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Biomedical subjects

K Sugihara

Publications and source records attributed to K Sugihara.

At least 109 records · Page 6Linked to original sources

Histochemical study of apoptosis and cell proliferation in hereditary intestinal diseases.

The occurrence of apoptosis and cell proliferation in hereditary intestinal diseases was analyzed for possible diagnostic markers that could discriminate the formation of tumors that would develope into cancer. In all, 15 adenomas in familial adenomatous polyposis, 3 juvenile polyposis, 5 Peutz-Jeghers syndrome, 14 sporadic adenomas, and 46 colorectal carcinomas were investigated. Tissue specimens were examined for apoptotic cells by TdT-mediated dUTP-biotin nick end labeling (TUNEL), and proliferating cells by immunohistochemistry of proliferating cells nuclear antigen (PCNA). In hereditary intestinal diseases, the apoptotic and proliferating indexes were significantly lower than those in colorectal carcinoma, and higher apoptotic and proliferating indexes were observed in poorly differentiated colorectal adenocarcinoma and in subserosal stages of invasion. There were no significant differences in proliferating and apoptotic indexes between adenoma in FAP and sporadic adenoma. No apoptotic and proliferating cells were observed in juvenile polyposis, and only occasional proliferating cells were seen in Peutz-Jeghers syndrome. These findings demonstrated that TUNEL and PCNA staining are useful in correctly reflecting disease progression in hereditary intestinal diseases.

Adenocarcinoma↗

Recurrence of unicystic ameloblastoma: a case report and review of the literature.

Unicystic ameloblastoma is believed to be less aggressive and responds more favorably to conservative surgery than the solid or multicystic ameloblastomas. We report a case of unicystic ameloblastoma that was initially treated by marsupialization and later by enucleation under suspicion of a dentigerous cyst. The neoplastic nature of the lesion became evident only when the enucleated material was available for histologic examination. Apart from an ameloblastomatous epithelial lining and luminal tumor nodules, the cystic tumor contained numerous tumor islands within its fibrous capsule. The lesion recurred 8 years after the enucleation. This case supports the view that the presence of tumor islands in the fibrous capsule may indicate a high risk of recurrence for unicystic ameloblastomas. Relevant diagnostic problems and choice of treatment are presented along with a review of the literature.

Ameloblastoma↗

[Intra-arterial injection therapy of mitoxantrone for locally advanced breast cancer].

Mitoxantrone (MIT) is a new anthraquinone anticancer agent. We treated 14 patients with locally advanced breast cancer, 3 of which were inflammatory breast cancers, by pre-operative arterial injection of MIT. The treatment protocol was MIT 12 mg/m2 injected into both the internal mammary and the subclavian arteries with oral administration of 5'-DFUR 1,200 mg/day for 20 days. After 2 courses, all tumors were decreased over 50% in size. Down-staging was obtained in all of 8 cases. Mastectomy could be carried out on all patients, without microscopically residual tumor cells. Preoperative arterial injection of MIT might be the treatment of choice for locally advanced breast cancer to perform down-staging, however the survival benefit has remained equivocal. These preliminary results are encouraging to further studies.

Antineoplastic Combined Chemotherapy Protocols↗

The significance of peritoneal cytology in uterine cervix and endometrial cancer.

OBJECTIVE: The purpose of this study was to determine the incidence of positive peritoneal cytology and to elucidate the prognostic value of peritoneal cytology in patients with uterine cervix and endometrial cancer. MATERIALS AND METHODS: The incidence of positive peritoneal cytology was investigated in 642 patients including 339 uterine cervix and 303 endometrial cancers. Survival was estimated by the Kaplan-Meier method in a subgroup of 116 stage II cervix and 199 stage I endometrial cancers, and multivariate analysis using Cox's proportional hazards model was used to identify an independent prognostic factor. RESULTS: The incidence of positive peritoneal cytology was found to be 9% in uterine cervix cancer and 15% in endometrial cancer. The incidence was higher in patients with some clinicopathologic status such as advanced stage, lymph node metastasis, ovarian metastasis, and deeper myometrial invasion. The 5-year survival rate for patients with positive or negative peritoneal cytology was 44 or 80% in stage II cervix cancers and 80 or 92% in clinical stage I endometrial cancers, respectively. Multivariate analysis revealed that independent prognostic determinants were pelvic and paraaortic lymph node metastasis and peritoneal cytology in stage II cervix cancer and peritoneal cytology in stage I endometrial cancer. Proper treatment protocol should be scheduled for patients with positive peritoneal cytology.

Endometrial Neoplasms↗

Triple-stapled low colorectal anastomosis for the narrow pelvis.

