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Biomedical subjects

J Kiely

Publications and source records attributed to J Kiely.

At least 19 recordsLinked to original sources
PubMed2000

Fungal atopy in adult cystic fibrosis.

This study set out to estimate the prevalence of atopy to a variety of common ubiquitous fungi, including A. fumigatus, in cystic fibrosis (CF), and to evaluate the investigations by which the diagnosis was made. Particular attention was paid to the usefulness of skin testing and immunoassays in detecting which patients had simple fungal atopy, and which patients were at high risk of developing allergic bronchopulmonary mycoses. This cross-sectional study included 21 adult CF patients and 20 matched controls. Serum samples were taken for the measurement of total serum IgE and specific serum IgE to nine common fungi. Immediate hypersensitivity skin prick testing to each of the fungi was also performed. Simple fungal atopy was described in subjects fulfilling the following criteria: total serum IgE > 100 KU l(-1) with specific radioimmunoassay > or = grade 1 to at least one fungus and a positive skin prick test (SPT) > or = 3 mm to the same fungus. 'High risk' for developing allergic bronchopulmonary mycosis (ABPM) was described in subjects fulfilling the following criteria: total serum IgE > 200 KU l(-1) with specific radioimmunoassay > or = grade 2 to at least one fungus and a positive skin prick test (SPT) > or = 6 mm to the same fungus. The adult CF group had a significantly higher total SPT score (P=0.005) and mean total serum IgE (P<0.05) than controls. Forty-three percent of CF patients fulfilled the criteria for fungal atopy to at least a single fungus. Over half this group had an atopic tendency to more than one fungus. Nineteen percent of the CF group were at least 'high risk' of developing ABPM. Skin prick testing is a better marker of fungal atopy and a better predictor of those adult CF patients at higher risk of developing ABPM than specific radioimmunoassay serum testing. There is a high prevalence of fungal atopy in the adult CF population. Total serum IgE and skin prick testing are good predictors of fungal atopy and help predict those at risk of developing ABPM in CF.

Adolescent↗
PubMed2000

Functions of fission yeast orp2 in DNA replication and checkpoint control.

orp2 is an essential gene of the fission yeast Schizosaccharomyces pombe with 22% identity to budding yeast ORC2. We isolated temperature-sensitive alleles of orp2 using a novel plasmid shuffle based on selection against thymidine kinase. Cells bearing the temperature-sensitive allele orp2-2 fail to complete DNA replication at a restrictive temperature and undergo cell cycle arrest. Cell cycle arrest depends on the checkpoint genes rad1 and rad3. Even when checkpoint functions are wild type, the orp2-2 mutation causes high rates of chromosome and plasmid loss. These phenotypes support the idea that Orp2 is a replication initiation factor. Selective spore germination allowed analysis of orp2 deletion mutants. These experiments showed that in the absence of orp2 function, cells proceed into mitosis despite a lack of DNA replication. This suggests either that the Orp2 protein is a part of the checkpoint machinery or more likely that DNA replication initiation is required to induce the replication checkpoint signal.

Base Sequence↗
PubMed2000

Conditions predisposing to maternal mortality in twins and singletons, US birth cohort 1989.

Twin pregnancy is one of the most important conditions associated with increased perinatal mortality and morbidity. The consequences of twin pregnancy on the mother have not been explored in great detail. The aim of this study was to analyze the population-based data from the United States and delineate the various conditions of twin pregnancies which predispose to maternal mortality. Results of this study show that multiple pregnancy is strongly associated with maternal mortality and requires further analysis in order to prepare appropriate therapeutic and prophylactic protocols.

Adolescent↗
PubMed1998

Changing sex ratio in the United States, 1969-1995.

