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Biomedical subjects

M Kodama

Publications and source records attributed to M Kodama.

At least 199 records · Page 11Linked to original sources

Expression of inducible nitric oxide synthase in rat experimental autoimmune myocarditis with special reference to changes in cardiac hemodynamics.

Excessive NO produced by an inducible NO synthase (iNOS) has been implicated in many types of immune-associated disorders of the cardiovascular system, but it remains to be determined whether NO plays a role in myocarditis. Thus, the significance of iNOS expression in the development of experimental autoimmune myocarditis (EAM), an animal model of human giant cell myocarditis, was investigated. Lewis rats were immunized with cardiac myosin and were killed 7, 14, 21, 28, and 49 days after immunization. The development of severe myocarditis was observed on days 14, 21, and 28 in association with significant deterioration of hemodynamics determined by cardiac catheterization, which peaked on day 21. In parallel with histological severity of myocarditis and deterioration of cardiac performance, iNOS activity in the heart measured by [14C]L-citrulline formation was markedly increased on days 14, 21, and 28. The expression of iNOS was confirmed by immunoblotting and was localized to the infiltrating inflammatory cells found in the vicinity of necrotic myocytes by immunohistochemical analysis. Aminoguanidine, a selective inhibitor of iNOS, significantly decreased the iNOS activity (1.04 +/- 0.37 compared with 29.1 +/- 8.62 pmol.min-1.mg protein-1 in untreated myosin-immunized rats, P < .01) and effectively attenuated histopathological changes of EAM on day 21. Hemodynamic parameters were also improved from 64 +/- 3 to 89 +/- 3 mm Hg for mean blood pressure, from 80 +/- 2 to 113 +/- 4 mm Hg for left ventricular systolic pressure, from 7.8 +/- 0.3 to 3.2 +/- 0.3 mm Hg for left ventricular end-diastolic pressure, from 2867 +/- 137 to 4180 +/- 102 mm Hg/s for +dP/dt, and from 2717 +/- 132 to 4180 +/- 184 mm Hg/s for -dP/dt (P < .01). The values after aminoguanidine treatment were not significantly different from the control values. These results suggest an important role for NO in mediating pathophysiological changes in myocarditis of autoimmune origin.

Animals↗

Blood compatible phospholipid-containing polyurethanes: synthesis characterization and blood compatibility evaluation.

A new diol, bis[2-(2-hydroxyethyldimethylammonio)ethyl] butylenediphosphate, that contains two phosphatidylcholine analogous moieties in one diol molecule, was synthesized and characterized. The diol together with 1,4-butanediol as chain extender was further incorporated into the propolymer of poly(ethylene oxide) (Mn = 1000, 2000, 6000) and 4,4'-methylenediphenyl diisocyanate. The resulting phospholipid poly(ether urethane)s show viscosity behavior of common polyelectrolytes. The bulk and surface characteristics of the new phospholipid poly(ether urethane)s were investigated by IR, GPC, ATR-FTIR, ESCA and contact angle measurements. The new polymers possessed relatively hydrophilic surface revealed by contact angle measurements. The blood compatibilities of the polyurethanes were evaluated by platelet rich plasma contacting studies and scanning electron microscopy observation using medical grade PVC as the reference. No platelet adhesion was observed for all new phospholipid polyurethane casting films. This new type of phospholipid polyurethane is expected to have potential biomedical applications.

Animals↗

Expression of MAGE genes in colorectal carcinomas.

The human genes MAGE-1 and MAGE-3 encode tumor rejection antigens recognized on melanoma cells by cytotoxic T lymphocytes (CTL). These antigens are potentially useful as targets for specific immunotherapy. Expression of MAGE genes in some malignant tumors has been reported, but MAGE gene expression in colorectal carcinomas has not been studied adequately. Therefore, we studied MAGE-1,2,3, and 4 a/4 b expression at the mRNA level, in 40 cases of surgery for colorectal carcinoma, using the reverse transcription polymerase chain reaction (RT-PCR). MAGE-1,2,3, and 4 a/4 b genes were expressed in 3 (7.5%), 6 (15.0%), 13 (32.5%), and 5 (12.5%), respectively, of these 40 cases. A total of 19 of the 40 samples (47.5%) expressed at least one of the MAGE genes. The relationships between clinicopathologic factors and MAGE gene expression were also examined. The frequency of lymph node metastasis was significantly higher in MAGE-3-positive than in MAGE-3-negative cases (p < 0.05). All these cases classified as Duke's D expressed the MAGE-3 gene. This rate of expression was significantly higher than that for all other the Duke's classifications together (p < 0.05). Our findings suggest that MAGE-specific immunotherapy against colorectal carcinomas may be feasible.

Aged↗

Genetic profiles of newly inbred Dahl/Iwai salt-sensitive and salt-resistant rats.

