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Biomedical subjects

H Allen

Publications and source records attributed to H Allen.

At least 37 records · Page 2Linked to original sources
PubMed1997

Characterization of mice deficient in interleukin-1 beta converting enzyme.

Interleukin-1 beta converting enzyme (ICE) processes the inactive prolL-1 beta to the proinflammatory mature IL-1 beta. ICE belongs to a family of cysteine proteases that have been implicated in apoptosis. To address the biological functions of ICE, we generated ICE-deficient mice through gene targeting technology. ICE-deficient mice developed normally, appeared healthy, and were fertile. Peritoneal macrophages from ICE-deficient mice underwent apoptosis normally upon ATP treatment. Thymocytes from young ICE-deficient mice also underwent apoptosis when triggered by dexamethasone, gamma irradiation, or aging. ICE-deficient mice had a major defect in the production of mature IL-1 beta and had impaired IL-1 alpha production on LPS stimulation in vitro and in vivo. ICE-deficient mice were resistant to LPS-induced endotoxic shock.

Adenosine Triphosphate↗
PubMed1997

Effects of unsaturated fatty acids on interleukin-1beta production by human monocytes.

Dihomogammalinolenic acid is derived from gammalinolenic acid, administration of which suppresses joint inflammation. It is reported here that interleukin 1beta (IL-1beta) production by human monocytes is enhanced markedly when cells are incubated 18-24 h with the polyunsaturated fatty acids dihomogammalinolenic acid (DGLA) and arachidonic acid (AA), then stimulated with lipopolysaccharide. Effects of eicosapentaenoic acid (EPA) on IL-1beta production are minimal, and palmitic acid (PA) does not influence IL-1beta production.

8,11,14-Eicosatrienoic Acid↗
PubMed1997

Postoperative analgesia with preoperative oral ibuprofen or acetaminophen in children undergoing myringotomy.

Previous studies have shown over 70% of children require analgesics following bilateral myringotomy and tube placement (BM&T). This double-blind, placebo-controlled study compared the postoperative analgesic effects of preoperatively administered oral acetaminophen or ibuprofen. Forty three ASA I or II children age six months or older scheduled for elective BM&T were randomized to receive acetaminophen (paracetamol) 15 mg.kg-1, ibuprofen 10 mg.kg-1, or placebo. Postoperative pain was assessed using the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) upon arrival to the PACU and at 5, 10, 15, 30, 45, and 60 min. CHEOP scores did not differ between the groups at any time. There was no difference in the number of children receiving rescue analgesia. This study showed no benefit of preoperatively administered oral ibuprofen 10 mg.kg-1 or acetaminophen 15 mg.kg-1 over placebo for the relief of postoperative pain in children undergoing BM&T.

Acetaminophen↗
PubMed1997

Depression in dementia: a study of mood in a community sample and referrals to a community service.

The association between degree of cognitive impairment and severity of depressive symptoms was examined in a randomly selected community-based sample of elderly people and in a sample of patients referred to an old age psychiatry service. Findings contradict previous reports of less cognitive impairment in demented patients with depressive symptoms. We suggest that sample selection bias has contributed to the earlier reports.

Affect↗
PubMed1996

Proteolytic activation of protein kinase C delta by an ICE/CED 3-like protease induces characteristics of apoptosis.

Recent studies have shown that protein kinase C (PKC) delta is proteolytically activated at the onset of apoptosis induced by DNA-damaging agents, tumor necrosis factor, and anti-Fas antibody. However, the relationship of PKC delta cleavage to induction of apoptosis is unknown. The present studies demonstrate that full-length PKC delta is cleaved at DMQD330N to a catalytically active fragment by the cysteine protease CPP32. The results also demonstrate that overexpression of the catalytic kinase fragment in cells is associated with chromatin condensation, nuclear fragmentation, induction of sub-G1 phase DNA and lethality. By contrast, overexpression of full-length PKC delta or a kinase inactive PKC delta fragment had no detectable effect. The findings suggest that proteolytic activation of PKC delta by a CPP32-like protease contributes to phenotypic changes associated with apoptosis.

Amino Acid Sequence↗
PubMed1996

Non-erythroid alpha-spectrin breakdown by calpain and interleukin 1 beta-converting-enzyme-like protease(s) in apoptotic cells: contributory roles of both protease families in neuronal apoptosis.

