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Biomedical subjects

M Hall

Publications and source records attributed to M Hall.

At least 163 records · Page 9Linked to original sources
PubMed1995

Oxidation and genotoxicity of fecapentaene-12 are potentiated by prostaglandin H synthase.

The potential importance of prostaglandin H synthase (PGHS) in the genotoxicity of fecapentaene-12 (fec-12) has been indicated by the finding that non-steroidal anti-inflammatory agents (NSAIDs) block the induction of oxidative DNA base damage by fec-12 in HeLa cells. To further investigate the role of PGHS in the metabolic 'activation' and genotoxicity of fec-12, we have measured: (i) oxygen uptake by fec-12 with purified preparations of PGHS; and (ii) the induction of DNA single-strand breaks (SSBs) in HeLa cells exposed to fec-12 in the absence or presence of PGHS inhibitors. Oxygen uptake occurred spontaneously with fec-12 alone but was stimulated 3-fold by the presence of PGHS. The potentiation of fec-12 oxygenation by PGHS was independent of arachidonate and inhibited 45% by indomethacin (INDO). Methylphenylsulphide (MPSI), a reducing substrate expected to compete with fec-12 in peroxidase-dependent co-oxidation reactions, also inhibited PGHS-mediated oxygen uptake with fec-12 by 55%. These results, together with the observation that the inhibitory effects of these agents in combination were additive, suggest that both the cyclooxygenase and peroxidase components of PGHS are involved in the oxidation of fec-12. INDO and MPSI also blocked the induction of DNA SSBs by fec-12 in HeLa cells, indicating that both components of PGHS are also involved in potentiating the genotoxicity of fec-12. It is proposed that this occurs in two ways: firstly, by formation of highly reactive fec-12 hydroperoxides which would generate oxygen radicals through Fenton-like reactions, and secondly, by the generation of oxygen radicals through peroxidase-mediated co-oxidation of fec-12.

Cyclooxygenase Inhibitors↗
PubMed1995

Identification of an Mhc-DPB1 allele involved in susceptibility to experimental autoimmune encephalomyelitis in rhesus macaques.

Experimental autoimmune encephalomyelitis (EAE) is an inducible autoimmune disorder that in rodents is known to be influenced by genetic background, specifically the Mhc class II region. Immunization of a group of outbred rhesus macaques with bovine high homogenate results in induction of the disease in approximately 65% of the animals. No clear association between the Mamu-DR or -DQ subregion of the rhesus macaque MHC (MhcMamu) and susceptibility or resistance to the disease has been documented. In this communication we describe a CD4+ Th cell line, isolated from an animal diagnosed with EAE, which proliferated in response to purified bovine myelin basic protein (MBP), a major constituent of the myelin sheath surrounding nerve cells. More specifically it only recognized a peptide including residues 61-82 of the molecule. Analysis of the T cell receptor (Tcr) usage of this MBP reactive T cell line showed functional transcripts for only two members of the V alpha 1 and one of each of the V beta 3 and V beta 6 families. The antigen-specific proliferative response was inhibited by a mAb reactive with MHC-DP molecules. Molecular analysis of the Mamu-DP region, in concert with allogeneic antigen presentation studies, demonstrated that the Mamu-DPB1*01 gene product functions as the restriction element for MBP peptide presentation. Retrospective analyses showed that this particular allele is frequently found in the group of EAE susceptible animals but is absent in the resistant animals (P < 0.01). As a consequence, the Mamu-DPB1*01 allele may represent one of the risk factors involved in determining susceptibility to EAE in an outbred population of rhesus macaques.

Alleles↗
PubMed1995

The spontaneous reporting of adverse drug reactions by nurses.

In an attempt to improve the low reporting rate of adverse drug reactions (ADR) we examined the potential for hospital nurses to report ADRs through a spontaneous 'yellow card' system. Over 14 months 100 cards were received (compared with 28 cards from doctors). Although reports from doctors for the same period were of a more substantial nature, nurses nevertheless reported many life threatening (17%) or moderately severe (76%) reactions. Nurses identified uncertainty concerning their role and deficient in-service education on drug therapy as major constraints in their participation. Given their unique position in drug administration and recording observations on patients, we believe that nurses could contribute significantly and in a complementary fashion to the spontaneous reporting of adverse reactions.

Adverse Drug Reaction Reporting Systems↗
PubMed1995

Role of elevated plasma soluble ICAM-1 and bronchial lavage fluid IL-8 levels as markers of chronic lung disease in premature infants.

