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Biomedical subjects

A Howard

Publications and source records attributed to A Howard.

At least 37 records · Page 2Linked to original sources
PubMed2001

Clinical call centres: does low-bandwidth video have a place?

Low-bandwidth video has a place in health service delivery. Videoconferencing systems commonly used in telehealth have a high capital cost, take days or weeks to install at specific locations, and have high communications charges. A range of circumstances can be envisaged where video may be of benefit but would not justify the cost of large systems. There are projects in community nursing, home dialysis and post-acute respiratory care where various low-bandwidth video technologies have been added as a supplement to the humble telephone call. It can be expected that at least some of these projects will be able to demonstrate tangible improvements in health outcomes, such as decreased readmission rates, reduced acute episodes of a chronic illness and improved health status from the additional social support.

Community Health Nursing↗
PubMed2001

Growth hormone secretagogue receptor family members and ligands.

We have previously reported the cloning and characterization of a new orphan G-protein-coupled receptor (GPC-R), the growth hormone secretagogue receptor (GHS-R), and shown that this receptor mediates the activity of the growth hormone-releasing peptides (GHRPs) and nonpeptide ligands such as L-692,429 and MK-0677. Because the GHS-R obviously does not belong to any of the known GPC-R subfamilies, we searched for GHS-R family members by screening a human genomic library using low-stringency hybridization and screening a Pufferfish genomic library. The Pufferfish was selected because of its compact genome. From the human genomic library, a homolog, GPR38, with 52% identity to the GHS-R was isolated. From the Pufferfish library, three family members were isolated. The Pufferfish gene having 58% identity to the GHS-R, on expression in HEK293 cells, was activated with GHRP-6 and MK-0677. These results indicate that the GHS-R has been conserved for at least 400 million years and that the Pufferfish genome is appropriate for isolation of GHS-R family members. In our search for endogenous ligands for the orphan receptors GHS-R and GPR38, we showed that adenosine is a partial agonist of the GHS-R and that motilin is the endogenous ligand for GPR38. We also confirmed that the endogenous ligand ghrelin is a full agonist of the GHS-R.

Adenosine↗
PubMed2001

Children in crashes: mechanisms of injury and restraint systems.

OBJECTIVES: To explore the levels of protection offered to children involved in motor vehicle collisions. DESIGN: A joint study by the Children's Hospital of Eastern Ontario (CHEO) and Transport Canada, Ottawa, conducted in 2 phases: retrospective from 1990 to 1997 and prospective from 1998 to 2000. SETTING: CHEO, a university affiliated tertiary care centre. PATIENTS: Children admitted to CHEO between 1990 and 2000 with spinal trauma due to motor vehical crashes (MVCs). Phase I of the study involved analysis, in a series of 45 children after MVAs, by location of spinal injury versus belt type. Phase 2 was a prospective study of 22 children injured in 15 MVAs. INTERVENTIONS: A biomechanical assessment of the vehicle and its influence on the injuries sustained. MAIN OUTCOME MEASURES: The nature and extent of the injuries sustained, and the vehicle dynamics and associated occupant kinematics. RESULTS: The odds ratio of sustaining a spinal injury while wearing a 2-point belt versus a 3-point belt was 24 (95% confidence interval 2.0-2.45, p < 0.1), indicating a much higher incidence with a lap belt than a shoulder strap. CONCLUSIONS: Proper seat-belt restraint reduces the morbidity in children involved in MVCs. Children under the age of 12 years should not be front-seat passengers until the sensitivity of air bags has been improved. Three-point pediatric seat belts should be available for family automobiles to reduce childhood trauma in MVCs.

Accidents, Traffic↗
PubMed2000

Isolation of the pathogen Vibrio tapetis and defense parameters in brown ring diseased Manila clams Ruditapes philippinarum cultivated in England.

The Manila clam Ruditapes philippinarum was introduced for aquacultural purposes to Europe in the 1970s. In 1987, brown ring disease (BRD), caused by Vibrio tapetis, appeared in clams cultivated in Brouënou (Finistère, France) and later became increasingly widespread and was reported in cultivated and wild clams existing on the Atlantic coasts of France and Spain. The present study reports, for the first time, the presence of BRD in clams cultivated in England. The etiologic bacterium was isolated and identified using bacteriological and serological techniques. The defence response of affected clams was also studied and significant changes in the hematological and biochemical characteristics of hemolymph and extrapallial fluids were demonstrated. Significant mobilization of hemocytes toward the extrapallial fluids, in contact with the main site of infection (mantle-periostracal lamina area), was observed, suggesting a role for these pseudo-internal compartments in the preservation of clam health.

