Characterization of mixed lymphocyte reaction blocking antibodies (MLR-Bf) in human pregnancy

Abstract Background It is known that during normal pregnancy and after immunotherapy blocking antibodies are developed, these antibodies inhibit mixed lymphocyte reaction and are also anti-mitogenic in nature. Mixed lymphocyte reaction blocking antibodies are specific to the husband's lymphocytes. In the present study an attempt has been made to characterize the mixed lymphocyte reaction blocking antibodies in normal pregnancy and in women with recurrent spontaneous abortion after immunotherapy. Methods Serum was obtained from women of different gestational windows of pregnancy (Ist, IInd, IIIrd trimesters and post delivery period of normal pregnancy), recurrent spontaneous aborters from pre and post immunization. Healthy (male and females) controls were screened for the presence of mixed lymphocyte reaction blocking antibodies. The standard mixed lymphocyte reaction technique was used to evaluate the inhibitory effect of serum in the mixed lymphocyte reaction. Each serum was tested for cytotoxic antibodies. Immunoglobulin G and its isotypes were isolated according to the standard protocol. Results In the present study we have observed that there was significant inhibition of proliferation response when immunoglobulin G from different trimesters of pregnancy were added to one way mixed lymphocyte reaction or to phytohemagglutinin activated lymphocyte proliferation assay. Similar pattern was seen when immunoglobulin G isolated from adequately immunized women with recurrent spontaneous abortion was used. It was further confirmed that amongst all the isotypes of immunoglobulin G, only immunoglobulin G-3 was found to be positive for the inhibitory effect. Conclusions Present study indicates that mixed lymphocyte reaction blocking antibodies are immunoglobulin G-3 in nature. It is developed during pregnancy and also after immunotherapy in women with recurrent spontaneous abortion who subsequently have the successful pregnancy.</p

Female Behaviour Drives Expression and Evolution of Gustatory Receptors in Butterflies

Secondary plant compounds are strong deterrents of insect oviposition and feeding, but may also be attractants for specialist herbivores. These insect-plant interactions are mediated by insect gustatory receptors (Grs) and olfactory receptors (Ors). An analysis of the reference genome of the butterfly Heliconius melpomene, which feeds on passion-flower vines (Passiflora spp.), together with whole-genome sequencing within the species and across the Heliconius phylogeny has permitted an unprecedented opportunity to study the patterns of gene duplication and copy-number variation (CNV) among these key sensory genes. We report in silico gene predictions of 73 Gr genes in the H. melpomene reference genome, including putative CO2, sugar, sugar alcohol, fructose, and bitter receptors. The majority of these Grs are the result of gene duplications since Heliconius shared a common ancestor with the monarch butterfly or the silkmoth. Among Grs but not Ors, CNVs are more common within species in those gene lineages that have also duplicated over this evolutionary time-scale, suggesting ongoing rapid gene family evolution. Deep sequencing (∼1 billion reads) of transcriptomes from proboscis and labial palps, antennae, and legs of adult H. melpomene males and females indicates that 67 of the predicted 73 Gr genes and 67 of the 70 predicted Or genes are expressed in these three tissues. Intriguingly, we find that one-third of all Grs show female-biased gene expression (n = 26) and nearly all of these (n = 21) are Heliconius-specific Grs. In fact, a significant excess of Grs that are expressed in female legs but not male legs are the result of recent gene duplication. This difference in Gr gene expression diversity between the sexes is accompanied by a striking sexual dimorphism in the abundance of gustatory sensilla on the forelegs of H. melpomene, suggesting that female oviposition behaviour drives the evolution of new gustatory receptors in butterfly genomes

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Health-related quality of life and long-term prognosis in chronic hypercapnic respiratory failure: a prospective survival analysis

