Verapamil inhibits serotonin uptake of endothelial cells in culture by a mechanism unrelated to Ca2+ channel blockade

Verapamil inhibited Na+-dependent uptake of serotonin (5-HT) by bovine pulmonary artery endothelial cells in culture both exposed to room air and stimulated by prior exposure to anoxia. The effect of verapamil occurred even in the absence of Ca2+ from the assay medium. Although absence of Ca2+ from the medium moderately reduced 5-HT uptake, stimulation of uptake was nevertheless observed for cells previously exposed to anoxia. Verapamil altered the Km, but not the Vmax, of 5-HT uptake. There was no change in 45Ca2+ uptake or release by cells previously exposed to anoxia as compared to those exposed to room air and verapamil did not influence 45Ca2+ fluxes by either set of cells. It is concluded that verapamil inhibits 5-HT uptake by endothelial cells through a mechanism other than Ca2+ channel blockade; the results are consistent with competitive inhibition of a 5-HT carrier. The stimulatory effect of anoxia on 5-HT uptake does not occur through a change in Ca2+ fluxes.     

Hypogammaglobulinemia: therapeutic rationale.

Hypogammaglobulinemia is a feature of several B-cell disorders and is manifested clinically by recurrent infection, most commonly chronic upper and lower respiratory tract disease. Immunoglobulin replacement therapy is available, with at least four different routes of administration. There are as yet no convincing data that allow comparison of the cost-effectiveness of these methods. However, by individualizing therapy for each patient, it is possible to prevent life-threatening acute infections, reduce the severity of chronic upper and lower respiratory tract disease, improve pulmonary function and achieve normal levels of IgG. These are the currently acceptable goals of therapy in patients with hypogammaglobulinemia.     

Immunocytochemical localization of lactoferrin in human neutrophils

Summary The subcellular localization of lactoferrin in human neutrophils was studied by an electron-microscopic immunoperoxidase method. This molecule was detected in small granules of blood polymorphonuclear leukocytes. A morphometrical analysis showed that there was no significant difference in the mean size between lactoferrin-positive and myeloperoxidase-negative granules. In contrast, the mean size of myeloperoxidase-positive granules was significantly larger than that of lactoferrin-positive granules. This indicates that lactoferrin is contained in the myeloperoxidase-negative, secondary, granules of human neutrophils. In immature bone marrow mononuclear neutrophils, lactoferrin was present in cytoplasmic granules of somewhat larger size than lactoferrin-positive granules of polymorphonuclear leucocytes. A morphometrical study showed that the mean size of lactoferrin-positive granules was significantly greater in immature bone marrow cells than in polymorphonuclear leucocytes. This indicates that lactoferrin-positive granules decrease in size as the cells mature. Besides cytoplasmic granules, lactoferrin was demonstrated in the Golgi complex and a part of the rough endoplasmic reticulum of immature bone marrow neutrophils, probably myelocytes and early metamyelocytes. These results show that lactoferrin is synthesized and packed into secondary granules in immature bone marrow neutrophils and therefore that the secondary granules are a type of secretory granule.     

Effect of zearalenone and estradiol benzoate on serum concentrations of LH, FSH and prolactin in ovariectomized gilts

Six ovariectomized gilts were given zearalenone (Z), estradiol benzoate (EB) or vehicle in a replicated 3 x 3 Latin square design. Zearalenone was added to 2.3 kg of a corn-soybean ration at a dose of 1 mg Z/kg body weight; EB was given intramuscularly at 0.1 mg EB/kg body weight. Control gilts received vehicle solvent for both Z and EB. Blood samples were collected from indwelling jugular cannulas at 6-h intervals for 48 h before Z, EB or vehicle was given. After treatment, blood samples were drawn at 6-h intervals for an additional 84 h. Serum concentrations of luteinizing hormone (LH) decreased (P<0.001) from 4.67 ng/ml to 0.29 ng/ml within 6 h of EB. From 54 to 84 h after EB, serum concentrations of LH rose to 15.60 ng/ml (P<0.001). Serum concentrations of LH were reduced (P<0.001) in a similar pattern after Z (3.70 ng/ml to 0.49 ng/ml), but a rise in serum LH was not observed 54 to 84 h after Z (1.30 ng/ml). Serum concentrations of LH remained unchanged (P=0.55) in gilts given vehicle. Serum concentrations of follicle stimulating hormone (FSH) were suppressed (P<0.03) at 6 h in EB (19.10 vs 11.35 ng/ml) and Z gilts (16.16 vs 11.41 ng/ml) but remained unchanged in vehicle gilts. Serum concentrations of FSH did not change in EB or Z gilts during the next 36 h. These data indicate that the suppressive action of Z on serum concentrations of LH and FSH was similar to that of EB, while the biphasic stimulatory effect of EB for LH was not manifested by Z.     

米团花的化学成分研究

从米团花(Leucosceptrum canum Smith)鲜叶中分到三个化学成分,经光谱测定和化学反应已确定它们的化学结构分别为异香紫苏醇(isosclaveol)Ⅰ;柳穿鱼黄素(pectolinarigenin)Ⅱ;β-谷甾醇(β-sitosterol)Ⅲ。其中化合物Ⅰ为新的天然存在的labdane类型二萜化合物。     

Class II MHC molecules and the HIV gp 120 envelope protein interact with functionally distinct regions of the CD4 molecule.

A murine T cell hybridoma with a receptor specific for the class I molecule H-2 Dd was transfected with an expressible cDNA for human CD4. Expression of the human class II MHC molecule HLA-DP on Dd-positive murine fibroblasts resulted in a greatly enhanced response of the CD4-positive T cell hybridoma, measured either by lymphokine production or by rosette formation. Inhibition of these functional assays with anti-CD4 monoclonal antibodies implicated the two amino-terminal domains of CD4 in an interaction with the HLA-DP molecule. This interaction was blocked by incubation with recombinant gp120 envelope protein of HIV. In contrast, recombinant soluble CD4 did not inhibit and was able to prevent the inhibition by gp120. Anti-CD4 antibody blocking experiments clearly indicated that distinct regions of CD4 interact respectively with gp120 and with class II MHC molecules.     

Immunohistochemical localization of proteoglycans in interstitial elements of human pancreas and biliary system

Summary The immunohistochemical localization of large proteoglycan and small proteoglycan was observed, using antibodies 2B1 and 6B6 (Sobueet al., 1988, 1989a), in fetal and adult pancreas and biliary system as well as in tumour tissues, obtained from 11 autopsies and 74 biopsies. The distribution of chondroitin 4- and 6-sulphate side chains, type I and IV collagen and elastin were also studied. In adult pancreas and all the biliary tracts examined, periductal fibrous tissues consisted mainly of dermatan sulphate small proteoglycan with networks of fibrous elements, which were composed of large proteoglycan, elastin, type I collagen and type IV collagen. In the interstitial components of cystadenoma of pancreas and biliary duct carcinoma, similar small proteoglycan-rich components were relatively abundant, although large proteoglycan was present in much larger amounts than that in non-neoplastic adult tissues. In some cholangiomas, the extra-and intracellular hyaline globules formed by the carcinoma cells were found to contain chondroitin sulphate large proteoglycan, laminin and fibronectin.The distribution of proteoglycans was observed to be different in the arterial walls of the interlobular tissues of the adult and the fetal pancreas. The biological significance of large and small proteoglycans in the interstitial connective tissues was discussed.