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Biomedical subjects

D Baker

Publications and source records attributed to D Baker.

At least 253 records · Page 14Linked to original sources
PubMed1993

Faculty research productivity in allied health settings: a TQM approach.

Faculty research productivity in colleges of allied health has often been discussed in the literature over the last five years. Articles have focused on the problem of faculty research productivity from various viewpoints, but none have used a theoretical framework to analyze the problem. The total quality management (TQM) framework is currently being used in health care to improve quality and productivity. This article uses the TQM framework to synthesize literature concerning faculty research productivity and verifies the current relevance of synthesis findings using an allied health faculty survey. These analyses show that the TQM framework is useful in suggesting ways to increase faculty research productivity in colleges of allied health.

Allied Health Personnel↗
PubMed1993

Today or in the past? The origins of ischaemic heart disease.

Recent studies have suggested that regional differences in death rates from ischaemic heart disease (IHD) may result from exposure to poverty in foetal and early infant life. The suggestion is that such influences 'permanently set structures and metabolic processes, so-called programming'. On this theory, current falls in IHD death rates reflect much earlier reductions in poverty. If the theory were correct, the fall in rates would begin with younger age groups and be reinforced only at the pace at which each new birth cohort reached adult life. There is no evidence of such a cohort effect. Rates fell simultaneously over a very brief period in each country and region examined. The results are more compatible with theories involving contemporary lifestyle changes.

Adult↗
PubMed1993

Characterization of experimental allergic encephalomyelitis-susceptible, Biozzi AB/H (H-2dq1) mice which express H-2Anod: analysis of T-cell receptor expression and the detection of a deletion ligand encoded by Mtv-7.

Biozzi (H-2dq1) AB/H mice are marked not only by their high titre antibody responses following immunization with protein antigens but are also susceptible to experimental allergic encephalomyelitis (EAE) induction. The T-cell receptor (TcR) repertoire in this recently characterized strain was analysed. Biozzi AB/H mice were found to express the Thy-1a, Ly-1b, Ly-2b and Ly-5b alleles. Serological typing of the TcR-V beta + peripheral T cells suggested that the AB/H mice belong to the TcR-V beta b haplotype and express a deletion ligand for TcR-V beta 6+ and TcR-V beta 8.1+ T cells. This was confirmed by Southern blot analysis which revealed the presence of Mtv-17, Mtv-23, Mtv-31 (Y chromosome) and notably Mtv-7. Therefore the AB/H mice are Mls-1a. Despite the depletion/absence of the majority of TcR-V beta families in EAE-resistant (BALB/c) x EAE-susceptible (AB/H) F1 mice it was possible to induce EAE in these F1 animals. This suggests either that the deleted TcR-V beta-bearing T cells were not the principal encephalitogenic cells or that the TcR-V beta usage is sufficiently heterogeneous to accommodate such deletion events, in spinal cord-induced EAE.

Animals↗
PubMed1992

A protein-folding reaction under kinetic control.

Synthesis of alpha-lytic protease is as a precursor containing a 166 amino-acid pro region transiently required for the correct folding of the protease domain. By omitting the pro region in an in vitro refolding reaction we trapped an inactive, but folding competent state (I) having an expanded radius yet native-like secondary structure. The I state is stable for weeks at physiological pH in the absence of denaturant, but rapidly folds to the active, native state on addition of the pro region as a separate polypeptide chain. The mechanism of action of the pro region is distinct from that of the chaperonins: rather than reducing the rate of off-pathway reactions, the pro region accelerates the rate-limiting step on the folding pathway by more than 10(7). Because both the I and native states are stable under identical conditions with no detectable interconversion, the folding of alpha-lytic protease must be under kinetic and not thermodynamic control.

Chemical Phenomena↗
PubMed1992

Protease pro region required for folding is a potent inhibitor of the mature enzyme.

alpha-Lytic protease, an extracellular bacterial serine protease, is synthesized with a large pro region that is required in vivo for the proper folding of the protease domain. To allow detailed mechanistic study, we have reconstituted pro region-dependent folding in vitro. The pro region promotes folding of the protease domain in the absence of other protein factors or exogenous energy sources. Surprisingly, we find that the pro region is a high affinity inhibitor of the mature protease. The pro region also inhibits the closely related Streptomyces griseus protease B, but not the more distantly related, yet structurally similar protease, elastase. Based on these data, we suggest a mechanism in which pro region binding reduces the free energy of a late folding transition state having native-like structure.

Cloning, Molecular↗
PubMed1992

Inhibition of chronic relapsing experimental allergic encephalomyelitis in the Biozzi AB/H mouse.

