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Biomedical subjects

Isao Ito

Publications and source records attributed to Isao Ito.

14 recordsLinked to original sources

Asymmetrical allocation of NMDA receptor epsilon2 subunits in hippocampal circuitry.

Despite its implications for higher order functions of the brain, little is currently known about the molecular basis of left-right asymmetry of the brain. Here we report that synaptic distribution of N-methyl-D-aspartate (NMDA) receptor GluRepsilon2 (NR2B) subunits in the adult mouse hippocampus is asymmetrical between the left and right and between the apical and basal dendrites of single neurons. These asymmetrical allocations of epsilon2 subunits differentiate the properties of NMDA receptors and synaptic plasticity between the left and right hippocampus. These results provide a molecular basis for the structural and functional asymmetry of the mature brain.

Animals↗

Increased uptake of liposomal-DNA complexes by lung metastases following intravenous administration.

We have investigated the effects of an improved liposomal formulation (extruded DOTAP:cholesterol (DOTAP:Chol)-DNA complex) on transgene expression in tumor cells and normal cells of murine and human origin both in vitro and in vivo. In vitro, transgene expression was significantly increased (P = 0.01) in human tumor cells compared to normal human cells. The increased transgene expression was due to increased uptake of the liposome-DNA complex by tumor cell phagocytosis. Furthermore, immunohistochemical analysis demonstrated a greater transgene expression in lung tumors than in surrounding normal tissues. Increased transgene expression due to enhanced uptake of the liposome-DNA complexes by tumor cells in vivo was also demonstrated using fluorescently labeled DOTAP:Chol liposomes. Finally, evaluation of lung tissue explants obtained from patients undergoing pulmonary resection demonstrated significantly higher (P = 0.001) transgene expression in tumor cells than in normal cells. Thus, we demonstrated that intravenous injection of DOTAP:Chol-DNA complex results in increased transgene expression in tumor and is due to increased phagocytosis of the complexes by tumor cells.

Animals↗

MDA-7 negatively regulates the beta-catenin and PI3K signaling pathways in breast and lung tumor cells.

mda-7 is a novel tumor suppressor with cytokine properties. Adenoviral mda-7 (Ad-mda7) induces apoptosis and cell death selectively in tumor cells. The molecular mechanisms underlying the anti-tumor activity of Ad-mda7 in breast and lung cancer lines were investigated. Microarray analyses implicated both the beta-catenin and the PI3K signaling pathways. Ad-mda7 treatment increased protein expression from tumor suppressor genes, including E-cadherin, APC, GSK-3beta, and PTEN, and decreased expression of proto-oncogenes involved in beta-catenin and PI3K signaling. Ad-mda7 caused a redistribution of cellular beta-catenin from the nucleus to the plasma membrane, resulting in reduced TCF/LEF transcriptional activity, and upregulated the E-cadherin-beta-catenin adhesion complex in a tumor cell-specific manner. Expression of the PI3K pathway members (p85 PI3K, FAK, ILK-1, Akt, and PLC-gamma) was downregulated and expression of the PI3K antagonist PTEN was increased. Consistent with this result, pharmacological inhibition of PI3K by wortmannin did not abrogate killing by Ad-mda7. Killing of breast cancer cells by Ad-mda7 required both MAPK and MEK1/2 signaling pathways, whereas these pathways were not essential for MDA-7-mediated killing in lung cancer cells. Thus, in breast and lung tumor cells MDA-7 protein expression modulates cell-cell adhesion and intracellular signaling via coordinate regulation of the beta-catenin and PI3K pathways.

Adenoviridae↗

Sarcoidosis with bilateral epididymal and testicular lesions.

We report a case of genital sarcoidosis that presented characteristic features on MRI. A 25-year-old man sarcoidosis patient with ocular and lung lesions presented a painful mass in the left scrotum together with systemic symptoms of fever, appetite loss, headache, and stomach-ache during the tapering of steroids. The patient was hypercalcemic, and this was thought to be the cause of his systemic symptoms. MRI showed multiple nodules of bilateral testes and enlargement of bilateral epididymis; the patient was diagnosed with testicular and epididymal lesions of sarcoidosis. An increased steroid dosage improved his hypercalcemia and genital lesions.

Adult↗

Nicorandil prevents epinephrine-induced arrhythmias in halothane-anesthetized rats by nitric oxide-dependent mechanism.

