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Biomedical subjects

C O'Brien

Publications and source records attributed to C O'Brien.

At least 19 recordsLinked to original sources
PubMed1992

Neurotoxic damage evokes regenerative responses from adult rat sensory neurones.

When adult rats were pre-treated systemically with the excitotoxin, capsaicin, a subset of their dorsal root ganglion (DRG) sensory neurones responded as if they had been axotomised. Firstly, an increased proportion of capsaicin-sensitive DRG neurones (identified by using a cobalt stain) vigorously extended processes in vitro. Additionally, a subset of small dorsal root ganglion neurones expressed elevated levels of the growth-associated protein-43 (GAP-43) in situ. Both vigorous neuritogenesis and elevated GAP-43 levels are characteristics of neurones that are actively regenerating following mechanical damage. Although capsaicin-treated adult DRG neurones show these regenerative responses, their C-fibers fail to regenerate in vivo.

Animals↗
PubMed1992

Hyperhomocysteinaemia: a risk factor for extracranial carotid artery atherosclerosis.

Hyperhomocysteinemia arising from impaired methionine metabolism, and usually due to a deficiency of cystathionine beta-synthase is a significant and independent risk factor for symptomatic vascular disease. It is not known if hyperhomocysteinemia in apparently healthy asymptomatic subjects is associated with atherosclerosis and whether such a relationship is independent of conventional risk factors. The prevalence of asymptomatic extracranial carotid artery atherosclerosis was determined by duplex ultrasound examination in 25 obligate heterozygotes with respect for cystathionine beta-synthase deficiency (whose children were known to be homozygous for this genetic defect) and in 21 controls. Hyperhomocysteinemia was determined by a standard methionine-loading test and conventional risk factors were also recorded. Twelve of 25 obligate heterozygotes and 8 of 21 normal controls had evidence of extracranial carotid artery atherosclerosis. Hyperhomocysteinemia as a genetic trait was not a significant risk marker, but the actual homocysteine level was associated with an increased risk of carotid disease. After adjustment for the effects of other significant risk factors, the odds ratio of hyperhomocysteinemia for carotid disease was 1.038 per unit increase in homocysteine level (P = 0.03). Hyperhomocysteinemia is a weak risk factor for asymptomatic extracranial carotid atherosclerosis and the relative risk associated with this genetic trait is less than that observed in a study of patients presenting with clinical manifestations of vascular disease.

Adult↗
PubMed1992

A randomized double-blind study of neuroelectric therapy in opiate and cocaine detoxification.

Prior research on the use of transcranial neuroelectric stimulation suggested that the application of low-amperage, low-frequency alternating current via surface electrodes placed in the mastoid region could relieve the physiological signs and subjective symptoms of withdrawal and craving during opiate detoxification. These effects were reported without gradual tapering of the opiate or the addition of other medications. To test the efficacy of one particular form of neuroelectric therapy (NET), a double-blind, randomized, placebo-controlled study was conducted comparing active NET and placebo NET in the treatment of withdrawal and stabilization of 18 opiate-dependent and 25 cocaine-dependent subjects. Scores on scales for measuring substance withdrawal and craving for each abused substance, as well as the multiple dimensions of mood, were compared for degree of difference across the 10 days of treatment. There was an overall completion rate of 88%, with both cocaine and opiate groups reporting a comfortable detoxification and substantial improvement over the course of a 12-day hospitalization. There was no significant difference between the active or placebo groups, suggesting that placebo was as effective as active NET in reducing drug withdrawal or craving during cocaine and opiate detoxification. However, all placebo patients received 0.2 mA of current, which may have provided a degree of active current. Suggestions are offered for future research.

Adult↗
PubMed1992

Doppler carotid artery studies in asymmetric glaucoma.

Doppler carotid artery studies were performed in 12 glaucoma patients with marked asymmetry in bilateral visual field loss. The resistance index and the pulsatility index of the internal carotid artery velocity waveforms were significantly greater on the same side as the eye with the greater visual field loss. The increased resistance to blood flow in the internal carotid artery on the side with advanced field loss might predispose the eye on this side to the effects of raised intraocular pressure by causing a reduction in the perfusion pressure at the optic nerve head. The role of ocular perfusion pressure in the pathogenesis of glaucoma is discussed. More extensive studies are necessary.

Carotid Arteries↗
PubMed1992

Childhood lymphoma in Yorkshire.

