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Biomedical subjects

H Nagano

Publications and source records attributed to H Nagano.

At least 145 records · Page 8Linked to original sources

Features of the aperiodic microfibrils associated with mouse dental basement membrane demonstrated by ultrastructural histochemistry.

Histochemical features of aperiodic microfibrils (AMF) in mouse tooth germs were examined at the electron microscopic level. Intact and EDTA-isolated materials obtained from one day old first molars were used for ruthenium red (RR) staining, ferritin permeability, periodic acid-silver methenamine (PAM) impregnation, fibronectin localisation, negative staining on cryo-sections and tannic acid fixation. Electron microscopy and negative staining demonstrated that AMF traverse the basal lamina and penetrate below the inner enamel epithelium. In addition to RR staining, PAM impregnation and tannic acid fixation showed deposition on the AMF which was associated with basal laminae. RR staining and tannic acid fixation also indicated the presence of glycoprotein-rich materials in the lamina lucida. The AMF were derived from the lamina lucida which was closely associated with tannic acid-positive granular materials. The precipitation of silver particles by PAM impregnation was seen on banded collagen fibrils, basal lamina and AMF, but the staining features of AMF differed distinctly from those of collagen fibrils. The distribution of ferritin particles revealed that the basal lamina covering EDTA-isolated papilla tissue is a continuous structure. Immuno-reactions for fibronectin were detected on the basal lamina and AMF. Our results suggest that AMF are derived from the glycoprotein-rich lamina lucida and that their histochemical characteristics resemble those of basal lamina.

Animals↗

[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↗

[Long-term postoperative courses of hepatocellular carcinoma with and without cirrhosis].

Until the end of August 1988, 158 patients with hepatocellular carcinoma underwent curative hepatic resection in our department. One-hundred and twenty-one patients (77%) had liver cirrhosis (Group A), and the remaining 37 (23%) did not (Group B). Background factors and postoperative courses were compared between Group A and Group B. With regard to clinical stage and curability, there were no significant differences between the two groups. On postoperative follow-up on 1- to 5-year survival, no differences were recognized between the two groups, but on and after 6-year survival, the former were significantly worse than the latter. The main cause of death was cancer in both groups. In group B, all intrahepatic recurrences happened within 3 years after surgery. On the other hand, intrahepatic recurrences of Group A were also found on postoperative 4- and 5-year to be as numerous as the recurrences found at 1-, 2- and 3-year after surgery. Moreover, with recurrent cases on and after 4 years in Group A, the frequency of solitary focus was high. The differences of postoperative courses between these two groups might be caused by metachronous carcinogenesis of cirrhotic liver.

Adult↗

[Chemoembolization for liver metastasis from colorectal cancer].

Chemoembolization using Lipiodol, cisplatin, angiotensin II and Gelfoam (modified sandwich therapy) was carried out for the patients with liver metastasis from colorectal cancer. 1. Ten of 30 patients who underwent hepatic resection received TAE before operation, and the remaining 20 underwent surgery without preoperative TAE. Three-year survival of the former was 66%, and that of the latter was 44% (not significant). 2. Twenty-two patients who were assessed as non-resectable were surgically catheterized into the hepatic artery. Thirteen patients received TAE (totally 38 times) and intra-arterial infusion chemotherapy, and the remaining 9 underwent intra-arterial chemotherapy alone. The 50% survival of the former and the latter was 545 and 285 days, respectively. One year survival of the former was significantly better than that of the latter. 3. Fourteen patients had intrahepatic recurrences after hepatic resections. Eight patients received TAE and the remaining 6 did not. The 50% survival of the former was 615 days and that of the latter was 190 days. For one-year survival, the former was significantly better than the latter. These results suggested that TAE is an effective modality for liver metastasis from colorectal cancer.

Angiotensin II↗

[Intraarterial and intraportal chemotherapy combined with decollateralization for cholangiocellular carcinoma and metastatic liver cancer].

Two patients with cholangiocarcinoma and one patient with liver metastasis from inflammatory breast cancer underwent catheterization into both hepatic artery and portal vein following decollateralization using silicone rubber sheeting. They received arterial chemoembolization and chemotherapy and portal chemotherapy through the catheters repeatedly. Two patients with cholangiocarcinoma are still alive more than one year after the beginning of the treatments without regrowth of the tumors. The patient with metastatic liver cancer died of lung metastasis, although the liver foci were controlled by procedure. Thus, both intraarterial and intraportal chemotherapy combined with decollateralization by silicone rubber sheeting seems to be effective for advanced cholangiocarcinoma and metastatic carcinoma.

Adenoma, Bile Duct↗

[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↗

[Hypoxemia of liver cirrhosis--an autopsy case study].

