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Biomedical subjects

A Russell

Publications and source records attributed to A Russell.

At least 55 records · Page 3Linked to original sources
PubMed1999

Daily sunscreen application and betacarotene supplementation in prevention of basal-cell and squamous-cell carcinomas of the skin: a randomised controlled trial.

BACKGROUND: The use of sunscreens on the skin can prevent sunburn but whether long-term use can prevent skin cancer is not known. Also, there is evidence that oral betacarotene supplementation lowers skin-cancer rates in animals, but there is limited evidence of its effect in human beings. METHODS: In a community-based randomised trial with a 2 by 2 factorial design, individuals were assigned to four treatment groups: daily application of a sun protection factor 15-plus sunscreen to the head, neck, arms, and hands, and betacarotene supplementation (30 mg per day); sunscreen plus placebo tablets; betacarotene only; or placebo only. Participants were 1621 residents of Nambour in southeast Queensland, Australia. The endpoints after 4.5 years of follow-up were the incidence of basal-cell and squamous-cell carcinomas both in terms of people treated for newly diagnosed disease and in terms of the numbers of tumours that occurred. Analysis of the effect of sunscreen was based only on skin cancers that developed on sites of daily application. All analyses were by intention to treat. FINDINGS: 1383 participants underwent full skin examination by a dermatologist in the follow-up period. 250 of them developed 758 new skin cancers during the follow-up period. There were no significant differences in the incidence of first new skin cancers between groups randomly assigned daily sunscreen and no daily sunscreen (basal-cell carcinoma 2588 vs 2509 per 100,000; rate ratio 1.03 [95% CI 0.73-1.46]; squamous-cell carcinoma 876 vs 996 per 100,000; rate ratio 0.88 [0.50-1.56]). Similarly, there was no significant difference between the betacarotene and placebo groups in incidence of either cancer (basal-cell carcinoma 3954 vs 3806 per 100,000; 1.04 [0.73-1.27]; squamous-cell carcinoma 1508 vs 1146 per 100,000; 1.35 [0.84-2.19]). In terms of the number of tumours, there was no effect on incidence of basal-cell carcinoma by sunscreen use or by betacarotene but the incidence of squamous-cell carcinoma was significantly lower in the sunscreen group than in the no daily sunscreen group (1115 vs 1832 per 100,000; 0.61 [0.46-0.81]). INTERPRETATION: There was no harmful effect of daily use of sunscreen in this medium-term study. Cutaneous squamous-cell carcinoma, but not basal-cell carcinoma seems to be amenable to prevention through the routine use of sunscreen by adults for 4.5 years. There was no beneficial or harmful effect on the rates of either type of skin cancer, as a result of betacarotene supplementation.

Adult↗
PubMed1999

Cyclin D1 and D3 associate with the SCF complex and are coordinately elevated in breast cancer.

D-type cyclins are important cell cycle regulators that promote cellular proliferation in response to growth factors by inactivation of the retinoblastoma protein (Rb). Cyclin D1 has been shown to be overexpressed in several cancer types and to act as an oncogene in breast cancers. As D-type cyclins are rate limiting for progression into S phase, the level at which they accumulate must be carefully regulated. Several mechanisms leading to overexpression of cyclin D1 have been reported including amplification, translocation and stabilization of the mRNA. Here, we present data showing elevated cyclin D1 protein in breast cancer samples in the absence of elevated mRNA level. Further, we found that in these cases, cyclin D3 protein also accumulates and that the coordinate increase in cyclin D1 and D3 occurs in 15% (7/47) of breast cancers. In addition we show that blocking the activity of the 26S proteosome results in the accumulation of cyclin D1 and D3, that both D-type cyclins are ubiquitinated and associate with Cul-1, a component of the SCF ubiquitin ligase complex. Finally, we show that the coordinated elevation of cyclin D1 and D3 is also observed in the breast cell line MCF-7 and demonstrate that the degradation of cyclin D1 and D3 is deficient in this cell line. These results indicate that cyclin D1 and cyclin D3 share a common mechanism of degradation and we propose that the coordinate increase of D-type cyclins observed in primary breast cancers reflects a defect in their proteolysis.

Breast Neoplasms↗
PubMed1999

Increased severity of Candida vaginitis in BALB/c nu/nu mice versus the parent strain is not abrogated by adoptive transfer of T cell enriched lymphocytes.

