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Biomedical subjects

A L James

Publications and source records attributed to A L James.

At least 55 records · Page 3Linked to original sources

Genetic linkage of T-cell receptor alpha/delta complex to specific IgE responses.

IgE responses to inhaled proteins underlie the clinical syndrome of allergic (atopic) asthma and rhinitis. We have investigated genetic linkage between specific IgE reactions to highly purified major allergens and the T-cell receptor (TCR) alpha and beta gene complexes on chromosome 14 and 7, respectively. Antigens tested included highly purified proteins from the housedust mite Dermatophagoides pteronyssinus, the domestic cat and dog, grass pollen, and the mould Alternaria alternata. Affected sibling-pair methods were used in two independent sets of families, one in the UK and one in Australia. No linkage of IgE serotypes to TCR-beta was detected, but significant linkage to TCR-alpha was seen in both family groups. For several of the IgE phenotypes investigated (positive responses to whole allergen sources or purified antigens or serum IgE above the 70th percentile in the population) the affected sibling-pairs showed significant sharing of TCR-alpha microsatellite alleles from both parents. The results show that a gene (or genes) in the TCR-alpha region modifies specific IgE responses.

Alleles↗

Proposed nomenclature for quantifying subdivisions of the bronchial wall.

There is increasing interest in the structural components of the airway wall because of the airway remodeling that is observed in conditions such as asthma and chronic obstructive pulmonary disease and because of their contribution to changes in airway mechanics. This interest has stimulated several groups to make morphometric measurements on airway cross sections, and their results have been reported using a variety of nomenclature. We propose the adoption of a standard system of nomenclature that is based on accepted terms for subdivisions of the airway wall and has been agreed to by several groups working in this field.

Bronchi↗

A rapid heat-resistant technique for presumptive identification of Salmonella on desoxycholate-citrate agar.

A caprylate esterase chromogenic test, which was considered to indicate positivity in 5 minutes if a bright colour appeared on the filter paper inoculum site to which one colony had been applied, was used to test 534 Salmonella, 535 other bacteria capable of growth on desoxycholate-citrate agar (DCA), and 517 non-lactose fermenting colonies from stool cultures on DCA. It was found to be 100% sensitive for Salmonella, 99% specific, and more accurate than either direct antiserum agglutination or a urease test in these respects. The test kit could be stored at room temperature.

Agar↗

Polyphasic taxonomic study of the genera Gordona and Tsukamurella including the description of Tsukamurella wratislaviensis sp. nov.

Representatives of the genera Gordona and Tsukamurella together with related actinomycetes were the subject of chemotaxonomic, numerical taxonomic and DNA homology studies. In the numerical analysis the organisms were examined for 116 unit characters and the data sorted using the simple matching, Jaccard and pattern coefficients; clustering was achieved using the unweighted pair group method with arithmetic averages algorithm. The numerical groupings were not affected by the statistics used or by test error, estimated at 1.9%. The numerical taxonomic data supported the integrity of the four validly described species of Gordona but indicated that the genus Tsukamurella might encompass a species in addition to Tsukamurella paurometabola. The putative new strains had chemical, enzymic, nutritional and tolerance properties consistent with their assignment to the genus Tsukamurella and formed a DNA homology group corresponding to the one formed by the Tsukamurella paurometabola strains. It is proposed that the new taxon be assigned to the genus Tsukamurella as Tsukamurella wratislaviensis.

Actinomycetales↗

Relative risks of bronchial hyper-responsiveness associated with skin-prick test responses to common antigens in young adults.

We studied 143 young subjects by skin-prick testing to common allergens and by the measurement of non-specific bronchial responsiveness (NSBR). A logistic regression model showed a prevalence odds ratio (POR) for bronchial hyper-responsiveness (PD20 less than 10 mumol methacholine) in house dust positive subjects of 4.10 (95% CI 1.77-9.51, P less than 0.001), and in mould positive subjects 5.72 (95% CI 2.06-15.9, P less than 0.001): the PORs for epithelia (2.05, P = 0.12) and grasses (1.78, P = 0.19) were not significant. If bronchial reactivity was assessed as measurable (PD20 less than 102 mumol methacholine) or not, the POR for house-dust-positive subjects was 4.83 (95% CI 2.23-10.5, P less than 0.001), for moulds was 10.5 (95% CI 2.33-47.5, P less than 0.001), for epithelia was 4.79 (95% CI 1.91-12.0, P less than 0.001), and for grasses was 2.21 (95% CI 1.11-4.4, P = 0.022). The results show the risk of bronchial hyper-responsiveness is greater in subjects sensitive to house dust and mould than in those reactive to grasses, and suggests that the presence or absence of increased NSBR in atopic individuals may depend on the antigens to which they become sensitized.

