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Biomedical subjects

J O'Brien

Publications and source records attributed to J O'Brien.

At least 181 records · Page 10Linked to original sources

The fastest contracting muscles of nonmammalian vertebrates express only one isoform of the ryanodine receptor.

The skeletal muscles of chickens, frogs, and fish have been reported to express two isoforms (alpha and beta) of the sarcoplasmic reticulum calcium release channel (ryanodine receptor or RYR), while mammals express only one. We have studied patterns of RYR isoform expression in skeletal muscles from a variety of fish, reptiles, and birds with immunological techniques. Immunoblot analysis with a monoclonal antibody that recognizes both nonmammalian RYR isoforms and a polyclonal antibody specific to the alpha isoform show two key results: (a) two reptilian orders share with mammals the pattern of expressing only the alpha (skeletal) RYR isoform in skeletal muscle; and (b) certain functionally specialized muscles of fish and birds express only the alpha RYR isoforms. While both isoforms are expressed in the body musculature of fish and birds, the alpha isoform is expressed alone in extraocular muscles and swimbladder muscles. The appearance of the alpha RYR isoform alone in the extraocular muscles and a fast-contracting sonic muscle in fish (toadfish swimbladder muscle) provides evidence that this isoform is selectively expressed when rapid contraction is required. The functional and phylogenetic implications of expression of the alpha isoform alone are discussed in the context of the mechanism and evolution of excitation-contraction coupling.

Animals↗

Streptococcus pneumoniae colonization, bacteremia, and immune response among persons with human immunodeficiency virus infection.

Although invasive pneumococcal infections are common among men infected with human immunodeficiency virus (HIV), the prevalence of pharyngeal colonization with Streptococcus pneumoniae was not significantly different among HIV-infected patients (8 [14%] of 56) and HIV-seronegative men (9 [9%] of 99) attending a sexually transmitted disease clinic. Sixteen HIV-infected men (mean CD4+ T cell count, 132 +/- 37/microL) developed pneumococcal bacteremia, accounting for 13.6% of 117 total cases and 42% of 38 cases in men 16-55 years old. Serum killing activity, a measure of functional humoral response to S. pneumoniae, was lower in 4 (67%) of 6 acute sera and 6 (54%) of 11 convalescent sera from bacteremic HIV-infected patients when compared with baseline sera of 7 HIV-seronegative healthy subjects. These findings suggest that the high rates of pneumococcal bacteremia among HIV-infected patients may be associated with low numbers of CD4+ T cells and impaired humoral responses to S. pneumoniae rather than to increased exposure to the organism.

Adolescent↗

Quantitative evaluation of hepatitis C virus RNA in patients with concurrent human immunodeficiency virus infections.

Quantitation of the hepatitis C virus (HCV) provides a powerful epidemiologic and therapeutic method for the evaluation of infected patients. In this study semiquantitative reverse transcriptase polymerase chain reaction (PCR) is compared with a new branched DNA signal amplification methodology. Samples from HCV-infected patients as well as from human immunodeficiency virus-infected patients were evaluated. Reverse transcriptase PCR correlated well with the branched DNA assay (r = 0.7036, P < 0.05). HCV RNA was found to occur at significantly higher titers (P < 0.05) in patients coinfected with the human immunodeficiency virus compared with titers in those infected with HCV alone. Immune status as defined by the CD4+ count was not associated with the observed difference in viral titer.

Base Sequence↗

Isolation of seven respiratory viruses in shell vials: a practical and highly sensitive method.

The isolation of respiratory viruses in shell vials was compared with isolation in tube cultures in order to determine the sensitivity of the former, rapid method. Twenty of 21 influenza virus and 15 of 15 parainfluenza virus isolates were recovered in shell vials. One hundred twenty-seven of 138 respiratory syncytial virus isolates were detected in shell vials, but only 10 of 21 adenovirus isolates were positive by the rapid method. Shell vials are very effective for the diagnosis of respiratory viral infections, except for those caused by adenovirus.

Adenoviruses, Human↗

A 5' splice site mutation in fucosidosis.