Standard linear staplers for transverse occlusion of the rectum is sometimes too large to be applied in a narrow pelvis. A proximate TL 30 (Ethicon, Inc., Somerville, NJ) is easily introduced and applied twice for occlusion of the rectum, followed by anastomosis with a circular stapler. This triple-stapling technique is a safe and easy procedure for low colorectal anastomosis in a narrow pelvis.

Anastomosis, Surgical↗

Limitations and pitfalls of transrectal ultrasonography for staging of rectal cancer.

PURPOSE: This study was designed to evaluate the accuracy of preoperative staging by transrectal ultrasonography (TRUS) and to clarify the limitations and pitfalls of TRUS by clinicopathologic analysis for staging errors. MATERIALS AND METHODS: Results of TRUS for 164 consecutive patients with rectal cancer were compared prospectively with histopathologic findings according to the newest TNM classification. Clinicopathologic factors that may influence staging errors were analyzed by reviewing both resected specimens and hard copies of TRUS. RESULTS: There were 13 patients histopathologically staged as pTis, 21 as pT1, 34 as pT2, 84 as pT3, 12 as pT4, 73 as pN0, and 91 as pN1-3. Of these, 85, 86, 56, 93, 75, 74, and 77 percent, respectively, were correctly staged by TRUS. Excluding 12 cases with incomplete examinations because of annular constricting tumors, overstaging of tumor invasion depth was mostly caused by tumor invasion close to the deeper uninvolved layer, inflammatory cell aggregation, desmoplastic change, and hypervascularity around the tumor, mimicking tumor invasion on TRUS. The understaging was mostly the result of microscopic invasion beyond the estimated layers and difficulties in examination because of the tumor location being close to the anal canal or on the Houston's valves or the tumor shapes being polypoid or bulky and fungating. Overstaging in lymph node status was caused by reactive lymph node swelling and understaging by the presence of only small involved node and metastasis in the extramesorectal nodes. CONCLUSIONS: An awareness of the limitations and pitfalls of TRUS, as demonstrated by the present study, should improve staging accuracy and contribute to optimum clinical decision-making.

Endosonography↗

Importance of extended lymphadenectomy with lateral node dissection for advanced lower rectal cancer.

A total of 448 patients with advanced lower rectal cancer who underwent curative wide lymphadenectomy with autonomic nerve preservation were reviewed with respect to surgical techniques, operative burdens, node status, survival rate, and mode of recurrence. Operative time and blood loss in patients who underwent lateral dissection were much greater than those encountered with conventional resection. According to the direction of lymphatic spread in patients with Dukes C disease, the incidence of upward spread was 94% and lateral spread 27%. The overall incidence of lateral metastasis was 14%. The overall 5-year survival was 70%. According to the Dukes classification, the 5-year survival rates were 92% for Dukes A, 79% for Dukes B, and 55% for Dukes C, whereas it was 43% in patients with lateral node metastasis. An analysis of the survival rate was carried out with regard to the number of node metastases, direction of lymphatic spread, and autonomic nerve preservation. The overall incidence of local recurrence was 9.3% and amounted to 16.0% in patients with Dukes C disease. The case of advanced lower rectal cancer was characterized by positive lymph nodes or circular lesions around the circumference (both diagnosed by endorectal ultrasonography). We recommend extended lymphadenectomy with lateral node dissection, as it preserves the autonomic nerve.

Adult↗

Interferon-alpha therapy in patients dually infected with hepatitis C virus and GB virus C/hepatitis G virus--virological response of HGV and pretreatment HGV viremia level.

BACKGROUND/AIMS: The response to interferon-alpha (IFN) therapy of recently isolated GB virus C and hepatitis G virus (HGV) is still unclear. To investigate the biochemical and virological response to IFN therapy in patients with chronic hepatitis C virus (HCV) infection concomitantly infected with HGV, 196 patients with HCV who had received IFN therapy were retrospectively studied. METHODS: HGV and HCV RNA were detected by reverse transcription nested polymerase chain reaction (RT-PCR). Serum HGV RNA levels were quantified by competitive RT-PCR. The HGV genotype was detected by restriction fragment length polymorphism analysis using the PCR products. RESULTS: Of 196 patients, 16 (8.2%) were positive for both HCV and HGV RNA before IFN therapy. There were no significant clinical and virological differences between the patients with dual infection and those with only HCV infection. During the therapy, a decrease or loss of serum HGV RNA level was observed in these patients. Six months after cessation of the therapy, five of 16 patients became negative for HGV RNA by RT-PCR. The pretreatment HGV RNA level of the patients who lost HGV RNA after cessation of IFN was low (median=10(3) copies/ml), compared to the level (median=10(7) copies/ml, p<0.01) in the patients with positive HGV RNA after the therapy. The HGV genotype of these 16 patients was the same type. CONCLUSIONS: These data suggest that: 1) there is no significant difference in response to IFN therapy between patients with dual and single infection; 2) HGV shows sensitivity to IFN therapy; and 3) in the patients who show a low pretreatment HGV RNA level, serum HGV RNA becomes undetectable by RT-PCR after cessation of IFN therapy.