Chronic relapsing experimental allergic encephalomyelitis (CREAE) can be reproducibly induced in Biozzi AB/H mice following injection of spinal cord homogenate (SCH) emulsified in complete Freund's adjuvant (CFA). Active clinical disease is associated with mononuclear cell infiltration of the central nervous system (CNS), mainly the spinal cord. Whole brain homogenate (BH), however, failed to induce clinical or histological disease. In contrast, substituting sciatic nerve homogenate in the inoculum induced experimental allergic neuritis (EAN). Clinical disease was manifest earlier (13.1 +/- 0.3 days) than CREAE (16.2 +/- 1.4) and was accompanied by mononuclear infiltration of the peripheral nervous system (PNS). In comparison to CREAE induction, pretreating mice with SCH or BH in incomplete Freund's adjuvant (IFA) suppressed the development of SCH-induced disease. The BH was more tolerogenic than the SCH and this hyporesponsiveness was CNS antigen-specific as PNS tissue failed to inhibit the course of CREAE. Tolerance induced by pretreatment with SCH or BH in IFA was reversed by a single injection of 200 mg/kg cyclophosphamide, 2 days prior to CREAE induction. This suggests that IFA-induced hyporesponsiveness is actively regulated, possibly via the action of suppressor cells. In addition, treatment with neuroantigens in IFA appears to be mainly afferent acting as it serves to prevent initial disease induction. This treatment after immunization for CREAE, however, fails to prevent disease progression. Furthermore, treatment with CNS antigens emulsified in IFA during the post-acute remission stage appeared to synchronize and induce (32 +/- 1 days) the onset of clinical relapse, compared with untreated controls (41 +/- 5 days). This indicates that such IFA treatment has minimal value in controlling an ongoing immune disease of the CNS.

Animals↗
PubMed1992

Therapy of chronic relapsing experimental allergic encephalomyelitis and the role of the blood-brain barrier: elucidation by the action of Brequinar sodium.

The immunosuppressive effect of the novel 4-quinoline carboxylic acid derivative Brequinar sodium on the chronic relapsing experimental allergic encephalomyelitis CREAE model in the Biozzi AB/H mouse was investigated. Although Brequinar sodium actively inhibited peripheral immune responses, it showed a limited potential to control an ongoing disease of the central nervous system (CNS). Doses of 25 mg/kg inhibited in vivo induced proliferative response and prevented EAE when treated from day 9 post-inoculation (p.i.). However, when administered from day 12 p.i. or during the post-acute remission phase-limited effects on the course of disease were observed. By comparison, treatment with a single high dose of cyclophosphamide (200 mg/kg) at these time points was significantly effective in controlling disease. As a possible explanation of the observed results it is suggested that for a compound to be effective in treating an ongoing immune response in the CNS, it must be capable of crossing the blood-brain barrier and act on the disease-inducing cells activated within the CNS. This hypothesis is supported by the finding that intracerebral injections of Brequinar sodium on day 12 p.i. significantly inhibited disease progression. This suggests that strategies aimed at controlling immune-mediated disease of the CNS require therapeutic doses of the compounds to be delivered into the CNS.

Animals↗
PubMed1992

Control of immune-mediated disease of the central nervous system requires the use of a neuroactive agent: elucidation by the action of mitoxantrone.

Mitoxantrone was used as an immunosuppressive probe to elucidate a means for the control of experimental allergic encephalomyelitis (EAE) induced in Biozzi AB/H mice following injection of spinal cord homogenate emulsified in Freund's adjuvant. A single i.p. injection of 2.5 mg/kg of mitoxantrone, 1-2 days before the anticipated onset of EAE, failed to prevent the majority of animals from developing clinical disease, whereas when the compound was injected directly into the central nervous system (CNS), at this time point, significantly increased therapeutic benefit was evident, with most animals failing to develop clinical EAE. Although the clinical use of intrathecal mitoxantrone is strongly contraindicated, these data suggest that increased therapeutic benefit may be achieved in immune-mediated disease of the CNS by targeting immunosuppressive doses of suitable agents, on lymphocyte activation within the CNS. In addition, direct administration of immunosuppressive doses into the CNS may reduce potentially unwanted (side) effects in the periphery.

Animals↗
PubMed1992

Adult domestic violence.

Adult domestic violence in Leicestershire was reviewed by examining the clinical notes of all patients aged 14 years and over attending the Accident and Emergency Department of the Leicester Royal Infirmary in 1988 with a history of assault. Of the 341 patients so classified, 297 victims were identified. This paper describes the results of the review, including the age and gender of the victims, and the nature and cost of the violence. Suggestions are made to improve the management of adult domestic violence.

Adult↗
PubMed1992

The ergonomic challenge of repetitive motion with varying ergonomic stresses. Characterizing supermarket checking work.