Dahl-Iwai salt-sensitive (S) and salt-resistant (R) rat strains were established as inbred strains at Brookhaven National Laboratory, NY, and were introduced into Eisai Co., Ltd., Japan, and designated DIS/Eis and DIR/Eis. To examine whether there are different allele distributions among the substrains of inbred Dahl S and R rats, we determined biochemical and immunological alleles of DIS/Eis and DIR/Eis, and SS/Sea and SR/Sea, which were derived from SS/Jr and SR/Jr, which were developed by Rapp and Dene. Several differences of allele distribution were observed, indicating that the substrains have different genetic backgrounds. The phenotypic differences between the substrains, such as the severity of the hypertension induced, could be ascribed to the different genetic backgrounds.

Alleles↗

Protective effect of nafamostat mesilate in early wound healing.

BACKGROUND: Tensile strength in rat ileal anastomosis is diminished after injection with superoxide dismutase. We have studied the immunohistochemistry of extracellular matrix to investigate changes associated with this loss of tensile strength. A serine proteinase inhibitor, Nafamostat mesilate, was used to evaluate its potential for maintaining tensile strength. STUDY DESIGN: Four groups of rats underwent ileal anastomosis, Groups 1 and 2 were controls. Groups 3 and 4 were given superoxide dismutase and Nafamostat mesilate, respectively, after anastomosis. RESULTS: In controls, groups 1 and 2, tensile strength decreased to 58 percent and 57 percent, respectively, of the initial value measured immediately after anastomosis 1 day postoperatively and both dropped to 33 percent 3 days postoperatively. After 5 days, tensile strength recovered to 83 percent of initial value. In comparison with controls, administration of superoxide dismutase significantly attenuated the loss of tensile strength on day 1 (94 percent of initial value, p < 0.01) and on days 3, 5 and 7 (p < 0.05). Similar results were found after administration of Nafamostat mesilate on days 3 and 5 (p < 0.05). In group 1, degradation of the collagen layer in the anastomosis was observed, with disappearance of immunostaining for fibronectin and vitronectin on day 3. In both groups 3 and 4, these changes were significantly attenuated with intense immunostaining for plasminogen activator inhibitor-1; fibronectin and vitronectin were seen particularly among collagen fibers on both sides of the anastomosis. CONCLUSIONS: These findings suggest that degradation of extracellular matrix causes loss of tensile strength early after anastomosis. Nafamostat mesilate may be clinically useful to prevent breakdown of intestinal anastomoses.

Anastomosis, Surgical↗

[Evaluation of ileocolon interposition after total gastrectomy].

The most serious complaints after total gastrectomy are alkaline esophagitis and postalimentary syndrome. We have performed ileocolon interposition as a gastric substitution which uses the ileocecal valve to prevent bile reflux. The ileocolon segment consists of 7 cm of terminal ileum and 10 cm of coecum and ascending colon on a vascular pedicle. This isolated segment is rotated upwards between the esophagus and the duodenum. To evaluate the function of the ileocolon as a gastric substitute, Barium X rays, O-GTT and gastric emptying time (99Tc EDTA) were examined. Barium X-rays showed that the air at the coecal portion looks like a gastric fornix and there is no barium reflux into the esophagus even in the supine position. Likewise, there were no complaints from patients of symptoms of reflux esophagitis. In case of Rouxen-Y reconstructions, blood sugar level after O-GTT show oxyhyperglycemia. Those in ileocolon interposition rose rapidly, but almost to the same degree as in normal subjects. The appearance of the gastric emptying curve using Tc-DTPA in case of ileocolon interposition shows that there is good reservoir function.

Colon↗

Evaluation of plasma (1-->3)-beta-D-glucan measurement by the kinetic turbidimetric Limulus test, for the clinical diagnosis of mycotic infections.

The present multicentre clinical study was conducted to assess the clinical utility of a new diagnostic method for deep mycosis in which (1-->3)-beta-D-glucan, a fungal cell wall component existing in plasma, was quantitatively measured by the kinetic turbidimetric Limulus test (WB003). Plasma (1-->3)-beta-D-glucan concentrations were 0.57 +/- 0.10 microgram/l in 92 healthy subjects and 0.62 +/- 0.32 microgram/l in 26 patients with non-mycotic diseases (disease control group). In comparison with these healthy subjects and patients with non-mycotic diseases, patients with mycosis had significantly higher plasma (1-->3)-beta-D-glucan concentrations: 19.63 +/- 73.28 micrograms/l in 12 patients with candidaemia, 11.28 +/- 21.42 micrograms/l in 7 patients with urinary Candida infection, 4.84 +/- 12.71 micrograms/l in 5 patients with pulmonary candidiasis, and 12.21 +/- 31.31 micrograms/l in 4 patients with invasive pulmonary aspergillosis. On the statistical analysis of these data, a cut-off value was set at 1.0 microgram/l. Using this cut-off value, 3 patients with pulmonary cryptococcosis and 4 patients (4/6) with pulmonary aspergilloma were all negative with low plasma (1-->3-beta-D-glucan levels. The test WB003 provided equivalent or higher efficiency of diagnosis of candidiasis and aspergillosis, in comparison with commercially available antigen detection kits, demonstrating its utility as a diagnostic reagent. It may also be useful in assessing therapeutic effectiveness when used periodically after treatment.

