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Biomedical subjects

F Watanabe

Publications and source records attributed to F Watanabe.

At least 37 records · Page 2Linked to original sources
PubMed2000

A patient with undifferentiated carcinoma of gallbladder presenting with hemobilia.

Hemobilia is relatively rare among hemorrhages in the digestive tract, and hemobilia caused by tumors of the biliary tract is particularly rare. We treated a 74-year-old-man with undifferentiated carcinoma of the gallbladder presenting with hemobilia. During hospitalization for neurogenic bladder at the Department of Urology, he showed progressive anemia. Since hemorrhage in the digestive tract was suspected, endoscopy of the upper gastrointestinal tract was performed, and bleeding from the papilla of Vater was observed. On ultrasound examination, findings were indicative of cholecystic cancer, and hemorrhage from the cystic duct was found on percutaneous transhepatic cholangioscopy. On perioral cholecystoscopy, however, masses of coagulated blood were found only in the gallbladder. Abnormalities such as dense staining of tumors or extravasation were not found on angiography. The patient died of hepatic failure due to rapid invasion of the liver by the tumor, associated with biliary infection and disseminated intravascular coagulation. At autopsy, a nodal tumor was found in the gallbladder, and the cavity of the gallbladder was filled with coagulated masses of blood. Direct invasion of the tumor to the liver, diaphragm, and transverse colon was found. The histopathological diagnosis was undifferentiated carcinoma (pleomorphic large-cell type).

Aged↗
PubMed2000

Scavenging effect of nicorandil on free radicals and lipid peroxide in streptozotocin-induced diabetic rats.

Free radicals and lipid peroxide (LPO), easily formed in the diabetic state, play an important role in the development of diabetic complications. Potentially, nicorandil may reduce the production of free radicals and LPO in various organs. In fact, increased LPO levels in the serum, kidney, and cardiac muscle of diabetic (DM) rats were reduced by nicorandil treatment (N treatment). Xanthine oxidase (XOD), which produces free radicals, was decreased in the liver and increased in the kidney of DM rats compared with control rats, and these changes were prevented by N treatment. The concentration of Cu, Zn-superoxide dismutase (SOD) decreased in the cardiac muscle and increased in the kidney of DM rats, and these changes returned to normal after N treatment. The decreased concentration of Mn-SOD in the liver, kidney, and cardiac muscle from DM rats was also reversed by N treatment. The changes in catalase and glutathione peroxidase (GSH-PX) activities in DM rats were not improved effectively by N treatment. Another K-adenosine triphosphate (K-ATP) channel opener, tilisolol hydrochloride, had an effect similar to that of nicorandil. The effects of nicorandil and tilisolol were studied only in DM rats. These data imply that N treatment, as an antioxidative therapy, may be beneficial in preventing diabetic complications due to lipoperoxidation and free radicals in DM rats.

Animals↗
PubMed2000

Adenocarcinoma of the rectum with various grades of atypia in association with Crohn's disease: a case report and immunohistochemistry of p53 and Ki-67.

A case of adenocarcinoma of the rectum in a 41-year-old woman, in association with Crohn's disease is presented. The patient had suffered diarrhea and constipation, and Crohn's disease was suspected. Although the endoscopy did not reveal the presence of any tumors, biopsy specimens demonstrated adenocarcinoma. A Miles' operation was performed. The adenocarcinoma was composed of various grades of atypia and had invaded the non-peritonealized perirectal tissues. The infiltration of lymphocytes and plasma cells was moderate at the perimeter of the carcinoma and mild in the distant regions. Epithelioid cell granulomas were found. The p53 labeling index (LI) increased with the grade of atypia over the entire length of the carcinomatous gland. In carcinomas with high grade atypia, the p53 LI was high in both the upper and the lower halves of the gland. In carcinomas with low or moderate grade atypia however, the p53 LI was high in the lower half and low in the upper half of the gland. The Ki-67 LI over the entire gland was higher in carcinomas with high grade atypia than in carcinomas with low or moderate grade atypia.

Adenocarcinoma↗
PubMed2000

Preoperative diagnosis of ileal lipoma by endoscopic ultrasonography probe.

The occurrence of tumor in the small intestine is relatively rare. It has been demonstrated that lipoma of the ileum is a cause of intussusception. We report a 59-year-old man admitted to our hospital for lower abdominal pain. Diagnosis of intussusception was made by abdominal x-ray and ultrasonography. Enema contrast studies revealed ileocolic intussusception. Colonoscopy revealed a tumor with an submucosal tumor (SMT)-like head and coil-spring appearance in the ascending colon. Endoscopic ultrasonography (EUS) revealed a hyperechoic submucosal lesion with features compatible with lipoma. Subsequently, this was confirmed histopathologically after resection. To our knowledge, this is the first report of preoperative diagnosis of ileal lipoma by EUS.

Endosonography↗
PubMed2000

Characterization of a vitamin B12 compound in the edible purple laver, Porphyra yezoensis.

