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Biomedical subjects

R Rose

Publications and source records attributed to R Rose.

At least 37 records · Page 2Linked to original sources

Radar and optical observations of asteroid 1998 KY26

Observations of near-Earth asteroid 1998 KY26 shortly after its discovery reveal a slightly elongated spheroid with a diameter of about 30 meters, a composition analogous to carbonaceous chondritic meteorites, and a rotation period of 10.7 minutes, which is an order of magnitude shorter than that measured for any other solar system object. The rotation is too rapid for 1998 KY26 to consist of multiple components bound together just by their mutual gravitational attraction. This monolithic object probably is a fragment derived from cratering or collisional destruction of a much larger asteroid.

Journal Article↗

Metabolism of [(1)(4)C]prometryn in rats.

[(1)(4)C]Prometryn, 2, 4-bis(isopropylamino)-6-(methylthio)-s-triazine, was orally administered to male and female rats at approximately 0.5 and 500 mg/kg; daily urine and feces were collected. After 3 or 7 days rats were sacrificed, and blood and selected tissues were isolated. The urine and feces extracts were characterized for metabolite similarity as well as for metabolite identification. Over 30 metabolites were observed, and of these, 28 were identified mostly by mass spectrometry and/or cochromatography with available reference standards. The metabolism of prometryn was shown to occur by N-demethylation, S-oxidation, S-S dimerization, OH substitution for NH(2) and SCH(3), and conjugation with glutathione or glucuronic acid. Rat liver microsomal incubations of prometryn were conducted and compared to the in vivo metabolism. Both in vivo and in vitro phase I metabolisms of prometryn were similar, with S-oxidation and N-dealkylation predominating. The involvement of cytochrome P-450 and flavin-containing monooxidase in the in vitro metabolism of prometryn was investigated.

Animals↗

Alcohol consumption in a national sample of the Russian population.

AIMS: Alcohol has been suggested as an important determinant of mortality in Russia but survey data on individuals' alcohol consumption in Russia are sparse. We have analysed the levels and distribution of alcohol consumption in a national sample of the Russian population. DESIGN: Cross-sectional survey. PARTICIPANTS: A multi-stage random sample of men and women of the Russian Federation (N = 1599, response rate 66%). MEASUREMENTS: Data on frequency of drinking alcohol and the average amount consumed at one occasion were collected in an interview. Information was also collected on smoking, self-rated health and a broad range of socio-economic factors and political attitudes. FINDINGS: Nine per cent of men and 35% of women reported that they never drink alcohol; 10% of men and 2% women drink several times a week; 44% of men and 6% of women reported that they drink an equivalent of 25 cl of vodka or more at one occasion and 31% of men and 3% of women would do so at least once a month (25 cl of vodka contains 78.5 g of absolute alcohol). There were differences in alcohol consumption between geographical areas. Material deprivation was not related to alcohol consumption. Among men, smokers, unmarried, unemployed and men reporting poor health consumed more alcohol; women with higher education, widows, non-smoking and with worse health consumed less alcohol. Variables related to reaction to economic and political changes, rating of family economic situation general satisfaction or political preferences were not related to alcohol consumption. CONCLUSIONS: While the overall levels of alcohol consumption appeared low, possibly due to under-reporting, the proportion of men who can be considered as "binge drinkers" was relatively high. The absence of sizable socio-economic differences suggest that drinking may be spread relatively uniformly in Russia, especially among males. Alcohol consumption seems unrelated to individuals' perception of the recent societal changes.

Adolescent↗

Socioeconomic factors, perceived control and self-reported health in Russia. A cross-sectional survey.

