Einfluß der Temperatur auf die RNA-Synthese von Escherichia coli CRT 266 (dna Bts) nach Infektion mit dem Bakteriophagen T3

Infection of the temperature-sensitive E. coli CRT 266 (dna B^ts) with T3-phages at the temperature of 30°C and 35°C, respectively, induced T3-specific RNA synthesis with a maximum rate at 7 min (30°C) and 4.5 min (35°C) afte infection. At temperatures above 40°C no T3-induced RNA synthesis could be observed. Infection of E. coli CR 34–45 (dna B⁺) with T3 phages at 30°C, 35°C and at temperatures above 40°C, however, produced T3-specific RNA synthesis. The maximum of T3-induced RNA synthesis could be observed between 7 min and 3 min depending on the temperature during infection. The inability to form T3-specific RNA after infection of E. coli CRT 266 at nonpermissive temperatures may be a cause for the absence of the formation of T3 phages and lysis of the host cells.     

Haploidentical Peripheral Blood Stem Cell Transplantation Demonstrates Stable Engraftment in Adults with Sickle Cell Disease

We report on the screening and development of haploidentical hematopoietic stem cell transplantation (HSCT) for adult patients with clinically aggressive sickle cell disease (SCD) at our institution. Of 50 adult SCD patients referred for HSCT between January 2014 and March 2017, 20% were denied by insurance. Of 41 patients initially screened, 10% lacked an available haploidentical donor, 29% had elevated donor-specific antibodies (DSAs), and 34% declined to proceed to HSCT. All 10 patients who were transplanted received peripheral blood stem cells. The initial 2 were conditioned with alemtuzumab/total body irradiation (TBI) 3?Gy followed by post-transplant cyclophosphamide and failed to engraft. The next 8 patients received the regimen developed at Johns Hopkins University with TBI 3?Gy. Granulocyte colony-stimulating factor was administered from day +12 in those with HbS < 30%. All 8 patients engrafted with a median time to neutrophil >.5 × 10⁹/L of 22 days (range, 18 to 23). One patient subsequently lost the graft, and 7 (87.5%) maintained >95% donor cell chimerism at 1-year post-HSCT. Two patients developed acute graft-versus-host disease (GVHD) of at least grade II. One had chronic GVHD and died >1 year after HSCT of unknown causes. With a median follow-up of 16 months (range, 11 to 29), 7 patients (87.5%) are alive. Our findings suggest that limited insurance coverage, high rate of DSAs, and patient declining HSCT may limit the availability of haploidentical HSCT in adult SCD patients. The modified Hopkins regimen used here demonstrates high engraftment and low morbidity rates and should be tested in larger, multicenter, prospective clinical trials.     

Bilateral cataract and high serum ferritin: a new dominant genetic disorder?

This paper reports the cosegregation in a three generation pedigree of dominantly inherited cataract with an abnormally high level of serum ferritin. In this family, circulating L ferritin was raised in all subjects affected by cataract independently of iron overload. We suggest that a disorder of ferritin metabolism could be a new genetic disorder leading to lens opacity. Cataract-hyperferritaemia syndrome could also be a new contiguous gene syndrome involving the L ferritin gene and the gene coding for the lens membrane protein (MP19), which both map to the same region of chromosome 19q.     

Interleukin-10 inhibits IgE-mediated nitric oxide synthase induction and cytokine synthesis in normal human keratinocytes

Human keratinocytes (HK) generate nitric oxide (NO) and proinflammatory mediators following activation with either IgE/anti-IgE immune complexes or a combination of lipopolysaccharide (LPS) and interferon-γ (IFN-γ). Recently, interleukin-10 (IL-10) has been shown to down-regulate various inflammatory responses and to be secreted by lymphocytes and dendritic cells during skin inflammatory reactions. We show here that IL-10 down-regulates the production of tumor necrosis factor (TNF)-α and IL-6 by activated HK. Also, induction of inducible nitric oxide synthase (iNOS) expression in HK by IgE/anti-IgE or LPS/IFN-γ is significantly reduced by the addition of IL-10. This effect is dose dependent and correlates with reduction of iNOS mRNA production and enzyme level. Therefore, IL-10 down-regulates NO-mediated HK inflammatory responses and may thus participate in the regulation of the skin immune network.     

