Modulation of Immune Response in Lambs

Experiments using different types of antigen-adjuvant preparations were conducted in outbred sheep to compare effects of adjuvants on immune responses. Trinitrophenyl-ovalbumin (TNP-ovalbumin) incorporated in a preparation with nonionic block copolymers elicited high antibody titers to both ovalbumin and TNP. Different humoral immune responses were observed when Pasteurella haemolytica lipopolysaccharide (LPS) was added to the preparations. Responses to ovalbumin and TNP were reduced when Pasteurella haemolytica LPS was added to copolymer L121. The antibody titers to ovalbumin or TNP were not affected by the addition of LPS to the preparation containing copolymer L180.5. Lymphocyte proliferation assays demonstrated high stimulation indices at day 17 to ovalbumin by lymphocytes from lambs receiving preparations containing copolymers without Pasteurella haemolytica LPS

All-trans retinoic acid inhibits proliferation of intestinal epithelial cells by inhibiting expression of the gene encoding Krüppel-like factor 5

AbstractRetinoids are known inhibitors of epithelial cell proliferation. Previous studies indicate that Krüppel-like factor 5 (KLF5) is a pro-proliferative transcription factor. Here, we examined the effect of all-trans retinoid acid (ATRA) on proliferation of the intestinal epithelial cell line, IEC6. Treatment of IEC6 cells with ATRA inhibited their proliferation due to G1 cell cycle arrest. This inhibition was correlated with a decrease in the levels of KLF5 mRNA and promoter activity. In contrast, constitutive expression of KLF5 in stably transfected IEC6 cells with a KLF5-expressing plasmid driven by a viral promoter abrogated the growth inhibitory effect of ATRA. Moreover, ATRA inhibited proliferation of several human colon cancer cell lines with high levels of KLF5 expression but not those with low levels of KLF5 expression. Our results indicate that KLF5 is a potential mediator for the inhibitory effect of ATRA on intestinal epithelial cell proliferation

Phonon Universal Transmission Fluctuations and Localization in Semiconductor Superlattices with a Controlled Degree of Order

We study both analytically and numerically phonon transmission fluctuations and localization in partially ordered superlattices with correlations among neighboring layers. In order to generate a sequence of layers with a varying degree of order we employ a model proposed by Hendricks and Teller as well as partially ordered versions of deterministic aperiodic superlattices. By changing a parameter measuring the correlation among adjacent layers, the Hendricks- Teller superlattice exhibits a transition from periodic ordering, with alterna- ting layers, to the phase separated opposite limit; including many intermediate arrangements and the completely random case. In the partially ordered versions of deterministic superlattices, there is short-range order (among any $N$ conse- cutive layers) and long range disorder, as in the N-state Markov chains. The average and fluctuations in the transmission, the backscattering rate, and the localization length in these multilayered systems are calculated based on the superlattice structure factors we derive analytically. The standard deviation of the transmission versus the average transmission lies on a {\it universal\/} curve irrespective of the specific type of disorder of the SL. We illustrate these general results by applying them to several GaAs-AlAs superlattices for the proposed experimental observation of phonon universal transmission fluctuations.Comment: 16-pages, Revte

Krüppel-like factor 5 is an important mediator for lipopolysaccharide-induced proinflammatory response in intestinal epithelial cells

Lipopolysaccharide (LPS) is a bacterially-derived endotoxin that elicits a strong proinflammatory response in intestinal epithelial cells. It is well established that LPS activates this response through NF-κB. In addition, LPS signals through the mitogen-activated protein kinase (MAPK) pathway. We previously demonstrated that the Krüppel-like factor 5 [KLF5; also known as intestine-enriched Krüppel-like factor (IKLF)] is activated by the MAPK. In the current study, we examined whether KLF5 mediates the signaling cascade elicited by LPS. Treatment of the intestinal epithelial cell line, IEC6, with LPS resulted in a dose- and time-dependent increase in KLF5 messenger RNA (mRNA) and protein levels. Concurrently, mRNA levels of the p50 and p65 subunits of NF-κB were increased by LPS treatment. Pretreatment with the MAPK inhibitor, U0126, or the LPS antagonist, polymyxin B, resulted in an attenuation of KLF5, p50 and p65 NF-κB subunit mRNA levels from LPS treatment. Importantly, suppression of KLF5 by small interfering RNA (siRNA) resulted in a reduction in p50 and p65 subunit mRNA levels and NF-κB DNA binding activity in response to LPS. LPS treatment also led to an increase in secretion of TNF-α and IL-6 from IEC6, both of which were reduced by siRNA inhibition of KLF5. In addition, intercellular adhesion molecule-1 (ICAM-1) levels were increased in LPS-treated IEC6 cells and this increase was associated with increased adhesion of Jurkat lymphocytes to IEC6. The induction of ICAM-1 expression and T cell adhesion to IEC6 by LPS were both abrogated by siRNA inhibition of KLF5. These results indicate that KLF5 is an important mediator for the proinflammatory response elicited by LPS in intestinal epithelial cells