The effect of opening ATP-sensitive K(+) channels on the genesis of arrhythmias is still controversial. We investigated the effect of nicorandil, an ATP-sensitive K(+) channel opener, on the genesis of halothane-epinephrine arrhythmias in rats. We also clarified the involvement of nitric oxide in the effect of nicorandil. Furthermore, we studied the effect of levcromakalim, another ATP-sensitive K(+) channel opener, for comparison. Nicorandil and levcromakalim significantly increased the arrhythmogenic thresholds of epinephrine in a dose-dependent manner. On the other hand, nitroprusside, a potent vasodilator (5.0 micro g/kg per min), did not exert antiarrhythmic action significantly. Both glibenclamide (non-specific ATP-sensitive K(+) channel blocker) and 5-hydroxydecanoate (mitochondrial ATP-sensitive K(+) channel blocker) inhibited the antiarrhythmic action of nicorandil. Although pretreatment with N-omega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, did not modulate the genesis of halothane-epinephrine arrhythmias in the absence of nicorandil, it completely abolished the antiarrhythmic action of nicorandil, but not the effect of levcromakalim. We concluded that nicorandil dose-dependently inhibited halothane-epinephrine arrhythmias through mitochondrial ATP-sensitive K(+) channels and nitric oxide is required for the antiarrhythmic effect of nicorandil.

Anesthetics, Inhalation↗

Hyper-IgM syndrome with systemic tuberculosis.

A 33-y-old man with Hyper-IgM syndrome developed a severe tuberculous disease complicated by pleuritis and spondylitis. An abnormally decreased CD4/CD8 ratio, decreased CD4 + T-cell count and depressed natural killer cell activity implicated a coexistent cell-mediated immunodeficiency. To our knowledge, this is the first detailed report of tuberculosis associated with Hyper-IgM syndrome.

Adult↗

Familial cases of psittacosis: possible person-to-person transmission.

A 29-year-old woman with primary myelofibrosis developed severe pneumonia, and 20 days later her 31-year-old sister also contracted pneumonia. The first patient had been in contact with parakeets but the second patient had not been in contact with any birds. Psittacosis was diagnosed in both cases by microplate immunofluorescence antibody technique. Person-to-person transmission between the sisters was suspected to have taken place.

Adult↗

Hot spring bath and Legionella pneumonia: an association confirmed by genomic identification.

A 59-year-old man developed pneumonia 9 days after bathing in a hot spring spa. Bilateral shadows on his chest radiograph rapidly progressed after admission. He was successfully treated with erythromycin and rifampicin. Legionella pneumophila serogroup 6 was recovered from an intratrachial specimen and a significant elevation was observed in a paired indirect fluorescent antibody to Legionella. Persistent slight fever and chest rentogenographic shadows resolved after administering low-dose prednisolone to treat organizing pneumonia shown by transbronchial lung biopsy. The same serotype of Legionella was recovered from the water of the hot spring spa where the man had bathed. When the extracted DNA of these two strains showed identical restriction fragments by pulsed-field gel electrophoresis, we had direct evidence that hot spring spas can be a source of Legionella pneumonia.

Anti-Bacterial Agents↗

Efficacy of combination chemotherapy for stage IV colon cancer with extensive peritoneal dissemination and multiple liver metastases: a case report.

A patient was diagnosed as having subacute ileus due to advanced cancer of the descending colon with multiple liver metastases and was treated by palliative left hemicolectomy. He was considered to have Stage IV cancer based on the finding of extensive peritoneal dissemination. Histopathological examination showed that the tumor was moderately differentiated adenocarcinoma. Postoperative palliative chemotherapy was given with 5-FU and LV twice a month as 1 course, and he received a total of 3 courses. As a result, the multiple liver metastases were completely eliminated. However, his liver metastases recurred, so CPT-11 was added to 5-FU and LV for another 3 courses. When bilateral pleural effusions developed about 1 year postoperatively, CPT-11 was changed to CDGP. Jaundice and massive ascites eventually developed, and he died about 1 year and 5 months postoperatively.

Adenocarcinoma↗

Is temporary loop colostomy of the right transverse colon appropriate for complete obstruction by colorectal cancer?

We experienced 12 consecutive cases of complete bowel obstruction due to primary colorectal cancer. Among these patients, temporary loop colostomy (loop C) was performed within the resection zone for the primary tumor in 10 cases, and Hartmann's operation was performed in two cases. The loop C was located in the sigmoid colon in five cases and on the left side of the transverse colon in five cases. The interval until radical resection was from 13 to 35 days (mean: 20 days), the duration of surgery was from 2 h 5 min to 4 h 55 min (mean: 4 h 7 min), and the length of resected bowel ranged from 22.5 cm to 51.2 cm (mean: 29.8 cm). Mild wound infection was observed in two cases. Dukes' clinical stage was as follows: A in 0 case, B in 5 cases, C in 6 cases and D (distant metastasis) in 1 case. We have achieved good results over the past two years without performing standard loop C on the right side of the transverse colon.

Adenocarcinoma, Mucinous↗

Improvement of 10-year survival by Japanese radical lymph node dissection in patients with Dukes' B and C colorectal cancer: a 17-year retrospective study.

