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Biomedical subjects

T Konno

Publications and source records attributed to T Konno.

At least 163 records · Page 9Linked to original sources

Effect of VAB-6 combination chemotherapy on malignant germ cell tumours in childhood.

The VAB-6 protocol was applied to 5 children with malignant germ cell tumour. Four of them achieved complete remission after 3 inductions of this protocol and surgery. Death in one case was attributed to chemotherapy. Complete responders have been in remission now for 4 months to 2 years without maintenance chemotherapy. Adverse effects including myelosuppression, ototoxicity, cardiotoxicity and pulmonary toxicity were observed. The VAB-6 protocol is an effective chemotherapy in children with malignant germ cell tumour and requires only 3 to 4 months of treatment.

Adolescent↗

Incidence of subacute sclerosing panencephalitis following measles and measles vaccination in Japan.

The Japanese Committee for the National Registry of Subacute Sclerosing Panencephalitis (SSPE) confirmed that 215 cases of SSPE occurred in the 20 years from 1966 to 1985, as discovered in the 10-year surveillance from April 1976 through March 1986. The annual incidence in recent years has been between 10 and 23 cases. Among cases with a certain history of measles illness or measles vaccination, 184 (90.2%) had a history of measles illness without receiving measles vaccine. There were 11 probable measles vaccine-associated cases (5.4%), three (1.5%) being vaccinated with a combined use of killed and live vaccine and eight (3.9%) with further attenuated live vaccine. There were nine cases (4.4%) without a history of either measles illness or measles vaccination. Intervals between measles illness and the onset of SSPE varied from 1 to 16 years (mean, 7.0 years). The periods following measles vaccination with further attenuated live vaccine were 2 to 11 years (mean, 4.6 years). Annual incidence rates of SSPE per million cases of measles ranged between 6.1 and 40.9 (mean, 16.1) in the 10 measles epidemic years 1968-1977, and those following vaccination with further attenuated live vaccine were zero in most years and at the highest 3.08 (mean, 0.9) per million doses of distributed vaccine.

Adolescent↗

Comparison between in vivo and in vitro cutaneous penetration of fenvalerate in tobacco budworm (Lepidoptera: Noctuidae).

In vivo and in vitro penetration of fenvalerate were compared in the 3-d-old fifth-instar tobacco budworm, Heliothis virescens (F). In the in vitro studies, a piece of cuticle was excised and mounted on a diffusion cell, and the amount of radioactivity present in the cuticle and medium was determined at various time intervals. At 24 h, approximately 7.4% of the dose was located in the cuticle, whereas only 1.6% actually penetrated. In the in vivo studies, approximately 7.4% of the radioactivity was recovered from the body after cuticular wash.

Animals↗

Broad-spectrum antiviral activities of neplanocin A, 3-deazaneplanocin A, and their 5'-nor derivatives.

The neplanocin A analogs, 3-deazaneplanocin A, 9-(trans-2',trans-3'-dihydroxycyclopent-4'-enyl)adenine (DHCA), and 9-(trans-2',trans-3'-dihydroxycyclopent-4'-enyl)-3-deazaadenine (DHCDA), all potent inhibitors of S-adenosylhomocysteine (AdoHcy) hydrolase, were studied for their broad-spectrum antiviral potential. 3-Deazaneplanocin A, DHCA, and DHCDA proved specifically effective against vesicular stomatitis virus, vaccinia virus, parainfluenza virus, reovirus, and rotavirus. Their selectivity was greater than that of neplanocin A, particularly against vesicular stomatitis virus and rotavirus. As could be expected from adenosine analogs that are directly targeted at AdoHcy hydrolase, 3-deazaneplanocin A, DHCA, and DHCDA were fully active in adenosine kinase-deficient cells, implying that their activity did not depend on phosphorylation by adenosine kinase. None of the AdoHcy hydrolase inhibitors showed selective activity against human immunodeficiency virus (type 1). 3-Deazaneplanocin A at a dose of 0.5 mg/kg per day conferred marked protection against a lethal infection of newborn mice with vesicular stomatitis virus.

Adenosine↗

Physical and chemical changes of medicinals in mixtures with adsorbents in the solid state. II. Application of reduced pressure treatment for the improvement of dissolution of flufenamic acid.

