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Biomedical subjects

J Smith

Publications and source records attributed to J Smith.

At least 379 records · Page 21Linked to original sources
PubMed1998

Gene transfer using a disabled herpes virus vector containing the EMCV IRES allows multiple gene expression in vitro and in vivo.

The design of recombinant HSV-1 vectors for delivery of transgenes to the central nervous system is undergoing constant development. Problems associated with the construction and use of such vectors include the requirement for detection of recombinant versus nonrecombinant virus in vitro and also the identification of transduced cells in vivo. This could be overcome by the insertion of reporter genes such as lacZ or green fluorescent protein (GFP) under a separate promoter to the transgene to be expressed. In this case, however, reporter gene expression does not necessarily confirm transgene expression as a separate RNA must be produced. This study reports the use of an encephalomyocarditis virus internal ribosome entry site (IRES) to enable the translation of two reporter genes from a single mRNA transcript driven by the same promoter within a disabled HSV vector, and discusses the potential advantages of this approach.

Animals↗
PubMed1998

Parameters of the chicken genome (Gallus gallus).

As more information on the chicken genome is gathered, it is becoming increasingly more important to be able to correlate genetic and physical maps. Quantitation of the chicken karyotype is important in establishing parameters which define the genome. Here we report on the physical lengths of the chicken macrochromosomes and establish the DNA content of each, thus identifying implicitly how much of the genome is represented by the microchromosomal component. For the first time, genetic and physical data on the chicken karyotype are presented in relation to one another.

Animals↗
PubMed1998

The practice of venepuncture in lymphoedema.

Patients at risk of developing lymphoedema following local treatment for cancer will also have compromised local immunity. Inflammation or infection may be the precipitating factor for the development of chronic swelling. A small group of breast cancer patients, who identified venepuncture as a significant event in the history of their swelling, were examined. Management of these patients includes emphasis on the care of their skin, with the aim of reducing the risk of developing lymphoedema.

Breast Neoplasms↗
PubMed1998

Are electronic thermometry techniques suitable alternatives to traditional mercury in glass thermometry techniques in the paediatric setting?

Three thermometers, mercury in glass, Becton-Dickinson digital and IVAC tympanic membrane thermometer, were compared. The study was designed to test the null hypothesis that there is no difference between the thermometer recordings, meaning that electronic thermometry is a suitable alternative to traditional mercury in glass thermometry. Children aged between 0 and 15 years old were entered into the study, n = 114. Standard procedures were used throughout the study to minimize the risk of errors in the data collection and technical errors were recorded. The data were analysed using graphical techniques described by Bland and Altman. The differences between the temperature recordings were plotted against their mean (the estimated true value), with the bias and limits of agreement (2 standard deviations from the mean) calculated for the mercury in glass/digital, mercury in glass/tympanic and digital/tympanic temperature recordings. The range of temperatures were 35.1 degrees C-38.5 degrees C, with a mean of 36.85 degrees C for the mercury in glass thermometer, 36.8 degrees C for the digital thermometer and 36.65 degrees C for the tympanic thermometer. The bias for each comparison was 0.36 degrees C, 0.21 degrees C and 0.17 degrees C and the limits of agreement were wide, -0.516 degrees C to 1.234 degrees C, -0.84 degrees C to 1.252 degrees C and -0.940C to 1.244 degrees C for the mercury in glass/digital, mercury in glass/tympanic and digital/ tympanic recordings respectively. A difference of 0.2 degrees C is usually accepted for clinical practice, therefore the null hypothesis was rejected.

Adolescent↗
PubMed1998

Delivery of a constitutively active form of the heat shock factor using a virus vector protects neuronal cells from thermal or ischaemic stress but not from apoptosis.

The heat shock proteins (HSPs) are induced by stressful stimuli and have a protective effect. Different HSPs protect with different efficiencies against different stresses indicating that optimal protection would be obtained with a non-stressful agent which induced a range of HSPs. We have prepared a herpesvirus vector expressing a constitutively active mutant form of heat shock factor 1 (HSF1) which, unlike the wild-type form of this transcription factor, does not require stress for its activation. Upon infection of neuronal cells, this virus induced a more restricted range of HSPs than in non-neuronal cells. Infection with the virus protected neuronal cells against subsequent thermal or ischaemic stress in accordance with its ability to induce HSP70 expression but did not protect them against apoptotic stimuli. The mechanisms of these effects and their significance for the use of HSF to manipulate HSP gene expression is discussed.

