Relationship between numbers of beta adrenergic receptors in lymphocytes and disease severity in asthma

In order to assess the status of beta adrenergic receptors in bronchial asthma, binding studies using (−) [³H] dihydroalprenolol (DHA) were performed on lymphocytes of 10 control subjects and 11 stable asthmatic patients. Specific DHA binding was generally lower at all DHA concentrations in asthmatics. At 12 nM DHA concentration, specific DHA binding was 391 ± 40 fM/mg protein in controls and 263 ± 35 fM/mg protein for asthmatic subjects (p < 0.05). A highly statistically significant positive correlation between specific DHA binding (at 12 nM DHA) and FEV₁/FVC% was observed (r = 0.93, p < 0.01), with those asthmatic subjects with the more severe airway obstruction and disease severity showing lower DHA binding. The results of the study suggest that a lymphocyte beta adrenergic receptor defect may be present among some patients with asthma. The magnitude of the receptor abnormality appears to be related to disease severity and degree of airway obstruction as measured by FEV₁/FVC%. Documentation of drug consumption was made, and restriction of beta adrenergic agonists was attempted; theophylline and corticosteroids were the predominant drugs used in the study. Even with these precautions, it is possible that the differences in DHA binding observed among subjects are the results of greater drug (e.g., theophylline and corticosteroids) consumption by the clinically more severe patients. On the other hand, the lymphocyte receptor alteration noted may reflect a more general beta adrenergic receptor abnormality in bronchial asthma.     

IL-4–BATF signaling directly modulates IL-9 producing mucosal mast cell (MMC9) function in experimental food allergy

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The biopsychosocial approach: Clinical examples from a consultation-liaison service

In this second of three articles exploring Engel's biopsychosocial model, five case histories illustrate how psychological factors, sometimes related to organic trauma or illness, may precipitate psychiatric conditions. The patients’ disorders, and their management by a consultation-liaison team, demonstrate the interaction of biologic, psychological, and social systems in assessment and treatment of disease.     

A comparison of digital subtraction angiography and noninvasive testing in the diagnosis of cerebrovascular disease

Among the 1,892 patients who underwent cerebrovascular digital subtraction angiography at our hospital over the past 18 months, there was a subgroup of 34 patients (65 carotid arteries) for whom noninvasive cerebrovascular test results and standard cerebral arteriograms were also available. These patients were reviewed retrospectively and the ability of both methods to detect hemodynamically significant lesions, defined as a greater than 50 percent reduction in the diameter of the carotid artery, was determined using the arteriograms as the "gold standard." Noninvasive cerebrovascular tests had a sensitivity of 81 percent, a specificity of 95 percent, a positive predictive value of 92 percent, a negative prediction value of 88 percent, and an overall accuracy of 89 percent. Digital subtraction angiography had a sensitivity of 84 percent, a specificity of 92 percent, a positive predictive value of 88 percent, a negative predictive value of 89 percent, and an overall accuracy of 89 percent. If the four cases of hemodynamically significant stenosis of the carotid siphon not detected by digital subtraction angiography had been considered as false-negatives, its sensitivity would have been reduced to 72 percent. In patients with hemispheric cerebral ischemia, we found noninvasive cerebrovascular tests neither necessary nor cost-effective. Digital subtraction angiography, on the other hand, often provided definitive diagnostic information in such patients if the intracranial circulation was well defined and the extracranial lesion corresponded to the patients' symptoms. Noninvasive cerebrovascular testing was the safest and most cost-effective technique for screening patients with asymptomatic bruits, atypical, nonhemispheric cerebral symptoms, and those who have undergone carotid endarterectomy. If the noninvasive cerebrovascular test result was positive or equivocal, digital subtraction angiography was performed to localize the responsible lesion and exclude carotid occlusion.     

Release of vasoactive intestinal peptide in the central nervous system in man.

