Chromosome analysis of human refrozen embryos following fluorescence in situ hybridization

Purpose  Several recent reports have discussed refrozen and thawed embryo transfer; however, the process may cause a degree of chromosomal damage and subtle genomic mutation. In view of this possibility, the purpose of this study was to investigate the incidence of aneuploidy in refrozen embryos. Methods  In order to investigate the incidence of aneuploidy and mosaicism observed in chromosome 1, fluorescent in situ hybridization (FISH) was used on surviving embryos that first underwent one freeze-thaw cycle, then were allowed to develop to the blastocyst stage, and subsequently survived a second freeze-thaw cycle. Results  Of 1,132 blastomeric nuclei analyzed from 15 refrozen embryos, disomy was found in 82.9%. In contrast, for the 11 blastocysts subjected to only one freeze-thaw cycle, disomy was noted in 78.4%. Of the 197 blastomeric nuclei analyzed in all arrested embryos, disomy was found in 51.8%. Conclusions  The refreezing process did not increase aneuploidy. The good and fair morphology groups demonstrated a higher percentage of disomy than the poor morphology group regardless of whether they were frozen once or twice.     

Effect of COMT Val108/158Met Genotype on Risk for Polydipsia in Chronic Patients with Schizophrenia

Polydipsia is a serious condition often seen among patients with schizophrenia (SCZ). The cause of polydipsia is unknown; hence, it is hard to treat or manage. Animal studies showed that the drinking behavior is regulated by central dopaminergic neurotransmission at the hypothalamus. Meanwhile, the existence of a genetic predisposition to polydipsia in patients with SCZ has been suggested. The purpose of this study was to assess whether a functional polymorphism, Val^108/158Met in the gene for catechol-O-methyltransferase (COMT), is associated with susceptibility to polydipsia using a Japanese sample of SCZ. Our sample includes 330 chronic patients with SCZ (83 polydipsic patients and 247 non-polydipsic controls). The common COMT Val^108/158Met polymorphism was genotyped, and the differences in genotype distribution and allele frequency between cases and controls were evaluated using the χ ² test. A significant association between the COMT Val^108/158Met polymorphism and polydipsia was found (genotype distribution: χ ² = 13.0, df = 2, p = 0.001; allele frequency: χ ² = 7.50, df = 1, p = 0.006). The high-COMT activity group (Val/Val) was more frequent among patients with polydipsia compared with the low-COMT activity group (Val/Met + Met/Met) [odds ratio (OR) = 2.46]. The association survived after controlling for other possible confounding factors, including gender, age, age of onset, current antipsychotic dose, and smoking status. Our results suggest that the COMT Val^108/158Met genotype may confer susceptibility to polydipsia in SCZ. To our knowledge, this is the first association study between the COMT gene and polydipsia in SCZ. Further studies with larger sample sizes are warranted to confirm present findings.     

Characteristics of anal canal motility after ileoanal anastomosis.

This study attempted to determine the mechanism of anal canal motility after ileoanal anastomosis with the use of alpha-, beta- and muscarinic receptor agents. Forty-five patients, 19 +/- 2 months after operation (mean plus or minus S.E.M.) and 48 control volunteers were studied. Anal manometry indicated no difference in maximum resting pressure and squeeze pressure between the patients and the normal controls. Greater amplitude and less frequent anal canal slow waves were a particular characteristic during the postoperative period. Phentolamine (alpha-blocker) exhibited a stimulatory effect on anal resting tone in the normal rectum, while propranolol (beta-blocker) and atropine (muscarinic blocker) had no effect. However, alpha-, beta- and muscarinic receptors all had stimulatory effects on postoperative anal tone. The muscarinic receptor had dominant effects on the reduction in anal canal slow wave frequency after ileoanal anastomosis. Our results indicated that neorectum after ileoanal anastomosis had hybrid characteristics of both rectum and ileum. Through analysis of receptor-related motor function, we may be able to improve our understanding of dyscontinence after ileoanal anastomosis.     