Adolescent↗

Classification and identification of rhodococci.

Ninety-nine representative strains of Rhodococcus were compared through 129 unit characters and the data examined using the simple matching, Jaccard and pattern coefficients. Clustering was achieved using the unweighted pair group method with arithmetic averages algorithm. The numerical classification was not affected by the statistics used or by test error, estimated at 1.95%. Sixteen multimembered and 23 single member clusters were defined by the simple matching coefficient at or above the 89% similarity level. The numerical phenetic data support the taxonomic integrity of all 13 validly described species of Rhodococcus, including Rhodococcus aichiensis. Rapid enzymic tests based upon fluorophores 7-amino-4-methylcoumarin and 4-methylumbelliferone provide valuable data for rhodococcal systematics.

Bacterial Typing Techniques↗

Exposure to grain dust and changes in lung function.

Respiratory symptoms and lung function were assessed in 41 seasonal grain handlers and related to duration of employment and level of exposure to grain dust. Ten public works department employees, not exposed to grain dust, were examined during the same period. Respiratory symptoms, forced expired volume in one second (FEV1), and bronchial responsiveness (dose of methacholine provoking a 20% fall in FEV1-PD20) were assessed before starting work and at weekly intervals during a period of employment lasting up to four weeks. Two atopic grainhandlers with pronounced bronchial hyperresponsiveness (PD20 less than 1 mumol) and a history of asthma withdrew from the study within two weeks because they developed severe asthma. Respiratory symptoms were more frequent and more often attributed to work in the grainhandlers than in the non-exposed subjects. In the grainhandlers the FEV1 decreased by a mean (95% confidence intervals) of 321 ml (198-444) (p less than 0.05) and the mean (95% confidence interval) PD20 decreased from 20.6 mumol (10.3-41.2) to 6.0 mumol (2.8-12.5) (p less than 0.05) after one week of work. Over the next three weeks the mean FEV1 returned towards the prestudy values. The mean PD20, however, remained significantly lower than the initial value. The mean FEV1 and PD20 did not change significantly in the non-exposed subjects. The frequency of symptoms and decreases in FEV1 were greater in grainhandlers when working in jobs where total exposure to dust was greater than 20 mg/m3 than when working in jobs where it was less than 10 mg/m3. The results indicate that occupational exposure to grain dust results in respiratory symptoms and changes in lung function, including increased airway responsiveness, within the first week of exposure to grain dust at work. These changes appear to be determined by the degree of dust exposure and suggest a direct effect of grain dust on the lung in these subjects.

Agricultural Workers' Diseases↗

Effect of breathing pattern during inhalation challenge on the shape and position of the dose-response curve.

To examine the effect of breathing pattern on the dose-response curve, 4 mild asthmatic and 9 normal subjects inhaled increasing concentrations of methacholine (0.03-256 mg/ml) using a quiet tidal breathing pattern or tidal breathing with a forced expiratory phase. The provocative concentration of methacholine causing a 20% decrease in the forced expired volume in 1 s (PC20FEV1) or a 200% increase in pulmonary resistance (PC 200RL) was determined. In addition, the maximal change in FEV1 and RL and the slopes of the dose-response curves were measured. The forced expiratory pattern caused an increase in the central/peripheral deposition ratio of a [99m]technetium-labeled aerosol (n = 3). There were no differences in mean tidal volume, minute ventilation, inspiratory flow rates, or baseline FEV1 or RL between the quiet breathing or forced expiration studies, although mean expiratory flows were increased in the latter (p less than 0.001). PC20FEV1 and PC200 RL decreased (p less than 0.001) but the maximal change in FEV1 and RL was unchanged in the forced expiration studies. Forced expiration during inhalation challenge did not alter the slope of FEV1 or RL dose-response curves. These results suggest that the sensitivity (PC20, PC200) and maximal response of in vivo dose-response curves may be affected independently by factors such as aerosol deposition.

Adult↗

The mechanics of airway narrowing in asthma.

This study was designed to determine the potential importance of airway wall thickening in the pathogenesis of the excess airways narrowing of asthma. The airways in postmortem specimens of lung obtained from 18 patients who suffered from asthma were compared to similar airways from 23 patients without asthma. Each airway was projected onto a digitizing board of a microcomputer to trace the internal and external perimeter of the airway and to calculate the submucosal and mucosal thicknesses. The relaxed length of the airway smooth muscle and the shortening required to occlude the airway lumen were calculated. These data show that the wall area was greater (p less than 0.001) in the membranous and cartilaginous airways of asthmatic patients and the airway smooth muscle shortening required to occlude the lumen was less in asthmatic than nonasthmatic airways (p less than 0.001). The increased wall area was due to increased areas of epithelium, muscle, and submucosa. We conclude that the walls of the airways of patients with asthma are thickened by chronic inflammation and that this thickening could be as important as smooth muscle shortening in determining the airway responsiveness of these patients.

