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Biomedical subjects

C Davis

Publications and source records attributed to C Davis.

At least 109 records · Page 6Linked to original sources
PubMed1998

Activated T-lymphocytes express occludin, a component of tight junctions.

T-lymphocytes routinely traffic from the lymphoid and vascular compartments to the tissues during immune surveillance and inflammatory responses. This egress occurs without compromising endothelial barrier, which is maintained by tight junctions (zonula occludens). We report that T-lymphocytes up-regulate the expression of occludin, a major component of the tight junction in response to stimulation with phorbol ester (PMA) + calcium ionophore, CD3 antibody or T-cell receptor (TCR) antibody. Only activated T-lymphocytes express occludin; this adhesion molecule is nearly absent in resting T-lymphocytes. By immunofluorescence, occludin is seen in lymphocyte aggregates, but does not appear to mediate aggregation since only 50% of the cells in these clusters express occludin. Occludin is expressed between 8 and 24 h following stimulation, and persists for at least 48 h. These data indicate that activated T cells produce occludin which may regulate lymphocyte adhesion and trafficking.

Animals↗
PubMed1998

Human submandibular saliva inhibits human immunodeficiency virus type 1 infection by displacing envelope glycoprotein gp120 from the virus.

Human submandibular saliva reduces human immunodeficiency virus type 1 (HIV-1) infection in vitro. To define the mechanism of inhibition, virus was incubated with saliva or medium, velocity sucrose gradient centrifugation was performed, and fractions were analyzed for p24 and gp120. The results show that after incubation with saliva, the envelope glycoprotein was displaced from both a laboratory-adapted and a low-passage clinical HIV-1 isolate. To identify the salivary protein(s) responsible, submandibular saliva was fractionated by anion- exchange chromatography. Protein fractions containing anti-HIV activity were assayed for their ability to strip gp120 from virus. The partially purified active fractions contained two high-molecular-weight sialyated glycoproteins identified as salivary agglutinin and mucin, as well as several lower-molecular-weight proteins. It thus appears that specific salivary proteins interact with HIV-1 to strip gp120 from the virus with a resultant decrease in infectivity.

Antiviral Agents↗
PubMed1998

Major histocompatibility complex genotype is associated with disease progression and virus load levels in a cohort of human immunodeficiency virus type 1-infected Caucasians and African Americans.

To assess the influence of HLA on AIDS-free survival, human immunodeficiency virus load, and CD4 cell counts, 91 Caucasian and 48 African-American seroprevalent men were typed for HLA classes I and II and TAP alleles. HLA associations with these markers were assessed by assigning sum integer scores based on 7 class I allele-TAP variants (+1) and 13 class I-class II-TAP combinations (-1) with different AIDS-free survival times found in a prior study. Subjects in both racial groups and combined with positive sum scores were less likely to have CD4 cell decline (P=.0004), to have increased virus burden (P=.014), and to develop AIDS (P=.034) in the follow-up period than were Caucasians and African Americans with scores of 0 or -1. These results confirm the reported associations of specific major histocompatibility complex genes with AIDS-free survival time in Caucasians and specifically extend them to African Americans and to two established markers of disease progression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Effects of aerosolized synthetic surfactant, atovaquone, and the combination of these on murine Pneumocystis carinii pneumonia.

An immunosuppressed rat model was used to determine the pharmacokinetics of aerosolized atovaquone (administered with and without a synthetic surfactant) and to evaluate the efficacy of inhaled atovaquone in the prevention and treatment of Pneumocystis carinii pneumonia (PCP). After a single dose by aerosol, mean peak concentrations of atovaquone averaged 52 microg/mL in plasma and 31 microg/g in lungs of rats infected with P. carinii. When atovaquone was combined with surfactant, mean peak concentrations of 94 microg/mL in plasma and 51 microg/g in lung were achieved. Aerosolized synthetic surfactant alone significantly increased survival of rats with PCP and, when combined with atovaquone, increased plasma and lung concentrations of the drug and eradication of the organism.

Administration, Inhalation↗
PubMed1998

US Department of Agriculture School Breakfast Program.

This article reviews the history of the US Department of Agriculture School Breakfast Program (SBP) and provides a synthesis of factors influencing participation rates. Certain children are more likely to participate than others, such as those in lower grades and those from low-income households, and African American, Hispanic, and male students. A few studies in the past 25 y have examined the effectiveness of the SBP in improving the diets and nutritional status of children. The overall pattern that emerges from these studies is that the SBP contributes to improved nutrient intake in program participants. Less attention has been devoted to assessing the effects of SBP on cognitive development. Some of the evidence reviewed here suggests that the SBP significantly improves school performance and reduces absenteeism and tardiness. Future directions for research and operation of the SBP are discussed in light of the changing dietary profile of American children.

