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Biomedical subjects

B W Robinson

Publications and source records attributed to B W Robinson.

At least 109 records · Page 6Linked to original sources

Enhanced alveolar macrophage-mediated antigen-induced T-lymphocyte proliferation in sarcoidosis.

Expansion of T-lymphocyte numbers is a characteristic feature of the alveolitis of pulmonary sarcoidosis. One mechanism that may influence the numbers of T-lymphocytes in the lung is the process of antigen presentation in which alveolar macrophages, in the presence of antigen, induce T-lymphocytes to replicate. To evaluate this process in sarcoidosis, alveolar macrophages were obtained by bronchoalveolar lavage, pulsed with tetanus toxoid, and co-cultured with purified autologous T cells. Strikingly, antigen-pulsed alveolar macrophages from sarcoid patients induced more than a twofold increase in autologous T-lymphocyte proliferation compared with the response seen using cells from normal or patients with idiopathic pulmonary fibrosis (P less than 0.001), all comparisons). In contrast, when monocytes were used as the antigen presenting cell, no significant differences were observed in T cell proliferation induced by antigen among the three groups. The enhanced T-lymphocyte proliferation induced by sarcoid alveolar macrophages was not dependent on the compartment from which the T cells were derived, and was independent of the specific antigen used. One possible explanation for augmented antigen presentation seen in sarcoid is that an increased percentage of sarcoid alveolar macrophages express HLA-DR or HLA-DS surface antigens. However, most normal and sarcoid alveolar macrophages express HLA-DR and HLA-DS surface antigens, and the percentage of macrophages expressing these antigens was not significantly different in the two groups. Thus, while the mechanisms of the enhanced antigen presentation in the sarcoid lung are unknown, the process of antigen-driven, alveolar macrophage-modulated lung T cell proliferation may explain, at least in part, the expansion of lung T-lymphocyte numbers that characterizes this disease.

Adolescent↗

Gamma interferon is spontaneously released by alveolar macrophages and lung T lymphocytes in patients with pulmonary sarcoidosis.

Gamma interferon (IFN gamma) is a potent immune mediator that plays a central role in enhancing cellular immune processes. This study demonstrates that while lung mononuclear cells from normal individuals spontaneously release little or no interferon (less than 10 U/10(6) cells per 24 h), those from patients with pulmonary sarcoidosis spontaneously release considerable amounts (65 +/- 20 U/10(6) cells per 24 h, P less than 0.02 compared to normals). Furthermore, cells from patients with active disease release far more interferon than those from patients with inactive disease (101 +/- 36 compared to 24 +/- 8 U/10(6) cells per 24 h, P less than 0.02). Characterization of this interferon using acid sensitivity, specific antibody inhibition, and target cell specificity criteria demonstrated that it was almost entirely IFN gamma. This spontaneous release of IFN gamma appeared to be compartmentalized to the lung of these patients in that their blood mononuclear cells spontaneously released little or no IFN gamma (P less than 0.02, compared to sarcoidosis lung mononuclear cells) and no IFN gamma was detected in their serum. Both lung T lymphocytes and alveolar macrophages contributed to the spontaneous release of IFN gamma by lung mononuclear cells from sarcoid patients; purified preparations of T lymphocytes and alveolar macrophages from these patients spontaneously released similar amounts of IFN gamma (56 +/- 21 and 32 +/- 11 U/10(6) cells per 24 h, respectively, P greater than 0.3). At least one role for IFN gamma in the pathogenesis of sarcoidosis appeared to be related to activation of alveolar macrophages, as alveolar macrophages recovered from patients with active disease spontaneously killed [3H]uridine-labeled tumor cell targets (17.7 +/- 4.5% cytotoxicity compared with 2.8 +/- 0.9% in normals, P less than 0.02) and purified IFN gamma enhanced the ability of alveolar macrophages from sarcoidosis patients with inactive disease to kill similar targets (P less than 0.001, compared to alveolar macrophages cultured in medium alone). Treatment of sarcoid patients with corticosteroids, a therapy known to suppress the activity of the disease, caused a marked reduction in the level of spontaneous IFN gamma release by lung mononuclear cells compared with untreated patients (P less than 0.02), which suggests that the effectiveness of corticosteroid therapy in controlling active pulmonary sarcoidosis may, at least in part, be due to suppression of IFN gamma release.

Adrenal Cortex Hormones↗

Natural killer cells are present in the normal human lung but are functionally impotent.