The cytoskeletal protein non-erythroid alpha-spectrin is well documented as an endogenous calpain substrate, especially under pathophysiological conditions. In cell necrosis (e.g. maitotoxin-treated neuroblastoma SH-SY5Y cells), alpha-spectrin breakdown products (SBDPs) of 150 kDa and 145 kDa were produced by cellular calpains. In contrast, in neuronal cells undergoing apoptosis (cerebellar granule neurons subjected to low potassium and SH-SY5Y cells treated with staurosporine), an additional SBDP of 120 kDa was also observed. The formation of the 120 kDa SBDP was insensitive to calpain inhibitors but was completely blocked by an interleukin 1 beta-converting-enzyme (ICE)-like protease inhibitor, Z-Asp-CH2OC(O)-2,6-dichlorobenzene. Autolytic activation of both calpain and the ICE homologue CPP32 was also observed in apoptotic cells. alpha-Spectrin can also be cleaved in vitro by purified calpains to produce the SBDP doublet of 150/145 kDa and by ICE and ICE homologues [ICH-1, ICH-2 and CPP32(beta)] to produce a 150 kDa SBDP. In addition, CPP32 and ICE also produced a 120 kDa SBDP. Furthermore inhibition of either ICE-like protease(s) or calpain protects both granule neurons and SH-SY5Y cells against apoptosis. Our results suggest that both protease families participate in the expression of neuronal apoptosis.

Amino Acid Sequence↗
PubMed1996

Prelacteal feeds are negatively associated with breast-feeding outcomes in Honduras.

The 1991/92 Epidemiology and Family Health Survey (ENESF) from Honduras was examined for associations between prelacteal feeds and breast-feeding outcomes. The ENESF is a self-weighted nationally representative survey that included 2380 women with children under the age of two. Multivariate logistic regression was used to examine the association between prelacteal feeds and breast-feeding practices among 0- to 6-mo-old infants (n = 714), and to identify factors associated with milk-based prelacteal feeds. Providing milk-based prelacteal feeds was negatively associated with both exclusive (odds ratio = 0.18) and any breast-feeding (0.21). Prelacteal water was negatively associated with exclusive breast-feeding (0.19). Both water- and milk-based prelacteal feeds were associated with a delayed milk arrival and a delay in the time at which the child was offered the breast for the first time. Our findings suggest that prelacteal feeds have an adverse effect on breast-feeding outcomes.

Adolescent↗
PubMed1996

Nebulized budesonide is as effective as nebulized adrenaline in moderately severe croup.

OBJECTIVE: Nebulized budesonide and nebulized adrenaline have been shown to be effective in the treatment of moderately severe croup. However, there has been no direct comparison of these therapies. We undertook a multicenter, randomized, double-blind, parallel group study in 66 hospitalized children with viral or spasmodic croup. METHODS: Children 0.5 to 6 years of age were assessed using a validated croup symptom score (stridor, 0 through 4; cough, 0 through 3; retractions, 0 through 3; dyspnea, 0 through 3; and color, 0 through 4) at 0.5, 1, 1.5, 2, 12, and 24 hours after nebulization. Patients received either budesonide (2 mg/4 mL) or L-adrenaline (4 mg/4 mL) via nebulization. The primary outcome measure was change in the total croup symptom score. RESULTS: Thirty-five children received budesonide and 31 received adrenaline. There was no significant difference in baseline features, including croup score (mean [95% confidence interval]: budesonide, 7.1 [6.7-7.5]; adrenaline, 7.7 [7.3-8.1]). All patients had significant improvement from baseline, and there was not significant difference between the two treatments, as measured by change in croup scores, change in oxygen saturation, duration of hospitalization, number of subsequent treatments with systemic steroids or adrenaline, and adverse events. No child required intubation. CONCLUSION: This study does not show any difference in efficacy and safety between nebulized budesonide and nebulized adrenaline in the treatment of acute upper airway obstruction in patients with moderately severe croup.

Administration, Topical↗
PubMed1995

Identification and characterization of ICH-2, a novel member of the interleukin-1 beta-converting enzyme family of cysteine proteases.

Interleukin-1 beta converting enzyme (ICE) is a cytoplasmic cysteine protease required for generating the bioactive form of the interleukin-1 beta cytokine from its inactive precursor. We report the identification of ICH-2, a novel human gene encoding a member of the ICE cysteine protease family, and characterization of its protein product. ICH-2 mRNA is widely expressed in human tissues in a pattern similar to, but distinct from, that of ICE. Overexpression of ICH-2 in insect cells induces apoptosis. Purified ICH-2 is functional as a protease in vitro. A comparison of the inhibitor profiles and substrate cleavage by ICH-2 and ICE shows that the enzymes share catalytic properties but may differ in substrate specificities, suggesting that the two enzymes have different functions in vivo.

Amino Acid Sequence↗
PubMed1995

Mice deficient in IL-1 beta-converting enzyme are defective in production of mature IL-1 beta and resistant to endotoxic shock.

IL-1 beta-converting enzyme (ICE) cleaves pro-IL-1 beta to generate mature IL-1 beta. ICE is homologous to other proteins that have been implicated in apoptosis, including CED-3 and Nedd-2/lch-1. We generated ICE-deficient mice and observed that they are overtly normal but have a major defect in the production of mature IL-1 beta after stimulation with lipopolysaccharide. IL-1 alpha production is also impaired. ICE-deficient mice are resistant to endotoxic shock. Thymocytes and macrophages from the ICE-deficient animals undergo apoptosis normally. ICE therefore plays a dominant role in the generation of mature IL-1 beta, a previously unsuspected role in production of IL-1 alpha, but has no autonomous function in apoptosis.

