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Biomedical subjects

T Iwanaga

Publications and source records attributed to T Iwanaga.

At least 253 records · Page 14Linked to original sources

[Pharmacokinetics and prophylactic effect of intraperitoneal administration of mitomycin C resulting in IC50 of gastric cancer].

In order to prevent peritoneal metastasis after gastrectomy for gastric cancer, we conducted a study to find a clinical dose of MMC which would result in IC50, the drug concentration which inhibits the growth of colonies of cells by 50%. After closure of the abdomen, MMC dissolved in 1,000 ml of physiological saline was administered. In the 40 mg group, the mean intraperitoneal MMC concentration after 60 min was 8.2 micrograms/ml, which exceeded IC50 of 7.6 micrograms/ml. In the group, peak serum concentration of MMC was 0.29 micrograms/ml. Seventy to 80% of intraperitoneally administered MMC was transferred in blood. Serious adverse effects were not observed. One-year survival rate of absolute noncurative resection with peritoneal metastasis was 33% in the control group and 78% in the treated group. Two-year survival rate of curative resection with free cancer cells in the peritoneal cavity was 11% in the control group and 60% in the treated group.

Cell Division↗

[Evaluation of preoperative chemoembolization using ethiodized oil, cisplatin and gelatin sponge (sandwich therapy) for hepatocellular carcinoma].

The significance of preoperative chemoembolization using ethiodized oil, cisplatin and gelatin sponge (Sandwich therapy) for resectable hepatocellular carcinoma (HCC) was evaluated. One hundred and thirteen patients with solitary and less than 10 cm sized HCC who underwent radical hepatic resection were chosen for this study. Fifty-three patients received Sandwich therapy before surgery (Group A), and the remaining 60 patients under-went surgery without any preoperative treatments (Group B). Any background factors between two groups were not significantly different. The anticancer effects of this therapy were evaluated by histologic examination in 31 patients who had preoperative Sandwich therapy. In 22 of 31 patients (71%), the main nodules were completely necrotic. The ratios of patients with complete necrosis in daughter nodules were 7/12 (58%), in portal vein tumor emboli, 7/10 (70%), in intracapsular invasions, 11/21 (52%), in extracapsular invasions, 4/11 (36%). The 4-year disease-free survival rates in Group A and Group B were 56% and 27% respectively, and the rate of the former was significantly higher than that of the latter (p less than 0.05). The 4-year survival rates in Group A and Group B were 83% and 53% respectively. The rate of Group A was also significantly higher than that of Group B (p less than 0.01). We concluded that preoperative Sandwich therapy was very significant to obtain successful long-term disease-free survival and survival in regard to relatively early stage HCC.

Carcinoma, Hepatocellular↗

[Problems concerning the diagnosis and treatment of multiple primary carcinoma of the lung].

Data on 44 patients with multiple primary carcinoma of the lung are presented. Twenty had metachronous tumors, and 24 had synchronous tumors. Twenty-one patients had undergone complete resection for both tumors, and 14 had undergone resection for only one of two tumors. The remaining 9 patients underwent no operation and were treated with photodynamic, radiation and/or chemotherapy. Long-term survival of more than 3 years was achieved for 11 patients, nine of whom had synchronous lesions. Furthermore, they included 3 patients who underwent nonsurgical therapy for both lesions. On the other hand, the prognosis after resection of the second tumor in patients with metachronous lesions was poor. This was thought to be the result of failure to diagnose the second lesion due to incomplete long-term follow-up. We conclude that careful attention to the operative indications is necessary for patients with multiple lesions, particularly lesions such as early squamous cell carcinomas.

Adenocarcinoma↗

Decollateralization with silicone rubber sheeting for advanced hepatocellular carcinoma: a preliminary report.

A new treatment method, interception of collaterals with a silicone rubber sheet, was applied to three patients with advanced hepatocellular carcinoma in whom arterial chemoembolization was assessed as ineffective because of the developed collateral feeding arteries. This procedure was followed by arterial chemoembolization or intraportal infusion chemotherapy or both. Follow-up celiac angiography confirmed that the long-term decollateralization was achieved by shielding the liver with silicone rubber sheeting. This technique resulted in partial responses without serious complications in all the patients including two who had no responses to chemoembolization before the procedure. The response durations were 5, 21, and 27, months, respectively. One patient died of gastrointestinal bleeding 7 months after the decollateralization. The other two patients are still alive, and the survivals after the procedure are 28 and 30 months, respectively. This therapy is considered promising and may be worth choosing as an adjuvant treatment for advanced hepatic malignancies uncontrolled by arterial chemotherapy or chemoembolization.

