STRL33, A novel chemokine receptor-like protein, functions as a fusion cofactor for both macrophage-tropic and T cell line-tropic HIV-1

The chemokine receptors CXCR4, CCR2B, CCR3, and CCR5 have recently been shown to serve along with CD4 as coreceptors for HIV-1. The tropisms of HIV-1 strains for subgroups of CD4(+) cells can be explained, at least partly, by the selective use of G protein-coupled receptors (GPCRs). We have identified a novel human gene, STRL33, located on chromosome 3 that encodes a GPCR with sequence similarity to chemokine receptors and to chemokine receptor-like orphan receptors. STRL33 is expressed in lymphoid tissues and activated T cells, and is induced in activated peripheral blood lymphocytes. When transfected into nonhuman NIH 3T3 cells expressing human CD4, the STRL33 cDNA rendered these cells competent to fuse with cells expressing HIV-1 envelope glycoproteins (Envs). Of greatest interest, STRL33, in contrast with CXCR4 or CCR5, was able to function as a cofactor for fusion mediated by Envs from both T cell line-tropic and macrophage-tropic HIV-1 strains. STRL33-transfected Jurkat cell lines also supported enhanced productive infection with HIV-1 compared with control Jurkat cells. Despite the sequence similarities between STRL33 and chemokine receptors, STRL33-transfected cell lines did not respond to any in a panel of chemokines. Based on the pattern of tissue expression of the STRL33 mRNA, and given the ability of STRL33 to function with Envs of differing tropisms, STRL33 may play a role in the establishment and/or progression of HIV-1 infection.     

Screening demand-side management programs with a value-based test

A value-based test is presented for economic screening of electric utility demand-side management (DSM) programs. The widely used least cost test is valid if the programs do not alter the amount or value of energy services provided to customers. But, in general, DSM programs have such effects and, as a result, the value consumers receive is changed. A more general economic efficiency test, the most value test, provides a practical method for considering the effects of DSM on customer value. The version presented allows for multiple load periods and can account for rate impacts on several customer classes. Four typical DSM programs are evaluated as illustrations     

An epidemiologic, clinical, and therapeutic study of childhood Guillain-Barré syndrome in Kuwait: is it related to the oral polio vaccine?

We studied Guillain-Barré syndrome, affecting children 12 years old or less, throughout Kuwait, in the period between January 1, 1992, and March 31, 1997. Nineteen children had the diagnostic criteria of Guillain-Barré syndrome, with an overall annual incidence rate of 0.95/100,000 population at risk. Female patients outnumbered male patients with a sex ratio of 1.4:1. There was a clustering of cases in winter and spring and in the year 1996. The disease symptoms were relatively severe in our patients because only 16% (3 of 19) of them were able to walk at the height of their illness, whereas the rest were bed or chair bound or needed assisted ventilation. Two patients had the electrodiagnostic features of axonal neuropathy and both had residual deficits on follow-up, whereas the rest recovered fully. All the patients received intravenous immunoglobulin. The mean time to walk unaided was 23.5 days (range, 2-84 days) after intravenous immunoglobulin and excluding the two patients with axonal neuropathy, and full recovery was achieved in a mean time of 103 days (range, 30-300 days). Contrary to previous studies, we found no correlation between oral polio vaccine administration and Guillain-Barré syndrome in 2 successive years (1995 and 1996) during a nationwide campaign targeting children less than 5 years old.     

Tissue specific expression of FMR-1 provides evidence for a functional role in fragile X syndrome