BACKGROUND: Pulmonary neutrophilia characterises both the relatively transient inflammation associated with infant respiratory distress syndrome (IRDS) and the persistent inflammation of chronic lung disease. The possibility that persistently raised markers of inflammation indicate the development of chronic lung disease in low birth weight (< 1730 g) preterm (< 31 weeks) infants was therefore investigated. METHODS: Soluble ICAM-1 (sICAM-1) levels in plasma, and interleukin (IL)-8 and myeloperoxidase (MPO) levels in bronchial lavage fluid (BLF) obtained from 17 infants on days 1, 5, and 14 following birth were measured and correlations with the number of neutrophils in BLF sought. Peripheral neutrophils were isolated on Polymorphoprep and chemotactic responsiveness to IL-8 was assessed using micro Boyden chambers. RESULTS: Sixteen infants developed IRDS and, of these, 10 infants subsequently developed chronic lung disease. Levels of IL-8 in BLF at 14 days of age correlated with the long term requirement for intermittent positive pressure ventilation (IPPV). Interleukin 8 levels in BLF correlated with neutrophil numbers and MPO concentration, suggesting both recruitment and activation in response to this cytokine. Antibody depletion studies showed that approximately 50% of total neutrophil chemotactic activity in BLF was due to IL-8. No difference in peripheral neutrophil chemotactic responsiveness at any age was observed for infants with IRDS or chronic lung disease. Plasma soluble intercellular adhesion molecule (sICAM-1) was higher at 14 days of age in infants who developed chronic lung disease than in those with resolving IRDS, and correlated with severity of disease, as indicated by duration of IPPV. CONCLUSIONS: The results indicate that high levels of plasma sICAM-1 and IL-8 in BLF at day 14 correlate with the development of chronic lung disease and indicate the severity of disease.

Biomarkers↗
PubMed1995

Adults' responses to self-injurious behavior. An experimental analysis using a computer-simulation paradigm.

The behavior of staff who care for people with mental retardation has been identified as a significant factor in the development and maintenance of challenging behaviors. In a recent analysis, Hastings and Remington (1994a) suggested that both environmental contingencies and rules from other people may affect staff actions. The present study tested this analysis by asking participants to respond to a computer simulation of a work situation involving the care of two individuals who engaged in self-injurious behavior. Fifty participants "interacted" with an attention-seeker and a social-avoider on a simulated teaching task. Results showed that rules were the main factor governing performance. The aversive nature of the contingencies between the self-injury and participants' "attending" behavior also appeared to be influential. The implications of these results for work with care staff, the analysis of challenging behaviors, and experimental research on rule-governed behavior are discussed.

Adolescent↗
PubMed1995

Homelessness and substance use among alcohol abusers following participation in project H&ART.

Project H&ART was a randomized intervention trial for homeless alcohol abusers in Albuquerque, N.M. Interventions were four months in duration and included: a high intensity program (case management plus peer-supervised housing), a medium intensity group (peer-supervised housing only); a housed, and a nonhoused control group. Clients were interviewed at baseline and re-interviewed ten months following program entry to determine substance use, housing stability and employment status. Program graduation rates were about 25% for the three housed groups. The outcome evaluation revealed significant within groups improvements in all of the outcomes, no between groups or racial outcome differences, and more favorable alcohol use and housing stability outcomes among program graduates than dropouts. On follow-up, women in the study had fewer days of alcohol use and had more days of stable housing, but were less likely to be employed, compared with men. We suggest that clients' personal motivation for recovery, rather than program-related factors, were most influential in determining outcomes.

Adolescent↗
PubMed1995

Induction of rodent hepatic drug-metabolizing enzyme activities by the novel anticonvulsant remacemide hydrochloride.

Remacemide hydrochloride [FPL 12924AA; 2-amino-N-(1-methyl-1,2-diphenylethyl) acetamide hydrochloride] is being evaluated as a novel neuroprotective treatment for epilepsy and stroke. Preliminary safety evaluation studies in the rat have shown that repeated doses of the compound produce histological and biochemical changes consistent with hepatic enzyme induction. To examine this further, the levels and activities of the major drug metabolizing cytochrome P450 (CYP) subfamilies (CPY1, CYP2, and CYP3) were monitored in microsomal samples from male Sprague-Dawley rats dosed by gavage with FPL 12924AA (250 mg base.kg-1.day-1 for 28 days) or an equivalent volume of vehicle (controls). The interpretation of the findings was aided by comparison with the effects of phenobarbitone (75 mg.kg-1.day-1 ip for 4 days) and beta-naphthoflavone (a single intraperitoneal dose at 80 mg.kg-1.day-1). No significant changes in total hepatic P450 levels (1.44 +/- 0.40 nmol.mg-1 vs. 1.31 +/- 0.19 nmol.mg-1 in controls) or ethoxyresorufin O-deethylase activity (a CYP1A induction probe) were observed after remacemide treatment. The pattern of induction produced by remacemide was very similar to that observed with phenobarbitone. The nonspecific CYP-dependent reaction ethoxycoumarin O-deethylation was induced approximately 2-fold. The specific CYP2B markers pentoxyresorufin O-depentylase and 16 beta-hydroxytestosterone production were both increased markedly by FPL 12924AA (approximately 100- and 20-fold, respectively). 2 beta- and 6 beta-Hydroxytestosterone production were also elevated, indicating the induction of CYP3A1/2. Similar effects on isoform-selective P450-dependent activities were observed in male and female mice treated with remacemide as part of a dose-ranging study.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetamides↗
PubMed1994

Possible pathogenic role of IgE in Henoch-Schönlein purpura.

