Dolphin beta-glucocerebrosidase, map position 1q22.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
S Davis
Publications and source records attributed to S Davis.
Should women be treated with testosterone?
Explore the source record for details and available documents.
Adult↗
Increase in syntaxin 1B and glutamate release in mossy fibre terminals following induction of LTP in the dentate gyrus: a candidate molecular mechanism underlying transsynaptic plasticity.
A growing body of evidence suggests that modulation of certain proteins of the exocytotic machinery is, in part, involved in the biochemical changes that underlie long-term synaptic plasticity. We have previously shown that the induction of long-term potentiation (LTP) at perforant path to dentate granule cell synapses in the rat hippocampus induces changes in the mRNA levels of syntaxin 1B and synapsin I, known to be involved in neurotransmitter release. Immunohistochemical staining suggested that concomitant changes in these proteins occurred at mossy fibre synapses, downstream of those synapses at which LTP was induced, leading us to postulate that such a mechanism might underlie a form of transsynaptic plasticity. Here we have used a specific mossy-fibre synaptosome preparation to quantify levels of proteins and measure, using a chemiluminescent glutamate assay, depolarization-induced glutamate release from these synaptosomes after induction of LTP in the dentate gyrus in vivo. We show that 5 h after the induction of LTP, there is an increase in the protein levels of syntaxin 1B and, although to a lesser extent, the synapsins I and II, associated with an increase in depolarization-induced release of glutamate within these terminals. Increases in both the protein levels and glutamate release were not observed when dentate gyrus LTP was blocked by an NMDA receptor antagonist. From these results we propose a molecular mechanism for the propagation of synaptic plasticity through hippocampal circuits.
Animals↗
Induction of long-term potentiation in vivo regulates alternate splicing to alter syntaxin 3 isoform expression in rat dentate gyrus.
The regulation and specificity of the interactions between the proteins involved in neurotransmitter release are obvious targets for the cellular control of synaptic plasticity. Previous research has identified one of these proteins, syntaxin 1B, as a potential target for mediating the propagation of synaptic plasticity through neural networks. The expression of syntaxin 1B is modified in the hippocampus after the induction of long-term potentiation (LTP) and during learning. Here, we describe the identification of two other members of the syntaxin family from rat brain, syntaxins 3A and 3B, and show that they are generated from the same gene by alternate splicing. In situ hybridization and immunohistochemical staining confirm the expression of syntaxins 3A and 3B in the adult rat brain. The transcripts and proteins show a lower abundance but a similar pattern of expression as syntaxins 1A and 1 B. By using quantitative competitive PCR, we show that the mRNAs that encode syntaxins 1B and 3A are increased in dentate granule cells 6 h after the induction of LTP in vivo, whereas syntaxin 3B mRNA is decreased as rapidly as 30 min, and lasts for at least 6 h, after the induction of LTP. These findings identify coordinated changes in the expression of several syntaxin isoforms with different substrate specificities and suggest that regulation of the splicing machinery by LTP induction is one of the diverse strategies used during the long-term modification of the synapse in the vertebrate nervous system.
Alternative Splicing↗
Linkage and association between inflammatory bowel disease and a locus on chromosome 12.
Genetic epidemiological studies have shown that genetic factors are important in the pathogenesis of the idiopathic inflammatory bowel diseases (IBD), Crohn disease (CD), and ulcerative colitis (UC). A genome screen in the United Kingdom found linkage of IBD to a 41-cM region of chromosome 12, surrounding D12S83. We aimed to replicate this linkage and to narrow the region of interest. Nonparametric linkage analyses at microsatellites surrounding D12S83 were performed in 122 North American Caucasian families containing 208 genotyped IBD-affected relative pairs. Transmission/disequilibrium tests (TDTs) were also performed. We confirmed that IBD is linked to chromosome 12 (peak GENEHUNTER-PLUS LOD* score 2.76 [P = .00016] between D12S1724 and D12S90). The evidence for linkage is contributed by both the group of CD-affected relative pairs (peak GENEHUNTER-PLUS LOD* score 1.79 [P = .0021] between D12S1724 and D12S90) and the group of UC-affected relative pairs (peak GENEHUNTER-PLUS LOD* score 1.82 [P = .0019] at D12S335). The TDT is positive at the D12S83 locus (global chi2 = 16.41, 6 df, P = .012). In conclusion, we have independently confirmed linkage of IBD to the chromosome 12 region that we investigated. A positive TDT at D12S83 suggests that we have greatly narrowed the chromosome 12 region that contains an IBD locus.
Chromosomes, Human, Pair 12↗
Total parenteral nutrition via multilumen catheters does not increase the risk of catheter-related sepsis: a randomized, prospective study.
