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Biomedical subjects

T Sakuma

Publications and source records attributed to T Sakuma.

At least 217 records · Page 12Linked to original sources

Free vascularized fibular grafts in the treatment of congenital pseudarthrosis of the tibia.

Five patients with congenital pseudarthrosis of the tibia treated by a free vascularized fibular graft are described. Follow-up evaluation ranged from 15 to 81 months, with a mean of 40 months. Bony union was attained in three of five cases as determined roentgenographically. The remaining two cases failed to attain bony union. All cases except one, who was treated with a below-knee amputation, subsequently attained bony union. However, four cases had five fractures after bony union. We discussed unsolved problems regarding the free vascularized fibular graft and fracture after bony union.

Child↗

Antiviral activity of phosphonylmethoxyalkyl derivatives of purine and pyrimidines.

Various 3-hydroxy-2-phosphonylmethoxypropyl (HPMP) and 2-phosphonylmethoxyethyl (PME) derivatives of purine [adenine (A), guanine (G), 2,6-diaminopurine (DAP), 2-monoaminopurine (MAP), hypoxanthine (HX)] and pyrimidine [cytosine (C), uracil (U), thymine (T)] have been evaluated for their antiviral properties. PMEDAP, (S)-HPMPA [and the cyclic phosphonate thereof, (S)-cHPMPA)], (S)-HPMPC, PMEG, PMEA, HPMPG and HPMPDAP proved to be effective inhibitors of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). (S)-HPMPA and (S)-cHPMPA were the most effective inhibitors of varicella-zoster virus (VZV), and (S)-HPMPC was the most effective inhibitor of cytomegalovirus (CMV). Against adenovirus (types 2, 3 and 4) and vaccinia virus again (S)-HPMPA and (S)-cHPMPA showed the greatest inhibitory activity. As a rule, the PME derivates were much less inhibitory to VZV, CMV, vaccinia and adenovirus than the HPMP derivatives. However, PMEA, PMEDAP and PMEMAP showed marked and selective activity against the human immunodeficiency virus (HIV). (S)-HPMPA was selected for further evaluation in animal model infections. It proved efficacious in the topical treatment of HSV-1 keratitis in rabbits and cutaneous HSV-1 infection in hairless mice, and in the systemic treatment of both HSV-1 and vaccinia virus infections in mice.

Animals↗

Role of interferon in the augmented resistance of trehalose-6,6'-dimycolate-treated mice to influenza virus infection.

Mice inoculated intravenously with 10 to 100 micrograms trehalose-6,6'-dimycolate in an oil-in-water emulsion (TDM emulsion) acquired high resistance to intranasal infection by influenza virus at 7 to 14 days, but not at 1 day, after treatment. Mice inoculated with an oil-in-water emulsion without TDM (control emulsion) did not resist infection. The activity of the reticuloendothelial system of mice inoculated with TDM emulsion or control emulsion was greatly stimulated 1 day and 14 days after treatment. Interferon production in response to influenza virus was augmented in lung and serum of TDM emulsion-treated mice. The augmented interferon production was greatly diminished in the TDM emulsion-treated mice by treatment with anti-Thy-1.2 monoclonal antibody. Production of haemagglutination-inhibiting antibody in the TDM emulsion-treated or control emulsion-treated mice was higher than that in untreated mice, although no difference was observed between the TDM emulsion-treated and control emulsion-treated mice. On the other hand, TDM emulsion treatment of mice did not influence the appearance of antibody-producing cells, nor the activity of natural killer cells in the mice. The enhanced resistance of mice was diminished by inoculating anti-interferon-alpha/beta serum before influenza virus infection. No detectable interferon activity was observed in lung and blood of mice inoculated with anti-interferon-alpha/beta serum prior to influenza virus infection. These results suggest that the augmented early interferon production in T-lymphocytes of TDM emulsion-treated mice in response to influenza virus may play an important role in the enhanced resistance.

Animals↗

Intracellular phosphorylation of broad-spectrum anti-DNA virus agent (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine and inhibition of viral DNA synthesis.

The acyclic nucleotide analogue (S)-9-(3-hydroxy-2-phosphonyl-methoxypropyl)-adenine [(S)-HPMPA], which contains a phosphonate-substituted aliphatic chain, is a potent and selective inhibitor of the replication of various DNA viruses, including herpes simplex virus type 1 (HSV-1). We have synthesized radiolabeled (S)-[U-14C-adenine]HPMPA and investigated its metabolism by HSV-1-infected and mock-infected cells. The drug is as such taken up by the cells and subsequently converted to its monophosphoryl [(S)-HPMPAp] and diphosphoryl [(S)-HPMPApp] derivatives by cellular enzymes. It is incorporated to a very low extent into DNA of both mock-infected and HSV-1-infected Vero cells. (S)-HPMPA inhibits HSV-1 DNA synthesis at a concentration that is several orders of magnitude lower than the concentration required for inhibition of cellular DNA synthesis. Thus the selectivity of (S)-HPMPA as an antiviral agent cannot be attributed to a differential phosphorylation by virus-infected or uninfected cells but resides in a specific inhibitory effect on viral DNA synthesis. The exact basis for the latter effect is under investigation.

