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Biomedical subjects

G Brown

Publications and source records attributed to G Brown.

At least 145 records · Page 8Linked to original sources
PubMed1998

Ethnoveterinary medicines used for ruminants in Trinidad and Tobago.

Ethnoveterinary research was conducted in Trinidad and Tobago in 1995, in order to document existing ethnoveterinary practices. This paper describes 20 medicinal plants used to treat ruminants. The main plants used were Azadirachta indica and Curcuma longa. Medicinal plants were used predominantly for endoparasites, internal and external injuries and pregnancy-related conditions. A 4-stage process was used to conduct the research and document the ethnoveterinary practices. This documentation could provide a foundation for the further scientific study and verification of those practices which merit such study.

Animals↗
PubMed1998

Stimulation of melanogenesis in a human melanoma cell line by bistratene A.

The polyether toxin, bistratene A, induced morphological and functional differentiation of a human melanoma cell line (MM96E). The cells became blocked at the G2/M transition and elaborated a number of processes. Tyrosinase activity and melanin content were substantially increased. Northern blot analysis showed up-regulation of mRNA for several genes known to be involved in melanin biosynthesis (pmel17, pmel34, and tyrosinase related proteins, TRP-1 and TRP-2). Bistratene A induced the phosphorylation of several proteins as assessed by 2D gel electrophoresis and one of these was identified as stathmin (oncoprotein 18), a cell-cycle regulated phosphoprotein. Bistratene A specifically induced the translocation of protein kinase Cdelta (PKCdelta) from a soluble to a particulate fraction without affecting other isoforms. These results implicate a role for protein kinase Cdelta in the induction of differentiation of this human melanoma cell line.

Acetamides↗
PubMed1998

Observations on ethnoveterinary medicines in Trinidad and Tobago.

In 1995 research was conducted in Trinidad and Tobago with the aim of collecting knowledge on ethnoveterinary medicines in order to lay a foundation for further scientific study and validation. This paper describes only the ethnoveterinary practices used in the poultry sub-sector. A four stage process was used to conduct the research and document these ethnoveterinary practices. 28 ethnoveterinary respondents were identified using a modified Rapid Rural Appraisal (RRA) technique, the student essay method. Semi-structured interviews were conducted with these respondents as well as with 30 veterinarians, 27 extension officers and 19 animal health assistants/agricultural officers, and the 7 key respondents that they identified. 5 participatory workshops were then held with 55 of the respondents interviewed to discuss the data generated from the interviews and to determine dosages for some of the plants mentioned. 12 plant species were used to treat 4 categories of health problems common to poultry production. Aloe vera, Bryophyllum pinnatum, Citrus sp. and Momordica charantia were the main medicinal plants being used.

Agriculture↗
PubMed1998

Pattern and morphogenesis in skin.

Models dealing with the development of hair and feather follicles commonly predict that the factors initiating morphogenesis also specify patterns of follicle distribution. The factors have been postulated as chemical or mechanical instabilities which, at certain threshold concentrations, determine both the location of follicles and their form. The models tend to focus on the earliest waves of induction, where follicles develop at separate, non-randomly spaced initiation sites in skin. However, in many animals, there are later waves of initiation, some of which give rise to compound follicles. These are bundles of follicles that arise by branching from the necks of those formed earlier and share a common pilary canal when mature. In some species, compound follicles make the greatest numerical contribution to the follicle population. Measurements of the frequencies of single and branched follicles in sheep selection lines with different follicle densities (from previous studies by Moore et al.) revealed that the follicles which formed first during foetal life (primary and original secondary populations) were established at separately identifiable sites in the skin, called here "initiation sites". However, there were also later waves of development, contributing follicles exclusively by the process of branching (the derived secondary population). Final follicle densities were not correlated with the densities of initiation sites. The observations suggested that mechanisms specifying the positional values of initiation sites differed from those determining follicle number. The final densities of the follicle populations in the sheep lines were also highly negatively correlated with the diameters of the wool fibres grown. The close statistical relationship suggested that the two parameters were developmentally linked. However, whereas fibre characteristics are realised when the follicle is mature, density is established earlier, during foetal life. We have reconciled these observations with the following hypothesis: a population of cells, committed to a follicular pathway of development, differentiates in the skin at or before the first wave of initiation. Subpopulations of the committed cells subsequently participate in each follicle initiation event, the number in each subpopulation ultimately determining fibre dimensions. Follicle initiation continues until most or all of the original population have been utilised. Transplantation and skin recombinant studies have demonstrated that the cells forming the dermal papilla of the follicle participate in follicle initiation and have inductive effects on epidermal tissue. Papilla size is also correlated with fibre diameter in the mature follicle. These attributes are consistent with those described for the committed cell population.

