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Biomedical subjects

T Nagata

Publications and source records attributed to T Nagata.

At least 577 records · Page 32Linked to original sources

Studies on DNA content of hepatocytes in cirrhosis and hepatoma by means of microspectrophotometry and radioautography.

In order to clarify the underlying mechanism of malignant transformation from cirrhosis to hepatoma the cell kinetics of hepatocytes were studied in these two conditions. The content and synthesis of DNA in hepatocyte nuclei were investigated, by means of Feulgen-microspectrophotometry and tritiated thymidine radioautography, in cirrhotic and noncancerous parts of hepatoma with concomitant cirrhosis. The distribution of ploidy patterns was widely spread, from hypodiploid to hyperpolyploid, in the noncancerous parts of a cirrhotic liver containing hepatoma. In normal liver, each paired nuclear DNA content of a binucleate cell recorded almost the same amount, whereas in the noncancerous as well as in hepatoma cells much difference of DNA content was observed between the paired nuclei of the binucleate cells. The ploidy pattern of hepatocytes in patients with liver cirrhosis, who had developed hepatoma during follow-up periods of several months to several years, appeared to resemble that in noncancerous parts of hepatoma cases. On the other hand, the incorporation of tritiated thymidine into hepatocytes was found to be markedly increased in noncancerous parts as well as in cirrhotic liver developing hepatoma during follow-up periods. These results suggest the possibility that the hepatocytes in noncancerous parts of hepatoma have deranged cell-kinetics which might be a driving factor for the development of malignancy.

Acute Disease↗

Histochemical study of the postnatal development of autonomic nerves in the mouse iris, using a whole-mount preparation method.

Postnatal development of autonomic nerves in the mouse iris was studied histochemically from one day to five months of age. For the demonstration of aminergic nerves the glyoxylic acid method was used, while for cholinergic nerves, Karnovsky and Roots' method was utilized on the whole-mount preparations of irises. The results obtained were as follows. In one-day-old mice, many aminergic nerves could already be seen, while cholinergic nerves were scarcely observable. Both types of nerve increased rapidly in the first 2 weeks. Both completed development between 3 and 4 weeks, although aminergic nerves were observed to develop earlier than the cholinergic.

Animals↗

Nucleic acid synthesis in proliferating peroxisomes of rat liver as revealed by electron microscopical radioautography.

Thirty albino rats were fed with a diet containing 1, 2 or 4% di-(2-ethylhexyl)-phthalate (DEHP), a peroxisome-proliferating agent. Others were fed with normal diet as controls. Both groups were sacrificed at varying intervals from 3 days to 4 weeks. The livers were either removed and fixed in glutaraldehyde and osmium tetroxide or fixed in glutaraldehyde, incubated in a diaminobenzidine (DAB) medium, postfixed, embedded in Epon, and sectioned. Other tissues were incubated in Eagle's MEM containing either [P3H-thymidine or [3H]uridine, fixed, embedded in Epon, sectioned, and radioautographed. Specimens were observed in a Hitachi H-700 electron microscope. The number of peroxisomes showing DAB reactivity increased in DEHP-fed animals as compared with normal controls. In radioautograms of normal rats labelled with [3H]thymidine, no silver grains were observed, whereas grains were observed overt some nuclei, mitochondria and peroxisomes of DEHP-fed animals. In contrast, radioautograms of tissue labelled with [3H]uridine revealed a few grains in nuclei and mitochondria or endoplasmic reticulum of normal rats, although grains appeared in nuclei, mitochondria, endoplasmic reticulum and peroxisomes of DEHP-fed animals more frequently. From these results, it is concluded that [3H]thymidine and [3H]uridine were incorporated in the proliferating peroxisomes, suggesting that nucleic acid synthesis had taken place.

Animals↗

Immune complex-mediated glomerulonephritis and interstitial pneumonia simulating Goodpasture's syndrome.

An autopsy case of what was clinically considered to be Goodpasture's syndrome was investigated. The lung had hemorrhagic interstitial pneumonia, showing granular patterns of IgG and C3 along the alveoli by the immunofluorescent method and electron-dense subepithelial deposits by electron microscopy. The kidney had crescentic and segmental necrotizing glomerulonephritis associated with membranous nephropathy. Uneven, continuous patterns of immunofluorescent IgG and C3 along the GBM were noted. Electron microscopy showed numerous subepithelial deposits, and immunoelectron microscopy revealed that IgG was not present in the GBM itself but present in the subepithelial deposits. Anti-GBM antibody activity was not detected in the serum or the kidney eluate. It was suggested that renal and pulmonary lesions occurred through the same mechanism and in association with immune deposits. We propose that there is a disease having immune complex-mediated deposits. We propose that there is a disease having immune complex-mediated renal and pulmonary lesions which clinically resembles the conventional Goodpasture's syndrome.

