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J Burke

Publications and source records attributed to J Burke.

At least 73 records · Page 4Linked to original sources
PubMed1997

CD11b mRNA expression in neutrophils isolated from peripheral blood and gingival crevicular fluid.

Adhesion molecule CD11b/CD18 expressed by neutrophils (PMNs) participates in cell migration and phagocytosis of C3bi derivatized bacteria. It is this phagocytic function that eliminates some of the known periodontal pathogens in periodontal pockets. In patients with advanced periodontitis, homotypic aggregation of crevicular fluid PMNs (CF-PMNs) may occur due to overexpression of CD11b/CD18 and this may lead to ineffective elimination of periodontal pathogens. We have previously shown that CF-PMNs isolated from the periodontal pockets overexpress CD11b compared to PB-PMNs. This study tested the hypotheses that (1) overexpression of surface CD11b correlates with expression of CD11b mRNA in CF-PMNs isolated from advanced periodontitis subjects, and (2) the intrinsic capacity of CD11b mRNA upregulation by PB-PMNs from periodontitis patients differs from that of control subjects. CF-PMNs and peripheral blood PMNs (PB-PMNs) were isolated from 13 subjects with healthy gingiva (control group) and 13 subjects with advanced periodontitis (patient group). The surface expression of CD11b was determined by flow cytometry and CD11b mRNA was determined by extraction of mRNA and reverse transcription to cDNA followed by DNA amplification using primers to detect a segment of the cDNA which encodes CD11b. The results of this study confirm that the surface expression of CD11b on CF-PMNs is significantly higher in periodontitis subjects vs control subjects (p = 0.03), whereas surface CD11b expression on PB-PMNs does not differ significantly between groups (p = 0.06). The level of surface CD11b expression on CF-PMNs did not correlate with the amount of mRNA present in CF-PMNs in either group (p = 0.056, 0.07 for control and periodontitis patients, respectively). Most (9 of 13) individuals in the patient group expressed CD11b mRNA whereas very few control subjects (2 of 11) had CD11b mRNA in their CF-PMNs. This difference between groups was statistically significant (p = 0.004). The capacity to upregulate CD11b mRNA upon stimulation with fMLP and/or GM-CSF was highly variable and there was no statistical difference between the 2 groups.

Adult↗
PubMed1997

A comparison of the biochemical composition of equine follicular fluid and serum at four different stages of the follicular cycle.

Samples of blood and follicular fluid were recovered from 27 Welsh Pony mares at 4 distinct stages of follicular development. Eighteen biochemical parameters were measured in each sample, including sodium, potassium, chloride, glucose, urea, creatinine, calcium, inorganic phosphate, total bilirubin, total protein, albumin, magnesium, triglyceride, total cholesterol, nonesterified fatty acids, alkaline phosphatase, gamma-glutamyltransferase and aspartate aminotransferase. The concentrations of progesterone, 17beta oestradiol and testosterone, pH and osmolarity, were also measured in all the follicular fluid samples. The concentrations of all proteins measured were lower in follicular fluid than serum whereas the reverse was true in the case of the lipids. Analysis of variance indicated that serum and follicular fluid concentrations of most of the parameters measured varied in parallel.

Animals↗
PubMed1997

Brimonidine.

Brimonidine tartrate is a highly selective alpha2-adrenergic receptor agonist indicated for the chronic treatment of glaucoma and ocular hypertension. Glaucoma, a serious worldwide public health problem causing blindness in 5.2 million people, is treated by drugs that lower the intraocular pressure (IOP), a primary risk factor in glaucomatous optic neuropathy. Currently, beta-blockers are the most common therapy. In two 12-month clinical comparison trials with timolol 0.5% (n = 926), twice-daily brimonidine produced IOP lowering comparable to twice-daily timolol. In a 3-month trial with betaxolol 0.25% suspension (n = 206), twice-daily brimonidine was more effective in lowering IOP than twice-daily betaxolol. Brimonidine was well-tolerated ocularly and systemically in these trials. It caused no clinically significant mean changes in heart rate or blood pressure. Brimonidine produced no significant effect on FEV1 in clinical trials, and it is not contraindicated in patients with cardiopulmonary disease. Brimonidine 0.2% dosed twice daily has clinical utility as a first-line drug therapy. It is an effective and safe alternative to beta-blockers, particularly in patients at risk for pulmonary or cardiovascular disease. It decreases aqueous humour production and increases uveoscleral outflow, and has an additive ocular hypotensive effect used concomitantly with other agents. Brimonidine has demonstrated neuroprotective properties in laboratory animal studies. Additional studies are warranted to determine whether brimonidine has clinical benefit in protecting the optic nerve head from glaucomatous damage. Brimonidine is an important contribution to glaucoma management.

