Mutation Analysis of the WT1 Gene in Myelodysplastic Syndromes

The WT1 tumor suppressor gene was examined for mutations in a panel of 44 patients with myelo-dysplastic syndromes (MDS) including acute myelogenous leukemias (AML) secondary to MDS, using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis and sequencing analysis. A WT1 mutation was detected in one out of 17 cases of AML secondary to MDS. This mutation exists upstream of the zinc finger region and is predicted to produce a truncated WT1 protein lacking the zinc finger region. No mutations were detected in 27 MDS patients who had not progressed to AML. This is the first report of analysis for WT1 mutations in a large number of MDS patients, suggesting that WT1 mutations are uncommon in MDS. Abnormalities in this gene may, however, contribute to a small proportion of cases showing progression from MDS into AML.     

Chemoradiation therapy for squamous cell carcinoma of anal canal cancer: report of a case

We report a case of anal canal cancer in a 65-year-old woman who had complained of bloody stool. Physical examination revealed a 2.5 cm ulcerated tumor in the anterior wall of the anal canal astride the dentate line. Histological examination of biopsy specimens confirmed the diagnosis of moderately differentiated squamous cell carcinoma. Chemoradiation therapy included whole pelvic irradiation amounting to 4140 cGy followed by conformal boost irradiation of 2000 cGy and 5-fluorouracil div 750 mg/24 hr 3 days, mitomycin C iv 10 mg day 1, and cisplatinum div 50 mg day 2. Six weeks later the tumor had completely regressed, and there was no evidence of recurrence 21 months later. Her anorectal function was retained.     

Assessment of intestinal viability using a non-contact laser tissue blood flowmeter

BACKGROUND: Intraoperative assessment of small intestinal viability following ischemic insult from arterial occlusion has remained difficult. The purpose of the present study was to assess the applicability of non-contact tissue blood flowmeter (NCLBF) with regard to intraoperative assessment of intestinal viability. METHODS: Using the ischemia-reperfusion model of rabbits, the relationship between the records of NCLBF, pulse oximetry (PO), and histological grade and the comparison of accuracy of intestinal viability among NCLBF, PO, and fluorescein (FL) were examined. RESULTS: There was a significant relationship between NCLBF and the histological grade (coefficient-0.80, P <0.0001); however, PO was not related. The accuracy and sensitivity of bowel viability of NCLBF (76%, 88%) were better than those of PO (58%, 23%) and FL (48%, 4%), respectively (P <0.001). CONCLUSIONS: NCLBF is useful to assess intestinal viability, suggesting the possibility of clinical use.     

An analysis of risk factors of perioperative bleeding in surgical repair of abdominal aortic aneurysm

BACKGROUND: In surgical repair of abdominal aortic aneurysm (AAA), excessive bleeding which causes postoperative complications is sometimes observed. To determine the risk factors of perioperative excessive blood loss, this retrospective study was performed. METHODS: Design. A retrospective study. Setting. An academic medical center. Participants. One hundred and forty patients underwent elective surgical repair of an abdominal aortic aneurysm (AAA) at our institution from 1995 through 1997. Measurements. The present study includes critical review of 140 consecutive charts of patients undergoing elective surgical repair of AAA. Preoperative laboratory data, intraoperative data and amount of blood loss to identify risk factors of perioperative blood loss. Factors which were found to be significantly associated with the amount of perioperative blood loss were preoperative plasma fibrin degradation product (FDP) level (r=0.445), amount of immediate re-infusion of shed blood (r=0.438), and duration of operation (r=0.411). RESULTS: Preoperative fibrinogen level correlated with perioperative blood loss little (r=-0.187). Preoperative platelet count or the other coagulation profile did not affect the amount of perioperative blood loss. The patients whose preoperative FDP were more than 40 microg x ml(-1) significantly increased the risk of excessive blood loss compared with less than 40 microg x ml(-1). CONCLUSIONS: The significant preoperative risk factor of perioperative blood loss was only FDP level in present study. Especially, the patients whose preoperative FDP were more than 40 microg x ml(-1) increased the risk of excessive blood loss.     

Detection of thyroid system-disrupting chemicals using in vitro and in vivo screening assays in Xenopus laevis.

