B cells express Ly-6C in a Th1 but not Th2 cytokine environment.

Interferon-alpha (IFN-alpha) is the primary regulator of transient Ly-6C expression on T cells. B cells, which do not express Ly-6C in the resting state, have been reported to express Ly-6C following exposure to proinflammatory stimuli. This study examined the factors controlling Ly-6C expression on B cells and the kinetics of Ly-6C expression in the presence of these factors. In vivo studies demonstrated that proinflammatory (Th1) cytokines transiently upregulate B cell Ly-6C expression. In vitro studies identified Th1 cytokines, particularly IFN-alpha and IFN-gamma, as the principal cytokines responsible for this induction. Polyclonal B cell activators (anti-IgM and recombinant CD40 ligand trimer) showed minimal ability to independently induce Ly-6C expression on B cells but did enhance the ability of IFNs to induce expression. Th2 cytokine environments did not result in B cell Ly-6C expression, and interleukin-4 (IL-4) actually antagonized the IFN-driven induction of Ly-6C. Ly6.1 strains of mice consistently demonstrated a greater ability to express Ly-6C on B cells than did Ly-6.2 strains. Together, these studies demonstrate the ability of Th1 but not Th2 cytokine environments to transiently induce the expression of Ly-6C on B cells and provide additional evidence for differences in the regulation of Ly-6C expression in Ly6.1 and Ly6.2 strains.     

Neurobehavioral phenotype in carriers of the fragile X premutation

There have been contradictory findings in the fragile X (fraX) literature about possible neurocognitive and psychological symptoms due to the fraX premutation (pM). The purpose of the present study was to investigate the relationship between CGG repeat length and neurobehavioral functioning in carriers of the fraX pM. Eighty‐five female carriers of the pM with allele sizes ranging from 59–166 were administered a comprehensive IQ test (WAIS‐III) and completed a questionnaire designed to measure psychopathology (Symptom Checklist (SCL)‐90‐R). No relationship between allele size and cognition was identified. A significant negative relationship between allele size and age was found, as well as a positive relationship between allele size and depression. Follow‐up analyses separating small and large allele sizes (below and above 100 CGG repeats) indicated that individuals with larger allele sizes scored significantly higher on the Interpersonal Sensitivity and Depression subscales of the SCL‐90‐R. Despite the limitation of few individuals with high CGG repeat lengths, our findings suggest that females with larger premutated alleles (≥ 100 repeats) display some clinical manifestations of fraX syndrome. © 2001 Wiley‐Liss, Inc.     

CD34(+) fibrocytes in normal cervical stroma,cervical intraepithelial neoplasia III,and invasive squamous cell carcinoma of the cervix uteri

CD34(+) fibrocytes are widely distributed in normal connective tissues but have been reported to be absent within the stroma associated with invasive carcinomas. In the present study we investigated the presence and distribution of CD34(+) fibrocytes and alpha-smooth muscle actin (alpha-SMA) positive myofibroblasts in cervical intraepithelial neoplasia III (CIN III; n=8), invasive carcinoma of the cervix ( n=18) and adjacent normal cervical stroma. Normal cervical stroma and the stroma adjacent to CIN III disclosed a dense network of CD34(+) fibrocytes, whereas the stroma of invasive carcinoma was virtually free of this cell population. Early stromal invasion by squamous carcinoma was characterized by a focal loss of CD34(+) fibrocytes. alpha-SMA-positive myofibroblasts were not seen in the normal cervical stroma but occurred in six of eight cases of CIN III adjacent to the atypical epithelium. The stroma of invasive carcinoma was made up of large amounts of haphazardly arranged alpha-SMA-positive myofibroblasts. In the setting of the present study, a loss of CD34(+) fibrocytes was specific for stromal alterations associated with invasive carcinoma and proved to be a sensitive tool in detecting small foci of stromal invasion. Therefore, detection of a loss of CD34(+) fibrocytes may constitute an adjunctive tool in detecting (1) early stromal invasion and (2) invasive carcinoma in small biopsy specimens. Moreover, the present study shows that CD34(+) fibrocytes and myofibroblasts play an important role in stromal remodeling associated with invasive squamous cell carcinoma of the cervix.     

Sites of arginine synthesis and urea production along the nephron of a desert rodent species,Meriones shawi

The distribution of arginine synthase and arginase activities along the successive nephron segments ofMeriones kidney was measured in vitro with single tubule enzymatic microtechniques making use of eitherl-[ureido-¹⁴C] Citrulline (0.108 mM) orl-[guanidion-¹⁴C]arginine (0.2 mM) as the respective substrates. Arginase activity (fmol urea formed per min per mm of tubule) was very low (5–25 fmol.min^–1.mm^–1) in most nephron segments including the early portions of proximal convoluted tubules (early PCT). It increased progressively after 3 mm of the PCT to reach a value of 200 fmol.min^–1.mm^–1 in the cortical portion of the straight proximal tubule (CPST), with a further increase, along the pars recta, of up to 250 fmol.min^–1.mm^–1 in the outer medullary portion (OSPST). In addition, arginase activity in OSPST and the adjacent descending thin limb (DTL) was higher in juxtamedullary nephrons (JN) than in the corresponding portions of superficial nephrons (SN). Arginine synthase activity (fmol arginine formed per mm of tubule per min) was present in proximal tubules exclusively, with a gradient decreasing along the PCT (about 600 fmol.min^–1.mm^–1 in the 1st mm, 65 fmol.min^–1.mm^–1 in CPST and 30 fmol. min^–1. mm^–1 in OSPST). It has been checked that CPST and OSPST (where the two enzyme systems are present) are able to convert citrulline directly into urea with a yield of 65%. It is suggested that: (1) in early PCT cells, arginine synthase activity permits the conversion of the reabsorbed citrulline into arginine (which then diffuses towards blood vessels); and (2) in pars recta cells, arginase activity results in a net entry of arginine across the basolateral membranes and in a net exit of the formed urea into the tubular fluid, if the permeability to urea of luminal membranes is greater than that of basolateral membranes. Such a mechanism of urea secretion might contribute to the maintenance of urea recycling in the medulla and, thereby, participate in the process of concentrating the urine.     

