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Biomedical subjects

A Moran

Publications and source records attributed to A Moran.

At least 37 records · Page 2Linked to original sources
PubMed2000

Carboxy terminal region of the Fanconi anemia protein, FANCG/XRCC9, is required for functional activity.

Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome with eight complementation groups. Four of the FA genes have been cloned, and at least three of the encoded proteins, FANCA, FANCC, and FANCG/XRCC9, interact in a nuclear complex, required for the maintenance of normal chromosome stability. In the current study, mutant forms of the FANCA and FANCG proteins have been generated and analyzed with respect to protein complex formation, nuclear translocation, and functional activity. The results demonstrate that the amino terminal two-thirds of FANCG (FANCG amino acids 1-428) binds to the amino terminal nuclear localization signal (NLS) of the FANCA protein. On the basis of 2-hybrid analysis, the FANCA/FANCG binding is a direct protein-protein interaction. Interestingly, a truncated mutant form of the FANCG protein, lacking the carboxy terminus, binds in a complex with FANCA and translocates to the nucleus; however, this mutant protein fails to bind to FANCC and fails to correct the mitomycin C sensitivity of an FA-G cell line. Taken together, these results demonstrate that binding of FANCG to the amino terminal FANCA NLS sequence is necessary but not sufficient for the functional activity of FANCG. Additional amino acid sequences at the carboxy terminus of FANCG are required for the binding of FANCC in the complex. (Blood. 2000;96:1625-1632)

Animals↗
PubMed2000

Tissue-engineered valved conduits in the pulmonary circulation.

OBJECTIVE: Bioprosthetic and mechanical valves and valved conduits are unable to grow, repair, or remodel. In an attempt to overcome these shortcomings, we have evaluated the feasibility of creating 3-leaflet, valved, pulmonary conduits from autologous ovine vascular cells and biodegradable polymers with tissue-engineering techniques. METHODS: Endothelial cells and vascular medial cells were harvested from ovine carotid arteries. Composite scaffolds of polyglycolic acid and polyhydroxyoctanoates were formed into a conduit, and 3 leaflets (polyhydroxyoctanoates) were sewn into the conduit. These constructs were seeded with autologous medial cells on 4 consecutive days and coated once with autologous endothelial cells. Thirty-one days (+/-3 days) after cell harvesting, 8 seeded and 1 unseeded control constructs were implanted to replace the pulmonary valve and main pulmonary artery on cardiopulmonary bypass. No postoperative anticoagulation was given. Valve function was assessed by means of echocardiography. The constructs were explanted after 1, 2, 4, 6, 8, 12, 16, and 24 weeks and evaluated macroscopically, histologically, and biochemically. RESULTS: Postoperative echocardiography of the seeded constructs demonstrated no thrombus formation with mild, nonprogressive, valvular regurgitation up to 24 weeks after implantation. Histologic examination showed organized and viable tissue without thrombus. Biochemical assays revealed increasing cellular and extracellular matrix contents. The unseeded construct developed thrombus formation on all 3 leaflets after 4 weeks. CONCLUSION: This experimental study showed that valved conduits constructed from autologous cells and biodegradable matrix can function in the pulmonary circulation. The progressive cellular and extracellular matrix formation indicates that the remodeling of the tissue-engineered structure continues for at least 6 months.

Animals↗
PubMed2000

Cystic fibrosis-related diabetes: an approach to diagnosis and management.

Diabetes is a common complication of cystic fibrosis (CF). Because of evidence that it is associated with increased morbidity and mortality, prompt diagnosis and aggressive management of CF-related diabetes (CFRD) is important. The Cystic Fibrosis Foundation held a consensus conference in 1998 to define the current standards for the diagnosis and care of this disease [Moran A, Hardin D, Rodman D et al. Diagnosis, screening, and management of CFRD: a consensus conference report. J Diabetes Res Clin Pract 1999: 45: 61-73]. This article reviews those recommendations, and presents the practical approach to the management of CFRD used at the University of Minnesota.

Journal Article↗
PubMed2000

Atopic eczema is associated with delayed maturation of the antibody response to pneumococcal vaccine.

