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Biomedical subjects

H Brown

Publications and source records attributed to H Brown.

At least 91 records · Page 5Linked to original sources
PubMed1997

Modulation of behaviour and testosterone concentration in immunodepressed male laboratory mice (Mus musculus).

Recent ideas suggest that current immunocompetence may act as a constraint on behavioural and physiological decisions, where these risk imposing an additional burden on immune function. We tested this in the context of time budgeting and the secretion of the potentially immunodepressive hormones testosterone and corticosterone, by treating adult male CFLP laboratory mice with antithymocyte serum (ATS) to depress thymus-mediated immune function. In comparison with males given a naive rabbit serum (NRS) vehicle control, ATS-treated mice showed a reduction in serum testosterone concentration, aggressive behaviour, and general activity, and maintained time spent sleeping, relative to pretreatment levels. Behaviours that differed between treatments correlated with measures of immunodepression (reduction in relative thymus weight or serum total IgG concentration), but relationships with behavioural changes were independent of those with testosterone. There was little evidence that changes were affected by social status. The results are discussed in the context of the adaptive modulation of immune function and physiological and behavioural decision-making.

Animals↗
PubMed1997

Immunity costs and behavioural modulation in male laboratory mice (Mus musculus) exposed to the odours of females.

In a previous study, male laboratory mice experimentally immunodepressed with anti-thymocyte serum (ATS) showed changes in behaviour (aggression, general locomotory activity, and sleeping) and testosterone that are consistent with decision-making being modulated adaptively with respect to immunocompetence. We tested this idea further by repeating the experiment with the addition of female odours (soiled sawdust) to the home cages of males following ATS/control treatment. We predicted that, in the presence of cues suggesting reproductive opportunity, immunodepressed males would trade off potential immunity costs by failing to modulate behaviour. This expectation was borne out in that ATS-treated mice showed no change in aggression, locomotory activity, mounting, or sleeping relative to control animals, and mice overall showed differences in behaviour in the expected direction compared with a previous study in which female odours were not presented. However, despite the lack of difference in behaviour between ATS and control treatments, there was still evidence of a degree of behavioural modulation in relation to measures of immunocompetence.

Animals↗
PubMed1997

Sexual abuse perpetrated by men with intellectual disabilities: a comparative study.

This paper compares cases of sexual abuse of adults with intellectual disabilities, reported across the South East of England, which were perpetrated by men with intellectual disabilities, with those committed by other male perpetrators. The comparison provides some support for the findings of other studies, which have suggested that men with intellectual disabilities offend against more male victims than non-disabled sex offenders and that their offences are somewhat less serious, but otherwise indicates common patterns of abusive behaviour across this divide but differential service responses and support for victims. So called 'peer abuse' is a widespread problem which service agencies have failed to address: repeated offences are frequent and lack of appropriate intervention is the norm.

Adult↗
PubMed1997

Measurement of cyclic variation in ultrasonic integrated backscatter in conscious, unsedated, clinically normal dogs.

OBJECTIVE: To assess the feasibility and repeatability of measuring ultrasonic integrated backscatter in unsedated conscious dogs, using a protocol previously validated in pigs with open thorax. ANIMALS: 11 clinically normal conscious unsedated German Shorthair Pointers. PROCEDURE: A modified commercially available echocardiography system was used to record long-axis views of the heart. The radiofrequency data from 15 consecutive frames were digitized and analyzed. Regions of interest were chosen within the myocardium, and the ultrasonic integrated backscatter within each region was calculated in the time domain for each frame. RESULTS: Cyclic variation in integrated backscatter values was observed, with maximal values at end-diastole and minimal values at end-systole. Mean +/-SD amplitude of cyclic variation was 5.81 +/- 3.86 dB over all the regions chosen. CONCLUSIONS: Results agreed with those obtained by other investigators working with dogs with open thorax and those with closed thorax while under general anesthesia. The analysis of the components of variance indicates that this is a consistent, reliable technique in conscious unsedated dogs. CLINICAL RELEVANCE: Integrated ultrasonic backscatter measurement provides a noninvasive means of tissue characterization. Use of this protocol reliably yields cyclic variation in integrated backscatter and could be applied clinically to dogs with myocardial disease.

Anesthesia, General↗
PubMed1996

Danazol relieves refractory pruritus associated with myeloproliferative disorders and other diseases.

Severe pruritus is frequently associated with myeloproliferative and other systemic illnesses, and often fails to respond to conventional measures. We used danazol (Danocrine), a synthetic attenuated androgen, in the treatment of severe pruritus refractory to conventional therapy. Eight patients had myeloproliferative disorders (MPD), seven had autoimmune disorders, and seven had skin diseases. Danazol at 400-800 mg/day was administered, and previous medications were tapered off. When itching was controlled with danazol alone, the dosage was reduced or discontinued, and resumed if itching recurred. Clinical responses were graded, and side effects were monitored. Overall, in 12 of 22 patients refractory to other measures, itching was controlled with danazol alone. In 10 patients itching returned when danazol was discontinued or dosage was continued for up to 5 years in responders. No serious side effects were observed. Our experience indicates that danazol is a good alternative for patients with severe pruritus associated with myeloproliferative and other systemic disorders.

