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Biomedical subjects

J Robertson

Publications and source records attributed to J Robertson.

At least 109 records · Page 6Linked to original sources
PubMed1996

Diagnostic sensitivity of immunodominant epitopes of glutamic acid decarboxylase (GAD65) autoantibodies in childhood IDDM.

The prevalence and titre of epitope-specific autoantibodies to glutamic acid decarboxylase (GAD65) in 155 insulin-dependent diabetic (IDDM) and 9 GAD65 antibody (Ab)-positive healthy children were determined using four GAD65/67 chimaeric molecules which discriminate among the N-terminal (N), middle (M) and C-terminal (C) epitopes of GAD65. Radioligand binding assays for IgGAb used immunoprecipitation of in vitro translated 35S-GAD. We found autoantibodies to GAD65 in 116 of 155 (75%), to GAD67 in 19 of 155 (12%) (p < 0.0001) and to the GAD65-N-67 chimaera in 25 of 155 (16%) (p < 0.0001) IDDM sera. GAD67Ab were found almost exclusively (17 of 19, 89%) in GAD65Ab-positive sera and the levels of GAD67Ab correlated with those of GAD65Ab (r2 = 0.5913; p = 0.009). GAD65Ab directed to GAD65-M were found in 104 of 155 (67%), to GAD65-C in 104 of 155 (67%) and to GAD65-M + C in 116 of 155 (75%) of IDDM sera, and indicated reactivity to at least two distinct epitopes. Among the nine GAD65Ab-positive healthy children, two (22%) were also positive with GAD67, nine (100%) with GAD65-M + C, seven (78%) with GAD65-M, eight (89%) with GAD65-C and two (22%) with GAD65-N-67. Titres of GAD65Ab (p = 0.007), GAD65-C-Ab (p = 0.002) and GAD65-C + M-Ab (p = 0.003), but not of GAD65-M-Ab (p = 0.101) were significantly higher in IDDM than in healthy children. We conclude that GAD65Ab in IDDM and healthy children are directed to middle and C-terminal epitopes, and propose that levels of antibodies specifically directed to the carboxy-terminal end of GAD65 may distinguish IDDM from healthy children.

Adolescent↗
PubMed1996

Visual acuity of eyes after vitrectomy for retinopathy of prematurity: follow-up at 5 1/2 years. The Cryotherapy for Retinopathy of Prematurity Cooperative Group.

PURPOSE: To provide long-term follow-up on the structural status and visual function at 5 1/2 years of age for 128 eyes of 98 infants who participated in the multicenter randomized clinical trial of cryotherapy for retinopathy of prematurity in whom total retinal detachment developed from retinopathy of prematurity (ROP) by the 3-month study examination. Fifty-four patients had lensectomy-vitrectomy procedures in one or both eyes before 1 year of age (n=72 eyes), and 44 patients did not (n=56 eyes). METHODS: When the children were 5 1/2 years of age, an eye examination was performed and residua of ROP was assessed. Recognition acuity (Early Treatment of Diabetic Retinopathy Study chart) and grating visual acuity (Teller acuity card procedure) assessments were undertaken by testers who were masked to the status of each of the child's eyes. RESULTS: At least partial retinal attachment was present at 5 1/2 years in 21% compared with 28% at 1 year of age (not significant). All except one of the eyes tested at 5 1/2 years had vision limited to light perception or no light perception, regardless of whether a vitrectomy had been performed. One eye that underwent vitrectomy had minimal pattern vision. The two eyes that were reported previously to have minimal pattern vision at 1 year of age were blind at the longer-term follow-up. CONCLUSIONS: The poor visual outcome after a lensectomy-vitrectomy procedure for retinal detachment due to ROP demands that emphasis be placed on prevention of retinal detachment in premature infants.

Child, Preschool↗
PubMed1996

Assembly properties of neurofilament light chain Ser55 mutants in transfected mammalian cells.

Ser55 within the head domain of neurofilament light chain (NF-L) is transiently phosphorylated by protein kinase A, and phosphorylation of this residue is thought to regulate assembly of neurofilaments. To understand how Ser55 phosphorylation influences NF-L assembly, wild-type and mutant NF-L genes in which Ser55 was mutated to alanine, so as to prevent phosphorylation, or to aspartate, so as to mimic permanent phosphorylation, were transfected into mammalian cells that contain or do not contain an endogenous intermediate filament network. Wild-type and mutant NF-Ls localised to the Triton X-100-insoluble fraction, which suggests that phosphorylation of Ser55 does not inhibit assembly of NF-L and NF-L/ vimentin polymers at or below the tetrameric stage. Immunofluorescence microscopy of transfected cells demonstrated that the wild-type and mutant NF-Ls all colocalised with vimentin to produce similar filamentous arrays. However, in cells lacking an endogenous intermediate filament network, the aspartate mutant produced a pattern of staining different from that of the wild-type or alanine mutant. These results suggest that phosphorylation of NF-L Ser55 is not a mechanism that precludes assembly of neurofilaments from monomers into intermediate filament structures but that phosphorylation/dephosphorylation of this residue might confer more subtle characteristics on neurofilament assembly properties and architecture.

