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Biomedical subjects

K Togashi

Publications and source records attributed to K Togashi.

At least 55 records · Page 3Linked to original sources

Laparoscopic adhesiolysis for recurrent small bowel obstruction: long-term follow-up.

BACKGROUND: Recurrent small bowel obstruction caused by postoperative adhesions has traditionally been treated by conventional laparotomy, but laparoscopic management of acute small bowel obstruction has been reported. The aim of this study was to assess the long-term efficacy and clinical outcome of laparoscopic adhesiolysis for recurrent small bowel obstruction. METHODS: After conservative treatment, elective laparoscopic treatment was attempted in 17 patients hospitalized for recurrent small bowel obstruction after abdominal or pelvic surgery. RESULTS: Postoperative adhesions were identified laparoscopically in all patients. Laparoscopic treatment was possible in 14 patients (82.4%). Conversion to laparotomy was required for 3 patients (17.6%) because of intestinal perforation (n = 1) or a convoluted mass of adherent bowel (n = 2). Long-term follow-up was possible in 16 patients. Two recurrences of small bowel obstructions were noted over a mean follow-up period of 61.7 months. CONCLUSIONS: Laparoscopic adhesiolysis is a safe and effective treatment for recurrent small bowel obstruction. Conversion to laparotomy should be considered in patients with dense adhesions.

Feasibility Studies↗

Inhibition of telomerase activity by fungus metabolites, CRM646-A and thielavin B.

We performed a screening program to identify telomerase inhibitors from our drug source obtained from fungus fermentations, and found that two compounds, CRM646-A and thielavin B, inhibited telomerase activity at doses of 3.2 and 32 microM, respectively. These compounds also inhibited the activity of viral reverse transcriptase at almost the same dose levels which inhibited telomerase activity.

Enzyme Inhibitors↗

Clinical value of positron emission tomography with FDG for recurrent ovarian cancer.

OBJECTIVE: Recurrence is often a major problem for patients who have undergone surgery for ovarian cancer. This prospective study was undertaken to evaluate the clinical contribution of positron emission tomography (PET) using (18)F-fluorodeoxyglucose (FDG) for recurrent ovarian cancer. SUBJECTS AND METHODS: Twenty-four women who had undergone surgery or chemoradiotherapy for histopathologically proven ovarian cancer were enrolled in this study. Ovarian cancer was thought to have recurred in 12 of these women because of evidence on conventional imaging modalities or tumor marker measurements (group A). Clinical findings for the remaining 12 women showed them to be disease-free (group B). PET findings for the women were compared with the final diagnoses obtained by histopathology or by clinical follow-up. The clinical contribution of PET was assessed by evaluating whether PET yielded information complementing the findings of conventional modalities and by examining its impact on treatment. RESULTS: PET gave valuable information for seven of 12 patients in group A in addition to the information obtained from findings on conventional imaging, and treatment was affected in five patients. On the other hand, in group B, additional information was obtained in only three of 12 patients, and treatment of only one patient was affected. Overall sensitivity, specificity, and accuracy of conventional imaging modalities were 72.7%, 75.0%, and 73.3%, respectively, and these rates improved to 92.3%, 100.0%, and 94.4%, respectively, by considering both conventional imaging modalities and PET findings. CONCLUSION: Our preliminary data suggest that whole-body PET with FDG can be a complementary modality for following up patients who have had ovarian cancer, especially patients believed to be at risk for recurrence.

Case-Control Studies↗

Construction of optimum index to maximize overall response across countries in the presence of genotype x environment interaction.