The purpose of this study was to determine in a randomized, prospective manner whether administration of total parenteral nutrition (TPN) via multilumen catheters increases the risk of catheter-related sepsis (CRS). All patients receiving hyperalimentation during a 24-month period were randomized to receive either a double-lumen catheter (DLC) or a triple-lumen catheter (TLC). A total of 101 catheters were placed in 79 patients, of which 49 were DLCs and 52 were TLCs. The patients with DLCs received a total of 784 days of TPN, whereas patients with TLCs received a total of 754 days of TPN. CRS was associated with one (2.0%) of the 49 DLCs vs. one (1.9%) of the 52 TLCs. In comparison, the rate of CRS associated with single-lumen catheters (historical control) at our institution was 1.4% (P > .90). We conclude that the use of multilumen catheters in TPN therapy does not result in an increased risk of CRS.
Catheterization, Central Venous↗
Formative research in a school-based obesity prevention program for Native American school children (Pathways).
This paper describes how formative research was developed and implemented to produce obesity prevention interventions among school children in six different Native American nations that are part of the Pathways study. The formative assessment work presented here was unique in several ways: (1) it represents the first time formative research methods have been applied across multiple Native American tribes; (2) it is holistic, including data collection from parents, children, teachers, administrators and community leaders; and (3) it was developed by a multi-disciplinary group, including substantial input from Native American collaborators. The paper describes the process of developing the different units of the protocol, how data collection was implemented and how analyses were structured around the identification of risk behaviors. An emphasis is placed on describing which units of the formative assessment protocol were most effective and which were less effective.
Child↗
Health education to increase screening for cervical cancer among Lumbee Indian women in North Carolina.
Although age-adjusted mortality rates from cancer among Native-Americans are generally lower than for the US population as a whole, cervical cancer mortality rates are higher. This report presents results from a National Cancer Institute-funded health education program conducted among the Lumbee tribe in North Carolina that was designed to increase the proportion of women, age 18 and older, who receive Pap smears to screen for cervical cancer. The Solomon Four Group research design was used for this project. Participants were selected at random from the enrollment records of the Lumbee tribe and data collection was carried out during face-to-face interviews. The health education program was provided one-on-one in women's homes by a trained lay health educator and included verbal, print and videotape information. A total of 979 women were enrolled in the study, and 125 were lost to follow-up between the pre-test and post-test. Women who received the education program were found to be more likely to have knowledge of the Pap smear and to report a Pap smear in the past year at the post-test than those in the control group, regardless of whether they received the pre-test interview, P < 0.05. Women most likely to respond to the education program were also likely to have reported that they receive an annual physical examination. Women with better knowledge of the Pap smear tended to have more education, higher income and greater identification with Native-American culture than those with less knowledge. We conclude that the health education program was associated with greater knowledge about cervical cancer prevention and higher proportions of Lumbee women obtaining Pap smears in the past year.
Adolescent↗
Preservation of hypoxic pulmonary vasoconstriction during sevoflurane and desflurane anesthesia compared to the conscious state in chronically instrumented dogs.
BACKGROUND: The authors' objective was to assess the extent to which sevoflurane and desflurane anesthesia alter the magnitude of hypoxic pulmonary vasoconstriction compared with the response measured in the same animal in the conscious state. METHODS: Left pulmonary vascular pressure-flow plots were generated in seven chronically instrumented dogs by continuously measuring the pulmonary vascular pressure gradient (pulmonary arterial pressure-left atrial pressure) and left pulmonary blood flow during gradual (approximately 1 min) inflation of a hydraulic occluder implanted around the right main pulmonary artery. Pressure-flow plots were generated during normoxia and hypoxia on separate days in the conscious state, during sevoflurane (approximately 3.5% end-tidal), and during desflurane (approximately 10.5% end-tidal) anesthesia. Values are mean+/-SEM. RESULTS: In the conscious state, administration of the hypoxic gas mixture by conical face mask decreased (P < 0.01) systemic arterial PO2 from 94+/-2 mmHg to 50+/-1 mmHg and caused a leftward shift (P < 0.01) in the pressure-flow relationship, indicating pulmonary vasoconstriction. The magnitude of hypoxic pulmonary vasoconstriction in the conscious state was flow-dependent (P < 0.01). Neither anesthetic had an effect on the baseline pressure-flow relationship during normoxia. The magnitude of hypoxic pulmonary vasoconstriction during sevoflurane and desflurane was also flow-dependent (P < 0.01). Moreover, at any given value of flow the magnitude of hypoxic pulmonary vasoconstriction was similar during sevoflurane and desflurane compared with the conscious state. CONCLUSION: These results indicate that hypoxic pulmonary vasoconstriction is preserved during sevoflurane and desflurane anesthesia compared with the conscious state. Thus, inhibition of hypoxic pulmonary vasoconstriction is not a general characteristic of inhalational anesthetics. The flow-dependent nature of the response should be considered when assessing the effects of physiologic or pharmacologic interventions on the magnitude of hypoxic pulmonary vasoconstriction.
