Surgery for non-Meckel's small-bowel diverticular perforation: two case reports and a literature review.

Background: Similar to colonic diverticula, small-intestinal diverticula are often asymptomatic, but may cause life-threatening acute complications. Non-Meckel's small-bowel diverticular perforation is rare, and the rate of mortality is high. However, there is currently no consensus regarding its therapeutic management.

Protein tyrosine nitration and thiol oxidation by peroxynitrite-strategies to prevent these oxidative modifications.

The reaction product of nitric oxide and superoxide, peroxynitrite, is a potent biological oxidant. The most important oxidative protein modifications described for peroxynitrite are cysteine-thiol oxidation and tyrosine nitration. We have previously demonstrated that intrinsic heme-thiolate (P450)-dependent enzymatic catalysis increases the nitration of tyrosine 430 in prostacyclin synthase and results in loss of activity which contributes to endothelial dysfunction.

Gene transfer therapy by either type 1 or type 2 adeno-associated virus expressing human prostaglandin I2 synthase gene is effective for treatment of pulmonary arterial hypertension.

Prostaglandin I(2) (PGI(2)) plays an important role in the clinical treatment of pulmonary arterial hypertension (PAH). However, the administration of PGI(2) involves continuous intravenous infusion using an indwelling catheter, which limits the patient's quality of life and increases the risk of infection. We therefore investigated whether human PGI(2) synthase (hPGIS) gene transfer using an adeno-associated virus (AAV) vector is still effective in a mouse model of PAH and tested for differences in the therapeutic efficacy of PAH among AAV serotypes.

AAV-PGIS gene transfer improves hypoxia-induced pulmonary hypertension in mice.

Although prostaglandin I2 is used to treat pulmonary hypertension (PH), continuous intravenous administration is necessary. We investigated whether human PGIS (hPGIS) gene transfer using adeno-associated virus (AAV) vector was effective in treating an animal model of PH. PH was induced by subjecting mice to 10% O(2).

Extranodal spreading of esophageal squamous cell carcinoma: clinicopathological characteristics and prognostic impact.

Background: Microscopic cancer spreading to extranodal connective tissues (extranodal spreading: ENS) is occasionally found in resected specimens from patients with esophageal squamous cell carcinoma (SCC), but the prognostic impact of ENS remains unclear. The aims of this study were to elucidate the prognostic impact of ENS to help determine the most suitable management for the patients with ENS.

Methods: We histologically re-evaluated 7,349 lymph nodes obtained from 171 patients with SCC of the thoracic esophagus who underwent potentially curable resection between 1992 and 2003.

Alpha2-adrenoreceptor mediated sympathoinhibition of heart rate during acute hypoxia is diminished in conscious prostacyclin synthase deficient mice.

Acute hypoxia increases ventilatory drive in conscious animals, resulting in tachycardia. Sustained hypoxia changes the initial chemoreflex ventilatory increase to secondary ventilatory depression, which then evokes a gradual secondary heart rate (HR) reduction. Prostacyclin (PGI(2)) release is known to potentiate alpha(2)-adrenoreceptor (alpha(2)-AR) mediated inhibition of sympathoactivation during ischaemia and hypoxia.

Activation of PPARbeta/delta induces endothelial cell proliferation and angiogenesis.

Objective: The role of the nuclear receptor peroxisome-proliferator activated receptor (PPAR)-beta/delta in endothelial cells remains unclear. Interestingly, the selective PPARbeta/delta ligand GW501516 is in phase II clinical trials for dyslipidemia. Here, using GW501516, we have assessed the involvement of PPARbeta/delta in endothelial cell proliferation and angiogenesis.

Successful management of esophageal perforation diagnosed 3 days after injury caused by an explosion in the workplace: report of a case.

We report a case of esophageal perforation caused by an explosion, but which was not diagnosed until 3 days after the injury. A 53-year-old worker sustained superficial dermal burns to his trachea, face, neck, and legs during an explosion. The burns were treated conservatively at a local hospital, but he was transferred to our hospital 3 days after the injury, when mediastinal emphysema and bilateral pleural effusion became evident.