Animals↗
PubMed1998

Spatially independent activity patterns in functional MRI data during the stroop color-naming task.

A method is given for determining the time course and spatial extent of consistently and transiently task-related activations from other physiological and artifactual components that contribute to functional MRI (fMRI) recordings. Independent component analysis (ICA) was used to analyze two fMRI data sets from a subject performing 6-min trials composed of alternating 40-sec Stroop color-naming and control task blocks. Each component consisted of a fixed three-dimensional spatial distribution of brain voxel values (a "map") and an associated time course of activation. For each trial, the algorithm detected, without a priori knowledge of their spatial or temporal structure, one consistently task-related component activated during each Stroop task block, plus several transiently task-related components activated at the onset of one or two of the Stroop task blocks only. Activation patterns occurring during only part of the fMRI trial are not observed with other techniques, because their time courses cannot easily be known in advance. Other ICA components were related to physiological pulsations, head movements, or machine noise. By using higher-order statistics to specify stricter criteria for spatial independence between component maps, ICA produced improved estimates of the temporal and spatial extent of task-related activation in our data compared with principal component analysis (PCA). ICA appears to be a promising tool for exploratory analysis of fMRI data, particularly when the time courses of activation are not known in advance.

Algorithms↗
PubMed1998

Identification of residues within the herpes simplex virus type 1 origin-binding protein that contribute to sequence-specific DNA binding.

Gene UL9 of herpes simplex virus type 1 encodes an 851-amino-acid protein which is essential for viral DNA synthesis and functions as a sequence-specific origin-binding protein and DNA helicase. We generated monoclonal antibodies against purified UL9 protein and identified one such antibody (MAb 13924) that can block the interaction of the UL9 C-terminal DNA-binding domain (amino acids 534-851) with its recognition sequence. MAb 13924 interacted with immobilized peptides containing residues 780-786 of UL9. Although the corresponding region of the homologous protein encoded by varicell-azoster virus differs at only a single position it was not recognized by MAb 13924. Site-directed mutagenesis experiments confirmed that residues within this region contribute to the epitope recognized by MAb 13924 and may be involved in sequence-specific DNA binding. In addition, all eight lysine residues within the DNA-binding domain were separately changed to alanine and the DNA-binding properties of the mutated proteins were examined. The results showed that lysine residues that are located close to the peptide recognized by MAb 13924 or lie within the region of the DNA-binding domain most highly conserved among homologous alphaherpesvirus proteins play a role in sequence-specific DNA binding. Moreover, alteration of a lysine residue 18 amino acids from the recognized peptide prevented the interaction of MAb 13924 with the UL9 C-terminal DNA-binding domain. Three helical segments are predicted to occur within the region containing mutations that affect sequence-specific binding and interaction with MAb 13924.

Amino Acid Sequence↗
PubMed1998

Implementation of a clinical practice guideline for stress ulcer prophylaxis increases appropriateness and decreases cost of care.