Adult↗

Gastrointestinal amyloid deposition in familial amyloid polyneuropathy.

We found degeneration of enteric nerve plexuses in two patients with type I familial amyloid polyneuropathy. Amyloid deposition was more severe in the wall of the stomach than in the rectum. Hypomotility of the upper gastrointestinal tract, resulting from both amyloid deposition in the stomach and upper bowel and degeneration of the intrinsic autonomic nerves, may be responsible for anorexia, nausea, and vomiting. Diarrhea and constipation may be caused by degeneration of the enteric nerve plexuses. Gastric biopsy is valuable and safe in the diagnosis to type I familial amyloid polyneuropathy.

Adolescent↗

[Arterial infusion of combination chemotherapy using adriamycin and mitomycin C for hepatoma and metastatic tumors of the liver].

Forty patients with hepatoma and metastatic tumors of liver were treated with rapid arterial infusion administered simultaneously using 30-40 mg of adriamycin and 10-20 mg of mitomycin C into the hepatic artery by Seldinger catheter. They were 16 patients with breast cancer, 21 with gastrointestinal tumors including hepatoma; 6, gastric cancer; 5, colon cancer; 7, gallbladder cancer; 2, pancreas cancer; 1, and three with other malignancies, respectively. Partial responses were obtained in 14 of 40 patients (35%). The response rate in patients with breast cancer was 44% (7/16), while it was 29% (6/21) with gastrointestinal tumors. The median duration of response was relatively short, being 3.5 months in the former patients and 2.3 months in the latter patients. The median duration of survival was 4.0+ months. The results indicate that this arterial infusion therapy is one of the useful treatments in the management of malignant tumors of the liver. Leukopenia less than 4 x 10(3)/cmm was seen in 63%, while thrombocytopenia less than 100 x 10(3)/cmm in 38%, and decreased hemoglobin value of more than 2 g/dl in 13%, which were quite tolerable. Gastrointestinal symptoms and hair loss were milder than those from systemic chemotherapy. Renal toxicity was seen in three patients, and two patients died of renal failure, thus the renal toxicity, which may be related to contrast media as well as anticancer agents, should be carefully prevented by proper hydration.

Adult↗

[Combination chemotherapy of Hodgkin's disease with vincristine, cyclophosphamide, procarbazine, and prednisolone].

Nineteen patients with stages II B-IV of Hodgkin's disease were treated with a combination of vincristine, cyclophosphamide, procarbazine, and prednisolone (CVPP regimen), given in a 3 week intervals for 3 months. Eighteen patients were available for responses. A complete remission (CR) was obtained in 9 (50%) out of 18 patients. The median duration of CR and relapse-free survival were 7 months and 26+ months, respectively. Hematologic toxicity was mild, although occasionally cumulative for aged patients and for previously treated patients. Other toxicities such as alopecia and neurotoxicity were troublesome but reversible. Thus, a further study by modification of the regimen warranted to improve the response rate and relapse-free survival.

Adult↗

[Phase I-II studies of a new antineoplastic agent, 4'-(9-acridinylamino)-methanesulfon-m-anisidide (AMSA)].

AMSA, an acridine derivative with significant antitumor activity in experimental tumors, was administered to 17 patients with advanced tumors refractory to standard chemotherapies. A phase I study was undertaken in 10 patients with solid tumors and lymphomas. Dose-limiting toxicity was myelosuppression. With a median dose of 90 mg/m2 (75-148 mg/m2), median lowest WBC count was 1,000/mm3 (100-3,200) on day 11 and its recovery up to 4,000/mm3 was seen on day 21, while lowest platelet count was 42 X 10(3)/mm3 (7-300 X 10(3) on day 12 and its recovery up to 100 X 10(3)/mm3 was on day 20. Non-hematological toxicities were nausea (39%), vomiting (11%) and phlebitis (17%) in 18 courses of therapy. The result indicated that the recommended dose schedule for a phase II evaluation was 90 mg/m2, every three weeks. Therapeutic activity was observed in patients with non-Hodgkin's lymphoma (one partial response and two minor responses out of four). Two out of five breast, one ovarian, and one melanoma patients showed stable diseases. Five leukemic patients (three AMLs, one MoL, and one blastic CML) were treated with AMSA, and in these cases cytoreduction of peripheral and bone marrow blasts was seen, but it was not adequate to induce remission. Further clinical trials with this agent are warranted, especially in patients with acute leukemia, lymphoma and breast cancer.

