Transendothelial migration of lymphocytes from HIV-1-infected donors: a mechanism for extravascular dissemination of HIV-1

To identify factors that cause HIV-1 to establish perivascular foci of infected cells, we studied the transendothelial migration of blood mononuclear leukocytes (MNL) from 76 HIV+ patients and 41 controls. The fraction of patients' lymphocytes that migrated across endothelial cell monolayers in vitro was significantly increased (p < or = 0.03) compared with that of control donors. Migration of patients' CD4+ T cells was particularly enhanced, whereas the migration of monocytes did not differ between patients and controls. Lymphocyte migration correlated with expression of CD11a/CD18 and CD49d/CD29 and with the quantity of TNF-alpha produced as MNLs migrated through the endothelium. Measurement of HIV-1 proviral DNA copies in the patients' MNLs (n = 26) suggested that in half the cases virus-infected cells accumulated preferentially amidst the migratory leukocytes. We observed the same behavior with normal donor MNLs infected, in vitro, with each of 4 strains of HIV-1. The number of HIV-1 proviral DNA copies per million MNLs was 40 to 178 times higher in the migratory population than in the original population added to the endothelium. To test whether only certain strains of HIV-1 stimulate transendothelial migration of infected cells, we used single strand conformation polymorphism analysis to identify quasispecies of HIV-1 in the MNLs. If all strains of HIV-1 were equal in their ability to stimulate transendothelial migration, we expected to find no differences in the quasispecies present in the original and migratory cell populations. In fact the quasispecies differed in 14 of 19 paired samples, suggesting that only certain HIV-1 quasispecies promote transendothelial migration of infected cells.     

一统天下--USB 2.0市场前景初探

2002年2月28日英特尔开发商论坛上首次展示了通用串口总线(USB)2.0,并表明高速USB2.0将得到广泛发展,从目前来着,USB2.0标准的普及只是早晚的事情,因为几乎所有的主板都提供了这个接口。与此同时,IEEE1394也保持着其在特定领域里的应用而享受着自己的那块份额。为了对这两种标准进行比较,我们在第九期的《电子与电脑》中以移动存储产品为代表进行了比较性的评测,并在文章中对这两种接口进行了简单的展     

Xanthine oxidase activity associated with arterial blood pressure in spontaneously hypertensive rats

Recent evidence in vivo indicates that spontaneously hypertensive rats (SHR) exhibit an increase in oxyradical production in and around microvascular endothelium. This study is aimed to examine whether xanthine oxidase plays a role in overproduction of oxidants and thereby may contribute to hypertensive states as a consequence of the increasing microvascular tone. The xanthine oxidase activity in SHR was inhibited by dietary supplement of tungsten (0.7 g/kg) that depletes molybdenum as a cofactor for the enzyme activity as well as by administration of (-)BOF4272 [(-)-8-(3-methoxy-4-phenylsulfinylphenyl)pyrazolo(1,5-alpha)-1,3, 5-triazine-4-monohydrate], a synthetic inhibitor of the enzyme. The characteristic elevation of mean arterial pressure in SHR was normalized by the tungsten diet, whereas Wistar Koto (WKY) rats displayed no significant alteration in the pressure. Multifunctional intravital videomicroscopy in mesentery microvessels with hydroethidine, an oxidant-sensitive fluoroprobe, showed that SHR endothelium exhibited overproduction of oxyradicals that coincided with the elevated arteriolar tone as compared with WKY rats. The tungsten diet significantly repressed these changes toward the levels observed in WKY rats. The activity of oxyradical-producing form of xanthine oxidase in the mesenteric tissue of SHR was approximately 3-fold greater than that of WKY rats, and pretreatment with the tungsten diet eliminated detectable levels of the enzyme activity. The inhibitory effects of the tungsten diet on the increasing blood pressure and arteriolar tone in SHR were also reproducible by administration of (-)BOF4272. These results suggest that xanthine oxidase accounts for a putative source of oxyradical generation that is associated with an increasing arteriolar tone in this form of hypertension.     

Confirmation of an association between a polymorphism in exon 3 of the low-density lipoprotein receptor-related protein gene and Alzheimer's disease

C766T, a polymorphism in exon 3 of the gene for the low-density lipoprotein receptor-related protein (LRP), was found to be associated with late-onset Alzheimer's disease (AD). We developed a PCR-restriction enzyme-based assay to analyze this allele in 234 AD patients and 103 controls. We confirmed that the LRP C766T polymorphism was in disequilibrium with AD--the C/C genotype was present in 76% of AD patients and 60% of controls (p < 0.01); however, the LRP polymorphism did not influence age at onset of AD.     