OBJECTIVE: To determine if the sex ratio of live births in the United States has changed during the 27 years from 1969 through 1995. DESIGN: Regression analysis of secular trends in sex ratios. SETTING: Population-based data. PATIENT(S): Liveborn infants in the United States 1969-1995. MAIN OUTCOME MEASURE(S): Sex of liveborn infant. RESULT(S): The sex ratio (number of male births divided by number of female births) declined significantly among whites during the 27 years under study. Among black newborns, the sex ratio significantly increased during the same time period. CONCLUSION(S): These secular trends could not be explained by changing maternal or paternal age, or by changing proportions of specific birth orders. Possible explanations for the observed changes in sex ratio include random fluctuations in sex ratio over time, changes in demographic characteristics of the population (other than the characteristics controlled for in this analysis), and changes in frequency or timing of intercourse. Environmental exposures are unlikely to account for the observed trends.

Black People↗
PubMed1998

Violence faced by staff in a learning disability service.

This study explores the issue of violence experienced by staff in the learning disability service of an NHS Trust. Based on the literature review a questionnaire survey was sent to all staff employed in the Trust's learning disability service (n = 295). The questionnaire sought: background details of respondents; numerical incidences and types of violence experienced over the previous 12 months; reporting mechanisms; reactions to and impact of violence on individuals and their work; support received. Vignettes provide a rich picture of the types of violent incidences and their impact. The findings show that 81% of staff in the learning disability service had experienced violence in the previous 12 months. Many had numerous experiences of violence. New and inexperienced staff are particularly vulnerable. Training and support systems are, on the whole, limited. Support received from colleagues is generally regarded as more helpful than that of line management. To explore good practice elsewhere, semi-structured interviews were held with individuals working with potentially violent clients in organizations other than the learning disability service. Suggestions are offered for putting in place human resource strategies to reduce the incidences of violence and provide appropriate post-incident support for staff on a continuing basis.

Adult↗
PubMed1997

Influenza vaccination in 22 developed countries: an update to 1995.

This study expands and updates through 1995 our earlier report on influenza vaccine use in 18 developed countries. Five of the six countries with high levels of vaccine use in 1992 (> or = 130 doses/1000 population) showed little change or slight declines over the subsequent 3 years. The exception was the United States, where a new federal program for vaccination reimbursement for the elderly helped to increase vaccine distribution from 144 to 239 doses/1000 population. The six countries with medium levels of vaccine use in 1992 (76-96 doses/1000 population) increased to > or = 100 doses/1000 population by 1995. Among the six low-use countries in 1992 (< or = 65 doses/1000 population), only Finland showed substantial improvement (96 doses/1000 population) in 1995. Four new countries were added to the study. In Germany, vaccine use increased to 80 doses/1000 population in 1995, but in Ireland it remained at a low level (48 doses/1000 population). In Korea, vaccine use increased from 17 to 95 doses/ 1000 population during the period 1987-1995. In Japan, very high levels of vaccine use (approximately 280 doses/1000 population) in the early 1980s were associated with vaccination programs for school children. However, vaccine use fell precipitously when these programs were discontinued, and only 2 and 8 doses/1000 population were used in 1994 and 1995, respectively. In all 22 countries, higher levels of vaccine use were associated with vaccination reimbursement programs under national or social health insurance and were not correlated with different levels of economic development. Excluding Japan, in 1995 there was still a greater than fourfold difference between the highest and lowest levels of vaccine use among the other 21 countries in the study. Given its well established clinical effectiveness and cost-effectiveness, none of these countries has yet achieved the full benefits of its programs for influenza vaccination.

Developed Countries↗
PubMed1995

Birth weight and perinatal mortality. A comparison of the United States and Norway.

