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Biomedical subjects

J O'Brien

Publications and source records attributed to J O'Brien.

At least 199 records · Page 11Linked to original sources

Recovery of leukotriene E4 from the urine of patients with airway obstruction.

The urinary excretion of leukotriene E4 (LTE4) was measured in subjects presenting for emergency treatment of airway obstruction. A total of 72 subjects presenting with airway obstruction performed peak flow determinations before and after three treatments with nebulized albuterol given at 20-min intervals. Of these subjects, 22 more than doubled their peak flow rates, while 19 failed to increase their peak flow rates more than 25% during the treatment period. These groups were designated "responders" and "nonresponders," respectively. Urinary LTE4 excretion was determined in 16 of the 22 responders and 12 of the 19 nonresponders as well as 13 normal subjects by precolumn extraction, analytic reversed-phase high-performance liquid chromatography, and enzyme immunoassay. In the normal subjects the urinary LTE4 excretion was significantly (p less than 0.0001) less than the urinary LTE4 measured in the responder subjects, but not less than the urinary LTE4 excretion in the nonresponder group (p = 0.071). The enhanced recovery of LTE4 from the urine of subjects with acutely reversible airway narrowing is consistent with a bronchoconstrictor role for the cysteinyl leukotrienes in spontaneous acute asthma.

Acute Disease↗

Closing the asylums: where do all the former long-stay patients go?

The ongoing closure of the old asylums has resulted in large numbers of potentially vulnerable people living in the community. Where are these patients now and how are they coping? This study answers these questions in relation to a cohort of former long-stay patients discharged between 1985 and 1989 in Somerset Health District. The findings show that, as a group, they are a settled non-mobile population whose residential setting is not under threat. However, day care arrangements are inadequate with 45% of the study population without any structured day care. Most patients had unmet needs in the categories 'living space', 'work' and 'leisure'. Such studies are simple to conduct, and require little research funding. This methodology is recommended as a crude means of measuring unmet needs in this group of vulnerable individuals.

Community Mental Health Services↗

Five DNA tumor viruses undetectable in human retinoblastomas.

Retinoblastoma (RB) is a childhood eye cancer that arises when a retinal cell lacks a functional RB gene. Recent data indicate the transforming proteins of adenovirus, papillomavirus, and the polyomaviruses BK and JC all can bind to the product of the RB gene. Furthermore, adenovirus 12, JC virus, and simian virus 40 are able to induce RB-like tumors in rodents. In view of these findings, 50 human RBs were tested for the presence of five human DNA tumor viruses: adenovirus 12, BK virus, JC virus, and human papillomaviruses 16 and 18. Using the polymerase chain reaction, no viral sequences were detected in 50 RB DNAs. These data provide no evidence that these viruses have an etiologic role in human RB.

Base Sequence↗

Urinary incontinence: prevalence, need for treatment, and effectiveness of intervention by nurse.

OBJECTIVE: To measure the unmet need of patients with regular urinary incontinence (incontinence twice or more a month) treatable by a nurse. DESIGN: Self completed postal questionnaire and randomised controlled trial of assessment and intervention by a nurse. SETTING: One urban and one rural general practice in Somerset. SUBJECTS: 7300 adults randomly selected from 10,300 aged 35 and over on the combined practice lists. 515 women and 185 men with regular incontinence were offered assessment and treatment, of whom 134 women and 49 men had no intervention for three months (historical controls). They then joined the assessment and treatment programme. INTERVENTION: Four sessions of pelvic floor exercises and bladder retraining supervised by non-specialist nurse who had taken a three week course on assessing and treating uncomplicated incontinence. MAIN OUTCOME MEASURES: Number of patients desiring treatment; self reported cure, improvement, or deterioration in continence after three months. RESULTS: The questionnaire achieved a 79% response. Validated responses showed a prevalence of 4.4% in men and 16.4% in women aged 35-64. 315 (45%) of the 700 patients offered assessment refused it and seven had moved away or died, 64 men and 41 women were referred to their general practitioner. 197 of 292 treated women (68%) reported cure or improvement compared with seven (5%) of controls. 22 of the 86 men desiring treatment were suitable for intervention by the nurse. Seventeen were cured or improved compared with none of the men in the control group. CONCLUSIONS: About half the people with regular urinary incontinence took up the offer of treatment (9.2% of women and 3.4% of men in the study population). This condition can be effectively managed by a nurse with limited training.

