Search PubMed⌕ Search

Biomedical subjects

G Scott

Publications and source records attributed to G Scott.

At least 19 recordsLinked to original sources
PubMed1995

A biomarker that identifies senescent human cells in culture and in aging skin in vivo.

Normal somatic cells invariably enter a state of irreversibly arrested growth and altered function after a finite number of divisions. This process, termed replicative senescence, is thought to be a tumor-suppressive mechanism and an underlying cause of aging. There is ample evidence that escape from senescence, or immortality, is important for malignant transformation. By contrast, the role of replicative senescence in organismic aging is controversial. Studies on cells cultured from donors of different ages, genetic backgrounds, or species suggest that senescence occurs in vivo and that organismic lifespan and cell replicative lifespan are under common genetic control. However, senescent cells cannot be distinguished from quiescent or terminally differentiated cells in tissues. Thus, evidence that senescent cells exist and accumulate with age in vivo is lacking. We show that several human cells express a beta-galactosidase, histochemically detectable at pH 6, upon senescence in culture. This marker was expressed by senescent, but not presenescent, fibroblasts and keratinocytes but was absent from quiescent fibroblasts and terminally differentiated keratinocytes. It was also absent from immortal cells but was induced by genetic manipulations that reversed immortality. In skin samples from human donors of different age, there was an age-dependent increase in this marker in dermal fibroblasts and epidermal keratinocytes. This marker provides in situ evidence that senescent cells may exist and accumulate with age in vivo.

Adult↗
PubMed1995

Prophylaxis against Pneumocystis carinii pneumonia among children with perinatally acquired human immunodeficiency virus infection in the United States. Pneumocystis carinii Pneumonia Prophylaxis Evaluation Working Group.

BACKGROUND: Pneumocystis carinii pneumonia (PCP) remains a common and often fatal opportunistic infection among children infected with the human immunodeficiency virus (HIV). HIV-infected infants between three and six months of age are particularly vulnerable. Current guidelines recommend prophylaxis in children from birth to 11 months old who have CD4+ counts below 1500 cells per cubic millimeter. METHODS: We used national surveillance data to estimate the annual incidence of PCP among children less than one year old. We reviewed the medical records of 300 children given a diagnosis of PCP between January 1991 and June 1993 to determine why treatment according to the 1991 guidelines for prophylaxis against PCP either was not given or failed to prevent the disease. RESULTS: In our study the incidence of PCP in the first year of life among infants born to HIV-infected mothers changed little between 1989 and 1992. Among 7080 children born to HIV-infected mothers in 1992, PCP developed in 2.4 percent. Of 300 children with PCP diagnosed from January 1991 through June 1993, 199 (66 percent) had never received prophylaxis, and for 118 of those children (59 percent) exposure to HIV was first identified 30 days or less before the diagnosis of PCP. Among 129 children less than one year old, the CD4+ count declined by an estimated 967 cells per cubic millimeter (95 percent confidence interval, 724 to 1210 cells per cubic millimeter) during the three months before the diagnosis of PCP. Among infants in whom CD4+ counts were determined within one month of the diagnosis of PCP, 18 percent (20 of 113) had at least 1500 cells per cubic millimeter, a level higher than the currently recommended threshold for prophylaxis. CONCLUSIONS: In the United States the incidence of PCP among HIV-infected infants has not declined. If this infection is to be prevented, infants exposed to HIV must be identified earlier, and prophylaxis must be offered to more children than the guidelines currently recommend.

AIDS-Related Opportunistic Infections↗
PubMed1995

pp125FAK in human melanocytes and melanoma: expression and phosphorylation.