Aged↗

[Combination chemotherapy with etoposide, ADM, and CDDP (EAP) for advanced gastric cancer].

EAP therapy has been performed on 50 cases of advanced gastric cancer from January 1988 to September 1989. Adriamycin 20 mg/m2, Cisplatin 40 mg/m2 and Etoposide 100 mg/m2 were administered on day 1 and 7, 2 and 8, and 4, 5 and 6, respectively, with not less than 2 courses every 3 to 4 weeks. Complete success, PR, NC and PD were obtained in 48, 21, 20 and 7 cases, respectively, the rate of effectiveness being 43.8% with a confidence interval 95% of 30-58%. The rate of effectiveness by lesions for evaluation was high (30.4, 100, and 50% for primary lesion, Virchow's lymphnodal metastasis and liver metastasis, respectively). MST was 5.1 months for EAP therapy, which was highly effective but led to no prolonged survival period. Thus, it is thought that good control of leukopenia, a dose limiting factor remains to be examined.

Adult↗

[Myelodysplastic syndrome with chromosomal abnormality of t(11;21) (q23;q22)].

A 33-year-old woman was hospitalized because of bleeding tendency. Hemoglobin was 10.7 g/dl, white blood cell 2,100/microliters and platelet 2.1 X 10(4)/microliters. Bone marrow showed marked dysplasia of trilineage blood cells. Atypical blasts and monocytoid cells accounted for 14.5% in the myelogram. Cytogenetic study of bone marrow cells revealed translocation with t(11;21) in all of 20 metaphasic cells analyzed by G-banding method. A diagnosis of RAEB was made. Familial survey revealed that her elder brother died of acute monocytic leukemia (AMoL). The patient received small dose therapy of Ara-C and BHAC-DMP therapy, but a remission was not obtained. The patient's general condition deteriorated with infection, bleeding tendency and chronic hepatitis due to transfusions, therefore we have followed up the patient with prednisolone and red blood cell transfusion. It has become evident that some types of acute leukemia with monocytic features have a cytogenetic change at 11 q 23. But it is rare that RAEB with increased monocytoid cells has a cytogenetic change at 11q23. In addition, the patient's elder brother died of AMoL. This case is important in relation to cytogenetic change at 11q23 and hematopoietic abnormalities.

Adult↗

Solid and papillary neoplasm arising from an ectopic pancreas in the mesocolon.

A case of solid and papillary neoplasm of a mesocolonic ectopic pancreas in a 13-yr-old girl is presented. An 8-cm, well-encapsulated, and partly calcified tumor which protruded from the mesocolon was resected surgically. Histologically, the tumor showed either solid sheets or papillary arrangements (around the vascular core) of uniformly small cells with alpha 1-antitrypsin-positive cytoplasm. Some of the tumor cells had zymogenlike granules, suggesting acinar cell differentiation. At the base of this tumor, small pancreatic tissues (islet, acinar, and ductular cells) were detected in the mesocolonic tissue. Incidences of both ectopic pancreas outside the gastrointestinal wall and solid and papillary neoplasm of the pancreas are rare, and this is the first case reported in the literature.

Adolescent↗

Morphologic characteristics of pancreatic carcinoma with diabetes mellitus.

For 81 cases of resectable pancreatic carcinoma, the site of cancer origin, cancer histologic features, and hyperplasia in the noninvolved duct were studied in relation to diabetes. They were classified into the following three groups: (1) fasting blood sugar (FBS) of less than 120 mg/dl (Group A, 26 cases); (2) FBS of more than 120 mg/dl with less than 2-year history of diabetes (Group B, 38 cases); and (3) FBS of more than 120 mg/dl with more than a 2-year history of diabetes (Group C, 17 cases). Although neither tumor size nor tumor location differed between the three groups, both the highest resectability (47%) and the lowest rate (71%) of extrapancreatic invasion were seen in Group C. A pancreatic ductogram showed that the pattern of the main pancreatic duct was intact in 0% in Group C versus 35% in Group A (P less than 0.05). Histologically, papillary/well-differentiated adenocarcinoma was present in 35% of Group A patients versus 61% of Group B and 71% of Group C patients (P less than 0.05). Papillary hyperplasia was present in the ducts of 27% of the patients in Group A; this was significantly lower than the other two groups. Atypical duct hyperplasia was present in 47% of Group C patients; this was significantly higher than in the other two groups. It appears that cells in the main pancreatic duct are vulnerable to hyperplastic and well-differentiated cancerous changes in patients with a history of diabetes of more than 2 years duration.

Adenocarcinoma↗

[Carcinoma of male breast--with special reference to noninvasive carcinoma].