Adult↗

Comparison of ZFY and ZFX gene structure and analysis of alternative 3' untranslated regions of ZFY.

We have cloned and sequenced transcripts from the X- and Y-linked zinc-finger genes ZFX and ZFY respectively and discuss a possible mechanism of post-transcriptional control by which these genes can be widely expressed but translated in only specific tissues. We report the identification of a novel 3'UTR (untranslated region) present in ZFY which is highly conserved among primates and contains a series of motifs implicated as mRNA instability determinants. These sequences can be substantially removed by polyadenylation directed from consensus (AATAAA) and non-consensus (AATATAAA) sequences in adult testis. The DNA-binding domains of the ZFY and ZFX proteins are compared using present models for zinc-finger/DNA interactions. Additionally, the genomic organisation of the ZFY coding sequence is presented as compared to that of ZFX.

Amino Acid Sequence↗

Polymerization site in the beta chain of fibrin: mapping of the B beta 1-55 sequence.

The formation of a fibrin clot occurs through binding of putative complementary sites, called fibrin polymerization sites, located in the NH2- and COOH-terminal domains of fibrin monomer molecules. In this study, we have investigated the structure of the NH2-terminal fibrin polymerization site by using fibrinogen-derived peptides and fragments. Fibrinogen was digested with Crotalus atrox protease III, to two major molecular species: a Mr 325,000 derivative (Fg325) and a peptide of Mr 5000. The peptide and its thrombin-cleavage product were purified by ion-exchange and reverse-phase HPLC; the authenticity of the B beta 1-42 and beta 15-42 peptides, respectively, was confirmed by amino acid sequencing. Since Fg325 had decreased thrombin coagulability, we addressed the question of whether the peptide B beta 1-42 contained a fibrin polymerization site. In order to identify and map the site, the peptides B beta 1-42 and beta 15-42 were tested for their ability to inhibit fibrin monomer polymerization. In addition the following peptides prepared by chemical synthesis were also tested: beta 15-18, beta 15-26, beta 24-42, beta 40-54, beta 50-55, and alpha 17-19-Pro. While B beta 1-42 had no inhibitory activity, the peptide devoid of fibrinopeptide B, beta 15-42, was a strong inhibitor. The peptides beta 15-18, beta 15-26, and beta 15-42 decreased the rate of fibrin polymerization by 50% at a molar excess of the peptide to fibrin monomer of 500, 430, and 50, respectively. The peptides beta 24-42, beta 40-54, and beta 50-55 were inactive.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Mitoxantrone, etoposide, mitoguazone and vinblastine chemotherapy (MV2) in relapsed and refractory lymphomas.

As part of a program to develop less leukemogenic chemotherapy regimens for the treatment of favorable prognosis Hodgkin's disease, a phase I-II trial of mitoxantrone, etoposide, mitoguazone, and vinblastine was used to treat patients with relapsed and refractory malignant lymphoma and Hodgkin's disease. An overall partial response rate of 41% was observed. Although useful responses were seen, the absence of complete remissions is disappointing.

Adolescent↗

Untoward reaction to adenosine therapy for supraventricular tachycardia.

Adenosine, a naturally occurring nucleoside that slows conduction through the atrioventricular node, has recently been approved for the treatment of supraventricular tachycardia. It has been shown to convert patients with supraventricular tachycardia to sinus rhythm in up to 92% of cases. Its intravascular half-life of only 10 seconds and absence of reported serious side effects have made adenosine an attractive antiarrhythmic agent. This report describes two cases in which significant side effects from the administration of adenosine were encountered including: (1) prolonged sinus arrest with syncope, and (2) syncope with prolonged bradycardia and hypotension. Emergency physicians should be cognizant of the potential complications resulting from adenosine administration, and should be prepared to deal with them when using this newly available agent.