Child↗
PubMed1998

Afr1p regulates the Saccharomyces cerevisiae alpha-factor receptor by a mechanism that is distinct from receptor phosphorylation and endocytosis.

The alpha-factor pheromone receptor activates a G protein signaling pathway that induces the conjugation of the yeast Saccharomyces cerevisiae. Our previous studies identified AFR1 as a gene that regulates this signaling pathway because overexpression of AFR1 promoted resistance to alpha-factor. AFR1 also showed an interesting genetic relationship with the alpha-factor receptor gene, STE2, suggesting that the receptor is regulated by Afr1p. To investigate the mechanism of this regulation, we tested AFR1 for a role in the two processes that are known to regulate receptor signaling: phosphorylation and down-regulation of ligand-bound receptors by endocytosis. AFR1 overexpression diminished signaling in a strain that lacks the C-terminal phosphorylation sites of the receptor, indicating that AFR1 acts independently of phosphorylation. The effects of AFR1 overexpression were weaker in strains that were defective in receptor endocytosis. However, AFR1 overexpression did not detectably influence receptor endocytosis or the stability of the receptor protein. Instead, gene dosage studies showed that the effects of AFR1 overexpression on signaling were inversely proportional to the number of receptors. These results indicate that AFR1 acts independently of endocytosis, and that the weaker effects of AFR1 in strains that are defective in receptor endocytosis were probably an indirect consequence of their increased receptor number caused by the failure of receptors to undergo ligand-stimulated endocytosis. Analysis of the ligand binding properties of the receptor showed that AFR1 overexpression did not alter the number of cell-surface receptors or the affinity for alpha-factor. Thus, Afr1p prevents alpha-factor receptors from activating G protein signaling by a mechanism that is distinct from other known pathways.

Cell Division↗
PubMed1998

Complications of mandibular fractures.

Timely repair of mandibular fractures remains an effective means to reduce pain, restore function, and prevent complications. This study addresses the effect of the time interval between injury and treatment on the overall complication rate, the complication rate between various treatment modalities (mandibular-maxillary fixation [MMF] alone, MMF with intraosseous wire bone fixation, and MMF with rigid internal fixation), and the relationship of inpatient vs. outpatient management. Cost was also examined with respect to choice of management. We report a retrospective series of 308 consecutive patients managed at the University of Miami/Jackson Memorial Hospital. Patients who received treatment 3 to 10 days following injury were found to have a lower complication rate than earlier or later repair. We postulate that most patients with mandibular fractures may be managed on an outpatient basis, which represents a considerable savings in cost.

Adolescent↗
PubMed1998

Needs assessment of rural and remote women travelling to the city for breast cancer treatment.

The purpose of this study was to assess the needs of rural women travelling to the city for breast cancer treatment. Participants included 80 women aged between 34 and 80 years living in rural NSW and South Australia who travelled for breast cancer treatment. After completing treatment, participants completed a brief telephone survey on the needs of rural women travelling for treatment. Findings revealed that more than 90% of women travelled for treatment due to the lack of available treatment centres closer to home and on average they spent 6.79 weeks (SD = 4.73) away from their home and family. Findings also showed that 89% identified specific problems for rural women, with social and practical support being primary concerns. Although the majority of women were provided with some type of social support, only 39% of women received financial assistance and 19% of these women had trouble claiming money for which they were eligible. Recommendations of appropriate interventions to ensure equity in the availability and access to breast cancer treatment for all women are discussed.

Adult↗
PubMed1998

Preventing disability and managing chronic illness in frail older adults: a randomized trial of a community-based partnership with primary care.

BACKGROUND: Effective new strategies that complement primary care are needed to reduce disability risks and improve self-management of chronic illness in frail older people living in the community. OBJECTIVE: To evaluate the impact of a 1-year, senior center-based chronic illness self-management and disability prevention program on health, functioning, and healthcare utilization in frail older adults. DESIGN: A randomized controlled trial. SETTING: A large senior center located in a northeast Seattle suburb. The trial was conducted in collaboration with primary care providers of two large managed care organizations. PARTICIPANTS: A total of 201 chronically ill older adults seniors aged 70 and older recruited through medical practices. INTERVENTION: A targeted, multi-component disability prevention and disease self-management program led by a geriatric nurse practitioner (GNP). MEASUREMENTS: Self-reported Physical function, physical performance tests, health care utilization, and health behaviors. RESULTS: Each of 101 intervention participants met with the GNP from 1 to 8 times (median = 3) during the study year. The intervention group showed less decline in function, as measured by disability days and lower scores on the Health Assessment Questionnaire. Other measures of function, including the SF-36 and a battery of physical performance tests, did not change with the intervention. The number of hospitalized participants increased by 69% among the controls and decreased by 38% in the intervention group (P = .083). The total number of inpatient hospital days during the study year was significantly less in the intervention group compared with controls (total days = 33 vs 116, P = .049). The intervention led to significantly higher levels of physical activity and senior center participation and significant reductions in the use of psychoactive medications. CONCLUSIONS: This project provides evidence that a community-based collaboration with primary care providers can improve function and reduce inpatient utilization in chronically ill older adults. Linking organized medical care with complementary community-based interventions may be a promising direction for research and practice.