Flufenamic acid (FFA) was mixed with magnesium aluminum silicate (MAS) and stored at 60 degrees C at a reduced pressure of about 2.5 mmHg. After storage, when its concentration was not more than 20%, FFA was observed by X-ray diffraction and polarizing microscopy to be amorphous. The dissolution of FFA was thus enhanced in comparison with that of a freshly prepared mixture. Furthermore, the dissolution curves showed a typical supersaturation pattern, and the supersaturation state continued longer, the higher the pH value of the dissolution medium. Flufenamic acid, in a mixture with MAS, became amorphous more rapidly at reduced pressure than at atmospheric pressure, and therefore the effect of improved dissolution appeared earlier at reduced pressure. Infrared spectral studies suggested that FFA, after storage at a reduced pressure with MAS, was dispersed monomolecularly in an ionic form. The technique of treating crystalline medicinals, that have poor solubility in water, with adsorbent at reduced pressure may be useful for improving their dissolution characteristics.

Adsorption↗

Chronic myelocytic leukemia probably promoted by growth hormone.

The study shows clinical evidence that growth hormone (GH) presumably promoted Ph1-positive chronic myelocytic leukemia in a 14-year-old boy who was receiving GH treatment for growth failure after surgery and irradiation for craniopharyngioma. Leukocytosis associated with immature myelocytic cells and low leukocyte alkaline phosphatase score appeared one year after GH treatment. Cytogenic study showed the presence of Ph1 chromosome.

Adolescent↗

Effects of in vitro treatment with 4-hydroperoxycyclophosphamide and hyperthermia on leukemic progenitor cells.

A key point of autologous bone marrow transplantation for leukemic patients is how to remove leukemic cells from their own bone marrow grafts. In this study a leukemic progenitor cell assay was used to evaluate the antileukemic efficacy of marrow-purging protocols that employed hyperthermia or 4-hydroperoxycyclophosphamide (4HC) against leukemic blasts obtained from patients. After the treatment of 2 x 10(7) nucleated bone marrow cells/ml with 100 micrograms/ml of 4HC in the presence of 7% suspension of packed autologous erythrocytes, leukemic colonies were eradicated in 10 of 13 cases and reduced to less than 0.3% as compared with the colony count in untreated cultures in two cases. More than 10% of leukemic progenitor cells survived after hyperthermia treatment (42 degrees C 60 min) in 7 of 9 cases. It is suggested that treatment of leukemic cells and 7% autologous erythrocytes with 100 micrograms/ml of 4HC is effective to eliminate leukemic progenitor cells. Treatment with hyperthermia may not be effective enough to eliminate leukemic progenitor cells from autologous bone marrow.

Adolescent↗

Preservation of immature hematopoietic progenitor cells responding to interleukin 3 in marrow treated with 4-hydroperoxycyclophosphamide.

The toxic effects of 4-hydroperoxycyclophosphamide (4HC) on different human hematopoietic progenitor cells were determined. Day 7 colonies supported by granulocyte colony stimulating factor (G-CSF), day 10 colonies supported by granulocyte-macrophage colony stimulating factor (GM-CSF) were counted. Approximately 2 X 10(2) granulocyte-macrophage colonies per 5 X 10(4) bone marrow (BM) mononuclear cells were formed in each assay system. A combination of interleukin 3 (IL3) and erythropoietin (EPO) induces 3 types of day 14 colonies; erythroid burst-forming units (BFU-E, 40 +/- 29/5 X 10(4) BM cells), granulocytes-macrophage colony forming units (CFU-GM, 143 +/- 29/5 X 10(4) cells and mixed colonies (CFU-GEMM, 24 +/- 13/5 X 10(4) cells). After treatment with 4HC, all the colonies were reduced. However, the recovery rate of day 14 colonies supported by the combination of IL3 and EPO (mean 12.1%) was significantly higher than the recovery rate of both day 7 colonies supported by G-CSF (mean 1.0%) and day 10 colonies supported by GM-CSF (mean 4.0%). The recovery rate of colonies supported by IL3 and EPO as also higher than that of day 14 colonies supported by GM-CSF and EPO. Immature pluripotent hematopoietic progenitor cells supported by IL3 and EPO appeared less sensitive to 4HC treatment than those supported by G-CSF and GM-CSF. Colony forming assays using IL3 may be useful in order to predict the hematological reconstitution after autologous bone marrow transplantation with 4HC treated graft.

Bone Marrow Transplantation↗

[Antitumor activities of oily suspended YM881 (SMANCS) against VX2 carcinoma].