Russia has the lowest life expectancy among industrialised countries, but little is known about other health outcomes and determinants of health in the Russian population. Here we report a cross-sectional study in a national sample of the Russian population of social and psychosocial determinants of two self-reported health indicators: self-rated health (shown to predict mortality in prospective studies) and physical functioning (validated against more objective health measures). A multi-stage sample of the Russian population aged 18 years and more was interviewed (n=1599, response rate 66%). The questionnaire included political attitudes, social and economic circumstances, psychosocial factors, smoking, alcohol consumption, self-rated health and physical functioning (from the SF36 instrument). Scores of perceived control over life and over one's health were calculated from 6 and 3 questions, respectively. Data were analysed in logistic regression for two dichotomised outcomes: poor self-rated health (worse than average) and low physical functioning (less than 60% of maximum). Overall, 25% of subjects rated their health as worse than average; this is substantially more than in western countries. Perceived control over life was strongly related to both outcomes; age- and sex-adjusted OR for 1 standard deviation increase in control were 0.60 (95% CI 0.52-0.69) for poor self-rated health and 0.67 (0.57-0.81) for low physical functioning. Adjustment for a battery of other factors reduced these estimates only slightly. Associations between control over one's health and both outcomes were also significant, but weaker and attenuated in multivariate models. Material deprivation was also strongly related to both outcomes. Education was inversely related to self-rated health, and unmarried men reported poor physical functioning substantially more often. Subjects not approving the economic changes reported poorer health but this association was removed by adjustment for socioeconomic factors and control. Subjects who could not rely on informal social structures when in problems reported worse health; this effect largely persisted in multivariate analyses. These results are consistent with the hypothesis that poor health status in Russia is related to dysfunction of social structures, socioeconomic deprivation, and lack of perceived control. The absence of informal social networks, vital for maintaining general welfare, seems to affect adversely self-rated health. Deprivation and low perceived control may be important mediators between the broad social environment and health in populations undergoing transition and can provide a useful framework for many biological and behavioural factors. Prospective studies are needed to address the issue of temporality and reporting bias, the major problems in interpreting these findings.

Activities of Daily Living↗

Patterns of smoking in Russia.

BACKGROUND: Tobacco is a leading cause of avoidable death in Russia but there is, as yet, relatively little information in the public domain on who is smoking and how this is changing. This information is important for those seeking to develop effective policies to tackle this issue. OBJECTIVE: To determine the prevalence of smoking in Russia and its association with sociodemographic factors. DESIGN: Cross-sectional survey on patterns of tobacco consumption. SETTING: Data were collected using the New Russia Barometer, a multi-stage stratified-sample survey of the population of the Russian Federation undertaken in the summer of 1996. PARTICIPANTS: Data were available on 1587 individuals (response rate 65.7%). Respondents differed little from the overall Russian population in terms of age, sex, education, and voting intention. MAIN OUTCOME MEASURES: Prevalence of current and past smoking. RESULTS: Smoking is common among males of all ages and in all areas. Of those aged 18-24 years, 65% smoke, rising to 73% in those aged 25-34 and then falling steadily to reach 41% in those aged 65 and older. Among women, smoking is much more common among the young (27% in those aged 18-34) than among the middle-aged and elderly (5% in those aged 55 and older), and more common among those living in urban areas than in rural areas. Smoking is also more common among men and women suffering material deprivation but there is no independent association with education. Among men, but not women, church attendance is inversely associated with smoking. In both sexes, but especially women, heavy drinking and smoking are associated. CONCLUSIONS: Tobacco poses a major threat to the health of future generations in Russia, especially among women. A robust policy response is required.

Adolescent↗

Radar detection of the nucleus and coma of comet hyakutake

Radar observations of comet Hyakutake (C/1996 B2) made at the Goldstone Deep Space Communications Complex in California have detected echoes from the nucleus and from large grains in the inner coma. The nucleus of this bright comet was estimated to be only 2 to 3 kilometers in diameter. Models of the coma echo indicate backscatter from porous, centimeter-size grains ejected anisotropically at velocities of tens of meters per second. The radar observations suggest that a comet's activity may be a poor indicator of its size and provide evidence that large grains constitute an important component of the mass loss from a typical active comet.

