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Biomedical subjects

Y Hoshi

Publications and source records attributed to Y Hoshi.

At least 181 records · Page 10Linked to original sources
PubMed1992

Establishment and characteristics of a T-cell acute lymphoblastic leukemia cell line, JK-T1, with a chromosomal translocation between 8q24 and 14q13.

A human leukemia cell line, JK-T1, was established from the bone marrow of a 10-year-old boy with T-cell acute lymphoblastic leukemia. The origin of the leukemic cell line, JK-T1, was demonstrated by its chromosomal and immunologic similarity to the patient's fresh leukemic cells. Karyotypic analysis revealed 46,XY,del(6)(q?),t(8;14)(q24;q13),der(9)t(9;?)(q34;?). In JK-T1, neither rearrangement nor amplification of the c-myc gene was observed apparently because the breakpoint of chromosome 14 was not q11 but q13. JK-T1 was independent of interleukin 2 (IL-2) because of little production of IL-2, little IL-2 receptor (CD25) on the surface, and no response to exogenous IL-2. JK-T1 had lymphocyte function associated antigen-1 (LFA-1) (CD11a, CD18) on its surface and could adhere to the hematologic stromal layer. These characteristics of JK-T1 cell line are considered to be useful not only for evaluating the role of t(8;14) but also in studying the adhesion molecules of leukemia.

Bone Marrow Cells↗
PubMed1992

Analysis of leukemic cell activity with a simple acridine orange staining method.

Leukemic cells from 28 patients with acute lymphoblastic leukemia (ALL) were supravitally stained with acridine orange (AO). Based on the staining characteristics of their cells, the patients were divided into an orange cell-dominant group (15 patients) and a green cell-dominant group (13 patients). The prognosis was better in the former than in the latter group. Orange cells which had high RNA contents were observed, while the proportion of dividing cells was high. Supravital staining with AO is a very simple and useful method for assessing the metabolic activity of leukemic cells in ALL; this method may thus be useful in assessing the prognosis of these patients.

Acridine Orange↗
PubMed1991

Effectiveness of high-dose MCNU therapy and hematopoietic stem cell autografts treatment of childhood acute leukemia/lymphoma with high-risk features.

Clinical and pharmacokinetic studies were performed regarding the toxicity of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU) with other drugs, in conjunction with a peripheral blood stem cell autograft (PBSCT), for treating 26 children with acute leukemia or lymphoma associated with high-risk features. In the early phase of the study, MCNU (300 to 500 mg/m2) was administered with cytosine arabinoside (Ara-C) (1.6 to 16 g/m2), etoposide (VP-16) (0.8 to 1.6 g/m2), cyclophosphamide (CY) (100 to 200 mg/kg), or busulfan (16 mg/kg). No acute toxicity was noticed after this high-dose therapy. The dose-limiting factor of the regimens was significant but reversible interstitial pneumonitis (IP). In a subsequent trial with an MCNU/VP-16/Ara-C/CY (MCVAC) regimen in which the dose of MCNU was reduced, the risk of IP diminished. This study is still in progress, but the clinical response has so far been encouraging. Fifteen of 26 children are alive and well in unmaintained complete remission (CR) with a median follow-up period of 11 months (range, 3 to 34 months) after transplantation. This MCNU-based regimen without total body irradiation (TBI) is especially important in children to avoid the serious sequelae of irradiation. Our results justify a broader clinical trial to evaluate the effects of the MCVAC regimen followed by PBSCT.

Adolescent↗
PubMed1991

Phosphorylation in the carboxyl-terminal domain of the capsid protein of hepatitis B virus: evaluation with a monoclonal antibody.

The capsid protein of hepatitis B virus (p21c) is made of 183 amino acids coded for by the C gene. By using p21c isolated from Dane particles (hepatitis B virus) as an immunogen, a monoclonal antibody (no. 2212) which recognized an epitope dependent on the phosphorylation of p21c was raised. The binding of no. 2212 antibody to authentic p21c was completely inhibited by a synthetic undecapeptide with a sequence of RRRSQSPRRRR, representing amino acids 165 to 175 of p21c, only when the peptide was phosphorylated. Either or both of Ser-168 and Ser-170 were phosphorylated in p21c in vivo, therefore, and contributed to the manifestation of the epitope. No. 2212 antibody bound to p21c from core particles derived from Dane particles or hepatocellular carcinoma tissues (PLC/342) propagated in nude mice but did not bind to p21c from core particles expressed in Escherichia coli or yeast cells, indicating different states of phosphorylation in them. Nonphosphorylated p21c showed a higher affinity for the viral DNA than did phosphorylated p21c. Since the serum from an asymptomatic carrier, with a high titer for antibody to hepatitis B core antigen, specifically bound to phosphorylated undecapeptide (amino acids 165 to 175), the epitope would stimulate humoral antibody responses in the human host.