Journal Article↗
PubMed1996

Glycosylation defect in Lec1 Chinese hamster ovary mutant is due to a point mutation in N-acetylglucosaminyltransferase I gene.

The Lec1 Chinese hamster ovary (CHO) mutant is a leuco-phytohemagglutinin resistant cell line unable to synthesize complex and hybrid N-glycans due to the lack of N-acetylglucosaminyltransferase I (GnTI) activity. Here we have identified the lec1 mutation. Using specific antibodies to GnTI we demonstrate that Lec1 cells synthesize an inactive GnTI protein identical in size to the wild-type CHO enzyme. We have cloned and sequenced the gene coding GnTI from parental CHO and Lec1 mutant cells. Comparison of GnTI sequences detected three mutations within the luminal domain of Lec1 GnTI, each resulting in an amino acid substitution. The effect of each mutation on enzyme activity was analyzed by site-directed mutagenesis of wild-type rabbit GnTI and transient expression in COS cells. One of the three mutations (Cys123 --> Arg123) resulted in complete loss of activity, whereas the other two mutations had no apparent effect on enzyme activity. This conclusion was confirmed by expression of GnTI mutants in the GnTI null background of Saccharomyces cerevisiae. Both Lec1 GnTI and the GnTI mutant (Cys123 --> Arg123) are correctly localized to the Golgi apparatus, indicating that the inactive GnTI molecules are sufficiently well folded for efficient transport from the endoplasmic reticulum. These results demonstrate that the lec1 mutation is a point mutation and that Cys123 is a critical residue for GnTI activity.

Amino Acid Sequence↗
PubMed1996

Irish study on high-density schizophrenia families: field methods and power to detect linkage.

Large samples of multiplex pedigrees will probably be needed to detect susceptibility loci for schizophrenia by linkage analysis. Standardized ascertainment of such pedigrees from culturally and ethnically homogeneous populations may improve the probability of detection and replication of linkage. The Irish Study of High-Density Schizophrenia Families (ISHDSF) was formed from standardized ascertainment of multiplex schizophrenia families in 39 psychiatric facilities covering over 90% of the population in Ireland and Northern Ireland. We here describe a phenotypic sample and a subset thereof, the linkage sample. Individuals were included in the phenotypic sample if adequate diagnostic information, based on personal interview and/or hospital record, was available. Only individuals with available DNA were included in the linkage sample. Inclusion of a pedigree into the phenotypic sample required at least two first, second, or third degree relatives with non-affective psychosis (NAP), one whom had schizophrenia (S) or poor-outcome schizo-affective disorder (PO-SAD). Entry into the linkage sample required DNA samples on at least two individuals with NAP, of whom at least one had S or PO-SAD. Affection was defined by narrow, intermediate, and broad criteria. The phenotypic sample contained 277 pedigrees and 1,770 individuals and the linkage sample 265 pedigrees and 1,408 individuals. Using the intermediate definition of affection, the phenotypic sample contained 837 affected individuals and 526 affected sibling pairs. Parallel figures for the linkage sample were 700 and 420. Individuals with schizophrenia from these multiplex pedigrees resembled epidemiologically sampled cases with respect to age at onset, gender distribution, and most clinical symptoms, although they were more thought-disordered and had a poorer outcome. Power analyses based on the model of linkage heterogeneity indicated that the ISHDSF should be able to detect a major locus that influences susceptibility to schizophrenia in as few as 20% of families. Compared to first-degree relatives of epidemiologically sampled schizophrenic probands, first-degree relatives of schizophrenic members from the ISHDSF had a similar risk for schizotypal personality disorder, affective illness, alcoholism, and anxiety disorder. With sufficient resources, large-scale ascertainment of multiplex schizophrenia pedigrees is feasible, especially in countries with catchmented psychiatric care and stable populations. Although somewhat more severely ill, schizophrenic members of such pedigrees appear to clinically resemble typical schizophrenic patients. Our ascertainment process for multiplex schizophrenia families did not select for excess familial risk for affective illness or alcoholism. With its large sample ascertained in a standardized manner from a relatively homogeneous population, the ISHDSF provides considerable power to detect susceptibility loci for schizophrenia.

Adult↗
PubMed1996

Effects of Outward Bound Experience as an adjunct to inpatient PTSD treatment of war veterans.