Journal Article↗

Effects of neurochemically excited group III-IV muscle afferents on motoneuron afterhyperpolarization.

When humans voluntarily and maximally contract a muscle under isometric conditions, the average firing rate of motor units decreases from an initially high value over several tens of seconds. The mechanisms underlying the rate reduction are probably manifold. One mechanism could involve changes in the motoneuron afterhyperpolarization, another reflex effects of group III-IV muscle afferents that are excited during developing muscle fatigue. It appears possible that changes in motoneuron afterhyperpolarization are mediated by these afferent inputs. We therefore studied effects on motoneuron afterhyperpolarization of small-diameter muscle afferents excited by intra-arterially injected metabolites such as bradykinin and serotonin. In decerebrate and mostly spinalized cats, lumbosacral alpha-motoneurons were recorded intracellularly. Current pulses were injected to test for input resistance and elicit action potentials and afterhyperpolarizations. Afterhyperpolarizations were averaged from c. 10 successive stimulus repetitions. Measurements were taken of afterhyperpolarization amplitude, half-width and area; and exponential functions were fitted to the afterhyperpolarization decay phase to determine afterhyperpolarization decay time-constants. In selected cases, the entire afterhyperpolarization trajectory was fitted with a sum of two exponentials to assess more precisely changes in afterhyperpolarization trajectory. Small catheters were inserted into side-branches of the sural artery and the accompanying vein to apply substances like bradykinin, serotonin and KCl to the calf muscles. Concentrations were in the range of those used by other workers. Intra-arterial injection of bradykinin and serotonin usually decreased blood pressure, which may at times have affected mean motoneuron membrane potentials. Afterhyperpolarization amplitude usually changed with membrane potential in a way expected from ensuing changes in driving potential. Whenever excitation of group III-IV muscle afferents caused moderate to strong increases in motoneuron synaptic noise, afterhyperpolarization amplitudes were reduced, usually in parallel to decreases in input resistance. Afterhyperpolarization half-widths were mostly unaffected, but occasionally decreased. There was a significant trend for afterhyperpolarization decay time-constants to increase during increased synaptic noise, this increase being inversely correlated with the reduction in afterhyperpolarization amplitude. The reduction in input resistance was associated with a decrease in the membrane time-constant, which could therefore not account for the prolongation of the afterhyperpolarization decay time-constant. The afterhyperpolarization area decreased, indicating that the reduction of afterhyperpolarization amplitude outweighed the prolongation of afterhyperpolarization decay time-constant. During a prolonged fatiguing muscle contraction group III-IV afferents become increasingly excited, produce augmenting synaptic inputs in motoneurons, and will change afterhyperpolarization properties. On average, these changes per se tend to diminish the effect of afterhyperpolarization on motoneuron discharge.

Animals↗

The effect of strenuous versus moderate exercise on the metabolism of proteoglycans in articular cartilage from different weight-bearing regions of the equine third carpal bone.