Animals↗
PubMed1998

Generation of a nude mouse tumor model for in vivo replication of human cytomegalovirus.

Human cytomegalovirus (HCMV) is a common opportunistic infection resulting in retinitis in 15%-40% of AIDS patients. Several anti-HCMV therapies are currently available, and new treatments are in various stages of development. An HCMV animal model involving in vivo infection of human cells without the dependence on human fetuses or multiple surgical procedures has been developed. A human glioblastoma cell line that is permissive for HCMV replication (U373MG) was adapted to grow as a subcutaneous tumor in nude mice. These tumors arise in approximately 7 days and grow progressively. An evaluation of HCMV DNA replication demonstrated an increase in the accumulation of HCMV DNA within infected tumors from 48 to 168 h after infection. Immunohistochemical analysis showed focal areas of HCMV infection in which expression of immediate-early and late antigens was detected. In addition, it was demonstrated that ganciclovir inhibited HCMV DNA replication in vivo in a dose-dependent manner.

Animals↗
PubMed1998

Stillbirth rates around the nuclear installation at Sellafield, North West England: 1950-1989.

BACKGROUND: The aim of the study was to investigate whether proximity to the nuclear installation at Sellafield, in Cumbria, North West of England, increases the risk of stillbirth in the resident population. The cohort consisted of all 256066 live and 4034 stillbirths to mothers usually domiciled in Cumbria, 1950-1989. METHODS: The study was a retrospective cohort analysis allowing for year of birth, social class and birth order using: (i) Poisson probability mapping, (ii) comparison of cumulative observed and expected numbers of stillbirths by distance from Sellafield, (iii) logistic regression of stillbirth risk in relation to distance and direction from Sellafield. RESULTS: Poisson probability mapping of stillbirths within 25 km of Sellafield provided no evidence to suggest that proximity to Sellafield increased the risk of stillbirth, either overall or in any specific direction. Comparison of the cumulative observed and expected numbers of stillbirths also showed no increased risk with proximity to Sellafield. Logistic regression analysis of all Cumbrian births supported these results, showing, in particular, that distance from Sellafield did not significantly influence stillbirth risk (P = 0.30). Although there was significant variation in stillbirth risk with direction (P = 0.0004), this was due to stillbirths in areas much further than 25 km from Sellafield. There was no significant effect with distance from Sellafield within any of six directional sectors (P > 0.05). CONCLUSIONS: There was no evidence to suggest that proximity to Sellafield increases the risk of stillbirth in the resident population.

Birth Order↗
PubMed1998

Antiatherosclerotic and antioxidative effects of captopril in apolipoprotein E-deficient mice.

The effect of the angiotensin-converting enzyme (ACE) inhibitor, captopril, on the development of atherosclerosis was determined in the apolipoprotein (apo) E-deficient mice. These mice develop severe hypercholesterolemia and extensive atherosclerotic lesions on chow diet, similar to those found in humans. Furthermore, in these mice, accelerated atherosclerosis is associated with increased plasma lipid peroxidation, a phenomenon that may play a crucial role in the buildup of the atherosclerotic lesions. Mice received either placebo or 50 mg/kg/day of captopril. After 12 weeks of treatment, captopril reduced the aortic-lesion area by 70% compared with that of the placebo-treated group. Captopril also increased the resistance of low-density lipoprotein (LDL) to CuSO4-induced oxidative stress, as shown by a significant reduction in the LDL content of malondialdehyde (MDA) by 30%, as well as by the prolongation of the lag time required for LDL oxidation from 55 min in the placebo-treated mice to 70 min in the captopril-treated mice, and reduction of the maximum LDL oxidation at 150 min by 35%. In vitro studies demonstrated that preincubation of LDL with captopril, inhibited the onset of CuSO4-induced LDL peroxidation up to 120 min, and reduced the LDL content of MDA by 90%. We conclude that captopril attenuates atherosclerosis in the apo E-deficient mice, and this phenomenon may be related to its inhibitory effect on the plasma LDL oxidation.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Intravenous delivery of 5'-iododeoxyuridine during hyperfractionated radiotherapy for locally advanced head and neck cancers: results of a pilot study.