Fucosidosis is a rare, autosomal recessive, lysosomal storage disease, resulting from a deficiency of the enzyme alpha-fucosidase (EC 3.2.1.51). It is characterised clinically by progressive mental and motor deterioration, growth retardation, coarse facies, and often recurrent infections, but the course of the disease is variable. The gene encoding lysosomal alpha-fucosidase has been mapped to the short arm of chromosome 1 at position 1p34.1-36.1 and has been called FUCA1. Two mutations causing disease have been described previously, a C-->T change in exon 8 giving rise to a premature, in frame TAA stop codon, and a deletion of at least two exons from the 3' end of the gene. In this paper we present evidence that a homozygous G-->A transition in the first position of the 5' splice site of intron 5 of FUCA1 is the disease causing mutation in a 9 year old child of distantly related parents. A new banding pattern was detected in the patient by Southern blotting of genomic DNA using TaqI restriction and a cDNA FUCA1 probe. The patient was homozygous for this pattern. Three sibs with alpha-fucosidase activity below the normal reference range and both parents were heterozygous. This pattern was not detected in 26 other fucosidosis patients and has not been found in any controls. The mutation was localised by a combination of restriction mapping using different cDNA probes, single stranded conformational polymorphism analysis of exons and flanking regions amplified by the polymerase chain reaction, and by direct sequencing of the amplified sequence. A view of the nature of the mutation, its cosegregation with the disease mutation and its absence in controls, it is probable that the 5' splice site mutation causes fucosidosis in this child.

Base Sequence↗

Partnership to prevent chemical dependency in nursing using Neuman's systems model.

1. Neuman's theory of optimal client system, which has the goal to maintain or to bring about the system's stability by the process of reconstitution, is used as the basis for the prevention efforts of the West Tennessee Nurses' Peer Assistance Program. Efforts are directed at bringing the client system to a state of stability or wellness that is higher than the previous state of chemical dependency. 2. The program has grown in both number of clients and in comprehensiveness of its prevention activities. Prevention in three specific areas--primary, secondary, and tertiary--is needed to combat the chemical dependency problem in nursing. 3. A continued partnership between the university, the school of nursing, the TNF, the TBN, and the various health care providers and nurse practitioners is needed to address the problem of chemical dependency in nursing.

Adult↗

Why do village health workers drop out?

A study in the Solomon Islands has revealed that training before the age of 20 and irregularity of remuneration are the main factors explaining why village health workers leave their posts. Other causes are dissatisfaction with levels of payment and promotion, lack of community support, and family concerns.

Attitude of Health Personnel↗

Management of joint and soft tissue injuries in three general practices: value of on-site physiotherapy.

A prospective study was undertaken to determine the potential benefits in patient management and cost effectiveness of physiotherapists employed by general practitioners compared with direct hospital access and access via consultants. The study involved 401 patients from three rural general practices in south Cheshire and north Staffordshire and took place over six months. On-site physiotherapy in general practice premises resulted in higher referral rates to the physiotherapist compared with the practice using direct hospital access or the practice with access via consultants. Both on site and direct access physiotherapy were associated with fewer prescriptions and lower overall prescribing costs per patient than access to physiotherapy via consultants. There was less time lost from work and normal duties for patients attending the practice with on site physiotherapy compared with those attending the practice which required referral via hospital consultants. Access to physiotherapy via hospital specialists resulted in considerably longer delays than on site physiotherapy and greatly increased the financial costs for the patient. Physiotherapy in general practice premises is a cost effective way of dealing with joint and soft tissue complaints. Direct access to the physiotherapy department within hospitals results in longer delays but provides a satisfactory service. There is little to recommend the utilization of hospital consultants as a means of access to physiotherapy.

Connective Tissue↗

Spectrum of sialylated and nonsialylated fuco-oligosaccharides bound by the endothelial-leukocyte adhesion molecule E-selectin. Dependence of the carbohydrate binding activity on E-selectin density.

Carbohydrate recognition by the human endothelial-leukocyte adhesion molecule, E-selectin, has been investigated by binding studies using 3H-labeled Chinese hamster ovary cells expressing different levels of the transfected full-length adhesion molecule and a series of structurally defined oligosaccharides linked to the lipid phosphatidylethanolamine dipalmitoate (neoglycolipids) and synthetic glycolipids chromatographed on silica gel plates or immobilized on plastic wells. Evidence is presented for density-dependent binding of the membrane-associated E-selectin not only to 3'-sialyl-lacto-N-fucopentaose II (3'-S-LNFP-II) and 3'-sialyl-lacto-N-fucopentaose III (3'-S-LNFP-III) which express the sialyl Le(a) and sialyl Le(x) antigens, respectively, but also to the nonsialylated analogue LNFP-II; there is a threshold density of E-selectin required for binding to these sialylated sequences, and binding to the nonsialylated analogue is a property only of cells with the highest density of E-selectin expression. The presence of fucose linked to subterminal rather than to an internal N-acetylglucosamine is shown to be a requirement for E-selectin binding, and although the presence of sialic acid 3-linked to the terminal galactose of the LNFP-II or LNFP-III sequences substantially enhances E-selectin binding, the presence of 6-linked sialic acid abolishes binding. E-selectin binding is unaffected in the presence of the blood group H fucose (alpha 1-2 linked to galactose to form the Le(b) antigen). However, the binding is abolished when in addition alpha 1-3-linked N-acetylgalactosamine to the galactose (blood group A antigen) is present. These results indicate that some E-selectin-mediated adhesive events may be influenced by blood group status.

