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Biomedical subjects

T Ishida

Publications and source records attributed to T Ishida.

1,366 records · Page 76Linked to original sources
PubMedDate not supplied

Isolation and identification of urinary metabolites of oxycodone in rabbits.

Metabolism of oxycodone was studied in the rabbit and found to proceed through five metabolic pathways: O-demethylation, N-demethylation, N-oxidation, 6-keto reduction, and glucuronidation. Six urinary metabolites were isolated and identified in the unconjugated form: 14-hydroxydihydromorphinone, 14-hydroxydihydrocodeine, 14-hydroxydihydrocodeinone N-oxide (oxycodone N-oxide), 14-hydroxydihydroisocodeine, 14-hydroxydihydrocodeine N-oxide, and noroxycodone, together with unchanged oxycodone. Identification was made by means of various chromatographic and spectral comparisons with authentic samples. Oxycodone, 14-hydroxydihydromorphinone, 14-hydroxydihydrocodeine, 14-hydroxydihydroisocodeine, and noroxycodone were also identified as aglycons of conjugated metabolites.

Animals↗
PubMedDate not supplied

Studies on the mechanism of covalent binding of morphine metabolites to proteins in mouse.

The disposition of N--14CH3-labeled and C-6--3H-labeled morphines in mouse tissue was determined over 48 hr after sc injection. 3H radioactivity in tissues decreased more rapidly than 14C radioactivity, and 14C activity at 48 hr after injection was 2 to 3 times greater than 3H activity in brain, blood and liver. Only 14C radioactivity in the brain and other tissues accumulated significantly by repeated co-administrations of N--14CH3- and C-6--3H-morphines. However, 3H radioactivity did not show much accumulation in brain. The ratio of 14C radioactivity irreversibly bound to macromolecules (insoluble in HCl-methanol) to the total radioactivity increased with time in the liver. [14C]Morphinone-cysteine conjugate was detected in proteolytic digests of mouse liver protein dosed with radiolabeled morphine. Morphinone-glutathione conjugate was also detected in an incubation mixture of morphine and cytosol fraction of mouse liver. These results seem to indicate that morphine is metabolized to morphinone, which then binds covalently to the thiol group of cysteine residues in protein.

Animals↗
PubMedDate not supplied

Malignant pleurisy and intrathoracic dissemination in carcinoma of the lung: diagnostic, therapeutic and prognostic implications.

Of T4 disease of lung cancer, malignant pleurisy and intrathoracic dissemination are the greatest factor preventing a cure, despite the best efforts of surgery and various adjuvant therapy modalities. Preoperative evaluation of this disease is of first importance using conventional radiology and computed tomography. Of the 43 patients who were intraoperatively diagnosed to be the disease, 8 (18%) appeared on the conventional radiology as small amounts of pleural effusion, and 9 (21%) with a interlobar pleural thickening. Based on CT findings, 16 (67%) had one or more of some disseminated nodules, interlobar pleural thickening and broad pleural indentation. In patients with T4 disease, the 5-year survival rate was 14% in patients with malignant pleurisy and/or intrathoracic dissemination, compared with the 18% in those with direct invasion to great vessels, with no significant difference. According to intrapleural instillation as postoperative adjuvant therapy, the 5-year survival rate was 25% in the patients given interleukin-2, compared with 38 months of survival time for patients prescribed doxorubicin and 33 months for those underwent exploratory thoracotomy. A more favorable prognosis of patients whose malignant pleurisy and/or intrathoracic dissemination are first found at thoracotomy can be expected when postoperative intrapleural instillation of interleukin-2 is prescribed following the resection of the intrathoracic tumors.

Adenocarcinoma↗
PubMedDate not supplied

Antihypertensive effects of a new transdermal delivery system for clonidine (M-5041T) in spontaneously hypertensive rats.