The aim of this study was to investigate a previously undocumented observation, that children with atopic eczema under 9 years of age tended to have a poor antibody response to Pneumococcal vaccination. Thirty-five children (mean age 8.8 years, range 3-16 years) with moderate to severe atopic eczema but no history of systemic infection were studied retrospectively. Pneumococcal antibody responses after immunization with Pneumovax II were compared with a hospital control group consisting of 36 children (mean age 6.0 years, range 3-16 years) with recurrent upper respiratory tract infections. Only 17% of children with atopic eczema aged 3-8 years responded to Pneumovax. This response was significantly poorer than that of the controls (57%) (odds ratio 0.20, 95% confidence interval (CI) 0.05-0.84, P = 0.03). There were no significant differences in the levels of total IgG2, the component of IgG associated with protective antibody responses to Pneumococcus between the two groups. Delay in maturation of the total IgG and IgG2 antibody response to Pneumococcus is a feature in this group of children with moderately severe atopic eczema.

Adolescent↗
PubMed2000

Trends in pulmonary function in patients with cystic fibrosis correlate with the degree of glucose intolerance at baseline.

In patients with cystic fibrosis, CF-related diabetes mellitus (CFRD) has been associated with increased morbidity and mortality. Whether glucose intolerance is also associated with poor outcomes is unclear. To better define these relationships we prospectively followed a group of 152 patients with CF without diabetes for 4 yr. Patients were classified as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or CFRD without fasting hyperglycemia (CFRD-No FH). FEV(1), FVC, and body mass index (BMI) were measured at baseline and quarterly. At baseline 45% of the patients had NGT, 38.8% had IGT, and 15.8% had CFRD-No FH. FEV(1), FVC, and BMI at baseline were comparable among these groups (all p > 0.1). After 4 yr an overall decline in FEV(1) and FVC occurred, with no change in BMI. The rates of decline for FEV(1) and FVC correlated with the glucose tolerance groups, with the highest rates of decline occurring among the CFRD-No FH group. In addition, patients in the lowest quartile for insulin production at baseline experienced the highest rates of pulmonary function decline over time, suggesting a relationship between insulin deficiency and clinical deterioration. We conclude that the degree of glucose intolerance is a strong determinant of future lung function decline in patients with CF.

Adolescent↗
PubMed2000

Absence of a numerical memory span advantage in Japanese Kanji.

Research suggests that people's memory span for Arabic numerals is consistently greater than that for digit words written in an alphabet, even when these stimuli have been matched for word length, lexicality, and semantics. It is not clear whether this "numeral advantage" holds true for other scripts. The present study tested this possibility in the case of Japanese kanji (the Chinese characters used in Japanese). 23 Japanese adults responded to stimuli comprised of two sets of random number sequences, one set presented in Arabic numerals and the other in digit word kanji. Each set began with three two-item sequences followed by three three-item sequences and so on, until three 12-item sequences were presented. Consecutive repetition of stimuli was avoided. Memory span was measured as the length of the last correctly recalled item sequence. Results indicated no numeral advantage effect, as there was no significant difference between people's recall of numerals and digit words. Memory strategy in dealing with kanji appears to bear more resemblance to numerals than to words in English.

Adult↗
PubMed2000

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Journal Article↗
PubMed2000

Smoking and quitting among Irish teenage males.

Nicotine addiction in adulthood is usually preceded by exposure to cigarettes in adolescence. A minimal exposure may be sufficient to produce addiction. Strategies to reduce adult smoking must address those factors, which influence teenage smoking. In this study we aimed to establish the prevalence of smoking in male secondary schools, to measure the association between student's smoking status and parental, peer and sibling smoking and to describe attempted quitting. An anonymous questionnaire was given to 1070 male secondary school pupils in two schools in County Louth. Twenty-seven percent of respondents smoked every day or on most days. Having a best friend who smoked was associated with personal smoking (O.R. 11.75, C.I. 8.6-16.08) as was sibling smoking (O.R. 3.49, C.I. 2.67-4.57.) Seventy percent of smokers stated that they wanted to stop and 75% that they had tried to stop. Only five smokers (1.2%) had been advised to quit by their general practitioner. We conclude that smoking is as prevalent among teenage boys in Ireland as it has been shown to be elsewhere and that most teenagers are unable rather than unwilling to stop.

Adolescent↗
PubMed1999

Regulation by P2 agonists of the intracellular calcium concentration in epithelial cells freshly isolated from rat trachea.

