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Biomedical subjects

J M Forrester

Publications and source records attributed to J M Forrester.

8 recordsLinked to original sources

Preferential T-cell receptor beta-chain variable gene use in myelin basic protein-reactive T-cell clones from patients with multiple sclerosis.

Multiple sclerosis is an autoimmune disease in which T lymphocytes reactive to myelin basic protein (BP) could play a central role. T cells specific for BP were cloned from the blood of multiple sclerosis patients and normal individuals, and expression of T-cell receptor variable region genes was analyzed. A remarkable bias for use of beta-chain variable region (V beta) 5.2 and, to a lesser extent, V beta 6.1 was seen among BP-specific clones from patients but not from controls. The preferential use of V beta 5.2 for BP recognition did not reflect altered expression of this V beta in the peripheral repertoire. Interestingly, shared V beta 5.2 usage was apparent for clones specific for different BP determinants, even when derived from the same individual. The concurrent demonstration by others (J. R. Oksenberg, M. A. Panzara, A. B. Begovich, H. Erlich, R. Murray, M. Sherritt, S. Stuart, C. C. Bernard, and L. Steinman, personal communication) that T cells within demyelinating areas of multiple sclerosis brains preferentially express V beta 5.2 and V beta 6.1 suggests that the BP-specific clones derived from blood may be relevant to disease pathogenesis. These findings may have important implications for the treatment of multiple sclerosis.

Base Sequence

Crack lung: an acute pulmonary syndrome with a spectrum of clinical and histopathologic findings.

In this report, we review the hospital course of four patients who presented with an acute pulmonary syndrome after inhaling freebase cocaine and compare them with previously described case reports. Two patients had prolonged inflammatory pulmonary injury associated with fever, hypoxemia, hemoptysis, respiratory failure, and diffuse alveolar infiltrates. Lung tissue specimens from both patients revealed diffuse alveolar damage, alveolar hemorrhage, and interstitial and intraalveolar inflammatory cell infiltration notable for the prominence of eosinophils. Immunofluorescent staining performed on one of the biopsy specimens showed a striking deposition of IgE in both lymphocytes and alveolar macrophages. Both patients were treated with systemic corticosteroids and rapidly improved. In contrast, two patients presented acutely with diffuse pulmonary alveolar infiltrates associated with dyspnea and hypoxemia, but without fever, and within 36 h of discontinuing cocaine their pulmonary infiltrates and symptoms had spontaneously resolved. Our report further supports the finding that an acute pulmonary syndrome can occur after inhalation of freebase cocaine. Furthermore, the lung injury may respond to systemic corticosteroid therapy when it is associated with a prominent inflammatory cell infiltration.

Acute Disease

Altered norepinephrine metabolism in Shapiro's syndrome.

We studied a 66-year-old woman with spontaneous periodic hypothermia (Shapiro's syndrome) to determine the mechanisms that result in increased plasma norepinephrine (NE) levels. In comparison with age-matched control subjects, compartmental analysis of NE kinetics revealed an increased NE release rate into the extravascular compartment and decreases in NE clearance and volume of distribution of NE in the intravascular compartment. Clonidine therapy was associated with an initial dramatic decrease in the frequency of diaphoretic episodes as well as with a fall in NE release rate and increases in NE clearance and volume of distribution. We conclude that increased NE release and decreased plasma NE clearance result in elevated plasma NE levels in Shapiro's syndrome. Clonidine, which was associated with changes in NE kinetics, may provide effective treatment for this disorder.

Aged

Consequences of partial and subtotal colectomy in the rat.

Rats were subjects to right hemicolectomy (including removal of the caecum), left hemicolectomy or subtotal colectomy. Body weight resumed and maintained a rate of increase very similar to that in control rats. After hemicolectomy, food intake showed no change. Faecal weight increased by about one-third after right hemicolectomy, but did not increase after left hemicolectomy. After right hemicolectomy, the remaining--that is, downstream--portion of the colon showed increase in weight, and so did the (upstream) small intestine, in which the increase involved all three-thirds of its length and was predominantly mucosal. No such changes in the remaining colon or in small intestine were found after left hemicolectomy. After subtotal hemicolectomy, rats ate 30-40% more food than control rats, and faecal weight increased 60% at three months after operation. Study of energy intake and output indicated diminished absorption. All three-thirds of the small intestine showed increase in weight, predominantly mucosal in the upper two-thirds and predominantly seromuscular in the lowest third; villi were taller at all levels. Evidence suggests that the increase in food intake is not due to cessation of coprophagy, and that the small intestine changes are not due solely to increased food intake and occur when the colon is bypassed but not removed.

Animals