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Biomedical subjects

Kazuhiro Nishikawa

Publications and source records attributed to Kazuhiro Nishikawa.

At least 19 recordsLinked to original sources

Dai-kenchu-to, a Chinese herbal medicine, improves stasis of patients with total gastrectomy and jejunal pouch interposition.

BACKGROUND: Intestinal motility after gastric surgery frequently is disturbed and results in postoperative intestinal symptoms and poor quality of life (QOL). The purpose of this study was to examine the effects of Dai-kenchu-to on intestinal motility and postoperative QOL of patients. METHODS: Seventeen patients who underwent total gastrectomy with jejunal pouch interposition for gastric cancer in the Department of Surgery of Osaka University Medical Hospital were enrolled. The patients were assigned randomly to the cross-over study with or without 15 g/d of Dai-kenchu-to. Questionnaires and emptying tests using (111)In-labeled liquid and (99m)Tc-labeled solid test meal were performed at the end of each treatment period. A manometric study was performed in 6 patients to measure contractile activity with or without Dai-kenchu-to. RESULTS: Stasis-related symptoms were reduced significantly by Dai-kenchu-to (P = .032). In the emptying test, Dai-kenchu-to accelerated emptying of both liquid (P < .01) and solid (P = .015) meals from the pouch. The pouch showed bursts of contractions, which were increased significantly by oral intake of Dai-kenchu-to (P = .028). CONCLUSIONS: Dai-kenchu-to increased intestinal motility and decreased postoperative symptoms of patients with total gastrectomy with jejunal pouch interposition.

Cross-Over Studies↗

Motility of the pouch correlates with quality of life after total gastrectomy.

BACKGROUND: Jejunal pouch reconstruction is used to provide reservoir function after total gastrectomy, but controversy remains regarding pouch functions and quality of life (QOL). In this study, pouch motility was studied in conjunction with postoperative QOL. METHODS: Pouch motility of 23 patients with jejunal pouch interposition after total gastrectomy was examined by manometry under fasting conditions and by an emptying test using dual-scintigraphy under postprandial conditions. Residual food was graded by endoscopic examinations. QOL was evaluated using the Gastrointestinal Quality of Life Index, and a stasis- or dumping-related symptom score. RESULTS: The pouch showed interdigestive contractile activity. Bursts of contractile activity occurred frequently and were long-lasting compared with the migrating motor complex phase III of the control jejunum. The percentage of time of contractile bursts correlated with postprandial pouch emptying (liquid: R(2) = 0.229, P < .03; solid: R(2) = 0.243, P < .02). Patients with little or no residual food had more percentage of time of contractile bursts than those with moderate residual food (P < .01). The percentage of time of contractile bursts was correlated with the Gastrointestinal Quality of Life Index score (R(2) = 0.262, P < .02), stasis-related symptoms (R(2) = 0.279, P < .01), and dumping-related symptoms (R(2) = 0.218, P < .03). CONCLUSIONS: An interposed jejunum pouch showed bursts of contractile activity that affected postoperative gastrointestinal function and patient QOL.

Duodenum↗

Esophagobronchial fistula in a patient with Behçet's disease: report of a case.

Esophageal involvement in Behçet's disease is generally considered to be very uncommon. So far, six cases of esophageal ulcers associated with perforation, penetration, or fistula in Behçet's disease have been described in the English literature. This report describes esophagobronchial fistula in a patient with intestinal Behçet's disease. A 62-year-old man was transferred to our hospital for peritonitis due to a small intestinal perforation after an appendectomy. At the age of 14 years he had had recurrent oral ulcers. Ulcerations of the ileum and epididymitis were found, and a pathological examination revealed nonspecific inflammation. Furthermore, an esophageal ulcer with esophagobronchial fistula was diagnosed. The fistula required not only endoscopic treatment but also surgical intervention. The patient's clinical features were consistent with the active phase of intestinal Behçet's disease. The symptoms gradually resolved without any treatment. Four years after remission, however, the symptoms recurred with gastrointestinal hemorrhage and polyarthritis. In the ileocolic region, punch-out ulcerations were noted. The clinical history and features led to a diagnosis of Behçet's disease associated with recurrent gastrointestinal ulcerations. Steroid therapy (prednisolone, 20 mg daily) was started, and led to a rapid resolution of the symptoms. The patient is now being followed up as an outpatient while receiving prednisolone (10 mg per day), without complaint of any gastrointestinal symptoms.

Adrenal Cortex Hormones↗

Jejunal pouch interposition with fundic-like plication after total gastrectomy.