Epithelial cells were isolated from rat trachea by incubation of the organ in a calcium-free medium. The intracellular concentration of calcium ([Ca(2+)](i)) was measured with the calcium-sensitive fluorescent dye fura2. In resting conditions, the cells maintained a low [Ca(2+)](i) in spite of the presence of millimolar concentration of calcium in the incubation medium. These cells had retained intracellular stores of calcium which were emptied after exposure of the cells to thapsigargin, an inhibitor of intracellular calcium ATPases. Substance P (125 nM) transiently increased 2.5-fold the [Ca(2+)](i). ATP (1 mM) doubled the [Ca(2+)](i) after a few seconds and further induced a sustained increase of the [Ca(2+)](i). Coomassie blue fully blocked the response to ATP and extracellular magnesium only inhibited the delayed response to ATP. Among purinergic analogs, only benzoyl-ATP (Bz-ATP), an agonist on P2X ionotropic purinergic receptors, reproduced the response to ATP. UTP and 2-methylthioATP (two agonists on P2Y metabotropic purinergic receptors) transiently increased the [Ca(2+)](i). Thapsigargin, ATP and Bz-ATP increased the uptake of extracellular calcium. RT-PCR analysis revealed that two metabotropic receptors (P2Y(1) and P2Y(2)) and two ionotropic receptors (P2X(4) and P2X(7)) were expressed by the cells present in the suspension. It is concluded that purinergic agonists can modulate the response of rat tracheal epithelial cells by several mechanisms. The activation of metabotropic receptors should mobilize intracellular IP(3)-sensitive calcium pools. The activation of the ionotropic receptors should not only open a non-specific cation channel leading to the entry of calcium but should also induce the formation of pores in cells expressing the P2X(7) receptors, which could be deleterious to these cells.

Adenosine Triphosphate↗
PubMed1999

Morphometry of the dorsal raphe nucleus serotonergic neurons in suicide victims.

BACKGROUND: The serotonin deficiency hypothesis of suicide has been important heuristically. Few studies have directly examined the brainstem dorsal raphe nucleus (DRN) serotonin neurons. We determined the number and morphometry of DRN serotonergic neurons in suicide victims (n = 7) compared to controls (n = 6). METHODS: Brainstems were collected at autopsy, fixed and cryoprotected. Tissue was sectioned, stained for Nissl and processed with an antiserum that cross-reacts with tryptophan hydroxylase. All DRN neurons were identified, counted and analyzed every 1000 microns. Neuron morphometry was characterized by soma area (micron 2), sphericity, perimeter, length and density (neurons per mm3). RESULTS: Neuron number and density was higher in suicide victims (1,780 +/- 127 neurons/mm3) than controls (1,349 +/- 68). The DRN volume did not differ between groups (66 +/- 9 mm3 for controls vs. 67 +/- 5 mm3 for suicides). Mean neuronal area and sphericity did not differ between suicides and controls. The total number and the density of DRN neurons did not correlate with age. CONCLUSIONS: The finding of an increased number of neurons indicates that impaired serotonergic transmission found in association with serious suicide attempts is not due to fewer neurons.

Adolescent↗
PubMed1999

Defective antibody production in patients with rheumatoid arthritis and bronchiectasis.

Bronchiectasis (BR) occurs in about 3% of patients with rheumatoid arthritis (RA). Defective antibody production is a rare but well-recognised cause of both BR and inflammatory arthritis. We examined the hypothesis that subtle specific antibody defects might play a role in the pathogenesis of BR associated with RA. Identification of defects in antibody production is important because substantial benefits may be gained from immunoglobulin replacement. Specific antibody production was assessed in 20 patients with RA and BR, 20 with BR alone, 20 with RA alone and 20 healthy controls (all groups matched for age and sex). All had normal total IgG. IgA and IgM and IgG subclass levels. Specific antibody production was assessed by assay of antibodies to representative polysaccharide and protein antigens. Subjects with subprotective titres were challenged with the appropriate vaccine. Defective antibody production was defined as a subprotective level despite immunisation. Three out of 20 patients with RA and BR had a defective IgG2 response to the polysaccharide antigen, but normal responses to the protein antigen. All of the subjects in the BR alone or healthy control group had normal antibody production. Two out of 20 patients with RA alone had defective production of antibodies against both protein and polysaccharide antigens; both were receiving gold therapy, a recognised cause of functional antibody defects. It was concluded that some patients with RA and BR have functional antibody defects and may benefit from antibody replacement. An unexpectedly high proportion of patients with RA alone also have functional antibody defects, possibly secondary to gold therapy.

Adult↗
PubMed1999

Purines, a new class of agonists in salivary glands?

