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Biomedical subjects

A Hoshino

Publications and source records attributed to A Hoshino.

At least 19 recordsLinked to original sources
PubMed1991

Role of serum albumin as a carrier of 99mTc-complex to tumor tissue.

To elucidate a factor required for tumor-imaging 99mTc-labeled radiopharmaceuticals, in vivo behaviors of 99mTc-L-cysteine (99mTc-Cys) and 99mTc-2-mercaptoethylamine (99mTc-ME) were compared with that of 99mTc-DL-homocysteine (99mTc-Hcy) which had been found to accumulate in several experimental tumors. When these three complexes were intravenously injected into mice bearing Ehrlich solid tumor, their tumor affinity was found to depend on their binding ability to serum albumin; 99mTc-Hcy, the albumin-binding ability of which was highest of the three, was the most tumor-tropic. When the albumin-bound complexes of these three were injected, their tumor distributions were enlarged. These results suggest the importance of serum albumin in serving as a carrier for the transport of 99mTc-Hcy-related compounds to tumor tissue.

Animals↗
PubMed1991

[Biphenotypic acute leukemia with Ph1 chromosome, M-BCR-, myeloperoxidase+, and CALLA+].

A 63 year-old woman was referred to our hospital because of fever and increased number of blasts in the bone marrow. On physical examination she had slight hepatomegaly but no splenomegaly. Laboratory tests disclosed a hemoglobin level of 8.5 g/dl; a WBC count of 13,200/microliter with 26% blasts; a platelet count of 51,000/microliter. A bone marrow aspirate was normocellular with 74% blasts and 37% blasts were stained positive for myeloperoxidase. Cell surface markers for HLA-DR, CD10, CD19, CD13, CD33 were positive. Karyotype analysis revealed 46, XX, t (9q+; 22q-) and 45XX, -7, t (9q+; 22q-). Southern analysis showed rearrangement of immunoglobulin heavy chain but not T cell receptor beta gene. Rearrangements in M-BCR were not detected with 5' or 3' bcr probes. After 2 courses of chemotherapy, blasts decreased to 7% with recovery of normal elements and 11 out of 20 metaphases of the bone marrow cells were normal karyotype. These findings suggest that this case was de novo Ph1 positive acute leukemia which demonstrated both lymphoid and myeloid features.

Acute Disease↗
PubMed1990

Antitumor activity of MST-16, a novel derivative of bis(2,6-dioxopiperazine), in murine tumor models.

We studied the antitumor activity of newly synthesized bis(1-acyloxymethyl) derivatives of 4,4'-(1,2-ethanediyl)bis(2,6-piperazinedione) using i.p.-i.p. models of P388 leukemia and B16 myeloma. As a result, we found 4,4'-(1,2-ethanediyl)bis(1-isobutoxycarbonyloxymethyl-2,6-piperazi nedione) (MST-16) to possess considerable therapeutic activity. MST-16 showed not only marked life-prolonging effects in both P388 leukemia- and B16 melanoma-bearing mice but also a greater therapeutic ratio than did its parent compounds, ICRF-154 and ICRF-159. Further studies revealed that MST-16 has considerable therapeutic activity against a number of other tumors such as ascitic forms of L1210 leukemia, colon 26 adenocarcinoma, and MH-134 hepatoma and solid forms of B16 melanoma, Lewis lung carcinoma, colon 38 adenocarcinoma, and M5076 fibrosarcoma. These results suggest that MST-16 is very promising as an antitumor agent.

Animals↗
PubMed1990

Tumor accumulation mechanism of 99mTc-DL-homocysteine, a model compound for the development of tumor-imaging radiopharmaceuticals.

To elucidate the tumor accumulation mechanism of 99mTc-DL-homocysteine (99mTc-Hcy), the role of mercaptalbumin, a carrier protein of 99mTc-Hcy in blood, was studied. 99mTc-Hcy bound to serum mercaptalbumin was carried to tumor tissue, efficiently adsorbed onto the cell surface, released from albumin, and taken up by the cells. An enlarged capillary permeability observed in tumor tissue played an important role in the transport process.

Animals↗
PubMed1990

[Phase I study of MST-16].

Phase I study with a new oral anticancer agents. MST-16 (Sobuzoxane), was conducted by 3 administration schedules: single, 5 consecutive days and 10-15 consecutive days. No toxicity was observed in the single administration at doses escalated up to 1,500 mg/m2. Dose-dependent leukopenia was observed from 560 mg/m2/day in consecutive 5 day administration, and median days to the nadir and recovery were about 2 and 1 week, respectively. GI-disorders were also observed sporadically from 800 mg/m2/day. One patient with Hodgkin's disease receiving 1,000 mg/m2/day achieved complete response. Consecutive administration for 10-15 days was carried out at a dose of 800 mg/m2/day. Six out of 7 evaluable patients demonstrated leukopenia, and all 2 patients treated for 15 days experienced leukopenia with a nadir corresponding to grade 3. Median days to nadir and recovery were both about 2 weeks. Doses recommended for phase II study were considered to be 1,600 mg/body/day for 5 days and 1,200 mg/body/day for 10-14 days.

