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Biomedical subjects

T Davis

Publications and source records attributed to T Davis.

At least 37 records · Page 2Linked to original sources

Histone deacetylase inhibitors decrease proliferation and modulate cell cycle gene expression in normal mammary epithelial cells.

Full-term pregnancy early in reproductive life is protective against breast cancer in women. The protective effects of parity have variously been attributed to the differentiation that accompanies pregnancy and lactation, alterations in ovarian hormone receptor levels, and altered sensitivity to ovarian hormones. Butyrate, a short-chain fatty acid, induces differentiation in breast cancer cell lines and decreases hormone receptor expression. Butyrate also inhibits proliferation in breast cancer cell lines and modulates expression of key cell cycle-regulatory proteins including cyclin D1. Given these properties, butyrate could be considered a promising agent for breast cancer prevention. Therefore, this study aimed to determine the effects of butyrate on normal human breast epithelial cells and to compare the effects of two stable butyrate derivatives with more favorable pharmacological properties: phenylacetate and its p.o. active precursor phenylbutyrate. Treatment with each agent resulted in concentration-dependent growth inhibition in a normal breast epithelial cell line and two breast cancer cell lines (MCF-7 and MDA-MB-231). Phenylbutyrate and butyrate inhibited proliferation to a similar extent, but phenylacetate was less effective in all of the cell lines. All three of the agents induced differentiation (accumulation of lipid droplets) in normal as well as in breast cancer cells and caused a decrease in estrogen receptor (ER) mRNA in MCF-7 cells. The butyrates decreased expression of cyclin D1, increased expression of p21(Waf1/Cip1), and hypophosphorylated pRB in the normal mammary epithelial cells. The effects on cyclin D1 expression correlated with the effects on cell proliferation, which suggests that modulation of cyclin D1 expression may underpin the antiproliferative effects of butyrates. We have shown that butyrate and butyrate-like agents are able to decrease proliferation and induce differentiation in normal breast cells as well as in malignant breast cells (ER-positive and ER-negative) and, as such, may be considered as candidate chemopreventative agents for women at high risk of developing breast cancer.

Anticarcinogenic Agents↗

Hedonics of binge eating in women with bulimia nervosa and binge eating disorder.

OBJECTIVE: Potential differences in the hedonics of binge eating between female subjects with bulimia nervosa (BN) and female subjects with binge eating disorder (BED) were examined. METHOD: Women seeking treatment for BN (N = 29) and BED (N = 49) completed the Eating Hedonics Questionnaire. RESULTS: Subjects in both groups reported similar precipitants and levels of distress associated with binge eating. Of interest, BED subjects were more likely to report that they enjoyed the food, the taste of the food, the smell and the texture of the food while binge eating. In addition, the BED group reported more relaxation and less physical discomfort and anxiety as a consequence of binge eating compared to the BN group. DISCUSSION: There are interesting and potentially important differences between individuals with BN and BED in the cognitions and behaviors associated with binge eating.

Adult↗

Demonstration and partial characterisation of phospholipid methyltransferase activity in bile canalicular membrane from hamster liver.

BACKGROUND/AIMS: Methylation of phosphatidylethanolamine to phosphatidylcholine predominantly takes place in mitochondrial-associated membrane and the endoplasmic reticulum of the liver. The transport of the phospholipids from endoplasmic reticulum to the bile canalicular membrane is via vesicular and protein transporters. In the bile canalicular membrane a flippase enzyme helps to transport phosphatidylcholine specifically to the biliary leaflet. The phosphatidylcholine then enters the bile where it accounts for about 95% of the phospholipids. We postulated that the increased proportion of phosphatidylcholine in the bile canalicular membrane and the bile compared to the transport vesicles may be due to a methyltransferase activity in the bile canalicular membrane which, using s-adenosyl methionine as the substrate, converts phosphatidylethanolamine on the cytoplasmic leaflet to phosphatidylcholine, which is transported to the biliary leaflet. The aim of our study was to demonstrate and partially characterise methyltransferase activity in the bile canalicular membrane. METHODS: Organelles were obtained from hamster liver by homogenisation and separation by sucrose gradient ultracentrifugation. These, along with phosphatidylethanolamine, were incubated with radiolabelled s-adenosyl methionine. Phospholipids were separated by thin-layer chromatography and radioactivity was counted by scintigraphy. RESULTS: We demonstrated methyltransferase activity (nmol of SAMe converted/mg of protein/h at 37 degrees C) in the bile canalicular membrane of 0.442 (SEM 0.077, n=8), which is more than twice that found in the microsomes at 0.195 (SEM 0.013, n=8). The Km and pH optimum for the methyltransferase in the bile canalicular membrane and the microsomes were similar (Km 25 and 28 microM, respectively, pH 9.9 for both). The Vmax was different at 0.358 and 0.168 nmol of SAMe converted/mg of protein/h for the bile canalicular membrane and the microsomes, respectively. CONCLUSION: The presence of the methyltransferase activity in the bile canalicular membrane may be amenable to therapeutic manipulation.