OBJECTIVE: To compare perinatal mortality in the United States and Norway, using a new analytic approach based on relative birth weight. DESIGN: Comparison of linked birth and perinatal death records for US and Norwegian births from 1986 through 1987, the most recently available 2-year period. SETTING: Norway and the United States. PARTICIPANTS: A total of 7,445,914 US births and 105,084 Norwegian births. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Perinatal weight-specific mortality after adjustment for each country's own mean birth weight. RESULTS: The higher rate of perinatal death in the United States compared with Norway is due to an excess of preterm deliveries in the United States. Low-weight, preterm births comprise 2.9% of US births compared with 2.1% of Norwegian births. If the United States could eliminate this slight excess of preterm delivery, perinatal mortality in the United States would decrease to the level in Norway. Unexpectedly, the survival of newborns at any given birth weight is virtually the same in the United States and Norway when newborns' birth weights are considered relative to their own nation's mean weight. CONCLUSIONS: Low rates of perinatal mortality in the Scandinavian countries have usually been attributed to the heavier weights of their newborns. Higher mortality among US infants is in fact due entirely to a small excess of preterm deliveries. The lighter weights of US newborns at term appear not to affect perinatal survival. Furthermore, the apparent survival advantage of low-weight US newborns (used by policymakers as evidence of superior US intensive neonatal care) may be at least partly an artifact. When weight-specific mortality rates are adjusted to relative birth weight, low-weight newborns have the same survival in Norway as in the United States. The prevention of excess mortality among US infants depends on the prevention of preterm births, not on changes in mean birth weight.

Birth Weight↗
PubMed1995

Birthweight, preterm births and neonatal mortality in Belgium and the United States.

Belgium is known to have a lesser low birthweight rate and a lower infant mortality rate than the United States. We used previously unpublished data to show that beneath this comparison lies a more complicated picture. Singleton live birth certificates for 1986-87 were analysed. Despite a lower mean birthweight in Belgium (3360 g) than in the United States (3420 g), Belgium had fewer (4.9%) low birthweight infants than the US (5.9%) because of fewer preterm births (4.4 vs. 9.3%). Consistent with the excess of preterm births in the US, the residual distribution of birthweight was smaller in Belgium (2.2% vs. 3.1%). Whereas neonatal mortality was 4.8/1000 in Belgium and 5.6/1000 in the US, birthweight-specific neonatal mortality was higher in Belgium. The challenge for Belgium is to improve the survival of newborns regardless of their birthweight. In the US, the task is to eliminate the excess of small preterm infants.

Belgium↗
PubMed1994

Glucocorticoids down-regulate beta 1-adrenergic-receptor expression by suppressing transcription of the receptor gene.

The expression of beta 2-adrenergic receptors is up-regulated by glucocorticoids. In contrast, beta 1-adrenergic receptors display glucocorticoid-induced down-regulation. In rat C6 glioma cells, which express both of these subtypes of beta-adrenergic receptors, the synthetic glucocorticoid dexamethasone stimulates no change in the total beta-adrenergic receptor content, but rather shifts the beta 1:beta 2 ratio from 80:20 to 50:50. Radioligand binding and immunoblotting demonstrate a sharp decline in beta 1-adrenergic receptor expression. Metabolic labelling of cells with [35S]-methionine in tandem with immunoprecipitation by beta 1-adrenergic-receptor-specific antibodies reveals a sharp decline in the synthesis of the receptor within 48 h for cells challenged with glucocorticoid. Steady-state levels of beta 1-adrenergic-receptor mRNA declined from 0.47 to 0.26 amol/microgram of total cellular RNA within 2 h of dexamethasone challenge, as measured by DNA-excess solution hybridization. The stability of receptor mRNA was not influenced by glucocorticoid; the half-lives of the beta 1- and beta 2-subtype mRNAs were 1.7 and 1.5 h respectively. Nuclear run-on assays revealed the basis for the down-regulation of receptor expression, i.e. a sharp decline in the relative rate of transcription for the beta 1-adrenergic-receptor gene in nuclei from dexamethasone-treated as compared with vehicle-treated cells. These data demonstrate transcriptional suppression as a molecular explanation for glucocorticoid-induced down-regulation of beta 1-adrenergic receptors.

Animals↗
PubMed1992

Alcohol and cigarette use in a pregnant Irish population.