Sire effect is partitioned into two parts: constant effect unaffected by environments and interaction effect specific to each environment and responsible for genotype x environment (GE) interaction. Response to selection for constant effect is the same across environments, thus increasing genetic stability, whereas response to selection for interaction effect would vary depending upon environments. The conventional measure of GE interaction based on genetic correlation (gammaG) considers both constant and interaction components even though the constant component plays no role in GE interaction. In contrast, the proposed measure of GE interaction based on interaction correlation (gammaI) deals only with interaction component responsible for GE interaction and thus indicates the intensity of GE interaction generated by responsible genes. Constant and interaction effects with different economic weights were combined into optimum index to improve both genetic stability and overall response across countries (countries represent environments). Optimum index was more efficient than the unpartitioned index which was more efficient than selection in a single country except when economic weights between constant and interaction effects were equal. Optimum index and unpartitioned index were the same when these economic weights were equal. The advantage of optimum index over the other selection methods increases as the intensity of GE interaction increases. When the relative economic weights are equivalent among countries and between constant and interaction effects, selection in a country with a larger sire variance is more effective than selection in a country with a smaller sire variance.

Animals↗

[Development of three-dimensional stereo viewer for high-resolution data].

In order to visualize high-resolution three-dimensional (3D) data as a stereogram, a real-time volume-rendering system using a hardware graphic board and conventional PC was developed. A 256(3) data set could be visualized at a redrawing rate of 12 Hz, and a 512(3) data set at a rate of 2.5 Hz. It was demonstrated that stereogram visualization using volume graphic hardware architecture potentially enables rapid examination of high-resolution 3D data by changing visualization parameters such as level, window, transfer function for opacity, and color map or coordinate direction.

Computer Graphics↗

Tumor targeting and imaging of intraperitoneal tumors by use of antisense oligo-DNA complexed with dendrimers and/or avidin in mice.

To establish an effective nonviral gene delivery and a corresponding imaging method for i.p.-disseminated tumors, various oligonucleotide-carrier complexes were synthesized, and their in vitro and in vivo properties were examined. The 20-mer multiamino-linked oligonucleotide (oligo), synthesized as antisense against the c-erbB-2 sequence, and the 3'-biotinylated form of the same oligonucleotide (oligo-Bt) were (111)In labeled through a diethylenetriaminepentaacetic acid chelate. (111)In-oligo was mixed with generation 4 polyamidoamine dendrimer (G4) or with biotinylated G4 (G4-Bt), which are positively charged to form electrostatic complexes. (111)In-oligo/G4-Bt and (111)In-oligo-Bt were conjugated to avidin ((111)In-oligo/G4-Av and (111)In-oligo-Av, respectively). (111)In-oligo/G4, (111)In-oligo/G4-Av, (111)In-oligo-Av, and carrier-free (111)In-oligo (2.96 kBq/22.4-45.9 ng of oligo) were examined for internalization in vitro in human ovarian cancer cells (SHIN3). Biodistribution of (111)In-oligo-carrier complexes or (111)In-oligo was examined in normal (n = 4-7) or i.p. SHIN3 tumor-bearing (n = 6-10) mice 2-24 h after i.p. injection (74 kBq/125-300 ng). Scintigraphy of i.p. tumor-bearing and normal mice was performed at various times postinjection of (111)In-oligo-carrier complex or (111)In-oligo (1.85 MBq/2.2 ng). (111)In-oligo-carrier complexes bound to the tumor cells were internalized at a rate of 34-56% at 24 h. In vivo, G4, G4-Av, and Av significantly enhanced tumor delivery of (111)In-oligo [9.1, 14.5, and 24.4% of injected dose per g of tissue (ID/g) at 24 h; P < 0.05, < 0.01, and < 0.0001, respectively] compared with delivery without carrier (0.8% ID/g). Scintigrams of (111)In-oligo delivered to the i.p.-disseminated tumors by the carriers were successfully obtained. In conclusion, G4, G4-Av, and Av can effectively deliver (111)In-oligo to i.p.-disseminated tumors. (111)In-oligo-carrier complexes also have potential as tracers for imaging and monitoring of gene delivery.

Animals↗

Role of reducing co-factors in catalytic reactions of 6-hydroxymellein synthase, a multifunctional polyketide biosynthetic enzyme in carrot cells.