Adult↗

Experimental study on the role of osteoclasts and free radicals in the mandibular invasion of VX2 carcinoma in Japanese white rabbits.

Oxygen-derived free radicals are stimulators of bone resorption in vitro and in vivo. We hypothesized that oxygen-derived free radicals or reactive oxygen species (ROS) generated around bone matrix invaded by cancer cells might be associated with the activation or formation of osteoclasts in bone metastasis, and thus the administration of an ROS scavenger or a free-radical scavenger might control osteoclastic bone destruction in tumor metastasis. We examined the ability of VX2 carcinoma cells to generate superoxide anion (O2-) as well as the effects of the O2- scavenger superoxide dismutase (SOD) and the hydrogen peroxide (H2O2) scavenger catalase (CAT) on the activation and formation of osteoclasts in VX2 carcinoma tissue of rabbits. VX2 carcinoma cells generated more O2- than tartrate-resistant acid phosphatase-positive (TRAP+) cells. The TRAP activity from TRAP+ cells in the presence of VX2 carcinoma cells was higher than that from TRAP+ cells in the absence of the carcinoma cells. The addition of SOD but not of CAT into the incubation medium inhibited the TRAP activity from TRAP+ cells in the presence or absence of VX2 carcinoma cells. Similar inhibitory effects were also observed with SOD plus CAT on TRAP+ cells in the presence or absence of carcinoma cells. Intravenous administration of SOD and SOD plus CAT, but not of CAT, caused a decrease in the number of osteoclasts in mandibles implanted with VX2 carcinoma cells, and showed a predominant occupation by osteoclasts with poorly developed ruffled borders in lesions of bone resorption. In contrast, the administration of CAT, but not of SOD and SOD plus CAT, decreased the more mature forms of osteoclasts in implanted mandibles. From the results obtained, it is suggested that O2- may stimulate bone resorption by increasing the activity and number of osteoclasts, and H2O2 may stimulate resorption by enhancing the formation of mature osteoclasts in tumor metastasis. The administration of some ROS or free-radical scavengers to patients with cancer may provide a defense against bone destruction in bone metastatic lesions.

Animals↗

Differences in aldehyde oxidase activity in cytosolic preparations of human and monkey liver.

This study presents data showing individual differences in aldehyde oxidase activity in human and monkey liver cytosols. When assayed with benzaldehyde as a substrate, a significant inter-subject variation in the activity was found in the human liver preparations. When assayed with N1-methylnicotinamide as a substrate, the inter-subject variation of the activity was also observed, but to a lesser extent compared with that of the activity with benzaldehyde. Similarly, variations in aldehyde oxidase activity were found in the monkey liver preparations when assayed with benzaldehyde or N1-methylnicotinamide. The present study suggested that at least two isozymes of aldehyde oxidase exist in the human liver preparations.

Aged↗

Nonenzymatic reduction of brucine N-oxide by the heme group of cytochrome P450.

Evidence showing that cytochrome P450-mediated reduction of brucine N-oxide to brucine by rat liver microsomes proceeds nonenzymatically in the presence of both a reduced pyridine nucleotide and FAD is presented. The microsomal N-oxide reduction appears to proceed in two steps: The first step is reduction of FAD by NADPH or NADH either enzymatically or nonenzymatically. The second step is nonenzymatic reduction of the tertiary amine N-oxide by the reduced flavin and is nonenzymatically catalyzed by the heme group of cytochrome P450.

Animals↗

Colonoscopy for frank bloody stools associated with cancer chemotherapy.

Diarrhea is a common complication of cancer chemotherapy, while bloody stool is rare. Pseudomembranous colitis has been reported as causing bloody diarrhea after chemotherapy. In this report, we describe nine consecutive patients who presented frank bloody stools within one month after cancer chemotherapy. Patients with a history of pelvic irradiation or with a previously identified colorectal tumor were excluded. Among nine patients, bleeding from tumor undetected before chemotherapy was seen in three, pseudomembranous colitis in four, ischemic colitis in one and methicillin-resistant Staphylococcus aureus enterocolitis in one. Of the three tumors, one was an adenomatous polyp and the other two were metastatic tumors. Two of the four patients with pseudomembranous colitis had not received antibiotics before the onset of colitis. Causes of bloody stools after chemotherapy were various and colonoscopy played an important role in diagnosis and prompt therapy.

Adenocarcinoma↗

Sclerosing sweat duct carcinoma in the peri-anal skin: a case report.