There is a paucity of studies on Outward Bound Experiences (OBE) with adult psychiatric populations and, more notably, with trauma victims. This study evaluates the efficacy of OBE as an adjunct to specialized inpatient PTSD treatment with survivors of chronic combat-related PTSD (N = 219) at two Veterans Administration Medical Centers. On several measures of PTSD and general adaptation, results showed that the five-day OBE did not differ from standard treatment of PTSD survivors. Two other issues were addressed: identification of successful and non-successful subjects as a result of OBE, and exploration of objective versus subjective measures among this chronic group. Finally, as a post-study analysis, inferred curative components of the OBE were discussed as each appeared to impact on the participants.

Adult↗
PubMed1996

Alerting effects on choice reaction time and the photic eyeblink reflex.

To test the possibility that a common mechanism might be responsible for alerting effects on voluntary and reflexive reactions, choice reaction times (RT) to intense flashes of light were compared with eyeblink reflexes simultaneously evoked by those stimuli. An acoustic accessory stimulus, irrelevant to the RT task, facilitated both voluntary and reflexive reactions. A time uncertainty manipulation also generated facilitation of both responses under conditions in which phasic arousal was presumably greatest. However, there were several dissociations between alerting effects on voluntary and reflexive reactions and between effects on the early and late subcomponents of the photic orbicularis oculi reflex. In conjunction with other research in humans and animals, these data support the assumption that alerting involves the activation of multiple neuromodulatory (e.g. monoamine) systems, each of which is characterized by a distinct behavioral, neuropharmacological, and electrophysiological profile.

Acoustic Stimulation↗
PubMed1996

Preclinical evaluation of brimonidine.

Preclinical studies of brimonidine show that it is a potent alpha 2-adrenoceptor agonist that is 1000-fold more selective for the alpha 2-vs. the alpha 1-adrenoceptor, and is 7-12-fold more alpha 2-selective than clonidine and 23- to 32-fold more alpha 2-selective than apraclonidine (p-aminoclonidine). Brimonidine decreased intraocular pressure (IOP) in various animal models but, unlike apraclonidine, brimonidine was not mydriatic. The site and pharmacology of the IOP response depends on the animal species. In rabbits, the IOP response to brimonidine is mediated by an ocular alpha 2-adrenoceptor while in monkeys, a central nervous system (CNS) 'imidazoline' receptor appears to be involved. Brimonidine decreased IOP by suppressing the rate of aqueous humor flow and enhancing uveoscleral outflow. Topical brimonidine resulted in posterior segment drug levels adequate to activate alpha 2-adrenoceptors, but was not vasoconstrictive in a model designed to assess the vasoactivity of the human retinal microvasculature. Brimonidine protected the rat optic nerve from secondary damage following mechanical injury to the optic nerve and was nontoxic in an array of experiments designed to evaluate ocular and organ toxicity. Taken together, the high alpha 2-adrenoceptor selectivity, ocular hypotensive efficacy, retinal bioavailability and neuroprotective properties make brimonidine an important addition to the field of antiglaucoma agents.

Adrenergic alpha-Agonists↗
PubMed1996

Within-compound associations mediate the retrospective revaluation of causality judgements.

The role of within-compound associations in the retrospective revaluation of causality judgements was investigated in a two-stage procedure in which the subjects were asked to learn whether or not different food stimuli caused an allergic reaction in hypothetical patients. In the compound-cue stage a number of compound cues, each consisting of a competing stimulus and a target stimulus, were associated with the reaction across a series of trials, whereas in the single-cue stage the subjects had the opportunity to learn which of the competing cues, when presented alone, caused the reaction. Each target stimulus was presented with the same competing cue across all compound trials in the consistent condition, but with a different competing cue on each trial in the varied condition. In a forward procedure, in which the single-cue stage preceded compound cue training, judgements of the causal effectiveness of the target stimuli were reduced or blocked by training them in compound with a competing cue that had been previously paired with the reaction. Moreover, the magnitude of this reduction was comparable in the consistent and varied conditions. This was not true, however, when the single- and compound-cue stages were reversed in the backward procedure. Judgements for target cues compounded with competing cues that were subsequently paired with the reaction were reduced only in the consistent condition. If it is assumed that stronger associations were formed between the competing and target stimuli during the compound-cue stage in the consistent condition than in the varied condition, this pattern suggests that the retrospective revaluation of causality judgements can be mediated by the formation of within-compound associations.

Allergens↗
PubMed1996

Screening protocol for Torulopsis (Candida) glabrata.

