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Biomedical subjects

L Davis

Publications and source records attributed to L Davis.

At least 91 records · Page 5Linked to original sources

A comparison of hyperthermia cisplatin sensitization in human ovarian carcinoma and glioma cell lines sensitive and resistant to cisplatin treatment.

Two pairs of human tumor cell lines (glioma and ovarian carcinoma (OvCa) each having a parental cell line and cisplatin-resistant variant, were evaluated for (a) cisplatin response, (b) hyperthermia response, and (c) combined hyperthermia and cisplatin response. The two resistant lines had comparable resistant responses while for the parental lines, the OvCa was more sensitive than the glioma to cisplatin doses up to 14 microgram/ml. For the hyperthermia response, the OvCa parental line was more resistant than the variant line at low-temperature hyperthermia (41 degrees C or 42 degrees C) but became more sensitive at high temperature (45 degree C). For the glioma, the parental line was more sensitive to hyperthermia at all temperatures tested. Hyperthermia caused sensitization to cisplatin in all cell lines but was generally greater in the glioma cell lines. In the OvCa system, hyperthermia had a slightly greater sensitizing effect on the resistant cell lines, while in the glioma the opposite was true. The degree of sensitization increased with hyperthermia temperature. In summary, the results showed that there is no cross- resistance for hyperthermia and cisplatin, that the degree of thermal sensitization is not reduced in cisplatin- resistant cell lines, and that cisplatin thermal sensitization is cell-line and temperature dependent. Thus, hyperthermia can effectively improve tumor cell response to cisplatin and may be useful in overcoming resistance to cisplatin.

Carcinoma↗

Interactive effects of depression symptoms, nicotine dependence, and weight change on late smoking relapse.

Signal detection methods were used to develop an algorithm useful in distinguishing those at risk for late relapse from those likely to maintain abstinence. Four subgroups with 24-month survival (nonrelapse) rates ranging from 79% to 33% were identified. Among participants whose depression symptoms decreased from baseline to the end of treatment, lower levels of nicotine dependence were associated with less relapse at the 24-month follow-up (odds ratio = 2.77; 95% confidence interval: 1.36-5.62). Among participants whose depression symptoms increased from baseline to the end of treatment, greater weight gain was associated with less relapse at follow-up (odds ratio = 2.90; 95% confidence interval: 1.41-5.96). This study suggested that it may become possible to use both baseline and treatment information to "titrate" interventions.

Algorithms↗

Minority use of community long-term care services: a comparative analysis.

A series of national surveys since 1982 have examined health needs of elders. Small proportions of minority elders in each sample have limited our understanding of service use by minorities. This research sought to determine (1) the extent to which minorities have restricted use of community long-term care services as a result of socioeconomic status, family structure, and health status, and (2) the replicability and validity of results across three national surveys: Supplement on Aging, National Long-Term Care, and National Medical Expenditure. Results indicate no bivariate or multivariate differences between African American, Hispanic, or White frail older persons in use of community long-term services. Living arrangements, Medicaid use, and overall health and functional status were primary predictors of service use. Taking methodological limitations into account, the results suggest similarity in processes influencing use of community long-term care services for African American and White older persons.

Black or African American↗

Feasibility of fitting contact lenses with apical clearance in keratoconus.

Despite the wide variety of rigid contact lens fitting philosophies for the visual correction of keratoconus, questions remain, including which approach-flat, divided support, or steep-contributes the most toward the preservation of a clear cornea. One goal of the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Pilot Study was to determine the feasibility of managing early keratoconus patients with apical clearance rigid contact lenses. Of 30 keratoconus patients identified with at least 1 nonscarred cornea, 17 patients (30 eyes) were randomly assigned to a steep lens fitting protocol. After trial fitting with a standardized lens design demonstrating minimum apical clearance, lenses were dispensed whose base curve was 0.2 mm steeper than the minimum apical clearance lens. Patients were re-evaluated on a quarterly schedule concluding at 12 months. Changes in keratometry between baseline and 12 months identified unequal steepening of the flat and steep corneal curvatures, suggestive of corneal molding. Best corrected rigid lens visual acuity measures illustrated no significant changes over the course of the study. Clinically significant corneal compromise was transiently observed in some patients. Only 1 of 22 eyes completing the pilot study and fitted with apical clearance developed mild corneal scarring.

Adolescent↗

Cytomegalovirus infections in Toronto child-care centers: a prospective study of viral excretion in children and seroconversion among day-care providers.