The edible purple laver, Porphyra yezoensis, contained 51.49+/-1.51 microg of vitamin B12 compounds per 100 g dry weight of the laver (mean +/- SEM, n = 4). A vitamin B12 compound was purified from the lyophilized purple laver and partially characterized. The silica gel 60 TLC and reversed-phase HPLC patterns of the purified pink-colored compound were identical to those of authentic vitamin B12, but not to those of vitamin B12 analogues inactive for humans.

Biological Availability↗
PubMed2000

Absence of linkage between radiosensitivity and the predisposing atp7b gene mutation for heritable hepatitis in the LEC rat.

The LEC rat is known to be a mutant strain that spontaneously develops heritable hepatitis due to copper accumulation, caused by mutation of the copper-transporting ATPase gene (Atp7b). Immunodeficiency and radiosensitivity have also been observed. Hayashi et al. extensively examined the radiosensitivity of the LEC rat and concluded that its hypersensitivity is controlled by a single autosomal gene. Furthermore, they suggested the possibility that it correlates to copper accumulation due to the Atp7b gene mutation, because ionizing radiation-induced hydroxyl radicals might act in concert with copper-induced hydroxyl radicals. In the present experiment, we analyzed linkage between radiosensitivity and the mutation responsible for hepatitis in F(1) animals of a cross with the F344 rat. Our results clearly demonstrated an absence of any significant association. In addition, partial dominance for radiosensitivity was observed, and radiosensitive (F(1) x LEC) backcross rats were twice as numerous as their radioresistant counterparts, suggesting the possibility of control by two or more recessive genes.

Adenosine Triphosphatases↗
PubMed2000

Lipid peroxidation levels in rat cardiac muscle are affected by age and thyroid status.

Free radicals, hydroxyperoxides and H(2)O(2) are all known to damage cell components. This study was designed to compare the concentrations of hydroxyperoxide and free radical scavengers in the cardiac muscles of old rats in the hyper- or hypothyroid condition, to determine whether rates of peroxidation would differ with age, thyroid status, or both. Rats were rendered hyper- or hypothyroid by administration of l-thyroxine or methimazole for 4 weeks. Among the old rats, the lipid peroxide (LPO) concentrations, measured as thiobarbituric acid (TBA) reactants, were significantly greater in the hyperthyroid than in the euthyroid state and the LPO concentrations measured as TBA+Fe(3+) reactants, which may be precursors of LPO, were significantly greater in the hyperthyroid state, whereas in young rats, the LPO concentrations measured by TBA or TBA+Fe(3+) methods did not differ significantly in the hyperthyroid state. In the euthyroid state, the concentration of LPO measured as TBA+Fe(3+) reactants was significantly reduced with age. Xanthine oxidase (XOD) activity also was markedly increased with age, being more pronounced in the hyperthyroid than in the euthyroid state. The Mn and Cu/Zn superoxide dismutase activities were greater in the hyperthyroid than in the euthyroid state. Glutathione peroxidase activity decreased with age in the euthyroid and, particularly, in the hyperthyroid state. Catalase activity was not affected in the old rats. Concentrations of alpha-tocopherol in the old rats were high in the hyperthyroid state and low in the hypothyroid state, whereas the levels of beta- and gamma-tocopherols in these rats were unchanged in both conditions as compared with the euthyroid state findings. Data suggest that the site of free radical generation differs in older rats, with additional shifts in the location of intracellular lipid peroxidation being noted during hyperthyroidism. Thus, as rats age, the reduction of the free radical scavenger system and the increase in LPO and XOD activities might induce myocardial dysfunction.

Aging↗
PubMed2000

[Arteriovenous fistula associated with Staphylococcus aureus sepsis in a patient with Rendu-Osler-Weber syndrome].

A 58-year-old man with a history of cerebral infarction and bleeding due to duodenal ulcer was admitted with fever and arthralgia. Methicillin-sensitive Staphylococcus aureus (MSSA) was isolated from his peripheral blood. Bacteremia with MSSA was diagnosed, and antibiotic therapy was started. However, chest X-ray films and computed tomographic scans disclosed mass shadows in both lungs accompanied by dilated vascular markings. Pulmonary arteriography and magnetic resonance angiography revealed the existence of arteriovenous fistulas in both lungs. Ga scintigraphy disclosed a hot spot in the left lower lobe, consistent with the location of one fistula. This indicated that the fistula might be the focus of MSSA sepsis. Because the patient also had telangiectasia in his gastric mucosa, oral cavity, and nasal cavity, he was given a diagnosis of Rendu-Osler-Weber syndrome.

Arteriovenous Fistula↗
PubMed2000

[Chemotherapy with mitoxantrone for the treatment of recurrent breast cancer].

