Chymase inhibitor ameliorates eosinophilia in mice infected with Nippostrongylus brasiliensis

BACKGROUND: Chymase is a chymotrypsin-like serine protease primarily stored in mast cells. Infection with helminth parasites is known to increase the level of mast cell chymase in the jejunum and serum in mice. The aim of the present study is to elucidate the role of chymase in helminth infection. METHODS: Chymase inhibitor SUN-C8257 was administered to mice infected with the nematode Nippostrongylus brasiliensis, and the number of eosinophils in the blood, serum IgE levels and fecal egg counts were determined. RESULTS: Administration of SUN-C8257 significantly inhibited blood eosinophilia in BALB/c mice infected with N. brasiliensis. The effect of SUN-C8257 was specific for eosinophils, in that it affected neither the number of total leukocytes nor serum IgE levels. SUN-C8257 did not alter the fecal egg counts in this model, showing that SUN-C8257 has no effect on infectivity and expulsion of the nematode. N. brasiliensis infection induced eosinophilia in mast cell-deficient mice (W/W(v)) as well as their littermates (+/+), and SUN-C8257 inhibited the eosinophilia in +/+ mice but not in W/W(v) mice. These results suggest that the eosinophil number may be regulated by different mechanisms in W/W(v) and +/+ mice, and that the effect of SUN-C8257 on nematode-induced eosinophilia is probably due to chymase inhibition. CONCLUSIONS: Chymase released by activated mast cells may play a role in helminth-induced eosinophilia.     

A HhaI/BstUI polymorphism in a novel gene at human chromosome 11p15.5

We found a HhaI/BstUI polymorphism in the 3′ untranslated region of a novel gene which was localized to 11p15.5. This region is one of prominent imprinting domains and contains multiple imprinted genes, such as H19, IGF2 , KVLQT1, and p57 ^KIP2 , which suggests that regional factors might contribute to the imprinting. This polymorphism will be useful in the allelic analysis of expression and methylation of the novel gene. Received: July 24, 1998 / Accepted: July 29, 1998     

Comparative chromosome mapping of sex-linked genes and identification of sex chromosomal rearrangements in the Japanese wrinkled frog (Rana rugosa, Ranidae) with ZW and XY sex chromosome systems

There are regional variations of sex chromosome morphologies in the Japanese wrinkled frog, Rana rugosa (2n = 26): heterogametic ZZ/ZW-type and XX/XY-type sex chromosomes, and two different types of homomorphic sex chromosomes. To search for homology between the ZW and XY sex chromosomes and the chromosome rearrangements that have occurred during sex chromosomal differentiation in R. rugosa, we performed chromosome mapping of sexual differentiation genes for R. rugosa by FISH. Three genes, AR, SF-1/Ad4BP and Sox3, were localized to both the ZW and XY chromosomes, and their locations were all different between the Z and W and between the X and Y. AR and SF-1/Ad4BP were located on the short arms of the W and X and the long arms of Z and Y, and Sox3 was mapped to the different locations on the long arms between the Z and W and between the X and Y, probably as a result of multiple rearrangements that occurred during the process of sex chromosome differentiation. However, the chromosomal locations of three genes were almost consistent between the Z and Y and between the W and X, indicating that the Z and Y chromosomes and the W and X chromosomes were respectively derived from the same origins. Dmrt1, which is located on avian sex chromosomes, was localized to autosomes in R. rugosa with both the ZW and XY sex chromosomes, suggesting that Dmrt1 might not be related to sex determination in this species.     