Amino Acid Sequence↗
PubMed1996

Aggregation of neurofilaments in NF-L transfected neuronal cells: regeneration of the filamentous network by a protein kinase C inhibitor.

Cytoplasmic inclusion bodies that are accumulations of neurofilaments are the pathological hallmark of many neurodegenerative diseases and have been produced in transgenic mice by overexpression of mouse (NF-L and NF-M; light and medium chains, respectively) and human (NF-M and NF-H; medium and heavy chains, respectively) neurofilament subunits. This report describes a neuronal culture model in which human NF-L was overexpressed to produce cytoplasmic accumulations of neurofilaments within cell bodies concomitant with the collapse of the endogenous neurofilament network. Electron microscopy showed that, within accumulations, neurofilaments retained a filamentous structure. The culture model thus provides a novel system in which the effect on neurofilament accumulations of manipulating protein phosphorylation can be studied. Treatment of cells containing neurofilament accumulations with bisindolylmaleimide, a specific protein kinase C inhibitor, resulted in regeneration of the filamentous network; this effect was not due to a change in the level of transfected NF-L expression. These findings lend support to the suggestion that an impairment in the regulation of protein phosphorylation may lead to the accumulation of neurofilaments seen in neurodegenerative disease.

Actin Cytoskeleton↗
PubMed1996

Comparison of exercise and normal variability on HDL cholesterol concentrations and lipolytic activity.

In order to compare the influence of a single bout of exercise on HDL-C metabolism with normal variability, 12 male runners (mean age: 24.9 +/- 4 yr) who ran 15-30 miles per week underwent exercise (E) and control (C) experimental conditions. During the E trial subjects ran on a motor driven treadmill at 75% (42.5 +/- 4.7 ml.kg-1.min-1) VO2max until 800 Kcals were expended. The C trial consisted of no exercise. Subjects were instructed to follow the same diet and keep a four d food diary during each experimental condition. Fasted blood samples were obtained at the same time of day in each condition at time points corresponding to 24 h pre-exercise (24 PRE), 6 h post- (6 h) and 24 h post-exercise (24 h). Plasma was analyzed for HDL-C, HDL2-C and HDL3-C (mg.dl-1). In addition post-heparin plasma samples were analyzed for lipoprotein lipase (LPL) and hepatic lipase (HL) activity (mumol.FFA-1.ml-1). All values were adjusted for changes in plasma volume and compared to Baseline. HDL-C levels were unaltered following the C trial. However, following the E trial, HDL-C increased (p < 0.01) above baseline values at 24 h. The increase in HDL-C was reflected in the HDL3-C subfraction (p < 0.05). Analysis of lipolytic activity revealed an overall greater LPL activity (p < 0.05) in the E trial vs the C trial. In addition, a decrease in HL was observed at 24 h (p < 0.05) but was not different between experimental conditions. These data suggest that exercise and not normal variability are responsible for alterations in lipolytic activity and corresponding increases in HDL-C levels.

Adolescent↗
PubMed1996

Time-based lag sequential analysis and the functional assessment of challenging behaviour.

This paper describes the application of time-based lag sequential analysis to the functional assessment of challenging behaviours shown by people with severe learning disabilities. The potential uses of the approach are illustrated with regards to identifying: (1) aspects of the stimulus control of challenging behaviour; (2) antecedents to the occurrence of challenging behaviour; and (3) the environmental consequences of challenging behaviour. The uses and limitations of the approach are discussed.

Adolescent↗
PubMed1996

Aortic and mitral annular remodeling using ultrasonic decalcification.

Mitral and particularly aortic valve replacements may be complicated by heavy calcification of the anulus, markedly impairing proper valve seating. From 1987 to 1996, we have used ultrasonic energy with the CUSA-device in valvular replacement to debride the aortic anulus in 90 patients and the mitral anulus in 2 patients. Annular debridement using ultrasonic decalcification is superior to other methods of debridement because it is safer, more thorough, and affords improved seating of the valve. As a result, placement of a larger valve is possible within a more compliant, wider anulus. There have been 0% incidence of paravalvular leak or valve failure. The operative mortality in our series was 1/92 (1.1%). Other than the fatality, the incidence of permanent stroke was 0%. Ultrasonic debridement to remodel the aortic and mitral valve anulus has been an invaluable adjunct in the heavily calcified anulus.

