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Biomedical subjects

B Davis

Publications and source records attributed to B Davis.

At least 91 records · Page 5Linked to original sources
PubMed1997

Benzidine-DNA adduct levels in human peripheral white blood cells significantly correlate with levels in exfoliated urothelial cells.

In a cross-sectional study of 33 workers exposed to benzidine and benzidine dyes and 15 non-exposed controls, we previously reported that exposure status and internal dose of benzidine metabolites were strongly correlated with the levels of specific benzidine-DNA adducts in exfoliated urothelial cells. We also evaluated DNA adduct levels in peripheral white blood cells (WBC) of a subset of 18 exposed workers and 7 controls selected to represent a wide range of adducts in exfoliated urothelial cells. Samples were coded and then DNA was analyzed using 32P-postlabeling, along with n-butanol extraction. One adduct, which co-chromatographed with a synthetic N-(3'-phospho-deoxyguanosin-8-yl)-N'-acetylbenzidine standard, predominated in those samples with adducts present. The median level (range) of this adduct in WBC DNA was 194.4 (3.2-975) RAL x 10(9) in exposed workers and 1.4 (0.1-6.4) in the control subjects (p = 0.0002, Wilcoxon Rank Sum Test). There was a striking correlation between WBC and exfoliated urothelial cell adduct levels (Pearson r = 0.84, p < 0.001) among exposed subjects. In addition, the sum of urinary benzidine, N-acetylbenzidine and N,N'-diacetylbenzidine correlated with the levels of this adduct in both tissues. This is the first study in humans to show a relationship for a specific carcinogen adduct in a surrogate tissue and in urothelial cells, the target for urinary bladder cancer.

Adult↗
PubMed1997

Deficits of [3H]D-aspartate binding to glutamate uptake sites in striatal and accumbens tissue in patients with schizophrenia.

The hypothesis involving glutamate in the neuropathology of schizophrenia has attracted great interest. Several studies report dysfunctions in glutamatergic systems, including alterations in kainate and N-methyl-D-aspartate (NMDA) receptors in various areas, as well as changes in the number of glutamate uptake sites. We have studied this further using [3H]D-aspartate binding to glutamate uptake sites as a measure of the integrity of presynaptic glutamate systems in several areas (caudate nucleus, putamen, nucleus accumbens, frontal cortex and temporal cortex) of brain tissue taken at autopsy from schizophrenic patients and controls. A significant decrease in the number of glutamate uptake sites was apparent in caudate nucleus, putamen and nucleus accumbens in the schizophrenia group, indicating an impaired glutamatergic innervation of these subcortical regions. However, no significant changes were found in the two cortical regions studied.

Aged↗
PubMed1997

Prevention of an increase in plasma cortisol during hypoglycemia preserves subsequent counterregulatory responses.

The aim of this study was to determine whether preventing increases in plasma cortisol during antecedent hypoglycemia preserves autonomic nervous system counterregulatory responses during subsequent hypoglycemia. Experiments were carried out on 15 (8 male/7 female) healthy, overnight-fasted subjects and 8 (4 male/4 female) age- and weight-matched patients with primary adrenocortical failure. 5 d before a study, patients had their usual glucocorticoid therapy replaced with a continuous subcutaneous infusion of cortisol programmed to produce normal daily circadian levels. Both groups underwent identical 2-d experiments. On day 1, insulin was infused at a rate of 1.5 mU/kg per min, and 2-h clamped hypoglycemia (53+/-2 mg/dl) was obtained during the morning and afternoon. The next morning, subjects underwent an additional 2-h hypoglycemic (53+/-2 mg/ dl) hyperinsulinemic clamp. In controls, day 2 steady state epinephrine, norepinephrine, pancreatic polypeptide, glucagon, growth hormone, and muscle sympathetic nerve activity were significantly blunted (P < 0.01) compared with day 1 hypoglycemia. In marked contrast, when increases of plasma cortisol were prevented in the patient group, day 2 neuroendocrine, muscle sympathetic nerve activity, hypoglycemic symptoms, and metabolic counterregulatory responses were equivalent with day 1 results. We conclude that (a) prevention of increases of cortisol during antecedent hypoglycemia preserves many critical autonomic nervous system counterregulatory responses to subsequent hypoglycemia; (b) hypoglycemia-induced increases in plasma cortisol levels are a major mechanism responsible for causing subsequent hypoglycemic counterregulatory failure; and (c) our results suggest that other mechanisms, apart from cortisol, do not play a major role in causing hypoglycemia-associated autonomic failure.

