The effect of the selective PAF antagonist CIS-19 on PAF- and antigen-induced bronchoconstriction, microvascular leakage and bronchial hyperreactivity in guinea-pigs

We investigated the effects of a novel platelet-activating factor (PAF) receptor antagonist, CIS-19 [cis-2-(3, 4-dimethoxyphenyl)-6-isopropoxy-7-methoxy-1-(N-methylformamido)-1, 2, 3, 4-tetrahydronaphthalene], on PAF-, histamine-, substance P- and antigen-induced bronchoconstriction and microvascular leakage, as well as PAF- and antigen-induced bronchial hyperreactivity to methacholine in urethane-anesthetized guinea-pigs. Administration of CIS-19 (0.5–5 mg/kg, i.v.) inhibited the increase in lung resistance induced by PAF (30 ng/kg, i.v.) in a dose-dependent manner, but failed to inhibit the increase induced by histamine (30 μg/kg, i.v.) or substance P (6.5 μg/kg, i.v.). CIS-19 (5 mg/kg, i.v.) did not inhibit the increase in lung resistance induced by ovalbumin (2 mg/kg, i.v.) in actively sensitized guinea-pigs. PAF (30 ng/kg, i.v.)-induced microvascular leakage, measured by the extravasation of Evans blue dye, was dose-dependently inhibited by CIS-19 (0.5–5 mg/kg, i.v.) in the trachea, main bronchi and intrapulmonary airways, but it did not affect histamine (30 μg/kg, i.v.)- or substance P (6.5 μg/kg, i.v.)-induced microvascular leakage at all airway levels. CIS-19 (2.5 and 5 mg/kg) did not affect ovalbumin (2 mg/kg, i.v.)-induced microvascular leakage in all airway levels in actively sensitized guinea-pigs. CIS-19 (2.5 and 5 mg/kg, i.v.) significantly inhibited PAF-induced enhancement of the bronchial response to methacholine, but had no effect on ovalbumin (0.05 mg/kg, i.v.)-induced bronchial hyperreactivity in actively sensitized guinea-pigs. It is concluded that CIS-19 is a potent PAF receptor antagonist which inhibits PAF- but not antigen-induced bronchoconstriction, microvascular leakage and bronchial hyperreactivity. These results suggest that PAF plays little or no role in early airway responses following antigen challenge. Received: 29 April 1996 / Accepted: 10 October 1996     

Follistatin and activin A production by the male reproductive tract

Follistatin is a binding protein for the activin and inhibin family of hormones, regulating their biological activity. In the male reproductive tract, the interaction of these factors is likely to be involved in the regulation of the proliferation of several cell types. We have investigated the presence of follistatin and activin A in seminal plasma using specific immunoassays and have localized follistatin and activin/inhibin subunits in the adult human testis, prostate and seminal vesicle to establish their likely sources. High concentrations of immunoreactive follistatin were present in seminal plasma in normal men (mean 97.9 ng/ml; 1.43 ng/ml in peripheral plasma) and were similar in men with oligo/azoospermia and following vasectomy. Follistatin immunoreactivity was localized to both Leydig and Sertoli cells of the testis, and to epithelial cells of the prostate gland and seminal vesicle, which are likely to be the predominant sources of the hormone in seminal plasma. Activin A was also present in seminal plasma in normal men but was undetectable following vasectomy, thus deriving from the testis. Consistent with this finding, the betaA-subunit was immunolocalized in Sertoli and Leydig cells but was not present in seminal vesicle or prostate gland. The functional significance of the high concentrations of follistatin secreted into seminal plasma by the prostate gland and/or seminal vesicle is uncertain, but they may regulate the biological activity of testis-derived activin A and inhibin B.      

Sequence analysis of the gene encoding the Chlamydia pneumoniae DnaK protein homolog.

The antigen-coding region of a 4.2-kb PstI fragment of Chlamydia pneumoniae (pLC3), which encodes a 75-kDa immunoreactive protein recognized during human C. pneumoniae infection, was localized to a 2.0-kb EcoRI fragment. This subclone expressed an immunoreactive fusion protein of ca. 82 kDa. Nucleotide sequence analysis of the C. pneumoniae gene revealed that it consisted of a 1,980-base open reading frame with an inferred 71,550-Da protein of 660 amino acids. Putative Escherichia coli-like promoters and a ribosomal binding site were located in the 5' upstream region, and an 11-base dyad forming a stable stem-loop structure following two in-frame stop codons was identified. The C. pneumoniae 75-kDa protein is a member of the hsp70 family of heat shock proteins and has 87% amino acid similarity with the Chlamydia trachomatis protein.     