Articular cartilage degeneration in the middle carpal joint is a common problem in racing horses. This study evaluated the effect of exercise on the in-vitro synthesis of the large aggregating proteoglycans (aggrecan) and two small proteoglycans, biglycan and decorin, in articular cartilage taken from three weight bearing regions of the third carpal bone of horses which were subjected to moderate or strenuous exercise. Twelve Standardbred horses free from clinical and radiographic disease of the middle carpal joint were subjected to an 8 week moderate exercise program. The horses were then randomly assigned to two groups: group A--continued moderate exercise and group B--strenuous exercise for 17 weeks. Horses were then rested for 16 weeks. Full-depth articular cartilage explants from the dorsal radial facet (DRF), dorsal intermediate facet (DIF) and palmar condyle (PC) of the third carpal bone were collected and cultured. Cartilage proteoglycan content and release into culture media were measured. Newly synthesized proteoglycans were labeled with 35SO4(2-) for 48 h and analyzed by size exclusion and hydrophobic chromatography, sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) and autoradiography. Histologic sections of adjacent osteochondral regions were evaluated for evidence of arthritic change. No histologic abnormalities or differences in proteoglycan content were detected in any of the articular cartilage regions examined. There was however, a significant reduction (P < 0.05) in aggrecan synthesis and a concomitant increase in decorin synthesis (P < 0.05) in articular cartilage from the DRF of group B animals. There was no change in biglycan synthesis, aggrecan hydrodynamic size or ability to aggregate in any articular cartilage region. This study has demonstrated that strenuous exercise in horses can lead to a disturbance in the biosynthesis of proteoglycans in articular cartilage regions subjected to high contact stresses (DRF). These metabolic abnormalities, which persisted for 16 weeks after cessation of exercise, could have deleterious effects on the biomechanical properties of the tissue. We suggest that the observed alteration in articular cartilage metabolism in CRF cartilage of strenuously exercised horses could represent a predisposing factor for cartilage degeneration and osteoarthritis at a later stage.

Aggrecans↗

Expression of acquired immunity to the hookworm Ancylostoma ceylanicum in hamsters.

Four experiments are described in which hamsters, initially exposed to primary infection with Ancylostoma ceylanicum, were given a homologous challenge and components of the secondary response were quantified and compared to relevant control groups. The initial establishment of the L3 larvae was not prevented in immunized hamsters but their growth was slowed and virtually all larvae were lost within a week of challenge, when the majority were still at the L4 stage of development. The loss of worms was associated with an accelerated mucosal mastocytosis and increased systemic antibody. Thus acquired immunity to hookworm larvae in this system acted on L3 and L4 stages, thereby preventing larvae from maturing in immunized animals. In contrast to primary infections, immunized hamsters responding to a challenge infection did not lose weight nor did they experience significant anaemia, because of the lack of adult worms. The secondary immune responses therefore prevented manifestation of hookworm disease among immunized-challenged animals.

Ancylostoma↗

Desipramine versus phenelzine in recurrent unipolar depression: clinical characteristics and treatment response.

We compared desipramine with phenelzine in a double-blind, parallel-groups study of 43 outpatients with recurrent unipolar depression. Response to the two drugs was similar, with an overall average reduction in scores on the Hamilton Rating Scale for Depression of about 50% over 6 weeks. Improvement was negatively correlated with initial severity of depression, especially in patients treated with desipramine. Response to desipramine was better in patients with moderate to severe stressors and no previous hospitalizations. Response to either treatment was better in patients whose course consisted of recurrent depressions with a stable baseline, even if the baseline was dysthymic.

Adolescent↗

Use of polymorphic short and clustered coding-region microsatellites to distinguish strains of Candida albicans.

We describe the identification of polymorphic microsatellite loci in the pathogenic yeast, Candida albicans. A search for all coding-region microsatellites with more than four repeats that can be found in Candida sequences in GenBank was conducted. Nine such microsatellite sequences consisting of trinucleotide motifs were found. Three of these were perfect microsatellites while the remaining six sequences were found in one imperfect microsatellite and two compound microsatellites. Because of the close proximity of some of these repeats, all could be assayed with six PCR primer pairs. All of these microsatellite sequences were found in five nuclear genes, ZNF1, CCN1, CPH1, EFG1, and MNT2. Except for a single (CTT)5 serine tract, all coded for polyglutamine tracts. Another locus with seven alleles, a region of the ERK1 protein kinase gene, was also examined, and may be a representative of a new class of highly polymorphic "clustered' microsatellites. Such loci, in which several non-contiguous but closely linked microsatellites are clustered together, may be a useful source of DNA polymorphisms in microorganisms in which long microsatellite sequences are unavailable. All seven regions amplified were polymorphic, having between two and seven variable length alleles in the 11 strains of Candida albicans examined. The results of this and similar searches will facilitate epidemiological and evolutionary studies of Candida and other microorganisms.