Adolescent↗

The effect on airway function of inspired air conditions after isocapnic hyperventilation with dry air.

The magnitude of postexercise or posthyperventilation bronchoconstriction in patients with asthma is related to the temperature and the water content of the inspired air during the exercise or hyperventilation period. Recent studies have suggested that the inspired air conditions during recovery from exercise may also be important in determining the magnitude of postexercise airway narrowing. In the present study, normal subjects (n = 8) and patients with asthma (n = 12) were studied on separate days. On day 1 the subjects performed isocapnic hyperventilation with warm dry air and recovered breathing warm dry air. On the second day, an identical warm dry air challenge was administered, but recovery occurred while they were breathing warm humid air. There was no significant bronchoconstriction in the normal subjects, irrespective of the inspired air conditions during recovery. The patients with asthma showed greater bronchoconstriction during recovery in warm, humid air (maximal decrease in FEV1 31% +/- 17%) than in dry air (maximal decrease in FEV1 19% +/- 20%; p less than 0.05). These results suggest that the inspired air condition during recovery from isocapnic hyperventilation of dry air is also a determinant of the magnitude of the bronchoconstrictor response.

Adult↗

Coding of stimulus parameters in autistic, retarded, and normal children: evidence for a two-factor theory of autism.

Phasic changes in respiratory period, electrodermal activity, and the vasoconstrictive peripheral pulse amplitude response, were examined in matched groups of autistic, retarded, and normal children using repeated presentation of simple visual and auditory stimuli of differing magnitudes. Analysis of response magnitudes as a function of group membership, trials, stimulus magnitude, and age, indicated both similarities and differences between the autistic and control groups. The autistic group differed from the control groups in its failure to show response habituation to repeatedly presented stimuli. However, data indicated that autistic children coded stimulus magnitude similarly to controls, suggesting that the failure to adequately process stimulus novelty does not reflect a general processing failure. Autistic children also exhibited relative hyperreactivity in all measures. Age effects showed this to be interpretable as reflecting developmental delay. These two differences support a recent two-factor theory of autism.

Adolescent↗

Detection of specific bacterial enzymes by high contrast metal chelate formation. Part II. Specific detection of Escherichia coli on multipoint-inoculated plates using 8-hydroxyquinoline-beta-D-glucuronide.

The use of 8-hydroxyquinoline-beta-D-glucuronide for the demonstration of beta-glucuronidase activity within the family Enterobacteriaceae has been investigated. The compound has been shown to be an effective substrate for the bacterial enzyme and the Michaelis constant for the association has been determined. A multipoint-inoculated method was employed to test 400 routine clinical isolates including those of urinary and faecal origin. When grown on an agar-based medium containing the substrate together with a ferric salt, glucuronidase-positive organisms were revealed by intense black pigmentation located only in the colony mass. The only organism yielding positive results by this method was Escherichia coli. The shigellae tested were negative by this procedure. Of the total biochemically profiled E. coli organisms 80% were specifically visualised by the method. This contrasts with 97% positively obtained by a fluorescence procedure involving use of 4-methylumbelliferone-beta-D-glucuronide but which also gives positive results with Shigella sonnei. A simple, cost-effective procedure involving use of both techniques for specific detection of E. coli is described.

Escherichia coli↗

Bronchial responsiveness, lung mechanics, gas transfer, and corticosteroid response in patients with chronic airflow obstruction.

Thirty patients with stable chronic airflow obstruction receiving regular bronchodilator treatment were studied to determine whether the level of bronchial responsiveness, transfer factor for carbon monoxide (TLCO), or the mechanical properties of the lung predicted a bronchodilator response to oral corticosteroid treatment. Before treatment mean (SD) FEV1 was 48% (16%) of the predicted value (% pred); the geometric mean concentration of methacholine required to produce a 20% fall in FEV1 (PC20) was 0.44 (range 0.07-3.32) mg/ml; and TLCO was 59% (21%) predicted. The exponential constant (k) defining the shape of the static volume-pressure curve was 146% (66%) predicted and pulmonary conductance relative to predicted lung volume at a transpulmonary pressure of 5 cm H2O (sGL5) was 72% (37%) predicted. After prednisolone treatment (0.6 mg kg-1 day-1 for two weeks) FEV1 increased by 8% (19%) (p less than 0.05) and daily mean peak flow (PEF) by 3% (10%) (p less than 0.01) over pretreatment values. Three patients had an increase in FEV1 of more than 30%, two of whom had sputum eosinophilia (p less than 0.05). The three were among the 13 patients with a reduced sGL5. The increase in FEV1 did not correlate with initial PC20 (r = 0.16), k (r = -0.12), or TLCO (r = -0.14). Thus measurements of bronchial responsiveness, lung distensibility, and TLCO did not predict corticosteroid response in patients with stable chronic airflow obstruction. Patients with sputum eosinophilia or reduced pulmonary conductance may be more likely to respond.