Animals↗

Exercise counseling by primary care physicians in the era of managed care.

BACKGROUND: Recommendations from the Centers for Disease Control and Prevention (CDC) and the American College of Sports Medicine (ACSM) advise all adults to accumulate at least 30 minutes of moderate intensity physical activity on most, if not all, days of the week, but many U.S. adults engage in no leisure-time physical activity. Since primary care providers can play an important role in exercise counseling and prescription, we wanted to assess the proportion of primary care physicians from four hospitals who asked about exercise habits, counseled about exercise, and prescribed exercise; and the factors that were associated with their counseling and prescription habits. DESIGN: Survey of 326 internists, family practitioners, and internal medicine and family practice residents. RESULTS: One hundred seventy-five physicians completed the questionnaire (54% response rate). Two thirds of physicians reported asking more than half of their patients about exercise, 43% counseled more than half of their patients about exercise, but only 14% prescribed exercise for more than half of their patients. Only 12% of physicians were familiar with the new ACSM recommendations. Physicians aged 35 and over were more likely than physicians less than 35 year old to ask about (82% versus 60%), counsel about (58% versus 37%), and prescribe (30% versus 8%) exercise. Family practitioners were more likely to ask about (85% versus 62%) and counsel about (59% versus 39%) exercise than internists. Physicians who felt they had adequate exercise knowledge were more likely to ask about (72% versus 49%) and counsel about (48% versus 29%) exercise than those who felt their knowledge was inadequate. Finally, physicians who felt that they were successful in changing behavior were more likely to ask about and counsel about exercise. The most important barriers to exercise counseling were not having enough time and needing more practice in effective counseling techniques. CONCLUSION: Many primary care physicians are not asking about, counseling about, or prescribing exercise for their patients. Since primary care physicians are in the best position to provide individualized exercise prescriptions for their patients, future research should focus on training physicians in effective counseling techniques that can be done as brief interventions.

Adult↗

Comparison of DNA probe technology and automated continuous-monitoring blood culture systems in the detection of neonatal bacteremia.

OBJECTIVE: The present study assessed the ability of a rapid chemiluminescent DNA probe assay to detect bacterial growth in blood culture specimens before their detection by continuous-monitoring blood culture (CMBC) systems. STUDY DESIGN: Three newborn intensive care units, which are members of the National Institute of Child Health and Human Development Neonatal Research Network, participated in this study. Each center employs an automated CMBC system against which the DNA probe was compared. A total of 1700 blood cultures were analyzed. A 3-ml aliquot of culture medium was removed from each culture during early incubation, processed, and analyzed by the DNA probe. RESULTS: Of 1700 blood cultures, 130 (7.6%) were detected positive by a CMBC system. Coagulase-negative staphylococci (CNS) were present in 90 (69%) of the positive cultures, and 26 (29%) were detected by the DNA probe. Other organisms accounted for the remaining 40 positive cultures, and 31 (78%) of these were detected by the probe assay. Seventy-six percent of all positive cultures were detected by a CMBC system within 24 hours. Ninety-eight percent of all positive cultures were detected by a CMBC system within 48 hours. Of the two organisms that grew in a CMBC system beyond 48 hours, both were CNS and one of these was considered a contaminant. Therefore, 99% of clinically significant organisms were detected by a CMBC system within 48 hours. CONCLUSION: This DNA probe is not sufficiently sensitive to be clinically useful; however, automated CMBC systems are sufficiently sensitive to aid in clinical decision-making regarding the continuance or discontinuance of antibiotic therapy following 48 hours of culture incubation.

Bacteremia↗

An exploration of the sequence of a 2.9-Mb region of the genome of Drosophila melanogaster: the Adh region.

A contiguous sequence of nearly 3 Mb from the genome of Drosophila melanogaster has been sequenced from a series of overlapping P1 and BAC clones. This region covers 69 chromosome polytene bands on chromosome arm 2L, including the genetically well-characterized "Adh region." A computational analysis of the sequence predicts 218 protein-coding genes, 11 tRNAs, and 17 transposable element sequences. At least 38 of the protein-coding genes are arranged in clusters of from 2 to 6 closely related genes, suggesting extensive tandem duplication. The gene density is one protein-coding gene every 13 kb; the transposable element density is one element every 171 kb. Of 73 genes in this region identified by genetic analysis, 49 have been located on the sequence; P-element insertions have been mapped to 43 genes. Ninety-five (44%) of the known and predicted genes match a Drosophila EST, and 144 (66%) have clear similarities to proteins in other organisms. Genes known to have mutant phenotypes are more likely to be represented in cDNA libraries, and far more likely to have products similar to proteins of other organisms, than are genes with no known mutant phenotype. Over 650 chromosome aberration breakpoints map to this chromosome region, and their nonrandom distribution on the genetic map reflects variation in gene spacing on the DNA. This is the first large-scale analysis of the genome of D. melanogaster at the sequence level. In addition to the direct results obtained, this analysis has allowed us to develop and test methods that will be needed to interpret the complete sequence of the genome of this species. Before beginning a Hunt, it is wise to ask someone what you are looking for before you begin looking for it. Milne 1926