Alleles↗

National Asthma Education and Prevention Program working group report on the financing of asthma care.

The financing of asthma care is the third topic of the National Asthma Education and Prevention Program Task Force Report on the Cost Effectiveness, Quality of Care, and Financing of Asthma Care. This working group explored the effects of financing on access to services, treatment of asthma, and potential health outcomes. Over the course of a year, the working group collected and analyzed information pertaining to the various types of public and private health care financing mechanisms, including both insurance-based and non-insurance-based issues. The group examined the published literature and gathered information from four public hearings conducted across the nation. The result of this synthesis of information on health care financing and asthma care is a set of 12 recommendations that seek to improve the financing of asthma care.

Asthma↗

A hyaluronate based gel for the prevention of postsurgical adhesions: evaluation in two animal species.

OBJECTIVE: To assess in two animal surgery models, the efficacy of a bioabsorbable gel to prevent postoperative adhesions. DESIGN: A randomized, prospective, blinded study using animal abdominal surgery models. SETTING: Two animals species with surgical traumas to induce adhesion formation. INTERVENTIONS: A chemically modified hyaluronate and carboxymethylcellulose-based gel formulation. MAIN OUTCOME MEASURES: The number of animals with no adhesions, mean number of adhesions, and total adhesion score. RESULTS: Treatment with the bioabsorbable gel increased the number of animals without any adhesion by 70% in a rat cecal abrasion model and by > 90% in a rabbit sidewall defect-bowel abrasion model when compared with nontreatment control animals. Other outcome measures showed similar efficacy. CONCLUSION: The modified hyaluronate-carboxymethylcellulose gel was effective in two animal species after surgery in the abdominal cavity. The gel appears to act as a physical barrier between damaged peritoneal tissue and may be appropriate for human clinical trials in open and laparoscopic surgical procedures.

Abdominal Muscles↗

Kinetics of circulating adhesion molecules and chemokines after mechanical trauma and burns.

OBJECTIVE: To assess the role of circulating adhesion molecules and chemotactic cytokines within different settings of major trauma. DESIGN: Retrospective study. SETTING: Teaching hospitals, USA and Germany. SUBJECTS: Two groups of patients with multiple injuries (group I n = 155 and group II n = 12) with mean (SEM) injury severity scores (ISS) of 35 (4) and 32 (4) points, respectively, and 18 burned patients with a mean of ISS 38 (9) points. INTERVENTIONS: Serum samples were collected at the site of the accident and on admission to the (Group I) as well as during the post-trauma course in the hospital (Group II: days 1, 3, 5, 7, 10; Group III; weekly, up to week 10). MAIN OUTCOME MEASURES: Measurement of concentrations of soluble (s) adhesion molecules (sE-selectin, sP-selectin), and chemotactic cytokines (interleukin-8 [IL-8], epithelial cell derived neutrophil activating peptide 78 [ENA-78]) in serum after major mechanical trauma and burns. RESULTS: High concentrations of ENA-78 and sP-selectin were already present at the site of accident as well as one hour after injury. During recovery from the injuries, persistently high concentrations of IL-8, ENA-78, and sP-selectin were found, but sE-selectin was increased only during the first week after major trauma. CONCLUSION: Massive tissue trauma causes immediate activation of selected chemokines and adhesion molecules within minutes of the injury which will then persist depending on the type and severity of the injury for a substantial length of time. There was, however, no correlation between serum concentrations of the mediators investigated and susceptibility to complications or outcome.

Adolescent↗

Characterization of a human immunodeficiency virus type 1 variant with reduced sensitivity to an aminodiol protease inhibitor.