Animals↗
PubMed1995

The impact of postnatal depression on boys' intellectual development.

A follow-up study was carried out to investigate the children of 204 mothers who had previously participated in a study of their mental health during pregnancy and the first postnatal year. One hundred and seventy two children, 170 mothers, and 99 fathers were assessed when the children were 3 years 10 months. Boys of mothers depressed in the first year postpartum scored approximately 1 standard deviation lower on standardised tests of intellectual attainment than boys whose mothers were well that year. The difference was reliable even when behaviour during the test was controlled for, and general behavioural problems, birth weight, parental IQ measures of the family climate and home environment, mother-child interaction, and breast-feeding during infancy were taken into account.

Adult↗
PubMed1994

Responsiveness and calibration of the General Well-Being Adjustment Scale in patients with hypertension.

We examined the discriminant ability and responsiveness of the General Well-Being Adjustment Scale in patients enrolled in a randomized clinical trial of antihypertensive therapy. We also tried to translate the effects of physical symptoms on general well-being. This secondary analysis used demographic, clinical, physical symptom, and general well-being data for 545 white, male hypertensive patients. General well-being was measured by the General Well-Being Adjustment Scale (GWB) collected on 2 occasions over 8 weeks of treatment. Patients with any one of 14 physical symptoms or problems, compared to those without symptoms, had lower GWB scores (p < 0.003 to p < 0.0001). Decreases of 2.83-8.76 points in GWB scores were observed in patients developing physical symptoms over the 8 week study period (p < 0.05 to p < 0.0001). These effects were demonstrated in patients developing cold sensitivity, sexual problems, chest pain, shortness of breath, loss of taste, nausea, hot or cold spells, numbness and tingling, dry mouth, blurred vision, and dizziness. We conclude that the GWB is responsive to clinically meaningful changes in symptoms and may provide a more complete evaluation of the effects of medical treatment. The GWB is a valid and responsive measure of health status outcomes in the evaluation of antihypertensive treatment.

Adult↗
PubMed1993

Pedigree analysis of alpha-L-fucosidase gene mutations in a fucosidosis family.

Fucosidosis is an autosomal recessive lysosomal storage disease resulting from absence of alpha-L-fucosidase activity. Lymphoid cell lines from two siblings with fucosidosis and a healthy individual (control) had alpha-L-fucosidase mRNA of normal size (2.3 kb) but the level of alpha-L-fucosidase mRNA in the patients' cells was reduced. cDNA was prepared and amplified from alpha-L-fucosidase mRNA of lymphoid cells of the patients, their carrier parents, and the control. Direct DNA sequencing demonstrated three mutations in the fucosidosis family. One mutation, C1282-->T, changed the codon (CAA) for Gln-422 to a stop codon (UAA). This mutation was heterozygous (C and T) in the patients and their father and independently confirms an earlier report (J. Mol. Neurosci. (1989) 1, 177). Another mutation, C247-->T, changed the codon (CAG) for Gln-77 to a stop codon (UAG) and was heterozygous (C and T) in the patients and their mother. The third mutation, A860-->G, changed the codon CAG for Gln-281 to the codon (CGG) for Arg and was heterozygous (A and G) in the patients but homozygous in their father. alpha-L-Fucosidase activity in cells of the father was 37% of controls indicating that homozygosity of the A860-->G mutation did not cause an absence of alpha-L-fucosidase activity and fucosidosis. This mutation probably results in a normal polymorphic variant of alpha-L-fucosidase. It is proposed that the combination of the C247-->T mutation on the maternal allele of the alpha-L-fucosidase gene and the C1282-->T mutation on the paternal allele caused fucosidosis in the patients.

B-Lymphocytes↗
PubMed1993

Rehabilitation and staffing levels in a 'new look' hospital-hostel.

The present study examined the utility of a new hospital-hostel with low staffing levels. Results showed that the hostel was able to maintain 9 of the 10 initially transferred patients and has been able to provide some improvements in their quality of life. However, unlike highly staffed hospital-hostels, it was not able to decrease patients' disabilities. Implications of this are discussed in relation to staffing levels and practices.

Activities of Daily Living↗
PubMed1993

Telephone advice in the accident and emergency department: a survey of current practice.

The objective of this study was to assess the standard of advice given by telephone by accident and emergency (A&E) departments following patients' enquiries. In order to do this patient enquiries were simulated and a telephone questionnaire was carried out. The study was carried out in 18 major and 16 minor A&E departments in Wales. Results achieved were that overall, correct telephone advice was given to 72 of 97 simulated patients (74%). Sixty calls were dealt with by the nursing staff (62%) who gave correct advice on 41 (68%) occasions. No A&E department had a formal policy nor provided staff training for handling patients' enquiries by telephone. It is concluded that A&E departments should train designated members of staff, preferably the triage nurse, who would formally deal with telephone enquiries requiring medical advice. There should be formal documentation of the enquiry and advice proffered as part of a departmental policy.

Counseling↗