OBJECTIVES: Locally advanced cancers of the head and neck require aggressive treatment, often with limited effectiveness and significant toxicity and morbidity. This pilot study was designed to assess tolerance using combined hyperfractionated radiotherapy and the halogenated pyrimidine radiosensitizer 5'-iododeoxyuridine (IdUrd). STUDY DESIGN: This was a prospective single-arm study open to patients with advanced head and neck cancers that had a poor chance of control with conventional radiation therapy. Patients were treated with hyperfractionated radiation therapy at standard doses in combination with an IdUrd infusion and observed for tumor response and normal tissue tolerances. METHODS: Radiation therapy was delivered in fractions of 1.2 Gy or 1.5 Gy twice daily to a total dose in the range of 70 to 76 Gy. IdUrd was delivered as an intravenous infusion (1000 mg/m2 per day) for a maximum of 14 days at the beginning and then again during the middle of the radiotherapy. RESULTS: Twelve patients with advanced squamous cell lesions were enrolled and 11 were observed to have complete clinical remissions. Seven patients remained clinically free of local disease at the time of death or most recent follow-up. Acute toxicities, usually hematologic or mucosal, were severe and all patients required treatment modifications and considerable supportive care. CONCLUSIONS: Although a high rate of response was achieved using this regimen, the toxicities are prohibitive. The kinetic profile of IdUrd incorporation suggests the need for future studies using repetitive short courses of IdUrd.

Adult↗
PubMed1998

Rural-urban differences in depression treatment and suicidality.

OBJECTIVES: Because there are fewer per capita providers trained to deliver mental health services in rural areas, the authors hypothesized that depressed rural individuals would receive less outpatient treatment and report higher rates of hospital admittance and suicide attempts than their urban counterparts. METHODS: The authors recruited 74% of eligible participants (n = 470) from a 1992 telephone survey and followed up 95% of subjects for 1 year. The authors collected data from subjects on psychiatric problems and service use and from insurers/providers on treatment and expenditures. RESULTS: Although there were no rural-urban differences in the rate, type, or quality of outpatient depression treatment, rural subjects made significantly fewer specialty care visits for depression. Depressed rural individuals had 3.05 times the odds of being admitted to the hospital for physical problems (P = 0.02) and 3.06 times the odds of being admitted for mental health problems (P = 0.08) during the year. Elevated rates of hospital admittance disappear in models controlling for number of specialty care depression visits in the previous month. Rural subjects reported significantly more suicide attempts during the period of 1 year (P = 0.05). CONCLUSIONS: Additional work is warranted to determine how to alter barriers to outpatient specialty care if the rural health care delivery system is to provide cost-effective depression care.

Adolescent↗
PubMed1998

Nitric oxide production in experimental gram-negative infection: studies with cytokine receptor-deficient mice.

Overproduction of nitric oxide (NO) upon expression of inducible NO synthase (iNOS) may be responsible for refractory hypotension in septic shock. Whereas high levels of NOS activity have been documented in experimental models of endotoxemia or intravenous challenge with Escherichia coil, much less is known concerning tissue models of Gram-negative infection. We examined NO production (measured as the accumulation of plasma NO3- + NO2-) in a murine model of Gram-negative peritonitis. Plasma NO3- + NO2- increased progressively from 25 microM to peak levels of 50-150 microM 24 h after intraperitoneal challenge with E. coli 0111:B4, similar to values reported for septic shock patients. Treatment of infected mice with NG-monomethyl-L-arginine, an inhibitor of NOS activity, resulted in the efficient inhibition of NO3- + NO2- production. In order to evaluate the roles of interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF-alpha) in the induction of NO synthesis in murine peritonitis, mice deficient in the respective cytokine receptors were studied. In control in vitro experiments, macrophages from IFN-gammaR- or TNFR55-deficient mice, while failing to respond to IFN-gamma or TNF-alpha, respectively, produced high levels of NO under appropriate stimulation. When challenged intraperitoneally with E. coli, IFN-gammaR- or TNFR55-deficient mice exhibited similar levels of bacteremia and NO production as their wild-type controls. These data thus suggest that enhanced NO production during focal Gram-negative infection may occur in the absence of signaling through either IFN-gammaR or TNFR55.