OBJECTIVE: To develop, implement and evaluate a practice guideline for stress ulcer prophylaxis. DESIGN: Before-after study. SETTING: Ten-bed Intensive Care Unit (ICU) and 4-bed Step-down Unit in a teaching hospital. PATIENTS AND PARTICIPANTS: Fifty patients admitted during 1 year before and 50 patients admitted 3-6 months after introduction of the guideline. INTERVENTION: Introduction of the practice guideline by dissemination of pocket cards, seminars and "academic detailing". MEASUREMENTS AND RESULTS: Appropriateness (defined as proportion of days in which the prophylaxis met the criteria in the guideline), incidence of gastrointestinal bleeding and of ventilator-associated pneumonia, length of stay in ICU and in hospital, ventilator days. ICU mortality and medication costs for stress ulcer prophylaxis. After the introduction of the guideline, appropriateness increased from 75.8% to 91.1%, and medication costs decreased from C $2.50/day to C $1.30/day. There were no differences in any clinical outcomes. Predictors of appropriate use or the withholding of prophylaxis were the introduction of the guideline, lack of an indication for prophylaxis and number of days studied. CONCLUSIONS: Introduction of this guideline was associated with an increase in appropriateness of prophylaxis and a decrease in medication costs.

Algorithms↗
PubMed1998

Hairpin coding end opening is mediated by RAG1 and RAG2 proteins.

Despite the importance of hairpin opening in antigen receptor gene assembly, the molecular machinery that mediates this reaction has not been defined. Here, we show that RAG1 plus RAG2 can open DNA hairpins. Hairpin opening by RAGs is not sequence specific, but in Mg2+, hairpin opening occurs only in the context of a regulated cleavage complex. The chemical mechanism of hairpin opening by RAGs resembles RSS cleavage and 3' end processing by HIV integrase and Mu transposase in that these reactions can proceed through alcoholysis. Mutations in either RAG1 or RAG2 that interfere with RSS cleavage also interfere with hairpin opening, suggesting that RAGs have a single active site that catalyzes several distinct DNA cleavage reactions.

Alcohols↗
PubMed1998

Identification of transcription factors expressed during ATRA-induced neutrophil differentiation of HL60 cells.

A recent clinical therapeutic initiative has been the use of chemical agents which induce the leukaemic cells to overcome their block in differentiation. In order to understand this block the cascade of molecular events needs to be characterized. Haemopoietic differentiation is ultimately controlled at the level of gene transcription which is mediated by an array of transcription factors. Many transcription factors contain similar structural protein sequences, and we have used an RT-PCR-based approach to isolate sequences, from transcription factor gene families which share similar domains. Degenerate primers corresponding to the TFIIIA zinc-finger consensus amino acid sequences and to the POU-homeodomain and POU-specific domain were used to amplify genes on the basis that they contained similarities in structural motifs shared within these families of transcription factors. A serum-independent HL60 cell line was induced towards the neutrophil lineage by treatment with all-trans retinoic acid (ATRA) for 24 h. CD38+ cells committed towards this lineage were enriched and a population of these cells treated with dihydroxyvitamin D3 to induce neutrophil maturation. RNA extracted from uninduced, ATRA-induced CD38+ cells, and vitamin D3 treated maturing cell cultures were amplified using the degenerate primers. PCR fragments were cloned, sequenced, clustered into homologous groups, and the group sequences searched on the GenBank database. The Oct 1 transcription factor, and a very close homologue, KIAA0144, was identified using the POU family primers. The zinc-finger primers identified three zinc-finger genes. The pattern of gene expression was suggested from the number of clones in each group at neutrophil commitment and maturation. The differential expression of the genes in the zinc finger and POU families will lead to a better understanding of the cascade of gene expression which occurs following ATRA-induced differentiation.

Cell Differentiation↗
PubMed1998

Use of a focussed teen prenatal clinic at a military teaching hospital: model for improved outcomes of unmarried mothers.