OBJECTIVES: To prospectively determine the rate of cytomegalovirus shedding in children and the rate of seroconversion to cytomegalovirus in providers at 38 infant-toddler day care centers in Toronto, Canada. METHODS: Urine was collected for shell vial assay in 471 children between the ages of 3 and 42 months. Providers (n = 206) were tested for the presence of cytomegalovirus antibody by latex agglutination. Of the 68 providers who were seronegative, 56 were retested approximately 1 year later. RESULTS: Viruria was documented in 79 (17%) children and antibody in 67% of providers. Seropositivity was significantly related to country of birth outside Canada, presence of children at home < 5 years of age and increased household size. Seroconversion was documented in 12.5% (n = 7). Of these providers 71% worked at centers where workers never wore gloves for diaper changing vs. 33% of those who did not seroconvert (P = 0.06), and all were younger than 30 years vs. 59% of those who did not seroconvert (P = 0.04). In centers with viruria the association of seroconversion with lack of glove use was enhanced (P = 0.04). Seroconversion was marginally more likely in providers working with infants only than with infants and toddlers or with toddlers alone. Logistic regression confirmed that seroprevalence was more likely in providers who were born outside Canada, had children younger than age 5 years in the household and with an increased number of people in the household. Seroconversion was more likely if the provider worked at centers not using gloves for diaper changes, worked with infants only rather than with toddlers and infants and was < 30 years old, with each factor contributing independently to the model. CONCLUSIONS: Cytomegalovirus infection is common in children and providers in Toronto day-care centers.

Adolescent↗

Supplementary enteral nutrition maintains remission in paediatric Crohn's disease.

BACKGROUND: Liquid diets given enterally combined with "bowel rest' are efficacious in the treatment of active Crohn's disease, but rapid recrudescence of gastrointestinal symptoms after resumption of a normal diet is common. AIMS: This study examined whether continuation of enteral nutrition as a nocturnal supplement to an ad libitum daytime intake of a normal diet increased the length of remission of Crohn's disease in children. PATIENTS AND METHODS: Children and adolescents with active Crohn's disease treated successfully with exclusive enteral nutrition were classified retrospectively according to whether they continued supplementary enteral nutrition or not. Time to relapse and linear growth were compared between the two cohorts. RESULTS: Between January 1986 and December 1992, 65 patients aged 7-17 years (mean (SD) 13.6 (2.1) years) (36 males, 29 females) with Crohn's disease in exacerbation were treated for > or = four weeks by bowel rest and nasogastric tube feeding of an oligopeptide or amino acid based formula. At first follow up visit, remission (fall in Paediatric Crohn's Disease Activity Index, PCDAI to < or = 20) was achieved in 47 of 65 (72%) patients. Subsequently, 20 of these 47 (43%) relapsed by six months and 28 of 47 (60%) by 12 months. Patients who continued nasogastric supplementary feeding (n = 28) after resumption of an otherwise normal diet remained well longer than those who discontinued nocturnal supplements completely (n = 19) (p < 0.02). Furthermore, continued use of nasogastric supplements before completion of puberty was associated with improved linear growth. CONCLUSION: After successful treatment of active Crohn's disease by exclusive enteral nutrition, supplementary enteral nutrition without restriction of normal diet is associated with prolongation of remission and improved linear growth in children and adolescents.

Adolescent↗

Differential localization of prostaglandin E receptor subtypes in human kidney.

Four prostaglandin E2 (PGE2) receptors designated EP1, EP2, EP3, and EP4 have been pharmacologically identified, cloned, and sequenced. The present studies determined the intrarenal distribution of these EP-receptor subtypes in human kidney using in situ hybridization with riboprobes for the human EP receptors. mRNA for the phosphatidylinositol hydrolysis-coupled EP receptor was highly expressed in cortical, outer medullary, and inner medullary collecting duct. RNA for the Gi-coupled EP3 receptor was primarily expressed in the cortical and outer medullary collecting duct, as well as in the medullary thick ascending limb; however, it was absent from the inner medullary collecting duct. Expression of mRNA for EP1 and EP3 in connecting segment could not be excluded. There was no expression of the GS-coupled EP2 receptor mRNA detected in human kidney by in situ hybridization; however, mRNA for the GS-coupled EP4 receptor was highly expressed in the glomerulus. These studies demonstrate distinct regions of intrarenal expression for the different EP receptors and suggest that each receptor subtype may modulate different aspects of renal function in humans.

Autoradiography↗

Pharmacological evaluation of novel Alzheimer's disease therapeutics: acetylcholinesterase inhibitors related to galanthamine.