Seven cases of carcinoma of male breast were reported. The mean age of them was about 65 years, 17 years older than that of female breast cancer. Six tumors out of 7 were located under the areola. By histological examination, 4 of 7 cases were proved to be noninvasive ductal carcinoma, and the others are invasive ductal carcinoma (2 : scirrhous, 1 : solid-tubular). We focused on clinicopathological features of noninvasive carcinoma. There were two points to be mentioned. One is the nipple discharge as a chief complaint, and the other is cyst formation as a macroscopic observation. These features are characteristic to noninvasive carcinoma and contribute to diagnosis. Therefore, for screening the mass of male breast, ultrasonography (U.S.) is most useful. For preoperative final diagnosis, aspiration or smear cytology is essential. In regard to postoperative survival, all of the 3 invasive cases were dead but all of the 4 noninvasive cases are alive. So the prognosis of noninvasive carcinoma of male breast does not appear to be worse than the female one. These observations indicate that the prognosis of carcinoma of male breast can be improved by early diagnosis and appropriate surgical therapy.

Aged↗

Phorbol ester, 1,2-diacylglycerol, and collagen induce inhibition of arachidonic acid incorporation into phospholipids in human platelets.

We have shown that phorbol myristate acetate (PMA) enhanced A-23187-induced arachidonate release and thromboxane synthesis in human platelets (Mobley, A., and Tai, H. H. (1985) Biochem. Biophys. Res. Commun. 130, 717-723). The mechanism of enhancement by PMA was not elucidated. In the present study, we have shown that PMA-treated platelets exhibited significantly less [1-14C]arachidonate incorporation than did control platelets. However, no significant change in uptake of labeled linoleate or oleate was observed by PMA treatment. Examination of the two enzyme activities involved in arachidonate incorporation into phospholipids indicated that both arachidonoyl-coenzyme A (CoA) synthase and arachidonoyl-CoA lysophosphatide acyltransferase were inactivated following treatment with PMA or 1-oleoyl-2-acetyl glycerol. When platelets were stimulated with A-23187 plus PMA which produced a significant synergism in thromboxane synthesis, both enzyme activities were substantially less than those in platelets treated with A-23187 alone. In addition to PMA and 1-oleoyl-2-acetyl glycerol induced decreases in both enzyme activities, collagen, a platelet agonist which can activate protein kinase C (Ca2+/phospholipid-dependent enzyme), was also found to cause a concentration-dependent attenuation of both enzyme activities. These results suggest that protein kinase C activation induced by PMA or collagen may cause inactivation of both arachidonoyl-CoA synthase and arachidonoyl-CoA lysophosphatide acyltransferase resulting in inhibition of the reincorporation of arachidonate released by A-23187 and, consequently, greater availability of arachidonate for thromboxane synthesis.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

The ultrastructure of Ruffini endings in the periodontal ligament of rat incisors with special reference to the terminal Schwann cells (K-cells).

The Ruffini endings and associated cells in the periodontal ligament of rat incisors were investigated by means of immunohistochemistry for glia-specific S-100 protein and electron microscopy. Numerous Ruffini endings, which were immunoreactive for S-100 protein as well as for neurofilament protein, were distributed in the alveolus-related part of the lingual periodontal ligament. In electron microscopy, the Ruffini endings displayed expanded axoplasmic spines filled with a large number of mitochondria and neurofilaments; some of the spines directly contacted the surrounding collagen fibers via fingerlike projections. The axoplasmic spines and Schwann sheath, for the most part, were covered alternately by single or multiple layers of the basal lamina. Several rounded cells showing S-100 immunoreactivity occurred in the vicinity of the Ruffini endings. The rounded cells associated with Ruffini endings possessed a kidney-shaped nucleus and enveloped the axoplasmic spines with their cytoplasmic processes. From these morphological features, the cells in question were identified as the K-cells described by Everts et al. (1977). These K-cells developed Golgi apparatus and rough endoplasmic reticulum, suggesting active synthesis of proteins. Immunohistochemistry at the electron microscopic level revealed an intense immunoreactivity for S-100 protein in the cytoplasm of the K-cell and led to a conclusion that the K-cells were terminal Schwann cells associated with Ruffini endings, presumably corresponding to the lamellar cells in the inner bulb of sensory corpuscles.

Animals↗

Human thrombin plus 5 per cent ethanolamine oleate injected to sclerose oesophageal varices: a prospective randomized trial.