The role of the host immune system in combating candidal infections in the vagina is poorly understood. A murine model of Candida vaginitis was used to elucidate the role of T cells in a candidal infection. Athymic BALB/c nu/nu mice or normal BALB/c mice were induced into estrus and then infected with 1 x 10(6) Candida albicans intravaginally. The infection was monitored over 1 week. Samples from blood, small intestine, tongue, kidney, spleen, liver, uterus and vagina were tested for recoverable C. albicans. Histology of the vagina was assessed for both inflammation and extent of infection. Results indicated that the BALB/c nu/nu mice had similar levels of vaginal yeast load to the normal BALB/c mice. In 25-30% of nude mice Candida was also recovered from extra vaginal sites (kidney, liver, small intestine), however, extra vaginal dissemination was not observed in any normal BALB/c animals. Histologically, both the nu/nu and control BALB/c had similar levels of vaginal inflammation; however, the nu/nu mice had more florid fungal growth in the vaginal epithelium. Adoptive transfer of either immune or non-immune BALB/c T cells into nude mice had no affect on either infection or vaginal inflammation. Immunohistochemical staining of vaginal tissues from normal BALB/c mice or nude mice adoptively transferred with either immune or non-immune T cells with anti-CD3 monoclonal antibody revealed no significant difference between groups in the numbers of CD3+ vaginal T cells. However, in mice receiving either immune or non-immune T cells no yeast was recovered from any tissues except the vagina. These data show that T cells have a limited role in protecting the vagina from C. albicans infection.

Animals↗
PubMed1999

Human papillomavirus type 5 is commonly present in immunosuppressed and immunocompetent individuals.

DNA of a wide spectrum of epidermodysplasia verruciformis-associated human papillomavirus (HPV) types (EV-HPV) has been detected in skin lesions and plucked hairs from both immunosuppressed and a considerable proportion of non-immunosuppressed persons. Recently, the skin of psoriatic patients was claimed to be an important reservoir for a particular EV-HPV type, HPV 5, which is considered as a high-risk HPV type for skin carcinomas. In the present study, we analysed plucked hairs from immunosuppressed renal transplant patients and immunocompetent individuals, utilizing an HPV 5-specific nested polymerase chain reaction. HPV 5 was detected in hairs derived from 14 of 31 (45%) immunosuppressed patients and 21 of 135 (16%) immunocompetent individuals. Both the immunosuppressed and the immunocompetent groups consisted of individuals with and without non-melanoma skin cancer. HPV 5 DNA was detected in similar proportions of hair samples plucked from individuals with and without skin cancer in either group. Our results indicate that HPV 5 is commonly present in the population. The role of HPV 5 in the pathogenesis of skin carcinomas and psoriasis remains to be established.

Adult↗
PubMed1999

Case studies in osteoporosis: a problem based learning intervention for family physicians.

OBJECTIVE: To develop and evaluate a practice based small group (PBSG) learning intervention on osteoporosis for primary care physicians. METHODS: A needs assessment on osteoporosis was performed and objectives for a continuing medical education (CME) program developed by an interdisciplinary advisory committee. Nine clinical cases were developed for evaluation by CME participants with a trained facilitator and content expert using the PBSG format. The effect of the CME intervention was evaluated using a pre and post-test consisting of objective structured clinical examination stations and standardized patients. RESULTS: Fifty-four family physicians participated in 4 pilot PBSG learning sessions. The program format, content, and participant satisfaction was highly rated (> 3.35:4.0). Participants expected the program to have a significant effect on the practices (3:40:4.0). Ninety-eight percent of participants improved their pretest scores, with a mean increase of 13% (range 1-36%). CONCLUSION: Based on our experience, we advocate the use of PBSG learning interventions as an effective and acceptable method of providing CME by rheumatologists for their family physician colleagues. This format appears to be associated with a significant effect on knowledge, skills, and behavior as assessed by our study.

Aged↗
PubMed1999

Increasing gap in breast cancer mortality between black and white women.

Breast cancer mortality rates have declined in the United States and in Wisconsin. We examined racial differences in mortality trends among black and white women in Wisconsin and the United States from 1979 to 1996. During this time period, mortality rates increased 10% among black women and decreased 7% among white women in Wisconsin. These trends were similar nationally, with an 18% increase among black women and a 3% decrease among white women. The black:white gap in mortality increased among women of all ages--especially among women under age 55. The increasing racial disparity in breast cancer mortality may result from differences in trends in incidence and survival among black women. More research is needed to understand the underlying causes of the disparity in breast cancer mortality between black and white women.

Adult↗
PubMed1998

CDP840: a novel inhibitor of PDE-4.