The antihypertensive effects of a new transdermal delivery system for clonidine (clonidine tape; M-5041T) were investigated in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. In spontaneously hypertensive rats, M-5041T, at doses of 0.5-4.5 mg/kg (1.25-11.25 cm2/kg), produced a dose-dependent decrease of both systolic blood pressure and heart rate for 24 hr during transdermal application. These significant hypotensive effects lasted for 24 hr following the patching of M-5041T on the back of the animals at a dose of 4.5 mg/kg. In normotensive Wistar-Kyoto rats, the hypotensive and bradycardic effects of M-5041T were weak compared with those in spontaneously hypertensive rats. In both rat strains, M-5041T (4.5 mg/kg) caused behavioral changes such as sedation, piloerection and exophthalmos, accompanied by hypotensive effects. Both M-5041T (1.5 mg/kg) and clonidine (50 micrograms/kg, subcutaneously and 100 micrograms/kg, orally) induced similar hypotensive effects, accompanied by sedation. The hypotensive effects following transdermal M-5041T or systemic clonidine administrations were correlated with the time courses of the plasma clonidine concentration. In contrast to clonidine administered subcutaneously or orally, M-5041T produced a gradual increase in the plasma clonidine concentration, which persisted at a consistent level for at least 12 hr thereafter. Significant hypotensive effects lasted for 12 and 24 hr following M-5041T patching at 1.5 and 4.5 mg/kg, respectively. The present findings suggest that M-5041T can serve as an efficient and useful antihypertensive transdermal delivery system to achieve persistent blood pressure control.

Administration, Cutaneous↗
PubMedDate not supplied

Histopathology of uterine cervical carcinoma: diagnostic comparison of endorectal surface coil and standard body coil MRI.

OBJECTIVE: We compared body coil (BC) MR images and endorectal surface coil (ERC) images with respect to the visualization of the cervix and adjacent tissues and the histopathologic correlations of the imaging findings. MATERIALS AND METHODS: Twenty-one patients with cervical carcinoma underwent MRI using both coils for evaluation of the cervix and adjacent tissues. In all patients, surgical confirmation of the diagnosis was obtained after imaging. RESULTS: The ERC images were superior to BC images for visualization of the cervix, parametrium, anterior vaginal wall, and posterior bladder wall (p < 0.005). The accuracy of detecting parametrial invasion by ERC and BC imaging was, respectively, 95 and 79% (p < 0.05), while the differences of accuracy between BC and ERC imaging were not statistically significant in staging or in assessing for invasion to corpus, vagina, bladder, and rectum. All the false-positive sites of parametrial invasion on BC images were diagnosed correctly on ERC images. CONCLUSION: Endorectal surface coil imaging is useful in assessing the extent of cervical carcinoma, especially parametrial invasion, because it can delineate the tumor and the normal tissues in detail.

Adult↗
PubMedDate not supplied

Different site mutation of the K-ras gene in a patient with metachronous double lung cancers.

We present a case with metachronous double lung cancers proved by molecular analysis. A male patient first had lung cancer discovered when he was 67 years old, and a second lung cancer was found when he was 71 years old. Pathologically, the first cancer was moderately to well differentiated adenocarcinoma and the second cancer was well differentiated adenocarcinoma. These findings suggested that the second cancer was not metastasis from the first lung cancer but a second primary lung cancer. According to the PCR and oligonucleotide mutation specific dot blot hybridization, the first lung cancer had a GGT to GTT mutation, while the second lung cancer had a GGT to TGT mutation at codon 12 of the K-ras gene. These results thus prove that these tumors were metachronous double cancers.

Adenocarcinoma↗
PubMedDate not supplied

(S)-C alpha-ethyl, C alpha-benzylglycine [(S)-(alpha Et)Phe] peptides fold in left-handed helical structures.

The first x-ray diffraction structure analysis of a C alpha-ethyl, C alpha-benzylglycine [(alpha Et)Phe]-containing peptide, N alpha-benzyloxycarbonyl-alpha-aminoisobutyryl-alpha-amino-isobutyr yl-(S)- C alpha-benzylglycyl-alpha-aminoisobutyric acid (methanol solvate), has been performed. In the crystal state the N alpha-protected tetrapeptide is folded in an incipient, left-handed 3(10)-helical structure. This finding confirms that the relationship between (alpha Et)Phe alpha-carbon chirality and screw sense of the helix that is formed is opposite to that exhibited by protein amino acids, including Phe.

Chemical Phenomena↗
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Survival following resection for lung cancer as a second primary cancer.