Animals↗

The sonographically thick placenta: a predictor of increased perinatal morbidity and mortality.

In order to determine the prevalence and significance of sonographically thick placentas, we reviewed the computerized records of 18 827 viable, singleton pregnancies. Of these, 116 (0.6%) had thick placentas diagnosed by ultrasound examination. Perinatal mortality was markedly increased among pregnancies with thick placentas (odds ratio = 13.1, 95% confidence limits (CL) = 8.3-20.8), accounting for 6.2%; of the total. The rates of abruptio placentae (odds ratio = 2.9, CL = 1.1-8.1), neonatal intensive care unit admissions (odds ratio = 4.6, CL = 3.1-6.9) and anomalies (odds ratio = 8.4, CL = 4.9-14.4) were also significantly increased among the thick placenta cohort compared to controls. The 106 liveborn neonates with thick placentas had lower Apgar scores, were delivered at an earlier gestational age, and weighed less than controls. Anomalies, hydrops fetalis and abruptio placentae complicated 16 of the 24 cases of perinatal mortalities. Sonographically thick placentas should alert the clinician to the possibility of compromised perinatal outcome.

Journal Article↗

Localized conformational changes in the N-terminal domain of CD4 identified in competitive binding assay of monoclonal antibodies and HIV-1 envelope glycoprotein.

The CD4 antigen is established as a major cellular receptor for the human immunodeficiency virus (HIV). Previous studies have suggested that certain anti-CD4 monoclonal antibodies (MAbs) can inhibit or enhance the binding of the viral envelope glycoprotein gp120 to CD4 by allosteric effects. In the study reported here, 17 anti-CD4 MAbs were tested for their ability to influence the binding of each other to recombinant soluble CD4 in a solid-phase radioimmunoassay. Marked enhancement of binding between specific pairs of MAbs was seen, as well as inhibition or lack of interaction. Enhancement was seen less often when CD4+ cells were used as the target antigen. Information on patterns of enhancement and inhibition permitted grouping of MAbs on the basis of epitope specificity, and this grouping was in agreement with published findings based on X-ray crystallographic studies. These results demonstrate connectivity between epitopes in the first domain of recombinant CD4 and suggest a high degree of flexibility of surface structure. These findings may be of physiological significance both in the normal function of CD4 and in the interaction of CD4 with HIV. The data have implications for research or therapeutic strategies based on recombinant CD4 or CD4 mutants and highlight the problems of interpreting experimental findings based on abrogation of MAb binding.

Antibodies, Monoclonal↗

A methodology for collecting outcome measures for common hospital conditions.

An eight-month prospective analysis of routinely collected hospital data with 24-week follow-up of mortality and morbidity was carried out at two district general hospitals in Somerset Health District, to test the feasibility of collecting useful and valid outcome measures for two common hospital conditions, strokes and fractured hips. Data were collected on 163 consecutive admissions with a primary diagnosis of stroke (83 cases) or fractured hip (80 cases). At 24 weeks, 38 patients with stroke had died (mortality ratio 46 per cent, 95 per cent C.I. = 35.3-56.7 per cent) and 11 with fractured hip had died (mortality ratio 14 per cent, 95 per cent C.I. = 6.4-21.6 per cent). Seven patients (four with fractured hip and three with stroke) died after 24 weeks and before responding to the NHP questionnaire. One stroke patient could not be traced. Nottingham Health Profiles were received from 106 patients (41 with stroke and 65 with fractured hip). Both groups of patients had problems with physical mobility and lack of energy. Patients with fractured hips were more likely to complain of pain. It is concluded that the methods used to collect outcome measures in this study are widely applicable to other conditions, but the interpretation and comparability of the results require the collection of similar data elsewhere.

Aged↗

Patterns of regional cerebral blood flow in Alzheimer's disease.

Regional cerebral blood flow was assessed in 35 patients with Alzheimer's disease and the same number of matched normal volunteers. Images were scored for regional perfusion deficits. Mildly demented patients had parietal and temporal perfusion deficits, often unilateral. Moderate to severely demented patients had bilateral temporal and parietal perfusion deficits. All severely demented patients also had involvement of both occipital regions. Frontal lobe deficits were seen in 14 patients. Left cortical perfusion deficits were more severe than the right cortical perfusion deficits in general. Patients with early onset of the disease showed left frontal deficits, more often, however, the total perfusion deficit scores in early and late onset groups were not statistically significant. Also, the cognitive performance scores were not statistically significant in these two groups. These results suggest a stage-dependent reduction in regional cerebral blood flow in patients with Alzheimer's disease.

Aged↗