PURPOSE: We developed a technique of jejunal pouch interposition with a fundic-like jejunal plication (JPI-FP) for reconstruction after total gastrectomy (TG) for gastric cancer. The aim of this study was to investigate the advantages of JPI-FP over Roux-en-Y reconstruction (R-Y). METHODS: Twenty-two patients who had undergone TG more than 1 year earlier were classified into two groups according to the method of reconstruction used: Group A (n = 7) underwent R-Y, and group B (n = 15) underwent JPI-FP. Group B was subdivided into two groups to examine the usefulness of additional pylorus preservation: group B1 (n = 8), pylorus (-) and group B2 (n = 7), pylorus (+). RESULTS: Food intake and body weight were significantly higher in group B than in group A (P < 0.05). Reflux esophagitis was diagnosed in two of the group A patients, but in none of the group B patients. Excessive esophageal bile exposure, determined as the fraction time of esophageal bilirubin absorbance over 0.14 > 50%, was significantly higher in group A than in group B (P < 0.05). There was no significant difference in bile exposure in the jejunal pouch between groups B1 and B2. CONCLUSIONS: JPI-FP is a superior method of reconstruction after TG to prevent excessive esophageal bile reflux and from a nutritional aspect. The advantage of pylorus preservation remains unconfirmed.

Aged↗

The increase of antiglomerular basement membrane antibody following pauci-immune-type crescentic glomerulonephritis.

A 50-year-old woman was admitted because of high fever and fatigue. Proteinuria, hematuria, and elevated BUN (47.8 mg/dl) and creatinine (3.4 mg/dl) suggested rapidly progressive glomerulonephritis. The serological study revealed all negative results for rheumatoid factor, antinuclear antibody, serum cryoglobulins, MPO-ANCA, PR3-ANCA, and anti-streptolysin O. Antiglomerular basement membrane (GBM) antibody, as assessed by ELISA, was 11 EU (normal, <10). Kidney biopsy on the eighth hospital day demonstrated pauci-immune-type crescentic glomerulonephritis without ANCA. Methylprednisolone pulse therapy (500 mg/day, 3 days) and 45 mg/day prednisolone orally were started. At 3 weeks after kidney biopsy, the anti-GBM antibody value increased from 11 EU/ml to 116 EU/ml, and MPO and PR3-ANCA were still negative. HLA type was DR8 and DR 15(2), with a genotype of HLA-DRB1*08021 and HLA-DRB1*15011. The present case suggests that HLA-DR15 plays an important role on antibody production against alpha 3(IV) NC1 autoantigen after severe nephritis or tissue damage.

Anti-Inflammatory Agents↗

[Extracellular-superoxide dismutase production in mesangial cell growing in extracellular matrix].

To study the protective function against oxygen radicals in the mesangial area, we assessed extracellular superoxide dismutase (EC-SOD) production in mesangial cells (MCs) in vitro. These cells have a major protective function against oxygen radicals in the extracellular space. In two different kinds of culture conditions: "growth medium" with fetal cow serum, and "differentiation medium" with reduced growth factor, and four extracellular matrixes; type I collagen, type IV collagen, laminin and fibronectin, were added to the MC culture. With the difference in the culture media, differentiation medium induced EC-SOD hyper-production associated with the both of the slowing down of cell proliferation and the suppression of IL-6 and IL-8 production. With difference in the extracellular matrix, the presence of type VI collagen and laminin promoted higher production of EC-SOD than fibronectin and type I collagen. Type IV collagen and laminin associated with the physiological condition of the glomeruli promoted EC-SOD production compared with the presence of type I collagen and fibronectin dominantly located in pathological condition. Suppression of EC-SOD production in growth medium along with MC proliferation and chemokine hyper-production compared with production in differentiation medium might mimic reduction of the protective capacity against oxygen radical toxity during mesangial proliferation in the glomerular nephritis. MC proliferation with type I collagen and fibronectin might enhance oxygen radical toxity in the glomeruli, and accelerate glomerular sclerosis through the suppression of EC-SOD production.

Cell Proliferation↗

Establishment of anti-rat-Cu,Zn-superoxide dismutase monoclonal antibodies applied to a highly sensitive immunoassay and immunohistochemistry system.

