Adenocarcinoma arising from a hyperplastic polyp with adenomatous foci.
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Biomedical subjects
Publications and source records attributed to H Kubota.
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A 30-year-old female had twice experienced right pneumothorax within 2 months that was related to the onset of menstruation, suggesting catamenial pneumothorax. Right thoracoscopy revealed the presence of "blue berry spots" and pinhole at the lateral part of central tendon in the diaphragm. No bulla or bleb was found on the right lung. Partial resection of the diaphragm including these lesions was performed under small thoracotomy assisted by thoracoscopy. Histological findings showed endometriosis of the diaphragm. She was followed without hormonal therapy, but recurrent right pneumothorax occurred. Therefore she was given leuprorelin acetate for 5 months, and she is asymptomatic 7 months after surgery.
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Although it is well-known that cancers show intratumoral phenotypic heterogeneity, genotypic studies have been scarce. Using comparative genomic hybridization and laser scanning cytometric analyses, we investigated intratumoral cytogenetic heterogeneity in 21 surgically removed gliomas including 11 glioblastomas (GBMs), 8 anaplastic astrocytomas (AAs) and 2 low-grade astrocytomas. Comparative genomic hybridization analysis revealed gain or amplification of 7p in 63%, gain of 7q in 73%, loss of 9p in 53%, loss of 10p in 47%, loss of 10q in 47%, loss of 13q in 53%, and loss of 22q in 37% of high-grade astrocytomas. Because these aberrations were region-independent within the same tumor, they did not contribute to intratumoral cytogenetic heterogeneity. Such heterogeneity was due to cytogenetic changes other than the above region-independent aberrations. Intratumoral cytogenetic heterogeneity was detected in 8 of 11 GBMs, 4 of 8 AAs, and none of the 2 low-grade astrocytomas. These observations suggest that cytogenetic changes at chromosomes 7, 9p, 10, 13, and 22 are primary events in high-grade astrocytomas and that subsequent cytogenetic changes involving increases in copy number provide intratumoral heterogeneity. DNA aneuploidy was detected by laser scanning cytometry in 5 of 11 GBMs and 1 of 8 AAs. All tumors with DNA aneuploidy exhibited intratumoral cytogenetic heterogeneity, and there was a significant correlation between DNA aneuploidy and intratumoral cytogenetic heterogeneity. These results support the notion that cytogenetic heterogeneity results from genetic instability within a tumor.
(+/-)-1-Acyl-3-(3,4-dichlorophenyl)-3-[2-(spiro-substituted piperidin-1'-yl)ethyl]piperidines and their quaternary ammonium salts were prepared and evaluated for their NK1 receptor antagonistic activity. Some of these inhibited SP-induced contraction in guinea pig ileum with IC50 values at a level of 10(-9) M and showed potent inhibitory activity against selective NK1 receptor agonist-induced bronchoconstriction in guinea pigs.
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The 3-unsubstituted and substituted analogs of naltrindole (NTI) were synthesized using palladium-catalyzed transformations, and their binding affinity to opioid receptors was determined. Although the 3-desoxy analog showed comparable delta selectivity with that of NTI, all of the novel compounds possessed low affinity for delta receptors indicating the important role of the 3-oxygen atom of NTI for interaction with delta-opioid receptors.
BACKGROUND: Squamous cell carcinoma (SCC) of the esophagus is among the most malignant of neoplasms and is associated with a dismal prognosis. Although tumor microvessel density (MVD) is an important prognostic factor in several carcinomas, its role in SCC of the esophagus is still controversial. Also, the role of thymidine phosphorylase (dThdPase), a key angiogenic growth factor, is yet to be delineated in this disease. METHODS: Immunohistochemical staining using monoclonal antibodies was used to quantify microvessel and dThdPase expression in archival tissue specimens from 93 patients with SCC of the esophagus. RESULTS: High dThdPase expression and high MVD were associated with tumor progression (size and stage) and lymph node metastasis, but only MVD was a predictor of survival. dThdPase expression was significantly correlated with depth of tumor invasion (P = 0.015). In multivariate analysis, MVD was an independent predictor of survival in the lymph node negative cases. A significant correlation was noted between MVD and dThdPase expression, with a correlation coefficient of 0.083 (P = 0.002). CONCLUSIONS: MVD is an independent factor in determining the prognoses of lymph node negative patients with SCC of the esophagus. dThdPase could be a key factor in the angiogenesis of this disease and may be responsible for its aggressive behavior.