The response of rat submandibular glands to extracellular purines was tested. In crude cellular suspensions, ATP increased the [Ca2+]i mostly by promoting uptake of extracellular calcium. ATP caused the pHi to drop, a response blocked by chloride channel inhibitors. ATP also inhibited the basal and isoproterenol-stimulated activity of the Na+ -K+ -2Cl-cotransporter. These effects were reproduced by benzoyl-ATP, an agonist of ionotropic purinoceptors. In pure ductal suspensions, ATP activated a metabotropic P2Y1 purinergic receptor coupled to phospholipase C and opened a non-specific cation channel coupled to a P2X7 receptor. Activation of these receptors stimulated a Ca2+ -dependent and a Ca2+ -independent phospholipase A2, the latter resulting in kallikrein secretion. We conclude that purinergic agonists can modulate the activity of both acinar and ductal phases of secretion. Activation of metabotropic receptors coupled to phospholipase C could lead to responses resembling those to muscarinic or adrenergic agonists. Activation of ionotropic receptors could stimulate new intracellular responses also involved in secretory function.

Adrenergic Agonists↗
PubMed1999

Are salivary glands cell lines in culture a good model for purinergic receptors in salivary glands?

A major obstacle in studying the physiological and biochemical processes of salivary secretion is the lack of a good ductal cell line model. HSY, an immortalised cell line originating from human parotid gland intercalated ducts, provides a possible model for purinergic mechanisms in ductal cells. Unlike the biphasic dose response to ATP of isolated submandibular ductal cells, the rise in [Ca2+]i in HSY cells shows single Michaelis-Menten kinetics with an apparent Ka of 0.8 microM. Pre-incubation with thapsigargin inhibited the ATP induced [Ca2+]i rise. Both ATP (10 microM) and carbachol (100 microM) increased IP3 production. Intercalated duct cells may differentiate into acinar or ductal cells in response to appropriate stimuli from extracellular matrix We therefore attempted to induce a duct-like phenotype in the striated duct-derived HSY cells by growing them on microcarrier beads coated with type I collagen. In Ca-containing medium cells grown on all substrates showed similar responses to ATP. In contrast, in Ca-free medium, [Ca2+]i rose only slightly in cells grown on beads relative to those on glass. This probably resulted from reduced IP3 production. Carbachol also induced a much smaller increase in [Ca2+]i and less IP3 production in cells grown on Cytodex-3. The HSY response to purinergic stimuli by an increase in [Ca2+]i and IP3 means that they can be used to study the metabotropic purinergic pathway. The impairment in the HSY responses grown on Cytodex-3 can be used to probe phosposinositol signal transduction in salivary cells.

Adenosine Triphosphate↗
PubMed1999

Diabetes mellitus in cystic fibrosis.

Glucose intolerance and diabetes are common complications of cystic fibrosis (CF), affecting up to 75% of the adult population. This article discusses the prevalence and pathophysiology of glucose tolerance abnormalities in CF, and reviews recent recommendations for diagnosis, screening, and management of CF-related diabetes (CFRD).

Adolescent↗
PubMed1999

Guidelines for the diagnosis and therapy of diabetes mellitus in cystic fibrosis.

Diabetes is a common complication of cystic fibrosis. Because it is associated with increased morbidity and mortality, prompt diagnosis and aggressive management of cystic fibrosis-related diabetes is important. The Cystic Fibrosis Foundation held a consensus conference in 1998 to define the standards of care for patients with this disease [1[symbol: see text]]. In this article, pathophysiology and management of cystic fibrosis-related diabetes are reviewed.

Consensus Statements as Topic↗
PubMed1999

Effect of heat acclimation and heat shock on oscillations of carbamyl-choline-evoked Ca2+ signal in HSY cell line.

We studied effects of heat acclimation (HA) and acute heat stress (HS) on Ca2+ signal oscillations following supramaximal carbamyl-choline (CCh) stimulation, using HSY cell line as a model. In the control cells, oscillations decreased their amplitude with time. HS alone did not change either oscillation amplitude or frequency, although calcium release to the cytosol upon CCh stimulation was faster. HA increased maximal oscillation amplitude only. There was no change in basal cytosolic calcium level and peak evoked signal in all experimental conditions. Collectively, the data suggest that HA affects the oscillation profile. Changes in the oscillation profile did not correlate with changes in the resting and evoked Ca2+ signal, which suggests that the oscillations are a separate target for heat acclimation.

Acclimatization↗