Focal adhesion kinase (pp125FAK) is a nonreceptor tyrosine kinase which colocalizes with integrins to focal contacts, sites where multiple proteins interact to regulate the assembly of the actin cytoskeleton. Autophosphorylation and activation of pp125FAK occur after integrin clustering or cell adhesion to ligands through cognate integrin receptors and are postulated to mediate integrin signaling events. In this report we examined pp125FAK expression and phosphorylation in normal human melanocytes, an adherent human metastatic melanoma cell line (SKMEL28), and a nonadherent human metastatic melanoma cell line (SKMEL1). We show that SKMEL28 cells express constitutively phosphorylated pp125FAK and that pp125FAK phosphorylation in melanocytes is induced by phorbol esters and growth factors present in melanocyte growth medium. Focal adhesion kinase phosphorylation could be enhanced by b1 integrin-activating antibodies in human melanocytes, but not in SKMEL28 cells. In contrast with SKMEL28 cells, constitutive phosphorylation of pp125FAK was not observed in SKMEL1 cells, and incubation with activating b1 integrin antibodies had no effect on pp125FAK phosphorylation. Absence of pp125FAK phosphorylation in SKMEL1 cells was not due to lack of expression of pp125FAK, as shown by immunoprecipitation of the pp125FAK protein from cell lysates. However, b1 integrin expression was significantly less in SKMEL1 cells than in human melanocytes and SKMEL28 cells. This study further supports the importance of integrins in pp125FAK-mediated signaling and indicates that transformation-related changes in pp125FAK phosphorylation exist in human melanocytes and melanoma cells.

Antibodies↗
PubMed1995

HIV prevalence and risk factors in university students.

OBJECTIVE: To estimate HIV prevalence and risks in university students. DESIGN: Anonymous self-completion questionnaire and HIV survey with saliva samples. SETTING: University students at matriculation. PARTICIPANTS: All first and third year undergraduates and newly registering postgraduates at the University of Edinburgh, Scotland. MAIN OUTCOME MEASURES: HIV prevalence, sexual behaviour, condom use, drug use. RESULTS: The questionnaire responses were used to classify the 4665 respondents into four groups, ordered by risk of HIV positivity, and a sample of 2041 was selected for testing. All of the top two risk groups were tested (217 and 758 tests, respectively) as well as a random sample of the others. Five positive HIV-antibody tests were detected, all from the highest risk group. This gives an estimated rate of 1.2 per 1000 (95% confidence interval, 0.4-2.9) for all respondents. Only one of the five HIV-positives had been tested for HIV. The factors associated with HIV positivity were residence in Africa, intravenous drug use and male homosexuality. Overall, 74% of respondents reported ever having had sexual intercourse and this rate was the same for men and women. Reported intravenous drug use was very low: 0.5% for men and 0.1% for women. Condom use was more common for partners of short acquaintance, but unrelated to the number of sexual partners in the last year. CONCLUSIONS: There was no evidence of the spread of HIV infection beyond known high-risk groups in this population. This may be a result of relatively low levels of HIV risk-taking behaviour in the majority of respondents.

Adult↗
PubMed1994

Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group.

BACKGROUND AND METHODS: Maternal-infant transmission is the primary means by which young children become infected with human immunodeficiency virus type 1 (HIV). We conducted a randomized, double-blind, placebo-controlled trial of the efficacy and safety of zidovudine in reducing the risk of maternal-infant HIV transmission. HIV-infected pregnant women (14 to 34 weeks' gestation) with CD4+ T-lymphocyte counts above 200 cells per cubic millimeter who had not received antiretroviral therapy during the current pregnancy were enrolled. The zidovudine regimen included antepartum zidovudine (100 mg orally five times daily), intrapartum zidovudine (2 mg per kilogram of body weight given intravenously over one hour, then 1 mg per kilogram per hour until delivery), and zidovudine for the newborn (2 mg per kilogram orally every six hours for six weeks). Infants with at least one positive HIV culture of peripheral-blood mononuclear cells were classified as HIV-infected. RESULTS: From April 1991 through December 20, 1993, the cutoff date for the first interim analysis of efficacy, 477 pregnant women were enrolled; during the study period, 409 gave birth to 415 live-born infants. HIV-infection status was known for 363 births (180 in the zidovudine group and 183 in the placebo group). Thirteen infants in the zidovudine group and 40 in the placebo group were HIV-infected. The proportions infected at 18 months, as estimated by the Kaplan-Meier method, were 8.3 percent (95 percent confidence interval, 3.9 to 12.8 percent) in the zidovudine group and 25.5 percent (95 percent confidence interval, 18.4 to 32.5 percent) in the placebo group. This corresponds to a 67.5 percent (95 percent confidence interval, 40.7 to 82.1 percent) relative reduction in the risk of HIV transmission (Z = 4.03, P = 0.00006). Minimal short-term toxic effects were observed. The level of hemoglobin at birth in the infants in the zidovudine group was significantly lower than that in the infants in the placebo group. By 12 weeks of age, hemoglobin values in the two groups were similar. CONCLUSIONS: In pregnant women with mildly symptomatic HIV disease and no prior treatment with antiretroviral drugs during the pregnancy, a regimen consisting of zidovudine given ante partum and intra partum to the mother and to the newborn for six weeks reduced the risk of maternal-infant HIV transmission by approximately two thirds.