Alcohol Dehydrogenase↗

Optimum dose of ursodeoxycholic acid in primary biliary cirrhosis.

BACKGROUND: Ursodeoxycholic acid (UDCA) improves liver function tests and prolongs survival in primary biliary cirrhosis (PBC). The dose of 10- 15 mg/kg/day used in the large trials has largely been based on that used for gallstone dissolution. The only dose-response study of UDCA in PBC suggested that a dose of 8 mg/kg/day was the most efficacious. However, disease stage of the patients was not known, higher doses of UDCA were not tried and there was no 'washout period' between the different doses. The aim of this study was to determine the optimum dose of UDCA in early-stage PBC (stage 1 and 2). METHODS: Twenty-four biopsy-proven early-stage PBC patients (one male, 23 female) received five doses of UDCA (0, 300, 600, 900, 1200 mg/day) each for 8 weeks with 4-week washout periods between doses. Symptoms (pruritus, fatigue, diarrhoea) were assessed on a four-point scale (none, mild, moderate, severe). Liver function tests (LFTs) were performed using conventional methods, and serum bile acids were measured using gas liquid chromatography. RESULTS: The dose of 900 mg/day produced the greatest enrichment of UDCA in serum bile acids; although there was no difference in the enrichment of UDCA between the different doses. There was a trend towards normalization of the abnormal LFTs in a dose-dependent manner (for y-glutamyl transferase (yGT), alkaline phosphatase (ALP), alanine transaminase (ALT) and IgM). Multi-factorial analysis showed that UDCA treatment, irrespective of dose, was significantly better than placebo for all the variables. The 900 and 1200 mg doses were better than both 300 and 600 mg using yGT and total bilirubin as variables, better than 300 mg using ALP and IgM as variables, and better than 600 mg using albumin as a variable. No variables showed a significant difference between 900 and 1200 mg. CONCLUSION: The optimum dose of UDCA is 900 mg/day (equivalent to 13.5 mg/kg/day).

Adult↗

American Academy of Pediatrics. Committee on Practice and Ambulatory Medicine and Committee on Medical Liability. Pediatric physician profiling.

Employers, insurers, and other purchasers of health care services collect data to profile the practice habits of pediatricians and other physicians. This policy statement delineates a series of recommendations that should be adopted by health care purchasers to guide the development and implementation of physician profiling systems.

Benchmarking↗

Repressive and defensive coping styles predict resting plasma endorphin levels in the elderly.

Jamner, L.D., Schwartz, G.E., 1986, Psychosom. Med. 48, 211-223, have proposed that repressive and defensive coping are associated with greater central endogenous opioid activity. They reasoned that high-defensive (HD) participants' attenuated distress, increased pain tolerances, attenuated somatic symptomatology, and accentuated reports of positive emotions are consistent with actions of centrally active opioid peptides. The present study assessed plasma beta-endorphin (END) levels, Marlowe Crowne Social Desirability Scale (MCSD), and Taylor Manifest Anxiety Scale (TMAS) scores in men (n = 6) and women (n = 20) between the ages of 59 and 79. Contrary to predictions, HD had lower plasma endorphin levels than did low-defensive (LD) participants. Raw MCSD scores correlated negatively with endorphin levels. Findings were significant for women only, which may have been due to the small sample of men. The results are discussed as they related to the hypothesis that defensiveness involves alteration of central opioid systems.

Adaptation, Psychological↗

Oxygen permeability of a new type of high Dk soft contact lens material.