The lung is affected by disorders in which natural killer (NK) cells are thought to play an important defensive role. This study, however, demonstrated that normal lung lymphocytes actually express very little NK cell activity (P less than 0.001 compared with blood lymphocytes). This was true independent of the NK-sensitive target used (K562, U937, MOLT-3, or Daudi). This lack of lung lymphocyte NK activity occurred even though the proportions of lymphocytes in the normal lower respiratory tract with the morphology (large granular lymphocytes) and surface antigen markers of NK cells were similar to that of blood (P greater than 0.5). Although normal lung lymphocytes bound to known NK-sensitive targets, they did not lyse these cells (P less than 0.001 compared with blood), which suggested that the lack of lung NK cell activity resulted from a relative inability of lung NK cells to destroy their targets. While the mechanisms of this functional impotence of lung NK cells are not clear, normal human alveolar macrophages and lower respiratory tract epithelial lining fluid exerted a profound suppressive effect on blood NK cell activity (P less than 0.001 for both) by inhibiting their ability to lyse target cells after binding (P less than 0.001). Though impotent initially, when incubated for 24 h in medium alone, normal lung lymphocytes demonstrated markedly enhanced NK activity (P less than 0.02), which suggested that lung NK cells do have the potential to express NK activity. Interleukin-2 (IL-2) further augmented this effect (P less than 0.05), but gamma interferon did not (P greater than 0.2). Consistent with this observation, lung lymphocytes from patients with active sarcoidosis, a disease in which lung lymphocytes are spontaneously releasing IL-2, did express NK cell activity (P less than 0.01). These studies suggest that although NK cells are present in the normal lung, they are functionally inactive, due, at least in part, to local inhibitory influences. In the presence of IL-2, however, lung NK cell activity is expressed, which suggests that lung NK cell activity can be modulated.

Adult↗

Nitrofurantoin-induced interstitial pulmonary fibrosis. Presentation and outcome.

Four cases of interstitial pulmonary fibrosis associated with nitrofurantoin therapy are analysed along with 45 other reported cases of this disease in order to review the presenting features and outcome and to determine the role of steroid therapy. Most patients were elderly (mean age, 66 years); women were more commonly affected (71%). All patients had been treated with nitrofurantoin for longer than six months (mean, 31 months). The usual presenting symptoms were dyspnoea and non-productive cough which had been present for periods for two weeks to six years (mean, 9.4 months). After cessation of nitrofurantoin therapy, the condition of 32 patients improved. In seven patients the symptoms remained unchanged. In one case, progressive deterioration of the condition ensued. There was no difference in outcome between patients who were treated with steroids and those who were not. Steroid therapy is probably not indicated in mild cases.

Aged↗

Benign asbestos pleural effusion: diagnosis and course.

We have reviewed 22 patients with benign asbestos pleural effusion seen over a 17-year period. The mean duration of exposure to asbestos was 5.5 years and the mean interval between exposure and presentation was 16.3 years. In five the effusion was asymptomatic. Fever was uncommon but in 15 of 21 patients the ESR was elevated. Leucocytosis was noted in seven of 20 patients. Autoantibodies were rarely detected. The pleural fluid was usually blood-stained and the volume aspirated was rarely larger than 500 ml. Pleural biopsies revealed established pleural fibrosis and/or inflammatory infiltration with fibrinous exudate and mesothelial and fibroblastic proliferation. A positive mantoux test was noted in eight of 12 patients but there was no other evidence of tuberculosis. The mean duration to spontaneous resolution of the effusion was 4.3 months. During a follow-up period of 28.1 years from initial exposure to asbestos (mean 22.8 years) and up to 17.2 years from initial presentation with a pleural effusion (mean 6.3 years) seven patients had a single recurrence and only one patient had multiple pleural effusions. Only three patients experienced persistent pleural pain. It was not possible to predict the likelihood of recurrence of an effusion or the persistence of pleural pain from the data at presentation. No patient subsequently developed mesothelioma or other neoplasm.

Asbestos↗

Separation in Canada: new insights concerning marital dissolution.

"Interfaced between marriage and divorce lies an intermediate stage of separation which involves the emotional, physical, and sometimes legal termination of a marriage at some point in time. Examination of special cross-tabulations from the 1976 Census of Canada indicates that the proportion of the population separated is equal to or exceeds the proportion divorced in every five-year age category commencing at age fifteen. The difference between the levels of separation and divorce is most noticeable for the younger and older age ranges. Further differences are [evident] by sex and across provinces. Findings suggest that a reliance upon divorce statistics alone will lead to an underestimate of the magnitude of marital dissolution in Canada." (summary in FRE)

Age Factors↗

Intra-uterine healing of fetal rat cheek wounds.

Cheek wounds, involving skin, mucosa, and muscle, were surgically created in utero on Sprague Dawley rat fetuses at 19 1/2 days gestation. Fifty fetuses were used in the study. Twenty-five fetuses were in the experimental group and 25 in the control. Five fetuses in each group were sacrificed at 0, 6, 12, 18 and 24 hours post-operatively. Serial histological sections in the coronal plane were stained with haematoxylin and eosin. Restoration of continuity and primary epithelialisation of the oral mucosal and skin surfaces of the wound was observed to occur within 24 hours. The continuity of the muscle layer was not restored, but some mitoses were seen in the myeloblasts. There was a complete absence of acute inflammatory cells, and there was no scab formation. Healing occurred without scarring. These findings are discussed in comparison to previous findings on orofacial fetal wound healing (Goss 1976) and in regard to future prospects in intraceptive fetal surgery for the correction of deformities, in particular cleft lip.

Animals↗

Arachnoid cysts of the middle cranial fossa: surgical considerations.

Three cases of arachnoid cysts of the middle cranial fossa are presented. CT imaging before and after peritoneal shunting of these cysts demonstrates the therapeutic value of this cerebrospinal fluid diversionary procedure. Many important facets of this disease such as cyst genesis, histology, natural history and other forms of therapy as reported by various authors in the recent literature are discussed.

Arachnoid↗

The YY syndrome.

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Adolescent↗