Common polymorphisms of protein tyrosine phosphate non-receptor type 2 gene are not associated with risk of Crohn’s disease in Indian

BACKGROUNDMultiple genetic risk factors for Crohn’s disease (CD) have been identified. However, these observations are not consistent across different populations. The protein tyrosine phosphate non-receptor type 2 (PTPN2) gene plays a role in various aspects of host defense including epithelial barrier function, autophagy, and innate and adaptive immune response. Two common polymorphisms in the PTPN2 gene (rs2542151 and rs7234029) have been associated with risk of CD in Western countries. AIMTo evaluate the association of PTPN2 gene polymorphisms with risk of CD in Indian population.METHODSWe conducted a prospective case-control study. Patients with CD were recruited, and their clinical and investigation details were noted. Controls were patients without organic gastrointestinal disease or other comorbid illnesses. Two common polymorphisms in the PTPN2 gene (rs2542151 and rs7234029) were assessed. DNA was extracted from peripheral blood samples of cases and controls and target DNA was amplified using specific sets of primers. The amplified fragments were digested with restriction enzymes and the presence of polymorphism was detected by restriction fragment length polymorphism. The frequency of alleles was determined. The frequencies of genotypes and alleles were compared between cases and controls to look for significant differences.RESULTSA total of 108 patients with CD (mean age 37.5 ± 12.7 years, females 42.6%) and 100 controls (mean age 39.9 ± 13.5 years, females 37%) were recruited. For the single nucleotide polymorphism (SNP) rs7234029, the overall frequency of G variant genotype (AG or GG) was noted to be significantly lower in the cases compared to controls (35.2% vs 50%, P = 0.05). For the SNP rs2542151, the overall frequency of G variant genotype (GT or GG) was noted to be similar in cases compared to controls (43.6% vs 47%, P = 0.73). There were no significant differences in minor allele (G) frequency for both polymorphisms between the cases and controls. Both the SNPs had no significant association with age of onset of illness, gender, disease location, disease behaviour, perianal disease, or extraintestinal manifestations of CD.CONCLUSIONUnlike observation form the West, polymorphisms in the PTPN2 gene (rs7234029 and rs2542151) are not associated with an increased risk of developing CD in Indian patients.     

Presence of the red cell alloantibody anti-E in an 11-week-old infant

The development of red cell (RBC) alloantibodies in infants less than 4 months of age is believed to be rare. Though there are no well-documented published accounts, the formation of alloanti-E in a multiply transfused 11-week-old infant is reported here. The infant, blood group B, D +, developed necrotizing enterocolitis and renal failure requiring 31 transfusions of washed and unwashed RBCs (group B and group O), as well as fresh-frozen plasma and platelets. Six weeks after the first blood transfusion, alloanti-E was detected. The anti-E weakly agglutinated R2R2 screening RBCs at 37 degrees C and sensitized these RBCs to react with anti-IgG. The infant's RBCs were typed as E-. Passive transfer of alloanti-E was ruled out by the negative antibody screening tests of each donor unit and the absence of any RBC alloantibodies in the mother's serum. Stored samples of the infant's sera were tested, and anti-E was shown to be present approximately 11 days after exposure to a known E+ RBC unit. The appearance of alloanti-E in this time frame is consistent with a secondary immune response. Primary immunization most likely took place in the first 4 weeks of transfusion therapy.     

The antiatherogenic effects of components isolated from pollen Typhae

Based on the results of previous investigations that pollen Typhae, a Traditional Chinese Medicine, Had antiatherogenic effects, several components were isolated successively from the drug and their effects on porcine aortic endothelial cell (EC) and smooth muscle cell (SMC) cultures as well as on platelet aggregation were examined. 12 components isolated from Pollen Typhae have been identified on their chemical structures and biological effects. 4 of them showed different evident antiatherogenic effects. 1) Isorhamnetin-3-O-rhamnosyl-glucoside could stimulate EC to produce tPA and PGI; 2)Quercetin-3-O-neohesperidose could protect EC from injury by fibrin, as well as raise tPA activity; 3)β-Sitosterol palmitate could inhibit SMC proliferation and 4) β-Sitosterol glucoside showed an inhibitory effect on platelet aggregation. These results would provide some information for the search of new drugs in the treatment and prevention of atherosclerosis.     

