Stereochemistry-activity studies in 6-keto-prostaglandin-E1 (6-keto-PGE1) analogs.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to Y Sakai.
Explore the source record for details and available documents.
We report a case of a 29-yr-old man with a rectal carcinoid that metastasized to the liver, secreting somatostatin. The patient first presented with an abdominal mass and mild diabetes, and, subsequently, rectal tumor and hypersomatostatinemia. Microscopic examination of the rectal tumor showed characteristic features of carcinoid. Multiple liver metastases were recognized. The plasma level of somatostatin was remarkably high (2,839 pg/ml). Plasma gut glucagon and pancreatic polypeptide (PP) increased with progress of the disease. He died of hepatic failure 20 months after his first admission. Immunoperoxidase staining showed that rectal tumor cells contained somatostatin-like-immunoreactivity. Electron microscopy of tumor tissue showed neurosecretory (D-cell) granules. Somatostatin content of the rectal tumor was very high (5,629 pg/mg).
Explore the source record for details and available documents.
We have experienced 471 patients with anal bleeding during the past seven years. The Results are as follows: 1. As for the types of disease, incidence of hemorrhoid, colorectal cancer and ulcerative colitis (UC) was high, while that of small intestinal problems was low. 2. In the cases of remarkable bleeding from the lower intestinal tract, massive or acute progressive bleeding was less frequent than expected. 3. Inflammatory diseases were the main causes of massive bleeding. Bleeding by UC was the major indication for urgent operation. In the cases with acute massive hemorrhage, basic complications were often found and the possibility of the diseases of small intestine and blood vessel disorders also should be considered. 4. At the examination of bleeding patients, it is efficient to explore the lower colon and rectum first by colonoscopy or sigmoidoscopy, for most of the bleeding lesions are found in these portions. 5. As for surgical treatment, most of colorectal cancer patients with hemorrhage are able to be operated with wait- and -see management. For UC patients, complete cure operation is possible even if they have high-dose steroid medication.
CT scans of 52 patients with advanced gastric cancer were reviewed, and the layer structure of the gastric wall was analyzed. Administration of 600 ml water, orally, expanded the gastric wall, while patients were in the prone position. Intravenous infusion of contrast media was routinely administered. We found that the normal layer structure of the gastric wall could be shown despite the cancer in the lesion. Borrmann 3 and 4 types. We guess that CT has a possibility in the assessment of the spread in the wall of gastric cancer.
With the aid of colon-polyp phantoms, basal indentation (BI) of polypoid lesions on double-contrast examinations of the colon was studied. Our findings indicated that BI is a function of radio-geometric projections and its morphology (arcuate, angular and trapezoid) depends on size, shape and surface pattern of a polypoid lesion. These findings were also substantiated by specimen and clinical radiography.
Phase I study with a new oral purine antagonist, SM-108, was conducted in a total of 73 cases in a 5-day consecutive schedule with the dosage ranging from 20-2,500 mg/m2 at II institutes. The incidences of subjective and objective side effects were 20.5% (15/73) and 31.5% (23/73), respectively, however the correlation between these effects and their dosages was unclear. MTD and DLF values were not determined. SM-108 levels in serum reached maximum in 2-4 hours after oral administration of SM-108, and exhibited a dose-response relationship up to the dosage of 2,000 mg/m2/day. Forty to 60% of the administered drug was excreted into urine in 24 hrs; thus, the main excretory pathway was considered to be renal. An early phase II study was undertaken in patients with lung cancer in 5 cancer centers and university hospitals. Each patient had received 400 mg/m2/day (in two divided doses) or 600 mg/m2/day (in three divided doses) for more than 2 weeks. Only one case (adenocarcinoma) showed a minor response out of 27 cases but not reached partial response according to our criteria. In the 400 mg/m2/day group and the 600 m/m2/day group the incidences of subjective side effects (mainly GI tract disturbance) were 33.3% (4/12) and 40.0% (6/15), while objective side effects (hematological changes) were 16.7% (2/12) and 26.7% (4/15) respectively. In conclusion, we could not determine the dose limiting factor and maximum tolerated dose from our phase I clinical study and early phase II study for lung cancer.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A 36-yr-old man was admitted to our hospital complaining of severe vomiting and diarrhea. Upper gastrointestinal series showed deformity of the duodenum. Serum gastrin level was very high (1,829 pg/ml) and secretin provocative test presented a positive result (peak 4,535 pg/ml). We diagnosed his illness as Zollinger-Ellison syndrome, but failed to identify the site of tumor. His symptoms were controlled with cimetidine 1,600 mg qid, but serum gastrin level was increasing. A year after the first admission, computed tomographic scan and selective angiography demonstrated the tumor, and surgery was performed. A solitary 2-cm tumor was noted at the surface of mesenterium of the duodenum. Frozen and paraffin section of the tumor revealed islet cell tumor apparently within a lymph node. Immunohistological examination revealed positive staining for gastrin alone. No other tumors were detectable by inspection and palpation during the operation. After excision of the tumor, serum gastrin and secretion test were normalized, and the patient remains asymptomatic 1 yr after surgery.