Amino Acid Sequence↗
PubMed1991

An autoantibody cross-reactive to hepatitis C virus core and a host nuclear antigen.

GOR, an epitope borne by the amino acid sequence, GRRGQKAKSNPNRPL, is recognized by anti-GOR antibodies specifically found in patients with non-A, non-B hepatitis (NANBH). The epitope is not coded for by the hepatitis C virus (HCV), the presumed causative agent for NANBH, but by a single copy gene of the host. Anti-GOR antibodies, distinct from anti-HCV (c100-3) antibodies, were revealed to have dual specificities; they target both the presumed core gene product of HCV and a host component. This cross recognition is probably derived from homologous regions between the GOR epitope and a viral epitope on the core protein in HCV. It is therefore suggested that anti-GOR is an autoantibody induced by HCV infection. This may explain the autoimmune disease like aspect of NANBH pathogenesis.

Amino Acid Sequence↗
PubMed1991

[The effect of recombinant human granulocyte colony-stimulating factor (rG-CSF) on childhood neutropenias].

The clinical effect of recombinant human granulocyte colony-stimulating factor (rG-CSF), produced by Chinese hamster ovary cells, was studied in 27 patients with childhood neutropenias. The sample consisted of 8 patients with congenital neutropenia (Kostmann type), 9 with neutropenia with miscellaneous causes (5 chronic benign, 2 associated with hypogammaglobulinemia, 1 drug-induced, and 1 hypoplastic type), 3 with cyclic neutropenia, and 7 with severe aplastic anemia. The rG-CSF was given subcutaneously (or in a few cases intravenously) at a dose of 2 micrograms/kg/day for 7 days and 5 micrograms/kg/day for additional 7 to 28 days in cases with poor response. The rG-CSF was effective in 18 of 27 cases (67%). Patients with congenital neutropenia and aplastic anemia responded less frequently and poorly. The mean level of absolute neutrophil counts of 8 congenital neutropenia cases increased from 88/microliters to 2,718/microliters. That of 9 miscellaneous cases changed from 189/microliters to 7,224/microliters at a dose of 2 micrograms/kg/day. In 7 aplastic anemia cases pretreatment level of 220/microliters rose to 851/microliters, usually after increasing the dose up to 5 micrograms/kg/day. The rG-CSF was apparently effective in 3 cases of cyclic neutropenia. In any type of neutropenia, the effect was largely transient; after the discontinuation of rG-CSF, the absolute neutrophil counts tended to decrease to pretreatment levels within 1 to 2 weeks. The G-CSF was well tolerated, and only one case with mild lumbago and another with minimal elevation of transaminases were observed. We conclude that the rG-CSF can be effective for treating various types of childhood neutropenia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Treatment of acute lymphoblastic leukemia in the Tokyo Children's Cancer Study Group--preliminary results of L84-11 protocol.

The Tokyo Children's Cancer Study Group (TCCSG) has performed prospective randomized controlled studies since 1984 for childhood acute lymphoblastic leukemia (ALL). Four hundred and ninety-eight newly diagnosed patients were treated with 5 different regimens designated as S1, S2 for a standard risk group (SRG), H1 and H2 for a high risk group (HRG) and HEX for an extremely high risk group of patients. We added intermediate-dose methotrexate as early intensification therapy in the S2 and H2 groups to reduce extramedullary and medullary relapses. Event-free survival of all patients at 4 years 6 months from the start of this regimen (median follow-up period 32 months) was 67.5%. The CNS relapse rate was significantly decreased to 2.2% compared to previously reported studies and our own experience. There were some unexpected complications of the CNS such as myelopathy and/or leukoencephalopathy. For the SRG early ID-MTX seemed to be useful to improve the prognosis, but triple intrathecal injections (TIT) should be limited in number. The 24Gy cranial irradiation (CRX) was effective but possibly excessive for the HRG. As evidenced by the success of the HEX group regimen, more intensive multi-drug consolidation in the early post-remission phase might be necessary to improve further the prognosis and to make it possible to shorten the treatment periods.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Non-A, non-B hepatitis specific antibodies directed at host-derived epitope: implication for an autoimmune process.