Isolation and characterization of the GFA1 gene encoding the glutamine:fructose-6-phosphate amidotransferase of Candida albicans

Glutamine:fructose-6-phosphate amidotransferase (glucosamine-6-phosphate synthase) catalyzes the first step of the hexosamine pathway required for the biosynthesis of cell wall precursors. The Candida albicans GFA1 gene was cloned by complementing a gfa1 mutation of Saccharomyces cerevisiae (previously known as gcn1-1; W. L. Whelan and C. E. Ballou, J. Bacteriol. 124:1545-1557, 1975). GFA1 encodes a predicted protein of 713 amino acids and is homologous to the corresponding gene from S. cerevisiae (72% identity at the nucleotide sequence level) as well as to the genes encoding glucosamine-6-phosphate synthases in bacteria and vertebrates. In cell extracts, the C. albicans enzyme was 4-fold more sensitive than the S. cerevisiae enzyme to UDP-N-acetylglucosamine (an inhibitor of the mammalian enzyme) and 2.5-fold more sensitive to N3-(4-methoxyfumaroyl)-L-2,3-diaminopropanoic acid (a glutamine analog and specific inhibitor of glucosamine-6-phosphate synthase). Cell extracts from the S. cerevisiae gfa1 strain transformed with the C. albicans GFA1 gene exhibited sensitivities to glucosamine-6-phosphate synthase inhibitors that were similar to those shown by the C. albicans enzyme. Southern hybridization indicated that a single GFA1 locus exists in the C. albicans genome. Quantitative Northern (RNA) analysis showed that the expression of GFA1 in C. albicans is regulated during growth: maximum mRNA levels were detected during early log phase. GFA1 mRNA levels increased following induction of the yeast-to-hyphal-form transition, but this was a response to fresh medium rather than to the morphological change.     

Ileocecal tuberculosis as a cause of lower gastrointestinal hemorrhage in lupus erythematosus

BACKGROUND AND AIMS OF THE STUDY: The use of living, untreated autologous pericardium for patch repair in the left ventricular outflow tract was considered attractive in children. METHODS: Ventricular septal defect (VSD) closure with an untreated autologous pericardial patch was performed in 102 children of mean age 13.4 months (range: 1 to 73 months). Postoperative transthoracic Doppler echocardiography was performed in all children at a mean of nine weeks (range: one day to 50 weeks) after surgery. One pericardial patch, which was explanted at autopsy two months after surgery, was studied microscopically. RESULTS: At short-term follow up, no or only minor residual VSD was found in 97 patients, moderate VSD in two and severe VSD in one patient. One patient was reoperated for residual VSD and an aneurysmic patch first diagnosed seven days after surgery. Two more patients showed ballooning of the patch without VSD after five and seven days respectively. All aneurysmic patches were attributed to intraoperative patch oversizing. Patch integrity was confirmed in all other patients. No inflammatory or degenerative changes were observed at microscopy, rather a remodeling response had caused the patch to thicken, indicating an adaptation of the living tissue. CONCLUSIONS: The untreated autologous pericardial patch has shown to be a safe alternative for VSD closure, provided that the patch is properly sized.     

Secretory immune system of the duck (Anas platyrhynchos). Identification and expression of the genes encoding IgA and IgM heavy chains

We explored a novel approach to tolerance induction by the transplantation of bone marrow (BM) cells (BMCs) that themselves do not express a foreign histocompatibility Ag, but which give rise to mature lymphocytes that do so. Lines of transgenic (FVB) mice were generated that contained an MHC class I Dd cDNA regulated by a CD2 promoter. Because the CD2 promoter is lymphocyte-specific and activated relatively late in lymphocyte ontogeny, Dd is expressed on most mature lymphocytes in the periphery but only on developing B cells in the BM of transgenic mice. Transgenic BMCs are tolerogenic and reproducibly engraft in nontransgenic mice using a conditioning regimen that is nonpermissive for the engraftment of conventional (MHC promoter) Dd-transgenic BMCs. Engrafted BMCs generate transgene-expressing lymphocytes and confer a state of Ag-specific hyporesponsiveness on the host that is primarily attributable to a peripheral mechanism. The strategies by which tolerance can be optimized in this system are discussed.     

