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Biomedical subjects

J Ross

Publications and source records attributed to J Ross.

At least 91 records · Page 5Linked to original sources
PubMed2000

FHL2 (SLIM3) is not essential for cardiac development and function.

LIM domain-containing proteins play critical roles in vertebrate development and cellular differentiation. Recently, four members of the four and one-half LIM protein (FHL) family have been identified and cloned. One of these, FHL2, is expressed in a restricted manner in the cardiovascular system throughout development into adulthood, suggesting that FHL2 may play an important role in cardiovascular development and function. Here we describe the generation and analysis of mice carrying a null mutation of the FHL2 gene. FHL2-deficient mice are viable and maintain normal cardiac function both before and after acute mechanical stress induced by aortic constriction. These data suggest that FHL2 is not essential for cardiac development and function.

Animals↗
PubMed2000

Geomapping of chlamydia and gonorrhoea in Birmingham.

OBJECTIVE: To investigate if the core population hypothesis is applicable to patients with genital chlamydia infections. DESIGN: Retrospective cross sectional study. SETTING: Two genitourinary medicine (GUM) clinics in the city of Birmingham and eight adjacent clinics. SUBJECTS: All patients with chlamydia (n = 665) or gonorrhoea (n = 584) attending between 1 October 1995 and 30 September 1996 with a postcode within the Birmingham health district. Controls were 727 patients seen in the same period with no infection. METHODS: Postcodes were used to calculate population prevalence rates per 100,000 aged 15-65 in the 39 wards of the city and to estimate the socioeconomic status using the Super Profile (SP). Ethnic specific rates were also calculated. Data were obtained on gonorrhoea and chlamydia isolation from all the major laboratories of the city over the same time period. RESULTS: GUM clinic attenders accounted for 67.6% and 82.5% of all chlamydia and gonorrhoea isolates reported by the laboratories and that were available for our epidemiological analysis. Both infections were more common in men and in black ethnic groups. However, patients with gonorrhoea only infection were more likely to be of black ethnicity than those with chlamydia only infection (p = 0.0001) and to have different SP distribution (p = 0.0001). On logistic regression age < 20 years, male sex, black ethnicity, and living in neighbourhoods with SP J ("have nots") were predictive of both infections compared with controls. Overall chlamydia and gonorrhoea prevalence rates were 129 and 98.4 per 10(5) respectively. Corresponding rates for whites was 64.7 and 37.2 and for black ethnic groups 1105 and 1183 per 10(5) of each ethnic group. Eight adjacent wards accounted for 41% of the chlamydia and 66.5% of the gonorrhoea. CONCLUSION: In a large urban setting patients attending GUM clinics with chlamydia belong to core population groups with similar, but not identical, sociodemographic characteristics to patients with gonorrhoea infection.

Adolescent↗
PubMed2000

How much interest is the Internet to patients?

OBJECTIVES: To assess the accessibility of the internet, the level of interest from patients attending genitourinary (GU) medicine clinics, and explore potential concerns about confidentiality. METHODS: Questionnaire based survey of patients attending five GU medicine clinics in England. RESULTS: 41% of GU medicine clinic patients in 1999 had access to the internet (range 31%-52%) with access more common in younger age groups, and less common in women and black Caribbean patients. One in 10 patients (with internet access) had used the internet to find out more about the problem with which they had come to the clinic. 60% of patients replied that information on sexual health on the internet was of interest to them and a high proportion of patients said they would use the internet to access information about GU clinics (64%), book an appointment (64%) or get test results (63%). Almost a quarter of patients who made additional suggestions wanted an interactive website. CONCLUSIONS: A high proportion of patients attending GU clinics have access to the internet with potential uses for health education and service delivery.

Adolescent↗
PubMed2000

Altered membrane proteins and permeability correlate with cardiac dysfunction in cardiomyopathic hamsters.

A mutation in the delta-sarcoglycan (SG) gene with absence of delta-SG protein in the heart has been identified in the BIO14.6 cardiomyopathic (CM) hamster, but how the defective gene leads to myocardial degeneration and dysfunction is unknown. We correlated left ventricular (LV) function with increased sarcolemmal membrane permeability and investigated the LV distribution of the dystrophin-dystroglycan complex in BIO14.6 CM hamsters. On echocardiography at 5 wk of age, the CM hamsters showed a mildly enlarged diastolic dimension (LVDD) with decreased LV percent fractional shortening (%FS), and at 9 wk further enlargement of LVDD with reduction of %FS was observed. The percent area of myocardium exhibiting increased membrane permeability or membrane rupture, assessed by Evans blue dye (EBD) staining and wheat germ agglutinin, was greater at 9 than at 5 wk. In areas not stained by EBD, immunostaining of dystrophin was detected in CM hamsters at sarcolemma and T tubules, as expected, but it was also abnormally expressed at the intercalated discs; in addition, the expression of beta-dystroglycan was significantly reduced compared with control hearts. As previously described, alpha-SG was completely deficient in CM hearts compared with control hearts. In myocardial areas showing increased sarcolemmal permeability, neither dystrophin nor beta-dystroglycan could be identified by immunolabeling. Thus, together with the known loss of delta-SG and other SGs, abnormal distribution of dystrophin and reduction of beta-dystroglycan are associated with increased sarcolemmal permeability followed by cell rupture, which correlates with early progressive cardiac dysfunction in the BIO14.6 CM hamster.

