↗
PubMed1996

Protein binding of clindamycin in sera of patients with AIDS.

Patients with AIDS have altered pharmacokinetics of clindamycin compared with those of healthy control subjects. In an attempt to better understand these differences, we undertook a study of protein binding of clindamycin in sera of patients with AIDS. Fifteen patients with AIDS and 15 healthy volunteers were given a single 600-mg dose of clindamycin orally and intravenously, and serum samples were collected at three time points corresponding to high, midpoint, and low clindamycin concentrations. Protein binding was determined by ultrafiltration, and total and unbound clindamycin concentrations were measured with a gas chromatography assay. AIDS patients had alpha 1-acid glycoprotein values approximately twice those of healthy volunteers (mean +/- standard deviation, 103 +/- 27 versus 61 +/- 11 mg/dl; P = 0.001). Overall, serum protein binding levels were higher in AIDS patients (mean +/- standard deviation, 83 +/- 7 versus 78% +/- 8%; P = 0.0001), which is likely the result of increased alpha 1-acid glycoprotein levels in these patients. Total concentrations of clindamycin in plasma were significantly higher in AIDS patients at most time points studied, while unbound serum clindamycin concentrations did not differ among the groups at each sampling time after both oral and intravenous dosing. Increased protein binding may partly explain the altered pharmacokinetic disposition of clindamycin in AIDS patients; however, other factors cannot be excluded.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Translational control of programmed cell death: eukaryotic translation initiation factor 4E blocks apoptosis in growth-factor-restricted fibroblasts with physiologically expressed or deregulated Myc.

There is increasing evidence that cell cycle transit is potentially lethal, with survival depending on the activation of metabolic pathways which block apoptosis. However, the identities of those pathways coupling cell cycle transit to survival remain undefined. Here we show that the eukaryotic translation initiation factor 4E (eIF4E) can mediate both proliferative and survival signaling. Overexpression of eIF4E completely substituted for serum or individual growth factors in preserving the viability of established NIH 3T3 fibroblasts. An eIF4E mutant (Ser-53 changed to Ala) defective in mediating its growth-factor-regulated functions was also defective in its survival signaling. Survival signaling by enforced expression of eIF4E did not result from autocrine release of survival factors, nor did it lead to increased expression of the apoptosis antagonists Bcl-2 and Bcl-XL. In addition, the execution apparatus of the apoptotic response in eIF4E-overexpressing cells was found to be intact. Increased expression of eIF4E was sufficient to inhibit apoptosis in serum-restricted primary fibroblasts with enforced expression of Myc. In contrast, activation of Ha-Ras, which is required for eIF4E proliferative signaling, did not suppress Myc-induced apoptosis. These data suggest that the eIF4E-activated pathways leading to survival and cell cycle progression are distinct. This dual signaling of proliferation and survival might be the basis for the potency of eIF4E as an inducer of neoplastic transformation.

3T3 Cells↗
PubMed1996

Project Wellness: a collaborative health promotion program for older adults.

The health promotion program described in this article brought nurses, nursing students, interdisciplinary health professionals from the hospital setting, and community aging advocates together for the purpose of assisting senior citizens to maintain and improve their health. The 12-week course included pre- and posttesting of health promotion behaviors and physiologic outcomes of healthy behaviors. The article describes the planning, content, and outcomes as measured at 12 weeks and 6 months. Suggestions are given for replication of the course in other settings.

Aged↗
PubMed1996

Occupational exposure to permethrin during its use as a public hygiene insecticide.

