Search PubMed⌕ Search

Biomedical subjects

A Carmichael

Publications and source records attributed to A Carmichael.

At least 37 records · Page 2Linked to original sources
PubMed1999

Relationship between early life respiratory illness, family size over time, and the development of asthma and hay fever: a seven year follow up study.

BACKGROUND: The timing and mechanism of the inverse association between increasing sibling number and atopic disease are not yet understood. A study was undertaken to examine how family size at birth predicts early respiratory illness, to report the association between infant respiratory illness and childhood atopic disease, and to determine whether the protective effect of large family size operates during infancy or later childhood. METHODS: A prospective follow up study was carried out on 863 children (78%) of 1111 participants in the Tasmanian Infant Health Survey performed in 1988. In 1988 household size and history of respiratory illness were obtained by parental interview at home (median age 35 days) and later by telephone (median age 85 days). In 1995 asthma, hay fever, and household size were assessed by parental questionnaire in a large cross sectional survey. RESULTS: In 1988 increasing resident number (per resident) (adjusted odds ratio (AOR) 1.17 (95% CI 1.05 to 1.31)) and resident density (AOR 1.77 (95% CI 1.07 to 2.94)) were related to parental report of an upper respiratory tract infection (URTI) by one month of age. Children with a reported URTI by home interview were more likely to have subsequent asthma (adjusted relative risk (ARR) 1.27 (95% CI 1.05 to 1.53)). The association between lower respiratory tract infection (LRTI) at telephone interview (relative risk (RR) 1.34 (95% CI 1.02 to 1.75) and asthma was reduced after adjustment for family history of asthma (ARR 1.27 (95% CI 0.98 to 1.66)). Antibiotic use by home interview was not associated with subsequent asthma or hay fever. Indicators of family size in 1988 were associated with hay fever but not asthma but, in contrast, resident number in 1995 was inversely associated with asthma (AOR 0.82 (95% CI 0.72 to 0.92) per resident) and hay fever (AOR 0.82 (95% CI 0.71 to 0.96) per resident). Children with no siblings were at risk for current asthma, particularly if symptoms began after the age of four (RR 2.81 (95% CI 1.36 to 5.84)). CONCLUSIONS: The apparent protective effect of large household size and asthma could not be explained by an increase in reported early respiratory illness. The first year of life may not be the most critical time for the protective effect of large household size to be mediated in relation to asthma, but this effect occurred by the seventh year of life.

Adult↗
PubMed1998

Progressive loss of IL-2-expandable HIV-1-specific cytotoxic T lymphocytes during asymptomatic HIV infection.

In HIV-1 infection, circulating HIV-1-specific cytotoxic T lymphocytes (CTL) exist in different states of activation, including activated cytotoxic cells and memory cells. We report that a subpopulation of HIV-1-specific CTL is capable of clonal expansion upon culture with IL-2 without exogenous antigen. The IL-2-expandable HIV-1-specific CTL precursor frequency was reduced in patients with advancing infection, although HIV-1-specific memory CTL could still be detected by stimulation in vitro with allele-specific HIV-1 peptide. Longitudinal analysis during advancing infection showed a progressive decline in the IL-2-expandable HIV-1-specific CTL precursor (CTLp) frequency without a decline in Epstein-Barr virus (EBV)-specific or allo-specific CTLp frequencies. To address mechanisms that may contribute to the decline in the IL-2-expandable HIV-specific CTL response, the requirements for in vitro generation of HIV-1-specific and EBV-specific effector CTL were examined. In the absence of exogenous IL-2 in limiting dilution, generation of EBV-specific CD8+ effector CTL was dependent upon help from CD4+ cells. CD4+ help for EBV-specific CD8+ CTL was observed in asymptomatic HIV infection but not in advanced infection. In the presence of exogenous IL-2, CD4+ cells could also provide help for the optimal generation of HIV-1 peptide-specific CD8+ CTL, because in vitro depletion of CD4+ cells prior to culture using stimulation with an MHC class I-restricted HIV-1 peptide reduced the peptide-specific CD8+ CTL response. We conclude that there is a decline in the IL-2-expandable HIV-1-specific CTL response during advancing infection. There are a number of possible mechanisms for this decline, including a reduction in CD4+ T cell help for in vivo antigen-activated CD8+ T cells.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Cross sectional study of the relation between sibling number and asthma, hay fever, and eczema.