41 year-old male with liver cirrhosis accompanying severe hypoxemia was presented. Shortly after the diagnosis of liver cirrhosis, he suffered from exertional dyspnea and cyanosis. Though home oxygen therapy had been prescribed for 2 years, hypoxemia gradually progressed accompanied by persistent cough, mucous sputa and intermittent fever. The chest X-ray revealed bilateral interstitial shadow particularly localized in lower lung fields. The arteriovenous shunt ratio was shown to be 24% by oxygen method. Perfusion lung scan using 99mTc-labeled MAA revealed perfusion defects in bilateral lung fields and radionuclide uptake was strongly demonstrated in the kidneys. These clinical data suggested that severe hypoxemia was probably due to multiple arteriovenous shunt. With further progression of hypoxemia for 4 months, he died of hepatic failure and pulmonary infection. Autopsy showed Miyake's type B cirrhosis. Multiple pleural and subpleural arteriolar nevi were demonstrated grossly and microscopically. There were no arteriovenous malformations demonstrated after injection of barium-gelatin solution into the pulmonary artery. Histologically, irregularly dilated vessels were found in the lung parenchyma beneath the pleura and filled with blood and injection material. These clinical and pathological findings provided evidence that the mechanism of arterial desaturation was pulmonary arteriovenous shunting due to liver cirrhosis.

Adult↗

Purification of infectious bronchitis coronavirus by Sephacryl S-1000 gel chromatography.

A procedure was developed to purify infectious bronchitis virus (IBV) by gel chromatography (GC) with a Sephacryl S-1000 column. Virus samples concentrated by centrifugation were applied to a Sephacryl S-1000 column and eluted by 0.02 M phosphate buffer (pH 7.2) containing 0.15 M NaCl. Virus particles were recovered mainly in the first peak. Purity of the samples was evaluated by both sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electron microscopy. Using electron microscopy, it was found that there were more spike-rich particles in the virus samples purified by GC than in those purified by sucrose density gradient centrifugation (SDGC). In addition, the hemagglutination unit [log10 (infectivity titer/hemagglutination titer)] of GC-purified virus samples was approximately 10 times lower than that of SDGC-purified virus samples. These results indicate that Sephacryl S-1000 gel chromatography is useful for purification of IBV.

Animals↗

Ifosfamide, adriamycin and cisplatin (IAP) plus bleomycin (B) combination chemotherapy in patients with recurrent cancer of the uterine cervix.

A combination chemotherapy of ifosfamide, adriamycin and cisplatin (IAP) plus bleomycin (IAP plus B) was used to treat nine patients with recurrent cervical cancer of the uterus. All patients had received conventional radiation therapy with or without hydroxyurea as a potential radiation sensitizer, and seven of them had measurable disease in a previous irradiated field (4 cases) or distant area (3 cases). The tumors included 5 squamous cell carcinomas (non keratinizing: 2, keratinizing: 3), two adenosquamous (including one glassy cell carcinoma), one adenocarcinoma (endometrioid type) and one argyrophil cell carcinoma. All histologic type cancers except argyrophil cell carcinoma responded to IAP plus B treatment. In seven evaluable cases, three complete responses (CR) and 3 partial responses (PR) were recorded (response rate was 85.7%), including 3 responded tumors within previously irradiated pelvic tissue. The median duration of CR was over 7 months and that of PR was 3.5 months. Side effects of IAP plus B were severe in hematologic toxicity (100% of grade 4 leucopenia) but acceptable, permitting five courses of treatments at four week intervals. The results obtained were encouraging, although therapeutic benefits of IAP plus B were not evident in a patient with argyrophil cell carcinoma and the intractable nature of this histologic type cancer in the uterine cervix was again emphasized.

Adenocarcinoma↗

[Blood concentration of granulocytic elastase, surgical invasion and postoperative complications--with special reference to surgical resection of liver cirrhosis].

The blood concentrations of granulocytic elastase (PMN-E), alpha 1-antitrypsin and alpha 2-macroglobulin were examined to evaluate their clinical significance in patients who underwent hepatectomy due to liver cancer with liver cirrhosis (n = 31, Group A), due to liver cancer with chronic hepatitis (n = 5, Group B) and without hepatic complications (n = 6, Group C) and other major surgeries (n = 10, Group D). In all groups, on the first postoperative day, blood PMN-E increased rapidly more than three times of the preoperative levels. Despite a decreasing tendency from postoperative Day 3, the value in Group A reincreased on Day 5. The peak PMN-E values within 24 postoperative hours showed significant positive correlations (p less than 0.01) with the amounts of hemorrhage and blood transfusion during operation in all groups. Even in 18 cases without blood transfusion, peak PMN-E was positively correlated (p less than 0.05) with the operative time and the amount of blood loss during operation. In Group A, patients in whom blood PMN-E increased after postoperative Day 3 developed infection and adult respiratory distress syndrome. After temporary reduction after operation except for Group C, blood alpha 1-antitrypsin increased from postoperative Day 3. However, alpha 1-antitrypsin in Group A was significantly low (p less than 0.01), compared to the increased levels in Group C and D. Blood alpha 2-macroglobulin showed no tendency of postoperative increase in all groups.

Granulocytes↗

[Intra-arterial and intraportal therapy combined with decollateralization in unresectable cholangiocellular carcinoma--a case report].

