Differential ability of Th1 and Th2 T cells to express Fas ligand and to undergo activation-induced cell death

Stimulation of previously activated T cells through the antigenreceptor can result in the apoptotic death of the respondingcell, a process referred to as activation-induced cell death(AICD). This process appears to involve Fas (CD95) and tts ligand(Fas-L). The distribution of Fas and Fas-L on various T cellsubsets has not been extensively characterized. We have thereforeanalyzed cells committed to a T_h1- or T_h2-type differentiationpattern for the expression and function of Fas-L. Using botha sensitive bloassay and flow cytometry, we demonstrate thatcloned T_h1 cells express high levels of Fas-L, whereas clonedT_h cells express only low levels. The expression of Fas-L byT_h1 and T_h2 cells correlates with the relative abilities ofthese two cell types to undergo AICD. Whereas AICD is readilyobserved in cultures of cloned T_h1, but not T_h2 cells, T_h2 cellsare capable of undergoing apoptosls in the presence of T_h1 cellsexpressing Fas-L The ability of T cells to undergo AICD appearsto be unrelated to the presence of various cytokines. Thus,the Fas/Fas-L pathway appears to be critical for the inductionof AICD and this pathway is differentially regulated in cellscommitted to either T_h1 or T_h2 differentiation.     

Exogenous carbohydrate oxidation from maltose and glucose ingested during prolonged exercise

Summary Intestinal perfusion studies have shown that glucose absorption from maltose occurs faster than from isocaloric glucose. To determine whether ingested maltose might be a superior source of carbohydrate (CHO) for endurance athletes, we compared the rates of gastric emptying, absorption and oxidation of 15 g · 100 ml^–1 solutions of maltose and glucose. Six endurance-trained cyclists drank 1200 ml of either U-¹⁴C maltose or U-¹⁴C glucose as a 400-ml loading bolus immediately before exercise, and as 8 × 100-ml drinks at 10-min intervals during a 90-min ride at 700% of maximal oxygen consumption. The rates of gastric emptying [maltose 690 (SD 119) ml · 90 min^–1; glucose 655 (SD 93) ml · 90 min^–1], the appearance of U-¹⁴C label in the plasma, and the peak rates of exogenous CHO oxidation [maltose 1.0 (SD 0.09) g · min^–1; glucose 0.9 (SD 0.09) g · min^–1] were not significantly different. Further, the 51 (SD 8) g of maltose and the 49 (SD 9) g of glucose oxidised during exercise were similar. Each accounted for approximately 2001o of the total CHO oxidised during the 90 min of exercise. Since only half of the CHO delivered to the intestine was oxidised in the 90-min ride (maltose 49%; glucose 50%), we conclude that neither the rate of gastric emptying, nor digestion limited the rate of ingested CHO utilisation during the early stages of exercise. Rather, we hypothesise that, initially, it could be the rate at which the CHO diffuses across the unstirred water layer of the brush-border of the intestinal villi that limits the utilisation of soluble CHO ingested during prolonged exercise.     

Maternal self-medication and provision of nevirapine to newborns by women in Rakai, Uganda

To assess the effectiveness of maternal self-administration of nevirapine for prevention of mother-to-child transmission (MTCT) of HIV, we conducted a program to provide maternal and newborn doses of nevirapine to pregnant women in rural Uganda. Women provided blood for HIV testing and were offered voluntary counseling and testing (VCT) during annual community HIV surveys. HIV-positive women who accepted VCT were offered nevirapine tablets and syrup. Blood samples were collected postpartum from women and their babies. Infants were tested for HIV by polymerase chain reaction (PCR), and a subsample of maternal and infant blood was assayed for nevirapine. Among the 981 women tested for HIV, 900 (91.7%) accepted VCT, of whom 105 (11.7%) were HIV-positive. Ninety-three women accepted nevirapine, of whom 81 (87.1%) were followed postpartum; 75 (92.6%) reported receipt of the drug, and 69 reported taking the tablets (85.2%). There were 81 liveborn babies (3 sets of twins), and 67 (84.8%) received the syrup. In a subsample of 25 mothers reporting receipt of the drug, nevirapine was detected in 22 (88.0%) and 24 (96.0%) babies tested. PCR of 67 infant blood samples identified 5 HIV-positive (MTCT rate = 7.5%, 95% confidence interval [CI]: 0.3%-16.6%). Mothers can administer nevirapine to themselves and their newborns and can achieve low rates of perinatal HIV infection.     

Characterization of an inversion duplication of the short arm of chromosome 8 by fluorescent in situ hybridization

A de novo chromosome aberration in a woman with severe mental retardation and minor anomalies has been characterized cytogenetically. The patient's karyotype was described as 46, XX, inv dup (8)(p12 → p23.1). Previous Southern blot dosage studies with the marker locus D8S7 demonstrated that the patient was monosomic for this locus, suggesting that the rearrangement generated a duplication-deficiency chromosome. We have reinvestigated this patient using fluorescent in situ hybridization with chromosome 8 cosmids and an Alu-PCR product specific for 8p. These studies have confirmed directly that the duplicated chromosome also has undergone deletion. © 1992 Wiley-Liss, Inc.     

