Improvement of tricuspid regurgitation after transcatheter ASD closure in older patients.

BACKGROUND: Adult patients with undiagnosed atrial septal defect (ASD) may have right heart cavity enlargement and functional tricuspid valve insufficiency. Moderate or more severe tricuspid regurgitation has been associated with a worse prognosis, and more serious complications are typically seen in older patients. This study aimed to evaluate the improvement in functional tricuspid regurgitation and heart geometry after transcatheter ASD closure in older patients. PATIENTS AND METHODS: The data of 111 patients over 60 years of age with moderate or severe tricuspid regurgitation before ASD closure were analyzed. RESULTS: At the 1­month and 6­month follow-up after closure, both tricuspid regurgitation jet area and right atrial volume decreased significantly. Right ventricular volume decreased 1 month after closure, showing a further decrease at the end of the 6­month follow-up. However, 24 patients (21.6%) still had persistent severe tricuspid regurgitation after the procedure. Multivariate analysis revealed that patient age at ASD closure and pulmonary artery systolic pressure determined by echocardiography before closure were predictors of persistent tricuspid regurgitation after closure. CONCLUSION: Transcatheter ASD closure in older patients could significantly decrease tricuspid regurgitation and improve right heart geometry.

Factors influencing seasonal influenza vaccination behaviour among elderly people: a systematic review.

OBJECTIVES: To explore the behaviour-related factors influencing influenza vaccination among elderly people using a framework derived from the Health Belief Model (HBM) and the Theory of Reasoned Action (TRA). STUDY DESIGN: Systematic review. METHODS: Five databases were searched using predetermined strategies in March 2016, and 1927 citations were identified. Articles were selected according to inclusion and exclusion criteria. Key information was extracted from selected studies using a predesigned sheet. Both authors assessed study quality using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) or Critical Appraisal Skills Programme (CASP) checklist. RESULTS: Thirty-six articles were selected. A new framework was proposed that contributes to shared understanding of factors influencing health behaviour. Possible determinants of influenza vaccination among elderly people were knowledge, health promotion factors, all constructs of the HBM, and some concepts of the TRA. Key factors were threat perception, behavioural beliefs, subjective norms, recommendations, past behaviour and perceived barriers. CONCLUSIONS: This is the first systematic review to analyse the factors influencing influenza vaccination behaviour of elderly people using a framework integrating the HBM and the TRA. The framework identified key factors of influenza vaccination and presented the inter-relation of behaviour-related variables. However, further well-designed studies are required to explore the inter-relationships accurately and comprehensively.

Ecteinascidins. A review of the chemistry, biology and clinical utility of potent tetrahydroisoquinoline antitumor antibiotics.

The ecteinascidin family comprises a number of biologically active compounds, containing two to three tetrahydroisoquinoline subunits. Although isolated from marine tunicates, these compounds share a common pentacyclic core with several antimicrobial compounds found in terrestrial bacteria. Among the tetrahydroisoquinoline natural products, ecteinascidin 743 (Et-743) stands out as the most potent antitumor antibiotics that it is recently approved for treatment of a number of soft tissue sarcomas. In this article, we will review the backgrounds, the mechanism of action, the biosynthesis, and the synthetic studies of Et-743. Also, the development of Et-743 as an antitumor drug is discussed.

Hypermethylation of the nel-like 1 gene is a common and early event and is associated with poor prognosis in early-stage esophageal adenocarcinoma.

