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D M Mitchell

Publications and source records attributed to D M Mitchell.

At least 91 records · Page 5Linked to original sources
PubMed1991

Analysis of human T-cell epitopes in the 19,000 MW antigen of Mycobacterium tuberculosis: influence of HLA-DR.

The potential number of T-cell epitopes in the 19,000 molecular weight (MW) antigen has been investigated using overlapping peptides which comprise the complete sequence. Sixteen potential epitopes could be deduced from the responses to these peptides by polyclonal T cells derived from 22 antigen-responsive donors. The majority of epitopes were not predicted by either of the major paradigms, the Rothbard motif and the amphipathic helix. A hierarchy of epitopes was indicated by the responses, which ranged from strong and frequent in the N-terminal region, to moderate or weak elsewhere. Some epitopes were restricted by single HLA-DR determinants, or families of determinants sharing structural features in common, whilst the two N-terminal peptides were recognized by donors with a diversity of DR types. The high degree of T-cell recognition of the N-terminal region may be of relevance to the design of a sub-unit vaccine capable of priming T cells against Mycobacterium tuberculosis.

Amino Acid Sequence↗
PubMed1991

The clinical course of Felty's syndrome compared to matched controls.

In a cohort of 919 patients with definite or classic rheumatoid arthritis followed prospectively since 1966, we identified 36 patients with Felty's syndrome (FS). Their clinical course was compared to that of 72 matched controls from the same cohort. Patients with FS had more extraarticular features and more infections than control patients. The presence of joint erosions, serial Lansbury indices, and death rates were similar in both groups. Cardiovascular disease was the commonest cause of death in both groups, accounting for 32% of all deaths. Sepsis accounted for 10% of deaths in the group with FS and 13% of deaths in the controls.

Adolescent↗
PubMed1990

Alveolar macrophages in AIDS patients: increased spontaneous tumour necrosis factor-alpha production in Pneumocystis carinii pneumonia.

In order to assess the role of alveolar macrophages and their products in the control of Pneumocystis carinii pneumonia (PCP) and other infections in AIDS, bronchoalveolar lavage cells and peripheral blood mononuclear cells from HIV-positive AIDS/ARC patients (with and without PCP) and HIV-negative patients were counted and cultured in vitro; spontaneous and LPS-induced tumour necrosis factor-alpha (TNF-alpha) production was measured. Markedly increased spontaneous TNF-alpha production by alveolar macrophages and, to a lesser extent, peripheral blood monocytes was found in HIV-positive patients with active PCP but not in patients without the infection. Higher TNF production was associated with lower counts of Pneumocystis in the bronchoalveolar lavage fluid. These results suggest that TNF-alpha production by macrophages may play an important role in the control of Pn. carinii infection in AIDS.

Bronchoalveolar Lavage Fluid↗
PubMed1990

Mycobacterial infection in patients infected with the human immunodeficiency virus.

Of 207 homosexual or bisexual patients with the acquired immune deficiency syndrome (AIDS), 24 with the AIDS related complex, and 39 with asymptomatic HIV infection, 32 patients were found to have mycobacterial infection. Mycobacterium tuberculosis was found in 13 patients with AIDS and in two with the AIDS related complex. M avium-intracellulare was found in 15 patients with AIDS and was disseminated in 12. One patient was infected with M kansasii and one with M ulcerans. Invasive procedures were frequently required to obtain positive bacteriological results. Subclinical carriage of M avium-intracellulare and other mycobacteria thought to be nonpathogenic was common in patients seronegative for the human immunodeficiency virus and at all stages of human immunodeficiency virus infection. All but one isolate of M tuberculosis were fully sensitive to standard antimycobacterial antibiotics. Response to treatment was usually rapid. M avium-intracellulare isolates were all resistant to first line agents in vitro, and antibiotics such as ansamycin and amikacin were required to obtain a clinical response.

AIDS-Related Complex↗
PubMed1990

A case of disseminated phaeohyphomycosis caused by Cladosporium devriesii.

In 1984, Gonzalez and co-workers reported a new fungus, Cladosporium devriesii. This was obtained from a young woman living in Grand Cayman, and was associated with deep organ involvement. Subsequently, this patient was treated at the University Hospital of the West Indies, Mona. There was no evidence of HIV infection. Following her demise, a full autopsy was performed, and fungal cultures were examined by electron microscopy. This is the first autopsy report of disseminated phaeohyphomycosis in the West Indies.

Adult↗
PubMed1989

Diagnostic problems in AIDS and the lung.

