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Biomedical subjects

D M Mitchell

Publications and source records attributed to D M Mitchell.

At least 127 records · Page 7Linked to original sources

Fine specificity of the in vitro antibody response to influenza virus by human blood lymphocytes.

The fine specificity of anti-influenza antibody produced in vitro by human PBM stimulated with different strains of influenza virus was examined by competition binding in solid phase enzyme immunoassay. Most of the antibody produced in vitro is directed to strain-specific or cross-reactive determinants on the hemagglutinin molecule. The extent of cross-reactivity is dependent on the strain of virus used to stimulate PBM as well as the individual tested and presumably on his previous exposure to influenza viruses. PBM from some individuals produced antibody that bound to the stimulating strain of influenza virus but not to other strains of the same subtype. In other individuals, antibody was produced in vitro that cross-reacted with all viruses in the same subtype (e.g., H3N2; A/X31, A/X47, and A/Texas) but did not bind to other (H2N1 or H1N1) subtypes, and in a few individuals, extensive cross-reaction between subtypes was seen. The presence of antibody to hemagglutinin in these culture supernatants was confirmed by competition binding to highly purified hemagglutinin. This in vitro culture system allows the immunologic memory of individuals to a wide range of stimulating virus strains to be examined simultaneously in terms of specificity of the antibody response by human PBM to influenza virus after natural infection or immunization.

Adult↗

Accessory cell and HLA compatibility requirements for the generation of specific in-vitro antibody responses to influenza virus by human blood lymphocytes.

The role of antigen presenting cells in specific in-vitro antibody responses to influenza virus by human lymphocytes was investigated. Demonstration of a requirement for accessory cells necessitated vigorous depletion procedures. Accessory cells were removed by passage of mononuclear cells through a Sephadex G10 column followed by separation of cells bearing antigens defined by the monoclonal antibodies OKM1 and UCHM1 by fluorescence-activated cell sorting or panning. Peripheral blood mononuclear cells treated in this way were unable to respond to influenza virus by antibody production in either round-bottom or flat-bottom culture wells. The response could be reconstituted by either irradiated plastic-adherent cells or G10 non-adherent OKM1/UCHM1 positive cells in both autologous or allogeneic (HLA-DR different) combinations. The absence of HLA restriction was not due to non-specific allogeneic effects and was confirmed using irradiated, antigen-pulsed accessory cells which were extensively washed, incubated overnight and washed again to remove free antigen. These data suggest that the normal T-cell repertoire contains T helper cells specific for antigen plus self and antigen plus allo MHC.

Antibodies, Monoclonal↗

An analysis of the American Rheumatism Association criteria for rheumatoid arthritis.

When a community-derived population of 840 rheumatoid arthritis patients was used to test the American Rheumatism Association's 11 diagnostic criteria for rheumatoid arthritis, these criteria divided patients into 3 reasonably distinct classifications (probable, definite, and classic). The severity of disease increased in direct proportion to the number of positive criteria. Three criteria involve invasive procedures that are rarely performed; they are unnecessary for effective use of the other 8 criteria. Although 256 possible combinations of these 8 criteria exist, the criteria function principally to classify patients into only 7 major clinical syndromes, each of which corresponds to a major clinical presentation. By identifying the logical interrelationships between criteria in this report, we have confirmed their applicability and provided insight into the manner by which criteria classify patients.

Adolescent↗

Kinetics of specific in vitro antibody production following influenza immunization.

In vitro specific antibody responses to influenza viral antigens by peripheral blood mononuclear leucocytes following stimulation with influenza virus or pokeweed mitogen have been measured before and at time intervals after influenza immunization in 11 healthy volunteers. There was an early increase in specific antibody produced by lymphocytes stimulated with influenza virus in vitro, in all subjects immunized. The magnitude of the response varied considerably between individuals as did its duration. Virus specific antibody production by cells stimulated with pokeweed mitogen also increased after immunization in all donors. Cells from six of the 11 individuals produced specific antibody in vitro seven days after immunization without antigen or mitogen stimulation. Seven of the 11 subjects had a greater than four-fold increase in serum titre of haemagglutination inhibiting antibody. This study shows an early brisk increase in the ability of lymphocytes to respond to influenza virus in vitro following immunization consistent with a secondary immune response.

Antibodies, Viral↗

Kinetics of specific anti-influenza antibody production by cultured lymphocytes from patients with systemic lupus erythematosus following influenza immunization.

Specific antibody responses to influenza viral antigens produced by cultured peripheral blood mononuclear leucocytes stimulated with influenza virus or pokeweed mitogen (PWM) have been measured in seven patients with systemic lupus erythematosus (SLE) before and at time intervals after influenza immunization. Cells from two patients stimulated with influenza virus in vitro produced high levels of specific antibody 7 days after immunization. Cells from a third patient produced small amounts of specific antibody at day 14. No antibody was produced by cells from the remaining four patients. Responses were of short duration and were not detectable 1 month after immunization. Specific anti-influenza antibody was induced by PWM only from cells of those patients who responded to virus antigen although absolute levels of antibody produced were not as high. In six patients serum haemagglutination inhibiting antibody to influenza virus was measured, and all six had a greater than four-fold increase. The disparity between in vitro antibody production by peripheral blood mononuclear leucocytes and changes in serum antibody suggests that in patients with systemic lupus erythematosus, in vitro functions of peripheral blood lymphocytes do not reflect the immune system as a whole.