Animals↗
PubMed2000

Pharmacological treatments for alcoholism: revisiting lithium and considering buspirone.

OBJECTIVE: Previous research has suggested that both lithium and buspirone could lessen alcoholics' desire to drink as well as reduce the actual amounts of alcohol consumed. The purpose of this study was to compare lithium and buspirone monotherapy with placebo on outcomes of abstinence, alcohol quantity consumed, treatment retention and compliance, and medication side effects. METHODS: We conducted a randomized, double-blind, placebo-controlled, three-arm parallel group, clinical trial that compared lithium and buspirone with placebo in 156 alcohol-dependent men. RESULTS: Study retention rates for the three treatment groups at 3 and 6 months, respectively, were 61% and 46% for lithium, 44% and 27% for buspirone, and 52% and 38% for placebo (p = NS, for 3 and 6 months). Overall abstinence rates were 28% and 19% at 3 and 6 months, respectively. However, mean daily quantities of alcohol consumed and percentage of drinking days decreased significantly (p < 0.0001) over time in all treatment groups. Differential improvement was seen only for the decrement in quantity consumed in the buspirone group, compared with the placebo group, but only at a trend level (p = 0.07). According to pill counts, compliance did not differ significantly among the treatment groups. CONCLUSIONS: These results do not support the hypothesis that either lithium or buspirone, compared with placebo, produces differential reductions in alcohol consumption. The results suggest the need to enhance treatment retention to maximize outcomes.

Adult↗
PubMed2000

Presentation with influenza-like illness in general practice: implications for use of neuraminidase inhibitors.

General practitioners in the Midlands Research Practice Consortium (MidReC), combined list size 140,000, completed questionnaires about 918 patients in whom they had made working diagnoses of influenza-like illness during an outbreak of influenza A H3N2 from 1 December 1999 to 4 February 2000. Adults, more females than males consulted most, reflecting the age and sex distribution reported to the Royal College of General Practitioners Weekly Returns Service. Illness at presentation was considered severe in 4%, moderately severe in 49%, mild in 45%, and asymptomatic (for example, attended for certificates) in 1% of patients. In seven tenths of patients, the practitioner estimated that the likelihood of influenza was 70% or more and in just over half, 80% or more. Half of patients aged over 75 years were seen at home, but only 7% of those under 55 years. Less than a quarter of patients consulted within two days of having become ill, with the highest consultation frequency on the third and fourth days. Preschool children presented earliest: 75% were seen within two days, compared with only 17% of adults over 75 years. Four fifths of patients were seen on the same day as they contacted the practice, and 12% on the following day. Given the brief time window for effective antiviral treatment, only a small proportion of patients are likely to be prescribed these drugs unless consulting behaviour, especially in elderly people, changes considerably.

Adolescent↗
PubMed1999

Chronic phospholamban-sarcoplasmic reticulum calcium ATPase interaction is the critical calcium cycling defect in dilated cardiomyopathy.

Dilated cardiomyopathy and end-stage heart failure result in multiple defects in cardiac excitation-contraction coupling. Via complementation of a genetically based mouse model of dilated cardiomyopathy, we now provide evidence that progressive chamber dilation and heart failure are dependent on a Ca2+ cycling defect in the cardiac sarcoplasmic reticulum. The ablation of a muscle-specific sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) inhibitor, phospholamban, rescued the spectrum of phenotypes that resemble human heart failure. Inhibition of phospholamban-SERCA2a interaction via in vivo expression of a phospholamban point mutant dominantly activated the contractility of ventricular muscle cells. Thus, interfering with phospholamban-SERCA2a interaction may provide a novel therapeutic approach for preventing the progression of dilated cardiomyopathy.