Adult↗
PubMed1994

Staining of amyloid precursor protein to study axonal damage in mild head injury.

The most common definition of cerebral concussion is that of a transient loss of neurological function without macroscopic or microscopic abnormality in the brain. However, some patients have persistent symptoms and subtle neuropsychological deficits, particularly affecting memory. We have studied five patients aged 59-89 years who sustained mild concussive head injury and died of other causes (2-99 days post-injury). Immunostaining with an antibody to amyloid precursor protein, a marker of fast axonal transport, showed multifocal axonal injury in all five. All had axonal damage in the fornices, which are important in memory function.

Aged↗
PubMed1994

HIV in Zambia: myth or monster?

Despite attempts by a few journalists to portray the spread of AIDS in African countries as fictitious, the situation in Zambia shows that such views are completely misguided.

Female↗
PubMed1994

The effects of BTS 54,505, a metabolite of sibutramine, on monoamine and excitatory amino acid-evoked responses in the rat dorsolateral geniculate nucleus in vivo.

1. The effects of BTS 54,505, the primary amine metabolite of the non-tricylic putative antidepressant sibutramine, on the responses evoked by visual stimulation and ionophoretic application of noradrenaline (NA), 5-hydroxytryptamine (5-HT) and excitatory amino acids (EAAs) in the rat dorsolateral geniculate nucleus (dLGN) have been investigated. 2. Ionophoretic application of 5-HT to dLGN neurones attenuated visually-evoked (n = 46), NMDA-evoked (n = 21) and AMPA-evoked responses (n = 21), while ionophoretic application of NA potentiated visually-evoked activity in these cells (n = 27). 3. Simultaneous application of BTS 54,505 with 5-HT (over 120 s) resulted in a prolongation of the recovery time (i.e. the period required by a neurone to recover by 50%, RT50) from the 5-HT-mediated suppression of discharge activity (approximately 275% increase in RT50). BTS 54,505 also prolonged the recovery time from a NA-mediated potentiation of firing (approximately 450% increase in RT50). These effects on recovery time are attributed to the inhibition of uptake of both 5-HT and NA by BTS 54,505. The amplitude of the response to 5-HT or NA was unaffected by co-ejection of BTS 54,505. 4. Ionophoretic application of N-methyl-D-aspartate (NMDA) produced a current-dependent increase in neuronal firing, as did application of the non-NMDA receptor agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). A simultaneous 120 s application of BTS 54,505 inhibited the NMDA response in all cells studied (mean ED50 = 16 +/- 5 nA) but had no effect on AMPA-evoked activity in the majority of the same cells (n = 15/21).5. Short 10 s applications of BTS 54 505, at ejecting currents (>30 nA) that attenuated NMDA-evoked activity in all cells studied, had no effect on either response amplitude or recovery time from ionophoretic application of 5-HT, suggesting that inhibition of NMDA-evoked activity by BTS 54 505 was not mediated by 5-HT uptake blockade.6. These results suggest that BTS 54 505 inhibits NMDA-evoked activity, and the observation that this effect is unlikely to be due to raised levels of endogenous 5-HT following monoamine uptake blockade indicate that BTS 54 505 may interact directly with the NMDA receptor ionophore complex.

Animals↗
PubMed1994

Hypertrophic lichen planus in three HIV-positive patients: a histologic and immunological study.