Airway Resistance↗

Effects of lung volume, bronchoconstriction, and cigarette smoke on morphometric airway dimensions.

To examine the role of airway wall thickening in the bronchial hyperresponsiveness observed after exposure to cigarette smoke, we compared the airway dimensions of guinea pigs exposed to smoke (n = 7) or air (n = 7). After exposure the animals were anesthetized with urethan, pulmonary resistance was measured, and the lungs were removed, distended with Formalin, and fixed near functional residual capacity. The effects of lung inflation and bronchoconstriction on airway dimensions were studied separately by distending and fixing lungs with Formalin at total lung capacity (TLC) (n = 3), 50% TLC (n = 3), and 25% TLC (n = 3) or near residual volume after bronchoconstriction (n = 3). On transverse sections of extraparenchymal and intraparenchymal airways the following dimensions were measured: the internal area (Ai) and internal perimeter (Pi), defined by the epithelium, and the external area (Ae) and external perimeter (Pe), defined by the outer border of smooth muscle. Airway wall area (WA) was then calculated, WA = Ae - Ai. Ai, Pe, and Ae decreased with decreasing lung volume and after bronchoconstriction. However, WA and Pi did not change significantly with lung volume or after bronchoconstriction. After cigarette smoke exposure airway resistance was increased (P less than 0.05); however, there was no difference in WA between the smoke- and air-exposed groups when the airways were matched by Pi. We conclude that Pi and WA are constant despite changes in lung volume and smooth muscle tone and that airway hyperresponsiveness induced by cigarette smoke is not mediated by increased airway wall thickness.

Airway Resistance↗

The use of the internal perimeter to compare airway size and to calculate smooth muscle shortening.

Previous studies from our laboratory suggest that the internal airway perimeter (Pi) defined by the folded epithelial surface remains constant as the airways narrow. To test this hypothesis, we treated adjacent slices of resected lung lobes with either theophylline or carbachol and determined the dimensions of the airways in these lung slices. Transverse sections of contracted (n = 58) and relaxed (n = 55) airways were used to measure the Pi defined by the epithelial surface, lumen area (Ai), external perimeter (Pe) defined by the outer edge of the smooth muscle layer, and the external area (Ae). Wall area (WA = Ae - Ai) was calculated. The frequency distribution of internal perimeters was not significantly different for the contracted and relaxed airways, and when the square root of wall area was plotted against Pi, the regression lines for the contracted and relaxed airways were almost identical. The "relaxed" external perimeter was calculated Per = square root Pi2 + (4 pi WA), and the percentage of muscle shortening (PMS) was determined: PMS = [(Per - Pe)/Per] x 100. We conclude that Pi and WA are constant in airways whether the smooth muscle is relaxed or contracted and that Pi can be used as a marker of airway size and, under controlled conditions, can be used to calculate the smooth muscle shortening present in a given airway.

Carbachol↗

Detection of specific bacterial enzymes by high contrast metal chelate formation. Part I. 8-Hydroxyquinoline-beta-D-glucoside, an alternative to aesculin in the differentiation of members of the family Enterobacteriaceae.

8-Hydroxyquinoline-beta-D-glucoside has been shown to be a useful alternative substrate for the differentiation of members of the family Enterobacteriaceae based on the presence or absence of beta-glucosidase. In an identification protocol based on multipoint-inoculated plates 8-hydroxyquinoline-beta-D-glucoside when incorporated into an agar based medium supplemented with a ferric salt produced intense black pigmentation localised solely in the immediate vicinity of beta-glucosidase positive organisms. In contrast, using conventional aesculin plates, positive organisms produced a brown ferric-aesculetin complex, the diffusibility of which limited interpretation especially where large numbers of colonies were involved. Almost complete agreement was found when 1964 routine 'coliform' organisms were tested by both methods. The method described allows use of a 36 place 'minipin' inoculator without any danger of 'nearest neighbour' interference and constitutes a cost-effective method suitable for either manual or automatic reading.

Chemical Phenomena↗