Acetylcholinesterase (AChE) inhibitors from several chemical classes have been tested for the symptomatic treatment of Alzheimer's disease; however, the therapeutic success of these compounds has been limited. Recently, another AChE inhibitor, galanthamine hydrobromide (GAL), has shown increased clinical efficacy and safety. Using biochemical, behavioral and pharmacokinetic analyses, this report compares GAL with two of its analogs, 6-O-acetyl-6-O-demethylgalanthamine hydrochloride (P11012) and 6-O-demethyl-6-O[(adamantan-1-yl)-carbonyl]galanthamine hydrochloride (P11149), for their therapeutic potential. P11012 and P11149 were found to be potent, competitive and selective inhibitors of AChE, demonstrating central cholinergic activity, behavioral efficacy and safety. P11012 and P11149, though pharmacokinetic analyses, were shown to act as pro-drugs, yielding significant levels of 6-O-demethylgalanthamine. In vitro, 6-O-demethylgalanthamine was 10- to 20-fold more potent than GAL as an inhibitor of AChE, and it demonstrated greater selectivity for inhibition of AChE vs. butyrylcholinesterase. Like GAL, both P11012 and P11149 showed central cholinergic activity biochemically, by significantly inhibiting rat brain AChE; physiologically, by causing hypothermia; and behaviorally, by attenuating scopolamine-induced deficits in passive avoidance. In addition, GAL, P11012 and P11149 enhanced step-down passive avoidance, another measure of behavioral efficacy. By comparing efficacious doses with primary overt effects, P11012 and P11149 had better oral therapeutic indices than GAL. Oral pharmacokinetic analyses of GAL, P11012 and P11149 revealed differences. Although P11012 and P11149 exhibited similar area under the curve values, 191149 had slower, lower and more sustained concentration maximum levels. P11012 and GAL rapidly reached their concentration maximums, but GAL, in brain had the highest area under the curve and concentration maximum. Because of its composite profile, including duration of action, oral therapeutic index and pharmacokinetics, P11149 is considered the better therapeutic candidate for the treatment of Alzheimer's disease.

Alzheimer Disease↗

Stability of plasma GABA at four-year follow-up in patients with primary unipolar depression.

The biology of mood disorders involves gamma-aminobutyric acid (GABA), a neurotransmitter whose levels in plasma likely reflect brain GABA activity. Previous research has shown that a subset of patients with primary unipolar major depression have low plasma GABA levels, which parallels findings from studies of cerebrospinal fluid. We have completed a 4-year follow-up on 46 male patients with primary unipolar depression. Plasma levels of GABA were stable over this time. For the group, mean plasma GABA levels on follow-up did not change significantly from entry levels. Plasma GABA levels measured on follow-up were significantly (p < .001) correlated with entry levels. Patients with low plasma GABA levels (< 100 pmol/ml) on entry into the study were likely to remain low on follow-up, and patients with plasma GABA levels in the control range (> or = 100 pmol/ml) at entry similarly remained in this category (chi 2 = 7.23, p = .007). This was true whether or not the patient had recovered from depression on follow-up. Levels of plasma GABA did not significantly correlate with severity of depression at either entry (p = .40) or follow-up (p = .52), nor was there a significant correlation between change in plasma GABA and change in the 17-item Hamilton Depression Rating Scale score from entry to follow-up (p = .89). These data are consistent with the notion that plasma GABA is independent of clinical state in patients with primary unipolar depression. Low plasma GABA may be a trait marker of illness in a subset of patients with mood disorder.

Adult↗

2-Amino-3-ketobutyrate-CoA ligase from beef liver mitochondria: an NMR spectroscopic study of low-barrier hydrogen bonds of a pyridoxal 5'-phosphate-dependent enzyme.

A study of protons associated with low-barrier hydrogen bonds in 2-amino-3-ketobutyrate-CoA ligase (AKB-ligase, EC 2.3.1.29) by NMR is reported. Three resonances are observed in the range of delta H = 15-20 ppm when the NMR spectrum of AKB-ligase is recorded at 600 MHz. These low-barrier hydrogen bonds are associated respectively with a side chain proton, the PLP pyridinium ring nitrogen proton, and the PLP Schiff base proton at the active site of the ligase. The pyridinium proton has been assigned a chemical shift of 19.10 ppm and the Schiff base proton 14.90 ppm. The third low-barrier hydrogen bond associated proton resonating at 16.20 ppm is assigned to a proton of a side chain group. All three resonances disappear when pyridoxal phosphate is removed from the ligase. Consistent with NOE coupling, the side chain group proton should be close to the proton of the Schiff base nitrogen of the pyridoxal 5'-phosphate. The effects of temperature, pH, substrate, and NOE on the three resonances are also studied, in order to assign the protons. The three low-barrier hydrogen bonds described in this report may serve to anchor the cofactor in the active site of 2-amino-3-ketobutyrate-CoA ligase.

Acetyltransferases↗

An SH3 domain is required for the mitogenic activity of microinjected phospholipase C-gamma 1.