One hundred women were selected at random and interviewed. All were postnatal. The object was to establish the level of alcohol and cigarette consumption and the level of knowledge to potential adverse effects. Of the 100 women interviewed 89% drank prior to pregnancy, six drank between 100-120 grams/week and 19 drank > 120 grams/week. 11 women stopped drinking when they became pregnant. In the group which drank 100-120 grams/week, 66% decreased their alcohol consumption considerably ie > 100 grams/week while pregnant, while in the group which drank > 120 grams/week only 15% decreased their alcohol consumption. 38 women binged on at least one occasion while 21 said they had binged on at least one occasion during the first trimester. 58% of women were aware of the harmful effects of alcohol during pregnancy. They compared with 93% who were aware of the harmful effects of smoking during pregnancy. Only 11% of women said a doctor had mentioned alcohol as harmful, while 57% said that a doctor had mentioned the hazard of smoking in pregnancy. The overall results show a general ignorance to the effects of alcohol consumption in pregnancy compared to the level of knowledge about smoking. The results also highlight the fact that doctors do not make patients aware of the effects of alcohol in pregnancy while they make an effort to educate people about the problems of smoking during pregnancy.

Alcohol Drinking↗
PubMed1989

High-efficiency expression of mammalian beta-adrenergic receptors in baculovirus-infected insect cells.

Infection of a clonal isolate of Spodoptera frugiperda cells (Sf9) with a baculovirus expression vector harboring the cDNA encoding the beta-adrenergic receptor resulted in a high efficiency expression. At 48 hr post-infection, the level of expression of beta-adrenergic receptors was approximately 12 million/cell. Specific activities of crude lysates of infected Sf9 cells were approximately 30 pmol/mg of protein, 5-fold greater than those of membranes of high-expressor Chinese hamster ovary cells stably transfected with an SV-40 expression vector. One liter of infected Sf9 cells expresses 20-40 nmol of receptor. Autoradiography of membranes incubated with the beta-adrenergic antagonist [125I]iodoazidobenzylpindolol, photolyzed, and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed 46,000- (presumably unglycosylated) and 48,000-Mr peptides for Sf9 cells as compared to approximately 65,000-Mr for Chinese hamster ovary cells. The baculovirus Sf9 system provides high-efficiency expression of receptor sufficient to permit physicochemical analyses.

Animals↗
PubMed1989

Immune-related alterations in aged gut-associated lymphoid tissues in mice.

To study whether senescence-induced changes in the gut-associated lymphoid tissue (GALT) are mainly quantitative, several parameters were examined in three age groups of BALB/c mice (1-2, 12-14, and 24-28 months old). A substantial senescence-associated decline in the number of lymphoid cells was found in the mesenteric lymph nodes (MLN) and spleen (SPN), and especially in the Peyer's patches (PP), but not in the lamina propria (LP). The distribution of lymphocyte subsets in these tissues was also altered with an absolute reduction of T cells--in particular, a L3T4+ helper/inducer T-cell marker-bearing subset. These changes were most remarkable in PP, followed by MLN. The in vitro proliferative reactivity and the production of each isotype-specific immunoglobulin (Ig) by PP, MLN, and SPN were profoundly affected when T-cell-dependent (Td) B-cell mitogens were used, but minimally affected when T-cell-independent (Ti) B-cell mitogens were used. The isotype-specific Ig content of small-intestinal perfusates was also influenced by aging, but only to a minor extent, as exemplified by a decrease in IgA levels in the fasting condition. Thus, despite the defects in the quantity and distribution of lymphocytes in aged PP and MLN, the finding of little change in the total amount of secreted IgA in aged intestine suggests that gut IgA-mediated luminal immune responses could remain nearly unaltered with senescence. The constancy of intraluminal IgA levels could be of physiological significance in host defense at the gut mucosal surface in aged mice.

Aging↗
PubMed1989

Impaired non-specific suppressor-inducer T-cell activity in aged murine Peyer's patches, which can be corrected largely by IL-2 in vitro.