Permethrin is an active ingredient found in many public hygiene insecticide products and exposure to it was assessed in a survey of 45 professional users. The exposures measured were over a wide range, with more than a 100-fold difference between average levels and the highest levels. Dermal contamination was evident on 93% of the operators, the highest contamination resulting from the use of leaking application equipment, demonstrating that proper maintenance of equipment is vital. Where the insecticide was applied at ground level most contamination was on the legs, indicating the importance of appropriate footwear. Contamination of the hands occurred despite the use of protective gloves, higher levels of contamination occurring when liquids were used. Dermal contamination was not always the principle route of exposure, and high airborne concentrations were linked with use in confined areas. Airborne concentrations were also associated with the physical form of the product used and the treatment method. To help in assessing the effectiveness of protective clothing and control measures, biological monitoring was carried out. Monitoring of metabolites in urine showed that systemic uptake occurred but evidence from toxicological studies indicates that the levels found were well below those considered to cause harm.

Environmental Monitoring↗
PubMed1995

Sleep electroencephalogram delta-frequency amplitude, night plasma levels of tumor necrosis factor alpha, and human immunodeficiency virus infection.

We tested the hypothesis that increases in tumor necrosis factor alpha (TNF-alpha) induced by human immunodeficiency virus (HIV) are associated with the increases in slow-wave sleep seen in early HIV infection and the decrease with sleep fragmentation seen in advanced HIV infection. Nocturnal sleep disturbances and associated fatigue contribute to the disability of HIV infection. TNF-alpha causes fatigue in clinical use and promotes slow-wave sleep in animal models. With slow progress toward a vaccine and weak effects from current therapies, efforts are directed toward extending productive life of HIV-infected individuals and shortening the duration of disability in terminal illness. We describe previously unrecognized nocturnal cyclic variations in plasma levels of TNF-alpha in all subjects. In 6 of 10 subjects (1 control subject, 3 HIV-seropositive patients with CD4+ cell number > 400 cells per microliters, and 2 HIV-positive patients with CD4+ cell number < 400 cells per microliters), these fluctuations in TNF-alpha were coupled to the known rhythm of electroencephalogram delta amplitude (square root of power) during sleep. This coupling was not present in 3 HIV-positive subjects with CD4+ cell number < 400 cells per microliters and 1 control subject. In 5 HIV subjects with abnormally low CD4+ cell counts ( < 400 cells per microliters), the number of days since seroconversion correlated significantly with low correlation between TNF-alpha and delta amplitude. We conclude that a previously unrecognized normal, physiological coupling exists between TNF-alpha and delta amplitude during sleep and that the lessened likelihood of this coupling in progressive HIV infection may be important in understanding fatigue-related symptoms and disabilities.

Adult↗
PubMed1995

Construction of thiostrepton-inducible, high-copy-number expression vectors for use in Streptomyces spp.

A high-copy-number plasmid expression vector (pIJ6021) was constructed that contains a thiostrepton-inducible promoter, PtipA, from Streptomyces lividans 66. The promoter and ribosome-binding site of tipA lie immediately upstream from a multiple cloning site (MCS) which begins with a NdeI site (5'-CATATG) that includes the tipA translational start codon (ATG), allowing the synthesis of native proteins. Transcriptional terminators occur just upstream from PtipA and immediately downstream from the MCS. To demonstrate the utility of pIJ6021, two streptomycete genes and a growth hormone-encoding gene from flounder (Paralichthys olivaceus) were cloned in the vector and expressed in S. lividans or S. coelicolor A3(2). A derivative of pIJ6021, pIJ4123, has a unique NdeI site positioned downstream from a nucleotide sequence that encodes a His6 sequence and thrombin cleavage site. pIJ4123 can be used to produce His-tagged fusion proteins that can be readily purified by Ni(2+)-affinity chromatography; if necessary, the His6 tag can be removed by digestion with thrombin. The vectors contain a kanamycin-resistance-encoding gene for the selection of transformants.

Amino Acid Sequence↗
PubMed1995

A YAC contig encompassing the XRCC5 (Ku80) DNA repair gene and complementation of defective cells by YAC protoplast fusion.