Animals↗
PubMed2000

The immunogenicity of single and combination DNA vaccines against tuberculosis.

DNA immunization is a promising new approach for the development of novel tuberculosis vaccines. In this study, the immune responses following the administration of single and combination tuberculosis DNA vaccines were evaluated. Single DNA vaccines encoding the MPT-63 and MPT-83 tuberculosis antigens evoked partial protection against an aerogenic challenge with M. tuberculosis Erdman in the mouse model of pulmonary tuberculosis. Immunization with a multivalent combination DNA vaccine (containing the ESAT-6, MPT-64, MPT-63, and KatG constructs) generated immune responses that indicated an absence of antigenic competition since antigen-specific cell-mediated and humoral responses were detected to each component of the mixture. More importantly, the combination vaccine elicited a strong protective response relative to the protection evoked by live BCG vaccine.

Aerosols↗
PubMed2000

Crystallization and 1.1-A diffraction of chorismate lyase from Escherichia coli.

Chorismate pathway enzymes are important as producers of nonnucleotide aromatic compounds. The enzyme chorismate lyase from Escherichia coli has been crystallized in four distinct forms, three of which have been characterized by X-ray diffraction. Despite widespread screening, all four crystal forms grow from the same chemical conditions. The wild-type enzyme tends to aggregate, even in the presence of reducing agent, and yielded only one crystal form (monoclinic, form 1) that grew in intricate clusters. Chemical modification of the cysteines mitigated problems with aggregation and solubility but did not affect crystal growth behavior. Protein aggregation was largely eliminated by mutating the protein's two cysteines to serines. The double mutant retains full enzymatic activity and crystallizes in three new forms, one of which (triclinic) diffracts to 1.1-A resolution.

Bacterial Proteins↗
PubMed2000

The population impact of MRSA in a country: the national survey of MRSA in Wales, 1997.

Continuous data collection on all new isolates of MRSA via CoSurv has taken place in Wales since January 1996. In order to audit this data collection, and to address some of the issues that it does not include, a survey of MRSA was carried out. Questionnaires were completed by infection control teams. Rates were calculated using hospital throughput denominators. Results from the one-day prevalence survey, the two-week incidence survey, and the follow-up survey carried out on new MRSA patients identified in the incidence survey, are presented. Results were found to be broadly similar to those collected via routine surveillance. MRSA was found frequently and disproportionately in the elderly, with higher rates in male than female patients. The highest incidence of total and invasive MRSA was in males aged 75 and over (total: 12.5/1000 finished consultant episodes; invasive: 2.8/1000). Although there was a large community reservoir of MRSA, most appeared to have been acquired in hospital, since most patients had a history of hospitalization, often with multiple hospital admissions. Community-based isolates from cases with no hospital history tended to have been from ulcers. Prevalence and incidence of MRSA was relatively low compared with hospital throughput (mean prevalence: 2.4/100 occupied beds; mean incidence: 3.6/1000 finished consultant episodes), there was also quite large variation between sites, even when screening samples were removed. Patients with MRSA had strikingly long stays before isolation of the organism (prevalence survey: 39 days; incidence survey: 31 days) and highest incidence occurred in elderly care wards. The outcome survey showed that approximately half of the patients were treated with some type of antimicrobial therapy for MRSA. Decontamination therapy was associated with clearance of MRSA only when controlling for sex of the patient. The majority of patients were discharged still with MRSA, mostly to their own homes. The survey emphasizes the need to continue surveillance to detect any changes, to allow guidelines based on evidence to be developed and to monitor the effectiveness of such guidelines.

Adolescent↗
PubMed2000

DNA vaccination against tuberculosis: expression of a ubiquitin-conjugated tuberculosis protein enhances antimycobacterial immunity.

