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Biomedical subjects

M Kirby

Publications and source records attributed to M Kirby.

At least 109 records · Page 6Linked to original sources
PubMed1989

Expression of HLA class II genes in alveolar macrophages of patients with sarcoidosis.

Sarcoidosis is characterized by the accumulation of activated helper/inducer T-cells and macrophages at sites of disease. The accumulation of these T-cells may be related to the ability of sarcoid alveolar macrophages to present antigen and stimulate lymphocyte proliferation in an exaggerated fashion. In the context that HLA Class II gene (HLA-DR, DQ, and DP) expression is essential to the interaction of lymphocytes with antigen-presenting cells such as macrophages, we have evaluated the hypothesis that the expression of Class II genes may be up-regulated in sarcoid alveolar macrophages. Northern blot and dot blot analysis with 32P-labeled cDNA probes for HLA-DR, DQ, and DP genes revealed that both normal and sarcoid alveolar macrophages contain Class II mRNA transcripts, but that the levels in sarcoid and normal alveolar macrophages are similar (p greater than 0.3, all comparisons). Furthermore, evaluation of surface expression of Class II molecules with monoclonal antibodies and flow cytometry analysis demonstrated that alveolar macrophages of both patients with sarcoidosis and normal subjects express all three Class II molecules, DR, DQ, and DP, but there were no significant differences between sarcoid patients and normal subjects in the proportions of macrophages expressing these surface molecules. However, there was a significantly higher surface density of Class II molecules on sarcoid alveolar macrophages (p less than 0.05, all comparisons sarcoid to normal).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

AIDS and law.

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AIDS Serodiagnosis↗
PubMed1988

Contractile responses of isolated adult rat and rabbit cardiac myocytes to isoproterenol and calcium.

Myocytes were isolated by Langendorff perfusion of rat or rabbit hearts with low calcium solution followed by collagenase and hyaluronidase, or by incubation of chunks of rat ventricular tissue in similar media. Cells were then placed in a bath on a microscope stage, superfused and electrically stimulated. Contraction amplitude and rate of change of length during contraction were measured using a video camera and edge detection monitor. Cells were selected for study using a number of criteria developed to identify and define a cell population able to give consistent inotropic responses over a long period. The maximum contraction amplitude with isoproterenol in rabbit cells was 0.244 micron (sarcomere length change) or 13.1% (percentage change in cell length), and the EC50 was 12.8 nM. The maximum contraction amplitude with isoproterenol did not differ significantly between rat and rabbit, between cells prepared by perfusion and those made from chunks, or when determined from non-cumulative rather than cumulative curves. The EC50 for isoproterenol in rat cells made by the perfusion method (cumulative curves) was 3.81 nM, significantly lower than in rabbit. The maximum amplitude obtained with increasing concentrations of calcium was not significantly different from that with isoproterenol under any condition. The EC50 for calcium averaged 2.78 mM in rat cells made by the perfusion method (cumulative curves) and was significantly greater than that in rabbit (1.4 mM). Maximum rates of contraction for rat cells averaged 4.59 micron/s in 8 mM calcium. Rat cells contracted faster than they relaxed, whereas rabbit cells in 8 mM calcium relaxed faster than they contracted. Rat cells, maximally activated by either calcium or isoproterenol, contracted significantly faster than rabbit. There was no difference in rates of contraction (or relaxation) between rat cells prepared by perfusion and those made from chunks of tissue.

Animals↗
PubMed1988

AIDS--legal issues.

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Acquired Immunodeficiency Syndrome↗
PubMed1988

Spontaneous expression of the interleukin 2 receptor gene and presence of functional interleukin 2 receptors on T lymphocytes in the blood of individuals with active pulmonary sarcoidosis.