Animals↗
PubMed1998

pp90rsk1 regulates estrogen receptor-mediated transcription through phosphorylation of Ser-167.

The estrogen receptor alpha (ER), a member of the steroid receptor superfamily, contains an N-terminal hormone-independent transcriptional activation function (AF-1) and a C-terminal hormone-dependent transcriptional activation function (AF-2). Here, we used in-gel kinase assays to determine that pp90rsk1 activated by either epidermal growth factor (EGF) or phorbol myristate acetate specifically phosphorylates Ser-167 within AF-1. In vitro kinase assays demonstrated that pp90rsk1 phosphorylates the N terminus of the wild-type ER but not of a mutant ER in which Ser-167 was replaced by Ala. In vivo, EGF stimulated phosphorylation of Ser-167 as well as Ser-118. Ectopic expression of active pp90rsk1 increased the level of phosphorylation of Ser-167 compared to that of either a mutant pp90rsk1, which is catalytically inactive in the N-terminal kinase domain, or to that of vector control. The ER formed a stable complex with the mutant pp90rsk1 in vivo. Transfection of the mutant pp90rsk1 depressed ER-dependent transcription of both a wild-type ER and a mutant ER that had a defective AF-2 domain (ER TAF-1). Furthermore, replacing either Ser-118 or Ser-167 with Ala in ER TAF-1 showed similar decreases in transcription levels. A double mutant in which both Ser-118 and Ser-167 were replaced with Ala demonstrated a further decrease in transcription compared to either of the single mutations. Taken together, our results strongly suggest that pp90rsk1 phosphorylates Ser-167 of the human ER in vivo and that Ser-167 aids in regulating the transcriptional activity of AF-1 in the ER.

Animals↗
PubMed1998

Investigation of the effect of occult invasive cancer on progress towards successful cervical screening.

OBJECTIVES: To describe the effect of occult invasive disease on progress towards meeting the Health of the Nation target for reducing the incidence of cervical cancer, and to investigate the possible effect of a higher risk of cervical cancer in women born since 1940. SETTING: Southampton and South West Hampshire (SSWH), with a total female population of 218,549 in 1990, the midpoint of a study period covering 1985 to 1995. METHODS: Incidence was calculated per 100,000 women years at risk in overlapping three year periods for symptomatic and screen detected cancers. The same methods was used for cohorts of women born before and after 1940. Screen detected stage Ia1 cancers were identified as a subgroup. RESULTS: The incidence of invasive cervical cancer fell by 27.4%, from 16.8 to 12.2 per 100,000 women years at risk between 1985-87 and 1993-95, which was a significant linear trend (chi 2 = 4.494, df = 1, p = 0.034). The corresponding figures adjusted for age in a standardised European population were 16.3 and 11.5: a fall greater than required to meet the Health of the Nation target set for the year 2000. Incidence remained relatively high until screen detected cancers, more than one third of which were stage Ia1, had passed a peak in 1992. When screen detected stage Ia1 cancers were excluded, incidence fell by 41.2%, from 16.5 to 9.7 per 100,000 women years at risk: a highly significant linear trend (chi 2 = 12.391, df = 1, p < 0.001). The incidence in the first three years of the study was higher in women born between 1940 and 1954 than in those born between 1925 and 1939, though the reverse would be expected by age and the natural history of the disease. In the 1940-54 birth cohort 44% (23/52) of screen detected cancers were stage Ia1, with a peak in 1992. When these were excluded, incidence fell by 57.1%, from 31.7 to 13.6 per 100,000 women years at risk: a highly significant linear trend (chi 2 = 13.704, df = 1, p < 0.001), whereas an increase would be expected for a cohort aged from 30-45 to 40-55. In the 1925-39 cohort only 24% (8/33) of screen detected cancers were stage Ia1. When these were excluded, incidence fell by 35.3%, from 24.9 to 16.1, which was not a significant linear trend (chi 2 = 0.409, df = 1, p = 0.522). CONCLUSION: An overall decline in incidence was not achieved until prevalent occult invasive disease had been detected by improved screening. The data confirm the effectiveness of screening, particularly in a high risk cohort of women born between 1940 and 1954.