AIMS: A histopathological review of 43 cases of childhood non-Hodgkin's lymphoma (NHL) in an attempt to identify histological variables of prognostic importance. METHOD: Each case was reclassified according to the Working Formulation and an attempt made to allocate an immunophenotype using a panel of monoclonal antibodies. Results were correlated with clinical data on site and survival. RESULTS: Of the 43 cases, 30 were males and 13 females. There were 17 cases of lymphoblastic lymphoma, 15 cases of small non-cleaved cell lymphoma (SNCC), and four cases of large cell lymphoma. The SNCC group was subdivided into 10 cases of Burkitt's lymphoma and five cases of non-Burkitt's lymphoma. An immunophenotype was allocated in 65.1% of cases (23 B, 5 T). The SNCC cases were spread throughout the 0-16 year age range while the lymphoblastic lymphoma cases tended to occur in older children. Most mediastinal tumours were lymphoblastic lymphoma and most abdominal tumours were SNCC. Statistical analysis failed to show a significant difference in survival among histological subgroups or immunophenotypes. CONCLUSION: No histological variables of prognostic importance were identified partly due to the great variation in treatment regimens, standard of supportive care, and prognosis over the period of the study (1972 to 1988).

Adolescent↗
PubMed1992

Cloning of a complementary DNA coding for the 100-kD antigenic protein of the PM-Scl autoantigen.

Anti-PM-Scl antibodies are associated with polymyositis-scleroderma overlap or either disease alone. Among sera from 39 patients with anti-PM-Scl, 23 recognized the 100-kD band in immunoblot against HeLa cell extract, 16 of which also stained the 70-kD band. A human thymocyte lambda gt11 cDNA expression library was screened with anti-PM-Scl serum, and two clones were identified whose products reacted with 33 and 37 of 39 anti-PM-Scl sera, respectively, but none of 26 negative control sera. Affinity-purified antibody reacting specifically with plaques of the clone stained the 100-kD band on immunoblot, reacted with nucleoli of HEp-2 cells, and immunoprecipitated the PM-Scl protein complex. Partial sequences of both inserts were identical. One insert was fully sequenced, and additional 5' and 3' sequence was obtained using a gene-specific primer to form a cDNA with HeLa cell RNA as template followed by PCR. The complete nucleotide sequence included 2,739-bp coding for a predicted full-length protein of 98,088 D. There was no homology with the PM-Scl 75-kD protein and no significant homology with other proteins. A mixed-charge cluster was identified, with 22 charged amino acids of 37. In conclusion, the full-length cDNA sequence was determined coding for the PM-Scl 100-kD protein, the most commonly antigenic protein of the PM-Scl complex.

Amino Acid Sequence↗
PubMed1992

Comparison of computer-assisted versus manual optic nerve head pallor measurement.

Computerized methods of examining the optic nerve head offer the possibility of providing consistent, reliable, and accurate measurements of the nerve head. The reliability and accuracy of such instruments must be examined to confirm this. This research was undertaken to gain an insight into the accuracy of such a system, which takes its measurements by tracking the luminance boundaries of the pallor area and the optic nerve head after an observer marks the starting points. Measurements made using the computer-tracked boundary were compared with those made using a boundary tracked by an image-processing system of greater sophistication, the human visual system. The comparison was made with images from one eye from each of 30 subjects (10 normal, 10 ocular hypertensive, and 10 glaucomatous). The measurements were made by two observers. Each observer made each set of measurements twice, and the results were analyzed with a five-factor analysis of variance. The measurements made using the computerized method did not differ significantly from those made using the manual boundary tracking for the two observers, and they were highly correlated (r = 0.99 for the area pallor-disc ratio). Significant differences (P < 0.05) were found between the two observers in both the manual and computerized boundary tracking. The computerized method, however, did not find differences between the two sets of measurements made by each observer; the manual method did show such differences. The computerized method appeared to trace the luminance boundaries successfully in the image, and it might reduce errors related to the observer marking the starting points on different occasions.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1991

Intraocular pressure and the rate of visual field loss in chronic open-angle glaucoma.