6-Hydroxymellein (6HM) synthase, a multifunctional polyketide biosynthetic enzyme in carrot cells, is capable of catalyzing the acyl-CoA condensation and the ketoreduction in the presence of the nucleotide reducing co-factors. Although free CoA at high concentrations functioned as the activator of the NADPH-dependent 6HM formation, the compound exhibited an appreciable inhibitory activity toward the reaction mediated by NADH. CoA showed a potent inhibitory activity against substrate entry into the reaction center of the NADH-associated enzyme while, in the presence of NADPH, the compound slightly inhibited the formation of the acylated enzyme. The catalytic rate of the synthase was appreciably decreased when NADPH was replaced by the deuterium-labeled compound, however, the kH/kD value was markedly reduced if NADH and [D]NADH were employed as the reducing co-factors. These results suggest that the phosphate group attached to 2'-position of the adenosyl moiety of NADPH associated with the ketoreducing domain of 6HM synthase plays an important role in the regulation of the enzyme activity.

Journal Article↗

Unusual arrangement of catalytic domains in head-to-tail associated homodimer of 6-hydroxymellein synthase, a multifunctional polyketide biosynthetic enzyme.

6-Hydroxymellein synthase, a multifunctional polyketide synthetic enzyme in carrot, is organized as a homodimer, and the activity of the synthase was appreciably inhibited upon the specific alkylation of cysteine- and cysteamine-SHs at the reaction center with iodoacetoamide and chloroacetyl-CoA, respectively. Dissociation and stoichiometric recombination of the unmodified and the SH-modified enzyme subunits yielded a combination of unmodified-unmodified, unmodified-modified and modified-modified hybrid dimers that together exhibit 50% activity. In contrast, hybrid dimers obtained by reconstruction of the two modified enzymes showed essentially no catalytic activity. These results suggest that the two subunits of 6-hydroxymellein synthase are aligned in head-to-tail orientation to organize two reaction centers which are comprised of a cysteine and a complementary cysteamine SH group, belonging to and contributed from the same subunit in the homodimer structure.

Journal Article↗

Predictive factors for detecting colorectal carcinomas in surveillance colonoscopy after colorectal cancer surgery.

PURPOSE: The aim of this study was to identify the high-risk groups for metachronous colorectal carcinoma among patients who undergo colorectal cancer surgery. METHODS: Three hundred forty-one patients undergoing colorectal cancer surgery who had undergone surveillance colonoscopy at least twice during a period of more than three years were analyzed. A metachronous colorectal carcinoma was defined as a new colorectal carcinoma detected by surveillance colonoscopy after surgery. RESULTS: Surveillance colonoscopy was performed 4.6 times per patient during an average of 6.2 years. Twenty-two metachronous colorectal carcinomas in 19 patients were detected, and 14 (64 percent) of 22 were detected within five years of surgery. The cumulative incidence of developing colorectal carcinomas during a five-year period was 5.3 percent. Seventeen (77 percent) of 22 carcinomas were 10 mm or less in size. Ten (71 percent) of the 14 carcinomas in early stages showed a flat appearance. Univariate analysis showed that extracolonic malignancy, coexistence of adenoma, and synchronous multiple colorectal carcinoma were significant predictive factors for detecting colorectal carcinomas in surveillance colonoscopy and that family history of colorectal carcinoma was a possible predictive factor. Multivariate analysis performed with Cox proportional hazards regression model showed that extracolonic malignancy and the coexistence of adenoma were significant predictive factors. CONCLUSION: We recommend that patients with the above predictive factors receive surveillance colonoscopy meticulously and regularly.

Adult↗

Monoclonal antibody-dendrimer conjugates enable radiolabeling of antibody with markedly high specific activity with minimal loss of immunoreactivity.