Adult↗
PubMed1996

Survival after trauma pneumonectomy: the pathophysiologic balance of shock resuscitation with right heart failure.

Emergency pneumonectomy for trauma has a high mortality. Although exsanguination is a major factor leading to death, mortality remains high even after adequate resuscitation and is thought to be related to pulmonary edema and right heart failure. We present a series of nine patients who underwent pneumonectomy at Harbor-UCLA from penetrating (7) and blunt (2) trauma. Two patients survived; three initially survived the surgery but died postoperatively of hypoxemia and right heart failure; four died intraoperatively (2 from right heart failure and 2 from exsanguination). One survivor required open cardiac massage for asystole. Careful attention to prevent volume overloading before and during trauma pneumonectomy and maintaining a negative fluid balance postoperatively may contribute to survival in these patients.

Adolescent↗
PubMed1996

Factors associated with staff support and resident lifestyle in services for people with multiple disabilities: a path analytic approach.

The quality and costs of residential services for 40 adults with severe learning disabilities and sensory impairments across four different service models were evaluated. A path analytic approach was used to calculate factors associated with four indicators of service quality: (1) assistance received by residents from staff; (2) positive contact received by residents from staff; (3) resident engagement in constructive activity; and (4) the level of physical integration of residents. The path analyses accounted for between 50 and 77% of the variance in the indicators. Factors found to be commonly associated with all four indicators included a community location, a specialized service orientation, the cognitive abilities of residents and a high level of scheduled activity. Service resources in the form of costs or staff ratios were not associated with any indicator of service quality. The findings strongly suggest an inverse system of care in that residents with greater skills receive more staff support. The implications of these and other findings for further research and service practice are discussed.

Adult↗
PubMed1996

[Dysphonia and inhalation of corticoids: a prospective study].

Dysphonia or hoarseness is a well recognised but poorly understood complication of inhaled steroid therapy. 20 asthmatics were investigated, using a perceptual rating score of hoarseness, videolaryngoscopy and videostroboscopy, prior to and after three months of high dose inhaled steroid therapy (1 mg/day). A group of 22 healthy volunteers acted as controls. Prior to commencing inhaled steroid therapy six of the asthmatics were hoarse. Erythema and oedema was noted in 10 asthmatics and vocal fold nodules in 2 asthmatics. 4 of the control group had erythema and oedema. There was significantly more vocal fold pathology in the asthmatic group, p = 0.0135. After three months of inhaled steroid therapy, improvement in voice was noted in 2 of the 6 hoarse asthmatics. This was associated with resolution of vocal fold nodules in one case and with resolution of oedema in another. One asthmatic developed a mid glottic chink. This study demonstrates that asthmatics have significantly more vocal fold pathology than healthy controls. These findings improve with commencement of inhaled steroid therapy. The development of steroid induced myopathy of the vocal folds is a possible cause for the development of a mid glottic chink in one of our subjects. Further studies are necessary to investigate this area further.

Administration, Inhalation↗
PubMed1995

Determination of morphine and related alkaloids in crude morphine, poppy straw and opium preparations by micellar electrokinetic capillary chromatography.

A rapid method for the determination of morphine and related alkaloids in crude morphine, poppy straw and opium preparations by micellar electrokinetic capillary chromatography (MEKC) has been developed. Morphine, codeine, thebaine, oripavine, papaverine, narcotine, narceine, cryptopine and salutaridine were separated in less than 10 min using a 70 cm x 50 microm I.D. uncoated fused-silica capillary column with a buffer consisting of 10% dimethylformamide, 90% 0.05 M cetyltrimethylammonium bromide, 0.01 M potassium dihydrogen orthophosphate, 0.01 M sodium tetraborate, pH 8.6. An applied voltage of -25 kV and a temperature of 28 degrees C gave the best separation of the alkaloids. Pholcodine was used as the internal standard. The compounds were detected by UV at 254 nm. The levels of morphine and related alkaloids determined by MEKC were in good agreement with those determined by high-performance liquid-chromatography (HPLC). The coefficients of variation for area calculation (%C.V.) for multiple sample and standard injections by MEKC were slightly greater than for HPLC but were still acceptable (morphine content of poppy straw: %C.V. MEKC 1.7%, %C.V. HPLC 0.3%).

Chromatography↗