We evaluated the utility of a focussed, multidisciplinary adolescent clinic in improving perinatal outcomes. The study population included all delivering unmarried teenagers (13-19 years) from January 1, 1993 to December 31, 1995 attending the focussed adolescent obstetrical clinic compared to a similar cohort of married teenagers (13-19 years), married 20-24 year-old patients, and unmarried 20-24 year-old patients. There were no statistical differences in chorioamnionitis, intrauterine growth retardation (IUGR), postpartum haemorrhage, maternal weight gain, mean gestational age at delivery, preterm delivery rates (<37 weeks), low birth-weight (<2,500 g), Caesarean delivery, postterm delivery rates (>41 weeks), macrosomia (>4,000 g), placental abruption, chronic hypertension, alcohol use, Apgar scores or stillbirth rates or neonatal death rates among the 4 groups studied. Statistical differences were noted in mean delivery weights (p<0.05), preeclampsia (p<0.004), gestational diabetes (p<0.01), history of substance abuse (p<0.0001), tobacco use (p<0.0001), and forceps delivery rates (p<0.004). However, in the teen cohort none of these differences appeared to adversely affect perinatal outcomes in our patients. The focussed, adolescent obstetrical clinic appears to provide perinatal morbidities equal to a low-risk, general population generating better than expected outcomes for pregnant teenagers.

Adolescent↗
PubMed1998

Intragastric intubation: important aspects of the model for administration of ethanol to rat pups during the postnatal period.

One technique for the controlled delivery of ethanol to neonatal rat pups is intragastric intubation. Often, the vehicle used for delivery of ethanol is composed of a nutrient mixture to compensate for decreased suckling or other possible nutritional compromise. This study analyzed the selection of nutrient vehicle, the combination of experimental treatment groups within a litter, and the overall litter size on the growth rate of ethanol-intubated and intubated-control pups, compared with mother-raised control pups. Sprague-Dawley rat pups were raised in litters of 8 or 10, and administered ethanol by intragastric intubation with 20% (v/v) Sustacal or 80% (v/v) Intralipid-II nutrient vehicle. Pups were treated between postnatal days 2 and 10, and body weight was analyzed on day 10. Pups were assigned to a treatment group as either intubated ethanol, intubated control, or nonintubated mother-raised controls. Experimental comparison by statistical analyses was performed to identify the optimal treatment design (mixed treatment groups in a single litter or a single treatment group per litter), the optimal vehicle (Sustacal or Intralipid-II), and the optimal number of pups per litter (8 vs. 10). The analyses demonstrate that the mixing of intubated control, intubated ethanol, and nonintubated mother-raised control treatment groups within a single litter introduced an uncontrolled variable that confounded measurement of ethanol-specific alterations. The sensitivity of treatment groups to inclusion in mixed litters was dependent on the nutrient vehicle and thus nutritional adequacy. Our results suggest that an optimal design was achieved with eight pups per litter. Furthermore, ethanol intubated and intubated control pups grow at a rate identical to parallel litters of eight mother-raised control pups when Intralipid-II is used as nutrient vehicle, and a single treatment group is present in a litter. Optimization of these experimental parameters has provided an excellent neonatal rat model for analysis of specific ethanol effects on brain development during the third trimester.

Animals↗
PubMed1998

Developing and implementing an OSCE in dentistry.

The processes of development, implementation and perceived usefulness of an objective structured clinical examination in restorative dentistry (OSCE(D)) are reported. An OSCE is a system of assessment. It consists of a set of standardised 'stations'. At each station, a student is tested on a specific clinical task. Each student moves from one station to the next so that by the end of the OSCE, every student has completed every station. The primary purpose of this OSCE was to provide feedback to 49 4th year students on their performance in the clinical areas of conservative dentistry, periodontology and prosthetics. Individual profiles were provided to students and the overall results discussed by staff. There were no significant differences in overall performance between genders or between students in the morning and afternoon examinations. There was a significant difference between performance in prosthetics and the other areas and there were some significant differences among the skill clusters of clinical knowledge, procedures, clinical reasoning, history-taking, techniques and communication. Students and staff perceived the OSCE(D) as a valuable tool for providing feedback. The development of the OSCE and the findings described in this paper will be of value to clinical staff who are developing OSCEs in all areas of dentistry.