Adult↗
PubMed1996

Influence of viraemia and genotype upon serological reactivity in screening assays for antibody to hepatitis C virus.

Detection of antibody to recombinant proteins derived from hepatitis C virus (HCV) genotype 1 represents the principal method for diagnosis of HCV infection. A method was developed for quantifying antibody reactivity in two third-generation enzyme immunoassays (Ortho EIA 3.0 and Murex VK48), and the influence of viraemia, HCV genotype, and host factors such as age, gender, and risk group upon antibody levels were investigated in a consecutive series of 117 anti-HCV-positive volunteer blood donors. Viraemic donors (as assessed by the polymerase chain reaction; PCR) showed significantly higher levels of anti-HCV by the Ortho EIA than those who were nonviraemic (adjusted mean difference of 10.1 fold after multiple regression analysis). The only other factor to influence significantly antibody level was genotype, where it was found that donors infected with type 1 showed 4 to 4.5 times greater serological reactivity by the Ortho assay than those infected with type 2 or 3. Antibody levels by the Ortho assay correlated closely to those detected by the Murex VK48 assay, and similar differences between PCR-positive and negative donors and between those infected with different genotypes were found. Differences in serological reactivity between genotypes indicate that a large proportion of epitopes of the type 1a or 1b recombinant proteins used in current assays are genotype specific. Variation in sensitivity of screening assays for different genotypes is of potential concern when used in countries where non-type 1 genotypes predominate in the blood donor or patient population.

Alanine Transaminase↗
PubMed1996

Lead-induced alterations of glial fibrillary acidic protein (GFAP) in the developing rat brain.

The developing nervous system is preferentially vulnerable to lead exposure with alterations in neuronal and glial cells of the brain. The present study examined early lead-induced alterations in the developing astrocyte population by examination of the developmentally regulated astrocyte specific protein, glial fibrillary acidic protein (GFAP). A developmental profile (Postnatal Day (PND) 6, 9, 12, 15, 20, and 25) for GFAP mRNA was generated for the cortex and hippocampus of developing Long-Evans hooded male rats under various lead exposure conditions: (1) prenatal (Gestational Day 13 to birth), (2) postnatal (Postnatal Day 1 to Postnatal Day 20), or (3) perinatal (Gestational Day 13 to Postnatal Day 20) exposure to lead acetate (0.2% in the drinking water of the dam). Control GFAP mRNA levels displayed a developmentally regulated profile of expression. In the cortex this was characterized by a transient elevation in peak level between PND 9 and PND 15 followed by a decline to within adult levels by PND 25. Under all lead acetate exposure conditions, the cortex showed an increase in the peak level of expression and extended the time of elevation of GFAP mRNA until PND 20. Levels of GFAP were elevated at PND 60 but not as early as PND 28. In the control hippocampus, levels of GFAP mRNA gradually increased until PND 20 followed by a sharp decline at PND 25. Postnatal and perinatal lead exposure followed a similar pattern; however, levels declined earlier at PND 20. Following prenatal lead exposure, levels of GFAP mRNA showed an earlier peak at PND 12 and a decrease as early as PND 15. By PND 60 protein level for GFAP was elevated in the postnatal lead exposure group only. As demonstrated by GFAP immunoreactivity, these lead-induced elevations were not associated with astrocyte hypertrophy. Following a physical injury in the cortex, astrocyte reactivity was similar between lead-exposed and control rats. These data suggest an alteration in the timing of astrocyte differentiation and maturation in the brain following developmental lead exposure.

Analysis of Variance↗
PubMed1996

Levels of hepatitis C virus in blood donors infected with different viral genotypes. International HCV Collaborative Study Group.

The level of hepatitis C virus (HCV) in the serum of 337 blood donors infected with different viral genotypes was investigated by branched DNA assay. Viral genotype was deduced by restriction analysis of the virus 5'-noncoding region. Samples included genotypes 1a, 1b, 2a, 2b, 3,4,5, and 6. Multivariate analysis revealed that the ranges of HCV levels were similar for all viral genotypes and subtypes (P=.18), with the possible exception of genotype 4. Virus levels were significantly lower in female than in male subjects (P<.001) but did not correlate with donor age (P=.06) or genotype or with donor age, sex, or country. These results indicate a similar replicative capacity in vivo for different HCV genotypes and clarify the influence of host and virus factors on disease severity and responsiveness to interferon treatment.

Blood Donors↗
PubMed1996

Long-term treatment of malignant gliomas with intramuscularly administered polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose: an open pilot study.

Polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC) (10-50 mcg/kg, administered intramuscularly one to three times weekly) was given for < or = 56 months to 38 patients with malignant gliomas. There was minimal or no toxicity. Twenty of 30 patients (66%) receiving at least twice weekly poly-ICLC showed regression or stabilization of gadolinium-enhancing tumor, as revealed by magnetic resonance imaging (median = 65% volume decrease). All but one patient with anaplastic astrocytomas who received continuous poly-ICLC remain alive, with a median progression-free survival of 54 months from diagnosis. Median Kaplan-Meier survival is 19 months for patients with glioblastomas who receive at least twice weekly poly-ICLC treatments. Tumor response was associated with 2',5' -oligoadenylate synthetase activation (P = 0.03) but not with serum interferon. We hypothesize clinical activation by poly-ICLC of a basic host tumor suppressor system. Prolonged, quality survival with tumor stabilization or regression confirmed by magnetic resonance imaging for most patients with anaplastic astrocytomas and glioblastomas suggests that more extensive laboratory and controlled clinical studies are warranted. The concept of long-term, broad spectrum stimulation of host defenses with nontoxic, inexpensive double-stranded ribonucleic acids, such as low-dose poly-ICLC, may be applicable to the treatment of other malignancies.

Adult↗
PubMed1995

Evaluation of serum eosinophilic cationic protein as a marker of disease activity in chronic asthma.

BACKGROUND: Serum eosinophil cationic protein (ECP) has been promoted as a direct marker of eosinophilic inflammation of the bronchi, especially helpful in patients with asymptomatic asthma. OBJECTIVE: To evaluate serum ECP against indirect clinical markers of disease activity, we compared symptom score, bronchial obstruction, bronchial responsiveness, and blood eosinophil counts with serum ECP levels in children with symptomatic and asymptomatic chronic asthma and assessed ECP in others with allergic rhinitis alone. METHODS: Twenty-four children with symptomatic asthma, 10 children with asymptomatic asthma, and 16 children with allergic rhinitis were studied. Measurements were made by standardized symptom questionnaire, spirometry, inhalation challenge with histamine or methacholine, blood eosinophil counts, and radioimmunoassay of serum ECP. RESULTS: There was no difference in serum ECP levels between the symptomatic asthma, asymptomatic asthma, or rhinitis groups, and most values were within the normal range. Activated eosinophil counts were higher in subjects with symptomatic asthma than in those with asymptomatic asthma but not in subjects with rhinitis. Serum ECP correlated with eosinophil counts (p < 0.01) but not symptom score, forced expiratory volume in 1 second (FEV1), forced expiratory flow, mid-expiratory phase (FEF25-75), or provocative concentration causing a 20% fall in FEV1 (PC20). Symptom scores correlated with PC20 (p < 0.005) and FEF25-75 (p < 0.01). CONCLUSION: Serum ECP is a poor indicator of disease activity in chronic asthma and cannot differentiate bronchial from nasal inflammation.

Adolescent↗
PubMed1995

Surgical management of pseudotumor cerebri in pregnancy: case report.

Little has been written concerning the surgical treatment of pregnant patients with pseudotumor cerebri. We present four cases of pregnant women who underwent lumboperitoneal shunt placement during pregnancy for progressive visual loss despite maximal medical therapy. The intraperitoneal pressure measured during surgery was significantly less than the cerebrospinal fluid pressure. Three of the four women had marked improvement in their vision after shunting, and one required optic nerve sheath decompressions for improvement. All delivered healthy babies. Pseudotumor cerebri in pregnant patients with progressive visual loss despite medical therapy is surgically treatable, and normal deliveries are expected. Therapeutic abortion to limit progression of the disease is not indicated.

Adult↗
PubMed1995

Ilya Mechnikov and his studies on comparative inflammation.

Mechnikov was born in Russia in 1845 and died in Paris in 1916. During his studies of embryogenesis and digestive function, he developed the concept of phagocytosis as a biologic phenomenon. He joined the Pasteur Institute in 1888 at Pasteur's invitation as Chef de Service there, studying inflammation and immunity in many species--both unicellular and high orders. In 1908, he was awarded the Nobel Prize in Medicine and Physiology with Paul Ehrlich.

Allergy and Immunology↗
PubMed1994

MAZ-dependent termination between closely spaced human complement genes.

The zinc finger protein MAZ, originally identified as a factor that binds to the c-myc P2 promoter, is associated with transcriptional termination. As shown in these studies, a termination sequence between the closely spaced human complement genes C2 and Factor B contains a protein binding site which interacts with three different proteins in vitro. Binding of one of these factors, MAZ, correlates with activity of the C2 termination sequence in vivo. Cloned MAZ was used to obtain a consensus binding site, G5AG5. This allowed identification of new sites, between the closely spaced human genes g11 and C4 and within an intron of the mouse IgM-D gene, where termination is known to occur and regulate the expression of IgD. The g11 and IgM MAZ sites lie within sequences that have activity in a termination assay and, furthermore, mutation of C2 or g11 MAZ sites severely reduces termination activity. MAZ bends DNA, and inherently bent DNA is highly active as a terminator, suggesting that MAZ-induced bending is important for C2 and g11 termination. We propose that MAZ sites exist in promoters which require protection against transcriptional interference, such as those of closely spaced genes, to cause efficient termination. The MAZ consensus sequence will facilitate the identification of further sites.

Base Sequence↗