Point mutations of ornithine decarboxylase gene are an infrequent event in colorectal cancer but a missense mutation was found in a replication error positive patient with hMSH2 germline mutation

BACKGROUND: Ornithine decarboxylase (ODC; EC 4.1.1.17) is the first rate-limiting enzyme in the biosynthesis of polyamines. ODC protein has a characteristic amino acid sequence, the PEST sequence, which is related to the enzyme's rapid degradation. ODC cDNA prepared from human hepatoma tissues has been reported to show nonsense or missense mutations. METHODS: We examined somatic mutations of ODC cDNA by RT-PCR-SSCP analysis and mRNA expressions by RT-PCR in 50 colorectal cancer tissues to investigate the involvement of ODC gene alterations in colorectal cancers. RESULTS: Increased expression of the ODC gene was observed in 36 cases (86%) out of the 42 examined by RT-PCR. In one case, a missense mutation was found in the cancer tissue but not in normal mucosa. The missense mutation from Asp to Asn at codon 424, in the PEST region, possibly stabilizes the ODC protein. In colorectal cancer, replication error and a germline mutation in hMSH2 gene were observed. CONCLUSIONS: The missense mutation at codon 424 is speculated to be a cause of stabilization and a passenger mutation owing to the mutator phenotype. Since only one of 50 colorectal cancers exhibited a missense mutation of the ODC gene, mutations in ODC gene are not frequent in colorectal cancer. The increased expression of the ODC gene was noted in 86% of colorectal cancer tissues by RT-PCR, however, it was not due to point mutations in ODC coding exons.      

Entire septal patch technique for postinfarction ventricular septal rupture

Postinfarction ventricular septal rupture is still a surgically challenging situation with high operative mortality. We report a case of ventricular septal rupture in a 75-year-old woman successfully treated with our newly devised technique, in which a pliable large septal path is fixed with transmural sutures placed in posterior left ventricular free wall and anterior ventriculotomy closing sutures, thus covering the septal wall almost entirely. Our method may simplify the operation and reduce the risk of residual leakage.     

Parkinsonism induced by atypical neuroleptics in a patient with severe iron deficiency.

Although still controversial, iron deficiency has been indicated as one of the risk factors for developing neuroleptic-induced extrapyramidal symptoms (EPSs), including akathisia, dystonia, and neuroleptic malignant syndrome. Here we report our experience of iron supplementation and alternating neuroleptics for treating Parkinsonism in a schizophrenic female patient having severe iron deficient anemia.     

Lack of toxicity or carcinogenicity of S-170, a sucrose fatty acid ester, in F344 rats.

A chronic combined toxicity and carcinogenicity study of S-170, a sucrose fatty acid ester, was performed in male and female F344 rats. S-170 was given ad libitum in the diet at levels of 0, 1.25, 2.5 or 5% to 10 rats/sex/group for 12 months to determine chronic toxicity and 0, 2.5 or 5% to 50 rats/sex/group for two years in the carcinogenicity study. Treatment with S-170 exerted no effect on survival in either sex. In the 12-month chronic toxicity study, no treatment-related effects on body weights, or hematological, blood biochemical, urinary and pathological parameters were demonstrated in any of the treated groups. In the carcinogenicity study, S-170 did not cause any dose-related significant increase in the incidences of tumors in any organs or tissues. Taken together, the results clearly demonstrate that S-170 has neither toxic nor carcinogenic activity in F344 rats under the conditions of the study. No observed adverse effect levels (NOAELs) calculated from the 12-month chronic toxicity and carcinogenicity study were 2.37 g/kg/day in males and 2.80 g/kg/day in females, and 2.12 g/kg/day in males and 2.42 g/kg/day in females, respectively.     

Effect of plaunotol on bacterial translocation in the rat small intestine

BACKGROUND AND AIMS: Bacterial translocation is precipitated by an increase in bacteria or endotoxin, depression of the membrane barrier, and an increase in mucosal permeability. Plaunotol is a mucosal protective agent, and observed to have a strong suppressive effect on superoxide production. In this study, the effect of plaunotol on bacterial translocation was examined using the model of ischemia and reperfusion. METHOD: Male Sprague Dawley rats were used to create the following model for evaluation of bacterial translocation: (i) the control group; (ii) the preventive dose group (plaunotol 30 mg/kg/day one week before surgery); (iii) the therapeutic dose group (plaunotol 30 mg/kg/day one week after surgery); and (iv) the full dose group (plaunotol 30 mg/kg/day one week before surgery and one week after surgery). Bacterial translocation was assessed as the blood concentration of the endotoxin. RESULTS: In the control group, the endotoxin increased significantly 3 days postsurgery (13.7+/-5.6 pg/ml) compared with before surgery (1.1+/-0.1 pg/ml). In the preventive and full-dose groups, the erndotoxin decreased significantly 3 days postsurgery (4.4+/-2.8 pg/ml, 5.7+/-2.7 pg/ml, respectively) compared with that of the control group. CONCLUSION: Plaunotol in the preventive and full-dose groups decreased the endotoxin. This suggests that plaunotol is one of the protectors for bacterial translocation.     