A screening test has been developed for the presumptive identification of Torulopsis (Candida) glabrata from other common clinical isolates of yeast-like fungi. An interlaboratory comparison of a protocol consisting of morphology on cornmeal Tween 80 agar and trehalose fermentation at 42 degrees C was successful in differentiating T. glabrata from other taxa that are frequent or possible clinical isolates. The screening results for 517 clinical yeast isolates, 241 of which were T. glabrata, were compared with their final identification via commercial systems (API20C Yeast Identification System [bioMERIEUX, Hazelwood, Mo.] and Rapid Yeast Identification Panel [Dade Microscan, Sacramento, Calif.]). The trehalose screening test has a sensitivity and a specificity of 97.8 and 95.8%, respectively, and a positive predictive value of 97.4% and a negative predictive value of 96.5%. Overall, the trehalose screen had an efficiency rating of 93.9% for ruling in or out T. glabrata. Since T. glabrata represents a substantial part of the workload in a clinical laboratory, a significant reduction in direct and indirect costs should be realized.

Candida↗
PubMed1996

Evidence for a schizophrenia vulnerability locus on chromosome 8p in the Irish Study of High-Density Schizophrenia Families.

OBJECTIVE: This study was an attempt to replicate evidence for a vulnerability locus for schizophrenia and associated disorders in the 8p22-21 region reported by Pulver and colleagues. METHOD: The linkage sample of the Irish Study of High-Density Schizophrenia Families consists of 265 multiplex families containing 1,408 individuals. Fifteen markers covering 30 centimorgans on chromosome 8p were tested. Three statistical methods were used: two-point and multipoint heterogeneity lod scores and a multipoint nonparametric test. RESULTS: According to two-point heterogeneity lod scores, the strongest evidence for linkage was found for markers D8S1731 (maximum lod score = 2.00), D8S1715 (maximum lod score = 2.52), and D8S133 (maximum lod score = 2.08) by assuming a phenotypic definition of all psychiatric illness and a range of genetic models. According to multipoint heterogeneity lod scores, the strongest evidence for linkage (maximum lod score = 2.34), found by using a dominant genetic model and a broad definition of the schizophrenia spectrum, extended over a 10-cM region between markers D8S1715 and D8S1739. Multipoint nonparametric linkage found the strongest evidence (maximum z = 2.51) over a broader region when either a diagnosis of core schizophrenia or a narrow definition of the schizophrenia spectrum was used. This putative vulnerability locus was segregating in 10%-25% of the families studied. CONCLUSIONS: This study supports the existence of a vulnerability locus for schizophrenia on chromosome 8p. In this sample, this locus appears to influence the risk of illness in only a modest proportion of families and predisposes to a range of schizophrenia spectrum and possibly nonspectrum disorders.

Chromosomes, Human, Pair 8↗
PubMed1996

Risk of dementia among relatives of Alzheimer's disease patients in the MIRAGE study: What is in store for the oldest old?

Despite recent advances in the molecular genetics of Alzheimer's disease (AD), several fundamental questions concerning risk of illness are unresolved, namely, if Mendelian factors account for the incidence of the disease, and if AD is an inevitable consequence of the aging process. This study was designed to address these issues and other aspects of familial aggregation of the disorder. A consecutive sample of 1,694 patients who met criteria for a diagnosis of probable or definite AD were ascertained in 13 centers participating in the Multi-Institutional Research in Alzheimer Genetic Epidemiology (MIRAGE) project. Lifetime risk and age at onset of AD among various strata of 12,971 first-degree relatives was estimated using survival analysis procedures. The lifetime risk of AD in first-degree relatives was 39.0% +/- 2.1% by age 96 years. Age-specific risk of AD declined after age 90 and the data set included 61 apparently unaffected persons who survived to age 96 without becoming demented. Female relatives had a higher risk of AD than male relatives at all ages. By age 80, children of conjugal AD couples had a cumulative risk of 54%, 1.5 times greater than the sum of the risks to children having affected mothers or fathers, and nearly 5 times greater than the risk to children having normal parents. Children of affected fathers had a cumulative risk that was 1.4 times the corresponding risk to children of affected mothers. Risk assessment in early-onset and late-onset families, using various strategies for determining the age cut-off, yielded contradictory results. These data suggest the following: (1) the lifetime risk among relatives does not support a simple autosomal dominant inheritance pattern of disease; (2) women are innately more susceptible to AD than men; (3) the proportion of hereditary cases may be higher in men than women; (4) distinction between early- onset and late-onset forms of AD has little meaning in the absence of a biological marker; (5) the risk of AD decreases after age 90; and (6) AD therefore may not be an inevitable concomitant of the aging process, a conclusion that has profound implications for basic and applied AD research. The age- and sex-specific lifetime risks derived from this study are sufficiently robust to be a reliable source of information for counseling relatives of AD patients.