Two cases of recurrent breast cancer are reported in which chemotherapy with mitoxantrone proved remarkably effective. Case 1 was a 61-year-old postmenopausal female. At 32 postoperative months, multiple metastases of lung and bone were found. Following unsuccessful treatment with anthracyclin and an antiestrogenic agent, we used MVP modified therapy (mitoxantrone (MIT) 16 mg and vincristine (VCR) 1.6 mg once per 4 weeks and medroxyprogesterone acetate (MPA) 1,200 mg/day) and 5'-deoxy-5-fluorouridine (5'-DFUR) 800 mg/daily. After 12 cycles were performed, the patient showed a partial response (PR) (nearly complete response (CR)) on a chest X-ray and bone scintigram. Case 2 was a 49-year-old premenopausal female. At 42 postoperative months, a local recurrence was found and resection was performed. However, after endocrine therapy with goserelin acetate (ZOL) and chemotherapy with CAF (cyclophosphamide, adriamycin and 5-FU) and UFT, local recurrence and pleural effusion were found 6 months after surgical operation. We then used MVP modified chemotherapy and endocrine therapy with ZOL. The patient showed a PR at 9 cycles after therapy. MVP modified chemotherapy is considered an effective treatment for recurrent breast cancer, especially for adriamycin or epirubicin resistant breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

[The evaluation of pamidronate therapy for bone metastases from breast cancer].

We devised a method to evaluate comprehensively the therapy to alleviate the pain of bone metastases from breast cancer according to the three items of bone pain and effects of analgesia and radiology. In 12 patients, we evaluated the therapeutic effect of pamidronate as an alleviative treatment for the pain of bone metastases from breast cancer. Bone pain was evaluated on a 6-grade scale, as was use of analgesics. Improvement in bone pain, in addition to improvement in use of analgesia, was evaluated as markedly improved, improved, unchanged, aggravated, no pain or undeterminable. Radiological improvement in bone lesions was evaluated as markedly improved, improved, unchanged, aggravated or undeterminable. An overall evaluation was made by combining the above two. In this evaluation method, pamidronate therapy resulted in an evaluation of markedly improved in 2 patients, improved in 5, unchanged in 4 and aggravated in 1, demonstrating that the therapy was very useful as an alleviative treatment for the pain of bone metastases from breast cancer. The evaluation method, in which pain, a subjective complaint, is combined with use of analgesics, an objective factor, and to which radiological evaluation is added for further objectively, may in the future to be applicable for evaluation of various alleviative treatments of pain of bone metastases.

Adult↗
PubMed1999

Tissue-specific alternative splicing of rat brain fructose 6-phosphate 2-kinase/fructose 2,6-bisphosphatase.

We have reported the occurrence of eight splice variants of rat brain fructose 6-phosphate 2-kinase/fructose 2,6-bisphosphatase (RB2K). In the present study, we quantified these splice variants in various tissues using a RNAse protection assay and found a tissue-specific pattern of alternative splicing of the RB2K gene. Splice variants containing exon F were specifically expressed in brain. Moreover, exons D and E were spliced in brain, skeletal muscle and heart. Consequently, eight, six, four and two splice variants were expressed in brain, skeletal muscle, heart and liver plus testis, respectively. These results suggest that distinct RB2K isoforms could be involved in regulation of glycolysis in a tissue-specific manner.

Alternative Splicing↗
PubMed1999

Homology modeling of gelatinase catalytic domains and docking simulations of novel sulfonamide inhibitors.

Three-dimensional models for the catalytic domain of gelatinases (MMP-9 and -2) have been constructed based on the X-ray crystal structure of MMP-3. Conformations of the loop segment which forms the bottom half of the S1' subsite but shows conformational diversity among the crystal structures of other MMPs have been explored by simulated annealing of each gelatinase model complexed with two highly potent "probe" inhibitors. Representative catalytic domain models have been selected for each gelatinase from the set of generated conformations based on shape complementarity of the loop to the probe inhibitors. The single model selected for MMP-9 was utilized to explain the structure-activity relationship of our novel sulfonamide inhibitors. Molecular dynamics (MD) simulations of the complex models revealed important features of the binding mechanism of our inhibitors: (i) the ligand carboxylate group coordinating to the catalytic zinc ion and hydrogen bonding to the Glu219 side chain, (ii) one of the sulfonyl oxygens forming hydrogen bonds with the main chain NHs (Leu181 and Ala182), (iii) the sulfonyl substituent making extensive hydrophobic contact with the S1' subsite. The gauche conformation exclusively adopted by the sulfonamide C-N-S-C torsion plays an important role in achieving the third binding feature by properly directing the substituent into the S1' subsite. Improvement of the inhibitory activity according to straight elongation of the sulfonyl substituent was attributed to an increase of the hydrophobic contact between the substituent and the S1' subsite. Structural modifications which alter the straight shape of the substituent lead to deterioration of the activity. On the other hand, the two candidate models selected for MMP-2 differ in the bottom shape of the S1' subsite: one with a channel-like subsite and the other with a pocket-like subsite resembling that of the MMP-9 model. The bottom shape was experimentally probed by chemical synthesis of inhibitors having elongated sulfonyl substituents whose terminal alkyl groups were shown by MD simulations to protrude from the S1' subsite bottom into the solvent. Gelatinase assays of these inhibitors showed that elongation of the substituent significantly reduces activity against MMP-9 while retaining activity against MMP-2, consequently increasing the selectivity between MMP-2 and -9. The results confirm that MMP-9 has a pocket-like S1' subsite with a floorboard and MMP-2 has a channel-like S1' subsite.

Amino Acid Sequence↗