Publications

Parasympathetic nerves play an important role in modulating smooth muscle tone and mucus secretion in the airways. This modulation can occur through a variety of afferent inputs, from the central nervous system, at parasympathetic ganglia, and on post-ganglionic efferent fibres themselves. Abnormalities at any of these sites could, and in some patients probably do, contribute to the abnormalities in smooth muscle contraction and mucus secretion that characterize a number of airway diseases, including asthma. Because these pathways play little or no role in the exaggerated bronchoconstrictor responses in many patients, however, an abnormality of the parasympathetic pathway cannot be the sole explanation for abnormal airway hyperresponsiveness.

Administration of the porphyrinogenic agent DDEP to PB-pretreated rats results in acute hepatic heme depletion, which is a characteristic of acute hepatic porphyria. Such acute heme depletion is associated with impaired hepatic tryptophan degradation and enhanced serotonergic tone in the CNS. We showed that intestinal motility in these rats is also significantly decreased, indicating that the serotonergic tone of the enteric nervous system may also be enhanced. In addition, the marked hepatic accumulation of glucogenic precursors, observed in parallel, indicates that the elevated tryptophan levels may also block hepatic glucogenesis. The clinical implications of these findings to acute heme-deficient states, such as the acute hepatic porphyrias, was discussed.

Cerebrospinal fluid (CSF) and serum concentrations of albumin and immunoglobulin G (IgG) were measured in 31 patients with presumptive Alzheimer's disease (AD) and in 14 healthy control subjects. The albumin and IgG quotients, and IgG index were calculated to evaluate the permeability of the blood-brain barrier and the intrathecal production of immunoglobulins. X-ray computerized tomography (CT) of the head was performed to investigate the relation between cerebral atrophy and CSF protein concentrations. The albumin and IgG quotients, and the IgG index did not differ significantly between the AD and control groups. Cerebral atrophy, as measured by CSF volume, was not related to CSF protein concentrations in either group. The results do not support the hypothesized roles of blood-brain barrier disruption or of immunologically-mediated injury of the central nervous system in the pathogenesis of AD.

cDNAs for human interleukin-2 receptor were recently cloned and sequenced (Leonard et al., 1984, Nature 311, 626-631; Nikaido et al., 1984, Nature 311, 631-635; Cosman et al., Nature 312, 768-771). In the studies reported here, we describe the expression of a cDNA clone for the human interleukin-2 receptor in E. coli using an "open reading frame" expression vector pMR100. The inserted cDNA was expressed in E. coli transformants as a tripartite fusion polypeptide fused to the lambda cI protein at its amino terminus and to beta-galactosidase at its carboxy terminus. We demonstrate that the bacterially produced IL-2 receptor protein can bind to IL-2.