Pneumocystis carinii shows DNA homology with the ustomycetous red yeast fungi

Pneumocystis carinii causes life-threatening pneumonia in T-lymphocyte-immunodeficient subjects in transplant and oncology units or with acquired immune deficiency syndrome (AIDS). Recent DNA homology studies show P. carinii to be a fungus. To investigate the biology and epidemiology of this parasite further, we elected to determine for it a more precise taxonomic assignment within the fungal kingdom. We screened a wide range of organisms representing the major orders of fungi using DNA amplification and subsequently sequenced a portion of the mitochondrial gene encoding the large subunit ribosomal RNA. Our data show that the opportunistic pulmonary pathogen P. carinii is closely related to the ustomycetous red yeast fungi, a group which includes organisms that are extensively distributed throughout the environment and which release many widely dispersed airborne spores.     

Lithium suppresses ovariectomy-induced surges in plasma gonadotropins in rats

We have reported earlier that administration of lithium, the widely-used drug for the treatment of acute mania and prophylaxis of recurrent manic-depressive bipolar disorders, leads to a disruption of estrous cycle and a significant suppression of the proestrous surge of luteinizing hormone (LH) in a number of laboratory rodents. In this report we have examined the effects of this antimanic drug on plasma and pituitary levels of LH and follicle stimulating hormone (FSH) in rats following ovariectomy (OVX), an altered endocrine state in which the levels of serum LH and FSH are highly and chronically elevated. Adult OVX rats, maintained under standardized laboratory conditions (LD 12: 12; white lights on at 06.00 h, CST) were injected (ip) with lithium, 40 days post-operation, at a dosage of 3.0 and 2.0 mEq/Kg b. wt. for 3 and 7 days respectively (twice daily at 08.00 and 16.00 h). Control OVX rats received nothing or saline injections, whereas an intact control (C) received no surgical manipulation or drug injections of any kind. As expected, the levels of plasma LH and FSH in OVX (only) group showed nearly 6-fold and 75-fold increase respectively compared to those in C. Lithium injections in OVX rats for 3 and 7 days resulted in a significant reduction in plasma LH (P less than .005 and P less than .02 respectively) and FSH (P less than .001) levels when compared with those in the OVX control groups. Lithium also led to a significant reduction in the levels of pituitary LH after both 3 (P less than .02) and 7 days (P less than .02), but the levels of pituitary FSH remained unchanged. These results suggest that the pituitary gonadotropes constitute a definitive target for lithium's action, either directly or via the hypothalamus.     

The structures of garcinones a,b and c: Three new xanthones from Garcinia mangostana

Three new tetraoxygenated xanthones (garcinones A, B and C), each disubstituted with C₅-units, have been isolated from the chloroform extract of the fruit-hulls of Garcinia mangostana. Their structures were established by a combination of spectral interpretation and chemical correlation.     

Majvinine: A new indole alkaloid of Vinca major

A new alkaloid, majvinine, was isolated from aerial parts of Vinca major. Its structure was determined by chemical and spectroscopic investigations     

Cyclo (His-Pro): a selective inhibitor of rat prolactin secretion in vitro

Cyclo (His-Pro) (10 ng/ml), inhibits KCl (59 mM) or thyrotropin-releasing hormone (10 ng/ml) stimulated, but not basal, release of prolactin from rat hemipituitaries $\text{in vitro}$. However, cyclo (His-Pro) has no effect on the basal or stimulated release of thyrotropin and growth hormone. Cyclo (His-Pro) does not inhibit the binding of thyrotropin-releasing hormone to pituitary membrane suggesting that cyclo (His-Pro) inhibition of prolactin release is not mediated via the pituitary TRH-receptor.     

Binding of Hyaluronan to the Native Lymphatic Vessel Endothelial Receptor LYVE-1 Is Critically Dependent on Receptor Clustering and Hyaluronan Organization

The lymphatic endothelial receptor LYVE-1 has been implicated in both uptake of hyaluronan (HA) from tissue matrix and in facilitating transit of leukocytes and tumor cells through lymphatic vessels based largely on in vitro studies with recombinant receptor in transfected fibroblasts. Curiously, however, LYVE-1 in lymphatic endothelium displays little if any binding to HA in vitro, and this has led to the conclusion that the native receptor is functionally silenced, a feature that is difficult to reconcile with its proposed in vivo functions. Nonetheless, as we reported recently, LYVE-1 can function as a receptor for HA-encapsulated Group A streptococci and mediate lymphatic dissemination in mice. Here we resolve these paradoxical findings and show that the capacity of LYVE-1 to bind HA is strictly dependent on avidity, demanding appropriate receptor self-association and/or HA multimerization. In particular, we demonstrate the prerequisite of a critical LYVE-1 threshold density and show that HA binding may be elicited in lymphatic endothelium by surface clustering with divalent LYVE-1 mAbs. In addition, we show that cross-linking of biotinylated HA in streptavidin multimers or supramolecular complexes with the inflammation-induced protein TSG-6 enables binding even in the absence of LYVE-1 cross-linking. Finally, we show that endogenous HA on the surface of macrophages can engage LYVE-1, facilitating their adhesion and transit across lymphatic endothelium. These results reveal LYVE-1 as a low affinity receptor tuned to discriminate between different HA configurations through avidity and establish a new mechanistic basis for the functions ascribed to LYVE-1 in matrix HA binding and leukocyte trafficking in vivo.