Phospholipase activity is elevated in dividing cells. In response to growth factor stimulation, phospholipase C-gamma (PLC-gamma) binds to activated tyrosine kinase receptors via SH2 binding domains, resulting in phosphorylation of PLC-gamma and activation of its enzyme activity. These observations suggest that PLC-gamma participates in the signal transduction pathway employed by growth factors to promote mitogenesis. Consistent with this hypothesis, microinjection of purified bovine PLC-gamma into quiescent fibroblasts has been previously reported to initiate a mitogenic response [Smith et al. (1989) Proc. Natl. Acad. Sci. 86, 3659]. We have reproduced this result using recombinant rat PLC-gamma protein. Surprisingly, however, a catalytically inactive mutant of PLC-gamma, H335Q, also elicited a full mitogenic response. The capacity to induce mitogenesis by microinjection of PLC-gamma was mapped to the 'Z' domain of the protein, which contains PLC-gamma's SH2 and SH3 motifs. Inactivation of the phosphorylated tyrosine binding properties of both SH2 domains had no effect on the mitogenic activity of the Z-domain peptide. However, deletion of the SH3 domain resulted in a complete loss of activity. These results suggest that PLC-gamma's mitogenic properties do not require the enzyme's phospholipase activity, but are instead mediated by a novel pathway for mitogenic stimulation which is dependent upon an intact SH3 domain.

3T3 Cells↗

A Project Alpha program for smaller chapters.

Smaller chapters cannot easily adapt to their groups the projects of larger chapters or programs at the national level. To address this problem, the Coosa Valley chapter of AORN, Rome, Ga, developed a program that offers perioperative experience to nursing students at a local college. Members of the chapter act as preceptors for the students and educate them before the students' preceptorships in the OR. This education seems to relieve some of the intimidation and fear related to the OR, and students in the program are more willing to participate in the program.

Curriculum↗

The importance of monitoring dialysis adequacy in chronic peritoneal dialysis.

The case of a patient who was noted to be malnourished but improved after his dialysis dose was increased is presented. This case and the discussion that follows emphasize the importance of proactively monitoring peritoneal dialysis adequacy and nutritional intake, supporting the notion that the dose of peritoneal dialysis is a major determinant of appetite and, consequently, of nutritional status. In the clinical setting, this influence is best indicated by changes in the serum albumin level and ultimately in long-term patient survival. The case discussion reviews the major principles and supporting literature, describing how we target peritoneal dialysis delivery and optimize nutritional status in an effort to reduce morbidity and mortality.

Adult↗

Comparative analysis of mouse NotI linking clones with mouse and human genomic sequences and transcripts.

NotI cleavage sites are frequently associated with CpG islands that identify the 5' regulatory sites of functional genes in the genome. Therefore we analyzed a sample of 22 NotI linking clones prepared from mouse brain DNA, to determine whether these mouse NotI site associated clones could be used for comparative analysis of mouse and human genomes by cross-reaction with both mouse and human genomic DNA and RNA in Southern and Northern hybridization. We further examined whether we could establish the identity of these clones with known genes by comparing the nucleotide sequences surrounding the NotI site with the GenBank database. We observed that 70% of the clones cross-hybridized with human DNA and that 4 of 11 tested clones (36%) detected a transcript in human HeLa cells RNA whereas 73% clones (8/11) detected transcripts in mouse RNAs from one or more organs. Single pass sequence analysis was successful on 16 of 19 clones. The GC content in these sequence was very high (48.8% to 73.8%) suggesting that 12 of 16 sequenced clones contained a CpG island. Three out of 19 clones showed significant similarity with previously analyzed mouse gene sequences in GenBank, including the mouse rRNA gene family, cathepsin and the scip POU-domain genes. In addition, two sequences showed significant similarity to the human and rabbit protein phosphatase 2A-beta subunit and the human transforming growth factor-beta. Thus, 5 of 16 clones showed homology with identified genes. These results and the recent work of using RLGS methods for genetic mapping indicate that NotI linking clones can be used to efficiently cross reference a comparative analysis of the mouse and human genomic maps.

Animals↗

Race, control, mastery, and caregiver distress.

This study investigated the relationship between race, psychological resources of sense of control and caregiver mastery, and distress outcomes of caregiver depression and role stain among 77 African American and 138 White spouse caregivers of persons with dementia. Patterns of association between psychological resources and caregiving distress outcomes varied by type of outcome. Sense of control had a direct negative relationship with depression. Caregiver mastery moderated the effects of stressors on depression and was the only significant psychological resource predicting role strain. Although African American caregivers were less likely to report caregiver depression and role strain, there were no race differences in the process influencing caregiver distress.

Aged↗