Anesthesia↗
Synergistic effects of combined converting enzyme inhibition and angiotensin II antagonism on blood pressure in conscious telemetered spontaneously hypertensive rats.
OBJECTIVE: To investigate the chronic effects of combined administration of an angiotensin II receptor antagonist (valsartan) and an angiotensin converting enzyme inhibitor (benazeprilat) on blood pressure and heart rate in conscious telemetered spontaneously hypertensive rats. METHODS: Blood pressure and heart rate were monitored (by radiotelemetry) during 2-week infusions of 0.5-10 mg/kg valsartan per day and 0.5-10 mg/kg benazeprilat per day, alone or in combination, into conscious spontaneously hypertensive rats. Also, responses of blood pressure in conscious spontaneously hypertensive rats to exogenous angiotensin I and II were determined. RESULTS: Synergistic antihypertensive effects were observed when valsartan and benazeprilat were coadministered at submaximal monotherapy doses in the range 0.5-1.5 mg/kg per day. For all combination groups, the area over the curve (mmHg x days) for lowering of blood pressure was significantly greater (synergy) than that predicted from the sum of the monotherapy responses. Combination therapy abrogated pressor responses to angiotensin I more effectively than did comparable doses of the monotherapies. CONCLUSIONS: These results demonstrate that combination therapy aimed at interrupting operation of the renin-angiotensin system simultaneously at multiple sites can prevent the partial escape which occurs during chronic angiotensin converting enzyme inhibitor monotherapy. Furthermore, multiple-site intervention results in a more efficacious antihypertensive response than that achieved with high doses of the individual monotherapies.
Angiotensin Receptor Antagonists↗
Gastrointestinal bleeding after cold biopsy.
Cold biopsy of the gastric mucosa is useful in many gastroduodenal disorders. Antral biopsies are done with increasing frequency to confirm Helicobacter pylori infection and to determine the type and content of gastritis. Gastrointestinal bleeding after gastric cold biopsy is rare. We report two patients who developed melena after cold biopsy of the gastric antrum. Repeat gastroscopies excluded lesions other than the biopsied sites as the source of bleeding. Colonoscopies in both cases did not reveal any evidence of lower GI bleed. Relevant medications include amlodipine, in case 1, and brufen, which was used in case 2 but discontinued before biopsy. Literature review has shown the rarity of clinically significant hemorrhage resulting from gastric cold biopsy. Nevertheless, all patients undergoing gastroscopy should be informed of this potential complication.
Amlodipine↗
Importance of ribosomal frameshifting for human immunodeficiency virus type 1 particle assembly and replication.
The recent development and use of protease inhibitors have demonstrated the essential role that combination therapy will play in the treatment of individuals infected with the human immunodeficiency virus type 1 (HIV-1). Past clinical experience suggests that due to the appearance of resistant HIV-1 variants, additional therapeutics will be required in the future. To identify new options for combination therapy, it is of paramount importance to pursue novel targets for drug development. Ribosomal frameshifting is one potential target that has not been fully explored. Data presented here demonstrate that small molecules can stimulate frameshifting, leading to an imbalance in the ratio of Gag to Gag-Pol and inhibiting HIV-1 replication at what appears to be the point of viral particle assembly. Thus, we propose that frameshifting represents a new target for the identification of novel anti-HIV-1 therapeutics.
Animals↗
Effect of continuous positive airway pressure on forced expiratory flows in infants with tracheomalacia.
Continuous positive airway pressure (CPAP) is used to minimize airway collapse in infants with tracheomalacia. Forced expiratory flows (FEFs) at functional residual capacity (FRC) increase with increasing CPAP in infants with tracheomalacia, and it has been suggested that CPAP prevents airway collapse by "stenting" the airway open. Since FEF is greater at higher than at lower lung volumes, we evaluated whether the increase in flow measured at FRC (V FRC) with CPAP could be explained by the increase in FRC with CPAP. We measured full FEF-volume curves at CPAP levels of 0, 4, and 8 cm H2O in six infants with tracheomalacia and five healthy control infants. In both groups of infants, FVC did not change with CPAP; however, inspiratory capacity (IC) decreased and thus FRC increased with increasing CPAP. FEFs at FRC increased with increasing levels of CPAP; however, the FEFs at 50% and 75% of expired volume were not different for the three levels of CPAP for both groups of infants. Our finding that FEFs measured at the same lung volumes did not differ for the different levels of CPAP indicates that CPAP affects forced flows primarily by increasing lung volume.
Forced Expiratory Flow Rates↗
Analysis of health service areas: another piece of the psychiatric workforce puzzle.