Genetic immunization is a promising new technology for developing vaccines against tuberculosis that are more effective. In the present study, we evaluated the effects of intracellular turnover of antigens expressed by DNA vaccines on the immune response induced by these vaccines in a mouse model of pulmonary tuberculosis. The mycobacterial culture filtrate protein MPT64 was expressed as a chimeric protein fused to one of three variants of the ubiquitin protein (UbG, UbA, and UbGR) known to differentially affect the intracellular processing of the coexpressed antigens. Immunoblot analysis of cell lysates of in vitro-transfected cells showed substantial differences in the degradation rate of ubiquinated MPT64 (i.e., UbG64 < UbA64 < UbGR64). The specific immune response generated in mice correlated with the stability of the ubiquitin-conjugated antigen. The UbA64 DNA vaccine induced a weak humoral response compared to UbG64, and a mixed population of interleukin-4 (IL-4)- and gamma interferon (IFN-gamma)-secreting cells. Vaccination with the UbGR64 plasmid generated a strong Th1 cell response (high IFN-gamma, low IL-4) in the absence of a detectable humoral response. Aerogenic challenge of vaccinated mice with Mycobacterium tuberculosis indicated that immunization with both the UbA64- and UbGR64-expressing plasmids evoked an enhanced protective response compared to the vector control. The expression of mycobacterial antigens from DNA vaccines as fusion proteins with a destabilizing ubiquitin molecule (UbA or UbGR) shifted the host response toward a stronger Th1-type immunity which was characterized by low specific antibody levels, high numbers of IFN-gamma-secreting cells, and significant resistance to a tuberculous challenge.

Animals↗
PubMed2000

Expression of GalR1 and GalR2 galanin receptor messenger ribonucleic acid in proopiomelanocortin neurons of the rat arcuate nucleus: effect of testosterone.

Previous studies have shown that galanin-containing fibers make synaptic contacts with POMC neurons in the arcuate nucleus. However, the ability of POMC neurons to express galanin receptors has never been assessed. The present study was designed to investigate whether POMC neurons express galanin receptor messenger RNA (mRNA) and whether testosterone could modulate galanin receptor gene expression. A dual-labeling in situ hybridization histochemistry, using 35S-labeled (galanin receptors GalR1 or GalR2) and digoxigenin-labeled (POMC) riboprobes, was performed on brain sections from intact, castrated, and testosterone-replaced adult male rats. For analysis, the arcuate nucleus was divided into four rostro-caudal areas. The results revealed that both GalR1 and GalR2 mRNAs were expressed in POMC neurons. Most POMC neurons expressing galanin receptor mRNAs were found in the rostral parts of the nucleus. Castration reduced the labeling density of galanin receptor mRNAs in POMC neurons, and testosterone prevented the effects of castration in all rostro-caudal subdivisions of the arcuate nucleus. Taken together, these data indicate that galanin can directly modulate the activity of POMC neurons, via an action on GalR1 or GalR2 receptors, particularly in the rostral-arcuate nucleus. In addition, testosterone can modulate the expression of GalR1 and GalR2. Because POMC neurons located in the rostral part of the nucleus are known to project preferentially to the preoptic area, POMC neurons expressing the galanin receptor genes may play an important role in the regulation of the GnRH neuroendocrine axis.

Animals↗
PubMed1999

Simulating cyanobacterial growth in a lowland reservoir.

MOTIVATION: There has been a rise in the incidence of reported cyanobacterial bloom contamination, in England and Wales associated with freshwaters, over the past 10 years. These blooms can, under certain environmental conditions, produce toxins, which can be harmful to mammals. This paper presents a new model of cyanobacterial growth that incorporates the functionality of earlier buoyancy regulation models. The model includes algorithms allowing temperature-correction of the main process rates; loss of colonies; net chlorophyll-a production and changes in colony size. RESULTS: The model was used to simulate cyanobacterial growth in a lowland impoundment in Southern England for 1994 and 1995. Predicted results were compared to observed data for the 2 consecutive years and the model results compare favourably with the observed data.

Algorithms↗
PubMed1999

Factors involved in the duodenal expression of the human calbindin-D9k gene.