YM881 (MW 15,000) is a conjugate protein preparation of two copolymer of styrene-maleic acid [SMA] (MW 1,500) and neocarzinostatin [NCS] (MW 12,000). Antitumor activities of YM881 and NCS with or without oily solvent injected arterially against VX2 carcinoma of rabbits were examined. Based on the growth and histological examination of the tumor, remarkable anti-tumor activities were observed with oily suspended YM881 but not with the other group. This results indicate that targeting of the anticancer agent to the tumor is most important for eliciting of antitumor activities.

Animals↗

[A case of massive hepatoma which responded to SMANCS/Lipiodol regimen with intra-arterial infusion].

Transcatheter arterial chemotherapy (SMANCS/lipiodol) was applied to massive hepatoma, which had a high AFP 213,000 ng/ml, A-P shunt, tumor thrombosis and metastatic lung cancer. After 3 months, the AFP value reduced to 18 ng/ml, massive hepatoma and the A-P shunt disappeared, but AFP-negative nodular hepatoma recurred around initial hepatoma. Each time, we injected SMANCS/lipiodol to the recurring hepatoma. The therapy in the initial stage was not so effective. The portal vein was not observed in the initial stage, but appeared after the second dosage. Metastatic lung cancer was declining in the initial dosage and 23 months later disappeared after the third dosage. The massive hepatoma occupied entirely the rt. lobe of the liver. The patient lived for 4 years, had total admission periods of 190 days and could return to life in society. In this case, we considered that transcatheter arterial chemotherapy (SMANCS/lipiodol) had remarkable effects.

Antibiotics, Antineoplastic↗

Rings of negatively charged amino acids determine the acetylcholine receptor channel conductance.

The structure-function relationship of the nicotinic acetylcholine receptor (AChR) has been effectively studied by the combination of complementary DNA manipulation and single-channel current analysis. Previous work with chimaeras between the Torpedo californica and bovine AChR delta-subunits has shown that the region comprising the hydrophobic segment M2 and its vicinity contains an important determinant of the rate of ion transport through the AChR channel. It has also been suggested that this region is responsible for the reduction in channel conductance caused by divalent cations and that segment M2 contributes to the binding site of noncompetitive antagonists. To identify those amino acid residues that interact with permeating ions, we have introduced various point mutations into the Torpedo AChR subunit cDNAs to alter the net charge of the charged or glutamine residues around the proposed transmembrane segments. The single-channel conductance properties of these AChR mutants expressed in Xenopus laevis oocytes indicate that three clusters of negatively charged and glutamine residues neighbouring segment M2 of the alpha-, beta-, gamma- and delta-subunits, probably forming three anionic rings, are major determinants of the rate of ion transport.

Amino Acid Sequence↗

Characterization of a precursor T-cell line (THP-6) with rearranged T-cell receptor beta chain gene.

A previously established human leukemia cell line, designated THP-6, was further characterized with respect to cell surface antigen expression and immunoglobulin(Ig) and T-cell receptor(TCR) gene status. THP-6 cells were positive for CD7 and CD5 antigens and terminal deoxynucleotidyl transferase, but negative for CD2, CD1, CD4, CD8, CD10, cytoplasmic and surface CD3 and HLA-DR antigens, suggesting a precursor T-cell line. Analysis of Ig and TCR beta chain genes revealed that THP-6 had a rearranged TCR beta chain gene and a germline Ig gene. These results, in agreement with its phenotype, confirmed that THP-6 was of the T-cell lineage.

Cell Line↗

Role of VP3 in human rotavirus internalization after target cell attachment via VP7.

A cell lysate prepared from MA104 cells that had been infected with human rotavirus KUN strain (HRV-KUN) contained a 35-kilodalton protein capable of binding to MA104 cells. The binding of the 35-kilodalton protein was inhibited by a serotype 2-specific antiserum but not by antisera to other serotypes. Not only trypsin-treated, infectious HRV-KUN but also untreated, noninfectious virions effectively competed with the 35-kilodalton protein for the same cell surface binding sites. One monoclonal anti-VP7 (AH6) absorbed the 35-kilodalton protein from the HRV-KUN-infected cell lysate, whereas another monoclonal anti-VP7 (S2-2G10) inhibited the virions to compete with the 35-kilodalton protein for the cell surface binding sites. Both anti-VP7 (S2-2G10) and anti-VP3 (K-1532, K-376) monoclonal antibodies had the virus-neutralization activity, but only anti-VP7 inhibited virus adsorption. On the other hand, anti-VP3 monoclonal antibodies were capable of completely inhibiting the infection of preadsorbed HRV-KUN as long as virions were not yet internalized. Subsequent studies with [35S]methionine-labeled and purified HRV-KUN showed that not only trypsin-treated, infectious virions but also untreated, noninfectious virions were capable of efficient target cell binding and internalization. The internalization modes of these two HRV-KUN preparations were, however, quite different. Only the components of the inner capsid were internalized from trypsin-treated virions, whereas no such selective internalization was seen with untreated virions. Furthermore, anti-VP3 inhibited this selective internalization of the inner capsid from the infectious virions. From these results we conclude that VP7 is the HRV-KUN cell attachment protein and that adsorption of HRV-KUN via VP7 is independent of trypsin treatment, whereas the limited cleavage of VP3 by trypsin, which is essential for the development of HRV-KUN infectivity, is needed for the selective internalization of the inner capsid components, a process that is apparently essential for HRV-KUN infection.