Many jobs leading to a risk of cumulative trauma do not have highly stereotyped motions. This study developed and employed a novel method of ergonomic characterization to describe quantitatively the actions associated with grocery checking. Fifty workers were videotaped for three 15-minute segments each. Eight object types were selected to represent the variety of items in a supermarket. Nine types of motion were coded for each of the eight objects for 10 replications for each subject. The motions coded were: grip type (power versus pinch), wrist flexion, wrist extension, radial deviation, ulnar deviation, supination, pronation, body (lumbar) flexion, and drag versus lift. The results were then weighted according to relative frequency of the object type. In this manner, an ergonomic risk index can be assigned to each specific object type. This method permits identification of objects presenting the greatest risk. It also allows specificity of preventive interventions (object redesign, work practice change) as well as providing a quantitative measure to evaluate work station redesign. Furthermore, it has the potential of quantitatively describing the risk of each individual worker.

Cumulative Trauma Disorders↗
PubMed1991

Role of neurogenic genes in establishment of follicle cell fate and oocyte polarity during oogenesis in Drosophila.

Oogenesis in Drosophila involves specification of both germ cells and the surrounding somatic follicle cells, as well as the determination of oocyte polarity. We found that two neurogenic genes, Notch and Delta, are required in oogenesis. These genes encode membrane proteins with epidermal growth factor repeats and are essential in the decision of an embryonic ectodermal cell to take on the fate of neuroblast or epidermoblast. In oogenesis, mutation in either gene leads to an excess of posterior follicle cells, a cell fate change reminiscent of the hyperplasia of neuroblasts seen in neurogenic mutant embryos. Furthermore, the Notch mutation in somatic cells causes mislocalization of bicoid in the oocyte. These results suggest that the neurogenic genes Notch and Delta are involved in both follicle cell development and the establishment of anterior-posterior polarity in the oocyte.

Animals↗
PubMed1991

Explaining outputs of primary health care: population and practice factors.

OBJECTIVE: To examine whether variations in the activities of general practice among family health service authorities can be explained by the populations characteristics and the organisation and resourcing of general practice. DESIGN: The family health services authorities were treated as discrete primary health care systems. Nineteen performance indicators reflecting the size, distribution, and characteristics of the population served; the organisation of general practice (inputs); and the activities generated by general practitioners and their staff (output) were analysed by stepwise regression. SETTING: 90 family health services authorities in England. MAIN OUTCOME MEASURES: Rates of cervical smear testing, immunisation, prescribing, and night visiting. RESULTS: 53% of the variation in uptake of cervical cytology was accounted for by Jarman score (t = -3.3), list inflation (-0.41), the proportion of practitioners over 65 (-0.64), the number of ancillary staff per practitioner (2.5), and 70% of the variation in immunisation rates by standardised mortality ratios (-6.6), the proportion of practitioners aged over 65 (-4.8), and the number of practice nurses per practitioner (3.5). Standardised mortality ratios (8.4), the number of practitioners (2.3), and the proportion over 65 (2.2), and the number of ancillary staff per practitioner (-3.1) accounted for 69% of variation in prescribing rates. 54% of the variation in night visiting was explained by standardised mortality ratios (7.1), the proportion of practitioners with lists sizes below 1000 (-2.2), the proportion aged over 65 (-0.4), and the number of practice nurses per practitioner (-2.5). CONCLUSIONS: Family health services authorities are appropriate systems for studying output of general practice. Their performance indicators need to be refined and to be linked to other relevant factors, notably the performance of hospital, community, and social services.

England↗
PubMed1991

Prolonged continuous acyclovir treatment of normal adults with frequently recurring genital herpes simplex virus infection. The Acyclovir Study Group.

In this 3-year study of suppressive acyclovir for recurrent genital herpes, patients with more than six recurrences per year were randomized initially to 400 mg of acyclovir or placebo orally two times per day, with recurrences treated with 200 mg of acyclovir five times per day for 5 days. In the second year of the study, all patients received acyclovir as a daily suppressive or intermittent acute therapy; in the third year, all received daily acyclovir. Among 525 patients completing 3 study years, 289 received 3 years of suppressive therapy and 236 received 1 year of acute therapy followed by 2 years of suppressive therapy. Of those who completed the third year, 61% were recurrence free that year; 25% of the suppressive therapy-only group were recurrence free for all 3 years. The annual recurrence rate dropped from more than 12 recurrences per year at baseline to 1.0 (suppressive therapy) and 1.4 (acute and suppressive therapy) recurrences during the third year. No significant toxic effects were detected. Daily suppressive acyclovir therapy was effective and well tolerated.

Acyclovir↗