Calbindin-D9k is expressed in the cytoplasm of intestinal cells, where it is critical for dietary calcium absorption. Two striking aspects of the expression of this gene are its vitamin-D dependency and regional differences in expression, with high levels only in duodenum. We report studies of the human calbindin-D9k promoter. Differences between the reported sequences of the human calbindin-D9k promoter were first clarified before undertaking a functional analysis of this sequence. Studies of the rat gene have indicated that several transcription factors, including the caudal-related homeobox factor (CDX-2), hepatic nuclear factor-4 and CCAAT-enhancer-binding protein alpha (C/EBPalpha), could interact with elements in the promoter. Although these elements are conserved in the human gene, we show here that their intestinal distribution makes them unlikely to be critical positive factors. The calbindin-D9k gene contains multiple potential binding sites for homeobox transcription factors; one of these, known as IPF-1 or PDX-1, co-localizes in the intestine with calbindin-D9k. We show in gel-shift assays that the sequence within a putative vitamin-D-response element in the human calbindin-D9k promoter can bind expressed IPF-1/PDX-1 protein, although we cannot confirm binding of the vitamin-D-receptor protein. CDX-2 binds to the region around the TATA box, as in the rat gene, and may act as a negative factor in the distal intestine. Transfection studies in Caco-2 and MCF-7 cells with heterologous reporter vectors containing up to 1303 bp of the gene showed that this functioned as a weak promoter and indicated the presence of suppressor sequences, but did not show vitamin-D responsiveness. This indicates that other elements are also needed for the control of human calbindin-D9k expression.

Animals↗
PubMed1999

A New Orphan Receptor Involved in Pulsatile Growth Hormone Release.

In all species studied to date, growth hormone (GH) is released episodically. Traditionally, the regulation of this process was considered to be mediated by two hypothalamic hormones, growth hormone-releasing hormone (GHRH) and somatostatin (sst). More recently, we identified a new orphan G-protein-coupled receptor that causes episodic GH release upon activation by synthetic ligands. These ligands include the GH-releasing peptides (GHRPs) first described by Bowers and their small molecule mimetics such as L-692,429 and MK-0677. Site-directed mutagenesis of this GH secretagogue receptor (GHS-R) has defined key amino acid residues essential for binding and activation by the synthetic ligands. The GHS-R is not activated by GHRH or sst. It is expressed exclusively in the anterior pituitary lobe and central nervous system and although this new receptor does not belong to any of the known families of G-protein-coupled receptors, the GHS-R is highly conserved across species. The Puffer fish homolog, in common with the human GHS-R, is activated by the structurally distinct ligands GHRP-6, MK-0677 and L-163,540. Thus, the GHS-R ligand-binding pocket has apparently been conserved for at least 400 million years. Studies in humans suggest that production of an endogenous ligand declines during aging. For example, chronic treatment with the synthetic ligand MK-0677 reverses the age-related physiological changes in the GH/IGF-I (insulin-like growth factor I) axis of 70-94 year old subjects. Based on the localization of expression of GHS-R in the brain, reduced production of the natural ligand might also be involved in age-associated changes in cognition, memory, mood and behavior.

Journal Article↗
PubMed1999

Expression of genes involved in calcium absorption in human duodenum.

BACKGROUND: The role of vitamin D metabolites in the regulation of expression of genes involved in dietary calcium absorption by the human intestine remains poorly understood despite much work in animals. MATERIALS AND METHODS: To investigate this, we measured the expression of transcripts for two of these genes, calbindin-D9k and the basolateral membrane calcium pumping ATPase, PMCA1, in duodenal endoscopic biopsies from 40 subjects. Northern blots were hybridized with previously characterized probes, and the signal was quantified by phosphor imaging. These transcript levels were related to circulating vitamin D metabolites and also analysed according to the vitamin D receptor gene TaqI polymorphism determined in DNA from blood. RESULTS: Plasma 1,25-dihydroxycholecalciferol correlated significantly with calbindin-D9k RNA (r = 0.4, P < 0.02) but not with PMCA1. Plasma 25-OH-cholecalciferol was not correlated with transcripts for either gene and, furthermore, the mean levels of these transcripts did not differ significantly when grouped by vitamin D receptor genotype. CONCLUSION: In normal humans, 1, 25-dihydroxycholecalciferol has a small but significant relationship to duodenal expression of calbindin-D9k, but not to PMCA1 expression.

Calbindins↗
PubMed1999

Physiological and psychometric variables for monitoring recovery during tapering for major competition.