Development of viral resistance to the aminodiol human immunodeficiency virus (HIV) protease inhibitor BMS 186,318 was studied by serial passage of HIV type 1 RF in MT-2 cells in the presence of increasing concentrations of compound. After 11 passages, an HIV variant that showed a 15-fold increase in 50% effective dose emerged. This HIV variant displays low-level cross-resistance to the C2 symmetric inhibitor A-77003 but remains sensitive to the protease inhibitors Ro 31-8959 and SC52151. Genetic analysis of the protease gene from a drug-resistant variant revealed an Ala-to-Thr change at amino acid residue 71 (A71T) and a Val-to-Ala change at residue 82 (V82A). To determine the effects of these mutations on protease and virus drug susceptibility, recombinant protease and proviral HIV type 1 clones containing the single mutations A71T and V82A or double mutation A71T/V82A were constructed. Subsequent drug sensitivity assays on the mutant proteases and viruses indicated that the V82A substitution was responsible for most of the resistance observed. Further genotypic analysis of the protease genes from earlier passages of virus indicated that the A71T mutation emerged prior to the V82A change. Finally, the level of resistance did not increase following continued passage in increasing concentrations of drug, and the resistant virus retained its drug susceptibility phenotype 34 days after drug withdrawal.

Amino Acid Sequence↗

Development of a lipopeptide-based therapeutic vaccine to treat chronic HBV infection. I. Induction of a primary cytotoxic T lymphocyte response in humans.

Our goal is to use peptide epitopes that are recognized by cytotoxic T lymphocytes (CTL) as immunogens for the development of prophylactic and therapeutic vaccines with chronic hepatitis B virus (HBV) infection being our first therapeutic target. Because most CTL peptide epitopes are poor immunogens, we specifically modified them by covalently attaching two additional components: a T helper peptide epitope and two lipid molecules. Using the murine influenza virus CTL epitope NP 147-155 as a model system, we found this construct to be highly immunogenic, and a single injection resulted in memory CTL induction that persisted for > 1 yr. Based on the animal studies, a vaccine was designed and tested for both safety and its ability to induce a primary CTL response in normal subjects. The three vaccine components included HBV core antigen peptide 18-27 as the CTL epitope, tetanus toxoid peptide 830-843 as the T helper peptide, and two palmitic acid molecules as the lipids. A dose escalation trial (5, 50, and 500 micrograms) carried out in 26 normal subjects showed that the vaccine was safe and able to induce a primary HBV-specific CTL response. A dose-response curve was observed and five out of five subjects responded to the 500-micrograms dose.

Adolescent↗

The role of the left prefrontal cortex in verbal processing: semantic processing or willed action?

This study was designed to test the various proposed explanations (semantic processing, willed action, production of a spoken response) for the unilateral activation of the left prefrontal cortex noted in PET studies of verbal processing. Twenty subjects underwent 15O-water PET scans while undertaking a lexical task (detecting the letter 'a' in visually presented words) and a semantic task (categorizing nouns into living/non-living). The semantic task resulted in a significant unilateral left dorsolateral prefrontal activation. This finding suggests that the left inferior prefrontal cortex is the anatomical region involved in 'working with meaning', and that the activation does not reflect willed action, is not task-specific and is not attributable to the requirements of a spoken response.

Adult↗

Resistance of the hookworms Ancylostoma ceylanicum and Necator americanus to intestinal inflammatory responses induced by heterologous infection.

Experiments were carried out to ascertain whether the acute inflammatory phase of the intestinal response of hamsters to infection with Trichinella spiralis would adversely affect hookworms in concurrently infected animals. The survival and growth of hookworms were unaffected. However, the presence of hookworms reduced the establishment of T. spiralis, the initial growth of female worms and their fecundity. The expulsion of T. spiralis was also significantly slower in concurrently infected animals and there was significant depression of the serum IgG antibody response to muscle stage and adult worm antigens of T. spiralis in concurrently infected animals. These results are discussed in relation to the chronicity of human hookworm infections.

Acute Disease↗