Interleukin-12 suppresses filaria-induced pulmonary eosinophilia, deposition of major basic protein and airway hyperresponsiveness

Tropical Pulmonary Eosinophilia (TPE) is a severe form of allergic asthma caused by the host inflammatory response to filarial helminths in the lung microvasculature, and is characterized by pulmonary eosinophilia, increased filarial-specific IgG and IgE antibodies, and airway hyperresponsiveness. The current study examined the effect of IL-12 on pulmonary eosinophilia, deposition of eosinophil major basic protein and airway hyperresponsiveness in mice inoculated i.v. with Brugia malayi microfilariae. Injection of recombinant murine IL-12 modulated the T helper (Th) response in the lungs from Th2- to Th1-like, with elevated IFN-γ, and decreased IL-4 and IL-5 production. Consistent with this shift in cytokine response, antigen-specific IgG2a was elevated, and IgG1 and total serum IgE were decreased. In addition, eosinophils in BAL fluid from IL-12 treated mice were reduced from 56% to 11%, and there was no detectable MBP on respiratory epithelial cells. Importantly, IL-12 suppressed airway hyperresponsiveness compared with saline-injected control animals. Taken together, these data clearly demonstrate that by modulating Th associated cytokine production, IL-12 down-regulates filaria-induced lung immunopathology .     

The latent dimensionality of DIS/DSM-III-R nicotine dependence: exploratory analyses

Decisions on DSM-IV criteria for alcohol dependence were based in part on latent structure analyses of field survey data on alcohol problems. Analogously, to investigate the latent structure of nicotine dependence in an epidemiological sample, we carried out a dichotomous item factor analysis of DSM-III-R symptom data gathered from 394 young adults who reported a history of sustained daily smoking. Smokers and their dependence symptoms were identified by means of the NIMH Diagnostic Interview Schedule version III revised, administered to a random sample of 1007 21–30-year-olds who were members of a health maintenance organization in the Detroit area. Comparing different latent structure models using LISCOMP software with bootstrap re-sampling, followed by multiple logistic regression, vie found that a two-factor model indicating a ‘general dependence’ and a ‘failed cessation’ dimension best accounted for the observed data. Current smoking status (persistent vs. past smoking) was associated with the two factors independently. Replication and additional research on construct, discriminant and convergent validity are needed.     

The Atrial Electrogram During Clinical Electrophysiologic Studies: Onset versus the Local/Intrinsic Deflection

The Local Atrial Deflection. Introduction : As a wave front passes unfiltered bipolar recording electrodes, the point of local depolarization is marked by a maximal change in voltage, i.e., the intrinsic deflection. However, during electrophysiologic studies, the depolarization (A) on the lead recording the His-bundle potential traditionally has been measured at the first rapid reproducible deflection on a filtered electrogram. This methodology permits considerable latitude for subjective interpretation. The purpose of this study was to assess the timing of the atrial electrogram using the intrinsic deflection of relatively unfiltered electrograms (0.1-4.0 to 1,250 Hz) or the equivalent on filtered recordings. Methods and Results : To do this we studied 70 patients without evidence of atrial or atrioventricular (AV) nodal disease, documenting the difference in timing between the A wave as traditionally measured and as measured at its peak local deflection (A_L) determined from simultaneously recorded filtered and relatively unfiltered electrograms. New ranges based on the A_L were established for timing of intra-atrial and AV nodal conduction intervals. The P-A (41 ± 11 msec) was significantly shorter than the P-A_L (55 ± 12) and the A-H (80 ± 20) was longer than the A_L-H (66 ± 21 msec), both P <0.001. Interobserver differences in measurements were smaller when using the local (A_L) rather than traditional criteria. Conclusions : Conventional measurement of the A deflection provides only a rough estimate of local depolarization of the atrium near the AV node. The criteria proposed in the present article may (1) provide a better estimate of the timing of local depolarization; (2) have application in computerized timing of intervals; and (3) decrease technical problems and subjective error.     

The Gay Bowel Syndrome

Our experience in the management of 260 male homosexuals with coloreetal problems is described. The increased incidence of amebiasis, shigellosis and hepatitis, specific and nonspecific protocolitides, venereal disease and anal warts, is emphasized. It is important to recognize homosexual patients and the conditions to which they are predisposed.     

The Influence of Hypoxemia and Cobalt on Erythropoietin Production in the Isolated Perfused Dog Kidney

Isolated dog kidneys were perfused with blood at normal and reducedoxygen tensions with and without cobalt. Erythropoietin titers were found to besignificantly increased in the blood perfusates from kidneys perfused withblood at lowered oxygen tensions, while no change in erythropoietin wasseen when kidneys were perfused with blood at a normal oxygen tension.Cobalt produced significant increases in erythropoietin levels in the perfusateswith normal as well as reduced oxygen tension blood, but its effect was moremarked when the kidneys were perfused with hypoxic blood. Renal blood flowswere higher when the dogs’ own lungs were used to oxygenate the bloodthan when a bubble oxygenator was used in the system. However, hypoxicblood resulted in significant increases in erythropoietin production in bothsystems. In studies of the kidney histology from both perfusion systems withhypoxic and normal oxygen tension blood, most of the kidneys demonstratedvarying degrees of glomerular congestion. No correlation was found betweenerythropoietin elaboration and renal congestion or other degenerative cellularchanges in the kidney. Therefore, it does not seem likely that erythropoietinproduced in the isolated perfused kidney is due to histologic damage to renalcells. These findings support the concept that increased erythropoietin production in the isolated perfused kidney in response to cobalt or hypoxic blood is adirect effect of these stimuli on the kidney.

Submitted on May 2, 1966 Accepted on July 21, 1966