Fifty cirrhotic Japanese patients with oesophageal varices underwent sclerotherapy in a prospective randomized trial carried out to examine the effects of human thrombin given concomitantly with the sclerosant 5 per cent ethanolamine oleate. The two groups (25 patients each) were comparable with regard to size of the oesophageal varices, and the aetiology and severity of the liver disease. Twenty-five patients, 13 and 12 in the thrombin + and - groups, respectively, had at least one episode of variceal bleeding. The remaining 25 were given prophylactic injections. There was a significantly lower rate of occurrence of bleeding from injection sites when the injection needle was removed at the initial session of sclerotherapy in the thrombin + group, where human thrombin was injected (0.2-0.3 ml, 100-150 units per injection) just before removal of the injection needle. Endoscopy at 1 week after the initial session showed a significantly (P less than 0.05) higher rate of disappearance of red colour signs on varices in the thrombin + group (96 per cent) than in the thrombin - group (72 per cent). Fibrin degradation product E-fraction (FDP-E) values increased 1 h, 1 day and 6 days after the initial session of sclerotherapy in the two groups. The rate of increase in FDP-E values 1 h after sclerotherapy was significantly larger (P less than 0.001) in the thrombin + than in the thrombin - group. There was no clinical sign of disseminated intravascular coagulation. Administration of human thrombin plus a sclerosant seems to be useful and efficacious, especially for patients with huge oesophageal varices.

Endoscopy↗

Liver-specific and high-level expression of human serum amyloid P component gene in transgenic mice.

To analyze the regulation of human serum amyloid P component (SAP) gene expression, we have produced seven transgenic mice. The 3.3 kb human SAP genes containing about 0.8 kb of 5' and 1.5 kb of 3' flanking region were injected into fertilized eggs of C57BL/6 mice. In five of the seven transgenic mice, human SAP was detected in the sera and serum concentrations were higher than that of human serum in three lines. The human SAP gene was expressed only in the liver. Amounts of human mRNA in the liver and serum concentrations of human SAP were roughly proportional to the copy number of the integrated gene. Human SAP production lowered the serum levels of mouse endogenous SAP. With the intraperitoneal administration of lipopolysaccharide, the mRNA levels in the liver and serum levels of mouse SAP increased several-fold in both the control and transgenic mice. On the other hand, neither the mRNA nor the serum levels of human SAP increased significantly.

Animals↗

Esophageal transection may well be the approach of choice for patient with portal venous obstruction and esophageal varices.

Thirty patients with esophageal varices, portal venous obstruction and a histologically proven normal liver underwent either one of 2 different types of surgery. Shunt surgery was performed on 20 patients: 9 had a mesocaval shunt, 3, a splenorenal shunt, 4, a left gastric venacaval shunt, and 4, a distal splenorenal shunt. Conversely, direct interruption was performed on the other 10 patients; 6 underwent an esophageal transection, and 4 underwent a resection of the proximal stomach. Re-hemorrhage occurred in 7 of the former 20 patients but not in any of the 10 on whom the direct interruption method was used. In 6 of these 7 patients who experienced rebleeding, subsequent direct interruption surgery led to control of the bleeding. One patient died of a variceal hemorrhage one month postoperatively. The total 10 year cumulative survival rate was 86.3 per cent. In the light of these findings, we believe that methods of direct interruption, such as esophageal transection, may well be the approach of choice for patients with esophageal varices caused by extrahepatic portal venous obstruction.

Adolescent↗

In vitro invasion of endothelial cell monolayer by rat ascites hepatoma cells.

To study the tissue preference of invasion, we developed an assay system for the invasion of endothelial cells as a modification of the previously established assay of tumor cell invasion of mesothelial cells. Rat ascites hepatoma cells (AH 130) that had been seeded on a monolayer of cultured endothelial cells penetrated and formed tumor cell colonies under the monolayer. The penetration was time-dependent and the number of penetrated tumor cells and colonies was proportional to the number of tumor cells seeded. Comparison of the in vitro tumor cell invasion of endothelial cell monolayer with that of cultured mesothelial cell layer showed that a clone from the tumor cells (Cl-30) which was highly penetrative into the mesothelial cell layer had only limited ability to penetrate the endothelial cell layer.

Animals↗

Demethylation by 5-azacytidine results in the expression of hepatitis B virus surface antigen in transgenic mice.

In 14p3HB transgenic mice, which carry three tandem copies of hepatitis B virus (HBV) DNA, the HBV DNA was significantly methylated and no viral proteins were produced. To analyze the causal relationship between hypermethylation and gene inactivity, 5-azacytidine was injected into the mice to demethylate HBV DNA. When postnatal 14p3HB mice were treated with the drug, hepatitis virus surface antigen was produced in these mice by 3 weeks of age, and the integrated HBV DNA of the liver was less heavily methylated. Our results suggest that injection of 5-azacytidine can be used to efficiently activate a silent transgene such as HBV DNA in transgenic mice.

Animals↗