Since the first case of AIDS in the United Kingdom was described in 1981 (1), there have been up to October 1988, 1794 AIDS cases reported, of whom 965 are dead and 8794 individuals known to be Human Immunodeficiency Virus (HIV) seropositive (2). In fact the actual number of seropositive individuals is likely to be far greater than this figure. A recent study of an HIV seropositive cohort suggests that the majority of individuals infected with HIV will eventually develop AIDS (3). Most of the cases in the U.K. have occurred in homo- or bisexual men, and the pattern of disease in the U.K. closely follows that of the epidemic in the United States. The association between AIDS and infection with HIV was demonstrated in 1983-4 (4,5) and HIV induced damage to the immune system with profound depression of cell mediated immunity is responsible for many of the manifestations of this extraordinary new disease (6). As the lung is the most frequently affected organ in AIDS (7), and as case numbers are likely to increase in the U.K., if the epidemic trend continues, Respiratory Physicians in the U.K. will be increasingly involved in the management of these patients. The purpose of this review is to highlight some of the diagnostic problems encountered in AIDS patients with lung disease.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Protective HLA-DR phenotypes in rheumatoid arthritis.

In a study of HLA-DR phenotypes in patients with rheumatoid arthritis (RA) and controls from the Saskatoon area and in Newfoundland, we found that certain phenotypes occurred more frequently in the patients than in healthy controls in both populations ("increased risk phenotypes"). The reverse was also true: certain phenotypes were reduced or excluded from patients with RA compared with controls. Three increased risk phenotypes with twice the expected frequencies or more were HLA-DR1,DR4; DR4 and DR4,DR5. Four "protective" phenotypes with half or less the expected frequencies were HLA-DR1, DR5; DR2; DR2,DR3 and DR3,DR7. We speculate that at least for the DR3,DR7 phenotype, the protective effect may be due to a hybrid DQw2 molecule.

Arthritis, Rheumatoid↗
PubMed1988

Lung function abnormalities in patients infected with the human immunodeficiency virus with and without overt pneumonitis.

Pulmonary function was measured in 169 male patients seropositive for the human immunodeficiency virus (HIV). The transfer factor for carbon monoxide (TLCO) in symptom free patients and patients with persistent generalised lymphadenopathy was normal (greater than 83% of predicted values). Patients with the AIDS related complex, non-pulmonary Kaposi sarcoma, and non-pulmonary non-Kaposi sarcoma AIDS (that is, opportunist infections affecting other organs) had lower mean values for TLCO (77%, 70%, and 70% of predicted respectively). These values were significantly lower than values for symptom free patients. Lower mean values of 50% and 63% predicted TLCO were observed in patients during the acute and recovery phases of Pneumocystis carinii pneumonia. TLCO was also low in patients with lung mycobacterial infection and in a patient with lung Kaposi sarcoma. Forced expiratory volume in one second, peak expiratory flow, and maximal expiratory flow at 50% of vital capacity were significantly reduced only in patients with acute pneumocystis pneumonia. This study shows that abnormalities in the results of pulmonary function tests, particularly TLCO, although greatest in patients with pulmonary complications of AIDS, are also present in patients with AIDS but without other evidence of pulmonary disease, and in patients with the AIDS related complex. The predictive and prognostic implications of these findings require further investigation.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Effect of particle size of bronchodilator aerosols on lung distribution and pulmonary function in patients with chronic asthma.

The particle size of bronchodilator aerosols may be important in determining the site of deposition in the lung and their therapeutic effect. The distribution of aerosols (labelled with technetium-99m diethylene triamine pentacetic acid) of two different particle sizes has been studied by gamma camera imaging. The particles had mass median aerodynamic diameters (geometric standard deviations) of 1.4 (1.4) and 5.5 (2.3) micron, and they were administered from a jet nebuliser to eight patients with chronic severe stable asthma. There was no significant difference in peripheral lung deposition with the two aerosols in any patient. The bronchodilator effect of the two aerosols was determined from cumulative dose-response studies. To avoid large doses that might mask possible differences in effect due to aerosol size, small, precisely determined incremental amounts of salbutamol (25-250 micrograms total lung dose) were used. The two doses were given via a nebuliser on separate occasions and the bronchodilator response was measured from FEV1, forced vital capacity, and peak expiratory flow 30 minutes after each dose. Bronchodilatation was similar with the two aerosols at each dose of salbutamol. There was therefore no difference in distribution within the lung or any difference in bronchodilator effect between an aerosol of small (1.4 micron) particle size and an aerosol of 5.5 microns in patients with severe but stable asthma.

Albuterol↗