Clinical Competence↗
PubMed1998

Interactions between epidermal growth factor and the Tabby mutation in skin.

Mutations of the X-linked genes Tabby (Ta) in mice and EDA in humans result in developmental and functional abnormalities, primarily in the skin and hair follicles. Although both genes are believed to encode membrane-associated proteins, it has been suggested that, in the mouse, the mutation is linked to a deficiency of epidermal growth factor (EGF). This study investigated relationships between the skin abnormalities of Ta mice and the EGF signal pathway. The distribution of endogenous EGF in tissues of Ta/Y and +/Y animals was examined and, because of its reported morphogenetic actions and ability to overcome receptor signalling defects in vivo, the effects of exogenous EGF on the hair follicle population were determined. EGF levels were similar in a number of tissues of Ta/Y and +/Y mice, but amounts in Ta/Y submaxillary glands were reduced, probably due to a smaller gland size. Exogenous EGF inhibited hair follicle development and decreased follicle density in both genotypes. It was concluded from comparisons of the distributions of EGF and its effects in skin with those in mice bearing mutations in the EGF signal pathway that the normal phenotype results from interactions between EGF and the Ta peptide in skin.

Animals↗
PubMed1998

Failure of hairpin-ended and nicked DNA To activate DNA-dependent protein kinase: implications for V(D)J recombination.

V(D)J recombination is initiated by a coordinated cleavage reaction that nicks DNA at two sites and then forms a hairpin coding end and blunt signal end at each site. Following cleavage, the DNA ends are joined by a process that is incompletely understood but nevertheless depends on DNA-dependent protein kinase (DNA-PK), which consists of Ku and a 460-kDa catalytic subunit (DNA-PKCS or p460). Ku directs DNA-PKCS to DNA ends to efficiently activate the kinase. In vivo, the mouse SCID mutation in DNA-PKCS disrupts joining of the hairpin coding ends but spares joining of the open signal ends. To better understand the mechanism of V(D)J recombination, we measured the activation of DNA-PK by the three DNA structures formed during the cleavage reaction: open ends, DNA nicks, and hairpin ends. Although open DNA ends strongly activated DNA-PK, nicked DNA substrates and hairpin-ended DNA did not. Therefore, even though efficient processing of hairpin coding ends requires DNA-PKCS, this may occur by activation of the kinase bound to the cogenerated open signal end rather than to the hairpin end itself.

Animals↗
PubMed1998

Diminished serotonin-mediated prolactin responses in nondepressed stroke patients compared with healthy normal subjects.

BACKGROUND AND PURPOSE: The purpose of this study was to use hormonal responsiveness to d-fenfluramine (d-FEN) challenge as a measure of central serotonin (5-HT) function in a comparative evaluation of serotonergic abnormalities between stroke patients and healthy elderly normal subjects to test the hypothesis that stroke may be associated with diminished serotonergic functioning. METHODS: Eight nondepressed medically stable stroke patients and 12 healthy volunteers completed a single-blind, placebo-controlled, fixed-order, crossover design challenge test with 30 mg of oral d-FEN. Baseline prolactin (PRL) and cortisol (CORT) and hormonal responses to d-FEN and placebo were measured at hourly intervals over a 4-hour period. Cardiovascular responses (pulse and blood pressure) and behavioral responses were also recorded at the same time points. RESULTS: The 2 groups were comparable in demographics, body weight, plasma drug concentration, and behavioral and CORT responses. A 3-way ANOVA for repeated measures showed group differences for baseline adjusted PRL responses (change of scores from baseline). Peak PRL responses (maximal PRL change from baseline scores after treatment with d-FEN) in nondepressed stroke patients were attenuated compared with healthy elderly subjects, suggesting diminished serotonergic responsiveness in stroke patients. CONCLUSIONS: The demonstrated serotonergic hypofunctioning poststroke may contribute to the high incidence of depressive disorders in stroke patients. Serotonergic agents may have a role in augmentation of stroke recovery.

Administration, Oral↗