This study investigated whether the Japanese radical lymph node dissection (J-LND) method was useful for improving the survival and outcome in patients undergoing surgical resection of primary colorectal cancer. The subjects were 434 patients with primary colorectal cancer treated over 17 years. The 10-year survival (10-YS), the number of retrieved and metastatic lymph nodes (LN), the extent of lymph node dissection (D0-D3), and the extent of lymph node metastasis (n0-n4) were compared with Dukes' classification by the Kaplan-Meier curves, log-rank test and multivariate analysis. Patients with a D number larger than their n number (D>n group) were defined as being treated according to J-LND principles, while those with a D number equal to their n number were used as controls (D=n group). Among Dukes' B patients, there was a significant difference of 10-YS between those with retrieval of > or =17 LN or < or =16 LN (p=0.0106). Among Dukes' C patients, a significant difference of 10-YS was observed between those with 1 metastatic node or > or =3 metastatic LN (p=0.0401). A significant difference of 10-YS was also noted between Dukes' C patients with D>n or D=n (p=0.0282). Multivariate analysis showed that retrieval of < or =16 LN (HR=9.051) and intramural invasion (se,si/a2,ai; HR=6.313) were independent determinants of 10-YS in Dukes' B patients, while D=n (HR=2.354) and > or =3 metastatic LN (HR=2.210) were independent determinants in Dukes' C patients. These results suggest that the J-LND method should be performed to retrieve at least 17 nodes when serosal dimpling of the primary tumor is observed during surgery. Effective post-operative adjuvant therapy, such as combination chemotherapy and/or radiotherapy, should be provided for Dukes' C patients with D=n and/or > or =3 metastatic nodes on histopathological examination.

Adult↗

Correlation between occult neoplastic cells in the lymph node sinuses and recurrence in patients with Dukes' C colorectal cancer.

The aim of this study was to investigate whether it was possible to select patients with Dukes' C primary colorectal cancer who had a high risk of metastasis and recurrence. Among 434 patients who underwent surgical resection of primary colorectal cancer, 115 patients (26.5%) had Dukes' C cancer. Among them, 35 patients (30.45%) suffered from metastasis/recurrence postoperatively. Thirty-two patients with recurrence for whom complete follow-up was possible (recurrence group) and 32 patients who survived for at least 5 years without recurrence (non-recurrence group) were compared by immunohistochemical staining of resected lymph nodes for cytokeratin using two antibodies (AE1/AE3 and CAM 5.2). AE1/AE3 staining was positive in 93.85% of the recurrence group versus 68.85% of the non-recurrence group (p=0.0250), while CAM 5.2 staining was positive in 84.45% vs. 53.15%, respectively (p=0.0152). The occult neoplastic cell count (mean +/- SD) in the peripheral lymph node sinuses was 6.28+/-5.17 vs. 2.38+/-3.03 (p=0.0002) in the AE1/AE3-positive patients from the recurrence and non-recurrence groups, while it was 5.13+/-4.84 vs. 1.53+/-2.37 (p=0.0003) in the CAM 5.2-positive patients in each group. Accordingly, the immunohistochemical positivity rate for both AE1/AE3 and CAM 5.2, as well as the occult neoplastic cell count, were significantly higher in the recurrence group. These results suggest that patients with Dukes' C primary colorectal cancer who have a higher risk of recurrence can be selected by immunostaining of resected lymph nodes for cytokeratin.

Antibodies↗

Correlation between occult neoplastic cells in the lymph node sinuses and recurrence in patients with curatively resected Dukes' B colorectal cancer.

This study investigated whether it is possible to detect patients who have a high risk of metastasis and recurrence after resection of stage II Dukes' B primary colorectal cancer. Among 434 patients who underwent curative resection of primary colorectal cancer, 167 (38.5%) had Dukes' B cancer. Among them, 19 patients (11.4%) suffered from postoperative metastasis or recurrence. In 17 patients with recurrence who could be followed-up completely (recurrence group) and 17 other patients who survived for at least 5 years without recurrence (non-recurrence group), immunohistochemical staining of resected lymph nodes for cytokeratin (AE1/AE3 and CAM 5.2) was performed. AE1/AE3 was positive in 76.5% and 47.1% of the patients from the recurrence and non-recurrence groups, respectively, while CAM 5.2 was positive in 52.9% and 17.6%, respectively. There were no significant differences of either AE1/AE3 or CAM 5.2 positivity between the groups. However, the occult neoplastic cell count (mean +/- SD) floating in the lymph node sinuses was significantly higher in patients from the recurrence group who were positive for AE1/AE3 or CAM 5.2 than in patients from the non-recurrence group (6.12+/-6.00 vs. 0.59+/-0.71; p=0.0019 and 3.94+/-5.06 vs. 0.29+/-0.69; p=0.0098, respectively). These results suggest that patients with Dukes' B primary colorectal cancer who have a higher risk of recurrence can be selected by immunostaining of resected lymph nodes for cytokeratin.

Antibodies↗