We developed a thyroid hormone (TH) inducible primary screening assay for the identification and assessment of man-made chemicals that interfere with the TH-signalling pathway within target cells. The assay was developed in a Xenopus laevis cell line that was transduced with a self-inactivating (SIN) lentivirus vector (LV) containing a luciferase gene. The luciferase activation in this cell line was TH-specific: 3,3',5-L-triiodothyronine (T(3)) > 3,3'5-L-triiodothyroacetic acid (Triac) > 3,3',5-D-triiodothyronine (D-T(3)), > L-thyroxine (T(4)) > 3,3',5'-L-triiodothyronine (rT(3)). The application of the ligand-dependent luciferase assay for screening for thyroid system-disrupting chemicals revealed that three phthalates (dicyclohexyl phthalate, n-butylbenzyl phthalate, and di-n-butyl phthalate), two herbicides (ioxynil and pentachlorophenol) and a miticide (dicofol) had 3,3',5-L-triiodothyronine- T(3)- antagonist activity at concentrations ranging from 10(-6) to 10(-5) M. These chemicals also inhibited the expression of the endogenous primary T(3)-response TH nuclear receptor beta (TRbeta) gene. The inhibitory characteristics of these chemicals were similar for both assays performed, although the assay for T(3)-dependent activation of TRbeta gene was more sensitive than the luciferase assay. These results indicate that the luciferase assay was a rapid method with a small intra-assay variation for the primary screening of thyroid system-disrupting chemicals. Of the six chemicals, only n-butylbenzyl phthalate and pentachlorophenol exhibited T(3)-antagonist activity in an in vivo metamorphosis-based assay. It should be noted that chemicals elicited thyroid system-disrupting activity in the luciferase assay did not always interfere with the thyroid system in vivo.     

A case of primary gastric small cell carcinoma with a rare pattern of lymph node metastasis

We report a very rare case of primary gastric small cell carcinoma (GSCC) that was accompanied with gastric tubular adenocarcinoma. A male in his 60s had an elevated tumor with a central ulceration in the middle stomach. The patient underwent a distal gastrectomy with lymph node dissection. The pathological examination showed two separated lesions of the stomach, which contained the components of primary GSCC and primary gastric tubular adenocarcinoma. Immunohistochemical (IHC) examination demonstrated that the tumor cells in the small cell carcinoma stained positive for synaptophysin, chromogranin A, and neural cell adhesion molecule (NCAM). GSCC cells and adenocarcinoma cells independently metastasized to each regional lymph node. Further studies on the biological behavior of individual tumors may allow the development of new treatment strategies for GSCC.     

The relationship between intraocular pressure and refractive error adjusting for age and central corneal thickness

PURPOSE: To investigate the relationship between intraocular pressure (IOP) and refractive errors after adjusting for age, central corneal thickness (CCT), and other related factors. METHODS: IOP, CCT and refractive errors were measured in the right eyes of 1855 subjects, aged 40-82 years, in a cross-sectional study design. Subjects were divided into groups by refractive status: hyperopia, emmetropia, mild myopia, moderate myopia, or high myopia. With adjustments for age, CCT, blood pressure, obesity, education, hypertension, diabetes, and smoking status, IOP was estimated for each refractive status using a general linear model. RESULTS: IOP increased with advancing degrees of myopia, even after adjustment for age, CCT, and other related factors (p = 0.011). Estimated IOP of moderate myopia was significantly higher than that of emmetropia (p = 0.022). CONCLUSIONS: Our results confirm the positive association between IOP and increasing degrees of myopia. This finding would support the hypothesis that the relationship between glaucoma and myopia might be pressure mediated.     

WF-10129, a novel angiotensin converting enzyme inhibitor produced by a fungus, Doratomyces putredinis

WF-10129 is an angiotensin converting enzyme (ACE) inhibitor produced by Doratomyces putredinis. IC50 of the compound is 1.4 X 10(-8) M for the ACE activity. WF-10129 was purified from cultured filtrate by successive ion exchange chromatography and HPLC. The chemical structure 1 was elucidated on the basis of spectroscopic and chemical evidence. The compound is a dipeptide composed of L-tyrosine and a novel amino acid. WF-10129 inhibits the pressor response of angiotensin I when administered intravenously at 0.3 mg/kg in rats.