A 45-year-old man was referred to our hospital due to obstructive jaundice by intrahepatic cholangiocellular carcinoma. At laparotomy, he was assessed as unresectable because of multiple foci in both lobes. Therefore, two catheters connected to implantable access devices were placed in both the hepatic artery and the portal vein following decollateralization using silicone rubber sheeting, in addition to choledochectomy and choledocho-jejunostomy. After the surgical procedure, he underwent chemoembolization twice using Lipiodol, cisplatin, and Gelfoam, and two intraportal infusions of cisplatin at a dose of 50 mg. Moreover, a total dose of 4 g of 5-FU and 20 mg of MMC was administered through the arterial and portal catheters, respectively. Administration of G-CSF was remarkably effective for severe thrombocytopenia, and leukopenia resulted from this active chemotherapy. He is still alive 7 months after the surgical procedure with the regression of the lesions.

Adenoma, Bile Duct↗

[A long-survival case of hepatocellular carcinoma treated by intra-arterial chemotherapy and immunotherapy].

Hepatic resection is generally considered to be superior to any other therapeutic procedures for hepatocellular carcinoma (H.C.C.). However, the resectability of the patients who have HCC. with liver cirrhosis is still low, and surgery is appropriate in only a minority of patients. Although some successful reports of intra-arterial chemotherapy for HCC. have been documented, most of the therapeutic effects are transient and the survival rate is not satisfactory. This report is of a rare case, that of a long-term survivor with HCC treated by intra-arterial chemotherapy and immunotherapy. A 66-year-old man, with a 10-year history of liver cirrhosis was admitted to The Center for Adult Diseases, Osaka, after detection of a tumor in the right lobe on US. On admission, serum AFP was within normal range, HBs-Ag was negative, and ICG-R 15 was 20.8%. On hepatic angiogram, a hypervascular tumor (6 cm in size) was recognized in the middle of the right lobe. He was assessed as unresectable because of insufficient reserve capacity, and the catheterization of the hepatic artery for intra-arterial chemotherapy and the injection 35 KE of OK-432 into the tumor were carried out under laparotomy. After the procedure, the patient was treated by intra-arterial infusion of doxorubicin (ADR) at a total dose of 150 mg and 5-FU in total dose of 25 g, with a hypodermic injection of OK-432 at a total dose of 161 KE. Hepatic angiography, carried out one year after the procedure, disclosed no foci in the liver. The duration of complete remission continued more than 5 years. The patient eventually died of intrahepatic recurrence, but he lived for 7 years and 3 months after the catheterization.

Aged↗

[Adjuvant surgery to enhance therapeutic effects of chemo-embolization in advanced hepatocellular carcinoma].

Different kinds of adjuvant surgery were carried out in three patients with advanced hepatocellular carcinoma (HCC) to enhance the therapeutic effects of chemo-embolization (TAE). The first patient, who had multiple foci localized in the right lobe, underwent ligation of the right portal vein in order to eliminate the small intrahepatic spreads and to protect against transportal metastasis to the left lobe. Afterward, TAEs were repeated a total of 5 times. The patient is still alive 24 months after the surgery with partial remission of the lesions. The second patient with severe cirrhosis had received TAE twice. Since one of the tumors, which existed in the hepatic hilus, did not respond to TAE, only the non-respondent tumor was removed surgically. This patient remains alive 28 months after the surgery with complete remission of the lesions. In the third patient, repeated TAEs resulted in collateral feeding arteries. Permanent decollateralization using silicone rubber sheeting was carried out following ligation of collaterals. Thus adjuvant surgery to enhance the therapeutic effects of TAE may be a significant palliative treatment for HCC.

Carcinoma, Hepatocellular↗

[Selective anticancer effects of intra-arterial infusion of 3',5'-dioctanoyl-5-fluoro-2'-deoxyuridine (TT82) in hepatocellular carcinoma].

3'-5'-Dioctanoyl-5-fluoro-2'-deoxyuridine (TT 82), one of the lipophilic prodrugs of 5-fluoro-2'-deoxyuridine mixed with Lipiodol (LPD), was injected into the hepatic artery before hepatic resection in 4 patients with hepatocellular carcinoma. Later, the anti-cancer effects of the drug were evaluated mainly by the examination of resected specimens. The serum alpha-fetoprotein levels of three patients in whom the values were over normal range fell to less than 50% of pretreatment values from 7 to 14 days after the injections. In pathological observation of the specimens, the necrosis rates of main tumors were 100%, 70%, 30% and 0%, respectively. In three patients whose main tumors showed complete or partial necrosis, selective depositions of LPD in the tumors were observed on soft X-ray photographs. The concentrations of TT 82 and its metabolites in the tissues of LPD-depositing areas were markedly higher than those in tissue of the regions without LPD deposits. These findings suggested that TT82-Lipiodol mixture remained selectively in the cancerous tissues and exhibited anticancer effects following injection into the hepatic artery.

Aged↗