A second operation was done on 59 patients with lung cancer (7.4% of all those with lung cancer) as a second primary (double primary), during 1974-1991. There were 16 synchronous tumors (interval less than one year) and 43 metachronous tumors (interval over one year). The criteria for diagnosing lung cancer as a second primary from intrapulmonary metastases were any of the following: 1) different histologic type; 2) origin from carcinoma in situ; 3) gross appearance suggestive of primary lung cancer. The initial operation was in the stomach in 14 patients and in the lung in 10. The overall 5-year survival rate in the double primaries was 57.8%, and the prognosis was similar to those in the single primaries of the lung. Nineteen patients died from the second tumor following the second operation, compared with 5 from the initial tumor. The incidence of primary lung cancer increases, and close follow-up after resection for malignant neoplasms detects a new shadow in the chest roentgenogram. It offers a chance of early detection of primary lung cancer and subsequent resection with acceptable results.

Adult↗
PubMedDate not supplied

Beneficial effect of thromboxane A2 synthetase inhibitor (OKY-046) on 24-hr simple hypothermic preservation of the canine pancreas graft.

This study was performed to investigate the potential protective effect of OKY-046, an inhibitor of thromboxane A2 synthetase, on the viability of 24-hr preserved canine segmental pancreas graft. Each graft was preserved in either cold Euro-Collins (E-C) solution (control group; n = 5) or E C+OKY-046(10(-4)M) solution (OKY-046 group; n = 5). In both groups, grafts were preserved for 24 hr and calculated the total levels of 6keto-prostaglandin F1 alpha (6ket-PGF1 alpha) and thromboxane B2(TxB2) in the preservation solution per pancreas graft weight at the time point of 0,3,7,12,24 hr after preservation. The efficacy of OKY-046 in protecting ischemically stressed grafts was examined by histological findings of the grafts before transplantation and blood flow of the transplanted pancreas graft. During 24-hr preservation time, increased production of 6ket-PGF1 alpha and decreased production of TxB2 were found in OKY-046 group. Histologically ischemic damage of the acinar cells was observed in the control group, but it was milder in the OKY-046 group. The blood flow of the transplanted pancreas in the OKY-046 group were higher than that in control group. In the OKY-046 group, all dogs survived with functioning grafts, although some grafts were lost in the control group. These results suggest that there is a possibility that OKY-046 may contribute to the improvement of the survival rate in segmental pancreas transplantation.

Animals↗
PubMedDate not supplied

CT diagnosis of pleural dissemination without pleural effusion in primary lung cancer.

We retrospectively reviewed the CT scans of 25 primary lung cancers with disseminated pleural nodules or minimal malignant pleural effusions that were not recognized preoperatively. Special attention was devoted to abutting interlobar fissures, thick major fissures, and disseminated nodules on the chest wall, the diaphragm, and in the interlobar fissures. Among 10 primary tumors abutting interlobar fissures, nine (90%) had at least one of these findings. Among 15 primary lung tumors which did not abut interlobar fissures, four (27%) had at least one of these findings. We conclude that CT is a useful modality for detecting the pleural dissemination of primary lung cancers when primary lung cancers abut interlobar fissures even if no pleural effusion is detectable on CT.

Adult↗
PubMedDate not supplied

Thoracoscopic limited resection of bronchogenic carcinoma in patients over the age of 80.

Video-assisted thoracoscopic surgery (VATS) has emerged as a minimally invasive therapy of bronchogenic carcinoma, when the diseases occur in patients unable to tolerate open thoracotomy who are 80 years old or older. We report on an 80-year-old man with poor pulmonary function and an 83-year-old man, who were treated with a complete VATS resection of bronchogenic carcinoma. Mean chest tube duration of the two patients was one day and mean postoperative hospital stay was 7 days with an uncomplicated postoperative course. Compared with patients with open thoracotomy, there were early mobility, less morbidity, and less mortality. We believe that when the indication for treatment of bronchogenic carcinoma in patients over the age of 80 with concomitant systemic disorders, a thoracoscopic limited resection should be considered.

Aged↗
PubMedDate not supplied

Antitumor effects of butyrolactone I, a selective cdc2 kinase inhibitor, on human lung cancer cell lines.