The superoxide anion has been implicated in a wide range of diseases. The major protector against superoxide anion in the cell cytosol is Cu,Zn-superoxide dismutase (Cu,Zn-SOD). In this study, anti rat Cu,Zn-SOD was established in murine monoclonal antibodies for the first time. These antibodies were applied to both a highly sensitive EIA system in serum and immunohistochemical methods for detection in gastric mucosa tissues. The proposed EIA method had a high sensitivity within the assay range, 10-300 pg/mL, good percentage, 96.9 +/- 5.60%, and good reproducibility; within-day assay CV = 8.6-10.2%, between-day assay CV = 6.5-11.7%. Inmmunohistochemically, Cu,Zn-SOD localized in the esophagus epithelial cells, gastric oxyntic cells, surface of the gastric lumen side in the small intestine and colonic epithelial cells. The establishment of anti-rat CuZn-SOD monoclonal antibody allows both specific analysis of immunoquantitation in rat Cu,Zn-SOD and highly specific detection of Cu,Zn-SOD location by immunohistochemical methods.

Animals↗

alpha-Tocopheryloxybutyric acid enhances necrotic cell death in breast cancer cells treated with chemotherapy agent.

The overexpression of HER-2 receptor contributes to malignant transformation of breast cancer cells. We have reported that alpha-tocopheryloxybutyric acid (TE), non-antioxidative vitamin E ether derivative inhibits the activation of HER-2 receptor. The present study was undertaken to estimate if TE could act as a useful anti-cancer agent against a breast cancer cell overexpressing HER-2 receptor (MDA-MB-453 cell line) in combination with a conventional chemotherapy agent, adriamycin (ADR). TE enhanced cytotoxic effect of ADR against the human breast cancer cell at low doses less than IC(50). The enhancing effect was mainly dependent on the elevation of necrotic-like cell death but not apoptotic cell death. In conjugation with this event, the inactivation of HER-2 receptor in the breast cancer cell was caused by the combination of TE with ADR. These results suggest that TE enhances necrotic-like cell death in the breast cancer cells and that the cell death relates to the inactivation of HER-2 receptor in the breast cancer cells.

Antibiotics, Antineoplastic↗

Down-regulation of connexin 32 gene expression through DNA methylation in a human renal cell carcinoma cell.

BACKGROUND: We have recently reported that connexin (Cx) 32 is down-regulated in a human renal cell carcinoma (RCC) cell (Caki-2 cell). HYPOTHESIS: We postulated that the down-regulation of Cx32 gene in the RCC cell is due to hypermethylation of its promoter region. METHODS: We estimated methylation status in the promoter region of Cx32 gene in the RCC cell by DNA digestion with methylation-sensitive restriction enzyme and PCR, and methylation-specific PCR (MSP). We also checked the recovery of Cx32 gene expression in the RCC cell treated with a DNA methyltranferase inhibitor, 5-Aza-2'-deoxycytidine (5-Aza-CdR). RESULTS: Treatment with 5-Aza-CdR resulted in induction of Cx32 expression in the RCC cell. Hypermethylation of the Cx32 promoter region in the RCC cell was confirmed by DNA digestion with methylation-sensitive restriction enzyme and PCR, and MSP. CONCLUSION: We suggest that hypermethylation in the promoter region is a mechanism for the Cx32 gene repression in the RCC cell.

Analysis of Variance↗

A new parameter for assessing postoperative recovery of physical activity using an accelerometer.

PURPOSE: While many retrospective and prospective observational studies have shown laparoscopic surgery to be less invasive than conventional open surgery, this issue has not been evaluated by objective parameters. Currently available clinical parameters, such as the day of first ambulation, the day food intake is commenced, and the length of postoperative hospital stay, are subjective. The purpose of this study was to investigate whether measuring postoperative physical activity with an accelerometer is a useful parameter for evaluating postoperative recovery after surgical stress. METHODS: The subjects included 20 patients who underwent laparoscopic partial gastrectomy (LPG group), 35 patients who underwent open distal gastrectomy (ODG group), and 20 patients who underwent open total gastrectomy (OTG group). The cumulative acceleration of voluntary movement, measured by an Active tracer AC-301 (ACT) accelerometer for 7 days postoperatively, was compared among these three groups. RESULTS: The cumulative acceleration of physical activity for 24 h was significantly better in the LPG group than in the ODG and OTG groups on each postoperative day. The recovery time, defined as the day that cumulative acceleration had recovered to more than 90% of the preoperative level, was significantly shorter in the LPG group (2.8 +/- 0.9 days) than in the ODG (6.6 +/- 2.1 days) and OTG (7.8 +/- 1.2 days) groups. CONCLUSION: These results showed that convalescence differed with the degree of surgical stress, and that measurement of the cumulative acceleration of voluntary movement by using an accelerometer could be a useful objective and quantitative parameter for evaluating postoperative recovery.