Adolescent↗
PubMed1990

[Molecular and immunological approach to hematological disease: detection and analysis of intracellular modified nucleosides by flow cytometry].

Modified nucleosides are components of ribosomal RNA (rRNA), transfer RNA (tRNA) and messenger RNA (mRNA). 1-methyladenosine and pseudouridine are members of those modified nucleosides. The urinary concentration of 1-methyladenosine and pseudouridine of cancer patients are higher than that of healthy controls, and those compounds were reduced after effective chemotherapy. Thus those compounds might be expected to use as tumor markers. In this study cellular origin of 1-methyladenosine and pseudouridine were analysed about two tumor cell lines (HUT-102, THP-1), peripheral blood lymphocytes (PBL) from healthy adult and PBL under the phytohemagglutinin stimulation, by flow cytometric analysis and immunofluorescent staining of cellular RNA using monoclonal antibodies specific for 1-methyladenosine (AMA) and pseudouridine (APU). Both 1-methyladenosine and pseudouridine were detected in more than 90% of tumor cells above the thresholds of flow cytometric detection (Spectrum III, Ortho). The PBL under the PHA stimulation also tended to take the same way of the tumor cell lines, whereas few of the PBL contained 1-methyladenosine above the thresholds. According to the DNA analysis of those cell lines, high contents of the modified nucleosides in the cell might follow DNA synthesis, this leads to one reason for high levels of the urinary excretion of the modified nucleosides in cancer patient.

Adenosine↗
PubMed1989

[Prevention of hepatitis B--HLA DR/DQ in HBs Ag nonresponder].

To evaluate the immunological background in HBs Ag nonresponders against hepatitis B vaccine, the lymphocyte surface marker and HLA-DR/DQ antigen were determined on hospital personnel, 70 males and 256 females, injected hepatitis B vaccine for three times. The vaccine made from the plasma of HBs Ag carriers was injected at the first and second vaccination and recombinant hepatitis B vaccine was injected at the third vaccination. A month after the third vaccination, blood was withdrawn for HBs antigen test by RIA. Border line cases (cut off index 1.0-1.9) are included in nonresponder (cut off index less than 0.9). Both nonresponders and low responders (cut off index 2-49) are more often seen in males than females and high responder (cut off index 50 or more) are seen more often in young females than males. Lymphocyte surface markers were studied by flow cytometry using the following monoclonal antibodies; OKT 3, 4, 8, DR, NK, Ia 1 and B7. No differences between lymphocyte surface markers of nonresponders and responders were noted. HLA-DR/DQ antigens were studied by the cytotoxicity test using Locus DR/DQ, Terasaki Second DR W-60 Tray and using following antibodies; DR 1, DR 2, DRW 15, DR 4, DR 5, DR 7, DR 9, DRW 10, DRW 8, DRW 12, DRW 13, DRW 6, DRW 52, DRW 53, DQW 1, DQW 6, DQW 2, DQW 3, DQW 7 and DQW 4. No significant differences between HLA-DR/DQ of nonresponders and responders were noted.

Adult↗
PubMed1989

[Impact absorbing properties of the human knee joint].

A biomechanical study has been carried out on 20 cadaveric knee joints to investigate the load absorbing mechanism of the knee. The impact load was applied using a falling weight onto the transected proximal femur and the force transmitted through the knee joint was measured at the transected distal tibia using a load transducer. The transmitted peak force applied through the joint was first measured through the intact knee (100%). After the lateral and medial menisci were cut radially the transmitted peak force increased to 113% and it reached 121% after the meniscus and all the soft tissues had been removed. Next the articular cartilage and subchondral bone were removed and this resulted in the transmitted peak force increasing to 135%. When a knee joint replacement was then carried out, the peak transmission force was found to increase to 180%. These results show that the knee joint has an impact absorbing property in each segment and comparison of the results reveals that osteoarthritic joint is capable of less shock absorption than the normal knee. The high impact force in an implanted knee suggests micro-fractures of the cancellous bone might be expected and may produce long term loosening.

Adult↗
PubMed1989

[A case of RAEB in transformation successfully treated by low-dose Ara-C treatment].

A 65-year-old male admitted to the Anjo Kosei Hospital due to pancytopenia. The findings at the time of admission were; leukocyte count 2,000/microliters, erythrocyte count 1,580,000/microliters, and platelet count 88,000/microliters. Bone marrow specimen revealed mild hypocellularity with 26% of the blast cells. He was diagnosed RAEB in transformation. Chromosome analysis showed 46, XY, -7, +8, -17, + marker in three cells and 45, XY, -7, -17, + marker in two cells out of five cells. He was treated with the low-dose Ara-C (20mg/body s.c. injections every 12 hrs) for 9 days. Twenty five days later, the blast cells in the bone marrow decreased to 4%, and the complete remission was obtained. The duration of remission is 27+ weeks. At the time of complete remission, the bone marrow cells showed the normal karyotype. In this case, the effect of low-dose Ara-C to the blast cells may have not resulted from induction of differentiation but cytocydal action.

Aged↗
PubMed1987

Treatment of acute leukemia and malignant lymphoma with (2"R)-4'-O-tetrahydropyranyladriamycin.