The Chinese hamster ovary xrs mutants are sensitive to ionizing radiation, defective in DNA double-strand break rejoining, and unable to carry out V(D)J recombination effectively. Recently, the gene defective in these mutants, XRCC5, has been shown to encode Ku80, a component of the Ku protein and DNA-dependent protein kinase. We present here a YAC contig involving 25 YACs mapping to the region 2q33-q34, which encompasses the XRCC5 gene. Eight new markers for this region of chromosome 2 are identified. YACs encoding the Ku80 gene were transferred to xrs cells by protoplast fusion, and complementation of all the defective phenotypes has been obtained with two YACs. We discuss the advantages and disadvantages of this approach as a strategy for cloning human genes complementing defective rodent cell lines.

Animals↗
PubMed1995

Comparison of lovastatin (20 mg) and nicotinic acid (1.2 g) with either drug alone for type II hyperlipoproteinemia.

Our study indicates that the combination of nicotinic acid (1.2 g/day) and lovastatin (20 mg/day) is more effective than either drug alone in reducing total and LDL cholesterol. Although HDL cholesterol was not significantly improved by these doses of agents over the duration of this study, LDL/HDL and HDL/total cholesterol ratios were improved due to the beneficial actions on total and LDL cholesterol. No serious side effects or changes in serum chemistries were observed, and the combination was well tolerated.

Aged↗
PubMed1995

In vitro and in vivo activity of topotecan against human B-lineage acute lymphoblastic leukemia cells.

Topotecan [(S)-9-dimethylaminomethyl-10-hydroxycamptothecin hydrochloride; SK&F 104864-A, NSC 609699], a water soluble semisynthetic analogue of the alkaloid camptothecin, is a potent topoisomerase I inhibitor. Here we show that topotecan stabilizes topoisomerase I/DNA cleavable complexes in radiation-resistant human B-lineage acute lymphoblastic leukemia (ALL) cells, causes rapid apoptotic cell death despite high-level expression of bcl-2 protein, and inhibits ALL cell in vitro clonogenic growth in a dose-dependent fashion. Furthermore, topotecan elicited potent antileukemic activity in three different severe combined immunodeficiency (SCID) mouse models of human poor prognosis ALL and markedly improved event-free survival of SCID mice challenged with otherwise fatal doses of human leukemia cells at systemic drug exposure levels that can be easily achieved in children with leukemia.

Adolescent↗
PubMed1995

Self screening for risk of melanoma: validity of self mole counting by patients in a single general practice.

OBJECTIVE: To validate self screening by patients of high mole counts, assess the within family association of sun protection behaviour and mole counts, and estimate prevalence of risk factors for melanoma. SETTING AND SUBJECTS: Systematic sample of families from a single affluent general practice population in Wessex. DESIGN: Subjects completed a questionnaire about risk factors for melanoma and counted their moles. Subsequently a mole count was done by a general practitioner trained at dermatology clinics. MAIN OUTCOME MEASURES: Validation of self counts by observer's count. Within family association of sun protection behaviour and mole counts; self reported risk factors. RESULTS: 199/237 subjects (84%) returned the questionnaire; 212/237 (89%) were examined. High counts by patients on the front of the trunk (> 7 moles of > or = 2 mm) were reasonably sensitive (79%), predictive (75%), and specific (97%) of the observer's mole counts (kappa = 0.74), unlike arm or total body counts. Sun protection behaviour correlated between individuals and other family members (Spearman's coefficient r = 0.50, P < 0.01). In the past three months 15/114 adults (13.2%, 95% confidence interval 7.0% to 19.4%) reported any change in a mole and 6/114 (5.3%, 2.0% to 11.1%) "major" changes; 6/109 adults (5.5%, 2.1% to 11.6%) had both high mole counts and freckling. CONCLUSIONS: Asking patients to count trunk moles could be a feasible way of identifying patients at high risk of melanoma. Concentrating on reported major changes in moles should avoid considerable workload in general practice. The generalisability of these findings and the adverse effects, net benefit in earlier diagnosis and prevention, and workload implications of such self screening need further research.

Adolescent↗