PURPOSE: This study attempted to identify variables that are useful in monitoring recovery during tapering. METHODS: Changes in physiological variables, tethered swimming force, mood states, and self-ratings of well-being were measured in 10 elite swimmers from before to after 2 wk of tapering for national championships. Physiological measures included resting heart rate (HR); blood pressure (BP); blood lactate concentration; red blood cell, white blood cell, and differential counts; and plasma cortisol, free testosterone, and catecholamine concentrations. Measures taken after 100-m maximal and 200-m standardized submaximal swims included HR, BP, and blood lactate concentration. RESULTS: Step-down regression analysis showed that changes in plasma norepinephrine concentration, heart rate after maximal effort swimming and confusion as measured by the Profile of Mood States (POMS) predicted the change in swimming time with tapering (r2 = 0.98); the change in plasma norepinephrine concentration predicted the change in swim time with tapering (r2 = 0.82) by itself. CONCLUSION: These data suggest that recovery after intense training can be monitored during tapering and that an accurate prediction of performance changes may be possible if the changes in a range of physiological and psychological variables are measured.

Adolescent↗
PubMed1999

Immunogenicity of DNA vaccines expressing tuberculosis proteins fused to tissue plasminogen activator signal sequences.

Novel tuberculosis DNA vaccines encoding native ESAT-6, MPT-64, KatG, or HBHA mycobacterial proteins or the same proteins fused to tissue plasminogen activator (TPA) signal sequences were evaluated for their capacity to elicit humoral, cell-mediated, and protective immune responses in vaccinated mice. While all eight plasmids induced specific humoral responses, the constructs expressing the TPA fusions generally evoked higher antibody responses in vaccinated hosts. Although most of the DNA vaccines tested induced a substantial gamma interferon response in the spleen, the antigen-specific lung responses were 2- to 10-fold lower than the splenic responses at the time of challenge. DNA vaccines encoding the ESAT-6, MPT-64, and KatG antigens fused to TPA signal sequences evoked significant protective responses in mice aerogenically challenged with low doses of Mycobacterium tuberculosis Erdman 17 to 21 days after the final immunization. However, the protective response induced by live Mycobacterium bovis BCG vaccine was greater than the response induced by any of the DNA vaccines tested. These results suggest that the tuberculosis DNA vaccines were able to elicit substantial immune responses in suitably vaccinated mice, but further refinements to the constructs or the use of alternative immunization strategies will be needed to improve the efficacy of these vaccine candidates.

Animals↗
PubMed1998

A comparative study of TLSO, Charleston, and Milwaukee braces for idiopathic scoliosis.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To determine which of TLSO, Charleston, or Milwaukee bracing best prevents curve progression and surgery in adolescent idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: Bracing has been shown to prevent curve progression in idiopathic scoliosis, when compared with no treatment. However, there is little literature available comparing the effectiveness of different brace designs. METHODS: One hundred seventy patients who completed brace treatment for adolescent idiopathic scoliosis between 1988 and 1995 were studied. Forty-five thoracolumbosacral orthoses, 95 Charleston braces, and 35 Milwaukee braces were used. Thoracolumbosacral orthoses and Charleston braces were used on comparable curves, whereas Milwaukee braces were used in a subgroup in which the other brace designs were considered inappropriate. Evaluated were the absolute increase in curve severity, the percentage of curves that progressed beyond 6 degrees and 10 degrees thresholds, and the percentage of patients who underwent surgery. RESULTS: Age, Risser stage, curve size, and time braced and observed did not differ among groups. Mean progression of the curve during bracing was 1.1 degrees with thoracolumbosacral orthosis, 6.5 degrees with the Charleston brace, and 6.3 degrees with the Milwaukee brace (P = 0.012; analysis of variance). Proportion of patients with more than 10 degrees of curve progression was 14% with thoracolumbosacral orthosis, 28% with the Charleston brace, and 43% with the Milwaukee brace (P = 0.017; chi-square). The proportion of patients who underwent surgery was 18% with thoracolumbosacral orthosis, 31% with the Charleston brace, and 23% with the Milwaukee brace (P = 0.26; chi-square). CONCLUSIONS: The thoracolumbosacral orthosis was superior at preventing curve progression in adolescent idiopathic scoliosis.

Adolescent↗