Amino acid transport in cerebral microvessels during Plasmodium yoelii infection in mice

Plasmodium yoelii infected cerebral microvessels of mice had an enhanced time-dependent, temperature-sensitive, and saturable uptake of [14C]-amino acid. viz. leucine, valine and glycine. Metabolic inhibitors caused a noticeable inhibition of amino acid uptake in normal microvessels as compared to infected cerebral microvessels indicating that the uptake of [14C]-L-leucine, [14C]-L-valine and [14C]-glycine is an energy dependent process.     

CTL response to Mycobacterium tuberculosis: identification of an immunogenic epitope in the 19-kDa lipoprotein

The successful resolution of infection with Mycobacterium tuberculosis (M.tb) is believed to involve the induction of CTLs that are capable of killing cells harboring this pathogen, although little information is known about the MHC restriction or fine specificity of such CTLs. In this study, we used knowledge of the HLA-A*0201-binding motif and an immunofluorescence-based peptide-binding assay to screen for potential HLA-A*0201-binding epitopes contained in the 19-kDa lipoprotein of M.tb (M.tb19). CD8+ T cells derived from HLA-A*0201+ patients with active tuberculosis (TB) as well as tuberculin skin test-positive individuals who had no history of TB were used as effector cells to determine whether these epitopes are recognized by in vivo-primed CTLs. An in vitro vaccination system using HLA-A*0201+ dendritic cells (DCs) as APCs was used to determine whether these epitopes can sensitize naive CD8+ T cells in vitro, leading to the generation of Ag-specific CTLs. The results show that an HLA-A*0201-binding peptide comprised of residues 88 to 97 of M.tb19 (P88-97) is recognized by circulating CD8+ CTLs from both healthy tuberculin skin test-positive individuals and patients with active TB but not by tuberculin skin test-negative subjects. Moreover, dendritic cells pulsed with this peptide induced class I MHC-restricted CTLs from the T cells of healthy unsensitized persons. Finally, CTL lines that were specific for P88-97 were shown to lyse autologous monocytes that had been infected acutely with the H37Ra strain of M.tb. These results demonstrate that M.tb19 elicits HLA class I-restricted CTLs in vitro and in vivo that recognize endogenously processed Ag. Epitopes of the type identified here may prove useful in the design of an M.tb vaccine.     

Significance of platelet-derived endothelial cell growth factor in the angiogenesis of human gastric cancer

Most patients with primary IgA nephropathy (IgAN) have a significantly higher memory repertoire of IgA1-producing B lymphocytes in their bone marrow together with high plasma levels of IgA1. The connection between the mucosal immune system and the bone marrow compartment is probably based on traffic of either antigen-presenting cells (APC) or antigen-specific lymphocytes. Cytokines play an important role in the proliferation and differentiation of lymphoid cells. In order to mimic the in vivo situation as much as possible, we assessed cytokine production profiles ex vivo in 23 IgAN patients and matched controls, using lipopolysaccharide (LPS)- or phytohaemagglutinin (PHA)-stimulated whole blood (WB) cultures. Interferon-gamma (IFN-gamma), IL-2, IL-6, IL-10 and tumour necrosis factor-alpha (TNF-alpha) production in culture supernatants were determined by cytokine-specific ELISAs. Compared with controls, PHA-stimulated cultures resulted in significantly higher IL-10 (P<0.001), IL-2 (P<0.005) and IFN-gamma (P<0.001) levels in IgAN patients, but no significant differences in TNF-alpha or IL-6 levels were found. In LPS-stimulated cultures, the only significant difference (P<0.001) between the two groups was the increased IL-10 production in IgAN patients. The enhanced cytokine production in stimulated WB cultures suggests altered monocyte-related T cell responses in patients with IgAN. Increased IL-10 production may eventually result in an increased number of IgA-producing B lymphocytes in the bone marrow. In addition, high levels of endogenous IL-10 may down-regulate the effector functions of monocytes, or possibly APC in general, and consequently the IgA response at the mucosal level.     