We present the in vitro characterization of a novel phosphodiesterase type 4 inhibitor, CDP840 (R-[+]-4-[2-¿3-cyclopentyloxy-4-methoxyphenyl¿-2-phenylethyl]pyridine), which has shown efficacy in a phase II allergen challenge study in asthmatics without adverse effects. CDP840 potently inhibits PDE-4 isoenzymes (IC50 2-30 nM) without any effect on PDE-1, 2, 3, 5, and 7 (IC50 > 100 microM). It exhibited no significant selectivity in inhibiting human recombinant isoenzymes PDE-4A, B, C or D and was equally active against the isoenzymes lacking UCR1 (PDE-4B2 and PDE-4D2). In contrast to rolipram, CDP840 acted as a simple competitive inhibitor of all PDE-4 isoenzymes. Studies with rolipram indicated a heterogeneity within all the preparations of PDE-4 isoenzymes, indicative of rolipram inhibiting the catalytic activity of PDE-4 with both a low or high affinity. These observations were confirmed by the use of a PDE-4A variant, PDE-4A330-886, which rolipram inhibited with low affinity (IC50 = 1022 nM). CDP840 in contrast inhibited this PDE-4A variant with similar potency (IC50 = 3.9 nM), which was in good agreement with the Kd of 4.8 nM obtained from [3H]-CDP840 binding studies. Both CDP840 and rolipram inhibited the high-affinity binding of [3H]-rolipram binding to PDE-4A, B, C, and D with similar Kd app (7-19 nM and 3-5 nM, respectively). Thus, the activity of CDP840 at the [3H]-rolipram binding site was in agreement with the inhibitor's activity at the catalytic site. However, rolipram was approximately 100-fold more potent than CDP840 at inhibiting the binding of [3H]-rolipram to mouse brain in vivo. These data clearly demonstrate that CDP840 is a potent selective inhibitor of all PDE-4 isoenzymes. In contrast to rolipram, CDP840 was well-tolerated in humans. This difference, however, cannot at present be attributed to either isoenzyme selectivity or lack of activity in vitro at the high-affinity rolipram binding site (Sr).

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Have women's voices lowered across time? A cross sectional study of Australian women's voices.

Various aspects of our communication are well known to have changed over time (1-3). This article describes a cross-sectional study that examined the acoustic characteristics of two groups of Australian women aged 18-25 years from recordings made in 1945 and 1993 and investigated the possible changes in the voice across generations. Archival recordings from 1945 which had been used in a longitudinal study (4) were compared to recordings made in 1993. The results of this study show that women in 1993 have significantly deeper voices than women of the same age recorded in 1945. The possible factors influencing this change are discussed.

Adolescent↗
PubMed1998

Prevalence of voice problems in teachers.

Teachers are frequently cited as experiencing a high rate of vocal dysfunction (1-7). Despite considerable research in the area of voice problems in teachers, the prevalence of voice disorders in this group is unknown. This study investigated the prevalence of self-reported voice problems in teachers using a mail survey of a simple random sample of 1168 state school teachers (preschool-Grade 12) in South Australia. As part of the survey, teachers were asked to report voice problems for the day of the survey, during the current teaching year, and during their careers. The response rate was 75%, with 16% of teachers reporting voice problems on the day of the survey, 20% reporting problems during the current teaching year, and 19% reporting problems at some time during their career. Females were twice as likely as males to report voice problems. These findings clearly indicate a need for further investigation of the causes of vocal dysfunction in teachers and for the development of educational programs aimed at preventing voice problems in this group of professional voice users.

Adult↗
PubMed1998

Learning voice analysis using an interactive multi-media package: development and preliminary evaluation.

An important outcome of education for speech-language pathology practice is the ability to analyze voices perceptually, a complex task that is often difficult for novices. This article describes an interactive multi-media package, "A Sound Judgement," that is designed to help students develop skills in perceptual voice analysis and to link their perceptions to laryngeal physiology. The package presents a range of clients with vocal impairments at increasing levels of complexity. Each case has a videoed interview, endoscopic views and animations of the larynx, and case history information. Students make perceptual ratings of clients' voices on a format designed specifically for this package and feedback is provided using ratings made by expert speech-language pathologists. High levels of consensus for the perceptual judgments were achieved among the expert raters. Preliminary evaluations by students have demonstrated that "A Sound Judgement" is likely to be a valuable educational tool.

Computer-Assisted Instruction↗
PubMed1998

IL-6, IFN-gamma and TNF-alpha production by liver-associated T cells and acute liver injury in rats administered concanavalin A.