Lotrafilcon A is a biphasic block-copolymer, comprising a highly permeable siloxane-based polymeric phase, coupled with a water phase (hydrogel phase). The high oxygen permeability of this material, and the fact that it is a hydrogel, places it outside the applicability of both the polarographic ISO standard and coulometric ISO draft standards for contact lens Dk determination. The oxygen permeability (Dk) and transmissibility (Dk/t) of lotrafilcon A lenses were determined by an adaptation of the standard coulometric method. Lenses with a thickness (t) range from 30 microns to over 300 microns were measured in a liquid-to-gas and a gas-to-gas configuration in an effort to combine features of the ISO (draft) standards to yield a valid measurement of the intrinsic material's oxygen transmission characteristics. The following results, for lotrafilcon A, are the mean values and SE for the oxygen permeability coefficient (Dk) determined at 34 degrees C: 140 +/- 2 barrer with water overlay (liquid-to-gas) at 2100 rpm stirring speed, 150 +/- 5 barrer with water overlay (liquid-to-gas) at "infinite" stirring speed, and 170 +/- 2 barrer without water overlay (gas-to-gas), where barrer = 10(-11) (mlO2.cm)/(sec.cm2.mm Hg). Clinical lenses produced from this material are expected to be in the 60 to 90 microns thickness range, with an average center thickness of 80 microns. Given that the Dkmaterial is greater than or equal to 140 barrers, for this material, a parallel sided lens of 80 microns central thickness would exhibit a lens transmissibility (Dk/t) of at least 170 x 10(-9) mlO2/(sec.cm2.mm Hg) at 34 degrees C. This transmissibility is well in excess of the 87 x 10(-9) mlO2/(sec.cm2.mm Hg) value postulated to be sufficient to prevent overnight lens-induced corneal swelling and places it in the hyper-permeable material category.

Contact Lenses, Hydrophilic↗

Neuromuscular stimulation for upper extremity motor and functional recovery in acute hemiplegia.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the efficacy of neuromuscular stimulation in enhancing the upper extremity motor and functional recovery of acute stroke survivors. METHODS: Forty-six stroke survivors admitted to an inpatient rehabilitation unit were randomly assigned to receive either neuromuscular stimulation or placebo. Twenty-eight subjects completed the study. The treatment group received surface neuromuscular stimulation to produce wrist and finger extension exercises. The control group received placebo stimulation over the paretic forearm. All subjects were treated 1 hour per day, for a total of 15 sessions. Outcomes were assessed in a blinded manner with the upper extremity component of the Fugl-Meyer Motor Assessment and the self-care component of the Functional Independence Measure at pretreatment, after treatment, and at 4 and 12 weeks after treatment. RESULTS: The treatment subjects and control subjects had comparable baseline characteristics. Parametric analyses revealed significantly greater gains in Fugl-Meyer scores for the treatment group after treatment (13.1 versus 6.5; P=0.05), at 4 weeks after treatment (17.9 versus 9.7; P=0.05), and at 12 weeks after treatment (20.6 versus 11.2; P=0.06). Functional Independence Measure scores were not different between groups at any of the time periods (P>0.10). CONCLUSIONS: Data suggest that neuromuscular stimulation enhances the upper extremity motor recovery of acute stroke survivors. However, the sample size in this study was too small to detect any significant effect of neuromuscular stimulation on self-care function.

Acute Disease↗

Protein phosphatase 4 is an essential enzyme required for organisation of microtubules at centrosomes in Drosophila embryos.

The protein serine/threonine phosphatase 4 (PP4), which localises to centrosomes/spindle pole bodies in human cells, is shown to exhibit a similar localisation in Drosophila cells and embryos and possess a highly conserved (91% identical) amino acid sequence from humans to invertebrates. A homozygous Drosophila melanogaster strain mutant in the PP4 gene at 19C1-2 has been produced using P element mutagenesis. This strain, termed centrosomes minus microtubules (cmm), has reduced amounts of PP4 mRNA, approximately 25% of normal PP4 protein in early embryos and exhibits a semi-lethal phenotype with only 10% viability in certain conditions. Reversion mutagenesis shows that the phenotype is due to the presence of the P element in the PP4 mRNA. In early cmm embryos, nuclear divisions become asynchronous and large regions containing centrosomes with no well defined radiating microtubules are visible. In such areas, most nuclei arrest during mitosis with condensed DNA, and mitotic spindle microtubules are either absent, or aberrant and unconnected to the centrosome. A reduction in the staining of gamma-tubulin at centrosomes in cmm embryos suggests a conformational change or relocation of this protein, which is known to be essential for initiation of microtubule growth. These findings indicate that PP4 is required for nucleation, growth and/or stabilisation of microtubules at centrosomes/spindle pole bodies.

Animals↗

Short report: Decrease in seroprevalence of antibodies to hantavirus in rodents from 1993-1994 hantavirus pulmonary syndrome case sites.

Rodent trapping was conducted at seven hantavirus pulmonary syndrome (HPS) case sites from June 1993 to March 1994 during the HPS outbreak in the southwestern United States. To determine if there were changes in the rodent population or the hantavirus seroprevalence in rodents since the HPS outbreak, rodents were trapped at the same sites three years later using the same trapping protocol. The trap success decreased from the numbers trapped during the outbreak, however, the number of Peromyscus, as a percentage of the total rodents captured, did not noticeably decrease. In addition, the seroprevalence of hantavirus antibodies in Peromyscus decreased significantly (P < 0.0001).

Animals↗