Animals↗
PubMed1999

Genetic alterations in early-onset invasive breast carcinomas: correlation of c-erbB-2 amplification detected by fluorescence in situ hybridization with p53 accumulation and tumor phenotype.

p53 tumor-suppressor gene mutation and p53 protein over-expression have been reported with higher frequency in early-onset breast carcinomas (EOBC). Given the role attributed to normal p53 protein in DNA-repair mechanisms, other somatic genomic alterations would be expected to be associated with this abnormality. Amplification of the c-erbB-2 (HER-2/neu) oncogene and over-expression of the corresponding p185erbB-2 protein have been linked to prognosis and response to therapy in breast cancer. In a retrospective study of 62 formalin-fixed paraffin-embedded invasive EOBC (diagnosed at 35 years or less), the amplification status of the c-erbB-2 gene detected by fluorescence in situ hybridization (FISH) using a unique sequence probe was compared with p53 protein accumulation measured by immunohistochemistry (IHC) and phenotypic features. p185erbB2-protein expression was also detected by immunohistochemistry, together with estrogen-receptor (ER) and progesterone-receptor (PR) expression. The data for a sub-set of 33 node-negative EOBC cases were compared with 70 node-negative tumors diagnosed in women above 36 years of age. Compared with node-negative BC in older women, node-negative EOBC was significantly more likely to feature high grade, high proliferation rate, negative ER and/or PR and p53 over-expression (p < 0.05). A trend toward a higher incidence of c-erbB-2 amplification in EOBC (21% vs. 9%) reached near-significance (p = 0.07). In EOBC, c-erbB-2 amplification and p53 over-expression were not associated with high tumor grade or high cell-proliferation rate, in contrast to the significant associations of these markers in tumors in older women. Abnormalities in tumor markers, including c-erbB-2 gene amplification and p53-protein over-expression, occur at different rates in women with EOBC as compared with BC developing in older women. This finding may reflect a different pathogenesis for EOBC, and warrants further investigation.

Adult↗
PubMed1999

Progressive cardiac dysfunction and fibrosis in the cardiomyopathic hamster and effects of growth hormone and angiotensin-converting enzyme inhibition.

BACKGROUND: Growth hormone (GH) improves cardiac function in the rat with myocardial infarction, but its effects in a model of primary dilated cardiomyopathy have not been reported. GH effects were examined at early (4 months) and late (10 months) phases of disease in the cardiomyopathic (CM) hamster, and the combination of GH with chronic ACE inhibition was assessed in late-phase heart failure. METHODS AND RESULTS: CM hamsters (CHF 147 line) at 4 months showed severe systolic left ventricular (LV) dysfunction with normal LV filling pressure, and at 10 months there was more severe systolic as well as diastolic dysfunction with increasing myocardial fibrosis. Recombinant human GH alone for 3 weeks at age 4 months increased LV wall thickness and reduced systolic wall stress without altering diastolic wall stress, whereas at 10 months, wall stress and fractional shortening did not improve. The LV dP/dt(max) was enhanced at both ages by GH, which at 4 months reflected increased contractility, but at 10 months was most likely caused by elevation of the LV filling pressure. The increasing degree of fibrosis correlated inversely with LV function but was unaffected by GH. In other CM hamsters, high-dose ACE inhibition alone (quinapril), started at 8 months and continued for 11 weeks, improved LV function and inhibited unfavorable remodeling, but the addition of GH for 3 weeks at age 10 months produced increased wall thickness with little additional functional benefit and increased the LV filling pressure and diastolic wall stress. CONCLUSIONS: GH treatment alone improved LV dysfunction at 4 months of age in CM hamsters by increasing contractility and reducing wall stress but had few beneficial effects at 10 months in severe LV failure. After chronic ACE inhibition, addition of GH at 10 months had no additional beneficial effects and further increased LV diastolic pressure. These differing effects of GH may relate to the progressive increase of LV fibrosis in the CM hamster.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Phenological changes reflect climate change in Wisconsin.

A phenological study of springtime events was made over a 61-year period at one site in southern Wisconsin. The records over this long period show that several phenological events have been increasing in earliness; we discuss evidence indicating that these changes reflect climate change. The mean of regressions for the 55 phenophases studied was -0.12 day per year, an overall increase in phenological earliness at this site during the period. Some phenophases have not increased in earliness, as would be expected for phenophases that are regulated by photoperiod or by a physiological signal other than local temperature.

Journal Article↗
PubMed1999

Loss of a gp130 cardiac muscle cell survival pathway is a critical event in the onset of heart failure during biomechanical stress.

Biomechanical stress is a major stimulus for cardiac hypertrophy and the transition to heart failure. By generating mice that harbor a ventricular restricted knockout of the gp130 cytokine receptor via Cre-IoxP-mediated recombination, we demonstrate a critical role for a gp130-dependent myocyte survival pathway in the transition to heart failure. Such conditional mutant mice have normal cardiac structure and function, but during aortic pressure overload, these mice display rapid onset of dilated cardiomyopathy and massive induction of myocyte apoptosis versus the control mice that exhibit compensatory hypertrophy. Thus, cardiac myocyte apoptosis is a critical point in the transition between compensatory cardiac hypertrophy and heart failure. gp130-dependent cytokines may represent a novel therapeutic strategy for preventing in vivo heart failure.

