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Biomedical subjects

J Robinson

Publications and source records attributed to J Robinson.

At least 307 records · Page 17Linked to original sources
PubMed1993

Functional and immunologic characterization of human immunodeficiency virus type 1 envelope glycoproteins containing deletions of the major variable regions.

Deletions of the major variable regions (V1/V2, V3, and V4) of the human immunodeficiency virus type 1 (HIV-1) gp120 exterior envelope glycoprotein were created to study the role of these regions in function and antigenicity. Deletion of the V4 region disrupted processing of the envelope glycoprotein precursor. In contrast, the deletion of the V1/V2 and/or V3 regions yielded processed exterior envelope glycoproteins that retained the ability to interact with the gp41 transmembrane glycoprotein and the CD4 receptor. Shedding of the gp120 exterior glycoprotein by soluble CD4 was observed for the mutant with the V3 deletion but did not occur for the V1/V2-deleted mutant. None of the deletion mutants formed syncytia or supported virus entry. Importantly, the affinity of neutralizing antibodies directed against the CD4-binding region for the multimeric envelope glycoprotein complex was increased dramatically by the removal of both the V1/V2 and V3 structures. These results indicate that, in addition to playing essential roles in the induction of membrane fusion, the major variable regions mask conserved neutralization epitopes of the HIV-1 gp120 glycoprotein from antibodies. These results explain the temporal pattern associated with generation of HIV-1-neutralizing antibodies following infection and suggest stratagems for eliciting improved immune responses to conserved gp120 epitopes.

Animals↗
PubMed1993

Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults.

BACKGROUND: Cigarette smoking is the most important modifiable risk factor for atherosclerosis. Endothelial dysfunction is an early event in atherogenesis, and we hypothesized that smoking might be associated with endothelial damage in the systemic arteries of otherwise healthy young adults. METHODS AND RESULTS: We studied noninvasively the brachial arteries of 200 subjects aged 15 to 57 years, all normotensive, nondiabetic with cholesterol level < or = 240 mg/dL and no family history of premature vascular disease: 80 control subjects aged 16 to 56 years (mean, 35), 80 current smokers aged 15 to 55 years (mean, 33), and 40 former smokers aged 25 to 57 years (mean, 38). Total lifetime amount smoked varied from 1 to 75 pack years in the smokers. Using high-resolution ultrasound, vessel diameter was measured at rest, during reactive hyperemia (with flow increase causing endothelium-dependent dilation), and after sublingual glyceryl trinitrate (GTN, an endothelium-independent vasodilator). Flow-mediated dilation (FMD) was observed in all the control subjects (10 +/- 3.3%; range, 4% to 22%) but was impaired or absent in the smokers (4 +/- 3.9%; range, 0% to 17%; P < .0001). FMD in the smokers was inversely related to lifetime dose smoked (6.6 +/- 4.0% in very light smokers, 4.0 +/- 3.1% in light smokers, 3.2 +/- 3.2% in moderate smokers, and 2.6 +/- 1.2% in heavy smokers; P < .01). FMD for the former smokers was 5.1 +/- 4.1% (range, 0% to 15%). In a multivariate model adjusting for age, sex, cholesterol, smoking history, and vessel size, former smoking was associated with a higher FMD than current smoking (P = .07); when only male former and current smokers were considered, the higher FMD was significant (P = .0001) but not for female smokers (P = .24). GTN caused dilation in all subjects (control subjects, 20 +/- 5.2%; smokers, 17 +/- 5.8%; former smokers, 17.4 +/- 5.4%). Vessel diameter, baseline flow, and degree of reactive hyperemia (Doppler estimated) were similar in all groups. CONCLUSIONS: Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent arterial dilation in asymptomatic young adults, consistent with endothelial dysfunction.

Adolescent↗
PubMed1993

A follow-up study of 'successful' IVF/GIFT couples: social-emotional well-being and adjustment to parenthood.