ET receptor blocker (TAK-044) and NO donor (FK409) were used to improve the hepatic microcirculation following ischemia-reperfusion injury. In the first experiment (60 minutes of ischemia), 15 dogs were divided into three groups: group A (control), saline; group B, TAK 5 mg/kg; and group C, FK 0.4 mg/kg. In the second experiment (90 minutes of ischemia), 38 dogs were divided into six groups that underwent 90 minutes of hepatic ischemia followed by reperfusion: group I (control), saline only; group II, TAK 5 mg/kg and FK 3.2 mg/kg; group III, TAK 5 mg/kg and FK 0.4 mg/kg; group IV, TAK 5 mg/kg; group V, FK 0.4 mg/kg; and group VI, FK3.2 mg/kg. All drugs were administered through the portal vein. Following 60 minutes of ischemia, both FK and TAK produced significant improvement in hepatic microcirculation and enzymatic status when compared with the control group. After 90 minutes of ischemia, low doses of FK and TAK significantly improved hepatic microcirculation and reduced portal pressure following reperfusion in group III compared with group I. Leakage of hepatic enzymes was prevented and tissue injury score was significantly lower in group III. In group VI, early protection was obtained to some extent; however, blood pressure was reduced significantly following reperfusion compared with group I. In contrast, hepatocellular function deteriorated and the tissue injury score was higher in group II animals. TAK pretreatment with low doses of FK provided the best protection for the hepatic microcirculation in ischemia-reperfusion injury of the liver.
In early gastric cancer, lymph node metastasis is known to be a prognostic factor. A retrospective study of 134 patients with submucosal gastric cancer (SMGC) who had undergone gastrectomy with lymph node dissection was performed to evaluate the prognostic factors and indication of postoperative chemotherapy. Five-year disease-free survival rate for 121 patients without nodal metastasis was 100% with (n = 62) or without postoperative chemotherapy (n = 59). On the other hand, it was 72.9% for 13 patients with nodal metastases, although all patients had undergone D2 or D3 resection and received postoperative chemotherapy. Tumor recurrence occurred only in three patients (n = 3) with alpha-fetoprotein (AFP) producing cancer and lymph node metastasis. Multivariate analysis with the Cox's proportional hazard model revealed AFP positivity to be a new independent prognostic factor in addition to lymph node metastasis in the patients with SMGC. Our findings suggest that routine use of postoperative chemotherapy does not appear rational for the patients without nodal metastasis and that new modalities of operation and chemotherapy may be necessary for the patients with AFP producing SMGC with nodal metastasis. The necessity of chemotherapy in conventional-type SMGCs with nodal involvement remains to be studied in future.
BACKGROUND: New prognosticators are necessary for optimizing the extent of thyroidectomy and adjuvant radiotherapy in differentiated thyroid carcinoma. METHODS: Tumor microvessel density (MVD), expression of thymidine phosphorylase (dThdPase) and CD68 stained macrophages were evaluated in 71 differentiated thyroid carcinomas by an immunohistochemical method. RESULTS: The recurrence-free survival was significantly (P <0.05) shorter in patients with hypervascular tumors but was not related to the dThdPase expression. Significant (R = 0.323, P <0.001) correlation between dThdPase expression score and increment in MVD was documented. Frequent high MVD and dThdPase expression were encountered in tumors >3 cm. Twenty-two of the 27 (82%) patients expressing high dThdPase were also evaluated positive for CD68 (P <0.001). CONCLUSIONS: Tumor MVD might be a new prognostic indicator of differentiated thyroid carcinoma, whereas dThdpase expression with high MVD might serve to identify a subgroup of thyroid carcinoma patients as potential candidates for adjuvant radiotherapy.