Eighty-four previously treated adult patients with acute leukemia and malignant lymphoma were treated with (2"R)-4'-O-tetrahydropyranyladriamycin (THP). THP (10-55 mg/m2) was administered by i.v. bolus injection daily for acute leukemia, and according to three different schedules for malignant lymphoma: daily, weekly or once every 3-4 weeks. Complete and partial remission (CR and PR) were achieved by 1 (5%) and 3 of 19 patients with acute myelogenous leukemia and by 2 (13%) and 3 of 15 patients with acute lymphoblastic leukemia, respectively. All CRs were in the groups receiving 25 mg/m2 THP daily. CR and PR were achieved by 6 (14%) and 8 of 42 patients with non-Hodgkin lymphoma (NHL) and by 4 (50%) and 2 of 8 patients with Hodgkin's disease (HD), respectively. No particular sensitivity was found among the subtypes of NHL and HD. Response (CR + PR) was noted in 10 (40%) of 25 patients treated every 3-4 weeks, in 1 (17%) of 6 treated weekly, and in 9 (47%) of 19 treated daily. The major side effects were myelosuppression and gastrointestinal toxicities. Alopecia was observed in only 10 (12%) patients. ECG abnormalities were observed in 7 (10%) patients, all of whom had previously been treated with other anthracyclines. No severe cardiotoxicity was observed.

Adult↗
PubMed1987

Inhibition by epidermal growth factor of glucocorticoid-induced epidermal alpha-type keratinization of chick embryonic skin cultured in the presence of delipidized fetal calf serum.

When a 13-day-old chick embryonic tarsometatarsal skin was cultured for 4 days in medium containing hydrocortisone (20 nM) and 5% delipidized fetal calf serum (FCS), epidermal growth factor (EGF, 100 ng/ml) decreased epidermal DNA content 42% and inhibited epidermal DNA synthesis 87%. Tonofilament bundles within the basal and intermediate cells of the EGF-treated epidermis were not as conspicuous as those in the glucocorticoid-induced keratinized epidermis, and the upper region of the EGF-treated epidermis did not form either the filament bundles or the electron-dense amorphous masses seen in the cytoplasm of the glucocorticoid-induced keratinized layer. EGF stimulated degradation of glucocorticoid-induced alpha-keratin. Furthermore, EGF caused a twofold increase in glucocorticoid-induced epidermal transglutaminase activity and in the amount of epidermal glucocorticoid receptor. In the absence of FCS, however, EGF did not inhibit steroid-induced alpha-type keratinization and did not affect either steroid-induced epidermal transglutaminase activity or amount of epidermal glucocorticoid receptor. Hence, the effect of EGF on glucocorticoid-induced epidermal transglutaminase activity was observed only in the presence of delipidized FCS and might be supported by an increase in the amount of glucocorticoid receptor.

Animals↗
PubMed1987

Impact-absorbing properties of the human knee.

A biomechanical study has been carried out on 20 cadaveric knees to investigate their load-absorbing mechanism. The impact load was applied using a weight falling onto the transected proximal femur and the force transmitted through the knee was measured at the transected distal tibia using a load transducer. The peak force transmitted increased as, sequentially, meniscus, articular cartilage and subchondral bone were damaged or removed. The most striking result was found in an implanted knee replacement where the transmitted force reached 180% of that in the intact knee. The results show that the joint has an impact-absorbing property in each segment and that in the osteoarthritic knee there is less absorption of shock than in the normal knee. The high impact force in an implanted knee suggests that microfractures of the cancellous bone might be expected and may produce loosening.

Adult↗
PubMed1987

Phase I clinical and pharmacokinetic study of orally administered N4-palmitoyl-1-beta-D-arabinofuranosylcytosine.

A phase I study of N4-palmitoyl-1-beta-D-arabinofuranosylcytosine (PLAC) was conducted in 88 patients; 36 with solid tumors and 52 with hematological malignancies, using 2 different schedules. Schedule 1 employed a single oral administration and Schedule 2, 5-day consecutive daily oral administration. In Schedule 1, the daily dose was initiated with 1 mg kg-1 which was escalated up to 24 mg kg-1 according to the modified Fibonacci's method. Side effects included nausea, vomiting and skin rashes, but myelosuppression was not seen within this dose range. In Schedule 2, the daily dose was started with 1 mg kg-1 which was escalated up to 24 mg kg-1. Major side effects were nausea, vomiting and anorexia, and mild myelosuppression was noted at 12 mg kg-1 or more. The dose-limiting toxicity was gastrointestinal toxicity, which appeared at 3.3 mg kg-1 or more and became frequent at 7 mg kg-1 or more. Pharmacokinetic study revealed that the plasma concentrations of PLAC and ara-C, obtained by the oral intake of 3.3 mg kg-1 or more of PLAC, were sufficient for these compounds to exert cytotoxic effects on various human leukemia cells in vitro. Based on these observations and plausible mechanism of action of PLAC, further clinical study should be carried out in a treatment schedule of considerably prolonged administration period with 3.3-6 mg kg-1 day-1 of PLAC.

Administration, Oral↗