Single-channel properties and regulation of pinacidil/glibenclamide-sensitive K+ channels in follicular cells from Xenopus oocyte

Follicular oocytes from Xenopus laevis contain K⁺ channels that are activated by members of the recently recognized class of vasorelaxants that includes the pinacidil derivative P1060. These channels are blocked by antidiabetic sulphonylureas such as glibenclamide. Opening of the glibenclamide-sensitive K⁺ channels with P1060 promotes follicular oocyte maturation. Whole-cell and single-channel patch-clamp configurations were used to monitor K⁺ channel activity in isolated follicular cells. In the presence of micromolar concentrations of intracellular Mg²⁺ ATP, P1060 activated a whole-cell K⁺ current that was blocked by glibenclamide. The P1060 response was depressed by millimolar concentrations of intracellular ATP and ATP[S]. Single-channel recordings identified two different types of K⁺ channel. These channels differed in their unitary conductances (19 pS and 150 pS), in their sensitivities to internal Ca²⁺, to charybdotoxin and to pinacidil and glibenclamide. Only the Ca²⁺-independent K⁺ channel (19 pS) was activated by the pinacidil derivative and blocked by glibenclamide. Opening of the 19-pS glibenclamide-sensitive K⁺ channel by P1060 critically required the presence of a low concentration of Mg²⁺ATP in the intracellular medium. The 19-pS K⁺ channel was opened by increasing intracellular cAMP. Similar effects were obtained by intracellular application of the catalytic subunit of protein kinase A in the presence of micromolar concentrations of Mg²⁺ATP. Both acetylcholine and the phorbol ester phorbol 12-myristate 13-acetate blocked the 19-pS K⁺ channel after it was activated by P1060.This work was supported by the Centre National de la Recherche Scientifique (CNRS) and the Fondation pour la Recherche Médicale (FRM)     

Seasonal analysis and acaricidal activity of the thymol-type essential oil of Ocimum gratissimum and its major constituents against Rhipicephalus microplus (Acari: Ixodidae)

Parasitology Research - The tick Rhipicephalus microplus affects cattle health, with production loss in tropical and subtropical regions. Moreover, the use of commercial acaricides has been reduced...     

Involvement of cysteinyl leukotrienes in angiotensin II-induced contraction in isolated aortas from transgenic (mRen-2)27 rats

OBJECTIVES : We have previously reported that 5-lipoxygenase-derived products, and particularly the cysteinyl leukotrienes (CysLTs), were involved in angiotensin II (Ang II)-induced contractions in isolated aortas from spontaneously hypertensive rats. DESIGN : The aim of this study was to assess the role of CysLTs in the vascular response to Ang II in an Ang II-dependent model of hypertension, the (mRen-2)27 transgenic rats (TGs). METHODS : Intact aortic rings from TG and normotensive Sprague-Dawley rats (SDs) were suspended in organ chambers for isometric tension development in response to Ang II. In addition, the release of CysLTs in response to Ang II (0.3 micromol/l) was measured by enzyme immunoassay. RESULTS : In isolated aortas from TG rats, pretreatment with the 5-lipoxygenase inhibitor (AA861, 10 micromol/l) or the CysLT1 receptor antagonist (MK571, 1 micromol/l) significantly (P < 0.05) reduced Ang II-induced contractions by 52 and 42%, respectively. In addition, Ang II induced a 2.6-fold increase in CysLT release (pg/mg dry weight tissue: 58.3 +/- 17.9 (Ang II, n = 7) versus 22.5 +/- 5.9 (basal, n = 7) P < 0.05), which was inhibited by the AT1 receptor antagonist losartan (1 micromol/l). In contrast, in aortas from SD rats, pretreatment with AA861 or MK571 did not alter Ang II-induced contraction and CysLT production remained unchanged after exposure to Ang II. CONCLUSION : These data suggest that CysLTs are involved in the contractile responses to Ang II in isolated aortas from TG but not from SD rats.