Surgical repair of the congenitally malformed mitral valve in infants and children

BACKGROUND: Mitral valve remodeling techniques were applied to 26 infants and children (mean age, 6.0 years, range, 0.4 to 15.9 years) with various forms of congenital mitral valve disease over a 7-year period. Patients with atrioventricular canal, L-transposition and single ventricle were excluded. Intraoperative transesophageal echocardiography (TEE) was utilized to assess the repair and guide the need for immediate intervention. METHODS: Twenty-one patients had mitral regurgitation: 10 with cleft anterior mitral leaflet, 7 with annular dilatation, 1 with normal leaflets with an obstructing cord, 2 with prolapsed leaflets and elongated cords, and 1 with restricted leaflet motion, normal papillary muscles, and shortened cords. Of the 5 mitral stenosis patients, 3 had supravalvular mitral ring, 1 had midvalvular mitral ring, and 1 had a parachute valve. Three of the mitral stenosis patients had additional stenotic lesions. Concurrent repair of associated lesions was performed in 21 patients (78%). RESULTS: Operative mortality was 3.8% (n = 1). There were no late deaths. Immediate rerepair in 4 patients resulted in improved function. All mitral stenosis patients improved. A total of 20 mitral regurgitation patients (95%) improved; 1 required mitral valve replacement. Mean follow-up is 31 months (range, 2 to 81 months). All patients are in New York Heart Association functional class I or II. CONCLUSIONS: Mitral valve repair can be successfully performed in infants and children with excellent short- and midterm results. Assessment using transesophageal echocardiography can guide the necessity for immediate rerepair to achieve improved function.     

Coupling protein stability and protein function in Escherichia coli CspA

Idiopathic thrombocytopenic purpura (ITP, also known as immune thrombocytopenic purpura) in adults is principally a disease of young women. Although in some patients the onset is acute and complete resolution occurs, in most patients, the onset is insidious and the course is chronic. In spite of the relative frequency of ITP, there are important unresolved issues in its diagnosis and management. For this reason, the American Society of Hematology (ASH) chose ITP as the disease topic for its initial sponsored practice guideline in 1993. A major conclusion of the published guideline was the lack of firm evidence on which to base diagnostic procedures and management strategies. This review describes the clinical features of ITP in adults, emphasizes the principal unresolved issues in diagnosis and management, and outlines the critical areas for future research.     

Suc-Phe-Leu-Phe-SBzl--a new substrate for functional study of Escherichia coli ATP-dependent Lon-proteinase and its modified forms

A new efficient substrate, Suc-Phe-Leu-Phe-SBzl, was proposed for studying the function of the Escherichia coli ATP-dependent Lon protease and its modified forms. The kinetic parameters of hydrolysis of the substrate were determined. The esterase activity of protease Lon was found to be nucleotide-regulated.     

Simultaneous cross-linking of CD6 and CD28 induces cell proliferation in resting T cells

In the present study, we showed that simultaneous ligation of the monoclonal antibodies (mAb) against CD6 and CD28 induces T-cell proliferation in purified resting T lymphocytes in the absence of T-cell receptor (TCR) occupancy. No cell proliferation was observed when the mAb were cross-linked alone or used simultaneously in the soluble form. T-cell proliferation mediated through CD6/CD28 is accompanied by the up-regulation of interleukin-2 (IL-2) mRNA and expression of IL-2 receptors on the cell surface. In the presence of IL-2-neutralizing mAb the proliferative response of the T cell induced through CD6/CD28 was inhibited dose dependently. Cross-linking mAb to CD6 and CD28 alone or together did not down-regulate the CD3/TCR complex. T-cell proliferation mediated through CD6/CD28 was only partially blocked by the immunosuppressive drug, cyclosporin A (CsA), whereas anti-CD28-induced T-cell proliferation in the presence of the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), was unaffected. In sharp contrast T-cell proliferation mediated by anti-CD6 in the presence of TPA was efficiently blocked by CsA. In addition, two protein kinase C (PKC) inhibitors, GF 109203X and H-7 dose-dependently inhibited T-cell proliferation mediated through CD6/CD28, suggesting that PKC activation may be involved. Furthermore, there was a marked differential dose-dependent inhibitory effect of the PKC inhibitors on T-cell proliferation mediated by the co-ligation of anti-CD6 or anti-CD28 in the presence of anti-CD3, with the former being more sensitive to PKC inhibition. Taken collectively, our results suggest that T-cell activation can occur through an antigen-independent pathway by cross-linking the accessory molecules, CD6 and CD28, and that these two cell surface antigens may have distinct signalling pathways.     