Animals↗
PubMed1999

A post-transcriptional compensatory pathway in heterozygous ventricular myosin light chain 2-deficient mice results in lack of gene dosage effect during normal cardiac growth or hypertrophy.

Our previous study of homozygous mutants of the ventricular specific isoform of myosin light chain 2 (mlc-2v) demonstrated that mlc-2v plays an essential role in murine heart development (Chen, J., Kubalak, S. W., Minamisawa, S., Price, R. L., Becker, K. D., Hickey, R., Ross, J., Jr., and Chien, K. R. (1998) J. Biol. Chem. 273, 1252-1256). As gene dosage of some myofibrillar proteins can affect muscle function, we have analyzed heterozygous mutants in depth. Ventricles of heterozygous mutants displayed a 50% reduction in mlc-2v mRNA, yet expressed normal levels of protein both under basal conditions and following induction of cardiac hypertrophy by aortic constriction. Heterozygous mutants exhibited cardiac function comparable to that of wild-type littermate controls both prior to and following aortic constriction. There were no significant differences in contractility and responses to calcium between wild-type and heterozygous unloaded cardiomyocytes. We conclude that heterozygous mutants show neither a molecular nor a physiological cardiac phenotype either at base line or following hypertrophic stimuli. These results suggest that post-transcriptional compensatory mechanisms play a major role in maintaining the level of MLC-2v protein in murine hearts. In addition, as our mlc-2v knockout mutants were created by a knock-in of Cre recombinase into the endogenous mlc-2v locus, this study demonstrates that heterozygous mlc-2v cre knock-in mice are appropriate for ventricular specific gene targeting.

Animals↗
PubMed1999

Effects of testosterone on sexual behavior and morphology in adult female leopard geckos, Eublepharis macularius.

The leopard gecko, Eublepharis macularius, is a species in which testosterone (T) is the primary circulating sex hormone in adults of both sexes. There are, however, sex differences in T physiology. Whereas males have prolonged periods with high T levels, T levels cycle in accord with follicular development in females. Specifically, T concentration increases during vitellogenesis, drops after ovulation, and then remains at previtellogenic levels until eggs are laid and the next follicular cycle begins. To determine the function of T in females, we manipulated both the level and the duration of T elevation using Silastic implants in intact, adult female leopard geckos. Females had low ( approximately 1 ng/ml), medium ( approximately 100 ng/ml), or high ( approximately 200 ng/ml) T levels for either a short (8 days) or a long (35 days) duration. Behavior tests with males were conducted on days 1-5 in the short-duration group or on days 29-33 in the long-duration group. For both short- and long-duration groups, T treatment decreased attractivity in females with medium and high T levels compared to females with low T levels. In contrast, females with a medium T level were more receptive than females with a low T level in the short-duration group. Females in the long-duration group were unreceptive regardless of T level. Females treated for a long duration also displayed more aggression toward and evoked more aggression from males than short duration females. Short-duration T treatment had no masculinizing effect on female morphology, whereas medium and high T levels for a long duration induced development of hemipenes. Overall, these results suggest that T can both increase and decrease sexual behaviors in the female leopard gecko.

Aggression↗
PubMed1999

Assays for analyzing exonucleases in vitro.

Ribonucleases play essential roles in cell growth, differentiation, and the response to stress. This article deals with exoribonucleases, enzymes that degrade RNAs beginning at either the 5' or 3' end and proceed down the length of the RNA. The preparation of a crude extract of a mammalian 3'-to-5' exonuclease is described. Assay conditions for both 5'-to-3' and 3'-to-5' exonucleases are given. One of these is a yeast enzyme that is known to be involved in mRNA decay. Others are vertebrate exonucleases that are presumed to have a role in mRNA stability but have not yet been proven to do so.

Animals↗
PubMed1999

Spatial limitations of temporal segmentation.

We investigated the spatial parameters that permit temporal phase segmentation. Subjects identified a stimulus quadrant which was modulated 180 degrees out of phase with the rest of the stimulus at temporal frequencies between 2 and 30 Hz. We determined the modulation sensitivity for regular square lattices of Gaussian spots and a stimulus made from solid quadrants with varying separation. Sensitivity declined rapidly when spatial separation of the modulating areas was approximately 0.4 degree, but was relatively unchanged by further spatial separations. The results suggest that there are two systems that can detect temporal phase differences. The first is a segregation process that operates below 10 Hz, where phase can be consciously followed and compared across large retinal distances. The second system is a segmentation mechanism that operates at higher temporal frequencies but only over a short range.

Humans↗