Adenine↗

[Microangiopathic hemolytic anemia (MAHA) and renal failure induced by anti-neoplastic agents--a case report].

A 65-year-old man underwent left-upper lobectomy for large cell carcinoma of the lung on November 8, 1984 (pT1N0M0: Stage I a). He was treated with MMC, Futraful, CDDP and CPM as adjuvant chemotherapy. In April 1985, he was re-admitted to our hospital because of progressive dyspnea. He was diagnosed as having drug-induced interstitial pneumonia, and so steroid therapy was started. In July 1985, he suffered from anemia, thrombocytopenia, proteinuria and azotemia progressively, and died due to pulmonary hemorrhage and edema. At necropsy, no cancer recurrence was found. It thus seemed that the cause of death was microangiopathic hemolytic anemia and renal failure induced by anti-neoplastic agents.

Acute Kidney Injury↗

[A case of extramedullary plasmacytoma].

The patient is 51-year-old male. A tumor arose on the upper eye lid at the age of 44 years and 6 years later, a tumor arose on the forearm. The tumor recurred 3 times on the forearm and were resected each times. When he was 51 years old, 3 tumors arose on the upper arm. Tumors were found in the cutis and subcutis of the jaw, back, forearm and thigh. A tumor was also found on the palatine tonsil. Bence Jones protein was negative in serum and urine. There were no particular findings in serum immunoelectrophoresis, bone X ray films, bone marrow aspiration and bone scintigram. The Borrmann 4-like pattern was revealed on the stomach by barium examination. By chemotherapy and radiotherapy, the tumors decreased markedly in size. Excisional biopsy showed that the tumor was composed of atypical plasma cells and gamma-chain and lambda-chain were immunohistologically detected.

Humans↗

[A case of angiosarcoma of both breasts].

A 19 year-old female, complaining of gigantic tumor on each breast and hemorrhagic diathesis, was admitted to our hospital. Laboratory data and clinical findings suggested the presence of DIC. Bilateral mastectomies reduced the bleeding tendency within a week. In conclusion, removal of the tumors was effective to avoid fatal hemorrhage.

Adult↗

[The significance of bronchoscopic findings as a prognostic factor in inoperable adenocarcinoma of the lung].

The clinical value of bronchoscopic findings as a prognostic factor has been studied in 136 cases with an inoperable adenocarcinoma of the lung. The survival time in 107 cases with pathological bronchoscopic findings was significantly shorter than in 29 cases without pathological bronchoscopic findings. In the three subtypes of bronchoscopic findings, classified according to the tumor proliferation pattern, i.e. polypoid type, submucosal type and exposing type, the exposing type proved to have the worst prognosis. In addition, our study suggests that the level of infiltrated bronchus is related to the survival time. The more central the tumor infiltration, the worse the prognosis.

Adenocarcinoma↗

Diagnostic value of high molecular weight alkaline phosphatase in detection of hepatic metastasis in patients with lung cancer.

High molecular weight alkaline phosphatase (HMW-ALP) was measured in the sera of 126 patients with lung cancer to determine its diagnostic value in the detection of hepatic metastasis. This isoenzyme was found in 21 of 24 patients with hepatic metastasis and in 27 of 102 patients without hepatic metastasis. When 10 U/L was used as a cut-off value, the sensitivity, specificity, and accuracy of this test were 71%, 89%, and 86%, respectively. From the standpoint of histologic type, this test was most useful in patients with small cell carcinoma. HMW-ALP was not detected in the sera of 15 controls. It is concluded that HMW-ALP is a useful marker for hepatic metastasis in patients with lung cancer.

Adenocarcinoma↗

Scanning electron microscopical studies of the arterial terminals in the red pulp of the rat spleen.

The arterial terminals in the red pulp of the perfused rat spleen were studied by scanning electron microscopy. The arterial terminals were tubular or funnel-shaped and ended openly in the splenic cord. No continuity was observed between the arteries and the sinuses. The endothelial cells of the arterial terminals extended their processes at the fringe of the terminal ends, and these endothelial processes were connected to the processes of the reticular cells of the splenic cord. In addition, large pores, measuring 0.5-8 microns in size, were found in the wall of the terminals adjacent to their end.

Animals↗

Splenic erythropoiesis in rats under hypoxic and post-hypoxic conditions.

In rats chronic hypoxia causes extramedullary haematopoiesis mainly localized in the spleen. It is not known how splenic erythropoiesis develops and how it regresses after termination of hypoxia. In this study the spleen of rats exposed to chronic hypoxia was studied by light and electron microscopy; the findings were compared to relevant peripheral blood values. Splenic erythropoiesis begins almost immediately after exposure to hypoxia and reaches its maximum after 2-4 weeks. It occurs mainly in the splenic cords drawing upon local erythroblasts and is accompanied by an increase in splenic weight as well as a decrease in splenic iron stores. After termination of hypoxia marked phagocytosis by splenic cord macrophages diminishes the number of erythroblasts and of erythrocytes with a concomitant increase in splenic iron stores. Thus, splenic erythropoiesis appears to be inhibited as part of a rebound phenomenon and returned to normal by phagocytosis of erythroid cells within 4 weeks after cessation of the hypoxic stimulus.

Animals↗