The nel-like1 (NELL1) gene maps to chromosome 11p15, which frequently undergoes loss of heterozygosity in esophageal adenocarcinoma (EAC). NELL1 promoter hypermethylation was examined by real-time methylation-specific polymerase chain reaction in 259 human esophageal tissues. Hypermethylation of this promoter showed highly discriminative receiver-operator characteristic curve profiles, clearly distinguishing esophageal squamous cell carcinoma (ESCC) and EAC from normal esophagus (NE) (P<0.001). NELL1 normalized methylation values were significantly higher in Barrett's metaplasia (BE), dysplastic Barrett's (D) and EAC than in NE (P<0.0000001). NELL1 hypermethylation frequency was zero in NE but increased early during neoplastic progression, to 41.7% in BE from patients with Barrett's alone, 52.5% in D and 47.8% in EAC. There was a significant correlation between NELL1 hypermethylation and BE segment length. Three (11.5%) of 26 ESCCs exhibited NELL1 hypermethylation. Survival correlated inversely with NELL1 hypermethylation in patients with stages I-II (P=0.0264) but not in stages III-IV (P=0.68) EAC. Treatment of KYSE220 ESCC and BIC EAC cells with 5-aza-2'-deoxycytidine reduced NELL1 methylation and increased NELL1 mRNA expression. NELL1 mRNA levels in EACs with an unmethylated NELL1 promoter were significantly higher than those in EACs with a methylated promoter (P=0.02). Promoter hypermethylation of NELL1 is a common, tissue-specific event in human EAC, occurs early during Barrett's-associated esophageal neoplastic progression, and is a potential biomarker of poor prognosis in early-stage EAC.

Transcriptional profiling suggests that Barrett's metaplasia is an early intermediate stage in esophageal adenocarcinogenesis.

To investigate the relationship between Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), we determined gene expression profiles of discrete pathological stages of esophageal neoplasia using a sequence-verified human cDNA microarray. Fifty one RNAs, comprising 24 normal esophagi (NE), 18 BEs, and nine EACs were hybridized to cDNA microarrays. Five statistical analyses were used for the data analysis. Genes showing significantly different expression levels among the three sample groups were identified. Genes were grouped into functional categories based on the Gene Ontology Consortium. Surprisingly, the expression pattern of BE was significantly more similar to EAC than to NE, notwithstanding the known histopathologic differences between BE and EAC. The pattern of NE was clearly distinct from that of EAC. Thirty-six genes were the most differentially modulated, according to these microarray data, in BE-associated neoplastic progression. Twelve genes were significantly differentially expressed in cancer-associated BE's plus EAC (as a single combined tissue group) vs noncancer-associated BE's. These genes represent potential biomarkers to diagnose EAC at its early stages. Our results demonstrate that molecular events at the transcriptional level in BE are remarkably similar to BE's-associated adenocarcinoma of the esophagus. This finding alarmingly implies that BE is biologically closer to cancer than to normal esophagus, and that the cancer risk of BE is perhaps higher than we had imagined. These findings suggest that changes modulated at the molecular biologic level supervene earlier than histologic changes, and that BE is an early intermediate stage in the process of EAC.

hobo Induced rearrangements in the yellow locus influence the insulation effect of the gypsy su(Hw)-binding region in Drosophila melanogaster.

The su(Hw) protein is responsible for the insulation mediated by the su(Hw)-binding region present in the gypsy retrotransposon. In the y2 mutant, su(Hw) protein partially inhibits yellow transcription by repressing the function of transcriptional enhancers located distally from the yellow promoter with respect to gypsy. y2 mutation derivatives have been induced by the insertion of two hobo copies on the both sides of gypsy: into the yellow intron and into the 5' regulatory region upstream of the wing and body enhancers. The hobo elements have the same structure and orientation, opposite to the direction of yellow transcription. In the sequence context, where two copies of hobo are separated by the su(Hw)-binding region, hobo-dependent rearrangements are frequently associated with duplications of the region between the hobo elements. Duplication of the su(Hw)-binding region strongly inhibits the insulation of the yellow promoter separated from the body and wing enhancers by gypsy. These results provide a better insight into mechanisms by which the su(Hw)-binding region affects the enhancer function.

Cloning, sequencing, overproduction, and purification of M. CviBI (GANTC) methyltransferase from Chlorella virus NC-1A [corrected].

We have cloned and sequenced the cvibIM gene from Chlorella virus NC-1A by selecting for the modification phenotype. The modification gene was cloned on a 7-kb BamHI fragment inserted into the BamHI site of the pUC13 plasmid. The cvibIM gene was localized at the 3' end of this fragment. Sequencing of this region revealed a large open reading frame that codes for methyltransferase (MTase; symbol M.) (predicting 260 amino acids). M.CviBI (GANTC) aa sequence is homologous to M.Dam(GATC), M.DpnII(GATC), and M.T4 (GATC), and not so to M.HinfI(GANTC), M.HhaII (GANTC), and M.DpnA(GATC). We also describe the use of the polymerase chain reaction technique to alter transcriptional and translational signals surrounding this gene so as to achieve overexpression in Escherichia coli. This construct yields M.CviBI at 2-3% of the total cellular protein. The MTase was purified by phosphocellulose, DEAE, and gel filtration chromatography. Its size by SDS-PAGE is approx. 28 kDa, in good agreement with that predicted from the nucleotide sequence.