The relationship between the development of acute hepatitis and the production of TNF-alpha IFN-gamma and IL-6 by liver-associated T lymphocytes following intravenous injection of concanavalin A (Con A) was studied in rats. Following a single injection of Con A, there was a dose and time-dependent correlation in the serum levels of serum alanine aminotransferase (ALT), IL-6, IFN-gamma and TNF-alpha. These increases correlated with an increase in the numbers of CD4+, CD8+ and CD25+ T cells in blood and CD4+ and CD25+ T cells in the liver perfusate, but not with CD8+ T cells in liver perfusate. Increased levels of IL-6, IFN-gamma and TNF-alpha were constitutively produced by liver-associated CD4+ T cells when cultured. In Con A-stimulated cultures, liver-associated CD4+ T cells secreted increasing levels of TNF-alpha in a time-dependent manner following Con A injection, but TNF-alpha production by peripheral blood lymphocytes was transient with peak levels detected at 1 h which then declined over 24 h. Histological examination of the liver revealed fatty change, hepatocyte degeneration and necrosis, with an associated cell infiltrate of neutrophils and CD4+ T cells both in the portal areas and around the central veins. These results support the hypothesis that Con A-induced liver damage is mediated by CD4+ T cells acting within the liver, at least in part through the secretion of TNF-alpha, IFN-gamma and IL-6.

Alanine Transaminase↗
PubMed1998

Neurologic injuries associated with all-terrain vehicles and recommendations for protective measures for the pediatric population.

OBJECTIVE: To present data and case studies illustrating the danger, especially in the pediatric population, of all-terrain vehicle (ATV) use, and to provide recommendations for pediatricians on how to educate parents concerning ATVs. DESIGN: Retrospective review of 33 patients with neurologic injuries sustained in ATV accidents presenting to one institution over a 40-month period. SETTING: Emergency department and neurosurgery service at Arkansas Children's Hospital and two other hospitals that make up the University of Arkansas for Medical Sciences. PATIENTS: All patients (n = 33) who presented between January 1993 and April 1996 at the emergency departments with neurologic injuries sustained in accidents involving either a three- or four-wheel ATV requiring hospitalization. INTERVENTIONS: Depending on the nature of the injury, various treatments, as described herein. MAIN OUTCOME MEASURES: Demographic measures, the mechanisms of injury, the types of injuries; the current data available regarding the number of injuries nationwide; and the precautionary measures parents should be advised to take. RESULTS: Ages ranged from four to 68 years (mean, 18; median, 14), 21 of the patients were < 16 years old. The predominant age range was 12 to 15 years; most common mechanisms of injury were being thrown to the ground, striking a tree, and flipping backward. Most injuries were cranial (21) or spinal (11). Nationwide, the proportionate number of injuries are decreasing, but the consequences remain severe. Using a helmet and restricting the use of these vehicles will reduce the number and magnitude of injuries. CONCLUSIONS: Although perceived as recreational toys, ATVs can be extremely unsafe, especially for children and adolescents; pediatricians should educate parents and patients on the dangers of riding these vehicles.

Accidents↗
PubMed1998

Acute neutropenia decreases inflammation associated with murine vaginal candidiasis but has no effect on the course of infection.

We have used a mouse model of vaginal candidiasis to determine the effect of neutrophil depletion on (a) the clearance of Candida albicans and (b) the degree of inflammation associated with infection. No differences in recoverable yeast number or rate of clearance were observed between normal and neutrophil-depleted mice; however, vaginal inflammation was significantly decreased in neutrophil-depleted animals.

Acute Disease↗
PubMed1998

Decreased tumor necrosis factor-alpha and interleukin-1alpha production from intrahepatic mononuclear cells in chronic ethanol consumption and upregulation by endotoxin.

The relationship between the changes in liver pathology and the production of interleukin (IL)-1alpha, IL-6, and tumor necrosis factor-alpha (TNF-alpha) by intrahepatic mononuclear cells was studied in rats fed alcohol and subsequently exposed to lipopolysaccharide (LPS). Rats were fed 40% ethanol in drinking water, whereas control rats were provided with a chow diet with isocaloric or 2% sucrose drinking solutions for up to 20 weeks. Decreased IL-1alpha and TNF-alpha production in 24-hr culture supernatants of mononuclear cells isolated from liver perfusate was detected while IL-6 remained unchanged over 20 weeks. When animals were injected with LPS (1.0 microg/kg body weight), there was a 5-fold rise in ALT levels in the ethanol-fed group, but not in control groups. Increased IL-6 and TNF-alpha levels in the serum and supernatant of cultured intrahepatic mononuclear cells stimulated with or without LPS or concanavalin A was observed. There was a correlation between levels of ALT and TNF-alpha, but not IL-6. T cells and Kupffer cells were the major source of TNF-alpha in culture supernatants of hepatic perfusate mononuclear cells from ethanol-consuming rats injected LPS. In addition, pathological liver injury was evident, which suggests a pathogenic role for TNF-alpha in alcohol-induced liver disease.