Epidemiology of ectopic pregnancy at Laquintinie Douala hospital (Cameroon): prevalence survey, clinical profile, therapeutic and transfusion issues

Background: Pregnancy is a serious pathology of the first trimester of pregnancy and is the leading cause of death. The objective of our work was to determine the hospital prevalence of ectopic pregnancy (EP), to describe the epidemiological, clinical and therapeutic profile given the often-haemorrhagic context at Laquintinie Hospital in Douala.Methods: We carried out a retrospective study over 10 years, from January 1st, 2007 to December 31st, 2016, using the operating theatre registers and the files of patients admitted during this period for ectopic pregnancy in the gynaecology and obstetrics department of the Laquintinie Hospital in Douala.Results: A total of 905 cases of EP for 32,595 deliveries were recorded, for an overall incidence of 2.8%. EP mainly affected the age group of 25 to 35 (60.6%), single people (57.9%) and housewives (46.6%). The risk factors found were similar to those of cervical cancer, namely multiple sexual partners (80.4%), the precocity of sexual intercourse under 18 years (54.1%) and sexually transmitted infections (52.5%). The symptomatic triad (pelvic pain, amenorrhea and metrorrhagia) was found in 46.1% of cases with a respective order of frequency of 96.9%, 77.3% and 63.6% The management was essentially surgical by radical laparotomy (97% of cases). Two of the 07 deaths were due to religious considerations.Conclusions: EP remains a frequent pathology in our environment with a heavy toll of tubal amputations and death

Benefits of sexual practice during pregnancy: myth or reality? Comparative study and outcome of childbirth in Douala (Cameroon)

Background: Pregnancy is the term used to describe the period in which a foetus develops in the uterus and lasts 40 weeks measured from the last menstrual period. Anatomic and physiologic changes in pregnant women usually make couples to change their emotional and sexual activities that may impact childbirth. There are few studies in our setting that describe the roles of sexual practice during pregnancy and maternal-foetal outcomes of childbirth.Objective of this study aimed at assessing the benefits of sexual practice during pregnancy in a target population and to assess the outcome.Methods: We carried out a comparative cross-sectional study from February 2018 to May 2018, at the maternity of Laquintinie Hospital in Douala. Socio-demographic, obstetric, sexual history in pregnancy, birth and neonatal data were collected using a structured questionnaire. Univariate and multivariate analyses were conducted at a 95% confidence interval.Results: A total of 300 respondents completed study and 69.6% were favourable to sexual intercourse during pregnancy. Induction or augmentation of labour was common in the unfavourable group [OR: 2.52 (1.53-4.15); p=0.004]. Almost one in two participants gave birth by caesarean section and the indications for caesarean section were similar in both groups. Participants without sexual intercourse in pregnancy had a 9-fold increased risk of perineal tears [OR: 8.99 (4.02-10.1); p=0.001] and 5.4-fold risk of cervical tears [OR: 5.44 (2.44-8.73); p=0.0001].Conclusions: Sexual practice in pregnancy appears to be protective against excessive use of oxytocin, perineal and cervical tears

