hElp3 Directly Modulates the Expression of HSP70 Gene in HeLa Cells via HAT Activity

Human Elongator complex, which plays a key role in transcript elongation in vitro assay, is incredibly similar in either components or function to its yeast counterpart. However, there are only a few studies focusing on its target gene characterization in vivo. We studied the effect of down-regulation of the human elongation protein 3 (hELP3) on the expression of HSP70 through antisense strategy. Transfecting antisense plasmid p1107 into HeLa cells highly suppressed hELP3 expression, and substantially reduced expression of HSP70 mRNA and protein. Furthermore, chromatin immunoprecipitation assay (ChIP Assay) revealed that hElp3 participates in the transcription elongation of HSPA1A in HeLa cells. Finally, complementation and ChIP Assay in yeast showed that hElp3 can not only complement the growth and slow activation of HSP70 (SSA3) gene transcription, but also directly regulates the transcription of SSA3. On the contrary, these functions are lost when the HAT domain is deleted from hElp3. These data suggest that hElp3 can regulate the transcription of HSP70 gene, and the HAT domain of hElp3 is essential for this function. These findings now provide novel insights and evidence of the functions of hELP3 in human cells

Weight-/height-related bone mineral density is not reduced after renal transplantation

Growth retardation is a frequent finding in patients after renal transplantation (Tx). Areal bone mineral density (BMD) in these patients has usually been reported to be low for age. We investigated the possible influence of height and weight retardation on the measurement of BMD in lumbar spine (BMD(L2-4)) and total body (BMDbody) using dual-energy X-ray absorptiometry in 44 (13 female) pediatric Tx patients with a median age of 13.1 (range 3.3-23.1) years. Patients were studied at 2.9 (range 1-10) years after Tx. Median body height in female and male patients was -2.10 (-3.6 to -0.3) and -2.35 (-5.3 to +1.0) standard deviation score (SDS), respectively. BMD expressed as grams per square centimeter bone area according to age was below the 5th percentile in 10 of 44 patients, but only 1 patient had low values for BMD(L2-4), and none for BMDbody, when the data were corrected for height or weight. BMDbody was closely correlated with height, weight, and body surface area (r=0.88), whereas the correlation for BMD(L2-4) was less (r=0.76). In 6 patients who achieved final height, height SDS was -2.27 (-4.3-0.4). Z-scores for BMDbody related to age, height, and weight were -1.0 (-2.6 to -2.3), 1.25 (0.1-3.4), and 0.81 (0.0-2.4), respectively. There was no age-dependent change when areal BMD values (g/cm2) were corrected for vertebral size to obtain bone volumetric density (BMDvol, g/cm3). Independent of height, cumulative methylprednisolone dose correlated negatively with BMD(L2-4) only in patients who had received a total dose of more than 6 g/m2 of the drug (r = -0.54, P= 0.045). In conclusion, BMD in pediatric patients after Tx is no longer diminished when the data are corrected for height or weight rather than age, or when the data are expressed as bone volumetric density

The Antimotility Action of a Trifluoromethyl Ketone on Some Gram-negative Bacteria

The inhibition of bacterial motility was studied by a trifluoro methyl ketone derivative on two Escherichia coli strains (wild strain having a proton pump system and the proton pump-deficient mutant strain) and two Helicobacter pylori strains (clarithromycin susceptible and clarithromycin resistant). Evidence is presented of the inhibitory action of 1-(2-benzoxazolyl)-3,3,3-trifluoro-2-propanone (TF18) on the proton motive forces of the two bacterial strains by affecting the action of biological motor and proton efflux in the membranes. The swimming, the forward motion was more sensitive than the vibration or tumbling to the inhibition. We suppose that the inhibiton of bacterial motility is related to the virulence of bacteria: consequently the pathogenicity can be reduced in the presence of TF18

Short-term effect of external cardioversion on patients with pacemakers and atrial fibrillation/flutter

Background: Previous case reports have demonstrated increased threshold and exit block due to external cardioversion (ECV).International guidelines from 2006 recommend that ECV is performed with anterior-posterior paddle orientation, that the anterior paddle is placed with minimum distance of 8 cm from the pulse generator, and that the cardiac device is interrogated before and after ECV. Currently, there are to our knowledge no larger studies that have examined the effect of ECV on pacemakers

Helicobacter pylori-Induced Immunological Responses in Patients with Duodenal Ulcer and in Patients with Cardiomyopathies

The interaction between the bacteria and the host is a key factor determining the clinical consequences of H. pylori infection. The immune system plays an important role in either promoting or preventing the disease. The mucosal production of TNF-a, IL-6, IL-8 and IL-10 and the CagA status were investigated in H. pylori-positive patients with duodenal ulcer (DU). The concentrations of these cytokines in gastric antral mucosal specimens from patients infected with H. pylori (n = 40) were determined by ELISA and compared with data on mucosal specimens from H. pylori-negative patients (n = 12). The local TNF-a, IL-6 and IL-8 concentrations in the antral biopsy samples were significantly higher (p < 0.001) in the patients infected with H. pylori than in the samples from the H. pylori-negative subjects. CagA positivity was demonstrated in 39 (97.5%) of the 40 patients with DU, and in 41 (70.7%) of H. pylori-positive (58 of 100) healthy blood donors. In complementary studies focusing on extragastric disease, it was found that 57% of patients with ischaemic heart disease were seropositive as concerns H. pylori, and 91% of them had antibodies against human heat shock protein 60, too. This study suggests that, besides the bacterial virulence factor, the host response of an increased mucosal production of inflammatory cytokines can be relevant to the gastric pathophysiology in H. pylori-induced DU. At the same time, in ischaemic heart diseases the role of autoimmune processes induced by H. pylori cannot be excluded