Addison Disease↗
PubMed1997

Hydrogen exchange in chymotrypsin inhibitor 2 probed by mutagenesis.

Two-dimensional NMR spectroscopy has been used to monitor hydrogen-deuterium exchange in chymotrypsin inhibitor 2. Application of two independent tests has shown that at pH 5.3 to 6.8 and 33 to 37 degrees C, exchange occurs via an EX2 limit. Comparison of the exchange rates of a number of mutants of CI2 with those of wild-type identifies the pathway of exchange, whether by local breathing, global unfolding or a mixture of the two pathways. For a large number of residues, the exchange rates were unaffected by mutations which destabilized the protein by up to 1.9 kcal mol(-1), indicating that exchange is occurring through local fluctuations of the native state. A small number of residues were found for which the mutations had the same effect on the rate constants for exchange as on the equilibrium constant for unfolding, indicating that these residues exchange by global unfolding. These are residues that have the slowest exchange rates in the wild-type protein. We see no correspondence between these residues and residues involved in the nucleation site for the folding reaction identified by protein engineering studies. Rather, the exchange behaviour of CI2 is determined by the native structure: the most protected amide protons are located in regions of hydrogen bonding, specifically the C terminus of the alpha-helix and the centre of the beta-sheet. A number of the most slowly exchanging residues are in the hydrophobic core of the protein.

Binding Sites↗
PubMed1997

Following co-operative formation of secondary and tertiary structure in a single protein module.

We have prepared a family of peptide fragments of the 64 amino acid protein chymotrypsin inhibitor (CI2), corresponding to progressive elongation from the N terminus, in order to elucidate the basis of conformational preferences in single-domain proteins and to obtain insights into their conformational pathway. Structural analysis of the fragment comprising the first 50 residues, CI2(1-50), indicates that it is mainly disordered, with patches of hydrophobic residues exposed to the solvent. Structural characterisation of the fragment CI2(1-63) which lacks only the C-terminal glycine, Gly64, shows native-like structure in all regions of the fragment. The study provides insights into the contribution of specific residues to the stability and co-operativity of the intact protein. We define a phiNMR value, derived from chemical shift analysis, which describes the build-up of structure at the level of individual residues (protons). All the macroscopic probes used to study the growth of structure in CI2 on elongation of the chain (circular dichroism, fluorescence and gel filtration) are in agreement with the residue-by-residue description by NMR. It is seen that secondary and tertiary structure build up in parallel in the fragments and show similar structures to those developed in the transition state for folding of the intact protein.

Amino Acid Sequence↗
PubMed1997

The adaptability of Escherichia coli thioredoxin to non-conservative amino acid substitutions.

The adaptability of Escherichia coli thioredoxin to the substitution of a series of non-natural amino acids has been investigated. Different thiosulfonated alkyl groups were inserted into the hydrophobic core of the protein in position 78 via disulfide bonding with a buried cysteine residue as previously described (Wynn R, Richards FM. 1993. Unnatural amino acid packing mutants of Escherichia coli thioredoxin produced by combined mutagenesis/chemical modification techniques. Protein Sci 2:395-403). The side chains added to the cysteine included methyl, ethyl, n-propyl, n-butyl, n-pentyl, and cyclo-pentyl derivatives. The side chains appear to exploit the presence of the large cavities to incorporate these variant forms, enabling the protein to fold and have some activity. Solution structural and kinetic data suggested that these substitutions had little effect on the overall fold of the protein. Thermodynamic data revealed that the entropic effect of restricting the side chains in the folded protein has an effect on the stability. The variant forms of thioredoxin have different propensities to form dimers despite the limited structural perturbations. Molecular modeling studies allow the conformation of the side chains to be assessed.

Calorimetry, Differential Scanning↗
PubMed1997

Systemic lupus erythematosus-associated lymphoproliferative disorder: report of a case and discussion in light of the literature.

A case of autoimmune disease-associated lymphadenopathy (ADAL) with histological, immunophenotypic, Epstein-Barr virus (EBV) in situ hybridization, and genotypic analyses is presented. The patient had a well-documented history of systemic lupus erythematosus (SLE) and was found at autopsy to have massive lymphadenopathy, thymic enlargement, pulmonary nodules, and polyclonal serum dysproteinemia. Histological examination revealed a polymorphous lymphoid infiltrate containing many plasma cells, rare immunoblasts, and a pronounced arborizing vasculature. No foci of necrosis were found and there was no evidence of lymphocyte depletion. The plasma cells were immunophenotypically polyclonal and no EBV mRNA (EBER-1) or gene rearrangements were identified. The unusual gross features, which resembled a malignant lymphoproliferative process, as well as the unusual histological features make this case a notable addition to the spectrum of atypical lymphoproliferative disorders associated with an autoimmune disorder. We conclude that although reminiscent of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD), this case lacks the diagnostic features of AILD, and is, perhaps, best classified as an autoimmune disease-associated lymphadenopathy (ADAL).