Adult↗

[A combination chemotherapy of ACNU and DTIC for advanced malignant melanoma].

Fourteen patients with advanced malignant melanoma were treated with a combination chemotherapy consisting of ACNU 100 mg/m2 i.v. on Day 1 in 6 week intervals and DTIC 200 mg/m2 i.v. on Days 1 to 5 at 3 week intervals. Four patients had prior chemotherapy and 2 had prior immunotherapy. Excluding 4 patients received the regimen for adjuvant chemotherapy, 10 of 14 patients were evaluable for response. There were 3 patients of partial responses, 3 minor responses, 1 no change, and 3 progressive diseases. The durations of partial responses were 1, 1, and 8 months, respectively, while the survival times in these patients were 5, 21, and 10 months, respectively. Leukopenia less than 4,000/cmm occurred in 10 of 14 patients (71%) and thrombocytopenia less than 100 X 10(3)/cmm in 9 of 14 patients (64%), moreover, these hematologic toxicities were cumulative. Serum GOT and GPT elevated to 3,460 mu/ml and 1,365 mu/ml, respectively in one patient, but this returned to a normal level one month later. Nausea and vomiting were mild to severe in 12 of 14 patients, being most marked on Day 1 and decreasing intensity during the next several days. Other non-hematologic toxicities including skin rash, fever, and phlebitis were noted in each one patient, respectively. Hematologic toxicity of this regimen was a dose limiting toxicity; therefore, intensive supportive therapy to prevent infection and hemorrhage is essential for the management of the patients during this chemotherapy.

Adult↗

[The combination chemotherapy of vincristine, methotrexate, ACNU, and adriamycin for anaplastic carcinoma of the lung].

Recent advances in the chemotherapy of malignant diseases, particularly, in hematopoietic malignancies, has opened oncologists' eyes in wonder, whereas the chemotherapy of solid malignant diseases including the carcinoma of the lung is not satisfactory compared with the results of other modalities such as radiotherapy and surgery. The chemotherapy, however, gradually becomes a great importance because the majority of the cases of lung cancer is that of advanced one. Between June, 1974 and December 1980 we experienced 54 inoperable cases of lung cancers among which there were 11 cases diagnosed as an anaplastic carcinoma. The combination chemotherapy of vincristine (1 mg/body, iv, day 1), methotrexate (30 mg/body, iv, day 1 and 5), ACNU (100mg/body, iv, day 2) and adriamycin (40mg/m2, iv, day 2) was employed. Vincristine and methotrexate were given every 3 weeks and ACNU and adriamycin were repeated every 9 weeks. If the moderate degree of neuropathy due to vincristine occurred it was suspended and methotrexate was stopped if WBC was less than 2000/mm or if patients were suffered from stomatitis which disturbed their swallowing. According to the response criteria of Koyama-Saito 4, cases were responded and one of them survived 17 months after the initiation of above 4-drug combination chemotherapy, although she received another combination chemotherapy because of the relapse of disease. The combination chemotherapy of ACNU and adriamycin was tried to utilize the advantage of their time different effects on the bone marrow suppression and to cover heterogenous histopathological diagnosis of anaplastic carcinoma. The heterogeneity of anaplastic carcinoma included undifferentiated squamous cell carcinoma, adenocarcinoma, large cell carcinoma and even small cell carcinoma. In taking consideration of these points, the drug-combination was designed. Clinically, however, the long resting period made the tumor regrow in some cases due to severe delayed myelosuppression by the combination of ACNU and adriamycin. Thus, more cautiously-designed combination should be considered.

Aged↗

[Clinical effects of human fibroblast interferon on malignant tumors].

Human fibroblast interferon(HFIF) was used in 26 patients with various malignant diseases, most of whom had previous chemotherapy. The dosages used were 3 X 10(6) IU or 6 X 10(6) IU of HFIF i. v. daily. Out of 24 evaluable patients, there were 2 partial remissions (CLL 1 and multiple myeloma 1), and 7 stable diseases (multiple myeloma 2, stomach cancer 2, non-Hodgkin's lymphoma 1, CLL 1 and malignant melanoma 1). The majority of the patients experienced fever exceeding 38 degrees C and chills, which became uncommon within several days of treatment. Other side effects included myelosuppression, general malaise, anorexia, hepatic dysfunction and renal dysfunction, which were mild and tolerable.