OBJECTIVES: To document the relation between sibling number and atopic disease, and to assess the contribution of possible confounding factors to the protective effect of siblings in relation to asthma and hay fever. DESIGN AND SUBJECTS: Cross sectional survey by parental questionnaire in Tasmania, Australia, on 6378 children (92% of those eligible) who reached 7 years of age during 1995. METHODS: Exercise challenge lung function testing was conducted on 428 children. Analyses reported were conducted on singleton births only (n = 6158). RESULTS: The prevalences of a history of asthma ever, hay fever, and eczema were 27%, 19%, and 22%, respectively. Asthma and hay fever, but not eczema, were inversely related to sibling number, with evidence of a dose-response trend. The mean age at onset for asthma or wheezy breathing decreased as the number of siblings increased. The inverse association between sibling number and asthma or hay fever persisted after adjustment for several confounders, such as parental smoking or breast feeding, but did not persist after adjustment for household size in 1995. CONCLUSIONS: The protective effect of high sibling number could not be separated from household size at age 7, and it appears to be operating after birth and influences the age at onset of asthma symptoms. Further work to increase knowledge of how the protective effect of the presence of siblings works might have important implications for the understanding of the pathogenesis of asthma.

Age of Onset↗
PubMed1996

Analysis of the human env-specific cytotoxic T-lymphocyte (CTL) response in natural human immunodeficiency virus type 1 infection: low prevalence of broadly cross-reactive env-specific CTL.

Major histocompatibility complex-restricted cytotoxic T lymphocytes (CTL) are part of the cellular immune response to persistent virus infections. Candidate vaccines against human immunodeficiency virus type 1 (HIV-1) should elicit broad cross-reactive immunity to confer protection against different strains of HIV-1. As it is likely that candidate vaccines will include the envelope gene product Env, we determined the proportion of CTL clones which recognized variable and conserved determinants in three env variants during natural infection. Limiting dilution analysis was used to characterize numerous short-term CTL clones derived from peripheral blood of HIV-1-infected subjects, using split-well analysis to assay cytotoxicity against target cells expressing gp160env of HIV-1 strains IIIB, MN, and RF. In 9 of 12 HIV-1-infected subjects, at the clonal level most env-specific CTL recognized determinant(s) within one env variant but not in the other variants. In some subjects, CTL recognized multiple nonconserved determinants in different variants. The pattern of recognition of different env variants was relatively stable over time. In most of the patients studied, the proportion of CTL which showed cross-recognition of conserved determinants shared among the three strains was low. Two novel CTL epitopes within gp41 were identified by using 15-mer peptides of the HIV-SF2 sequence. When specific peptide was used to stimulate CTL precursors in vitro, the frequency of peptide-specific CTL precursors was very high, but the CTL elicited by this stimulation were highly strain specific. We conclude that the use of a single HIV env variant to detect CTL activity can underestimate the magnitude and complexity of the env-specific CTL response. The low prevalence of CTL clones which show cross-recognition of conserved determinants may have implications for immunization strategies based solely on env; to elicit broadly cross-reactive CTL other, more conserved viral antigens are likely to be needed in addition to env. Because of its capacity to distinguish CTL responses against different virus strains, limiting dilution analysis is particularly appropriate to quantitate the immune responses generated by candidate env-based vaccines.

Adult↗
PubMed1996

Exercise-induced bronchial hyperresponsiveness and parental ISAAC questionnaire responses.