Identification of a new non-major histocompatibility complex genetic locus on chromosome 2 that controls disease severity in collagen-induced arthritis in rats

OBJECTIVE: To identify novel non-major histocompatibility complex (non-MHC) genetic loci controlling the severity of homologous rat type II collagen-induced arthritis (CIA). METHODS: We conducted a genome-wide scan to identify CIA regulatory quantitative trait loci (QTL) in an F2 cross between DA (CIA highly susceptible) and ACI (CIA resistant) inbred rats immunized with homologous rat type II collagen (RII). These strains share the MHC/RT1av1 haplotype required for susceptibility to RII-induced CIA. RESULTS: F2 females had higher median arthritis scores than did males. Relative resistance in the males was determined by inheriting either a DA or an ACI Y chromosome and was independent of the source of the X chromosome. In addition, a major QTL was localized on chromosome 2 (Cia7, logarithm of odds score 4.6). Cia7 is in a region that shows linkage conservation with chromosomal regions that regulate autoimmune diabetes and experimental autoimmune encephalomyelitis in mice and multiple sclerosis in humans. CONCLUSION: Sex chromosomes and Cia7 play an important role in regulating CIA in response to RII. This rat model should facilitate positional cloning and functional characterization of regulatory genes that may play a role in several forms of autoimmune disease, including rheumatoid arthritis.     

The dentin substrate: structure and properties related to bonding

OBJECTIVES: Dentin is a vital, hydrated composite material with structural components and properties that vary with location. These variations are reviewed along with alterations by physiological and pathological changes that allow classification into various forms of dentin. Structural characteristics and mechanical properties are reviewed and the limitations of our understanding of structure-property relationships for normal and modified forms of dentin are discussed with respect to their impact on dentin bonding. Recent progress in methods available to study dentin and its demineralization are emphasized with their promise to increase our understanding of dentin properties and structure. DATA SOURCES: Recent microstructural studies, focusing on scanning electron microscopy, atomic force microscopy and X-ray tomographic microscopy are included. A review of fundamental studies with emphasis on microstructurally sensitive methods, and prior reviews of basic mechanical properties are included with discussion of their correlation to composition and structure. STUDY SELECTION AND CONCLUSIONS: Emphasis in this work was placed on the major structural components of the tissue, including the collagen based organic matrix and its mineral reinforcement, the distribution of these components and their microstructural organization as related to mechanical properties and response to demineralization. Little information is included on biochemical and developmental studies or on non-collagenous proteins and other organic components for which limited understanding is available with respect to their role in structure-property relations and influence on bonding. In spite of the fact that the complexity of dentin precluded a comprehensive review, it is clear that local structural variations influence properties and impact nearly all preventive and restorative dental treatments. Much more work is needed in order to understand differences between vital and non-vital dentin, and dentin from extracted teeth. Although our knowledge is rudimentary in certain areas, increasingly sophisticated methods of studying dentin should provide the necessary information to model structure-property relations, optimize dentin bonding, and improve many aspects of preventive and restorative dentistry.     

Percutaneous gastrostomy with T-fastener gastropexy: results of 316 consecutive procedures

PURPOSE: To assess the rates of technical success and complications associated with radiologic gastrostomy or gastrojejunostomy performed with T-fastener gastropexy. MATERIALS AND METHODS: In 316 consecutive patients, radiologic gastrostomy or gastrojejunostomy with T-fastener gastropexy was performed over a 10-year period. Results of the procedures were reviewed. Results of follow-up were available for all patients. RESULTS: Of 316 procedures, 314 were successful (technical success rate, 99.4%). Six (1.9%) major complications occurred; 50% occurred in patients with peritoneal involvement from ovarian carcinoma. Ten (3.2%) minor complications occurred. Four minor complications occurred in patients with ovarian cancer and ascites. The 30-day mortality rate was 3.8% (12 patients) with one procedure-related death (0.3%). CONCLUSION: A T-fastener gastropexy may have a protective role in prevention of leakage of gastric contents into the peritoneum in patients with ascites. Ascites need no longer be considered a contraindication for radiologic gastrostomy. A gastropexy enables routine use of larger gastrostomy tubes and ready replacement of a displaced tube even before the development of a mature tract.