Adolescent↗

[A case of breast cancer metastasis to the skin and bone 13 years after, and to the brain 17 years after mastectomy].

A case of breast cancer metastasis to the skin and bone 13 years after, and to the brain 17 years after mastectomy in a 54-year-old woman, is reported. In 1978, the patient, who was then 37 years old, underwent standard radical mastectomy for left breast cancer. In 1991, because of skin and bone metastasis, systemic chemotherapy with cyclophosphamide, epirubicin, and 5-fluorouracil (CAF) was performed, and she partially responded to CAF therapy. In April 1995, the patient was admitted for pain of left hip joint and left knee joint. Computed tomography of the head revealed a bleeding tumor with marked peritumoral edema. Serum levels of carcinoembryonic antigen (250 ng/ml) and CA 15-3 (810 U/ml) were increased. Bone metastases were found elsewhere in the body. Again, systemic chemotherapy with CAF was performed. CAF chemotherapy stopped the brain metastasis bleeding.

Antineoplastic Combined Chemotherapy Protocols↗

[A case of multiple liver metastasis and local recurrence from rectal cancer effectively treated by arterial infusion chemotherapy using low-dose 5-fluorouracil, cisplatin and LV].

The case was a 43-year-old male who complained of anal bleeding and melena. He was diagnosed as rectal cancer with multiple liver metastases. Mile's operation with hepatic arterial cannulation was performed. This patient received 10 courses of arterial infusion chemotherapy using low-dose 5-FU, CDDP and LV. Tumor size of liver lesions significantly decreased. Internal iliac arterial cannulation was also performed for local recurrence. He received 3 courses of arterial infusion chemotherapy using the same regimen. The size of local recurrence also decreased. He had no side effect except mild epigastralgia and dermatitis around the stoma with good QOL.

Adult↗

Clinicopathological features of multiple primary gastric carcinoma.

The clinicopathological features of multiple primary gastric carcinoma in 107 patients who had undergone gastrectomy between 1972 and 1992 were studied and compared with those of single gastric carcinoma in 1,456 patients. The incidence of occurrence of multiple primary gastric carcinoma was 6.8% of patients who had gastrectomy for gastric cancer. Such carcinoma was detected less often in patients <49 years of age. Dominant findings involved an elevated gross appearance, papillary or well-differentiated adenocarcinoma in the histology, and invasion to the depth of mucosa. When multiple primary gastric carcinoma was classified by main and concomitant lesions based on the stage of the disease, concomitant lesions were detected more often in the lower third of the stomach and at the distal site of main lesions located in the upper or middle third of the stomach. These results indicate that the lower third of the stomach and the distal site of the main lesion must be investigated carefully to ensure that incidental concomitant lesions are not overlooked, especially when a patient has the clincopathological features described above.

Adenocarcinoma↗

Clinical significance of DNA ploidy pattern in stage III gastric cancer.

Nuclear DNA contents from stage III gastric cancers of 216 patients undergoing curative resection from 1972 to 1987 were measured by flow cytometry using paraffin-embedded materials. To determine the clinical significance of the DNA ploidy pattern, the correlation between it and conventional clinicopathologic findings was studied and a prognostic factor for gastric cancer was investigated by both univariate and multivariate analysis. Survivals were compared for diploidy and aneuploidy patterns in subclasses of stage III gastric cancer as well. The grade of each clinicopathologic factor showed no differences between diploidy and aneuploidy patients. The multivariate analysis revealed that the p value and Hazard ratio of the DNA ploidy patterns were 0.001 and 2.099, respectively. Consequently, it was a valuable independent prognostic factor that could be used in addition to lymph node metastasis and depth of invasion. For the most advanced subclass of stage III gastric cancer the 5-year survival rate of patients with a diploid tumor was significantly higher than that for those with aneuploid tumor. No difference was observed for the other subclasses. These results indicate that the DNA ploidy pattern is a valuable independent prognostic factor for gastric cancer, and that it is more useful for evaluating the prognosis of patients with more advanced lesions undergoing "curative resection."

Adult↗

Occurrence of tetrodotoxin in Alexandrium tamarense, a causative dinoflagellate of paralytic shellfish poisoning.

A significant amount of tetrodotoxin was identified in the cultured cells of Alexandrium tamarense, a causative dinoflagellate of paralytic shellfish poisoning. This result supports the hypothesis that both tetrodotoxin and paralytic shellfish toxins can be detected in organisms which possess either of them, although their proportion is different individually. The present result also supports our previous finding that A. tamarense is the origin of tetrodotoxin detected in the highly toxic scallop Patinopecten yessoensis during the bloom of A. tamarense.

Animals↗