Endovascular covered stents were successfully applied to temporarily halt hemoptysis and postpone surgical intervention in a 69-year-old man with a ruptured anastomotic false aneurysm of the distal aortic arch. Surgical graft implantation was performed successfully by the elephant trunk technique 14 days after the endovascular stent-grafting, at which time aspiration pneumonia had subsided.
BACKGROUND: The purpose of this study was to develop a method of atrial ablation. In the IRK-151 infrared coagulator, light from a tungsten-halogen lamp is focused into a quartz rod. The distal exit plane is connected to a tip made of sapphire to allow linear ablation. METHODS: Thirty-six lesions were created in 9 mongrel dogs. The beating ventricular myocardium was ablated from the epicardium. In each dog, 4 lesions were created by using the following durations of application: 3, 9, 15, and 21 seconds. After the ablation, the myocardium was fixed and stained. A linear lesion on the beating right atrial free wall was created. Before and after the ablation, epicardial plaque-electrode mapping was performed. Three months after ablation, remapping was performed. RESULTS: The ablated myocardium had well-demarcated necrosis without carbonization or vaporization. The maximum depth was 10.3 +/- 0.8 mm. The conducting pathway was blocked. The block, once made, continued for 3 months. CONCLUSIONS: The IRK-151 produces well-demarcated lesions that were deep enough for atrial ablation to block the conducting pathway.
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A series of substituted hydroxyphenylureas was synthesized, the chemical structure of which was designed based on structures of natural antioxidants, vitamin E (alpha-tocopherol) and uric acid. They exhibited high inhibitory activity against lipid peroxidation. In order to gain an insight into the mechanism of the inhibition reaction, we analyzed their structure-activity relationships quantitatively. Electronic and steric effects of substituents on the phenolic hydroxyl group were shown to be of importance in governing the inhibitory potency. An increase in the electron donating property of substituents toward the phenolic hydroxyl group enhanced the antioxidative activity by the stabilization of an electron-deficient radical-type transition state. The steric shielding by ortho-substituents stabilized the phenoxy radicals formed following the transition state. Derivatives having the carboxyl group were only weakly active presumably because of an intermolecular ion-dipole interaction of the phenolic hydroxyl group with the carboxylate anion which could retard the formation of the transition state.
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BACKGROUND: Although anti-viral capsid antigen (VCA)-immunoglobin M (IgM) is the most reliable serological marker of primary Epstein-Barr virus (EBV) infection, it could only be detected in limited cases of infectious mononucleosis in children. We analyzed anti-EBV antibodies by an enzyme-linked immunosorbent assay (ELISA), a sensitive method for detecting IgM antibody and compared these results with those obtained by a conventional indirect immunofluorescence (IF) method. METHODS: Anti-Epstein-Barr virus early antigen (EA)-IgM and nuclear antigen 1 (EBNA1)-IgG were examined by an ELISA assay in 180 sera from 70 infants and children with infectious mononucleosis, diagnosed serologically by standard IF methods. RESULTS: Although by IF, VCA-IgM was detected in only 37 of 70 (52.9%) of the sera from the acute phase of the disease, by ELISA, EA-IgM was detected in 65/70 (92.9%) of these sera. Among infants less than 12 months of age. EA-IgM was positive in 11/13 cases (84.6%) while VCA-IgM was detected in only 3/13 cases (23.1%). Anti-Epstein-Barr virus nuclear antigen 1-IgG was not detected by ELISA in the sera from the acute phase of infectious mononucleosis. Anti-EBNA was not detected by IF in about one-third of the sera during 6-8 months after onset of the disease, whereas by ELISA, EBNA1-IgG was detected in 93.0%. Sera that were positive or negative for both EA-IgM and EBNA1-IgG by ELISA were observed in several cases after the patients recovered from the disease. CONCLUSIONS: Although serodiagnosis by the combination of ELISA for EA-IgM and EBNAI-IgG was more sensitive than IF methods, especially in the case of infants and young children, several patients during convalescence and recovery might be judged as seronegative or as being in highly reactivated states.