Adenosine↗

Clinical use of dreams with latency-age children.

Although various authors have discussed the technical modification required for dream interpretation with children, the basic conceptualization of the psychotherapeutic use of the dream with children has remained virtually identical to that with adult analysands. Examining various sources including formal studies on the nature of children's dreams, clinical case reports and series, and cognitive theories, the authors conclude that a dream arising in the course of a child's therapy must be conceptualized theoretically as a posttraumatic phenomenon. This holds whether or not there has been overt trauma to the child. The reasons for the conceptualization include both the heightened degree of anxiety contained in a dream reported in the course of psychotherapy as well as the specific cognitive abilities of children to contain anxiety and abstract and generalize symbolic meanings. A specific technique based on this conceptualization is then detailed that calls for translation of the dream into more tangible expression (drawing, play, etc.) and a noninterpretative approach. The authors also discuss the more general problem of the nature of insight in children.

Child↗

Life events: the reliability of rating changes in routine and environment.

Alterations in routine and environment can affect clinical state in patients suffering from cognitive impairment. A method for rating life events for changes in routine and environment is described and found to be highly reliable even when used by inexperienced raters after brief training.

Activities of Daily Living↗

Amino acid receptors from insect muscle: electrophysiological characterization in Xenopus oocytes following expression by injection of mRNA.

Poly(A)+ Messenger ribonucleic acid (mRNA) was extracted from leg muscles of the locust Schistocerca gregaria and injected into oocytes of Xenopus laevis. After 5-10 days incubation, receptors for L-glutamate, L-quisqualate, DL-ibotenate and gamma-aminobutyric acid (GABA) were expressed. Agonist-induced currents were dose-dependent, and, in the concentration range 1 microM to 1 mM, generally had peak values of 50 nA. The responses to all agonists, apart from GABA, exhibited desensitization which could not be reversed even by prolonged washing with Ringer. Application of 100 microM GABA to oocytes voltage clamped at -60 mV produced a smooth inward current with a reversal potential of -22 +/- 1 mV, which is consistent with the involvement of chloride ions. At 100 microM, picrotoxin reversibly abolished this current, while 100 microM bicuculline had no effect. L-Glutamate elicited a smooth current with a reversal potential of -52 +/- 3 mV. L-Quisqualate elicited an inward current at -60 mV with a reversal potential of -9 +/- 2 mV; this current occasionally had an oscillatory component. The response to ibotenate comprised a smooth inward current with a reversal potential of -21 +/- 3 mV which was probably mediated by chloride ions.

Amino Acids↗

Production of thiosulphate during sulphide oxidation by mitochondria of the symbiont-containing bivalve Solemya reidi.

Isolated mitochondria of the bivalve Solemya reidi Bernard oxidize sulphide and couple this oxidation to ADP phosphorylation. The products of mitochondrial sulphide oxidation were analyzed by HPLC using monobromobimane derivatization. Concurrent measurements of respiration were made using sulphide-insensitive oxygen electrodes. S. reidi mitochondria oxidized sulphide exclusively to thiosulphate. The reaction occurred in two steps. One sulphide molecule was first oxidized to sulphite. A second molecule of sulphide was then added oxidatively to form the free product thiosulphate. This oxidation was obligately linked to mitochondrial electron transport and could be inhibited by the cytochrome c oxidase inhibitor hydrogen cyanide, or by low oxygen concentration. The site II inhibitor antimycin A did not inhibit thiosulphate production, indicating that sulphide oxidation is linked through only one ATP coupling site (site III). A calculation of the respiratory potential for ATP synthesis by fully intact mitochondria indicated that 2.0-3.25 ATP per sulphide may be synthesized using the proton potential generated by sulphide oxidation. This estimate far exceeds the published phosphorylation ratios for S. reidi (0.5-1.2 ATP per sulphide). This difference may be accounted for by partial uncoupling of phosphorylation from sulphide-based respiration. This hypothesis is supported by the observation that the respiratory control ratio of mitochondria respiring on sulphide is 41% lower than that of mitochondria respiring on succinate. The respiratory control ratio is an index of the tightness of coupling of respiration to ADP phosphorylation. When the adenylate pool of a eukaryotic cell is mostly phosphorylated, respiration is very slow, owing to the maintenance of a high mitochondrial membrane potential. Uncoupling of oxidative phosphorylation from respiration would be an adaptive advantage to the animal in that it allows for continuous, rapid removal of the toxic molecule hydrogen sulphide.