Current concepts of the pathogenesis of sarcoidosis suggest that the expanded numbers of activated T-helper/inducer cells at sites of disease activity result, at least in part, from their proliferation in the local milieu. Normal clonal proliferation of T cells involves activation and expression of the IL 2 receptor (IL 2R) gene. Thus, knowing that IL 2R mRNA transcripts are relatively long lived, we hypothesized that sarcoid blood T cells may contain IL 2R mRNA transcripts and express functional surface IL 2R, although the cells are probably activated elsewhere. Northern analysis using a 32P-labeled cDNA probe for the IL 2R p55 protein demonstrated that blood T cells of patients with active sarcoidosis, but not of normal patients, express 3.5- and 1.5-kb IL 2R mRNA transcripts, the same as those observed in normal T cells activated in vitro. Consistent with this, using flow cytometry and an MAb directed against the IL 2R p55 protein (2A3), we observed detectable levels of IL 2R surface protein on increased numbers of blood T cells of active sarcoidosis patients (4.7 +/- 0.9%) compared with blood T cells of normal patients (0.9 +/- 0.2%). Importantly, when the sarcoid blood T cells were exposed to IL 2 in vitro, they proliferated at a rate greater than that of normal blood T cells under the same conditions, suggesting that the IL 2R spontaneously expressed by sarcoid blood T cells were functionally active. In the context of the known compartmentalization of spontaneous IL 2 production and T cell proliferation at sites of disease in active pulmonary sarcoidosis, these IL 2R positive blood T cells would probably have a proliferative advantage if they trafficked to sites of active sarcoidosis, such as the lower respiratory tract.

Adult↗
PubMed1988

Bias toward use of a specific T cell receptor beta-chain variable region in a subgroup of individuals with sarcoidosis.

To evaluate the concept that biases in the usage of T cell antigen receptor beta variable (V) regions may be manifested in T lymphocytes that accumulate in nonmalignant, T cell-mediated human disorders, a V beta 8-specific antibody (anti-Ti3A, 5REX9H5) was used to evaluate lung and blood T cells in pulmonary sarcoidosis, a chronic granulomatous disorder of unknown etiology. Whereas normal patients had less than 5% Ti3A+ lung (n = 7) and/or blood (n = 9) lymphocytes, strikingly, a subgroup (8 of 21) with active pulmonary sarcoidosis had greater than 7% Ti3A+ lung and/or blood T cells and a higher proportion of Ti3A+ lymphocytes in the lung compared with blood. Dual-color flow cytometry demonstrated compartmentalization of Ti3A+ CD4+ lymphocytes to lung and Ti3A+ CD8+ lymphocytes to blood. Analysis with a 32P-labeled V beta 8 probe revealed that sarcoid lung T lymphocytes contained higher amounts of V beta 8+ mRNA than autologous blood T cells. However, Southern analysis of sarcoid lung and blood T cell DNA demonstrated no evidence of clonal rearrangements of V beta 8 genes. These observations demonstrate a clear bias toward the use of at least one V beta region in sarcoidosis, and suggests T cells accumulate secondary to external selective pressure, rather than in a random polyclonal fashion or by clonal expansion of one or few T cell clones.

Antibodies, Monoclonal↗
PubMed1988

MEDLINE on CD-ROM: end user searching in a medical school library.

End users at the Medical College of Pennsylvania enjoyed searching CD-ROM versions of MEDLINE and judged such searches "extremely useful." To assess the effectiveness of their searches, a sample of 500 search statements from Compact Cambridge (CC) MEDLINE was examined. A high proportion of search statements (224, or 45 percent) retrieved no documents. Over one-third of search statements (185, or 37 percent) contained at least one error, which usually resulted in zero retrieval for that search statement. Searchers attempting to enter Medical Subject Headings were frequently defeated by the elaborate punctuation requirement of CC MEDLINE. "Missed opportunities" were evident in over three-fourths of search statements. One-on-one instruction and library classes may increase search success, but these measures reach a limited audience. Improvement in the search software itself is needed to help searchers improve the effectiveness of their searches.

Computer Literacy↗
PubMed1988

The new AIDS virus--ineffective and unjust laws.