Twenty couples who conceived their babies by in vitro fertilization/gamete intrafallopian transfer (IVF/GIFT) were seen between 15 and 27 months postdelivery in order to evaluate social-emotional well-being and parental functioning. Emotional health and marital adjustment were assessed by standard questionnaires and compared with general population norms. Questionnaires measuring quality of life, parents' feelings about their babies and child-rearing attitudes were also administered. Scores from these were compared with those obtained from a group of parents who had conceived without medical assistance. Results indicated that IVF/GIFT parents were undifferentiated from the general population with respect to emotional health and marital adjustment. Also, relative to non-IVF parents, they gave higher positive ratings for their feelings about their babies and for one aspect of quality of life (feelings of freedom). Parenting attitudes for the two groups differed in only one respect, IVF/GIFT parents reported being more overprotective.

Adaptation, Psychological↗
PubMed1993

Genetic change and continuity from fourteen to twenty months: the MacArthur Longitudinal Twin Study.

Genetic change as well as continuity was investigated within the domains of temperament, emotion, and cognition/language for 200 pairs of twins assessed at 14 and 20 months of age in the laboratory and home. The second year of life is marked by change rather than continuity: correlations from 14 to 20 months averaged about .30 for observational measures of temperament and emotion, about .40 for language measures, and about .50 for mental development. 2 types of genetic change were examined: changes in the magnitude of genetic influence (heritability) and genetic contributions to change from 14 to 20 months. In general, heritability estimates were similar at 14 and 20 months. Evidence for genetic influence on change from 14 to 20 months emerged for several measures, implying that heritability cannot be equated with stability. Analyses of continuity indicated that genetic factors are largely responsible for continuity from 14 to 20 months.

Child Development↗
PubMed1993

Clinical and laboratory studies of a new immunoradiometric assay of parathyroid hormone-related protein.

Parathyroid hormone-related protein (PTHrP) was measured in plasma by a new immunoradiometric assay (IRMA) from Nichols Institute. The assay is specific for PTHrP and shows excellent parallelism when measuring keratinocyte fluid, samples with high PTHrP content, and PTHrP-supplemented plasma. A precision profile established the assay detection limit at 0.7 pmol/L. PTHrP was unstable in plasma, but the degradation rate was patient-specific. Because delay in separation resulted in loss of PTHrP immunoreactivity, samples were collected into tubes containing protease inhibitors (aprotinin, leupeptin, pepstatin, and EDTA) and separated within 30 min. Among normal subjects, 78% had PTHrP values greater than the detection limit; the reference range established was < 0.7-2.6 pmol/L. Of patients with hypercalcemia associated with malignancy, 46% had PTHrP > 2.6 pmol/L. PTHrP was increased in patients with breast (73%), genitourinary (64%), or lung (46%) malignancy but was rarely above normal in patients with hematological (29%) or gastrointestinal (33%) malignancy. PTHrP and nephrogenous cyclic adenosine monophosphate (NcAMP) were strongly correlated (r = 0.63, P < 0.01) in 37 patients with PTHrP values greater than the detection limit, but 8 patients had PTHrP and parathyroid hormone [PTH(1-84)] values below the limit of detection with inappropriate or increased NcAMP. Five of these eight patients had small cell carcinoma of lung. These patients may have secreted a factor that is not detected by the IRMAs of PTHrP or PTH used in this study but that produces hypercalcemia by means of cAMP-mediated mechanisms.

Adult↗
PubMed1992

A comparative analysis of two preparations of human chorionic gonadotrophin.

A biophysical analysis of two pharmaceutical preparations of human chorionic gonadotrophin (Endo and Profasi) demonstrated that both contained high hCG specific activity. HCG protein analysis by occlusion HPLC and SDS gel electrophoresis showed similar profiles for both products. Although the purified protein components of both preparations were similar their were differences in the contents of the unpurified preparations. The Endo preparation exhibited greater inter-vial variability and contained an unidentified aromatic substance which interacted with the desalting column.

Chemical Phenomena↗
PubMed1992

Activation of neutrophil reactive-oxidant production by synovial fluid from patients with inflammatory joint disease. Soluble and insoluble immunoglobulin aggregates activate different pathways in primed and unprimed cells.

