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Background: Carbonic anhydrase (CA) catalyzes the reversible hydration of CO(2) to bicarbonate and a proton, and alpha-class CA has been reported to facilitate the acid acclimation of Helicobacter pylori (hpalphaCA). The purpose of this study was to characterize the beta-class CA of H. pylori (hpbetaCA) and elucidate the role of this enzyme as a possible drug target for eradication therapy.Methods: We isolated DNA clones of independent H. pylori strains obtained from patients with gastritis (n = 15), gastric ulcer (n = 6), or gastric cancer (n = 16), and then studied genetic polymorphisms. In addition, the susceptibility of H. pylori to sulpiride, an antiulcer drug and efficient inhibitor of both hpalphaCA and hpbetaCA, was studied with an in vitro killing assay.Results: DNA sequences of all 37 hpbetaCA clones encoded a 221 amino acid polypeptide with a variety of polymorphisms (57 types of amino acid substitution at 48 residue positions). There was no polymorphism functionally relevant to the gastric lesion type. One strain included unique residues that were not seen in the other 36 clones from Japanese patients but which were found in a strain obtained from the United Kingdom. Sulpiride had killing effects at concentrations greater than 200 microg/ml for H. pylori, including strains resistant to clarithromycin, metronidazole, or ampicillin.Conclusions: Helicobacter pylori might have evolved independently in the Caucasian and Japanese populations. Dual inhibition of alpha-and beta-class CAs could be applied as alternative therapy for eradication of H. pylori. [ABSTRACT FROM AUTHOR]

Background: The goal of this study was to clarify morphogenetic development in colorectal neoplasms with depressions by examining isolated crypts and their pit patterns.Methods: Twelve colorectal neoplasms with depressions were examined endoscopically, stereomicroscopically, and histopathologically. The pit pattern was defined according to Kudo's classification. The HCl digestion method was used to isolate the crypts. For scanning electron microscopy observations of the surface structure, specimens were mounted on brass stubs, coated with gold, and then observed.Results: In isolated crypts with bifurcation extending to the middle or all the way to the lesion surface, the crypt orifice was round with a type IIIS pit pattern. In those with bifurcations extending up to the upper portion, the crypt orifice was oval with a type IIIS pit pattern. Some crypts were almost completely separated into two. The orifice diameter of a nonbifurcated crypt was 95.1 +/- 28.1 microm, whereas the diameters of crypts with bifurcations extending to the middle or the upper part were 114.7 +/- 40.8 and 208.1 +/- 71.4 microm, respectively. Thus, the orifice diameter of a crypt with the bifurcation reaching the upper part was about twice that of orifices of nonbifurcated crypts or those with bifurcations extending to the middle.Conclusions: Our results indicate that colorectal neoplasms with depressions may enlarge by a process of crypt bifurcation in which a single crypt divides into two crypts. [ABSTRACT FROM AUTHOR]

Elongin A is a transcription elongation factor that increases the overall rate of mRNA chain elongation by RNA polymerase II. To gain more insight into the physiological functions of Elongin A, we generated Elongin A-deficient mice. Elongin A homozygous mutant (Elongin A−/−) embryos demonstrated a severely retarded development and died at between days 10.5 and 12.5 of gestation, most likely due to extensive apoptosis. Moreover, mouse embryonic fibroblasts (MEFs) derived from Elongin A−/− embryos exhibited not only increased apoptosis but also senescence-like growth defects accompanied by the activation of p38 MAPK and p53. Knockdown of Elongin A in MEFs by RNA interference also dramatically induced the senescent phenotype. A study using inhibitors of p38 MAPK and p53 and the generation of Elongin A-deficient mice with p53-null background suggests that both the p38 MAPK and p53 pathways are responsible for the induction of senescence-like phenotypes, whereas additional signaling pathways appear to be involved in the mediation of apoptosis in Elongin A−/− cells. Taken together, our results suggest that Elongin A is required for the transcription of genes essential for early embryonic development and downregulation of its activity is tightly associated with cellular senescence.Cell Death and Differentiation (2007) 14, 716–726. doi:10.1038/sj.cdd.4402067; published online 15 December 2006 [ABSTRACT FROM AUTHOR]

PURPOSE : Resistin, a recently discovered adipocyte-derived cytokine, is reported to be associated with insulin resistance in mice and may play a similar role in humans. The relation between resistin and physical fitness has not been assessed. METHODS: Thirty-eight obese, non-diabetic patients(25F/13M, 33±9(20-53)yrs, BMI 33.1 ± 4.8)were studied. Serum resistin was measured by enzyme immunoassay(BioVendor Laboratory Medicine, Inc. Czech Republic). An all-out treadmill exercise test was performed, and after resting for ≥60 minutes, the walking speed at an intensity of 50%HRR was determined. The exercise time until exhaustion and the walking speed at 50%HRR were utilized as indices of physical fitness. Plasma glucose and serum insulin concentration were measured during three hours of 75g-oral glucose tolerance testing(GTT). The body composition was measured by underwater-weighing and abdominal fat distribution at the umbilical level was evaluated using a CT scan. RESULTS: 1)Serum resistin concentration was 24.3 ± 14.4 (3.6-72.4)ng/ml. 2)The exercise time was 16.4 ± 3.1 (7-23)min. and the walking speed was 4.9 ± 0.6(3.5-6.0)km/hr. These two parameters were positively correlated (r-0.65). 3)Mean glucose and insulin(i.e, area under the curve during 180 minutes of GTT divided by 180)were 132 ± 21(88-198) mg/dl. and 80 ± 11 (30-176)µU/ml, respectively. 4)The exercise time and the walking speed showed negative correlation with BMI, % body fat, fat mass, and the subcutaneous fat area (P<0.01), but not with HOMA-IR or mean insulin. Serum resistin concentration did not correlate with the exercise time and the walking speed. Serum resistin concentration did not correlate with any of the parameters of body composition, fat distribution. and insulin resistance, either. CONCLUSIONS: In these subjects, the value of serum resistin did not correlate with either insulin sensitivity or exercise capacity. [ABSTRACT FROM AUTHOR]

Fatigue of repetitive voluntary muscular effort and/or mental stress is defined as reduced physical and/or mental performance. This definition, in the field of sports and exercise, illustrates the likelihood that both central and peripheral factors may be involved. Peripheral mechanisms within muscle that cause fatigue include the accumulation of metabolites, lactate acid or ammonia leading to the loss of power development. Unit recently, the accumulation of these metabolites was considered as the one of the etiologies of muscle fatigue. However, it is reported that acidification led by increasing lactic acid counteracts the depressing effects of elevated extra cellular potassium on muscle force, To date, little information on the central mechanisms of fatigue has prevailed, but several biological mechanisms have been proposed to explain the central fatigue. This report focuses on the neurotransmitter serotonin [5-hydroxytryptamin (5-HT)] as the etiology of central fatigue, including the possible role of exercise and nutrition. [ABSTRACT FROM AUTHOR]