Stress and dental caries in the rat

The stress of crowding and exposure to inescapable electric shock increased both the incidence and the severity of dental caries in rats housed in a conventional animal facility. Male Osborne-Mendel rats were inoculated intraorally with cariogenic bacteria, fed a high-sucrose diet, and housed in either a conventional or a sheltered facility. Rats in both housing conditions were subdivided into control and stress groups. At the end of the 56-day trial period, stressed rats from conventional housing had a significant increase in both incidence and severity of dental caries in comparison to their controls. In contrast, stressed rats from sheltered housing had a trend toward increased cariogenesis which reached significance in only one of five scores. These rats also failed to gain weight comparable to their controls, making it possible that stress-induced reduction in appetite partially offset stress-induced exacerbation in cariogenesis.This investigation was supported in part by the following Grants from the United States Public Health Service: CA 20093, HL 22727, and HL 07374.     

A membrane cofactor protein transgenic mouse model for the study of discordant xenograft rejection

Background:  In recent years, interest has been revived in the possibility of transplanting organs into humans from a phylogenetically disparate species such as the pig (xenotransplantation). Such discordant xenografts, however, are subject to hyperacute rejection (HAR) and activation of host complement plays a major role in this rejection. This problem may be solved through the use of transgenic technology by providing the grafted tissue with molecules that down-regulate the action of host complement.
Results: Transgenesis with a yeast artificial chromosome (YAC) was used to produce transgenic mice with the complete genomic gene of the human complement regulator membrane cofactor protein (MCP). Transgenic mice were obtained that exhibit full regulation of MCP as normally observed in humans. Hearts from these mice were shown to be significantly protected from HAR caused by human serum in an in vivo experimental procedure.
Conclusions:  We conclude that MCP can protect discordant xenografts from HAR caused by human serum and that transgenic mice can be used effectively as in vivo models for the study of the role of human complement regulatory molecules in xenotransplantation.     

Linkage of chromosome 13q32 to schizophrenia in a large veterans affairs cooperative study sample

Several prior reports have suggested that chromosomal region 13q32 may harbor a schizophrenia susceptibility gene. In an attempt to replicate this finding, we assessed linkage between chromosome 13 markers and schizophrenia in 166 families, each with two or more affected members. The families, assembled from multiple centers by the Department of Veterans Affairs Cooperative Studies Program, included 392 sampled affected subjects and 216 affected sib pairs. By DSM-III-R criteria, 360 subjects (91.8%) had a diagnosis of schizophrenia and 32 (8.2%) were classified as schizoaffective disorder, depressed. The families had mixed ethnic backgrounds. The majority were northern European-American families (n = 62, 37%), but a substantial proportion were African-American kindreds (n = 60, 36%). Chromosome 13 markers, spaced at intervals of approximately 10 cM over the entire chromosome and 2-5 cM for the 13q32 region were genotyped and the data analyzed using semi-parametric affected only linkage analysis. For the combined sample (with race broadly defined and schizophrenia narrowly defined) the maximum LOD score was 1.43 (Z-score of 2.57; P = 0.01) at 79.0 cM between markers D13S1241 (76.3 cM) and D13S159 (79.5 cM). Both ethnic groups showed a peak in this region. The peak is within 3 cM of the peak reported by Brzustowicz et al. [1999: Am J Hum Genet 65:1096-1103].     

Immunochemical features of a macromolecule of Treponema denticola

In this study the extraction and the immunochemical features of a lipopolysaccharide-like (LPSL) macromolecule of T. denticola strains 35405, 35404, 33521 and 11 were investigated. The yield of LPSL molecule ranged between 0.5-0.9% of the cell dry weight, it possessed Limulus amebocyte lysate clotting activity, and it contained glucosamine, phosphate, heptose, glucose, small amounts of KDO, myristic and beta hydroxy myristic acid. Sera obtained from healthy individuals (ADA type I) periodontitis, from 3-8 month old infants, or the mouse monoclonal antibody, diluted 1:2, against T. pallidum did not react with the LPSL antigens of T. denticola strains 35405, 35404, 33521, and 11. Sera from patients with ADA type III-IV periodontitis were reactive with two 8-14 kDa bands even at serum dilutions of 1:2000. Sera from patients with ADA type II periodontitis showed good antibody response to the 8-14 kDa band at a dilution of 1:50, but were weekly reactive, or nonreactive at serum dilutions of 1:200. This study indicates that extraction of a lipopolysaccharide-like macromolecule is feasible from the assay spirochetes, and this macromolecule may be used as an antigen for the diagnosis of ADA types II-IV periodontitis.