Luteal deficiency caused by human ovarian follicular fluid peptide in post-partum marmosets, Callithrix jacchus

A peptide purified from human ovarian follicular fluid (hOFFP) was administered during the follicular phase of post-partum marmosets. Four of the five animals treated with hOFFP, ovulated as evidenced by the presence of ovarian stigmata at the time of laparotomy. However, only 2 of these animals became pregnant, one had a normal delivery while the other aborted. A shortening of the luteal phase was observed in the other three animals and all animals conceived in subsequent cycles. The results indicated that treatment with the ovarian follicular fluid peptide resulted in impairment of fertility as a result of luteal insufficiency.     

Studies of in vitro red cell autoantibody production in normal donors and in patients with autoimmune hemolytic anemia

The in vitro production of red cell autoantibodies (RBC AuAbs) has been investigated for better understanding of the pathogenesis of autoimmune hemolytic anemia (AIHA). Peripheral blood mononuclear cells (PBMNCs) were isolated and cultured for 14 days with or without added pokeweed mitogen (PWM), autologous RBCs, methyldopa, procainamide, and alpha-methylnorepinephrine. Also, isolated B cells were infected with Epstein-Barr virus (EBV) to produce polyclonal B-cell lines. Supernatants were tested for IgG and IgM RBC AuAbs by use of 125I-staphylococcal protein A (SPA). RBC AuAbs were detected in PBMNC cultures without additives to the culture medium of four of eight patients who had warm-antibody AIHA or a positive direct antiglobulin test (DAT) without hemolytic anemia. In two of these patients, RBC AuAb production was augmented by the addition of PWM, and in two additional patients, RBC AuAbs were detected only after the addition of PWM. Supernatants from PBMNC cultures from three of four normal donors produced RBC AuAbs independent of the presence of PWM; in two of these subjects, PWM augmented production of RBC AuAbs. PBMNC cultures from three DAT-negative patients with systemic lupus erythematosus produced RBC AuAbs, one in the presence of PWM and two in its absence. With one exception, there was no augmentation of AuAb production by the addition to the culture system of autologous RBCs or drugs. EBV infection of B cells from four patients with AIHA and four normal persons yielded B-cell lines secreting RBC AuAbs. The quantity of RBC AuAb after a 24-hour culture of EBV-transformed B cells was significantly greater in cultures from four patients who had AIHA than in cultures from four normal persons.(ABSTRACT TRUNCATED AT 250 WORDS)     

Progesterone antagonist lilopristone: a potent abortifacient in the common marmoset

The effects of a progesterone antagonist ZK 98.734 (lilopristone) on implantation, early pregnancy, and midpregnancy were studied in the common marmoset, Callithrix jacchus jacchus. Treatment (5 mg/da intramuscularly for 3 consecutive days) on day (n = 8) after the midcycle peak in estradiol levels in mated animals induced a premature drop in plasma progesterone levels and shortened the ovarian cycle length. Treatment on day 20 (n = 5) or day 40 (n = 5) induced a drop in progesterone levels and decidual collapse. In three animals treated on day 40, vaginal bleeding was observed within 46 hours of the initiation of treatment. Treatment on day 80 resulted in expulsion of the fetuses with a mean induction abortion interval of 39 hours (range, 20 to 48 hours). The progesterone antagonistic effects of ZK 98.734 could be a result of the decrease in progesterone synthesis by the corpus luteum and/or placenta in addition to the interference with the progesterone binding to its cellular receptors in the target organ. Our study suggests that ZK 98.734 has potential for fertility regulation. Clinical trials for postcoital contraception, induction of menstruation, and early abortifacient effects are warranted.     

Mode of action of iron (III) chelators as antimalarials: I. Membrane permeation properties and cytotoxic activity

We have designed two subfamilies of lipophilic iron (III) chelators previously termed reversed siderophores (RSFs). The agents display physicochemical properties that favor extraction of iron beyond membrane barriers of Plasmodium falciparum-infected red blood cells. We studied the in vitro antimalarial potency of RSFs and their relationship to the membrane permeation properties of these agents. The mode of RSF action involves: (1) fast access to intracellular compartments of parasitized cells; (2) selective and high-affinity chelation of iron (III) from parasitized cells; (3) fast exit from cells after iron (III) complexation; and (4) exertion of cell damage on parasites exposed for 3 to 5 hours to drugs, irrespective of the stage of parasite development. These results suggest that on reaching a critical intraerythrocyte target, RSFs induce an iron deficit that parasites in general, and rings in particular, have limited capacity to restore.