Adult↗
PubMed1997

Amplification and expression of the cyclin D1 gene in anal and esophageal squamous cell carcinomas.

Cyclin D1 is a cell-cycle regulator and candidate proto-oncogene implicated in the pathogenesis of numerous tumor types. Amplification of the cyclin D1 gene occurs commonly in esophageal squamous cell carcinomas. However, no studies have examined the role of cyclin D1 in anal carcinogenesis. We examined 20 esophageal squamous cell carcinomas and 24 anal carcinomas for cyclin D1 alterations. Protein expression was evaluated by immunohistochemistry using the cyclin DIGM antibody (Novocastra, Newcastle upon Tyne, UK). Cyclin D1 amplification was examined by fluorescent in situ hybridization (FISH), using a cyclin D1 probe obtained from Toshiya Inaba at St. Jude Children's Research Hospital, Memphis, TN. The FISH sections were analyzed using a Leica (Deerfield, IL) confocal microscope. By immunohistochemistry, 75% of esophageal carcinomas showed evidence of cyclin D1 expression. Cyclin D1 amplification was detected by FISH in 65% of esophageal cancers. There was good correlation between cyclin D1 protein expression and gene amplification, although some tumors showed protein overexpression in the absence of gene amplification. Among the 24 anal carcinomas studied, 8% showed weak cyclin D1 immunoreactivity in rare tumor cells. None of the anal tumors showed cyclin D1 amplification. We conclude that cyclin D1 alterations are common in esophageal carcinomas but do not appear to be important in anal carcinogenesis. Immunohistochemical detection of cyclin D1 protein overexpression is a good predictor of cyclin D1 amplification.

Anus Neoplasms↗
PubMed1997

Family support and conflict: prospective relations to adolescent depression.

The relations between family support, family conflict, and adolescent depressive symptomatology were examined longitudinally in a sample of 231 female and 189 male adolescents and their mothers. Structural equation models revealed that less supportive and more conflictual family environments were associated with greater depressive symptomatology both concurrently and prospectively over a 1-year period. Conversely, adolescent depressive symptomatology did not predict deterioration in family relationships. Depressive symptomatology and, to a greater extent, family characteristics showed high levels of stability over the 1-year period. Counter to our expectations, the relations between family variable and depressive symptomatology were similar for boys and girls. The results suggest that the quality of family interactions is relevant for understanding the development of depressive symptoms in adolescents.

Adolescent↗
PubMed1997

A computer-interfaced vertometer system for contact lenses.

BACKGROUND: The conventional vertometer (lensometer) is difficult to use for accurate measurement of contact lenses whose back vertex power (BVP) varies across the optic zone. BVPs of multifocal rigid and soft contact lenses have previously been measured using a conventional vertometer incorporating the Scheiner principle, which makes use of two light paths equidistant from the center of the lens. METHODS: We have developed a computer-based vertometer system based on the Scheiner principle which can be used to produce a profile of BVPs across rigid and soft contact lenses. A computer interface to the vertometer allows rapid acquisition of readings and software-based ray tracing derives in-air dioptric power readings across the optic zone at specific ray heights. RESULTS: Results are presented for soft and rigid, and spherical and aspheric surface contact lenses. CONCLUSIONS: The system improves the measurement resolution of a standard vertometer and shows an acceptable level of precision and accuracy for most applications.

Contact Lenses↗
PubMed1997

Differences between chest pain observation service patients and admitted "rule-out myocardial infarction" patients.

OBJECTIVE: To compare and contrast the patient characteristics of ED patients at low risk for acute cardiac ischemia who were assigned to a chest pain observation service vs those admitted to a monitored inpatient bed for "rule-out acute myocardial infarction" (R/O MI). METHODS: This was a retrospective, cross-sectional comparison of adult patients considered at relatively low risk for cardiac ischemia and who were evaluated in 1 of 2 settings: a short-term observation service and an inpatient monitored bed. All patients had an ED final diagnosis of "chest pain," "R/O MI," or "unstable angina" during the 7-month study period. Demographic features and presenting clinical features were examined as a function of site of patient evaluation. RESULTS: Of 531 study patients, 265 (50%) were assigned to the observation service. Younger age (OR = 1.75, 95% CI 1.26, 2.44, for each decrement of 20 years), the complaint of "chest pain" (OR = 2.35, 95% CI 1.34, 4.12), and the absence of prior known coronary artery disease (OR = 1.64, 95% CI 1.13, 2.38) were the principal independent factors associated with assignment to a chest pain observation service bed. CONCLUSIONS: Patients evaluated in a chest pain observation service appear to have different clinical characteristics than other individuals admitted to a monitored inpatient bed for "R/O MI." Investigators should address differences in clinical characteristics when making outcome comparisons between these 2 patient groups.