Effects of captopril (SQ 14, 225) on the renin-angiotensin-aldosterone system in normal rats.

High doses of captopril (SQ 14, 225) (120-160 mg/kg/day) were administered orally to normal rats, and the effects on the renin-angiotensin-aldosterone system were observed. Plasma angiotensin converting enzyme (ACE) activity was elevated significantly on the 3rd, 7th and 30th days of captopril administration. ACE activity in the lung and the kidney was significantly decreased on the 1st day then gradually increased, becoming significantly higher than that of controls by the 30th day. Plasma renin activity (PRA) was significantly elevated on the 1st day and remained at a high level until the 30th day. Renal renin content was found to be significantly lower on the 1st and 3rd days. Plasma aldosterone concentration was not affected by captopril treatment, whereas serum potassium concentration was found to be significantly lower on the 1st, 3rd and 30th days. It is suggested that besides its inhibitory action on ACE, captopril has a direct or indirect stimulating action on ACE production as well as on renin release.

The influence of Helicobacter pylori infection on the progression of gastric mucosal atrophy and occurrence of gastric cancer.

AIM: To study the effects of Helicobacter pylori infection on the progression of gastric mucosal atrophy and the development of gastric cancer. PATIENTS AND METHODS: We investigated the extension of the atrophic area as assessed on the basis of the Kimura-Takemoto atrophic patterns and the development of gastric cancer in a selected sample of 64 patients who were endoscopically followed up for more than 3 years, and who showed H. pylori infection by culture at the start of the investigation and at some stages during the follow-up. RESULTS: No progression of atrophy was observed in 14 patients who were H. pylori-negative at the beginning of the follow-up, whereas various degrees of expansion of the atrophic area were found in 22% of 50 positive cases. Well differentiated mucosal cancer was diagnosed in four patients during the follow-up. These patients displayed moderate to severe atrophy. At the beginning of the follow-up, 50% of patients were H. pylori culture-positive, but all patients had H. pylori antibodies in their blood. CONCLUSIONS: The results support the view that H. pylori infection influences the development of atrophic gastritis and is related to the pathogenesis of gastric cancer.

Dogger Bank Itch revisited: isolation of (2-hydroxyethyl) dimethylsulfoxonium chloride as a cytotoxic constituent from the marine sponge Theonella aff. mirabilis.

(2-Hydroxyethyl) dimethylsulfoxonium chloride (1), the well-known causative agent of Dogger Bank Itch, has been isolated as a cytotoxic constituent from the marine sponge Theonella aff. mirabilis. The structure of 1 was determined by spectral and X-ray crystallographic analyses.

Effects of transgalactosylated disaccharides on the human intestinal microflora and their metabolism.

The effects of transgalactosylated disaccharide (TD) intake on human fecal microflora and their metabolism were investigated in 12 Japanese males. TD is a mixture of sugars, galactosyl galactose, and galactosyl glucose, synthesized from lactose through the transgalactosylation reaction of Streptococcus thermophilus beta-galactosidase. Volunteers took 15 g of the test sugar daily for 6 days. The TD ingestion increased the number of bifidobacteria and lactobacilli, but decreased the number of Bacteroidaceae and Candida spp. in the feces. The ratio of bifidobacteria to total bacteria increased from 0.28 to 0.51. TD decreased the fecal concentrations of propionic acid, isobutyric acid, isovaleric acid, and valeric acid. This sugar also lowered the fecal pH, and the concentrations of fecal ammonia, p-cresol, and indole. Moreover, a positive correlation was found between the concentration of ammonia, and that of branched-chain fatty acids (isobutyric acid and isovaleric acid), p-cresol, and indole. All of these compounds are produced from amino acids through deamination by the intestinal bacteria. The depression of amino acid fermentation by intestinal bacteria may be involved in the reduction of fecal ammonia. These results suggest that a part of the transgalactosylated disaccharides passes into the colon, inducing changes in the colonic microflora composition, hastening carbohydrate fermentation, and depressing amino acid fermentation in the human gut.