We measured the rate of change of visual field threshold values over time (mean follow-up, 44.9 +/- 17.4 months) by trend analysis in 40 eyes of 40 patients with chronic open-angle glaucoma. Twenty-eight eyes had stable visual fields, and two eyes had significant visual field improvement. Ten eyes had significant visual field deterioration and showed a correlation between indices of intraocular pressure (standard error of the mean, P = .02; standard deviation, P = .04; and range, P = .05) and the rate of visual field loss in the superonasal region of the visual field, such that the greater the variation of intraocular pressure the greater the rate of loss. The group losing visual fields had a higher mean visual field threshold value and significantly less optic disk pallor and cupping at the start of the study than the stable visual field group. Thus, a significant rate of visual field loss occurred at an earlier stage of the disease and showed a correlation with intraocular pressure in this stage.

Aged↗
PubMed1991

Tyrosine phosphorylation of the Fc gamma RIII(CD16): zeta complex in human natural killer cells. Induction by antibody-dependent cytotoxicity but not by natural killing.

NK cells are large granular lymphocytes capable of killing certain tumor cells and virally infected cells in a non-MHC-restricted manner. NK cells can also effect an antibody dependent cytotoxicity that is triggered by CD16, an FcR for IgG. In NK cells, CD16 is expressed in association with zeta, a signal transducing subunit of the TCR complex. Here we show that, just as T cell activation via the TCR complex results in tyrosine phosphorylation of zeta TCR, NK cell activation via CD16 results in tyrosine phosphorylation of zeta NK. Whereas antibody-dependent cytotoxicity also results in tyrosine phosphorylation of zeta, natural cytotoxicity does not. Our results indicate that zeta functions as a transducing element for antibody dependent, but not antibody independent killing by NK cells. Consequently, NK cells are likely to express at least two distinct receptor complexes capable of triggering cytolytic effector function.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1991

CD2 is functionally linked to the zeta-natural killer receptor complex.

Natural killer (NK) cells express two distinct surface receptors capable of triggering cytolytic effector function. The first is CD16, an immunoglobulin Fc receptor that allows NK cells to mediate antibody-dependent killing (ADCC). NK cells express CD16 in association with zeta, a signal-transducing subunit that is also a component of the T cell receptor complex. Activation of NK cells via CD16 results in tyrosine phosphorylation of zeta. The second NK cell triggering receptor is CD2, a 50-55-kDa cell surface molecule that is also expressed on T cells. Here we show that NK cell activation induced by mAb reactive with CD2 (either anti-T11.1 alone or with anti-T11.2 in combination) also results in the tyrosine phosphorylation of zeta. Our results indicate that CD2 is functionally linked to the CD16-zeta complex and suggest that the zeta subunit plays a central role in the signal transduction pathways utilized by NK cells.

Antibodies, Monoclonal↗
PubMed1991

Viral involvement in Hodgkin's disease: detection of clonal type A Epstein-Barr virus genomes in tumour samples.

Thirty-five cases of Hodgkin's disease (HD) were analysed for the presence of Epstein-Barr virus (EBV) and human herpesvirus-6 (HHV-6) DNA. EBV genomes were detected in 11/35 cases while none of the cases was positive for HHV-6. Ten of the EBV-positive cases were subsequently analysed using a probe for the terminal region of the virus; the results suggested that the EBV-infected cells were clonally expanded. EBV subtypes specific DNA amplification was used to demonstrate that EBV subtype A, and not subtype B was present in the EBV-positive cases. The age distribution of the EBV-positive cases indicated a statistically significant trend for an increase in positivity with increasing age. This is the first indication that EBV is significantly associated with any subset of HD patients.

Adolescent↗
PubMed1991

The reproducibility of biometry and keratometry measurements.

Axial length and corneal curvature are entered into formulae to calculate intraocular lens power for cataract surgery and the absolute measurement of fundus structures such as neuroretinal rim area in glaucoma. The reproducibility (coefficient of variation, CV) of biometry and keratometry was investigated by taking five measurements of thirty phakic eyes. Although both techniques were found to be highly reproducible (CV less than 1%), keratometry was the more so. However, a clinically significant difference was noted between the first and the mean of five readings for both biometry (0.15 +/- 0.05 mm) and keratometry (0.05 +/- 0.03). Taken together, these errors would result in a postoperative refractive error of 0.65D using the SRK formula. Measurement errors were just as likely to occur with short or long eyes. Similar results were found when the analysis was performed on three measurements of both axial length and corneal curvatures. We recommend taking the average of three biometry and keratometry readings to improve the reliability of the techniques, and to increase the accuracy of calculating intraocular lens power and fundus structure dimensions.

Biometry↗