In a recent phase II trial we have shown a favorable response rate for sequential methotrexate-5-fluorouracil (MF) in advanced gastric and colorectal cancer. We determined the therapeutic effect of sequential MF in patients with advanced gastric cancer by comparing it to 5-fluorouracil alone (F) in a randomized multicenter trial. Since February 1987 to July 1988, 133 patients with advanced gastric cancer have been prospectively randomized to receive either MF (methotrexate 100 mg/m2 i.v. push, 5-fluorouracil 600 mg/m2 i.v. drip over 15 minutes one hour after methotrexate and leucovorin 15 mg p.o. q 6 hrs x 2 beginning 24 hrs after methotrexate) of F (the same 5-fluorouracil as described for MF). Each treatment was repeated weekly x 5, then q 2 weeks. The two treatment arms were balanced for 17 clinical characteristics. The response rate was 17.9% (10 of 56 patients) in the MF arm and 1.9% (one of 53 patients) in the F arm (p less than 0.01). Median duration of response was 6.8 weeks (MF) and 6 weeks (F), respectively. Median survival time was 7.9 months (MF) and 7.3 months (F) on interim findings. Leukocytopenia and GI toxicity were significantly more common in patients receiving MF, but the degree was similar for both arms. Other side effects were minimal and no different. This schedule of MF is more effective than F in inducing remission for patients with advanced gastric cancer.
Pancreatic enzymes in the bile of congenital choledochal cyst with anomalous pancreaticobiliary ductal union were analyzed. Almost all pancreatic proteases were already activated in the bile aspirated immediately after insertion of PTCD tube. However, inactive proteases gradually increased after continuation of drainage by PTCD. Pancreatic protease activities appeared again after clamping the PTCD tube. In vitro study of trypsin activities in the bile containing no initial trypsin activity, active type of trypsin did not appear throughout the experimental period. It is suggested that continuous reflux of pancreatic juice into the bile and certain incubation time are necessary for activation of pancreatic protease in bile of congenital choledochal cyst.
By this study, a survey has been made of the number and frequency (percentage) of the selections made by form of Trubyte Bioblend artificial teeth applied to 1,507 cases of removable denture fitted for 17 years from Number, 1971, to November, 1988, at Department of Prosthodontics, Dental hospital in Nihon Univ. School of Dentistry at Matsudo. As a result, significantly high selecting frequency was observed of all forms as: 2 forms of Square Tapering in 548 cases (36.4%) and Tapering Ovoid in 270 cases (17.9%); and by sex, single form of Square Tapering in 253 male cases (48.8%) and 2 forms of Square Tapering in 295 cases (29.9%) and Tapering Ovoid in 234 cases (23.7%).