The predictive value of parental questionnaire responses for exercise-induced bronchoconstriction in childhood asthma has not been fully clarified. The aim of this study was to compare exercise-induced bronchial hyperresponsiveness in 7 year old children with parental responses to core questions in the International Study of Asthma and Allergies in Childhood (ISAAC) study. A cross-sectional study was conducted on 191 (91% of eligible) children from seven randomly selected schools in Southern Tasmania. Study measurements included a parental questionnaire and exercise challenge testing, using a recently validated 6 min free-running protocol. The response to exercise was assessed using forced expiratory volume in one second (FEV1) measurement. The median percentage fall in FEV1 was significantly higher in children whose parents responded positively to ISAAC questions on a history of wheeze (p = 0.0031) or asthma (p = 0.0005), recent wheeze (p = 0.0005), sleep disturbance due to wheeze (p = 0.0005), or exercise-induced wheeze (p = 0.0015). Receiver operating characteristic (ROC) curve analysis showed exercise-induced bronchial hyperresponsiveness to be a good indicator of current asthma status. Using a 12% or greater fall in FEV1 postexercise as a positive test response, the exercise challenge had sensitivity and specificity estimates for current asthma and exercise-induced wheeze of (0.58 and 0.77) and (0.60 and 0.77), respectively. In conclusion, the respiratory response to exercise was consistent with parental responses to the ISAAC questionnaire in a population-based sample of 7 year old children. These findings will assist interpretation of large ISAAC studies in terms of asthma prevalence.

Adult↗
PubMed1993

Quantitative analysis of the human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocyte (CTL) response at different stages of HIV-1 infection: differential CTL responses to HIV-1 and Epstein-Barr virus in late disease.

Major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTL) are part of the cellular immune response to human persistent virus infections. Measurements of the frequency and specificity of human immunodeficiency virus type 1 (HIV-1)-specific CTL and their variation with time may indicate their relative importance in modulating the progression of HIV-1 infection. We have used limiting dilution analysis (LDA) to derive quantitative estimates of the frequency of HIV-1-specific CTL precursors in a cross-sectional study of 23 patients at different clinical stages of HIV-1 infection and to compare these with the frequency of CTL precursors specific for another persistent virus (Epstein-Barr virus [EBV]) in the same patients. Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with autologous HIV-1-infected lymphoblasts and assayed for cytotoxicity in 51Cr release assays against autologous and MHC-mismatched lymphoblastoid B cells infected with recombinant vaccinia viruses expressing the three HIV-1 structural gene products. The frequency of MHC-restricted precursors was high in asymptomatic HIV-1-infected patients (env-specific CTL precursors up to 73/10(6) PBMC; gag-specific CTL precursors up to 488/10(6) PBMC), although the relative frequency against the different structural gene products varied from patient to patient. The HIV-1-specific CTL precursor frequency was reduced in patients who had more severe (< 400/microliters) CD4+ lymphocyte depletion, while in the majority of such patients the frequency of CTL precursors against EBV was maintained at levels observed in healthy controls. Direct CTL activity in unstimulated PBMC was observed in three of nine patients but no correlation was found between the presence of an activated CTL response and the magnitude of the CTL response detected after stimulation in LDA. Thus, CTL precursors were detected against all three HIV-1 structural gene products in patients with CD4+ lymphocyte counts > 400/microliters, at frequencies that are high compared with those reported for other persistent viruses. A CTL response directed against multiple protein antigens of HIV-1 may protect the patient against epitope variation. The fact that the EBV-specific CTL precursor frequencies were maintained in advanced HIV-1 infection suggests that there may be selective impairment of the HIV-1-specific CTL response associated with disease progression.

Adult↗
PubMed1992

A novel tissue preservation medium for immunoperoxidase staining of skin biopsies.

The requirement for unfixed tissue is a major drawback in the use of immunohistochemistry for the diagnosis of inflammatory and neoplastic disease. We describe the use of a novel gel transport medium (U.K. Patent No. WO 90/07703, international patent applications pending) to preserve unfixed skin biopsies from allergic contact dermatitis reactions for 1 week prior to frozen section and immunohistochemistry for leucocyte antigens. The medium can be used with biopsies up to 6 mm3 and does not require any alteration in the usual frozen section or immunohistochemical staining procedures. The results show a subjective improvement in both morphology and staining quality. We believe this to be due to improved cutting of the sections and reduced background staining of collagen. This transport medium should be of considerable benefit to the provision of a clinical service, because it allows tissue for immunohistochemical examination to be taken at locations distant from the pathology laboratory.