It is well known that several dermatoses, such as psoriasis vulgaris and seborrheic dermatitis, present with more extensive and severe disease in patients infected with the human immunodeficiency virus (HIV-1). Except for one report, however, lichen planus (LP) has not been described in patients with HIV infection. In this report we describe the clinical and morphological features of 3 HIV-positive patients who presented with extensive hypertrophic LP. To determine if alteration in the immune status in HIV-positive hosts is reflected in the nature of the infiltrate in LP, we determined the proportion of T-helper and T-suppressor cells in the infiltrate in 1 case. The majority of the infiltrating lymphocytes in the dermis were of the T-helper phenotype. Epidermal lymphocytes, however, were predominantly of the T-suppressor phenotype. We conclude that LP in HIV-positive hosts may present with more extensive disease than in immunocompetent hosts. Based on our immunohistochemical studies, we conclude that, similar to immunocompetent hosts, T-helper cells are the predominant cells in the dermal infiltrate of LP in HIV-positive patients. However, in contrast with reports in the literature on LP in immunocompetent hosts, we found that, in the case studied, the epidermal lymphocytes were predominantly of the T-suppressor phenotype.

Adult↗
PubMed1994

Stem cell factor regulates human melanocyte-matrix interactions.

Stem cell factor (SCF) is hypothesized to play a critical role in the migration of melanocytes during embryogenesis because mutations in either the SCF gene, or its ligand, c-kit, result in defects in coat pigmentation in mice and in skin pigmentation in humans. In this report we directly show that SCF alters the adhesion and migration of human melanocytes to extracellular matrix (ECM) ligands and regulates integrin expression at the protein level. SCF decreased adhesion of neonatal and fetal cells to collagen IV, and increased attachment of fetal cells to laminin. Attachment of fetal cells to fibronectin was decreased, but was unchanged in neonatal cells. Flow cytometry analysis of neonatal melanocytes showed that SCF down-regulated the expression of the alpha 2 receptor, and up-regulated the expression of the alpha 3, alpha 5 and beta 1 integrin receptors. SCF down-regulated expression of alpha 2, alpha 5 and beta 1 integrins by fetal melanocytes, and up-regulated expression of the alpha v and alpha 3 integrin receptors. Analysis of melanocyte migration using time-lapse videomicroscopy showed that SCF significantly increased migration of neonatal, but not fetal, melanocytes on fibronectin (FN). We conclude that SCF regulates integrin expression at the protein level and that SCF has pleiotropic effects on melanocyte attachment and migration on ECM ligands. We suggest that this may be one mechanism by which SCF regulates melanocyte migration during development of the skin.

Cell Adhesion↗
PubMed1994

A prospective, double-blind trial of electrical capacitive coupling in the treatment of non-union of long bones.

Twenty-three patients who had an established non-union of a long bone were entered into a prospective, double-blind trial in which electrical capacitive coupling was used for treatment. Twenty-one patients completed the study: ten who were actively managed and eleven who were managed with a placebo unit. The non-union healed in six of the ten patients who had been managed actively but in none of the patients who had been managed with the placebo unit. This difference in the rates of healing between the actively managed and the placebo groups is highly significant (p = 0.004).

Adolescent↗
PubMed1994

Brain injury patterns in fatally injured pedestrians.

To study the relationship between the severity of impact to the head and the severity and distribution of injury to the brain in fatally injured pedestrians, events in vehicle-pedestrian collisions were reconstructed to determine the peak linear and angular acceleration sustained by the pedestrians' heads. The nature and distribution of injuries to the brain were determined by neuropathologic examination of coronal sections of the brain. Study of 13 cases with occipital impacts and 18 with lateral impacts showed that the brain appeared to be more susceptible to injury from lateral impacts. The frontal and temporal regions appeared to be more susceptible to injury at low accelerations in occipital impacts, providing an explanation for "coup" and "contrecoup" injuries. For occipital impacts, a positive relationship was found between linear acceleration and the extent of injury to the brain, suggesting that there was a threshold for observable and concussive brain injury at about 1500 m/s2 peak linear acceleration. These findings are important for the development of measures for preventing brain injuries.

Accidents, Traffic↗
PubMed1993

Subpopulations of bone marrow fibroblasts support VLA-4-mediated migration of B-cell precursors.