The incidences of clinical and biological markers of atopy were investigated in 16 children with IgA nephropathy (IgAN) (group A) and in 22 with Henoch-Schönlein purpura nephritis (HSPN) (group B). The incidence of increased plasma IgE levels according to age-matched normal values was significantly higher in group B (17/22, 77%) than in group A (7/16, 44%) (P < 0.05). Although not significant, the incidences of positive RAST tests and of a history of typical atopic symptoms were also higher in group B [10/22 (45%) and 11/22 (50%), respectively] than in group A [4/16 (25%) and 5/16 (31%), respectively]. Moreover, IgE deposits were demonstrated by a peroxidase/anti-peroxidase method on cutaneous Langerhans and mast cells in 4 of 6 patients with HSPN. Thus immunoallergy might account, in some cases, for the cutaneous, intestinal and pulmonary signs observed in HSPN, but not in IgAN. We postulate stimulation of IgE-sensitized mast cells by specific antigens in the presence of IgA circulating immune complexes (CIC), release of vasoactive substances, increased capillary permeability and perivascular deposition of IgA CIC.

Adolescent↗
PubMed1994

Effect of hyperfiltration on long-term follow-up of glomerular filtration rate in male Wistar rats.

It has been suggested that a prolonged course of hyperfiltration could lead to progressive deterioration of renal function. In order to test this hypothesis, the following protocol was applied to 60 male Wistar rats. At 12 weeks of life, the rats were submitted to a surgical procedure: sham operation (25 rats), unilateral nephrectomy (25 rats) or 3/4 nephrectomy (10 rats). The three groups were again divided into two subgroups: one with high-protein intake (36%) and one with a low-protein intake (12%). In order to avoid any additional traumatic procedure which could shorten the animal's life, the glomerular filtration rate (GFR) was measured without blood sampling, using a previously validated technique based on an image recorded by a gamma camera between the 9th and the 10th min after intravenous injection of 99m technetium diethylenetriaminepentaacetate (DPTA). The sum of both kidneys and bladder activity was expressed as a percentage of the injected dose. The test was performed before surgery and every month thereafter. Six weeks after surgery, the highest filtration rate was found in the rats with "two kidneys/high-protein diet", followed by the "two kidneys/low-protein diet", the "one kidney/high-protein diet", the "one kidney/low-protein diet" and the "1/2 kidney". The overall GFR in the one kidney/high-protein diet rat and in the 1/2 kidney rat was respectively 80% and 55% of the pre-operative values. Until 109 weeks of age, the survival rate was comparable in the five groups of rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Is antenatal care apportioned according to obstetric risk? The Scottish antenatal care study.

A retrospective cohort study of case records of antenatal care was carried out to describe and compare antenatal services in Scotland according to type of hospital and risk category of women. The study took place at 15 randomly selected maternity hospitals which were divided into teaching hospitals (n = 5), rural catchment hospitals (n = 2), and district general hospitals divided by size as those with 1000-1699 deliveries per year (n = 4), and those with > or = 1700 deliveries per year (n = 4). The subjects were 3574 (87.7 per cent) of 4069 eligible women who delivered in the last quarter of 1989 at these hospitals. Of those 3574, 19 per cent (675) were considered to be high risk at booking, 64 per cent (2899) continued low risk throughout their pregnancy and the remaining 17 per cent (608) changed from low risk to high risk during pregnancy. The main outcome measures were the number, timing, location and supervision of antenatal visits and antenatal admissions in relation to hospital types and obstetric risk categories, and adverse pregnancy outcomes in relation to risk categories. It was found that 97 per cent of all women had care shared by general practitioner (GP) and hospital specialist agreement. The majority (64 per cent) of antenatal visits took place away from the hospital of delivery, with GPs responsible for the largest proportion of all antenatal visits (43.5 per cent) compared with specialist hospital doctors (36 per cent) and midwives (11.5 per cent). Wide variations in the use of different personnel groups to deliver antenatal care were observed between hospitals, particularly in the use of midwives to supervise visits (4-34 per cent). The median number of antenatal visits was 14 (mean 13.9, SD 3.9). Within hospital types the differences in the mean number of antenatal visits between the three risk categories were small (one to two visits) and the direction inconsistent. In all types of hospital, outset high-risk women and those who changed to high risk were more likely to have hospital admission than those who continued as low risk. Significantly more women in the high-risk categories experienced adverse pregnancy outcomes than women who continued at low risk.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

When is "impulsiveness" not impulsive? The case of hyperactive children's cognitive style.