Activities of Daily Living↗
PubMed1998

Dominant-negative mutations in the G-protein-coupled alpha-factor receptor map to the extracellular ends of the transmembrane segments.

G-protein-coupled receptors (GPCRs) transduce the signals for a wide range of hormonal and sensory stimuli by activating a heterotrimeric guanine nucleotide-binding protein (G protein). The analysis of loss-of-function and constitutively active receptor mutants has helped to reveal the functional properties of GPCRs and their role in human diseases. Here we describe the identification of a new class of mutants, dominant-negative mutants, for the yeast G-protein-coupled alpha-factor receptor (Ste2p). Sixteen dominant-negative receptor mutants were isolated based on their ability to inhibit the response to mating pheromone in cells that also express wild-type receptors. Detailed analysis of two of the strongest mutant receptors showed that, unlike other GPCR interfering mutants, they were properly localized at the plasma membrane and did not alter the stability or localization of wild-type receptors. Furthermore, their dominant-negative effect was inversely proportional to the relative amount of wild-type receptors and was reversed by overexpressing the G-protein subunits, suggesting that these mutants compete with the wild-type receptors for the G protein. Interestingly, the dominant-negative mutations are all located at the extracellular ends of the transmembrane segments, defining a novel region of the receptor that is important for receptor signaling. Altogether, our results identify residues of the alpha-factor receptor specifically involved in ligand binding and receptor activation and define a new mechanism by which GPCRs can be inactivated that has important implications for the evaluation of receptor mutations in other G-protein-coupled receptors.

Amino Acid Sequence↗
PubMed1998

Gas tensions in cardiac lymph as a reflection of the interstitial space of the heart.

The purpose of this study was to determine the feasibility of measuring partial pressure of oxygen (pO2), partial pressure of carbon dioxide (pCO2), and pH in cardiac lymph and to evaluate the relationship of these parameters to comparable measurements in arterial and coronary sinus blood in the normal heart under various respiratory conditions. In four anesthetized open-chest dogs, the principal cardiac lymphatic as well as the femoral artery and coronary sinus were cannulated. Ventilation was varied by changing oxygen concentration, tidal volume, and respiratory rate. PO2, pCO2, and pH were measured in the cardiac lymph, arterial blood, and coronary sinus blood after each change in ventilation. For pH and pCO2, good correlations were observed between the arterial blood and cardiac lymph, arterial blood and coronary sinus blood, and coronary sinus blood and cardiac lymph. The correlation between the pO2 measured in the arterial blood and the pO2 measured in the cardiac lymph was not as strong, and this may have been related to difficulty achieving a steady state. Gas tensions (pO2, pCO2, and pH) can be measured in cardiac lymph and may provide a window to the interstitial compartment of the heart. This is an additional tool for the laboratory study of ischemia and other forms of heart disease.

Animals↗
PubMed1998

Submandibular salivary proteases: lack of a role in anti-HIV activity.

Whole human saliva contains a number of proteolytic enzymes, mostly derived from white blood cells and bacteria in the oral cavity. However, less information is available regarding proteases produced by salivary glands and present in salivary secretions. In the present study, we have analyzed submandibular saliva, collected without contaminating cells, and identified multiple proteolytic activities. These have been characterized in terms of their susceptibility to a series of protease inhibitors. The submandibular saliva proteases were shown to be sensitive to both serine and acidic protease inhibitors. We also used protease inhibitors to determine if salivary proteolytic activity was involved in the inhibition of HIV infectivity seen when the virus is incubated with human saliva. This anti-HIV activity has been reported to occur in whole saliva and in ductal saliva obtained from both the parotid and submandibular glands, with highest levels of activity present in the latter fluid. Protease inhibitors, at concentrations sufficient to block salivary proteolytic activity in an in vitro infectivity assay, did not block the anti-HIV effects of saliva, suggesting that the salivary proteases are not responsible for the inhibition of HIV-1 infectivity.

Anti-HIV Agents↗