Cell-free synovial fluid from patients with rheumatoid arthritis stimulated the NADPH oxidase activity in human neutrophils, which reached a peak 15-20 min after addition. Insoluble immunoglobulin aggregates isolated from these fluids activated a similar pattern of oxidase activity. However, when synovial fluid was added to neutrophil suspensions which had been previously exposed to granulocyte-macrophage colony-stimulating factor, the stimulated oxidase activity was biphasic, in that an additional transient activity was observed which reached a peak within 5 min of addition. The additional neutrophil-stimulating activity could not be sedimented by centrifugation at 330,000 g-min, and only activated oxidase activity in neutrophils which had previously been primed. The neutrophil-stimulating activity in this soluble fraction was removed by Protein A affinity chromatography, and activity was recovered in eluates from this column. Thus activity in this soluble fraction from synovial fluid is attributed to the presence of soluble immunoglobulin aggregates. Whereas oxidase activity stimulated by the isoluble immunoglobulin aggregates was inhibited by staurosporine (and hence largely dependent on the activity of protein kinase C), the activity stimulated by the soluble immunoglobulin aggregates was staurosporine-insensitive. The soluble immunoglobulin aggregates were present at significantly higher levels in synovial fluids from patients with rheumatoid arthritis compared with those from other joint arthropathies. Thus rheumatoid synovial fluids possess heterogeneous immunoglobulin aggregates which activate neutrophils via distinct molecular pathways. As neutrophils within rheumatoid joints are primed, the soluble immunoglobulin aggregates are likely to be of importance in disease pathology.

Alkaloids↗
PubMed1992

Light and the neonatal eye.

The lighting environment where the baby born prematurely is placed is different from that experienced in utero. As early exposure to light may affect the immature visual system we have attempted to quantify the neonatal ocular light dose. Lighting surveys performed in 7 neonatal units (NNUs) suggested that mean unit illuminance was 470 lux (range 192-890 lux) and intensive care areas within the NNU were significantly brighter than their corresponding low dependency nurseries. The spectral power distribution of fluorescent lights in NNUs was weighted towards the blue end of the spectrum. Datalogging studies demonstrated that between about 30% and 98% of environmental light was incident on the eyelid, which acts as a predominantly red-pass filter, permitting 21% transmission at 700 nm with less than or equal to 5% transmission at 580 nm. Eye-lid opening frequency was quantified: 45% less than or equal to 26 weeks gestational age and decreasing to 7% at 28 weeks gestational age. The onset of the pupillary reflex to light was between 30 and 34 weeks postmenstrual age, the mean diameter was 3.46 mm before this event and 3.02 mm afterwards. Retinal irradiance values calculated from these data show that it is a function of postmenstrual age. Further studies are required to determine its effect on the immature visual system.

Eye↗
PubMed1992

Hard labour.

Midwives have an ethically superior and more consumer-oriented code of conduct than doctors, argue Beverley Lawrence Beech and Jean Robinson, who claim women are safer in midwives' hands.

Clinical Competence↗
PubMed1992

Midwife crisis?

While most pressure groups have been asking for more for their part of the health service, AIMS has been demanding less for the last 30 years. In the first of two articles on maternity services, Beverley Lawrence Beech and Jean Robinson explain why obstetricians should take a backseat role to midwives.

Clinical Protocols↗
PubMed1992

Progressive vision loss. A rare manifestation of familial cavernous angiomas.

We studied four generations of a family in which the index case had progressive loss of vision secondary to a cavernous angioma of the optic nerve and chiasm. Magnetic resonance imaging of the brain revealed multiple, asymptomatic intracerebral cavernous angiomas. Brain magnetic resonance imaging scans of the family members revealed multiple cavernous angiomas in the brother and paternal grandfather, but none in the father or his siblings. Autopsy reports of the paternal great grandfather noted multiple cavernous angiomas in the brain and abdominal viscera. We believe our patient to be the sixth reported case in which a cavernous angioma involved the optic chiasm and optic nerve. Magnetic resonance imaging is a sensitive and specific method of detecting cavernous angiomas. Cavernous angiomas have an autosomal dominant pattern of inheritance with variable penetrance. Surgical intervention in patients with symptomatic cavernous angiomas depends on the location and size of the lesion and associated surgical risks.

Adolescent↗
PubMed1992

PCR amplification of HIV-1 proteinase sequences directly from lab isolates allows determination of five conserved domains.