Ocular tracking of moving targets: effects of perturbing the background

Primates are able to track a moving target with their eyes, even when the target is seen against a stationary textured background. In this situation, the tracking eye movement induces motion of the background images on the retina (reafference) that competes with the motion of the target's retinal image, potentially disrupting the tracking of the target. Previous work on humans reported that brief perturbations of the background in the opposite direction to pursuit were much less disruptive than perturbations in the same direction as pursuit. Furthermore, if the background moved together with the pursuit target--so as to effectively eliminate the reafference--then the effects of a subsequent background perturbation showed less dependence on direction. This suggested that the direction selectivity to background perturbations during pursuit against a stationary background was due, at least in part, to the prior motion of the background secondary to the pursuit. We now report similar findings in monkeys, and in addition, have investigated the effect of moving the background while the animal was fixating a stationary target. In this situation, the ocular tracking responses to subsequent brief perturbations of the moving background were weaker when the perturbations were in the same direction as the prior background motion than when in the opposite direction. This suggests that the selective insensitivity to the reafferent visual input associated with pursuit across a stationary background is, at least in part, independent of pursuit per se and attributable to a progressive reduction in the sensitivity to sustained background motion.     

Identity of the 3'-terminal sequences in ten genome segments of silkworm cytoplasmic polyhedrosis virus

The double-stranded RNA genome of cytoplasmic polyhedrosis virus consists of ten different segments. The RNA was oxidized and then reduced with [³H]sodium borohydride to label the ribose moieties of 3′-terminal nucleosides. The labeled genome segments were separated from each other by polyacrylamide gel electrophoresis, and their 3′-termini were analysed by alkaline digestion and column chromatography. It was concluded that all ten genome segments have the identical 3′-terminal structure, carrying cytosine in one RNA chain and uracil in another chain:

In the course of experiments, some radioactive non-nucleosidic materials were found to be associated with every ³H-labeled RNA segment. These materials were released from RNA by dilute alkaline solution, and not adsorbed on charcoal.     

Efficacy of radiofrequency catheter ablation in a patient with sinus node reentrant tachycardia

We performed electrophysiological study and catheter ablation on a 62-year-old patient with supraventricular tachycardia(SVT). This SVT was reproducibly initiated and terminated by atrial stimulation during the electrophysiological testing. The P-wave morphology and atrial activation sequence of intracardiac electrograms were identical to those in normal sinus rhythm. SVT was terminated with carotid sinus massage that increased vagal tone, and for this reason, the reentry circuit of SVT could be localized in sinus node. On the basis of these findings, the SVT was diagnosed as sinus node re-entrant tachycardia and was successfully eliminated by radiofrequency catheter ablation. Radiofrequency catheter ablation would be effective in patients with sinus node reentrant tachycardia refractory to anti-arrhythmic drugs. It should, however, be performed with careful consideration to the influence of the sinus node.     

Depletion of mitochondrial DNA in HIV-1-infected patients and its amelioration by antiretroviral therapy

Mitochondrial DNA (mtDNA) of peripheral blood mononuclear cells (PBMCs) collected from Human immunodeficiency virus 1 (HIV-1)-infected patients and healthy controls were measured longitudinally using real-time polymerase chain reaction to evaluate the effects of antiretroviral agents on mtDNA synthesis in vivo and to assess the value of monitoring mtDNA in PBMCs to predict adverse events amongst these patients. MtDNA levels in PBMCs were significantly decreased in treatment-naive HIV-1-infected patients compared with healthy people. MtDNA levels were not only significantly correlated with CD4(+) T-cell count, but also inversely correlated with HIV-1 viral load. MtDNA levels in untreated patients and healthy controls were stable during the period of observation. On the other hand, amongst patients treated with regimens containing AZT/3TC or d4T/3TC, mtDNA increased during treatment and recovered to levels comparable to healthy controls. In contrast, mtDNA decreased immediately after the initiation of an AZT/ddC-containing regimen. We did not find a correlation between mtDNA levels and changes in clinical parameters. There was no significant difference in mtDNA levels between patients with and those without lipoatrophy. Furthermore, there was no obvious difference in mtDNA levels amongst those patients exhibiting signs and symptoms of peripheral neuropathy. In conclusion, the decrease in mtDNA levels in PBMCs amongst HIV-1-infected patients and its amelioration by antiretroviral therapy may suggest the influence of direct effects on mitochondria or mtDNA by HIV-1 infection. Further investigations are needed to elucidate the mechanisms contributing to decreased mtDNA and the value of mtDNA measurement in the care of HIV-1-infected individuals.