Adsorption↗

Chronic granulomatous disease with neutrophil membrane cytochrome b deficiency: demonstration by immunochemical staining with monoclonal antibody.

Cytochrome b deficiency in the peripheral granulocytes of two male patients with chronic granulomatous disease was demonstrated by an immunocytochemical assay using a monoclonal antibody, 7D5, against human neutrophil cytochrome b. A mosaic of cytochrome b positive and negative neutrophils, indicating a carrier state in an X-linked trait, was found in the mother of patient 1 but not in the mother of patient 2.

Antibodies, Monoclonal↗

[Arterial administration of oily anticancer agents dissolved in lipiodol fluid in recurrence of hepatoma after hepatic resection and in metastatic liver cancer].

Oily anticancer agents such as SMANCS dissolved in Lipiodol fluid (Lipiodol) were administered to 18 patients with recurrence of hepatocellular carcinoma after hepatic resection and to 87 patients with metastatic liver cancer. The following results were obtained. i) It was proved and to that Lipiodol worked as a carrier of anticancer drugs and that targeting chemotherapy could be achieved. ii) The serum AFP level and tumor size showed a decrease in 91% and 87% of patients with recurrence of hepatoma, respectively. iii) This method could be applied to extrahepatic metastasis of hepatoma, and anticancer activity was also observed in these lesions. iv) The serum CEA level was decreased in 53 patients (83%) and reduction of tumor size was observed in 32 patients (46%) with metastatic liver cancer. v) In 5 out of 7 tumors resected after arterial injection of oily anticancer agents, necrosis was found histologically in over 95% of the tumor.

Antibiotics, Antineoplastic↗

[Targeting cancer chemotherapy using lipiodol as a carrier of anticancer drugs for hepatocellular carcinoma].

We have found that the lipid lymphographic agent, Lipiodol ultrafluid, remains selectively in hepatocellular carcinoma and other malignant solid tumors. Lipiodol administered arterially flows into the normal blood vessels of normal tissues and into the neovasculature of the tumor. Selective retention of Lipiodol in the tumor occurs due to early removal from the normal blood vessels and retention in the neovasculature and extravascular space in the tumor. Using this characteristic nature of Lipiodol, targeting cancer chemotherapy was achieved. It was shown that anticancer drugs had to be dissolved in Lipiodol and diffuse out gradually from the agent in order to achieve targeting cancer chemotherapy. Various kinds of oily anticancer agents which facilitate targeting cancer chemotherapy, such as SMANCS/Lipiodol, mitomycin/Lipiodol, adriamycin/Lipiodol and aclarubicin/Lipiodol were successfully developed. Clinically, these oily anticancer agents were administered to 260 patients with hepatocellular carcinoma. Selective long-lasting retention of Lipiodol in hepatocellular carcinoma was proved on the basis of CT and low-kVp X-ray examination, and persistent high biological activities of anticancer drugs in the tumor were also recognized. The serum AFP level and tumor size showed a decrease in 92% and 90% of cases, respectively. The survival period of these patients with unresectable tumor treated with this protocol was definitely longer than in the comparison group, i.e., the 50% survival period for the comparison group was 1.3 months, while that of the patients who received this protocol was 13 months. In patients administered a SMANCS dose of more than 0.25mg/cm2 of maximum cut-surface area, complete necrosis of the tumor was found, and importantly, non-cancerous liver tissue remained unaffected. Neither hematosuppression nor any severe side effects due to anticancer drugs were observed. Remarkable antitumor effects and reduced side effects could thus be achieved by targeting chemotherapy using Lipiodol as a carrier of anticancer drugs.

Antineoplastic Agents↗