Determinants of reflux perception in patients with non-erosive reflux disease who have reflux-related symptoms on potassium-competitive acid blocker therapy

Esophagus - This study investigated potential determinants of reflux perception in patients with non-erosive reflux disease (NERD) who had reflux-related symptoms on potassium-competitive acid...     

Saliva secretion is reduced in proton pump inhibitor-responsive non-erosive reflux disease patients

Esophagus - There is no consensus on the relationship between saliva secretion and non-erosive reflux disease (NERD). In this study, saliva secretion and salivary epidermal growth factor (EGF) in...     

Stimulated saliva secretion is reduced in proton pump inhibitor-resistant severe reflux esophagitis patients

Esophagus - Salivary secretion in patients with proton-pump inhibitor (PPI)-resistant severe reflux esophagitis has not been examined. In this study, saliva secretion and salivary epidermal growth...     

Identification of active sites in amidase: Evolutionary relationship between amide bond- and peptide bond-cleaving enzymes

Mainly based on various inhibitor studies previously performed, amidases came to be regarded as sulfhydryl enzymes. Not completely satisfied with this generally accepted interpretation, we performed a series of site-directed mutagenesis studies on one particular amidase of Rhodococcus rhodochrous J1 that was involved in its nitrile metabolism. For these experiments, the recombinant amidase was produced as the inclusion body in Escherichia coli to greatly facilitate its recovery and subsequent purification. With regard to the presumptive active site residue Cys203, a Cys203 → Ala mutant enzyme still retained 11.5% of the original specific activity. In sharp contrast, substitutions in certain other positions in the neighborhood of Cys203 had a far more dramatic effect on the amidase. Glutamic acid substitution of Asp191 reduced the specific activity of the mutant enzyme to 1.33% of the wild-type activity. Furthermore, Asp191 → Asn substitution as well as Ser195 → Ala substitution completely abolished the specific activity. It would thus appear that, among various conserved residues residing within the so-called signature sequence common to all amidases, the real active site residues are Asp191 and Ser195 rather than Cys203. Inasmuch as an amide bond (CO-NH₂) in the amide substrate is not too far structurally removed from a peptide bond (CO-NH-), the signature sequences of various amidases were compared with the active site sequences of various types of proteases. It was found that aspartic acid and serine residues corresponding to Asp191 and Ser195 of the Rhodococcus amidase are present within the active site sequences of aspartic proteinases, thus suggesting the evolutionary relationship between the two.     

Granulocyte colony-stimulating factor-producing undifferentiated carcinoma of the colon mimicking a pulmonary giant cell carcinoma: a case showing overexpression of CD44 along with highly proliferating nestin-positive tumor vessels

Granulocyte colony-stimulating factor (G-CSF)-producing tumors are known for their aggressive behavior. Only four cases of G-CSF-producing colorectal carcinoma have been previously reported. Herein, we present a case of an undifferentiated carcinoma of the descending colon showing G-CSF production and giant cell carcinoma morphology in a 93-year-old woman. A tumor with a diameter of 80 mm was identified in the descending colon via computed tomography. Descending colectomy was performed involving the abdominal wall where tumor invasion was observed. The white blood cell count, which was elevated before resection, decreased to normal levels after intervention. However, local recurrence at the resected site was detected 39 days after surgery. Upon recurrence, increased white blood cell counts and serum G-CSF were seen. The patient died because of respiratory failure 98 days after colectomy. By using immunohistochemistry, G-CSF expression was detected in tumor cells in the resected specimen, along with overexpression of CD44 and highly proliferating nestin-positive tumor vessels. The poor clinical outcome of this patient is consistent with previous reports that the expression of these three molecules predict poor prognosis. While G-CSF can be a therapeutic target considering its auto/paracrine function to induce tumor growth via the G-CSF receptor, CD44 and nestin may also be possible candidate therapeutic targets. Further studies are required to assess the efficacy of treatments targeting these three molecules.     