Animals↗
PubMed1998

Risk factors for gout: a hospital-based study in urban black South Africans.

The clinical features of 90 Black South African patients with gout seen at a large urban hospital were reviewed. The mean age of the patients was 54.3 and 55.3 years for men and women, respectively. The male:female ratio was 3.3:1. All except one of the women were postmenopausal. Seventy-nine percent of patients were from the lower income groups of "blue collar" workers, old-age pensioners or the unemployed. Polyarticular gout was observed in 44.4% of the patients. Tophi were noted in 51.1% of patients but none had a history of renal calculi. Risk factors were assessed by comparing the gouty patients to an equal number of age- and sex-matched hospital controls. Case-control analysis showed a "white collar" occupation (odds ratio = 7.4), obesity (odds ratio = 5.3), alcohol intake (odds ratio = 3.5) and hypertension (odds ratio = 3.3) to be significant risk factors for gout in the overall group of both men and women. In the subgroup of men only, obesity (odds ratio = 7.8), a "white collar" occupation (odds ratio = 6.4), hypertension (odds ratio = 4.9) and alcohol intake (odds ratio = 3.5) were similarly associated with gout. In women, a history of alcohol intake was the only significant risk factor associated with gout (odds ratio = 5.0). These findings suggest that in a population where gout was previously rare, changing dietary habits and lifestyle, together with improving socioeconomic conditions are contributing significantly to the increasing prevalence of the disease.

Adult↗
PubMed1997

Molecular cloning and transient expression in COS7 cells of a novel human PDE4B cAMP-specific phosphodiesterase, HSPDE4B3.

5'-Rapid amplification of cDNA ends, done on poly(A)+ RNA from human U87 cells, was used to identify 420 bp of novel 5' sequence of a PDE4B cAMP-specific phosphodiesterase (PDE). This identified an open reading frame encoding a putative 721-residue 'long-form' PDE4B splice variant, which we term HSPDE4B3. HSPDE4B3 differs from the two known PDE4B forms by virtue of its unique 79-residue N-terminal region, compared with the unique N-terminal regions of 94 and 39 residues found in HSPDE4B1 and HSPDE4B2 respectively. In transfected COS7 cells the two long forms, HSPDE4B1 and HSPDE4B3, had molecular masses of approx. 104 and approx. 103 kDa respectively. Expressed in COS-7 cells, the three HSPDE4B isoforms were found in the high-speed supernatant (cytosol) fraction as well as both the high-speed pellet (P2) and low-speed pellet (P1) fractions. All isoforms showed similar Km values for cAMP hydrolysis (1.5-2.6 microM). The maximal activities of the soluble cytosolic activity of the two long forms were very similar, whereas that of the short form, HSPDE4B2, was approx. 4-fold higher. Particulate-associated HSPDE4B1 and HSPDE4B2 were less active (approx. 40%) than their cytosol forms, whereas particulate HSPDE4B3 was similar in activity to its cytosolic form. Particulate and cytosolic forms of HSPDE4B1 and HSPDE4B3 were similarly inhibited by rolipram {4-[3-(cyclopentoxyl)-4-methoxyphenyl]-2-pyrrolidone}, the selective inhibitor of PDE4 (IC50 0.05-0.1 microM), whereas particulate-associated HSPDE4B2 was profoundly (approx. 10-fold) more sensitive (IC50 0.02 microM) to rolipram inhibition than its cytosolic form (IC50 0.2 microM). The various particulate-associated HSPDE4B isoforms showed very different susceptibilities to solubilization with the detergent Triton X-100 and high NaCl concentration. A novel cDNA, called pRPDE74, was obtained by screening a rat olfactory lobe cDNA library. This contained an open reading frame encoding a 721-residue protein that showed approx. 96% amino acid identity with HSPDE4B3 and is proposed to reflect the rat homologue of this human enzyme and is thus called RNPDE4B3. Alternative splicing of mRNA generated from both the human and rat PDE4B genes produces long and short splice variants that have unique N-terminal splice regions. It is suggested that these alternatively spliced regions determine changes in the maximal catalytic activity of the isoforms, their susceptibility to inhibition by rolipram and mode of interaction with particulate fractions.

3',5'-Cyclic-AMP Phosphodiesterases↗