Recent work has shown that vasoactive intestinal peptide (VIP), one of the many candidate hormones of the gut, also occurs widely in neurones. To determine whether the neuronal peptide may have a neurotransmitter function, we studied changes in immunoreactive VIP in dog plasma and human cerebrospinal fluid after the infusion of choline esterase inhibitors (neostigmine and physostigmine, respectively). Immunoreactive VIP was released in both situations. The systemic changes (in VIP levels) were enhanced five weeks after portacaval shunting in dogs. Our results demonstrate that the immunoreactive VIP level increases as a result of choline esterase inhibitors. The plasma "release" may originate either from peripheral peptidinergic nerve terminals or from APUD cells of the gastroenteropancreatic system. The increase in immunoreactive cerebrospinal fluid VIP may very well originate from central neurons, since the peptide does not apparently cross the blood-brain barrier.     

Modulation of hepatic protein kinase activity by indomethacin

We previously demonstrated that treatment with indomethacin in vivo significantly blunted the glucagon-induced glycemic response in the rat. This prostaglandin synthetase (cyclo-oxygenase) inhibitor also accentuated the evanescent effect of glucagon on hepatic glucose output in the intact, anesthetized rat. In this report, we present evidence that impairment of glucagon action in the rat liver by indomethacin is mediated through its inhibitory effect on both cAMP-dependent and cAMP-independent hepatic protein kinase. Indomethacin treatment did not have a measurable effect on any of the other components of the glucagon transducer system. Furthermore, infusion with glucagon for two hours that maintained plasma glucagon values at high physiological levels significantly reduced hepatic cAMP-dependent protein kinase activity without altering its Km. Glucagon infusion also down-regulated its own hepatic receptors and glucagon-stimulated cAMP production; prostaglandin E1-stimulated cAMP production was not affected. We concluded that prostaglandins may play a role in the regulation of hepatic protein kinases involved in the glucagon-stimulated glycogenolytic response and that glucagon-induced down-regulation extends at least to the hepatic protein kinases. However, a direct effect of indomethacin or protein kinase and the adenylate cyclase complex cannot be ruled out.     

Severe depression of high-density lipoprotein cholesterol levels in weight lifters and body builders by self-administered exogenous testosterone and anabolic-androgenic steroids

The effects of nonphysician prescribed, self-obtained, self-administered exogenous anabolic-androgenic steroids and testosterone on plasma total, high- and low-density lipoprotein cholesterol (HDLC, LDLC), and triglycerides were evaluated in 14 adult white men, 11 body builders and 3 power weight lifters. Lipids and lipoprotein cholesterols were quantified during active physical conditioning, both on (for at least 1 month, mean +/- SD 1.8 months) and off (for at least 4 months, 7.3 +/- 2.7 months) self-administered exogenous androgenic steroids. The subjects took 50 to 100 mg methandrostenolone daily plus weekly injections of testosterone 100 to 200 mg and nandrolone decanoate 100 to 200 mg per week. Mean (SD) HDLC on exogenous androgenic steroids, 29 +/- 8 mg/dL, was severely depressed, and was less than 50% of the consistently elevated mean HDLC when exogenous steroids were not used (61 +/- 14 mg/dL, P less than .01 for paired differences). During anabolic steroid use, HDLC was less than or equal to the age- race- and sex-specific 10th percentile in 11 of the 14 men, whereas while off anabolic steroids, HDLC was greater than or equal to the 90th percentile in 7 of the 13 men, and in the top quartile for 3 of the remaining 6 men. Mean LDLC was higher on androgenic steroids (150 +/- 44) than off (125 +/- 38 mg/dL), P less than .05 for paired differences. The ratio of LDLC/HDLC during exogenous steroid use (6.0 +/- 3.7) was nearly triple the ratio obtained when steroids were not taken (2.2 +/- 1.0), P less than .01 for paired differences.(ABSTRACT TRUNCATED AT 250 WORDS)