Age Factors↗
PubMed1996

The Saccharomyces cerevisiae processing alpha 1,2-mannosidase is localized in the endoplasmic reticulum, independently of known retrieval motifs.

The yeast-specific alpha 1,2-mannosidase, Mns1p, converts Man,GlcNAc2 to a single isomer of Man8GlcNAc2 during N-linked oligosaccharide processing in Saccharomyces cerevisiae. Mns1p is a 68 kDa type II integral membrane glycoprotein with a very short amino terminal cytoplasmic tail of only two amino acids and a large carboxy-terminal catalytic region that is homologous to class 1 alpha 1,2-mannosidases from mammalian and other species. We have used immunofluorescence and immunoelectron microscopy to demonstrate that Mns1p is localized in the endoplasmic reticulum in Saccharomyces cerevisiae. As Mns1p contains none of the known endoplasmic reticulum retrieval motifs (HDEL, KK or RR), these results suggest that Mns1p is localized in the endoplasmic reticulum by a different retentin mechanism.

Antibodies, Monoclonal↗
PubMed1995

Adrenergic and imidazoline receptor-mediated responses to UK-14,304-18 (brimonidine) in rabbits and monkeys. A species difference.

Brimonidine is a relatively selective alpha-2 adrenoceptor agonist that is being developed for the treatment of glaucoma. Because brimonidine is chemically related to clonidine and has affinity for the nonadrenergic imidazoline receptor, its ocular effects may be unrelated to alpha-2 receptor activation. The objective of this study was to determine the pharmacology of the intraocular pressure (IOP) response to brimonidine in rabbits and monkeys and the side effects (miosis, cardiovascular depression) in monkeys. Conscious albino rabbits and cynomolgus monkeys were pretreated topically with the following receptor antagonists: rauwolscine (alpha-2), idazoxan (alpha-2, imidazoline), SKF 105854 (vascular postjunctional alpha-2), and prazosin (alpha-1). Intraocular pressure, pupil size, or blood pressure/heart rate was monitored noninvasively for 6 hours following dosing. Binding experiments were performed using [3H]brimonidine in membrane preparations from rabbit iris/ciliary body and from monkey cerebral cortex and brain stem. In rabbits, the ocular hypotensive response to brimonidine was unilateral and was inhibited by rauwolscine > idazoxan >> SKF 105854 = prazosin; this ranked order of potency correlated with displacement of [3H]brimonidine in the rabbit iris/ciliary body. In monkeys, brimonidine decreased IOP bilaterally and suppressed cardiovascular function suggesting a CNS site of action. Intraocular pressure and cardiovascular responses to brimonidine were inhibited by idazoxan >> rauwolscine > SKF 105854 = prazosin; a similar profile was obtained for displacement of [3H]brimonidine in monkey brain tissue. Both rauwolscine and idazoxan inhibited the miotic response to brimonidine in monkeys. Taken together, these results indicate that brimonidine stimulates an ocular alpha-2 adrenoceptor to decrease IOP in the rabbit and a CNS imidazoline receptor to decrease IOP, blood pressure, and heart rate in the cynomolgus monkey. The miotic response in the monkey is mediated by an alpha-2 adrenoceptor. The alpha-1 and vascular postjunctional alpha-2 adrenoceptors do not appear to play a role in mediating these responses.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1995

A potential vulnerability locus for schizophrenia on chromosome 6p24-22: evidence for genetic heterogeneity.

In 265 Irish pedigrees, with linkage analysis we find evidence for a vulnerability locus for schizophrenia in region 6p24-22. The greatest lod score, assuming locus heterogeneity, is 3.51 (P = 0.0002) with D6S296. Another test, the C test, also supported linkage, the strongest results being obtained with D6S296 (P = 0.00001), D6S274 (P = 0.004) and D6S285 (P = 0.006). Non-parametric analysis yielded suggestive, but substantially weaker, findings. This locus appears to influence the vulnerability to schizophrenia in roughly 15 to 30% of our pedigrees. Evidence for linkage was maximal using an intermediate phenotypic definition and declined when this definition was narrowed or was broadened to include other psychiatric disorders.

Chromosomes, Human, Pair 6↗