Synthesis and antiallergic activity of pyridothienopyrimidines

The synthesis of a series of pyridothienopyrimidines and their evaluation as inhibitors or inducers of the release of histamine from rat mast cells is reported. The activity was measured after immunological stimulation with ovoalbumin and chemical stimulation with polymer 48/80 and the drugs adryamicin and vinorelbine. The experiments were carried out with and without preincubation of the stimulus with the cells before addition of the drug. Several pyridothienopyrimidines show inhibitory IC50 values in the range 2-25 microM, indicating they are up to 100 times more potent than cromoglycate (DSCG) and 10 times greater than Ketotifen. Compound 9l is a potent inhibitor in all the conditions tested and shows IC50 = 9-25 microM. Pyridothienopyrimidines 4l and 9e are very strong inducers of histamine release in the immunological (4l, 170-230%) and chemical (9e, 100-150%) assays, respectively. Compounds 4l and 9i are cytotoxic in vitro (IC50 = 0.1-0.2 microgram/mL) against P-388, A-549, HT-29, and MEL-28 tumor cell lines.     

Abortion surveillance--United States, 1995

CONDITION: Since 1990 (i.e., the year in which the number of abortions was highest), the annual number of abortions in the United States has decreased by 15%. REPORTING PERIOD COVERED: This report summarizes and reviews information reported to CDC regarding legal induced abortions obtained in the United States during 1995. DESCRIPTION OF SYSTEM: For each year since 1969, CDC has compiled abortion data received from 52 reporting areas: 50 states, the District of Columbia, and New York City. RESULTS: In 1995, a total of 1,210,883 legal abortions were reported to CDC, representing a 4.5% decrease from the number reported for 1994. The abortion ratio was 311 legal induced abortions per 1,000 live births, and the abortion rate was 20 per 1,000 women aged 15-44 years, the lowest ratio and rate recorded since 1975. Women who were undergoing an abortion were more likely to be young, white, and unmarried; most were obtaining an abortion for the first time. Approximately half of all abortions (54%) were performed at < or =8 weeks of gestation, and approximately 88% were performed before 13 weeks. Approximately 16% of abortions were performed at the earliest weeks of gestation (< or =6 weeks), approximately 17% at 7 weeks of gestation, and approximately 21% at 8 weeks of gestation. Few abortions were provided after 15 weeks of gestation -- approximately 4% of abortions were obtained at 16-20 weeks, and 1.4% were obtained at > or =21 weeks. Younger women (i.e., women aged < or =24 years) were more likely to obtain abortions later in pregnancy than were older women. INTERPRETATION: Since 1990, the number of abortions has declined each year. Since 1987, the abortion-to-live-birth ratio has declined; in 1995, it was the lowest recorded since 1975. This decrease in the abortion ratio reflects a trend that a lower proportion of pregnant women obtain induced abortion. ACTIONS TAKEN: The number and characteristics of women who obtain abortions in the United States should continue to be monitored so that trends in induced abortion can be assessed, efforts to prevent unintended pregnancy can be evaluated, and the preventable causes of morbidity and mortality associated with abortions can be identified and reduced.