5-Keto-3-cyano-2,4-diaminothiophenes as selective maternal embryonic leucine zipper kinase inhibitors.

Maternal embryonic leucine zipper kinase (MELK) is involved in several key cellular processes and displays increased levels of expression in numerous cancer classes (colon, breast, brain, ovary, prostate and lung). Although no selective MELK inhibitors have yet been approved, increasing evidence suggest that inhibition of MELK would constitute a promising approach for cancer therapy. A weak high-throughput screening hit (17, IC ≈ 5 μM) with lead-like properties was optimized for MELK inhibition.

Association of the physical activity with leptin blood serum level, body mass indices and obesity in schoolgirls.

Decreased physical activity is undoubtedly significantly associated with obesity. Similarly, the proper hormones secretion, the proper weight and body development. The aim of this study was to investigate the relationship between body mass composition and leptin concentration in relation to the degree of physical activity expressed in MET-h/week (metabolic equivalent per week).

A diadenosine 5',5''-P1P4 tetraphosphate (Ap4A) hydrolase from Arabidopsis thaliana that is activated preferentially by Mn2+ ions.

Asymmetrical diadenosine 5',5''-P(1)P(4) tetraphosphate (Ap(4)A) hydrolases are key enzymes controlling the in vivo concentration of Ap(4)A--an important signaling molecule involved in regulation of DNA replication and repair, signaling in stress response and apoptosis. Sequence homologies indicate that the genome of the model plant Arabidopsis thaliana contains at least three open reading frames encoding presumptive Ap(4)A hydrolases: At1g30110, At3g10620, and At5g06340. In this work we present efficient overexpression and detailed biochemical characteristics of the AtNUDX25 protein encoded by the At1g30110 gene.

Helicobacter pylori infection and serum gastrin, ghrelin and leptin in children of Polish shepherds.

Objective: Family unit is generally accepted as one of the contributors to Helicobacter pylori infection that is most frequently acquired in childhood, so it seems logical to diagnose and treat this infection in childhood. This study was designed to assess H. pylori prevalence in children from shepherd families having contacts with sheep.

The usefulness of capsulated 13C-urea breath test in diagnosis of Helicobacter pylori infection in patients with upper gastrointestinal bleeding.

Background: H. pylori infection and peptic ulcerations and their complications such as bleeding are causally related, but the available methods used in bleeding to confirm active H. pylori lack accuracy.

Prevalence of Helicobacter pylori infection in Polish shepherds and their families.

Background: Helicobacter pylori infection might, in some instances, be considered as zoonosis.

Aim: The aim of this study was to assess the H. pylori prevalence in Polish shepherds and in their families as compared to controls.

Cloning and characterization of the first member of the Nudix family from Arabidopsis thaliana.

The sequence motif commonly called a Nudix box, represented by (GX(5)EX(7)REVXEEXGU) is the marker of a widely distributed family of enzymes that catalyze the hydrolysis of a variety of nucleoside diphosphate derivatives. Here we describe the cloning and characterization of an Arabidopsis thaliana cDNA encoding a Nudix hydrolase that degrades NADH. The deduced amino acid sequence of AtNUDT1 contains 147 amino acids.

Tobacco BY-2 cells excise both 3-methyladenine and 7-methylguanine from methylated DNA.

Two of the major products in DNA resulting from exposure to alkylating agents are 7-methylguanine and 3-methyladenine. N-methylpurine-DNA-glycosylase is required for excision of these lesions. Recently, the 3-methyladenine-DNA-glycosylase gene of Arabidopsis thaliana was cloned and shown to be involved only in repair of 3-methyladenine.

Microdose 14C-urea breath test in detection of Helicobacter pylori.

Etiologic role for Helicobacter pylori (Hp) seems to be well established in gastric pathology. The high urease activity of Hp can be used to detect this bacterium by non-invasive urea breath tests (UBT). We validated the microdose version of the test in which 37 kBq 14C-urea is given orally in capsule.

A large DNA repeat of the dispersion pattern common to wheat and rye genomes.

A Hind III-generated fragment of wheat embryo nuclear DNA has been cloned and sequenced. The cloned fragment corresponds to a 1241 bp long, moderately repeated (60,000 copies/genome) segment of the genomic DNA. The repeat is AT-rich (67%), contains an open reading frame for 151 amino acids and several nucleotide blocks resembling the consensus domain of autonomously replicating sequences.

A moderately repeated DNA sequence of wheat and rye genomes.

A 371 base pair segment (bordered by Hind III and Eco RI cutting sites) of wheat embryo nuclear DNA has been cloned and sequenced. It is AT-rich (68%), shares some sequence features with autonomously replicating sequence (ARS) elements, and occurs in approximately 7600 copies per haploid genome. When used as probe for blot hybridization to Hind III-digested wheat DNA, it gives an irregular series of hybridization bands.

Generation of endogenous prostaglandins and thromboxanes in taurocholate-induced gastric mucosal lesions.