Planning for development of a national or regional psychiatrist workforce that is the appropriate size must consider numerous issues. They include the dynamics of workforce distribution, effects of managed care, reduction in potential residency slots, participation of international medical graduates, apathy toward the field of psychiatry, service area variations, and increased interest in allied mental health professions, along with the burgeoning global burden of psychiatric illness. This paper examines the application of two benchmark standards for the number of psychiatrists needed per 100,000 population--the standard developed by the Graduate Medical Education National Advisory Committee and the Average Requirement Benchmark--to the supply of psychiatrists in Georgia in 1996 by county and by health service regions, which are geographical units based on health care utilization patterns of Medicare and Medicaid recipients. Areas with a surplus or deficit of psychiatrists are identified. The findings provide contextual evidence of a surplus of psychiatric physicians in the most populous areas of the state, given a substantial presence of health maintenance organizations. The state's less populated rural areas may potentially benefit from a redistribution of the psychiatrist workforce. The authors recommend continued refinement of models to estimate psychiatric workforce needs and suggest development of a comprehensive model that uses needs-based, demand-based, and benchmarking approaches.
Benchmarking↗
Experience of an open referral system for stroke rehabilitation in the community.
OBJECTIVE: To examine referral patterns and characteristics of patients assessed by a community stroke rehabilitation service utilizing an open referral system. DESIGN: Descriptive study. SETTING: Two boroughs in a health district in South London, England. SUBJECTS: Two hundred and seventy-six patients with stroke assessed by the service in its first 18 months of operation. RESULTS: Patients were referred from a variety of sources including hospitals (38%), general practitioners (18%), district nurses (10%), social services (9%), self-referrals (8%), community physiotherapists (7%) and family or carers (2%). Referrals from hospital were younger (33% aged under 65 years) while referrals from community health and social services were older (44% aged 75-84 years) (chi(2) = 23, df = 9, p < 0.01). Fifty per cent of patients who had self-referred or had been referred by families or carers had longstanding stroke (> 1 year), 46% of patients from general practitioners had acute stroke (< 4 weeks) and 37% of hospital patients were seen between one and three months post stroke (chi(2) = 50.4, df = 12, p < 0.001). There was a marginally significant difference in the prevalence of incontinence and no significant differences in limb weakness, visual impairment and speech impairment. There were no significant changes in sources of referral between the first and second nine months of the service. There was a significant increase in the percentage of patients with recent stroke seen in the second nine months (chi(2) = 22.8, df = 5, p < 0.001). In this period, 36% of patients assessed were seen within four weeks of their stroke compared with 15% in the first nine months. Of patients with stroke, 8.7% were considered to have been inappropriate referrals but they were not significantly associated with any particular source of referral. CONCLUSIONS: Referrals were received from a wide variety of sources with significant differences in age and duration of stroke of patients from different referral sources. The results suggest that an open referral system may make rehabilitation accessible to a broader range of patients with stroke living in the community.
Aged↗
Why do the clinical sequelae of estrogen deficiency affect women more than men?
Explore the source record for details and available documents.
Estrogen Replacement Therapy↗
Improving prenatal care services for low-income African American women and infants.
Increasing the level of prenatal care among African American women may be one method of improving the health and well-being of African American women and children. This article identifies factors influencing access to and use of prenatal care and strategies for increasing the use of prenatal care among low-income African American women. Barriers to prenatal care, the strengths and limitations of prenatal care in reducing infant mortality and improving infant outcomes, and the importance of providing more comprehensive prenatal care that addresses both the medical and psychosocial needs of the low-income African American mother and her infant are discussed. Changes in prenatal care services that include the medical and lay communities, public health organizations, public policy organizations, and medical financing institutions are identified.
Adult↗
Injection drug use and HIV infection among the seriously mentally ill: a report from Vancouver.
A recently reported outbreak of HIV among injection drug users in Vancouver determined that, in early 1997, 23% of this population was HIV-positive, and that HIV-negative injection drug users were becoming positive at the rate of 18.6% per year, the highest rate reported in North America. One significant factor behind the outbreak is the high prevalence of injection cocaine use among drug addicts in Vancouver. Cocaine, because it has a short "high," creates a need for more frequent injections and therefore increases the likelihood of needle sharing and HIV transmission. The mentally ill in Vancouver are particularly at risk for HIV infection because of their vulnerability to substance misuse and because large numbers of them reside in the main drug-using neighborhood. The provincial and federal governments have made $4,700,000 available to respond to this public health emergency, to be spent on the expansion of community services, including a number of needle-exchange sites. Accessing these and other health care services continues to be a challenge for injection drug users who also suffer from serious mental illnesses; for these persons an assertive case management model may be the most effective way of maintaining continuity of care.
British Columbia↗