[Safety and efficacy of hypotonic CDDP intraperitoneal administration for gastric cancer with peritoneal dissemination].

We examined safety and efficacy of hypotonic CDDP intraperitoneal administration followed by systemic chemotherapy using MTX/5-FU and UFT. Between 1998 and 2004, seven patients who had histologically proven gastric adenocarcinoma with peritoneal metastases underwent palliative gastrectomy at Niigata University Medical Hospital. For residual peritoneal tumors, 100 mg/body of CDDP diluted with distilled water was intraperitoneally administered to the patients before closure of abdominal wall and was drained 30 to 60 minutes after administration.

[Safety and efficacy of chemotherapy using TS-1 followed by paclitaxel for advanced or recurrent gastric cancer with peritoneal dissemination].

There has been no standard treatment for gastric cancer with peritoneal dissemination. We have used TS-1 followed by paclitaxel for advanced or recurrent gastric cancer patients with peritoneal dissemination since January 2002. Twenty-three patients were enrolled to our prospective study and 19 of 23 patients completed the protocol.

Heterogeneous expression of GAGE, NY-ESO-1, MAGE-A and SSX proteins in esophageal cancer: Implications for immunotherapy.

Cancer/testis antigens (CTAs) elicit immune response in cancer patients and are therefore targets of immunotherapy. Current information on CTA expression is primarily based on mRNA assays and little is known about their expression at the protein level. The objectives of our study are to analyze GAGE, NY-ESO-1, MAGE-A and SSX protein expression in esophageal cancer and to correlate their expression patterns with clinicopathologic parameters and survival.

[Indication of hepatic resection for metastatic liver tumors from gastric cancer].

To clarify the benefit and indication of resection for metastatic liver tumors from gastric cancer, we reviewed the therapeutic outcomes at the Niigata University Medical Hospital and at a referred institution. From January 1982 to April 2004, thirty-nine patients with synchronous and 40 with metachronous liver metastases from gastric cancer had been treated. In synchronous cases, forty percent of the patients had many metastatic tumors in bilateral hepatic lobes and the majority of them had advanced gastric cancer with serosal invasion and widely spread of lymphatic metastases.

Gene transfer of hepatocyte growth factor with prostacyclin synthase in severe pulmonary hypertension of rats.

Objective: Hepatocyte growth factor (HGF) is a multi-potent growth factor, which has anti-fibrotic effects for lung injuries. In this study, we investigated whether human HGF gene transfer may attenuate the medial hypertrophy of pulmonary arteries and enhance the ameliorating effect of prostacyclin in monocrotaline (MCT)-induced pulmonary hypertension in rats.

Methods And Results: The day before MCT injection, HVJ-liposome complex with the cDNA encoding HGF gene (H group), PGIS gene (P group), and both HGF and PGIS gene (HP group) were transfected to the liver of rats as drug delivery system for the lung.

Purification and characterization of recombinant human prostacyclin synthase.

Prostacyclin synthase (PGIS), which catalyzes the conversion of prostaglandin (PG) H(2) to prostacyclin (PGI(2)), is a member of the cytochrome P-450 (P450) superfamily, CYP8A1. To study the enzymatic and protein characteristics of human PGIS, the enzyme was overexpressed in Spodoptera frugiperda 21 (Sf21) cells using the baculovirus expression system. PGIS was expressed in the microsomes of the infected Sf21 cells after culture in 5 microg/ml hematin-supplemented medium for 72 h.

Microsomal prostaglandin E synthase-1 is overexpressed in inflammatory bowel disease. Evidence for involvement of the transcription factor Egr-1.

Microsomal prostaglandin E synthase-1 (mPGES-1) catalyzes the conversion of cyclooxygenase-derived prostaglandin (PG) H(2) to PGE(2). Increased amounts of mPGES-1 were detected in inflamed intestinal mucosa from patients with inflammatory bowel disease (IBD). Treatment with tumor necrosis factor (TNF)-alpha stimulated mPGES-1 transcription in human colonocytes, resulting in increased amounts of mPGES-1 mRNA and protein.