We report a case of sclerosing sweat duct carcinoma, a rare tumor, occurring in the peri-anal skin, a rare position. The patient, a 41-year-old Japanese woman, was admitted to our hospital with recurrence of sclerosing sweat duct carcinoma in the peri-anal skin, which had been initially resected at a local hospital. She underwent abdomino-perineal resection. No lymph node metastases or distant metastases were found. Although we allowed a 2-cm resection margin around the tumor, microscopy showed that the tumor had extended to within 2 mm of this margin at several sites, indicating that sclerosing sweat duct carcinoma is locally aggressive. An ample resection margin should therefore be taken at initial surgery for this type of tumor. Moreover, surgical excision that is wider and deeper than primary excision is required when this tumor recurs.

Adult↗

An immunohistochemical study of thrombomodulin in oral squamous cell carcinoma and its association with invasive and metastatic potential.

Thrombomodulin (TM) is a glycoprotein that was originally identified on vascular endothelium and characterized as a natural endothelial anticoagulant. We reported previously that TM was also expressed at cell-cell boundaries of squamous epithelium, except in the basal layer cells and upper granular layer cells. The expression pattern of TM in the squamous cells implies that this molecule might be associated with keratinocyte differentiation, as well as being a potent anticoagulant. In the present study we examined TM expression immunohistochemically in biopsy specimens from 65 patients with primary oral squamous cell carcinoma (OSCC), and compared the results with the biological behavior of the carcinomas. The patients with intense TM expression in the carcinoma showed a significantly lower frequency of lymph node metastasis and significantly more favorable survival than those with negative TM expression. The TM expression was a better marker than the other prognostic factors, such as differentiation degree, tumor size and invasion mode. When TM expression was compared between the primary and metastatic lesions in the 36 patients who had lymph node metastasis, 14 (39%) showed decreased TM expression, 19 (53%) showed no change, and 3 (8%) showed an increase in the metastatic lesions. Wilcoxon's signed-rank test indicated that tumor cells positive for TM expression were significantly rarer in the metastatic lesions than in the primary tumors (P < 0.05). These results indicate that reduced expression of TM is associated with metastasis of carcinoma cells. The reduction of TM expression seems to play an important role in the metastatic process of OSCC, and to be related with a poor outcome for the patients.

Adult↗

The role of mammalian intestinal bacteria in the reductive metabolism of zonisamide.

Zonisamide (1,2-benzisoxazole-3-methanesulphonamide), a new anticonvulsant, is mainly metabolized to 2-sulphamoylacetylphenol by reduction of the benzisoxazole ring. Recent studies have shown that mammalian liver enzymes are responsible for the reduction of zonisamide. Because intestinal bacteria can also mediate the reduction of xenobiotics, this study was designed to evaluate the role of intestinal bacteria in in-vivo reductive metabolism of zonisamide. Treatment of rats with antibiotics significantly reduced the urinary and faecal excretion of 2-sulphamoylacetylphenol after oral administration of zonisamide. Re-contamination of the antibiotic-treated rats with microflora restored the excretion of the metabolite. The caecal contents of the control rats had significant zonisamide reductase activity, whereas little or no zonisamide reductase activity was observed with the caecal contents of the antibiotic-treated rats. Eight pure strains of intestinal bacteria were tested for zonisamide reductase activity and the highest was observed in Clostridium sporogenes. We concluded that intestinal bacteria play a major role in the reductive metabolism of zonisamide to 2-sulphamoylacetylphenol in-vivo.

Aldehyde Oxidase↗

Pharmacokinetics of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate. 1st communication: absorption, distribution and excretion after single administration of 14C-labeled compound to rats and dogs.

The absorption, distribution and excretion of radioactivity were studied in rats and dogs after intravenous or oral administration of NS-21 ((+/-)-4-diethylamino-1, 1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate, CAS 129927-33-4). 14C-NS-21 was rapidly absorbed from the gastrointestinal tract after oral administration to rats and dogs. NS-21 was absorbed throughout the whole area of the small intestine. NS-21 entered the systemic circulation via the portal vein because the transfer of radioactivity into the lymph was negligible. The presence of food did not affect the absorption ratio of NS-21. There was no difference in the plasma concentrations of radioactivity after intravenous and oral administrations of 14C-NS-21 to male and female rats. After oral administration of 3, 30 or 100 mg/kg of 14C-NS-21 to rats, the area under the plasma concentration-time curve increased in a dose-dependent manner. After oral administration of 14C-NS-21 to rats, radioactivity was distributed throughout the whole body. The concentrations of radioactivity in most tissues reached their maximums within 2 h, and then declined as the plasma concentration decreased. No radioactivity was detected in most tissues 168 h after administration. In vitro serum binding of 14C-NS-21 was more than 98% in all the animal species tested. NS-21 bound to both human serum albumin and alpha 1-acid glycoprotein. Radioactivity was mainly excreted into the feces via bile in rats, and evenly excreted into the urine and feces in dogs. No differences were observed in the excretion of radioactivity between male and female rats.

Administration, Oral↗