Cryopreservation↗
PubMed1992

Preservation of keratin expression in oral mucosa using a novel transport medium.

Cellular expression of keratins (intermediate filaments) can be demonstrated by immunocytochemistry using unfixed tissue. However, for practical reasons, provision of fresh tissue to the laboratory is often difficult. Recently a fresh tissue transport medium (Patent applied for) has been developed which allows keratin immunocytochemistry to be performed up to 4 days after biopsy. In this study oral mucosal biopsies from 10 patients were hemisected, half placed in the new transport medium at 4 degrees C and the other half immediately frozen in liquid nitrogen. After 4 days frozen sections of both halves of the biopsies were stained by immunocytochemistry using various antikeratin antibodies. The morphology and staining characteristics of the two halves of the biopsies were then assessed. No significant difference could be found in either morphology or preservation of keratin expression in specimens stored in transport medium, as compared to those in liquid nitrogen. This new transport medium may offer considerable advantage for the provision of a histologic and immunocytochemical diagnostic service.

Cacodylic Acid↗
PubMed1992

Immunohistochemical demonstration of B and T-lymphocyte cell surface markers: an assessment of tissue transport/storage media.

A number of solutions were tested on lymphoid tissue with a view to devising a tissue transport/long-term storage medium which would preserve the morphology and antigenicity of lymphocytes, for demonstration of B- and T-cell surface markers using monoclonal antibodies. Some of the solutions produced total loss of any recognisable tissue structure, but one newly-devised medium gave excellent preservation of morphology and nuclear detail, together with extremely good monoclonal antibody staining. This sterilised medium, Carmichael's medium*, contains a buffer and cryoprotectant: it forms a gel at 4 degrees C, but it is easily liquefied in warm water just prior to immersion of the biopsy. Sections from tissue preserved in Carmichael's Medium were found to be of equally good quality as, and in some cases better than, those which had been fresh frozen. *International patents are currently pending on the formulation of this medium, which will be available commercially through Raymond Lamb Ltd, London, England, UK.

Antigens, Surface↗
PubMed1991

Examination of induced sputum in the diagnosis of Pneumocystis carinii pneumonia.

The results of the examination of sputum induced by the inhalation of nebulized hypertonic saline in the diagnosis of Pneumocystis carinii pneumonia (PCP) are presented. In suspected cases of PCP in patients who were either HIV antibody positive or were receiving immunosuppressive therapy, 46 induced sputum specimens were stained using both Grocott's modified Gomori methenamine silver nitrate (GMS) and immunofluorescence staining. In 12 specimens P. carinii cysts were detected by both methods, in four specimens by GMS staining only and in five specimens by immunofluorescence only. The sensitivity of induced sputum examination in the detection of P. carinii cysts was increased by using both of these staining methods on each sputum specimen and the need for more invasive methods of diagnosis was reduced.

Bronchoalveolar Lavage Fluid↗
PubMed1991

Depression in mothers and behaviour problems with their preschool children.

A follow-up study of 224 families of a birth cohort of 272 families in a multi-ethnic poor socio-economic municipality in Melbourne when the children were 4 years old showed that 27% of the mothers were depressed. There was no difference in the depression rate between Australian-born and immigrant mothers, a finding in marked contrast to the first year of the study when the depression rate was significantly higher in those immigrant mothers who had been in Australia for less than 3 years, were unable to speak English and who did not have an extended family or close friends. Depression in this group of mothers was attributed to resettlement problems, which over a period of three years had ameliorated. At 4 years the most important factor associated with depression in both Australian-born and immigrant mothers was the quality of marital relationships. Lack of an intimate support relationship made mothers more vulnerable to the stresses of child care and rearing, home-making and life events. In Australian-born mothers only, another significant factor in vulnerability to depression, was their early childhood experiences of being reared in a disruptive home or in an institution and of being unwanted. In immigrant mothers, but not in Australian-born mothers, life events were significantly correlated with depression. The depressed mothers, both Australian-born and immigrant, perceived their 4 year old children to have significantly more behavioural problems than mothers who were not depressed.

Analysis of Variance↗