Determination of sucrose esters of fatty acids in food additive premixes by gas chromatography and confirmation of identity by gas chromatography/mass spectrometry.

A gas chromatographic (GC) method was developed for the determination of sucrose monoesters of fatty acids (mono-SuE) and sucrose acetate isobutyrate (SAIB) in food additive premixes. Mono-SuE and SAIB fractions were prepared by column chromatography with either a C8 or a silica gel solid-phase extraction column. The mono-SuE fraction was acetylated and applied to a wide-bore GC column (0.53 mm x 15 m) by splitless injection for determination. The SAIB fraction was applied to the GC column without derivatization. Gas chromatography/mass spectrometry was used to confirm the identity of GC peaks. The detection limits for mono-SuE and SAIB were 0.005 and 0.01%, respectively. Mono-SuE (C12, C14, C16, C18, and C18:1) and SAIB were found in commercial food additive premixes and some foods.

[Model genetic system for analysis of attachment of HeT-A elements to terminal deletions in Drosophila melanogaster]. / Model'naia geneticheskaia sistema dlia analiza prisoedineniia HeT-A-élementov k terminal'nym deletsiiam u Drosophila melanogaster.

Telomeres of Drosophila consist of multiple copies of LINE-like transposable elements. These elements are assigned to two classes, HeT-A and TART. They are attached to terminal deletions at their 3' end, thus compensating for the absence of telomerase in Drosophila cells. The attachment of HeT-A elements to the X-chromosome terminal deletions of the regulatory region of the yellow gene was studied. It was shown that, in the case of degradation of the yellow promoter sequence (chromosome underreplication), the Het-A promoter located at the 3' end of this element can activate transcription of the gene. The minimal size of the 3'-end HeT-A element sequence sufficient for the yellow expression was shown to be 400 bp. Since the yellow mutation is expressed phenotypically and the gene impairment is not lethal, we created a convenient model genetic system based on this effect. Using this system, the frequency of attachments of the HeT-A elements to the chromosome end can be visually recorded. This frequency varied in a wide range (from 0.2 x 10(-4) to 2 x 10(-3)) and was strain-specific.

[Is the bronchoscopic criteria of early lung cancer valid?].

We studied the validity of the bronchoscopic criteria of the early lung cancer using the surgical specimen excised between 1980 and 1999. Twenty-four cases with squamous cell carcinoma of the lung of clinical stage I were located subsegmental or more proximal bronchi and trachea, and the size less than 20 mm in greatest dimension. We histopathologically investigated the endoscopic features in relation to the width of superficial extent, the depth of cancer invasion, and lymph node metastasis. Tumors of the thickened type lesions less than 20 mm in greatest dimension showed no invasion into the cartilaginous layer and no lymph node metastasis. On the other hand, in the nodular and polypoid types, invasion beyond the cartilaginous layer was observed more or less, and lymph node metastasis was observed in 1 case. These cases would not be suitable for bronchoscopic (photodynamic) therapy. In conclusion, the bronchoscopic criteria of early lung cancer is valid in the thickened type, but not in the nodular type or polypoid type.

[Validity and controversies in the new postoperative pathologic TNM classification based on the results of surgical treatment of non-small cell lung cancer].

In 1997, the latest revision of the International System for Staging Lung Cancer was published. To validate the new pathologic TNM classification for non-small cell lung cancer (NSCLC), we analyzed the survival data of 455 patients who underwent pulmonary resection and pathologic staging at our institution from January 1980 through December 1999. The overall 5-year survival rate was 51.0%. Using the revised new stage classification, the survival rate for each stage was as follows; IA: 74.2%, IB: 66.4%, IIA: 56.0%, IIB: 51.8%, IIIA: 21.0%, IIIB: 16.0%, and IV: 0%. The current TNM classification well reflected the long-term prognostic hierarchy. There were significant differences in survival rates between patients with stage IA and IB, and between patients with stage IIB and IIIA. However, there was no significant difference between patients with stage IIA and IIB. No significant difference in survival was observed among patients with stage IIIA, stage IIIB, and stage IV. Five-year survival rate of 48.3% in the T3N0M0 category was significantly better than that of 21.0% found in the new stage IIIA. The survival of patients with intrapulmonary metastases in the same lobe (pm1) was not significantly better than that found in the stage IV. The TNM staging system accurately reflects the prognosis in NSCLC, but some stage definitions can be discussed.