On two computerized versions of the Matching Familiar Figures Test (MFFT; Kagan, Child Development, 36, 609-628, 1965) pervasively hyperactive and matched control children had to identify a target from among five similar foils. One version had a temporal structure similar to the manual MFFT and trial length was determined by response speed. Hyperactive children behaved in an "impulsive" manner; they responded more quickly and made more mistakes than controls. Despite this they completed each trial more quickly than controls by identifying the target. On the second version, the length of each trial was fixed at 45 seconds. Although both groups were equally "reflective", hyperactive children still made more mistakes. Implications of these results for research in impulse control in general and hyperactivity in particular are discussed.

Attention Deficit Disorder with Hyperactivity↗
PubMed1994

A gene for pachyonychia congenita is closely linked to the keratin gene cluster on 17q12-q21.

Pachyonychia congenita (PC) is a group of hereditary syndromes which have in common a hypertrophic dystrophy of the distal nail, and are associated with a variety of additional features, notably various dyskeratoses of skin and mucous membranes. The pathology is unknown but the array of clinical features suggests the possibility of a keratin abnormality. In the present report we describe linkage analyses in a large PC pedigree of the Jackson-Lawler type, a subtype which is characterised by multiple epidermal cysts, hair abnormalities, and natal teeth. The disease locus in this family was found to be tightly linked to markers mapping within, or very close to, the keratin type I cluster at 17q12-q21; maximum lod scores for linkage of the disease to a KRT10 polymorphism and to D17S800, a marker known to be very tightly linked to KRT10, were respectively +4.51 and +7.73, both at theta = 0.00. Although always likely, our findings provide strong evidence of a keratin gene anomaly underlying an inherited disorder affecting epidermis, nail, hair, and mucosa. These findings permit testing to see if pachyonychia congenita shows any locus heterogeneity and suggest specific candidate keratin genes for mutation searching studies. In addition, they suggest a role for keratins in the phenomenon of natal dentition.

Chromosomes, Human, Pair 17↗
PubMed1994

The surface structure of Leptotrichia buccalis.

Leptotrichia buccalis shows a mosaic of surface structure on its outer membrane consisting of curved ridges 35 mm high and 22 nm apart, and erect on that surface. Fimbriae (common pili) are not present and nor is an S layer. The flap-like ridges consist of strings of macromolecules radiating from the cell surface. This ridge structure is not soluble in any of the usual chaotropes and can only be released when the outer membrane has been damaged or dispersed by extracting envelope preparations with 0.5% SDS at room temperature. The ridge is then found to be attached firmly to the peptidoglycan sacculus, which may be the point of origin of the structure. When so prepared the macromolecules forming the ridge can be removed from the sacculus by treatment with 6 M guanidine HCl, and SDS-PAGE analysis of the extract reveals a 210-kDa polypeptide as a major component and a 15-kDa minor component. The latter is probably a peptidoglycan-associated protein and much of it remains with the sacculus. Each string forming the ridge is of a volume consistent with being made of three elongated 210-kDa molecules, which are united in series by strong hydrophobic association and laterally with neighboring strings by slightly weaker forces. We confirm that L. buccalis causes haemagglutination and the bacteria are known to attach to various tissue cells. Human group A red blood corpuscles remove both of the proteins from solution, which supports the hypothesis that the ridges are adhesin structures. It is likely but not proven that the 210-kDa molecule is the adhesin.

Bacterial Adhesion↗
PubMed1994

Rapid isolation and serum-free expansion of human CD34+ cells.

Human CD34+ cells were isolated from bone marrow from normal volunteers and expanded under serum-free culture conditions. CD34+ cells were cultured with interleukin-3 (IL-3), IL-1, and stem cell factor and expanded in granulocyte-macrophage colony-forming units, erythroid blast-forming units, and CD34+ cell number during the first 7-14 days of incubation. By contrast, cultures maintained in fetal calf serum under identical conditions showed much reduced expansion, as measured by all of the above parameters. The level of expansion of the CD34+ cells was dependent on the combination of growth factors used during culture. The data establish the feasibility of serum-free expansion of progenitors and suggest the clinical use of this procedure for the generation of expanded progenitor cell products for transfusion after chemotherapy to minimize treatment-related cytopenias.

Adult↗
PubMed1994

Patient restraint: choosing the proper equipment.

In response to the Ontario Hospital Association's position paper describing the use of restraints, the Toronto Hospital responded by developing a "least restraint" policy and procedure. In the developmental stages, various types of equipment were evaluated. This paper describes the equipment selected by the safety task force and the rationale for its use.

Humans↗