To shed further light on the mechanism of age-associated T-cell-mediated immunoregulatory alterations in gut non-specific mucosal immune responses, we studied in vitro the function of a variety of concanavalin A (Con A)-activated immunoregulatory T-cell subsets derived from aged murine Peyer's patches (PP) (BALB/c > 24 months old) in the production of class-specific immunoglobulins (Ig) by young (5-8 months old) lipopolysaccharide (LPS)-activated PP B cells. The in vitro induction of Con A-activated PP helper (Th) [L3T4+ Lyt-2- Vicia villosa non-adherent (VV-)], suppressor (Ts) L3T4- Lyt-2+ (VV-), and contrasuppresor (Tcs) (L3T4+ Lyt-2- VV+) T cells were compared for the two age groups. The activities of aged PP-derived Ts and Tcs cells were greatly impaired, in contrast to minor defects in activity of the aged Th cells. The induction of effector Tcs cells, however, depended on the presence of functionally effective Ts cells. Recombinant IL-2 (rIL-2) could largely correct this impaired generation of aged Ts and Tcs cells. Next, we determined the activities of Ts inducer (Tsi) (L3T4+ Lyt-2- VV-) T cells in aged PP in vitro. The cell activity was considerably diminished in aged mice. Then, we tested in vitro whether rIL-2 could reconstitute the impaired generation of the aged non-specific Tsi cell. The function of the latter cell was largely restored by rIL-2. Thus, the major functional (intrinsic) defect present in immunocompetent T lymphocytes of murine aged PP was confined to the Tsi cell.

Aging↗
PubMed1988

In vitro induction of a contrasuppressor immunoregulatory network by polyclonally activated T cells derived from murine Peyer's patches.

Much evidence suggests that Peyer's patch (PP) lymphocytes are capable of mounting both humoral and cell-mediated immune responses to luminal antigenic stimuli. To shed further light on T-T and T-B cell interactions in gut mucosal immune-associated processes, we studied in vitro the effects of a variety of PP-derived concanavalin A (Con A)-activated immunoregulatory T-cell subsets on class-specific immunoglobulin (Ig) production by lipopolysaccharide (LPS)-activated PP-derived B cells. Particular attention was focused on induction of a contrasuppressor T-cell immunoregulatory network in the above in vitro system. Three types of immunoregulatory effector T cells, a helper T (Th) cell, a suppressor T (Ts) cell and a contrasuppressor T (Tcs) cell were developed and isolated. The results showed that B cell Ig production was under the regulation of these T cells, and the L3T4+ Lyt-2- T cell, which bound to Vicia villosa (VV), had a contrasuppressor effector function. In addition, a L3T4+ Lyt-2- VV- Ts inducer (Tsi) subset and a L3T4- Lyt-2+ VV- Ts effector subset also appeared to participate in the sequential development of the suppressor and, probably, contrasuppressor immunoregulatory networks, respectively. Thus, PP T cells are likely to execute their highly sophisticated immunoregulatory functions, not only in the helper and suppressor circuits but also in the contrasuppressor circuit in response to intraluminal non-specific stimuli. However, IgA isotype-specific Ig production appears to be controlled primarily by the isotype-specific helper circuit, not by the contrasuppressor circuit, in polyclonal LPS-stimulated gut mucosal immune responses.

Animals↗
PubMed1987

Immunoregulatory defects in murine aged Peyer's patches.

Aging effect on immunoregulatory processes in Peyer's patches (PP) from BALB/c mice of 3-4 months and 24-28 months was studied in vitro. The magnitude of isotype-specific Ig production by aged or young PP B cells in co-culture with young or old fresh PP T cells strongly suggested that the suppressor activity of PP T cells was impaired in aged mice. Further studies on in vitro induction of concanavalin A-activated T helper cells, T suppressor-inducer cells and T suppressor cells from aged PP indicated that the generation of T suppressor cells was largely impaired, in contrast to a minor defect(s) in that of T helper cells. The findings obtained here at least suggest that in aged PP, a T suppressor-inducer cell subset appears to be more selectively impaired in the aging process than the other lymphocyte subpopulations, which possess minor intrinsic functional defects. Thus, these abnormal T and B cell responses in PP could be responsible for the senescence-associated gut mucosal immunologic dysfunction.

Aging↗