Prostaglandin E2 levels in isolated rat islets were increased from 64 +/- 11 pg/30 islets when incubated in medium containing 2 mM glucose to 115 +/- 9 pg/30 islets in medium containing 20 mM glucose. In contrast, glyceraldehyde (10 mM) reduced prostaglandin E2 levels to 29 +/- 6 pg/30 islets. Inhibition of glucose metabolism by mannoheptulose (10 mM) abolished the stimulatory effect of glucose on prostaglandin E2 levels and inhibited glucose-induced insulin release. The cyclooxygenase inhibitor, flurbiprofen (20 microM), did not affect insulin release caused by glucose or glyceraldehyde. In the presence of 1 mg/ml bovine serum albumin, insulin secretion induced by 20 mM glucose (6.9 +/- 1.1% of islet insulin content) was reduced by the lipoxygenase inhibitor BW755 C (20 microM) to 3.1 +/- 0.6%, and by the phospholipase A2 inhibitor, p-bromophenacyl bromide (10 microM), to 2.1 +/- 0.8%. In the absence of bovine serum albumin the inhibitory action of BW755 C and p-bromophenacyl bromide on glucose-induced insulin release was significantly more pronounced. These drugs whether in the presence or absence of bovine serum albumin, did not affect glyceraldehyde-stimulated insulin secretion. Glyceraldehyde (10 mM), potentiated glucose-induced insulin release in the presence of 2-8 mM glucose, but not for 10-20 mM glucose. Although the phospholipase A2 activator, melittin, initiated insulin release in the presence of 2 mM glucose and enhanced 10 mM glyceraldehyde-stimulated insulin secretion it had no effect on 20 mM glucose-induced insulin release. These two stimulatory effects of melittin on insulin release were totally abolished by p-bromophenacyl bromide.(ABSTRACT TRUNCATED AT 250 WORDS)     

Responses of ligamentous fibroblasts to mechanical stimulation

Mechanical stimulation, as provided by physiotherapy or controlled motion is essentially the only factor able to improve anterior cruciate ligament (ACL) healing. We investigate the cellular effects of such stimulus. Two types of stimulations are applied on canine ACL fibroblasts: repetitive stretch of an elastomeric adhesion substrate and a laminar flow of culture media over the culture surface. Cell orientation, proliferation rate, synthesis and type of collagen as well as proteoglycans (PG) synthesis and hydrodynamic characteristics have been studied. According to our results, the fibroblasts tend to align perpendicularly to the deformation axis of their substrate, and along a laminar flow. The shear stress induced by the laminar flow does not modify significantly proliferation rate nor extracellular matrix synthesis. Substrate stretching however, increases proliferation rate, collagen synthesis, mostly type III, and PG synthesis, principally of small sizes. The characteristics of fibroblasts submitted to repeated deformation match those of fibroblasts from ligament scar tissues. Their orientation perpendicular to substratum deformation differs from the one usually encountered in the undamaged tissue: aligned on the ligament axis.     

Hepatobiliary cystadenoma. A study of five cases with reference to histogenesis

Hepatobiliary cystadenoma is a rare hepatic lesion characterized by a multiloculated cyst lined by cuboidal or columnar epithelial cells. Four cases of hepatobiliary cystadenoma with mesenchymal stroma (HCMS) and one case of hepatobiliary cystadenoma with intracystic epithelial component were studied by light microscopy, immunohistochemical methods, and electron microscopy. Similar studies were conducted on six fetal gallbladder tissues, representing the biliary tree, and two adult ovarian tissues. By light microscopy, the columnar epithelium of the five cases of hepatobiliary cystadenoma was similar to the epithelium of the developing gallbladder. The spindle cell stroma of the HCMS and the subepithelial spindle cells of the developing gallbladders showed similar reactivity to smooth-muscle actin. Vimentin reactivity was strongly positive in the stroma of the HCMS, and in the fetal gallbladders it was only noted in the subepithelial spindle cells of the 15-week gestation fetal gallbladder tissues. By electron microscopy, the epithelium lining the hepatic lesions showed characteristic gastrointestinal features and was identical to the epithelia lining the embryonic gallbladders. Furthermore, the mesenchymal stroma of the HCMS recapitulated the features found in subepithelial tissues in developing gallbladders. Although the ovarian stroma resembled the stroma of the HCMS by light microscopy, the immunohistochemical reactions and the electron microscopic studies showed dissimilarities. This study supports the hypothesis that the hepatobiliary cystadenomas arise from ectopic embryonic tissues destined to form the adult gallbladder.     

ACAT inhibitors derived from hetero-Diels-Alder cycloadducts of thioaldehydes

Acyl-CoA:cholesterol acyltransferase (ACAT) is the enzyme largely responsible for intracellular cholesterol esterification. A systemic inhibitor of ACAT is believed to be able to slow or even reverse the atherosclerotic process. Towards that goal, a series of cyclic sulfides, derived from the hetero-Diels-Alder reaction of thioaldehydes with 1,3-dienes, and bearing carboxamide substituents, were prepared and evaluated for in vitro (in several tissues and species) and ex vivo ACAT inhibition. Minor changes in subsequent structure were found to have a significant effect in optimization of the biological activity of this series of compounds.