Postoperative deep vein thrombosis in the Taiwanese Chinese population

Reports of the incidence of postoperative deep vein thrombosis in the Chinese population of Taiwan are few in the literature. Over a 3 year period, the fibrinogen degradation products test, the pulse volume recorder, and venography were used to study 220 patients undergoing major operations at the Veterans General Hospital in Taipei, Taiwan. Deep vein thrombosis was found in 17 patients (7.7 percent). A comparison of the three diagnostic methods showed that the sensitivities of the fibrinogen degradation products test and the pulse volume recorder were 56.3 percent and 93.7 percent, respectively; the specificities, 97.4 percent and 95.7 percent, respectively; and the accuracies, 85.5 percent and 95.5 percent, respectively. These results support the combined use of the fibrinogen degradation products test and the pulse volume recorder for screening and diagnosing deep vein thrombosis.     

Concomitant translocation of Puralpha with its binding proteins (PurBPs) from nuclei to cytoplasm during neuronal development

Two Puralpha-binding proteins (PurBPs) were found in nuclear extract from mouse brain during P4-P10 by the overlay assay. At P14, they were decreased significantly in nuclear extract and increased in the S3 fraction, indicating their dynamic translocation during development. Western blot analysis also demonstrated concomitant translocation of Puralpha with the PurBPs during P7-P14, when neuronal circuit proceeds. Immunocytochemical study with cultured hippocampal neurons from rat E18 confirmed that nuclear Puralpha was translocated to cytoplasm after plating for 7-14 days. These results suggest that spatiotemporal translocation of Puralpha with the PurBPs from nuclei to cytoplasm has a crucial role in neuronal development.     

Inhibitory actions of serotonin on glutamate release in dorsal medulla suppress systemic arterial pressure of cats

The role of serotonin and glutamate release in dorsal medulla (DM) for regulation of systemic arterial pressure (SAP) was examined with microdialysis and high performance liquid chromatograph in anesthetized cats. KCl-perfusion in DM increased serotonin and glutamate concentrations in DM. Perfusion of serotonin resulted in decreases in glutamate concentration and SAP. Perfusion of alaproclate, a serotonin reuptake inhibitor that produced an increase in serotonin concentration in DM, had the same results as perfusion of serotonin. In conclusion, serotonin and glutamate appeared to be tonically and endogenously released from nerve terminals in DM, and the decrease in SAP could be attributed to the decreased glutamate release resulting from inhibitory action of serotonin in DM. The putative roles of serotonin and glutamate in DM may be important in SAP regulation.     

Differential cardiovascular effects of pharmacological agents in chickens selected for high and low body weight.

This study was conducted to investigate whether there are differences in the autonomic nervous system function of chickens from lines selected for high (HWS) or low body weight (LWS). The cardiovascular response to various pharmacological agents was used as an indicator of autonomic nervous system response. Ten individuals from each line and sex were used in the study. Catheters were introduced into the left brachial artery and vein and connected to a MP100-BIOPAC system to record blood pressure and heart rate (HR). Chickens were injected with phenylephrine, atropine, propranolol, and tetraethylammonium chloride (TEAC). The LWS birds exhibited a greater increase in mean arterial blood pressure (MABP) and a lesser increase in HR than the HWS birds following atropine. The response to atropine showed a line and sex interaction in which male birds had a greater increase in HR than females and LWS females had a lower increase in HR than the HWS females. Injection of phenylephrine following pretreatment with atropine caused a baroreceptor reflex in which males showed a greater decrease in HR than females. In response to the beta-adrenergic receptor blocker propranolol, females displayed a greater decrease in MABP than males and LWS birds had a greater decrease in HR than HWS birds. In response to the autonomic ganglionic blocker TEAC, MABP and HR decreased equally in both lines. The percentage of adrenal and sympathetic impact on regulation of HR showed that LWS females required greater adrenal activity than those from the other subclasses. Although changes in HR and MABP ratios in response to phenylephrine were different between lines, these responses were not different when phenylephrine was given following atropine. This pattern of response suggested that HWS birds had greater parasympathetic nervous system activity in order to maintain cardiovascular function. These results demonstrate that selection for HWS or LWS has resulted in greater parasympathetic and sympathetic nervous system tone in birds from the HWS and LWS birds, respectively, and suggest that differences between the lines could be at the level of the chromaffin tissue in the adrenal gland.     

Cellular immune response during uncomplicated genital infection with Chlamydia trachomatis in humans.

Extraction of staphylococcal abscesses by the Folch procedure revealed that all of the staphylocidal activity was present in the lipid fraction. Further separation of the lipids indicated that the bactericidal activity resided in the free fatty acid pool. Lipids similarly extracted from mesenteric or epididymal fat tissue, either before of after activation, did not possess comparable activity. Myristic, palmitic, palmitoleic, linoleic, and oleic acids, as well as lysolecithin, also failed to exhibit the properties of the fatty acid fraction obtained from abscess homogenates. These findings suggest the staphylocidal fatty acid is not a common host lipid.