A case of hemorrhagic cyst of the pancreas resembling the cystic endometriosis

A 47-year-old Japanese woman with a history of epigastric pain and a recent episode of acute pancreatitis (back pain, nausea, and vomiting) and anemia was found to have a pancreatic cyst of the tail on CT-scan and ultrasonography. Especially, ultrasonography revealed the papillary solid lesion in the cyst. With the tentative diagnosis of a cystic neoplasm, distal pancreatectomy was performed. Histological examination of sections showed massive hemorrhage, surrounded fibrous connective tissue, and numerous macrophages with hemosiderin deposits; these histological findings resembled cystic endometriosis. The clinicopathological features and pathogenesis of the pancreatic endometrial cyst are discussed.     

Determination of paroxetine in human saliva by reversed-phase high-performance liquid chromatography with UV detection.

A rapid and sensitive high-performance liquid chromatographic method was validated and described for determination of paroxetine in human saliva. Following liquid-liquid extraction of the drug and an internal standard (dibucaine), chromatographic separation was accomplished using a C18 analytical column with a mobile phase consisting of 0.05 mol/L sodium phosphate buffer, pH 5.0, and acetonitrile (A 30:70, v/v; B 60:40, v/v). Paroxetine and the internal standard were detected by ultraviolet absorbance at 205 nm. The average recoveries of the drug and internal standard were 92.5% and 89%, respectively. The lower limits of detection and quantification were 1 and 4 ng/ml, respectively, and the calibration curve was linear over a concentration range of 4 ng/ml. The saliva level of paroxetine in patients with depression taking 10 to 40 mg/day of the drug was significantly correlated with the plasma level of paroxetine in each patient (r = 0.617, P < 0.004, n = 19). These data indicate that the saliva level of paroxetine could be a useful marker to predict the plasma level of the drug.     

Genetic variations and haplotype structures of the ABC transporter gene ABCC1 in a Japanese population

Multidrug resistance-related protein 1 (MRP1), an ATP-binding cassette transporter encoded by the ABCC1 gene, is expressed in many tissues, and functions as an efflux transporter for glutathione-, glucuronate- and sulfate-conjugates as well as unconjugated substrates. In this study, the 31 exons and their flanking introns of ABCC1 were comprehensively screened for genetic variations in 153 Japanese subjects to elucidate the linkage disequilibrium (LD) profiles and haplotype structures of ABCC1 that is necessary for pharmacogenetic studies of the substrate drugs. Eighty-six genetic variations including 31 novel ones were found: 1 in the 5'-flanking region, 1 in the 5'-untranslated region (UTR), 20 in the coding exons (9 synonymous and 11 nonsynonymous variations), 4 in the 3'-UTR, and 60 in the introns. Of these, eight novel nonsynonymous variations, 726G>T (Trp242Cys), 1199T>C (Ile400Thr), 1967G>C (Ser656Thr), 2530G>A (Gly844Ser), 3490G>A (Val1164Ile), 3550G>A (Glu1184Lys), 3901C>T (Arg1301Cys), and 4502A>G (Asp1501Gly), were detected with an allele frequency of 0.003. Based on the LD profiles, the analyzed regions of the gene were divided into five LD blocks (Blocks -1 and 1 to 4). The multiallelic repeat polymorphism in the 5'-UTR was defined as Block -1. For Blocks 1, 2, 3 and 4, 32, 23, 23 and 13 haplotypes were inferred, and 9, 7, 7 and 6 haplotypes commonly found on > or = 10 chromosomes accounted for > or = 91% of the inferred haplotypes in each block. Haplotype-tagging single nucleotide polymorphisms for each block were identified to capture the common haplotypes. This study would provide fundamental and useful information for the pharmacogenetic studies of MRP1-dependently effluxed drugs in Japanese.