Adenosine Triphosphate↗

Differences in affinity of anti-CD4 monoclonal antibodies predict their effects on syncytium induction by human immunodeficiency virus.

A panel of 20 anti-CD4 monoclonal antibodies (mAb) was ranked in terms of affinity, using an inhibition radioimmunoassay. The ability of these antibodies to inhibit the induction of syncytia by human immunodeficiency virus (HIV) and to prevent binding of the HIV envelope glycoprotein 120 (gp120) to CD4 was also measured. Syncytium inhibition correlated strongly with affinity (P less than 0.001) but only weakly with inhibition of gp120 binding (P = 0.038). Some antibodies partially blocked binding of gp120 to CD4 but did not inhibit syncytia, and some antibodies inhibited syncytia but only weakly blocked binding of gp120. These results suggest that the syncytium inhibition assay is highly affinity-dependent, and that epitopes on CD4 concerned with virus binding are distinct from those involved in syncytium formation.

Antibodies, Monoclonal↗

Seasonal affective disorder.

Depression during winter has been found to respond to treatment with simulated daylight. Seasonal affective disorder should be distinguished from other forms of depression which can also occur in winter before prescribing light therapy.

Diagnosis, Differential↗

Evidence for distinguishable transcripts of the putative testis determining gene (ZFY) and mapping of homologous cDNA sequences to chromosomes X,Y and 9.

Oligonucleotide sequences based on the amino acid sequence of the putative testis determining gene ZFY have been used to isolate a 1.3 Kb Hind III Y genomic DNA fragment CMPXY1 and three human testis cDNA sequences (CMPXY2, CMPXY3 and CMPXY4). These sequences detect at least four potential exons on the Y (Y1, Y3, Y4 and Y5), three on the X (X1, X2 and X3) and three of autosomal origin (A1, A2 and A3) as determined by comparing the fragments detected by different clones. Analysis with subfragments of CMPXY4 shows that Y3 is unique to the Y and that Y4 and X1 are homologous. Y5 and X3 are detected by the same subfragment of CMPXY4. This is also the case for Y1, X2, A1, A2 and A3. Thus these exons may contain further regions of homology between the X, Y and an autosomal locus. The X-linked sequences all lie in Xp21.2-Xp22.1 and studies with XX males have placed the Y-linked sequences in distal Yp adjacent to the Y-autosomal homologous sequence GMGY3. We have confirmed these localizations by in situ hybridization with CMPXY4 and have shown additionally that the autosomal sequences of both the CMPXY4 sequence and GMGY3 map to 9p22-9pter. Restriction analysis demonstrates that CMPXY1/XY2/XY3 differ in sequence from CMPXY4 at three restriction enzyme sites, thus suggesting that they are transcribed from different but closely related genes and that CMPXY4 must be either X-linked or autosomal in origin. This indicates that more than one of the loci containing ZFY-related sequences are transcribed and potentially fulfil functionally distinct roles in the human sex determining pathway. Northern blot analysis of human foetal testis RNA has shown that three low abundance transcripts of 5, 6 and 8 Kb can be detected by ZFY-related DNA sequences.

Base Sequence↗