HIV-1 replication requires limited proteolysis of gag and gag-pol encoded precursor proteins by a specific viral proteinase (PR). Sequences of 20 different HIV-1 strains were compared in order to determine regions of conservation and variability within the PR gene. Viral strains included: (a) five new ones derived from New Orleans patient isolates, (b) four established ones grown in our laboratory, (c) eight, whose sequences were published in the Los Alamos Data Base (1990), (d) one Ugandan, and (e) two Brazilian isolates. In the first two groups, HIV proviral DNA extracted from infected lymphocytes was grown in tissue culture and directly amplified by PCR using specific primers flanking the PR gene. Amplified DNA was directly sequenced using a modified di-deoxy sequencing procedure. Sequence data showed a 25% variation among the 20 different HIV strains studied at the amino acid level, including 8% nonconservative changes and 17% conservative changes. Moreover, five noncontiguous regions were able to be delineated in which the PR showed no amino acid changes. These areas included amino acids (I) 1-9 (amino terminal sequence); (II) 21-32 (sequence around the active site); (III) 47-56 (top of the flap); (IV) 78-88; and (V) 94-99 (carboxy terminal sequence). Our results are consistent with those obtained from X-ray crystallography studies as well as single site mutational analysis.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Improved outcome of respiratory syncytial virus infection in a high-risk hospitalized population of Canadian children. Pediatric Investigators Collaborative Network on Infections in Canada.

PURPOSE: To determine the outcomes in children at high risk for death or complications from respiratory disease who are hospitalized with respiratory syncytial virus (RSV) infection. DESIGN: Retrospective chart review. SETTING: Twelve pediatric tertiary care centers. PATIENTS: All hospitalized children with an RSV infection diagnosed by a positive antigen detection test result or viral isolation during the study period from 1988 to 1991, encompassing three winter seasons. Charts from patients in the following high-risk groups were reviewed in detail: (1) congenital heart disease, (2) chronic lung disease, (3) immunodeficiency, (4) age less than 6 weeks, (5) gestational age less than 36 weeks, and (6) hypoxia (defined as oxygen saturation less than 90% or arterial oxygen pressure less than 60 mm Hg). MEASUREMENTS: The age of all children, the date of RSV identification, and the use of oxygen supplementation, intensive care, and ventilatory support. In addition, the duration of these treatments and the duration of hospitalization were noted. Left-to-right shunting and pulmonary hypertension before RSV infection were determined in those children with congenital heart disease. The nature of the chronic lung disease was noted. Death within 2 weeks of RSV identification was recorded, and the use of ribavirin, bronchodilators, and corticosteroids was determined. RESULTS: Significant year-to-year variation in the frequency of RSV infection was confirmed, with a peak during the 1989-1990 winter noted by the majority of centers (p = 0.0001). Of the 1584 patients in the study, 260 had underlying cardiac disease, 200 had chronic lung disease, 35 had compromised immune function, 378 had been premature, 373 were less than 6 weeks of age, and 338 had hypoxia. Seventeen patients died within 2 weeks (mortality rate 1%); significantly more patients with underlying cardiac disease (3.4%) or lung disease (3.5%) died. Immunocompromised patients had the longest hospital stay (median 39 days), followed by those patients with underlying cardiac or pulmonary disease (11 days); patients less than 6 weeks of age (5 days) and those with hypoxia (6 days) had the shortest hospital stays. Patients with underlying cardiac and pulmonary disease also required oxygen supplementation for a significantly longer period. CONCLUSION: The year-to-year variation in frequency of RSV infection was confirmed in this study. Morbidity and mortality rates associated with RSV infection in a high-risk population in Canada were significantly lower than previously reported.

Adolescent↗
PubMed1992

Myringoplasty for the anterior perforation: experience with the Kerr flap.

Surgical closure of the anteriorly located tympanic membrane perforation can present a problem. The lack of anterior support for the graft frequently leads to graft failure if an underlay method is used whereas anterior blunting is a complication of onlay techniques in this situation. The experience with the Kerr flap, an underlay graft fashioned to include a tab of fascia which is placed laterally under the annulus and the anterior meatal skin, is presented. This method gave a 97.5 percent closure rate with no cases of anterior marginal blunting and a mean auditory threshold gain of 8.5 dB (95 percent confidence limits 5 to 11.9 dB, P less than 0.01) was achieved at the frequencies tested. The use of the Kerr flap is recommended when repairing the anteriorly placed tympanic membrane perforation.

Adolescent↗