For the purpose of radioimmunotherapy, labelling of monoclonal antibody with high specific activity is often necessary, especially when using a radionuclide with a shorter half-life. Polyamine dendrimers (PAMAM) are novel synthetic polymeric molecules with large numbers of amine residues on their spherical surface. In order to bind large numbers of radiometals to single antibody molecules, the generation-4 PAMAM (G4), which has 64 amines, was conjugated with 43 molecules of 2-(p-isothiocyanatobenzyl)-6-methyl-diethylene triamine penta-acetic acid (1B4M), a derivative of DTPA. This product [G4-(1B4M)43] was then conjugated with OST7, a murine monoclonal IgG1. We evaluated the achievable specific activity for 111In labeling, immunoreactivity, biodistribution, and tumor targeting in mice of the 111In- or 153Gd-OST7-G4-(1B4M)43 as compared with radiolabeled OST7-1B4M or 56C-1B4M. The maximum specific activity of 111In-OST7-G4-(1B4M)43 and 111In-OST7-1B4M was 470 and 8.7 GBq/mg (12,700 and 263 mCi/mg), respectively. Immunoreactivity of radiolabeled OST7-G4-(1B4M)43 and OST7-1B4M, as determined by the binding to KT005 cells expressing the antigen, was respectively 91% and 84% of that of 125I-labelled OST7. Biodistribution studies for preparations with maximum specific activity in normal mice 3 h after injection showed that 111In- or 153Gd-OST7-G4-(1B4M)43 cleared faster from the blood and accumulated more in the liver than did 111In- or 153Gd-OST7-1B4M. The dendrimer 1B4M [G4-(1B4M)64] itself showed similar saturation effects with metals. The radioactivity in all the other organs reflected the rapid clearance of radioactivity from the blood. 153Gd-OST7-G4-(1B4M)43 showed specific accumulation in the KT005 tumor. In conclusion, we could successfully bind 49 times as many metal atoms to an antibody molecule as is possible with conventional metal labeling for indium and gadolinium, and did so with minimal loss of immunoreactivity. When we achieved radiolabeling with maximum specific activity, Gd conjugate showed better biodistribution than In conjugate.

Animals↗

Adnexal torsion: MR imaging findings of viable ovary.

We report a case of torsed ovarian cystic tumor, in which contrast-enhanced high-resolution MR images accurately contributed to the diagnosis of torsion despite the lack of symptoms and to the preoperative evaluation of viability of the edematous ovary. Accurate preoperative assessment by MR images and prompt conservative surgical approach succeeded in salvaging the involved ovary.

Adult↗

[Diagnostic pitfalls in evaluating MR images of the uterus].

The pitfalls in evaluating MR images of the uterus are briefly reviewed. These pitfalls are roughly divided into physiological conditions that simulate organic lesions, benign conditions that simulate malignancy, and malignant diseases that simulate benign conditions. It is important to distinguish these mimicking lesions from real organic lesions.

Female↗

[Myeloperoxidase-antineutrophil cytoplasmic antibody positive alveolar hemorrhage during propylthiouracil therapy for hyperthyroidism].

A 62-year-old woman had been treated with propylthiouracil(PTU) for hyperthyroidism. Because bloody sputum, dyspnea, and severe hypoxemia developed, the patient was admitted to our hospital. Chest X-ray and chest computed tomographic (CT) films disclosed diffuse infiltrative shadows in both lung fields. Bronchoalveolar lavage revealed abundant hemosiderin-laden macrophages. Alveolar hemorrhage associated with myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) positive vasculitis syndrome was diagnosed because of the high serum level of MPO-ANCA. After the initiation of steroid therapy and termination of PTU, the infiltrative shadows in both lung fields disappeared, PaO2 improved, and MPO-ANCA decreased. There have been some reports of MPO-ANCA positive vasculitis syndrome developing during PTU therapy, but most were concerned with renal disease. We concluded that PTU and similar agents should be given consideration as one of the possible causes of MPO-ANCA-induced alveolar hemorrhage.