Adolescent↗

Receptive field properties of rat ventral lateral geniculate cells projections to the superior colliculus.

Cells of the ventral lateral geniculate nucleus (LGV) in rats sending their axons to the superior colliculus (SC), were identified electrophysiologically as the ones responding antidromically to electrical stimulation of SC. They were located in the external part of LGV. Visual receptive fields of these cells were mostly of ON-tonic types and some of the movement-sensitive ones. Evidence was presented supporting existence of the reciprocal fiber connection between the LGV and the SC.

Animals↗

Histochemical studies on the postnatal development of autonomic nerves in mice cerebral arteries.

Postnatal development of autonomic nerves of major cerebral arteries was histochemically studied in mice from one day to five months of age. For demonstration of aminergic nerves the glyoxylic acid method was used, while for cholinergic nerves Karnovsky and Roots' technique was utilized consecutively on the same whole mount preparations. The results obtained were as follows: 1) In one-day-old mice a few aminergic nerves were seen while cholinergic nerves were scarcely observed. The cholinergic nerves were clearly observed in one-week-old mice. Then, both nerves increased rapidly in the first 2 weeks with a slight delay of maturation in the latter. They completed development between 3 and 4 weeks. 2) Longitudinal and circular distributional patterns were observed for the both nerves; the former pattern developed earlier than the latter.

Acetylcholinesterase↗

Adrenergic and cholinergic innervation of rat cerebral arteries. Consecutive demonstration on whole mount preparations.

A consecutive demonstration of both aminergic and cholinergic nerves of rat cerebral arteries was carried out on whole mount preparations. For demonstration of aminergic nerves the glyoxylic acid method was used, while for cholinergic nerves Karnovsky's technique was utilized consecutively. This procedure provided a highly sensitive and reproducible demonstration of the two systems on the same specimen. The results obtained were as follows: 1) Aminergic and cholinergic nerves were distributed densely in the proximal portions of the major cerebral arteries examined. They were dense in the arteries of the anterior circulation and sparse in the posterior circulation. Each nerve had two different patterns, i.e. circular and longitudinal. Both circular and longitudinal patterns were observed in the proximal portions of the arteries, while in the distal portions, longitudinal fibres were predominantly present. 2) Superior cervical ganglionectomy produced no change in cholinergic nerve distribution, while it caused decreased density of aminergic nerves on the ipsilateral side on the arteries of the anterior circulation. The contralateral anterior cerebral arteries were partially affected. Bilateral sympathectomies abolished aminergic nerves in all arteries except the vertebral artery.

Acetylcholine↗

Incorporation of 3H-befunolol (beta-blocking agent) into melanin granules of ocular tissues in the pigmented rabbits. I. Light microscopic radioautography.

3H-befunolol was administered intravenously to pigmented rabbits. Thirty minutes after the administration, the iris, ciliary body and retina were fixed, embedded and processed for light microscopic radioautography. Radioautographical silver grains were observed over the pigment granules of the iris, ciliary body, choroid and retina. From these results it is concluded that 3H-befunolol is incorporated into the pigment granules of these cells. The mechanism of incorporation is discussed.

Adrenergic beta-Antagonists↗

Treatment of postoperative respiratory distress syndrome.

We have studied 45 patients with postoperative adult respiratory distress syndrome (ARDS) who were treated by mechanical ventilation during the last four years. This period was divided into two periods, and the mortality and progress after treatment were analysed. The overall, mortality was 56%. In the first period this rate was as high as 76%, while in the second period this rate improved to 43%. This improvement in the second period was thought to have resulted from aggressive cardiorespiratory treatment and the diminution of infection. According to the course of ARDS after treatment, four types could be classified. Type 1 showed rapid improvement in respiratory function. Type 2 showed gradual improvement. Type 3 showed relapse of respiratory failure. Type 4 resisted mechanical ventilation. Patients of types 3 and 4 had extremely poor prognoses. Stricter management to avoid infection, specific treatment of multiple organ failure (which was seen frequently) seemed advantageous. High frequency positive pressure ventilation (HFPPV) may have some role in improving the respiratory function of the patients with ARDS.

Adult↗