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Biomedical subjects

C O'Brien

Publications and source records attributed to C O'Brien.

At least 199 records · Page 11Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Single night studies in obstructive sleep apnea.

The role of single night studies and the determinants of effective nasal continuous positive airway (CPAP) pressures were determined in 412 consecutive patients between 1984 and 1989. Patients chosen for analysis had an apnea index (AI) of greater than or equal to 20 hr-1 prior to CPAP. The AI was 67 +/- 30 hr-1, the body mass index (BMI) was 36 +/- 9 kg/m2, the age was 51 +/- 13 yr and the lowest oxygen saturation was 72 +/- 14%. Effective CPAP (9 +/- 3 cm H2O) was documented in 320 patients on single night studies and resulted in a 99% reduction in the frequency of obstructive events and improvement in the lowest O2 saturation to 94 +/- 5%. Only 18% of the variability in effective CPAP could be explained by AI and BMI. Single night studies are sufficient to establish effective CPAP in 78% of patients and offer considerable conservation of resources compared to routine multiple night studies. Effective CPAP pressures are variable and must be determined by incremental CPAP trials.

Arousal↗

Prediction of the exercise-heat tolerance of soldiers wearing protective overgarments.

The purpose of this investigation was to see whether subject characteristics and physiologic measurements predicted exercise-heat tolerance (EHT) and voluntary tolerance time in young soldiers. A total of 18 unacclimatized males attempted six 50-min periods of treadmill walking (4.0 km.h-1, 0% grade, 33 degrees C db, 20% rh) while wearing protective overgarments. Two post hoc groups of soldiers were defined: high EHT (H) and low EHT (L), having mean (+/- S.E.) tolerance times of 360 +/- 0 and 222 +/- 12 min, respectively. Significant (p less than 0.05) H vs. L differences were observed in pretrial body mass, percent fat, and mass-to-surface area ratio (M/SA), as well as 170 min HR, Tsk and heat storage. The first three of these factors indicated that preexercise anthropomorphic characteristics may be used to distinguish H from L. The HR and Tsk differences were interpreted to mean that L experienced greater cardiovascular strain in protective overgarments because of a higher Tsk, which resulted in increased pooling of blood in cutaneous vessels, decreased cardiac filling pressure, and increased fatigue. Because HR variables were the strongest correlates of exercise tolerance time (r2 = 0.60 for HR at 170 min, r2 = 0.83 for time to reach HR of 160 beats.min-1) a novel HR monitoring technique was proposed which uses a wrist-mounted cardiotachometer to predict tolerance time.

Adult↗