Antibodies, Antineutrophil Cytoplasmic↗

[Recent advances in colorectal cancer surgery].

Recent advances in colorectal cancer surgery have been made in improving the cure rate after surgery, the preservation of postoperative function, and the development of minimally invasive procedures. Indication for wide lymph node dissection in rectal cancer surgery is now limited to a smaller number of cases. Functional outcome is being improved thanks to the introduction of autonomic nerve preserving operations as well as the increasing number of sphincter preserving operations. Laparoscopic colectomy for cancer has been practiced for 7-8 years, and the advantages and disadvantages of this procedure are being clarified. Transanal endoscopic microsurgery (TEM) is a minimally invasive surgery for rectal tumors in early stages. The procedure is now overtaking the posterior surgical approach, which is used less and less in recent years. Future goals in colorectal cancer surgery are further improvements in the cure rate and the functional results. Minimally invasive surgery may become the established procedure after a careful assessment of its cure rate compared to the open surgical procedure.

Colorectal Neoplasms↗

The significance of microsatellite instability in predicting the development of metachronous multiple colorectal carcinomas in patients with nonfamilial colorectal carcinoma.

BACKGROUND: Patients with metachronous multiple colorectal carcinomas have been reported to have a higher frequency of a family history of colorectal carcinoma, associated colorectal adenomas, and extracolonic malignancies. These clinicopathologic factors also are considered to be related to the development of metachronous multiple colorectal carcinomas after surgery for colorectal carcinoma. In this article, the authors investigated whether genetic markers such as microsatellite instability (MSI) were helpful in predicting the development of metachronous multiple colorectal carcinomas. METHODS: Between 1990-1997, 312 colorectal carcinoma patients underwent yearly surveillance colonoscopy after surgery. Among these patients, there were 19 with nonfamilial colorectal carcinoma in whom metachronous multiple colorectal carcinomas were diagnosed during the yearly surveillance colonoscopy. A control group was comprised of 28 patients who did not demonstrate either synchronous or metachronous carcinomas over a period of > or =5 years. Six microsatellite markers (D2S123, D3S1029, D3S1611, TP53, Mfd26, and Mfd36) were used to determine MSI by polymerase chain reaction. RESULTS: The frequency of MSI positive cases was significantly higher in patients with sporadic metachronous multiple colorectal carcinomas than in those with a single carcinoma (17/19 [89%] vs. 4/28 [14%]; P<0.0001). In tumors occurring in the distal colon and rectum, the percentage of MSI positive carcinomas was significantly higher in the patients with metachronous multiple carcinomas than in those with a single carcinoma (13/15 [87%] vs. 0/19 [0%]; P<0.0001). No such difference was observed in the proximal colon. CONCLUSIONS: Based on the findings of the current study, the analysis of MSI in sporadic carcinomas of the distal colon and rectum may be helpful in predicting the development of metachronous multiple colorectal carcinomas.

Colonoscopy↗

Intraoperative localization of colorectal tumors in the early stages using a marking clip detector system.

In laparoscopic colectomy the identification of the site of a tumor is often difficult. The topical injection of india ink or blue dye by preoperative colonoscopy is the most prevalent method to mark the tumor site; however, such a procedure also includes the intrinsic danger of possibly injecting dye into the peritoneal cavity. In addition, the injected marker may also spread so widely that the intended site may become obscure. A marking clip detector system was used to detect metallic marking clips in the luminal side that had been applied to the mucosa adjacent to the lesion during the course of preoperative colonoscopy. This method was able to identify the marked site in 40 percent of cases in which only one clip was applied to the mucosa. However, when the lesion sites were marked with two or three clips, then the detection rate increased to 100 percent. Based on our findings, this procedure was found to be a safe and reliable method for identifying lesions during laparoscopic-assisted colectomy.

Colectomy↗