This study demonstrates that the suppression of thromboxane biosynthesis by OKY-1581, a selective inhibitor of thromboxane biosynthesis, prevents dose-dependently taurocholate-induced gastric mucosal necrosis and enhances the cytoprotective effect of low dose of taurocholate against mucosal necrosis by large dose of this agent. In all animals treated with OKY-1581, a decrease in mucosal generation of thromboxane was accompanied by an increased production of PGs probably due to availability of greater amounts of a common substrate in a cyclooxygenase pathway. This study provides direct evidence that gastric mucosa generates thromboxanes which may be involved in the pathogenesis of taurocholate-induced gastric mucosal lesions.

Effect of enkephalin and naloxone on vagal and hormonal stimulation of pancreatic secretion in man.

Pancreatic secretory responses to modified sham-feeding (MSF) and secretin (1 U/kg-h) infusion were examined in eight healthy subjects with and without administration of the stable enkephalin analogue (Ala-Enk) and/or naloxone. MSF produced a clear increase in pancreatic protein output, reaching about 45% of caerulein (0.5 microgram/kg-h) maximal output.

Comparison of enkephalin and atropine in the inhibition of vagally stimulated gastric and pancreatic secretion and gastrin and pancreatic polypeptide release in dogs.

Enkephalins have been detected in vagal nerves and myenteric plexus neurons but no study has been performed to determine their action on vagally stimulated gastric and pancreatic secretion. In this study we infused IV methionine-enkephalin (Met-enk) alone, naloxone (a pure opiate antagonist) alone, or their combination before, during and after vagal stimulation in 4 dogs with esophageal, gastric and pancreatic fistulas. For the comparison, atropine was given before, during and after vagal stimulation in the same animals.

Organ removal and disappearance half-time of synthetic human pancreatic polypeptide.

Human pancreatic polypeptide (HPP) was infused into 6 anesthetized dogs at a constant dose of 1.0 micrograms/kg/h over 60 min. Blood samples for RIA of pancreatic polypeptide were taken repeatedly from a carotid artery, jugular vein, femoral vein, renal vein and mesenteric vein.

Gastric secretory and plasma hormonal responses to sham-feeding of varying duration in patients with duodenal ulcer.

Gastric acid and serum gastrin, pancreatic polypeptide, and insulin responses to cephalic vagal stimulation were studied in eight patients with duodenal ulcer using modified sham-feeding for periods varying from four to 30 minutes. In addition, the maximal acid response to sham-feeding was compared with that induced by pentagastrin in 10 healthy subjects and 14 patients with duodenal ulcer. It was found that the gastric acid response to modified sham-feeding reached the maximal value after 15 minutes of sham-feeding and amounted to about 68% of the pentagastrin maximum.

Comparison of TRH and anorexigenic peptide on food intake and gastrointestinal secretions.

Thyrotropin releasing hormone (TRH), distributed throughout the gastrointestinal tract, and anorexigenic peptide (AP), isolated recently from the urine of females with "hypothalamic" anorexia nervosa, have been shown to affect food intake but no study has been performed to compare their action on gastrointestinal secretions. This report shows that both TRH and AP reduce dose-dependently the food intake during sham-feeding and inhibit gastric and pancreatic secretions in response to various exogenous and endogenous stimulants in conscious dogs. The results indicate that TRH and AP have similar inhibitory action on feeding and gastrointestinal secretory activity and that they may be involved in peptidergic mediation of satiety and gastrointestinal secretion.

Oligo(U)- and poly(U)-containing RNA of wheat embryo.

A UMP-rich RNA fraction was separated from the bulk cellular RNA by affinity chromatography of wheat embryo total RNA. The obtained preparation was heterogeneous and contained polyribonucleotide chain segments which were resistant to RNAase T1 and consisted mainly of UMP residues (87 mol%). The UMP-rich segments were of various sizes, including large oligonucleotides and polynucleotides (up to approx.

Effects of pirenzepine and atropine on gastric secretory and plasma hormonal responses to sham-feeding in patients with duodenal ulcer.

The effects of atropine and pirenzepine on sham-feeding stimulated gastric secretion and serum gastrin and pancreatic polypeptide levels have been studied in 12 patients with duodenal ulcer. Both atropine and pirenzepine caused a dose-dependent decrease in acid and pepsin secretion induced by sham-feeding. Serum gastrin response to sham-feeding was negative and it was enhanced by atropine but suppressed by pirenzepine.

Effect of methylated prostaglandin E2 analogue on insulin secretion in man.

Previous studies of the effect of E series prostaglandins /PGs/ on insulin secretion gave conflicting results in animals and little information in man. This study was designed to determine the effect of methylated PGE2 analogue /15/S/- 15-methyl PGE2 methyl ester/, given orally, intraduodenally or intravenously, on insulin secretion, both under basal conditions and in response to intraduodenal or intravenous administration of glucose in 22 male volunteers. Methylated PGE2 kept basal serum insulin level unchanged, but significantly reduced insulin response by 15 +/- 6 microunits/ml to intravenous glucose pulse injection /0.

High molecular weight UMP-rich RNA of germinating wheat embryo.

The synthesis of a relatively homogeneous RNA fraction was observed in germinating wheat embryo. The fraction synthesised within the first 3 h of germination had a high molecular weight (approx. 2.