Photoinduced suppression of the ferroelectric instability in PbTe

The interactions between electrons and phonons drive a large array of technologically relevant material properties including ferroelectricity, thermoelectricity, and phase-change behaviour. In the case of many group IV-VI, V, and related materials, these interactions are strong and the materials exist near electronic and structural phase transitions. Their close proximity to phase instability produces a fragile balance among the various properties. The prototypical example is PbTe whose incipient ferroelectric behaviour has been associated with large phonon anharmonicity and thermoelectricity. Experimental measurements on PbTe reveal anomalous lattice dynamics, especially in the soft transverse optical phonon branch. This has been interpreted in terms of both giant anharmonicity and local symmetry breaking due to off-centering of the Pb ions. The observed anomalies have prompted renewed theoretical and computational interest, which has in turn revived focus on the extent that electron-phonon interactions drive lattice instabilities in PbTe and related materials. Here, we use Fourier-transform inelastic x-ray scattering (FT-IXS) to show that photo-injection of free carriers stabilizes the paraelectric state. With support from constrained density functional theory (CDFT) calculations, we find that photoexcitation weakens the long-range forces along the cubic direction tied to resonant bonding and incipient ferroelectricity. This demonstrates the importance of electronic states near the band edges in determining the equilibrium structure.Comment: 9 page, 3 figure

Cost-effectiveness of a chronic pain intervention for people living with HIV (PLWH)

Background: Chronic pain is a common, disabling, and costly comorbidity, particularly in people living with HIV (PLWH). This study developed and pilot tested a pain self-management intervention for chronic pain tailored to PLWH called Skills TO Manage Pain (STOMP). Objectives: Given the additional resources needed to deliver STOMP in HIV clinical settings, an important objective of the pilot study was to assess not only STOMP’s preliminary efficacy, but also its cost-effectiveness. Research design and subjects: The present study draws from a 44-participant, 2-arm randomized pilot trial of the STOMP intervention vs usual care among PLWH and at least moderate chronic pain (Clinicaltrials.gov: NCT02824562). Cost-effectiveness is presented as the incremental cost-effectiveness ratio (ICER). Costs were considered from the clinic perspective over a 1-year time horizon using real costs from the pilot trial. It was conservatively assumed there would be no costs savings. The Standard Gamble (SG) method was used to directly measure utilities. Results: Thirty-six participants met inclusion criteria for the present analyses. Mean age was 52 years; 61% were female and 86% were black. The total cost of STOMP was $483.83 per person. Using the SG method, the change in QALYs was 0.15, corresponding to an ICER of$3,225. Conclusions: STOMP’s cost/QALY is substantially lower than the $50,000 to$100,000/QALY benchmark often used to indicate cost-effectiveness. Although based on a pilot trial and, therefore, preliminary, these findings are promising, and suggest the importance of cost analyses in future STOMP trials

BIRC6 mediates imatinib resistance independently of Mcl-1

© 2017 Okumu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Baculoviral IAP repeat containing 6 (BIRC6) is a member of the inhibitors of apoptosis proteins (IAPs), a family of functionally and structurally related proteins that inhibit apoptosis. BIRC6 has been implicated in drug resistance in several different human cancers, however mechanisms regulating BIRC6 have not been extensively explored. Our phosphoproteomic analysis of an imatinib-resistant chronic myelogenous leukemia (CML) cell line (MYL-R) identified increased amounts of a BIRC6 peptide phosphorylated at S480, S482, and S486 compared to imatinib-sensitive CML cells (MYL). Thus we investigated the role of BIRC6 in mediating imatinib resistance and compared it to the well-characterized anti-apoptotic protein, Mcl-1. Both BIRC6 and Mcl-1 were elevated in MYL-R compared to MYL cells. Lentiviral shRNA knockdown of BIRC6 in MYL-R cells increased imatinib-stimulated caspase activation and resulted in a ~20-25-fold increase in imatinib sensitivity, without affecting Mcl-1. Treating MYL-R cells with CDK9 inhibitors decreased BIRC6 mRNA, but not BIRC6 protein levels. By contrast, while CDK9 inhibitors reduced Mcl-1 mRNA and protein, they did not affect imatinib sensitivity. Since the Src family kinase Lyn is highly expressed and active in MYL-R cells, we tested the effects of Lyn inhibition on BIRC6 and Mcl-1. RNAi-mediated knockdown or inhibition of Lyn (dasatinib/ponatinib) reduced BIRC6 protein stability and increased caspase activation. Inhibition of Lyn also increased formation of an N-terminal BIRC6 fragment in parallel with reduced amount of the BIRC6 phosphopeptide, suggesting that Lyn may regulate BIRC6 phosphorylation and stability. In summary, our data show that BIRC6 stability is dependent on Lyn, and that BIRC6 mediates imatinib sensitivity independently of Mcl-1 or CDK9. Hence, BIRC6 may be a novel target for the treatment of drugresistant CML where Mcl-1 or CDK9 inhibitors have failed