t(8;21) prior to acute leukemia

A t(8;21)(q22;q22) without blood and bone marrow invasion by immature myeloid precursor cells occurred in a patient previously treated for polycythemia vera. The presence of a molecular rearrangement confirmed that the chromosomal abnormality was identical to that observed in acute leukemia with t(8;21). This case shows that the translocation, t(8;21), may occur in myelodysplasia and suggests that it can precede the appearance of overt leukemia.     

Use of type 1 /type 2 chimeric polioviruses to study determinants of poliovirus type 1 neurovirulence in a mouse model

We previously described the characteristics of a type 1/type 2 (PV-1/PV-2) chimeric poliovirus, v510, which contains the six amino acids specific for PV-2 in the B-C loop of VP1. This virus was found to be mouse-adapted, as PV-2 and in contrast with PV-1. Determinants of host range were studied in detail and are reported here. PV-1/PV-2 chimeras containing partial PV-1----PV-2 substitutions in the B-C loop of VP1 were obtained by making use of a mutagenesis cartridge on PV-1 cDNA. Analysis of mouse neurovirulence of these chimeras, when correlated with the three-dimensional structure of the v510 capsid, revealed that PV-2 residues important for mouse tropism are those which determine the particular conformation of the B-C loop of VP1 in v510. The mutation of the adenine residue at position 480 of the 5' noncoding region into a guanine residue has been shown to be an important determinant of PV-1 attenuation in monkeys. We show that introduction of this mutation in the v510 genome results in a virus which is partially attenuated for mice. This suggests that analysis of genomic determinants important for PV-1 neurovirulence could be carried out in a mouse model by making use of a mouse-adapted PV-1/PV-2 chimera.     

Childhood peer rejection and aggression as predictors of adolescent girls' externalizing and health risk behaviors: a 6-year longitudinal study

This 6-year longitudinal study examined girls' peer-nominated social preference and aggression in childhood as predictors of self- and parent-reported externalizing symptoms, substance use (i.e. cigarette, alcohol, and marijuana use), and sexual risk behavior in adolescence. Participants were 148 girls from diverse ethnic backgrounds, who were initially assessed in Grades 4-6 and again in Grades 10-12. Results supported a moderator model, indicating that social preference changed the nature of the association between childhood aggression and adolescent outcomes. When accompanied by peer rejection, aggressive behavior was moderately stable over time and significantly associated with adolescent girls' substance use and sexual risk behavior. However, under conditions of peer acceptance, no significant association between childhood aggression and adolescent outcomes emerged.     

Roxithromycin, Clarithromycin, and Azithromycin Attenuate the Injurious Effects of Bioactive Phospholipids on Human Respiratory Epithelium in Vitro

The effects of the bioactive phospholipids (PL), platelet-activating factor (PAF), lyso-PAF, and lysophosphatidylcholine (LPC) on the beat frequency and structural integrity of human ciliated respiratory epithelium were studied in vitro, in the presence or absence of polymorphonuclear leukocytes (PMNL), the antimicrobial agents, roxithromycin, clarithromycin, and azithromycin and the antioxidative enzymes catalase and superoxide dismutase (SOD). All three PL caused dose-dependent slowing of ciliary beat frequency (CBF) and epithelial damage (ED) at concentrations 1 g/ml, which were unaffected by inclusion of the antimicrobial agents and antioxidative enzymes. When epithelial strips were exposed to the combination of PMNL and PL, there was significant potentiation of ciliary dysfunction and ED, which was ameliorated by pretreatment of the PMNL with the antimicrobial agents or by inclusion of catalase, but not SOD. These results demonstrate that LPC, PAF, and lyso-PAF cause epithelial damage by direct mechanisms which are oxidant-independent, as well as by indirect mechanisms involving phagocyte-derived reactive oxidants. Macrolides and azalide antimicrobial agents may have beneficial effects on airway inflammation in asthma and microbial infections by protecting ciliated epithelium against oxidative damage inflicted by PL-sensitized phagocytes.     

Selective recognition of malaria antigens by human serum antibodies is not genetically determined but demonstrates some features of clonal imprinting

Malaria infection induces the production of serum antibodiesto a variety of malaria antigens but the prevalence of antibodiesto any particular antigen ins typically mucb less than 100%.It has been assumed that non-responsiveness to defined antigensin malaria immune subjects is due to HLA mediated restricutionof the Immune response. In this study we have investigated therole of HLA and non-HLA genes in the antibody response to twomerozoite surface antigens (MSP1 and MSP2) and a sexual stageantigen (Pfs260/230) opf P{lasmodium falcpartum, and concludethat host genotype is not a major determinant of responsiveness.Although antibody levels vary in accordance with seasonal variationsin malaria transmission in semi-immune children, antibiody levelsremain stable in clncall immine adults.