Public alarm about the spread of AIDS leads to public demand for drastic laws to contain the epidemic and to punish those who spread it. In this paper, attention is drawn to the limitations of the law in achieving the modification of human behavior. Successes and failures in public health education campaigns, directed to the same end, are mentioned. The author cautions against putting too much trust in the law to achieve containment of the AIDS virus. However, there are three reasons for optimism about the developing laws on AIDS. These are the necessity of a rare degree of international cooperation, the encouragement of attention to fresh approaches to laws on human sexuality and drug taking, and the vital importance of attention to the neglected issues of efficiency and cost effectiveness in the design of new laws. This last point leads to a suggestion that AIDS has produced three new viruses called "HIL" (highly inefficient laws). HIL-I is the mandatory testing of the entire population for HIV antibodies. HIL-II is the mandatory testing of specially vulnerable groups, especially foreigners. HIL-III is the mandatory requirement of HIV-free certificates at the frontier. The ineffectiveness and potential for injustice of such laws are exposed. The lesson derived is that there is no "quick fix" either for the AIDS virus itself or for the social and legal problems presented by it.

AIDS Serodiagnosis↗
PubMed1987

Low-dimensional procedure for the characterization of human faces.

A method is presented for the representation of (pictures of) faces. Within a specified framework the representation is ideal. This results in the characterization of a face, to within an error bound, by a relatively low-dimensional vector. The method is illustrated in detail by the use of an ensemble of pictures taken for this purpose.

Face↗
PubMed1985

Post-traumatic stress disorder after car accidents.

Survivors of car crashes often suffer from a post-traumatic fear of driving, generalized anxiety and depression. Unremitting pains are also common. As part of a pilot study 30 referred subjects were exposed to imagery of driving and accidents. Seventy-seven percent were phobic of driving. Fifty-three percent responded with increased anxiety to the imagery. Twelve treatment referrals received exposure therapy and six improved markedly. An additional four improved when a Benzodiazepine was added temporarily. Four out of eight subjects lost their unremitting pains along with their fears. When guided imagery evoked intense anxiety this seemed to predict a favourable outcome. A resumption of pleasure trips was a reliable criterion of recovery. The frequency of phobic symptomatology and it's importance to the understanding and management of post-traumatic anxiety states is discussed.

Accidents, Traffic↗
PubMed1984

Adrenergic innervation of the developing chick heart: neural crest ablations to produce sympathetically aneural hearts.

Ablation of various regions of premigratory trunk neural crest which gives rise to the sympathetic trunks was used to remove sympathetic cardiac innervation. Neuronal uptake of [3H]-norepinephrine was used as an index of neuronal development in the chick atrium. Following ablation of neural crest over somites 10-15 or 15-20, uptake was significantly decreased in the atrium at 16 and 17 days of development. Ablation of neural crest over somites 5-10 and 20-25 caused no decrease in [3H]-norepinephrine uptake. Removal of neural crest over somites 5-25 or 10-20 caused approximately equal depletions of [3H]-norepinephrine uptake in the atrium. Cardiac norepinephrine concentration was significantly depressed following ablation of neural crest over somites 5-25 but not over somites 10-20. Light-microscopic and histofluorescent preparations confirmed the absence of sympathetic trunks in the region of the normal origin of the sympathetic cardiac nerves following neural crest ablation over somites 10-20. The neural tube and dorsal root ganglia were damaged in the area of the neural-crest ablation; however, all of these structures were normal cranial and caudal to the lesioned area. Development of most of the embryos as well as the morphology of all of the hearts was normal following the lesion. These results indicate that it is possible to produce sympathetically aneural hearts by neural-crest ablation; however, sympathetic cardiac nerves account for an insignificant amount of cardiac norepinephrine. The adrenal medulla is the most likely source of cardiac norepinephrine in sympathetically aneural hearts.

Animals↗
PubMed1983

Detection of leptospires in tissue using an immunoperoxidase staining procedure.

An immunoperoxidase technique for the localisation of leptospires in sections of formalin fixed paraffin embedded kidney tissue is described. The procedure utilises a two-layered antibody sandwich with rabbit anti-leptospiral immunoglobin. Using antiserum to specific leptospiral serovars the presence and distribution of specific serovar in the tissue could be determined. The technique was also used to detect leptospires of given serovars in smears made from infected tissues and fluids. There was good correlation between culture results and results of the immunoperoxidase staining method on kidneys infected with leptospires. The diagnostic possibilities of the technique on formalin fixed tissue specimens are discussed.

Animals↗