Proliferation of normal human lymphoid progenitors in culture is dependent on interaction with bone marrow-derived fibroblast-like cells (BM-FB). To investigate possible heterogeneity in this lymphoid-supportive microenvironment, we studied the interaction of a human B-precursor cell line (NALM-6) with BM-FB. NALM-6 cells associate with BM-FB by either adhesion or migration underneath the fibroblast. Individual fibroblasts in the BM-FB layer showed significant variation in the number of migrating NALM-6 cells. Migration of NALM-6 cells was primarily VLA-4-dependent, although residual migration observable after blocking with anti-VLA-alpha 4 antibody was inhibited by anti-VLA-alpha 5 antibody. Migration was not inhibited by blocking either of the known VLA-4 counterreceptors (VCAM-1 or fibronectin), although slight inhibition was observed using a combination of blocking antibodies to VCAM-1 and fibronectin. In contrast, NALM-6 adhesion without migration was significantly inhibitable by anti-VCAM-1 antibody. VCAM-1 or fibronectin expression on individual BM-FB did not correlate with NALM-6 migration. These results indicate that the adhesion and migration of human B-lymphoid precursors in the bone marrow microenvironment are mechanistically separable events and suggest the possibility of novel VLA-4 ligand(s), which may be important in human lymphopoiesis. Subpopulations of cells in the bone marrow microenvironment may preferentially support important aspects of lymphoid progenitor development.

Adult↗
PubMed1993

[Nutritional evaluation of sweet potato cultivars Ipomea batata (L.) Lam used in bread as partial substitute of wheat flour].

Four hundred and forty entries of sweet potato tubers from the International Potato Center were evaluated for chemical characteristics related to nutritional value. Dry matter range in the group was 15 to 45g/100g. The native entries DLP 2393, DLP 1120, DLP 2312, DLP 1908 and the foreign RCB 361F were selected for use in bread manufacture. Their average dry matter and crude protein was 38.5 and 9.2% respectively. Sweet potato bread was made replacing 30% of wheat flour with grinded sweet potato tubers. This bread had 11.0% crude protein in dry matter basis which were the same for bread made of wheat flour. There were no differences in organoleptic characteristics or protein quality (Apparent biological value: 37 vs 42%; apparent digestibility: 81 vs 80%; net protein utilization: 33 vs 39%) between sweet potato or full wheat flour breads respectively.

Bread↗
PubMed1992

Effect of cilofungin on phagocytosis and intracellular killing of Candida albicans by human neutrophils.

The effect of a beta glucan synthase inhibitor, cilofungin, amphotericin B and 5-fluorocytosine on opsonization, phagocytosis and intracellular killing of Candida albicans blastospores by glass-adherent human neutrophils was determined by microscopy and dye exclusion staining. Pretreatment of blastospores for 2, 4, 6 and 18 h with 1.25 mg/l cilofungin resulted in 24-28% of neutrophils ingesting compared to 24% with no drug present. There was no significant difference in the phagocytic index with increased incubation time. Percentage ingestion and phagocytic index values were not significantly different when blastospores were pretreated for 2 h in the presence of 3, 7, 15, 31 and 62 mg/l cilofungin. Comparable concentrations of amphotericin B and 5-fluorocytosine gave similar results. In the absence of cilofungin, intracellular killing after 2 h was 54%. In the presence of 1 and 10 mg/l cilofungin, 85-90% of intracellular blastospores were killed. Therapeutic levels of amphotericin B or 5-fluorocytosine did not enhance intracellular killing. These data demonstrate the potentiation of intracellular killing of Candida albicans by neutrophils in the presence of cilofungin.

Amphotericin B↗
PubMed1992

A simple and rapid method for improving recording characteristics using multibarrelled micropipettes.

A method for the simple and rapid fabrication of multibarrelled micropipettes with improved signal-to-noise characteristics is described. The process of silicone coating the exterior of the multibarrel assembly was found to improve recording characteristics greatly and to reduce recording noise during the passage of ionophoretic current. This simple process of fabrication and silicone coating is completed within 15-20 min and is technically undemanding.

Action Potentials↗