Enhanced therapeutic angiogenesis by cotransfection of prostacyclin synthase gene or optimization of intramuscular injection of naked plasmid DNA.

Background: Although clinical trials of therapeutic angiogenesis by angiogenic growth factors with intramuscular injection of naked plasmid DNA have been successful, there are still unresolved problems such as low transfection efficiency. From this viewpoint, we performed the following modifications: (1) combination with vasodilation using prostacyclin and (2) changing the agents or volume of naked plasmid DNA in vivo.

Methods And Results: First, we examined cotransfection of the VEGF gene with the prostacyclin synthase gene in a mouse hindlimb ischemia model.

Application of L-cystein derivative to DNA microarray.

S-carboxymethyl-L-cystein derivatives of nucleic acid bases were prepared as DNA chip probe. These compounds in vitro have been found to form stable complex with oligo-DNA and RNA. This paper deals with preparing new DNA chip using L-cystein derivative synthetic nucleotides as probe and immobilized it to quartz plate by photosensitive PVA.

Growth stimulation and epidermal growth factor receptor induction in cyclooxygenase-overexpressing human colon carcinoma cells.

Recent epidemiological and experimental investigations suggest a close relationship between cyclooxygenase (COX) and pathogenesis of colorectal cancer. There are two isoforms, COX-1 and COX-2, which differ in physiological functions and distribution. This study is to investigate the possible roles of both isoforms in the proliferation of colon carcinoma cells.

Immunohistochemically detected micrometastasis in lymph nodes from superficial esophageal squamous cell carcinoma.

Background And Objectives: This study was conducted to determine the incidence and clarify the patterns of nodal micrometastasis, to elucidate the histopathologic parameters of tumor extension correlating with micrometastasis, and to evaluate whether nodal micrometastasis has clinical significance in patients with superficial esophageal cancer.

Methods: Lymph nodes resected from 78 patients with superficial esophageal squamous cell carcinoma were examined immunohistochemically using the monoclonal antibody cocktail AE1/AE3 to define histologically undetectable micrometastasis. Clinical records and pathologic features of all cases were reviewed.

Enhanced angiogenesis and improvement of neuropathy by cotransfection of human hepatocyte growth factor and prostacyclin synthase gene.

The current therapeutic angiogenesis strategy to treat ischemic disease by using angiogenic growth factors has been limited to use of a single gene. However, as vasodilator substances such as prostacyclin are widely used for the treatment of peripheral arterial disease, it might be useful to combine angiogenesis with vasodilation of new vessels. In a mouse hind limb ischemia model, cotransfection of the hepatocyte growth factor (HGF) gene with the prostacyclin synthase gene demonstrated a further increase in blood flow and capillary density compared with a single gene.

Cyclooxygenase isozymes and their gene structures and expression.

The cyclooxygenase (COX, prostaglandin endoperoxide synthase) is a key enzyme in prostaglandin biosynthesis. Two isoforms of COX, COX-1 and COX-2, have been identified by molecular biological methods. The amino acid sequence homology between COX-1 and COX-2 is about 60% for the human enzymes.

Cyclic mechanical stretch augments prostacyclin production in cultured human uterine myometrial cells from pregnant women: possible involvement of up-regulation of prostacyclin synthase expression.

Prostacyclin (PGI(2)), a potent smooth muscle relaxant, is a major prostaglandin secreted from human myometrium. The concentrations of PGI(2) metabolites in the maternal plasma were reported to be elevated during pregnancy, especially in labor. To clarify the mechanism in PGI(2) secretion from the myometrium, we first investigated the protein expression of cytosolic phospholipase A(2), cyclooxygenase (COX)-1, COX-2, and prostacyclin synthase (PGIS) in the human uterine myometrium at various gestational ages before labor.