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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
PubMed1998

The incidence of ophthalmologic interventions in children with birth weights less than 1251 grams. Results through 5 1/2 years. Cryotherapy for Retinopathy of Prematurity Cooperative Group.

OBJECTIVE: This study aimed to report the frequency of ophthalmologic surgical and medical therapies provided to children with birth weights less than 1251 g who had all stages of retinopathy of prematurity (ROP). In addition, this study aimed to report the initial age at which such procedures are provided and to report the frequency of cerebrospinal fluid shunts. DESIGN: Observational case series with prospective data collection. PARTICIPANTS: Children from the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) with birth weights less than 1251 g served as subjects. Group A included 257 children from all 23 CRYO-ROP study centers who had threshold ROP, who had participated in the randomized trial of cryotherapy, and who had survived to age 1 year. Group B included 1208 children from 5 of the 23 study centers who had varying severity of ROP (69 had threshold ROP) and who had participated in a 5 1/2-year study of the natural history of ROP. MAIN OUTCOME MEASURES: Investigators documented medical and surgical ophthalmologic interventions through age 5 1/2 years as well as cerebrospinal fluid shunting surgery for hydrocephalus through age 2 years. RESULTS: Group A was composed of 257 children with threshold ROP who underwent 226 ocular interventions in addition to cryotherapy (0.9 intervention per child). The most common treatments performed on the randomized cohort of children were vitrectomy (26% of patients), lensectomy (18%), amblyopia therapy (20%), and strabismus surgery (10%). Cataract surgery not associated with vitrectomy was performed infrequently (2%) and was performed equally often in treated and control eyes. Amblyopia therapy was prescribed as often for treated as for control eyes. Cerebrospinal fluid shunts were placed in 11% of these children. Group B was composed of 1208 natural history patients who underwent 239 ophthalmologic interventions (0.4 intervention per child). Strabismus surgery was the most commonly performed procedure for the natural history cohort of children (6% of the children). Amblyopia therapy was prescribed for 7% of the natural history patients. Cerebrospinal fluid shunts were required by 3% of the natural history infants, more often in children with more severe ROP. CONCLUSIONS: These premature infants underwent a large number of ophthalmologic treatments during the first 5 1/2 years of life. The long-term costs of both extreme prematurity and ROP include not only the initial ablative therapy for ROP and societal loss due to blindness that still occurs in some cases, but also the ongoing costs of caring for eye problems.

Amblyopia↗
PubMed1998

NMR analysis of the N-terminal SRCR domain of human CD5: engineering of a glycoprotein for superior characteristics in NMR experiments.

CD5 is a type-I transmembrane glycoprotein found on thymocytes, T-cells and a subset of B-cells. The extracellular region consists of three domains belonging to the scavenger receptor cysteine-rich (SRCR) superfamily for which the three-dimensional polypeptide fold is as yet unknown. Glycosylated CD5 domain 1 (CD5d1) has been obtained by expression by secretion from both Chinese hamster ovary (CHO) cells and Pichia pastoris. Recombinant CD5d1 expressed in this manner was shown to be correctly folded by binding to anti-CD5 L17F12/Leu1 monoclonal antibody. Preliminary nuclear magnetic resonance (NMR) spectra obtained for CD5d1 (residues 1-118) had spectral dispersion typical of a folded protein, but otherwise of such poor quality that NMR structural studies were not feasible. The analysis of glycoproteins by NMR is frustrated by sample heterogeneity and poor spectral quality associated with glycan resonance overlap and the potential for increased line-widths due to the large hydrodynamic volume. In order to pursue NMR structural studies of CD5d1 it was necessary to optimize the quality of NMR spectra of CD5d1. A range of constructs of varying length and carbohydrate content were expressed in CHO cells and in P. pastoris. In addition the P. pastoris CD5d1 proved susceptible to N-glycan cleavage with endoglycosidase H. The protein products were characterised using size exclusion chromatography, NMR measurement of translational self-diffusion coefficients and two-dimensional 1H nuclear Overhauser effect spectroscopy experiments. Removal of an eight residue O-glycosylated C-terminal peptide, in particular, resulted in significant improvements in the quality of the CD5d1 NMR data, while retaining native protein structure. Two-dimensional heteronuclear NMR spectroscopy of nitrogen-15 isotope labelled deglycosylated CD5d1 (residues 1-110) prepared from P. pastoris suggests that this protein product is now amenable to solution structure determination.

Amino Acid Sequence↗
PubMed1998

A lasting public health response to an outbreak of HIV infection in a Scottish prison?

Between April and June 1993, 8 cases of acute clinical hepatitis B infection and 2 seroconversions to HIV infection were detected among drug injecting inmates of HM Prison Glenochil in Scotland. To prevent the further spread of infection, an initiative which involved counselling and voluntary attributable HIV testing was conducted over a 10-day period commencing at the end of June. A team of 18 counsellors and phlebotomists was brought together rapidly as part of a unique organizational exercise in the field of public health. Fourteen cases of HIV infection were identified of which 13 were almost certainly infected in Glenochil. Following the exercise, a range of harm reduction measures for injecting prisoners was introduced; these included the availability of hepatitis B vaccine, provision of bleach tablets which could be used to clean injecting equipment, a methadone detoxification programme, increased training for prison officers and improved access to drug and harm minimization counselling for inmates. By mid-1996 all these measures had been sustained and several could be found in many other prisons throughout Scotland. Follow-up investigations showed no evidence of epidemic spread of HIV during the 12 months after the initiative. While the frequency of injecting and needle/syringe sharing may have decreased over the last 3 years, these activities are still being reported and it is highly likely that transmissions of bloodborne infections, in particular hepatitis C, continue to occur. The surveillance and prevention of infections associated with injecting drug use in the prison setting remain a high public health priority.

Disease Outbreaks↗
PubMed1998

Sensory deprivation and chronic pain: a review of the literature.

AIMS AND OBJECTIVES: The aim of this paper is to explore the literature into the use of 'Snoezelen' (Sensory Stimulation) for the management of chronic pain. Within the literature there are a number of research studies which have investigated the concept of sensory deprivation and these are considered. The studies indicate the potential of sensory input as a field of research in particular relation to the care of patients within hospital settings where they are removed from their 'normal' level of sensory input and could subsequently experience sensory deprivation. The relationship between sensory restriction and chronic pain is emphasized. This links with investigations of sensory stimulation (Snoezelen) as a potential strategy for the management of chronic pain. CONCLUSIONS: In conclusion, it is suggested that sensory deprivation cannot exist and the term 'sensory restriction' would be more appropriate. It is proposed that there is a need to develop a tool to assist carers in identifying the existence of sensory restriction in their specific client groups to provide a basis for intervention.

Adult↗
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↗