We tried to treat 13 patients with myelodysplastic syndromes (MDS), leukemias and myeloproliferative disorders, with alfacalcidol for their hematological improvement. Eight of them had MDS, 2 acute leukemia (M3, M4), 1 chronic myelogenous leukemia and 2 primary myelofibrosis. All patients were untreated except for 3 patients (PASA, RAEB, AML-M4) who had been treated with mepitiostane, prednisolone and BH.AC-AMP regimen, respectively, prior to alfacalcidol therapy. All patients received alfacalcidol orally for at least one month. The dosage of alfacalcidol ranged from 0.25 to 10 micrograms/day, and the medicine was administrated intermittently when the dosage exceeded 6 micrograms/day to prevent hypercalcemia. The therapeutic effectiveness of alfacalcidol was evaluated according to a criteria by Koeffler (Cancer Treat Rep 69: 1399, 1985) with minor modifications. Three patients (PASA, RAEB, CMML) showed partial response, 3 (RAEB, RAEB in T, AML-M4) minor response and rest of the patients did not respond. The hematological improvement of 6 responders was transient (from 1 to 2 months), however, one patient (PASA) is still responding to alfacalcidol therapy (0.25 microgram/day) for over 12 months. The dysplastic features of hemopoietic cells in the bone marrow showed no noticeable change during the hematological improvement in these responders, suggesting the improvement was obtained as a result of alteration in the proliferation or differentiation of neoplastic clone. None of 13 patients developed hypercalcemia. One patient (AML-M4) became excitable on high dose alfacalcidol (10 micrograms/day). In conclusion, alfacalcidol therapy is effective in some patients with MDS or leukemias and appears worthy especially in the clinical state in which chemotherapy is not indicated.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Quantitative analysis of the polar map obtained from T1-201 single photon emission computed tomogram was employed to assess regional myocardial viability in 66 patients with single vessel coronary artery disease and 16 control subjects. Counts of region of interest in the stenotic and infarcted lesions and normal reference areas were calculated on the polar map. Severity of hypoperfused myocardium was determined as initial percent uptake (%Ui) and delayed percent uptake (%Ud). Redistribution was analyzed as a ratio of %Ud to %Ui (%Ud/%Ui). In the control group, the average %Ui was 85.8 +/- 9.4 and %Ud/%Ui was 1.03 +/- 0.04. Twenty five with reversible defect showed reduced %Ui (51.5 +/- 13.3) and increased %Ud/%Ui (1.37 +/- 0.26). Forty one cases with non-reversible defect were divided into two groups according to the value of %Ui. In the first group with a high %Ui (n = 17), the average %Ui was 74.5 +/- 4.7 and %Ud/Ui was in normal range (1.06 +/- 0.06). In the second group (n = 24), %Ui was most reduced (31.7 +/- 8.7), although %Ud/%Ui was in normal range (1.05 +/- 0.17). No significant correlation was shown between %Ui and %Ud/%Ui in the two groups with non-reversible defect. Correlation between %Ui and %Ud/%Ui was high (r = -0.76) in the group of reversible defect and the group of non-reversible defect with minimal reduced %Ui. It is concluded that the quantitative criteria obtained from polar map is valid to assess regional myocardial viability. The quantitative imaging data were also compared with coronary angiographic and left ventriculographic data.
We quantitatively evaluated the cerebellar functions of 23 patients with spinocerebellar degeneration (SCD) and 10 normal controls using positron emission tomography (PET). Statistical analysis was performed using the Student's test. Regional cerebral blood flow (CBF) and regional cerebral metabolic rate (CMR) of the cerebellar hemisphere and cerebellar vermis were significantly lower in patients with SCD than in normal subjects (p less than 0.001). However, no significant difference between the both groups was seen in the CBFs and the CMRs of the occipital cortex and frontal cortex. Even in the patients with SCD who had not apparent cerebellar atrophy on CT, their CBFs and CMRs of the cerebellum were significantly low, and with advance of cerebellar atrophy, they tended to fall. In the patients with SCD, the fall of CMR was more prominent than that of CBF. Neither CBF, nor CMR of the cerebellum showed correlation to the duration of the illness. The present investigation suggested that PETs were valuable for the early diagnosis and the research on the pathogenesis of SCD.