Butyrolactone I, which is a naturally occurring specific inhibitor of the cdc2 kinase family, showed antitumor effects on several non-small- and small-cell-lung cancer cell lines with IC50 values the order of 50 micrograms/ml on the former. No cross-resistance of several drug-resistant cell lines, including those with the multidrug-resistant phenotype and five cisplatin-resistant cell lines to butyrolactone I was observed. The cdc2 kinase activity of PC-14 cells was inhibited by treatment with 20 micrograms/ml butyrolactone I, a concentration comparable to the IC50 value, for 2 hours. Longer exposure to butyrolactone I (> 24 hours) reduced the cdc2 kinase protein level. Butyrolactone I arrested the cells at the G2/M phase in a concentration dependent manner. These results suggest that butyrolactone I actually acts on cdc2 kinase, rather than other cdk kinases, in PC-14 cells. Inhibition of DNA synthesis, determined by measuring thymidine uptake, occurred earlier (2 hours) after initiating exposure than the decrease in the cdc2 protein level and was concentration dependent, suggesting that butyrolactone I inhibited DN4 synthesis. Cell permeabilization by digitonin enhanced DN4 synthesis inhibition by butyrolactone I, suggesting that the permeability of the membrane to this agent was the limiting factor for its growth inhibitory effect. Many anticancer agents, such as alkylating agents and cisplatin, cause cells to accumulate at the G2/M phase of the cell cycle. We investigated whether butyrolactone I had any modulatory effect on the antitumor effects of several anticancer drugs in vitro. Butyrolactone I showed no modulatory effects on vindesine, paclitaxel, or etoposide, but exposure of PC-9 and PC-14 cells to butyrolactone I together with or prior to treatment with cisplatin reduced the cytotoxicity of the latter. Thin-layer chromatographic analysis revealed that butyrolactone I bound to cisplatin, which was a possible cause of the reduced cisplatin cytotoxicity in the presence of bytyrolactone I.

4-Butyrolactone↗
PubMedDate not supplied

Thoracoscopy in the management of intrathoracic neurogenic tumors.

Video-assisted thoracoscopic surgery (VATS) has emerged as a minimally invasive therapy of intrathoracic neurogenic tumors, when the diseases occur in the adult and show no intraspinal extension. We have reviewed five cases: three tumors arose from the sympathetic chain with no intraspinal extension, vagus nerve in one, and intercostal nerve in one. For all five patients, hospitalization was brief, recovery was relatively rapid, and long-term results were excellent. We believe that when the indication for the treatment of patients with an intrathoracic neurogenic tumor are met in the adult, the procedure of choice should be the VATS approach.

Adolescent↗
PubMedDate not supplied

Comparison of breast-conserving therapy with mastectomy for treatment of early breast cancer.

The aim of this study was to compare the survival and recurrence rates of patients undergoing breast-conserving therapy with the rates of those undergoing mastectomy. Between August 1991 and June 1994, 229 patients were enrolled in this study, although one was later excluded because the tumor was histologically diagnosed as benign. A total of 119 patients with clinical stage TIS, I or II underwent breast-conserving therapy and 109 patients received mastectomy. Mastectomy was utilized more than breast-conserving therapy in the case of clinical stage II, greater age, larger tumor size or shorter distance between the tumor and the nipple. Twenty-seven patients (23.1%) of the 117 receiving breast-conserving surgery were surgical margin positive. There was no significant difference in the distance between the tumor and the nipple, tumor size or clinical stage in the incidence of surgical margin positive cases. Mean follow-up time of the breast-conserving therapy group and the mastectomy group was 42.4 and 39.7 months, respectively. There was no significant difference in the overall survival and disease-free survival between breast-conserving therapy and mastectomy. After adjustment for the clinical stage, there was no significant difference in the prognosis between breast-conserving therapy and mastectomy.

Adult↗
PubMedDate not supplied

Second primary cancers after resection of lung adenocarcinoma with ras gene mutation.

BACKGROUND: Ras gene mutations are associated with a poor prognosis in patients with adenocarcinoma of the lung. However, the association between cases with ras gene mutation and an occurrence of second primary cancer is unknown. MATERIALS AND METHODS: We examined 89 adenocarcinoma of the lung obtained from patients treated by curative resection, and four second primary cancers, for mutation at codons 12, 13, and 61 of three ras oncogenes using polymerase chain reaction and oligonucleotide hybridization techniques. RESULTS: Ras gene mutations were detected in 13 cases. Six patients died from recurrent disease within 3 years. Of the seven patients who survived over 5 years, three patients demonstrated a metachronous second primary cancer after the operation for lung cancer, and one patient had synchronous laryngeal cancer. Two of the cases with second primary cancer demonstrated the ras gene mutation. One had the same mutation as that of the primary lung cancer, and the other had a different mutation from the first lung cancer. CONCLUSION: Ras gene mutations play an important role in tumor progression of lung adenocarcinoma and also might have an role in the carcinogenesis in respiratory tract cancer.

Adenocarcinoma↗