SummaryWe investigated the transcription of the urease gene cluster ureABIEFGH in Helicobacter pylori to determine the regulation of gene expression of the highly produced enzyme urease. Northern blot hybridization analysis demonstrated that cells of the wild-type strain grown in an ordinary broth had transcripts of ureAB, ureABI, ureI, ureIE H and ure H FGH, but cells of a ureI-disrupted mutant had only the ureAB transcript. When the wild-type cells were exposed to pH 8 for 30 min, very little mRNA was detected. However, when exposed to pH 6, a large amount of the ureIE H H transcript, which was longer than the ureIE H transcript, together with the additional transcripts ureA-BIEFGH and ure H EFGH were detected. Rifampicin addition experiments demonstrated that urease mRNAs, and the ureIE H transcripts in particular, are more stable at pH 5.5 than at pH 7. In accord with these results, urease activity in the crude cell extract of the pH 5.5 culture was twice as much as that of the pH 7 culture, although the amounts of UreA and UreB detected by immunoblot analysis were similar. The transcription start point of ureI was identified by primer extension using a ureA promoter-deleted mutant, and a consensus sequence of RpoD-RNA polymerase was found in the ureI promoter. The 3 H
We have cloned and sequenced Helicobacter pylori alpha-class carbonic anhydrase (hpCA) from patients with different gastric mucosal lesions, including gastritis (n=15), ulcer (n=6), and cancer (n=16). Although several polymorphisms were newly identified such as 12Ala, 13Thr, 16Ile, and 168Phe, there was no significant relevance of any polymorphism with gastric mucosal lesion types. A library of sulfonamides/sulfamates has been investigated for the inhibition of hpCA, whereas new derivatives have been obtained by attaching 4-tert-butyl-phenylcarboxamido/sulfonamido tails to benzenesulfonamide/1,3,4-thiadiazole-2-sulfonamide scaffolds. All types of activity for inhibition of hpCA have been detected. Dorzolamide and simple 4-substituted benzenesulfonamides were weak inhibitors (KI 873-4360 nM). Sulfanilamide, orthanilamide, some of their derivatives, and indisulam showed better activity (KI 413-640 nM), whereas most of the clinically used inhibitors, such as methazolamide, ethoxzolamide, dichlorophenamide, brinzolamide, topiramate, zonisamide, etc., acted as medium-potency inhibitors (KI 105-378 nM). Some potent hpCA inhibitors were detected too (KI 12-84 nM) among acetazolamide, 4-amino-6-chloro-1,3-benzenedisulfonamide and some newly designed compounds incorporating lipophilic tails. Some of the newly prepared derivatives had selectivity ratios for inhibiting hpCA over hCA II in the range of 1.25-3.48, showing thus some selectivity for inhibiting the bacterial enzyme. Since hpCA is essential for the survival of the pathogen in acid, it might be used as a new pharmacologic tool in the management of drug-resistant H. pylori.
A jet discharged upward into an ambient of higher temperature than that of the jet fluid was investigated experimentally.The width of the upflow spread linearly to the distance from the nozzle exit, whereas the width of the whole jet was almost constant. The height of top of jet varied in proportion to the square root of the discharge Froude number,The time-averaged velocities and temperatures as well as the intensities of their fluctuations at the jet axis were well correlated with the same scaling law as that used for the buoyant jet. The radial distributions showed no similarity profiles for the timeaveraged velocities and temperatures, and the intensities of their fluctuations.
Experimentelle Untersuchung eines vertikalen turbulenten Freistrahls mit Strahlrichtung entgegengesetzt dem Auftrieb ZusammenfassungEin Freistrahl, der in eine Umgebung mit hSherer Temperatur als die der Strahlfliissigkeit ausstrSmt, wurde experimentell untersucht. Die Breite der Aufw~irtsstrSmung nahm linear mit der Entfernung der Dfise zu, w~ihrend die Breite des ganzen Strahls nahezu konstant war. Die maximale Eindringh6he des Strahls war proportional zur Quadratwurzel der Abstr6m-Froude-Zahl. Sowohl die mittleren Geschwindigkeiten und Temperaturen als auch die Intensit~iten der Schwankungsgeschwindigkeiten und -temperaturen in der Achse wurden mit dem )khnlichkeitsgesetz gut korreliert, das auf den Auftriebsstrahl angewandt wurde. Die radialen Verteilungen zeigten keine )khnlichkeitsprofile fiir die mittleren Geschwindigkeiten und Temperaturen sowie ftir die Intensitiiten der Schwankungsgeschwindigkeiten und -temperaturen.
A link between hyperthyroidism and pulmonary hypertension has been reported, but the underlying mechanisms of these two conditions have not been clearly identified. The aim of this study was to determine the clinical correlates of pulmonary hypertension in patients with Graves’ disease. Among 50 consecutive patients with Graves’ disease referred for echocardiography, 18 patients (36 %) had pulmonary hypertension measured by continuous-wave Doppler echocardiography (pulmonary artery systolic pressure >35 mmHg). The patients with pulmonary hypertension had significantly higher pulmonary vascular resistance (PVR), cardiac output and thyroid-stimulating hormone receptor antibody (TRAb) compared to those without (p < 0.001, p = 0.028 and p < 0.001, respectively). Pulmonary artery systolic pressure had a good correlation with TRAb (r = 0.74, p < 0.001), but was not related to free T4 (r = 0.12, p = 0.419) and free T3 (r = 0.22, p = 0.126). To determine the important variables present in patients with Graves’ disease that may be related to pulmonary artery systolic pressure, 4 variables (PVR, cardiac output, TRAb and free T3) were used in the multivariate analysis. In addition to PVR (standard regression coefficient = 0.831, p < 0.001) and cardiac output (standard regression coefficient = 0.592, p < 0.001), TRAb (standard regression coefficient = 0.178, p < 0.001) emerged as a significant variable related to pulmonary artery systolic pressure. Thus, in addition to the effect of thyroid hormone on the cardiovascular system, autoimmune-mediated pulmonary vascular remodeling may play a role in Graves’ disease-linked elevated pulmonary artery systolic pressure.
Lymph node micrometastasis was associated with poor outcome in patients with histologically node-negative gastric cancer. The number and the level of lymph node micrometastases are useful prognostic markers for deciding treatment strategies for additional therapy and follow-up.
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