Induction of cell death in adult T-cell leukemia cells by a novel IkappaB kinase inhibitor.

NF-kappaB is constitutively activated in adult T-cell leukemia (ATL) and is considered responsible for cell growth and prevention of cell death. In this study, we demonstrate that NF-kappaB is constitutively activated in various HTLV-1-infected T-cell lines and ATL-derived cell lines irrespectively of Tax expression as evidenced by the phosphorylation of IkappaBalpha and p65 subunit of NF-kappaB, activation of NF-kappaB DNA binding, and upregulation of various target genes including bcl-xL, bcl-2, XIAP, c-IAP1, survivin, cyclinD1, ICAM-1 and VCAM-1. The effects of a novel IkappaB kinase (IKK) inhibitor, 2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-piperidin-4-yl nicotinonitrile (ACHP), were examined on cell growth of these cell lines and fresh ATL leukemic cells. We found that ACHP could inhibit the phosphorylation of IkappaBalpha and p65, as well as NF-kappaB DNA-binding, associated with downregulation of the NF-kappaB target genes and induce cell growth arrest and apoptosis in these cells. When Tax-active and Tax-inactive cell lines were compared, ACHP could preferentially inhibit cell growth of Tax-active cells. Moreover, ACHP exhibited strong apoptosis-inducing activity in fresh ATL cells. These findings indicate that ACHP and its derivatives are effective in inducing ATL cell death and thus feasible candidates for the treatment of ATL.     

Severe complications of mediastinal pancreatic pseudocyst: report of esophagobronchial fistula and hemothorax

We report two patients with alcoholic pancreatic pseudocyst which communicated to the mediastinal space through the aortic hiatus, in one patient resulting in hypotensive shock due to hemothorax, and in the other, resulting in esophagobronchial fistula via the mediastinal cyst. The first patient was successfully treated by radical resection of the pancreatic body and tail, and the spleen, with an ultrasonic scalpel, although inflammatory changes caused by pancreatitis were so prominent that the splenic vein was occluded. The second patient could not be treated surgically, because the superior mesenteric vein had been occluded by chronic pancreatitis; he died of respiratory failure and sepsis due to aspiration pneumonia, despite receiving medical treatment. Received for publication on June 14, 1999; accepted on Aug. 10, 1999     

Thymidine phosphorylase expression in tumor stroma of uterine cervical carcinomas: histological features and microvessel density

Immunohistochemical staining was performed on 91 cases of uterine neoplasm in order to determine if expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase (TP) correlates with tumor microvessel density (MVD) and histological parameters of uterine carcinomas in tumor cells and in tumor stroma. The sample group consisted of 72 primary invasive squamous cell carcinomas of the cervix (ISC) and 19 cervical intraepithelial neoplasms (CIN) of the uterus. In ISC of the cervix, TP expression in tumor stroma showed a significant correlation with a non-keratinizing histological subtype (P < 0.001) and with an infiltrating invasive pattern (P < 0.001). However, in tumor cells the TP expression showed a higher correlation with a keratinizing histological subtypes (P = 0.009). MVD was significantly higher (P = 0.002) in tumors showing high TP expression in stroma than in tumors with low expression. These findings suggest that the TP expression in stromal cells, rather than in tumor cells, may play a role in promoting microvessel growth in cervical squamous cell carcinoma, and angiogenesis may also have an association with tumor cell invasion.     

Carcinoma of the urachus: report of two cases

Carcinoma of the urachus is a rare disease with poor prognosis. This is probably due to the difficulty of preoperative diagnosis. Radiological modalities have been considered to be of little value, but in many cases, preoperative diagnosis can be established with the aid of CT scan. In patients with urachal carcinoma, CT scan visualize the primary tumor and its extension beyond the bladder wall into the space of Retzius. Although about 150 cases of urachal tumor have been reported in the English literature, computerized tomographic findings have not been established. We present two cases and emphasize the usefulness of CT scan in preoperative diagnosis.