Adult↗
PubMed1997

Prospective study of equine colic incidence and mortality.

A prospective study of one year was conducted on 31 horse farms to obtain population based estimates of incidence, morbidity and mortality rates of equine colic. Farms with greater than 20 horses were enrolled by randomly selecting horse owners from 2 adjacent counties of Virginia and Maryland. Descriptive information for 1427 horses was collected at the initiation of the study and updated at 3 month intervals. Time on the farm during the study was tabulated for each horse. When colic was reported by the owner, investigators visited the farm to obtain information about the colic. The crude incidence density rate of colic was 10.6 colic cases/100 horse-years, based on 104 cases/358,991 horse-days. The median farm specific incidence density rate was 7 cases/100 horse-years, and the range for individual farms varied from 0 to 30 colic cases/100 horse-years. A specific diagnosis was not made for 84 (81%) of colic episodes. Seventy colic episodes (67%) were treated by a veterinarian. Drugs were used in 83 (80%) colic episodes, and 78 (75%) of colic cases were mild, requiring no treatment or resolving after only one treatment. Four horses required colic surgery. Fourteen (13%) horses had more than one episode of colic during the year. Mortality from all causes of death was 2.5 deaths/100 horse-years, mortality rate for colic was 0.7 deaths/100 horse-years. Proportional mortality rate of colic, 28%, was higher than for any other cause of death. Horses less than age 2 years or greater than age 10 years had lower incidence than horses age 2-10 years. No difference in colic risk between genders was identified. Arabian horses had the lowest and Thoroughbreds the highest breed specific incidence rates. Horses used for eventing, or in training had a statistically significant higher incidence rate of colic compared to mature horses with no use (pets, retired, on pasture with no stated purpose). Horses used for lessons or with no use had the lowest incidence rates.

Age Factors↗
PubMed1997

Prospective study of equine colic risk factors.

A 1 year prospective study was conducted on 31 horse farms to identify risk factors for equine colic. Farms were randomly selected from a list from 2 adjacent counties of Virginia and Maryland, USA. The association between colic and farm or individual horse risk factors related to management, housing, pasture, use, nutrition, health and events was first examined by univariate statistical analysis. Individually significant (P < = 0.25 for farm factors, P < = 0.10 for horse factors) variables were used in a stepwise multivariable forward logistic regression to select explanatory factors (P < = 0.05). Analysis was conducted at 2 levels: farm and individual horse with farm specified as a random effects variable. No farm-level variables were significant. Significant horse-level variables included: age, odds ratio (OR) = 2.8 for horses age 2-10 years compared to < 2 years; history of previous colic, OR = 3.6 relative to no colic; changes in concentrate feeding during the year (1 per year, OR = 3.6, more than 1, OR = 2.2) relative to no changes; more than 1 change in hay feeding during the year, OR = 2.1 relative to no changes; feeding high levels of concentrate (> 2.5 kg/day dry matter, OR = 4.8, > 5 kg/day dry matter, OR = 6.3) relative to feeding no concentrate; and vaccination with monocytic ehrlichiosis vaccine during the study, OR = 2.0 relative to no vaccination. Feeding a whole grain with or without other concentrate components reduced risk, OR = 0.4, relative to feeding no whole grain. Results of the study suggest that diet and changes in diet are important risks for colic in a population of horses on farms.

Analysis of Variance↗
PubMed1997

Effect of practice guidelines on therapeutic bed use.

Therapeutic beds, though clinically beneficial, can prove to be costly if their use is not directed. In this research utilization project, the use of therapeutic beds in five patient care units and one intensive care unit in a 300-bed acute care hospital were evaluated before and after the implementation of practice guidelines. Usage time and cost for each patient were measured and compared over the same four-month period in 1994 and 1995. Our findings indicated there were no significant differences between the two groups with regard to the time patients spent on therapeutic beds and the total cost of these beds. The mean time on the bed and the mean cost per patient were, however, lower for the practice guideline group. It was concluded that even without demonstrating significant differences, practice guidelines are a useful tool in providing a standard for nursing practice when caring for patients in the acute care setting.

Beds↗