Antibodies, Viral↗

Transbronchial lung biopsy with the fibreoptic bronchoscope: analysis of results in 433 patients.

Transbronchial lung biopsy was performed via the fibreoptic bronchoscope in 433 patients. In 183 patients, whose chest radiographs showed bilateral diffuse shadows a histologic diagnosis was established by transbronchial biopsy in 61%, including sarcoidosis (58), fibrosing alveolitis (18) and carcinoma (14). Histologically normal lung or inadequate pulmonary tissue for diagnosis was obtained from 71 patients in this group. In 225 patients with solitary chest radiography opacity, a diagnosis of bronchial carcinoma was finally made in 130, of whom 82 (63%) had a histological diagnosis established by transbronchial biopsy. In 84 patients finally shown to have sarcoidosis, 65 (77%) had positive histology by transbronchial biopsy whereas only 19 (40%) of 48 patients with fibrosing alveolitis yielded histology compatible with the diagnosis. Pneumothorax developed in three patients after the procedure but only one required intercostal drainage. Haemorrhage of 50-100 ml occurred in seven patients and bleeding ceased spontaneously in all cases. There were no fatalities.

Adolescent↗

Fibreoptic bronchoscopy: ten years on.

Fibreoptic bronchoscopy was introduced more than 10 years ago and is now in many centres a routine diagnostic procedure, having superseded rigid bronchoscopy. Its major role is in the diagnosis of bronchial carcinoma, where the results are as good as, if not better than, results with the rigid instrument. Other major applications have been found in investigating haemoptysis, transbronchial lung biopsy in interstitial lung disease, and in the critically ill patient in the intensive care unit. More recently, the instrument has been used to perform bronchoalveolar lavage in investigating interstitial lung diseases and to enable lobar and segmental lung function studies to be performed. Fibreoptic bronchoscopy is a major advance in the diagnosis of pulmonary diseases, but there will always be times when rigid bronchoscopy is preferable.

Adolescent↗

Transbronchial lung biopsy through fibreoptic bronchoscope in diagnosis of sarcoidosis.

Sarcoidosis was ultimately diagnosed in a consecutive series of 79 patients, of whom 24 presented with unusual features. Histological support for this diagnosis was obtained in 37 out of 42 patients who underwent transbronchial biopsy; epithelioid and giant-cell granulomas were also found on biopsy of the bronchial mucosa in 17 out of 22 patients. Kveim tests were completed in 44 patients: results were positive in 19, equivocal in 11, and negative in 14. In 16 patients histological support was obtained on biopsy of various other tissues. The clinical presentation of the disease and the degree of histological support provided by the various procedures used in reaching a diagnosis of sarcoidosis varied considerably. Transbronchial biopsy of the lung is a useful advance in diagnosing sarcoidosis and provided a higher diagnostic yield than any other method.

Biopsy↗

An evaluation of cusum analysis in asthma.

It has been claimed that cusum analysis may be a clearer way of expressing trends in serial peak flow (PF) measurements in asthma than visual inspection of peak flow charts. To assess this we have applied cusum analysis to serial PF measurements in patients receiving various forms of treatment for airflow obstruction. We found that cusum analysis usually gave no additional advantage over simple graphs of PF data. In cases in which trends were apparent only by cusum analysis, their dimension was such that they were unlikely to form the basis of decisions on treatment.

Asthma↗

Prognostic features of large cell anaplastic carcinoma of the bronchus.

The clinical features of 208 patients with large cell anaplastic carcinoma of the bronchus are reviewed. Of the sample 47.6% had disseminated disease at presentation, and 95% were cigarette smokers. The median survival was 6.0 months and five-year survival was 5.9%. Twenty-seven per cent of the patients had surgical resection of tumour. The median survival of resected patients was 13.0 months and five-year-survival was 21%. Radiotherapy was ineffective in controlling the disease in this series.

Adult↗

Large airway obstruction secondary to endobronchial coccidioidomycosis.

When clinically apparent, coccidioidomycosis usually presents either as an interstitial pulmonary infiltrate or, later in its course, a parenchymal nodule often with cavitation. The present report concerns a young adult woman whose presentation was one of shortness of breath with wheezing and stridor, secondary to a localized endobronchial coccidiodal granuloma producing nearly complete obstruction of the right mainstem bronchus. Such a presentation has not been reported previously in an adult. The possible association of serious fungal disease with previous jejunoileal bypass surgery is discussed.

Adult↗

Severe hyponatraemia in hospital inpatients.

A prospective study of severe hyponatraemia in adult hospital inpatients showed that 44 patients had plasma sodium concentrations below 125 mmol(mEq)/1. Eighteen cases (41%) were iatrogenic, caused by diuretic treatment or postoperative administration of intravenous 5% dextrose, or both. Chest infection, a seldom-recognised and ill-understood cause of hyponatraemia, proved more common than carcinoma of the bronchus. Thirty-one patients had symptoms attributable to the hyponatraemia, but these were severe in only five cases. Analysis of blood and urine was of no value in distinguishing the different diagnostic groups in an emergency.

Diuretics↗

Pituitary coma with continuing menstruation.

A case of pituitary coma with continuing menstruation is presented. This association is extremely rare, but a history of recent menstrual periods does not exclude advanced hypopituitarism from the differential diagnosis of severe hyponatraemia.

Coma↗