[A case of lung cancer underwent carinal resection with right upper lobectomy and carinal reconstruction with double-barreled anastomosis].

A 70-year-old male complaining cough was admitted to our hospital. Bronchoscopic examination revealed a tumor mass which occluded the orifice of the right upper lobe. Chest computed tomographic (CT) scans gave the image of tumor invasion at the carina. The pathological diagnosis of the tumor was squamous cell carcinoma. Operation was accomplished by right posterolateral thoracotomy approach through the fifth rib bed. The carinal resection with right upper lobectomy was followed by a double-barreled anastomosis of the right intermediate trunk and left main-stem bronchus into the carina. The operation was successfully performed and was considered curative. The length of resected airway measured 4.0 cm from tracheal line of resection to the divided the right intermediate trunk. Reinforcement of the anastomosis was not performed in this case. No postoperative complication occurred but mild ischemia of the anastomosis. The patient died of recurrent tumor in a year and 2 months after operation.

[Extrapleural pneumonectomy for malignant pleural mesothelioma].

Standard treatment for malignant pleural mesothelioma (MPM) has not been proved yet. However, it has been recognized that extrapleural pneumonectomy (EPP) is a treatment of choice for epithelial MPM when combined with adjuvant therapies though EPP may frequently cause fetal complications. We report 5 cases of MPM with EPP, including 1 with good prognosis. Sixteen patients with MPM were admitted to our hospital between 1988 and 2003. Five patients underwent EPP, among which 4 were male and 1 female with ages from 46 to 61 years old. Histologically, 3 of them were epithelial and 2 were biphasic. Those with biphasic experienced acute respiratory failure and empyema, and died 81 days and 8 months after the surgery respectively. Among those with epithelial MPM, 2 are alive with no recurrence at 129 and 29 months after the surgery, and the other, followed by postoperative radiotherapy, died at 12 months. More cases with EPP or randomized controlled trials regarding EPP are necessary to evaluate efficacy of EPP for MPM.

[Clinical pathological studies on colo-rectal cancer with a diameter of 1.5 cm or less].

This study was undertaken to investigate the average rate of carcinomatous occupation in 99 colorectal cancers with a diameter of 1.5 cm or less of each macroscopic form ("pedunculated", "tumor", plaque-like" and "central depression" type). The results were follows; The ratio carcinomatous occupation was low in "pedunculated" type in which "m" cancer was high in frequency . This ratio was high in "tumor" type a diameter of 1.0 cm or more in which "sm" cancer was high in frequency, showing that "tumor" type tend to invade from mucosal to submucosal layer. This ratio were high in "plaque-like" and "central depression" type in which "sm" and "pm" cancer were high in frequency, indicating that "plaque-like" and "central depression" type had little relation to adenoma.

[The effect of prostaglandin E1 and prostaglandin F2 alpha in the ischemic small intestine of dogs].

The effect of PGE1 and PGF2 alpha in the ischemic intestinal tract were examined. In 40 mongrel dogs, we studied ischemic models of small intestine. PGE1 or PGF2 alpha was injected into the anterior mesenteric artery after reperfusion according to each occlusion time, and the tissue blood flow was measured on both mucosal and serous sides of small intestinal loop by laser flowmeter to examine the relation to the extent of tissue damage. Tissue blood flow of the ischemic intestine after the injection of PGE1 increased by 148-208% in the 3-5 hr occlusion group and by 86-110% in the 7-10 hr occlusion group. Tissue blood flow after the injection of PGF2 alpha decreased by 39-59% in the 3-5 hr occlusion group and by 1-15% in the 7-10 hr occlusion group. These results indicate that the effect of PGE1 and PGF2 alpha in the ischemic intestine would be available up to 3-5 hr of ischemia. Histological examination revealed that viability of the remaining crypt was high in the PGE1 injection group but low in the PGF2 alpha injection group. These findings suggest that PGE1, if try at the early stage, would be effective for the treatment of ischemic lesion.