Aged↗

Effect of mucosal suture on the healing of mucosal defect in laparoscopic intragastric surgery.

BACKGROUND: The efficacy of mucosal suturing for the healing of a mucosal defect in laparoscopic intragastric surgery (LIGS) for gastric lesions is not yet known. METHODS: We prospectively studied ten patients who underwent mucosal resection by LIGS for gastric tumors: four patients with early gastric cancer and six with gastric adenoma. Patients were randomly divided into two groups: group I (n = 5); patients who underwent mucosal resection by LIGS with mucosal defect suturing and group II (n = 5); patients who underwent mucosal resection by LIGS without mucosal defect suturing. We performed endoscopy on day 10, and 1 month, 2 months, and 3 months after the operation to observe the healing process of the mucosal defect. The ulcer stage by endoscopy was classified as active, healing, or scarring according to the classification of Sakita and colleagues. Patients were given an H(2)-blocker daily until the mucosal defect improved to the scarring stage. RESULTS: There were no significant differences in sex, age, tumor location, size of mucosal resection, or the incidence of Helicobacter pylori infection between groups I and II. The ulcer stages in group I were significantly lower than those in group II on day 10, and 1 month, 2 months, and 3 months postoperation. The medication cost (H2-blocker) in group I was significantly lower than that in group II. CONCLUSION: Mucosal defect suturing after mucosal resection by LIGS promotes more rapid healing of mucosal defects and reduces drug costs for patients.

Adenoma↗

Multidetector CT of high-risk patients with occult gastrointestinal stromal tumors.

OBJECTIVE: Stromal tumors are an important cause of occult gastrointestinal bleeding in patients who are middle aged or older. This study evaluated the size at which stromal tumors become symptomatic and necrotic and examined the role and limitations of multidetector CT in detecting gastrointestinal stromal tumors. MATERIALS AND METHODS: Two hundred seventy-one patients with stromal tumors were retrospectively studied to examine the size of symptomatic, necrotic, or malignant stromal tumors. Next, five asymptomatic family members with germline c-kit mutations were prospectively screened to evaluate the role and limitations of multidetector CT. RESULTS: In this retrospective study, two thirds of the patients with stromal tumors had symptoms and signs that were correlated with tumor size. Stromal tumors larger than 3 cm were accompanied by necrosis, whereas this finding was rare for those smaller than 3 cm. In the prospective screening, multidetector CT with IV infusion of contrast material showed gastrointestinal stromal tumors of more than 2 cm as slightly enhanced intramural or extramural nodules and also detected most gastrointestinal stromal tumors between 1 and 2 cm. Stromal tumors of less than 3 cm were not accompanied by necrosis and appeared as slightly enhanced homogenous tumors with the administration of contrast media. CONCLUSION: Screening with multidetector CT should be feasible for detecting symptomatic stromal tumors of unknown location in the gastrointestinal tract.

Contrast Media↗

Genistein, a soy isoflavone, enhances necrotic-like cell death in a breast cancer cell treated with a chemotherapeutic agent.

Genistein is a major component of soybean isoflavone and has preventive effect against breast cancer. In breast cancer, the over-expression of HER-2 contributes to malignant transformation of the cancer cells. The present study was undertaken to estimate if genistein could act as a useful anti-cancer agent against a breast cancer cell overexpressing HER-2 in combination with a conventional chemotherapy agent, adriamycin (ADR). Genistein enhanced cytotoxic effect of ADR at low doses less than IC50 against the human breast cancer cell. The enhancing effect was mainly dependent on the elevation of necrotic-like cell death but not apoptotic cell death. In conjugation with this event, remarkable inactivation of HER-2 and Akt in the breast cancer cell was caused by the combination of genistein and ADR. These results suggest that genistein enhances necrotic-like cell death of the breast cancer cells through the inactivation of HER-2 receptor and Akt in combination with ADR.

Antineoplastic Agents↗

Extracellular superoxide dismutase and glomerular mesangial cells: its production and regulation.

Extracellular superoxide dismutase (EC-SOD) is synthesized in mesenchymally derived cells and prevents the oxygen radical-induced injury. We studied whether kidney mesangial cells (MCs) produce EC-SOD and how its production is associated with chemokine secretion. Under unstimulated condition, MCs produced EC-SOD, and its production was correlated positively with cyclic adenosine monophosphate (cAMP), but negatively with interleukin (IL)-6 or IL-8 production. By prednisolone or phorbol myristate acetate treatment, EC-SOD levels were correlated negatively with levels of IL-6 and IL-8. The presence of adenylate cyclase inhibitor 2',3'-dideoxyadenosine lost the prednisolone effect. The stimulation of EC-SOD production might be one of the important effects of prednisolone via cAMP pathway in MCs.

