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S Davis

Publications and source records attributed to S Davis.

At least 37 records · Page 2Linked to original sources
PubMed1998

MPP+ toxicity and plasma membrane dopamine transporter: study using cell lines expressing the wild-type and mutant rat dopamine transporters.

The Parkinsonism-inducing neurotoxin 1-methyl-4-phenylpyridinium (MPP+) causes specific cell death in dopaminergic neurons after accumulation by the dopamine transporter (DAT). COS cells, a non-neuronal cell line insensitive to high doses of MPP+, becomes sensitive to MPP+ when transfected with the rat DAT cDNA. We analyzed the bi-directional transport of MPP+ and its toxicity in several cell lines expressing wild or mutant DATs. Cell death in COS cells expressing wild DAT by exposure to MPP+ was concentration-dependent and cocaine-reversible. Increased wild DAT expression caused higher sensitivities to the toxin in HeLa cells. Although several mutant DATs demonstrated greater transport activity than the wild-type, they displayed similar or lower sensitivity to MPP+ toxicity. Reverse transport of preloaded [3H]MPP+ through DAT was facilitated in COS cells expressing certain mutant DATs, which consistently displayed less sensitivity to MPP+ toxicity. These results suggest that re-distribution of MPP+ due to influx/efflux turnover through the transporter is a key factor in MPP+ toxicity.

1-Methyl-4-phenylpyridinium↗
PubMed1998

Expression cloning and characterization of NSIST, a novel sulfotransferase expressed by a subset of neurons and postsynaptic targets.

Synapses are distinguished by localized concentrations of specific proteins, many of which bear the marks of posttranslational processing such as glycosylation and sulfation. One strategy to elucidate this posttranslational tailoring is to identify the enzymes that create these modifications. Monoclonal antibody 3B3 recognizes a carbohydrate-containing epitope expressed on dystroglycan and other constituents of Torpedo electric organ synaptic membranes. We used mAb 3B3 in an immunofluorescence-based expression-cloning method and isolated a cDNA clone conferring mAb-3B3 immunoreactivity to transfected COS cells. The deduced polypeptide has a predicted molecular weight of 51 kDa, a type II transmembrane topology, and four potential N-linked glycosylation sites. The polypeptide, which we term NSIST (nervous system involved sulfotransferase), shows extensive, although not complete, homology to a chondroitin-6-sulfotransferase and limited homology to other sulfotransferases. In NSIST-transfected COS cells, 35SO4 incorporation and chondroitin-sulfate-like immunoreactivity are increased. In vivo, NSIST occurs as a single 2.4 kb transcript abundant in Torpedo electric organ, moderately expressed in spinal cord and electric lobe, and undetectable in non-neural tissues. Immunohistochemistry shows that NSIST is expressed in a punctate distribution in the innervated portion of electrocytes. In the CNS, NSIST-like immunoreactivity is localized within the somas of motor neurons and neurons of the electromotor nucleus, whereas mAb-3B3 immunostaining is associated with cell surfaces and neuropil. Neuronal NSIST is therefore likely to exert its effects extracellularly; although NSIST is synthesized by neurons, its product, the 3B3 epitope, is found outside neuronal cell bodies. Our evidence indicates that NSIST participates in nervous system specific posttranslational modifications, perhaps including those at synapses.

Animals↗
PubMed1998

Projection of AIDS and HIV incidence among children born infected with HIV.

By 31 December 1995, 6285 children with perinatally acquired immunodeficiency syndrome (AIDS) had been reported to the Centers for Disease Control and Prevention (CDC) by the state and local health departments of all 50 states, the District of Columbia, Puerto Rico, and the U.S. territories. We present here the statistical methods used to estimate the number of infants born with HIV and to predict the number of diagnoses of perinatally acquired AIDS among children to 1997. We estimate that there were 13,900 children who had perinatally acquired HIV infection by the end of 1995 and who will eventually be reported with AIDS. If 85 per cent of all diagnoses are reported, this represents a total of more than 16,300 diagnoses. Of these, 6600 had developed AIDS by the end of 1995 and will eventually be reported to CDC. We project that, during 1996 and 1997, another 1500 HIV-infected children will be born.

Acquired Immunodeficiency Syndrome↗
PubMed1998

In search of the abominable consent form: the impact of readability and personalization.

This study assessed the impact of readability and personalization of informed consent forms on initial impressions of therapists and on recall of the information provided on the forms. Eighty-five participants received consent forms that varied in terms of readability and personalization, and were asked to rate their impressions of the therapist. More readable forms increased participants' impressions of the therapist's expertness and the form's helpfulness. Personalized forms increased ratings of the attractiveness of the therapist, and of the relevance of-and satisfaction with-the forms. Personalized forms also tended to increase recall. These properties of consent forms may indeed influence how clients initially react to therapists.

Adolescent↗
PubMed1998

Effects of valsartan and hydrochlorothiazide alone and in combination on blood pressure and heart rate in conscious-telemetered spontaneously hypertensive rats (SHR).

The purpose of this study was to examine the effectiveness of combined administration of the angiotensin AT1 receptor antagonist valsartan, with the diuretic hydrochlorothiazide (HCTZ), on blood pressure in conscious spontaneously hypertensive rats (SHR). Both drugs were administered continuously via subcutaneously implanted osmotic minipumps alone or in combination for a period of 2 weeks. Mean arterial pressure and heart rate were monitored throughout the infusion interval by means of chronically-implanted radiotransmitters. Coadministration of a diuretic with valsartan potentiated the blood pressure lowering effect in conscious SHR. Responses varied in magnitude from additive (valsartan at 1 mg/kg/day + hydrochlorothiazide at 3 and 10 mg/kg/day) to synergistic (valsartan at 3 mg/kg/day + hydrochlorothiazide at 10 mg/kg/day). The greater blood pressure lowering seen in SHR receiving combination therapy was associated with only a transient increase in heart rate. A similar potentiation of the antihypertensive effect was seen during coadministration of hydrochlorothiazide (HCTZ) with the angiotensin converting enzyme inhibitor benazeprilat. Additivity was noted with benazeprilat at 1 mg/kg/day + hydrochlorothiazide at 3 mg/kg/day, whereas a higher dose of HCTZ resulted in a synergistic response. These findings suggest that the similar results obtained with angiotensin converting enzyme inhibitors and AT1 receptor antagonists are due to the capacity to which diuretic-induced activation of the renin angiotensin system occurs.

Animals↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