Adolescent↗
PubMed1998

Expenditures for the treatment of major depression.

OBJECTIVE: Health policy makers lack accurate information about per capita spending for the treatment of major depression, the distribution of those expenditures, and the proportion of the health care dollar consumed by depression treatment. METHOD: The authors recruited and followed a community cohort of individuals with major depression; the 298 subjects were either enrolled in fee-for-service insurance plans or self-insured. Charges for all health care services received during the year following baseline were abstracted from medical and insurance records. RESULTS: Over the course of 1 year, 48.1% of the subjects received depression treatment. The per capita total expenditure for inpatient and outpatient depression treatment averaged $631, with a median of $152, for the treated subjects. Just 4.9% of the treated subjects consumed 45.0% of the outpatient expenditures. Depression treatment consumed only 8 cents of every health care dollar spent on the patients treated for depression. CONCLUSIONS: Studies are needed to examine how the level and distribution of expenditures for depression treatment change under managed care and to determine whether and how any differences affect outcomes in the afflicted population. Managed care attempts to contain costs by limiting outpatient care may not affect total health care expenditures dramatically, since depression treatment consumes such a minuscule portion of the health care dollar spent on this population.

Adolescent↗
PubMed1998

Non-insulin dependent diabetes mellitus in African-American youths of Arkansas.

Non-insulin dependent diabetes mellitus (NIDDM) occurs more frequently in certain adult populations, including African-Americans. Recently an increase in the incidence of NIDDM has been observed among African-American youths in Arkansas. Clinical presentations among these youths vary from asymptomatic to severe diabetic ketoacidosis. From a chart review, data were examined to determine which physical, biochemical, and autoimmune characteristics were most helpful in appropriate classification of NIDDM vs insulin dependent diabetes mellitus (IDDM). It is apparent that several diagnostic and treatment issues need to be addressed to improve the management of African-American youths with NIDDM.

Adult↗
PubMed1998

G-CSF association with prolonged survival in HIV-infected patients with disseminated Mycobacterium avium complex infection.

Clarithromycin can ameliorate symptoms and improve survival in disseminated Mycobacterium avium complex (DMAC) infection. Optimal combinations of this drug with other agents remain unknown. Granulocyte colony stimulating factor (G-CSF) is a cytokine that can improve phagocytosis of M. avium complex in vitro. We aim to determine if G-CSF administration is associated with improved survival in patients with DMAC in a retrospective, cohort study. Case records from 1991 to 1995 of 91 patients with DMAC at Parkland Memorial Hospital were reviewed for date of initial DMAC diagnosis, baseline CD4 count, race, sex, antiretroviral use, G-CSF use, therapy for DMAC (clarithromycin, ethambutol, ciprofloxacin and rifabutin) and date of death. Of 91 cases identified, 25 were treated with G-CSF and 66 never received this drug. Baseline characteristics were similar in each group including CD4 count (40 cells/mm3 vs 33 cells/mm3, P=0.68), clarithromycin use (18 patients vs 52 patients, P=0.90), and antiretroviral use (20 patients vs 42 patients, P=0.21). Subjects treated with G-CSF lived longer than those who did not receive this drug (355 days vs 211 days, P<0.01). In the subgroup treated with clarithromycin, G-CSF was also associated with increased survival (377 days vs 252 days, P<0.01). Cox proportional hazards model showed a decreased risk of death in patients treated with G-CSF (RH=0.22, P<0.01), clarithromycin (RH=0.13, P<0.01) and ethambutol (RH=0.51, P=0.02). Ciprofloxacin and rifabutin use did not influence survival. These data support the use of clarithromycin and ethambutol in the treatment of DMAC. Addition of G-CSF to a regimen of clarithromycin and ethambutol may increase survival in DMAC and should be studied prospectively.

AIDS-Related Opportunistic Infections↗