Hydrogen embrittlement of Ni-Ti superelastic alloy in fluoride solution

Hydrogen embrittlement of Ni-Ti superelastic alloy in a fluoride solution (0.2% APF) has been investigated by means of a tensile test (after immersion) and hydrogen thermal desorption analysis. Upon immersion, the tensile strength of the alloy decreased to the critical stress level of martensite transformation. Hydrogen desorption of the immersed specimens appeared with a peak at around 500 degrees C. The amount of absorbed hydrogen in the alloy ranged from 100 to 1000 mass ppm when immersed in the fluoride solution for 2 to 24 h. The immersion in the fluoride solution led to the degradation of mechanical properties due to hydrogen embrittlement. The results of the present study imply that one reason that Ti and its alloys fracture in the oral cavity is the fact that hydrogen is absorbed in a fluoride solution, such as prophylactic agents.     

Anticancer chemosensitivity profile of freshly separated human pancreatic cancer cells assessed by DNA synthesis inhibition assay

The chemosensitivity of 49 freshly separated human pancreatic cancers to seven kinds of anticancer agents were assessed by a DNA synthesis (³H-thymidine incorporation) inhibition assay. DNA synthesis is higher in involved lymph nodes (n=7), malignant effusion (n=15), liver metastasis (n=7), primary cancer (n=15), and skin metastasis (n=5). Chemosensitivity assay demonstrates that etoposide, 4-epirubicin, carboquone, and 5-fluorouracil are more effective than cisplatin, mitomycin-C, and Adriamycin. In general, metastatic lesions of pancreatic cancer tend to show higher chemosensitivity than primary lesions. Pathological analysis demonstrates that small primary pancreatic cancers tend to be more responsive than large primary cancers, and primary pancreatic cancers with no regional lymph node involvement also tend to be more responsive than those with nodal involvement. No significant differences are seen in terms of tumor spread, vascular involvement, sex of patient, and histological type. When chemosensitivity assay is not available, the results of the present study may be beneficial to choose the regimens. © 1994 Wiley-Liss, Inc.     

Possible involvement of multidrug-resistance-associated protein (MRP) gene expression in spontaneous drug resistance to vincristine,etoposide and adriamycin in human glioma cells

The multidrug-resistance phenotype in human tumors is partly associated with over-expression of the 170 kDa-P-glycoprotein encoded by the multidrug-resistance-1 (MDRI) gene. Another related, but non-P-glycoprotein, multidrug-resistance-associated protein (MRP) gene encodes a 190 kDa membrane ATP-binding protein. Glioblastoma multiforme is a highly malignant primary neoplasm of the central nervous system which is refractory to anti-cancer chemotherapy, but the mechanism underlying this drug resistance is unknown. Out of glioma cell lines, 2, namely IN500 and T98G, which had elevated MRP mRNA levels, showed the highest resistance to multiple anti-cancer agents such as etoposide, vincristine and adriamycin, and decreased intracellular accumulation of etoposide. In the remaining 5 cell lines, various degrees of sensitivity to adriamycin and etoposide appeared to correlate with their respective MRP mRNA levels. Our study proposes that MRP may be involved in spontaneous multidrug resistance in human gliomas.     

Genetic Complementation of the Immortal Phenotype in Group D Cell Lines by Introduction of Chromosome 7

Human immortal cell lines have been classified into at least four (A–D) genetic complementation groups by cell-cell hybrid analysis, i.e., a hybrid derived from different groups becomes mortal. Recently we have demonstrated that introduction of human chromosome 7 suppresses indefinite division potential in the non-tumorigenic human immortalized fibroblast lines KMST-6 and SUSM-1, both assigned to complementation group D. By extending our microcell-mediated chromosome transfer, we found that chromosome 7 also suppresses division potential in the human hepatoma line HepG2 (again, assigned to group D). Chromosome 7 was thus shown to suppress indefinite growth in the above group D cell lines irrespective of their cell types, or whether they are tumorigenic or not. Since chromosome 7 had no such effect on representative cell lines derived from complementation group A, B or C, these results indicate that the senescence gene(s) commonly mutated in the group D cell lines is located on chromosome 7.