Adenylyl Cyclase Inhibitors↗

Familial gastrointestinal stromal tumors associated with dysphagia and novel type germline mutation of KIT gene.

A family with multiple gastrointestinal stromal tumors (GISTs), a new type of germline mutation of KIT gene, and dysphagia is reported. The mutation was observed at Asp-820 in tyrosine kinase (TK) II domain. Mutations in TK II domain have been found in mast cell and germ cell tumors but not in GISTs, and the present family members are the first reported cases of GISTs with TK II domain mutations, including sporadic GISTs. Because interleukin 3-dependent Ba/F3 murine lymphoid cells transfected with the mutant KIT complementary DNA grew autonomously without any growth factors and formed tumors in nude mice, the mutation was considered to be gain-of-function type. Family members with the germline KIT mutation reported dysphagia, but those without the mutation did not. The mechanism of dysphagia was examined with gastrointestinal fiberscopy, endoscopic ultrasonography, and esophageal manometry. No mechanical obstruction was found, and the esophagus was not remarkably dilated. In the family members with dysphagia, endoscopic ultrasonography at the esophagocardiac junction showed a thickened hyperechoic layer between the circular and longitudinal muscle layers, suggesting hyperplasia of interstitial cells of Cajal at the myenteric plexus layer. Manometry showed low resting lower esophageal sphincter pressure and abnormal simultaneous contractions of the esophagus without normal peristalsis. These findings indicate that the dysphagia of the present family is different from typical achalasia. This is the first report of familial dysphagia caused by germline gain-of-function mutation of the KIT gene at the TK II domain.

Aged↗

Functional characteristics of the pylorus in patients undergoing pylorus--preserving gastrectomy for early gastric cancer.

BACKGROUND: This study investigates the functional characteristics of the pylorus in patients undergoing pylorus-preserving gastrectomy (PPG) for early gastric cancer. METHODS: In study 1, postprandial symptoms and gastric emptying were compared between 2 groups of 12 patients with early gastric cancer more than 1 year after either PPG (PPG group) or distal gastrectomy (DG) (DG group). Gastric emptying was evaluated with the dual isotope technique for liquids and solids separately. In study 2, pyloric motility was evaluated with a sleeve/sidehole manometric assembly in 7 patients undergoing PPG, which was compared with that in the preoperative patients. RESULTS: In study 1, the overall modified Visick score of postprandial symptoms and the Sigstad dumping score were significantly lower in the PPG group compared with the DG group (P <.05). Early accelerated gastric emptying was observed in both groups for liquids, but only in the DG group for solids. In study 2, isolated pyloric pressure waves induced by intraduodenal lipid infusion and phase III-like activity induced by intravenous erythromycin infusion were preserved after PPG. CONCLUSIONS: The quantitative analysis of postoperative symptoms revealed that PPG patients were associated with better clinical conditions than DG patients. The clinical benefits of PPG are considered to be based on the function of the preserved pylorus.

Adult↗

Impact of esophageal bile exposure on the genesis of reflux esophagitis in the absence of gastric acid after total gastrectomy.

OBJECTIVE: The role of duodenal contents refluxing into the esophagus in producing reflux esophagitis (RE) remains unclear. We aimed to assess the impact of esophageal bile exposure on the genesis of RE in reference to esophageal pH changes in the absence of gastric acid after total gastrectomy. METHODS: Thirty patients having undergone total gastrectomy were studied with concurrent 24-h esophageal pH and bilimetric monitoring, and were divided into two groups based on endoscopic esophageal mucosal findings: without RE, group 1 (n = 24) and with RE, group 2 (n = 6). Esophageal bile exposure was defined as bilirubin absorbance >0.14 detected in the esophagus. RESULTS: 1) The percentage total time of esophageal bilirubin absorbance >0.14 was not correlated with that of esophageal pH >7.0, >7.4, and >8.0. 2) All parameters for esophageal bilirubin absorbance >0.14 in group 2 were significantly higher than those in group 1, whereas none of the parameters for esophageal pH >7.0, >7.4, and >8.0 showed a significant difference between the two groups. 3) The percentage total time of esophageal bilirubin absorbance >0.14 was over 50% in all subjects with RE, and six of seven subjects with that over 50% had RE. CONCLUSIONS: Esophageal bile exposure plays an important role in the genesis of RE in the absence of gastric acid, which is assessed better with the measurement of esophageal bilirubin absorbance than that of esophageal pH.

Adult↗