Background: Health-related quality of life (HRQL) is considered as an important outcome parameter in patients with chronic diseases. This study aimed to assess the role of disease-specific HRQL for long-term survival in patients of different diagnoses with chronic hypercapnic respiratory failure (CHRF). Methods: In a cohort of 231 stable patients (chronic obstructive pulmonary disease (COPD), n = 98; non-COPD (obesity-hypoventilation syndrome, restrictive disorders, neuromuscular disorders), n = 133) with CHRF and current home mechanical ventilation (HMV), HRQL was assessed by the disease-specific Severe Respiratory Insufficiency (SRI) questionnaire and its prognostic value was prospectively evaluated during a follow-up of 2-4 years, using univariate and multivariate regression analysis. Results: HRQL was more impaired in COPD (mean +/- SD SRI-summary score (SRI-SS) 52.5 +/- 15.6) than non-COPD patients (67.6 +/- 16.4; p < 0.001). Overall mortality during 28.9 +/- 8.8 months of follow-up was 19.1% (31.6% in COPD, 9.8% in non-COPD). To identify the overall role of SRI, we first evaluated the total study population. SRI-SS and its subdomains (except attendance symptoms and sleep), as well as body mass index (BMI), leukocyte number and spirometric indices were associated with long-term survival (p < 0.01 each). Of these, SRI-SS, leukocytes and forced expiratory volume in I s (FEV(I)) turned out to be independent predictors (p < 0.05 each). More specifically, in non-COPD patients SRI-SS and most of its subdomains, as well as leukocyte number, were related to survival (p < 0.05), whereas in patients with COPD only BMI and lung function but not SRI were predictive. Conclusion: In patients with CHRF and HMV, the disease-specific SRI was an overall predictor of long-term survival in addition to established risk factors. However, the SRI predominantly beared information regarding long-term survival in non-COPD patients, while in COPD patients objective measures of the disease state were superior. This on one hand highlights the significance of HRQL in the long-term course of patients with CHRF, on the other hand it suggests that the predictive value of HRQL depends on the underlying disease

Cytokine Gene Expression in the Maternal-Fetal Interface in Somatic Cell Nuclear Transfer Pregnancies in Small Ruminants

The present retrospective study investigates pregnancy rates, incidence of pregnancy losses and large offspring syndrome (LOS), and immune-related gene expression of sheep and goat somatic cell nuclear transfer (SCNT) pregnancies. We hypothesized that significantly higher pregnancy losses observed in sheep SCNT pregnancies compared to goats are due to the increased amounts of T-helper 1 cytokines and pro-inflammatory mediators at the maternal-fetal interface. Sheep and goat SCNT pregnancies were generated using the same procedure. Control pregnancies were established by natural breeding. Although SCNT pregnancy rates at 45 days were similar in both species, pregnancy losses between 45 and 60 days and incidence of LOS were significantly increased in sheep compared with goats. At term, the expression of pro-inflammatory genes in sheep SCNT placentas was increased while the one of goat SCNT was similar to the control animals. Among the genes that had altered expression in sheep SCNT placentas are CTLA4, IL2RA, CD28, IFNG, IL6, IL10, TGFB1, TNF, IL1A and CXCL8. MHC-I protein expression was greater in sheep and goat SCNT placentas at term compared with control pregnancies. An unfavorable immune environment is present at the maternal-fetal interface in sheep SCNT pregnancies

Tyrphostins that suppress the growth of human papilloma virus 16‐immortalized human keratinocytes

ABSTRACT Human papilloma virus 16 (HPV16) is considered to be the causative agent for cervical cancer, which ranks second to breast cancer in women&apos;s malignancies. In an attempt to develop drugs that inhibit the malignant transformation of HPV16-immortalized epithelial cells, we examined the effect of tyrphostins on such cells. We examined the effect of tyrphostins from four different families on the growth of HPV16-immortalized human keratinocytes (HF-1) cells. We found that they alter their cell cycle distribution, their morphology, and induce cell death by apoptosis. The effects of tyrphostins on HF-1 cells are different from their effects on normal keratinocytes. Growth suppression by AG555 and AG1478 is accompanied by 30% apoptosis in HF-1 cells, but this is not observed in normal keratinocytes. Tyrphostin treatment produces distinctive morphological changes in HF-1 cells and in normal keratinocytes; however, the culture organization of normal keratinocytes is less disrupted. These differential effects of the tyrphostins on HPV16-immortalized keratinocytes compared with their effects on normal keratinocytes suggests that these compounds are suitable candidates for the treatment of papilloma. Previous and present results indicate that group 1 tyrphostins, which inhibit Cdk2 activation, and group 2 tyrphostins, represented by AG1478, a potent epidermal growth factor receptor kinase inhibitor, induce cell cycle arrest; and, in the case of HF-1 cells, apoptosis and differentiation. Cells accumulate in the G 1 phase of the cell cycle at the expense of S and G 2 ϩ M. These compounds block the growth of normal keratinocytes without inducing apoptosis or differentiation, causing them to accumulate in G 1 . AG17, which belongs to group 4, exerts its antiproliferative effect mainly by increasing the fractions of cells in G 1 with a concomitant decrease in the fraction of cells in S and G 2 ϩ M

Case report 511

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46790/1/256_2004_Article_BF00364055.pd

Case report 511

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46792/1/256_2004_Article_BF00366771.pd