A cDNA clone (GOR47-1) bearing an epitope with an aminoacid sequence GRRGQKAKSNPNRPL (GOR epitope) was isolated from the plasma of a laboratory chimpanzee infected with human non-A, non-B hepatitis (NANBH) agent. The epitope was not encoded by reported sequences of hepatitis C virus (HCV) but instead was coded for by a host cellular sequence. An enzyme-linked immunosorbent assay (ELISA) was developed for antibodies to the GOR epitope (anti-GOR). A patient with acute NANBH produced both IgM and IgG classes of anti-GOR in the acute phase of the illness, with concentrations of IgG class anti-GOR rising when anti-HCV became detectable. Anti-GOR was detected in serum from 59 (81%) of 73 patients with chronic NANBH, 40 (65%) of 62 with NANB liver cirrhosis, and 25 (63%) of 40 NANB patients with primary hepatocellular carcinoma, but in only less than 10% of patients with chronic liver diseases due to hepatitis B virus, alcohol, or an autoimmune disorder, and in only 2% of voluntary blood donors. Circulating HCV-RNA was detected by polymerase chain reaction (PCR) in most patients seropositive for anti-GOR but negative for anti-HCV. Detection of anti-GOR would therefore help in the diagnosis of NANBH and in reducing the occurrence of post-transfusion hepatitis.

Amino Acid Sequence↗
PubMed1990

Treatment of advanced neuroblastoma with emphasis on intensive induction chemotherapy. A report from the Study Group of Japan.

One hundred nine newly treated patients with advanced neuroblastoma were entered in this study between January 1985 and May 1989. The eligible patients included infants younger than 12 months of age with Stage IVA disease (bone cortex, distant lymph node, and/or remote organ metastases) and patients aged 12 months or older with Stage III or IV disease (IVA plus IVB with tumor crossing the mid-line and with metastases confined to bone marrow, liver, and skin). The patients first received six cyclic course of intensive chemotherapy (regimen A1), consisting of cyclophosphamide (1200 mg/m2), vincristine (1.5 mg/m2), tetrahydropyranyl adriamycin (pyrarubicin; 40 mg/m2), and cisplatin (90 mg/m2). Original tumors and the regional lymph node metastases were removed some time during these first six cycles of chemotherapy. The patients were further divided into three groups. Patients in course 1 received alternating treatment by regimen B (cyclophosphamide and ACNU) and intensified regimen A1, and those in course 2 were treated with alternating administration of regimen C (cyclophosphamide and DTIC) and intensified A1. Patients in course 3 were treated with bone marrow transplantation (BMT) preceded by high-dose preconditioning chemotherapy. Survival rates were 77% in Stage III and 54% in Stage IV at 2 years, and 70% in Stage III and 45% in Stage IV at 3 years. The major toxicities encountered were bone marrow suppression with leukocyte counts down to 100/mm3, mild cystitis, and hearing impairment. The 2-year survival rate was 78% in 21 patients who underwent BMT when complete remission was achieved. We concluded that our intensive induction chemotherapy is of significant value in increasing the rate of complete response, and in widening the indications for and achieving improved results of treatment with BMT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

[Clinical evaluation of recombinant human G-CSF in children with cancer].

Recombinant human granulocyte colony-stimulating factor (rG-CSF), produced by Chinese hamster ovary cells, was administered in 69 chemotherapy-induced neutropenic pediatric patients (pts) with malignant tumors. Each pt received two cycles of the same chemotherapy and had neutropenia with absolute neutrophil counts (ANC) less than 500/microliter in the first cycle. Initiating 72 hours after termination of chemotherapy in the second cycle, rG-CSF (2 micrograms/kg/day) was given subcutaneously or intravenously to each pt for 10 days. rG-CSF significantly increased ANC at nadir; 72 +/- 14 vs. 206 +/- 40/microliter (data in the first cycle vs. data in the second cycle, respectively), and reduced the period of neutropenia with ANC less than 500/microliter; 9.7 +/- 0.6 vs. 5.1 +/- 0.6 days, and the period for restoration to ANC greater than or equal to 1,000/microliter after initiation of chemotherapy; 25.5 +/- 0.6 vs 17.5 +/- 0.9 days. rG-CSF did not affect other components of peripheral blood. The number of days with fever greater than or equal to 38 degrees C was significantly reduced by rG-CSF treatment. Neck pain and lumbago were observed in one pt, pollakisuria in one pt, and elevation of the serum levels of LDH and uric acid in one pt, however these were mild to moderate, transient, and resolved without any specific treatment. We concluded that rG-CSF was effective in neutropenia induced by intensive chemotherapy for malignant tumors without any serious side effects.

Adolescent↗
PubMed1990

[Clinical evaluation of aztreonam for infections accompanying febrile neutropenic children with hematologic disorders and solid tumors. A cooperative study].

One hundred four children with infection accompanying hematologic disorders and solid tumors were treated with aztreonam (AZT) (120-150 mg/kg), either alone or in combination with one of the following drugs; cefmetazole (CMZ) (120-150 mg/kg), piperacillin (PIPC) (120-150 mg/kg), or amikacin (AMK) (5-10 mg/kg). The overall efficacy rate was 69.2%. Efficacy rates by regimen were as follows: AZT alone was 63.2%, AZT plus CMZ was 73.6%, AZT plus PIPC was 74.1% and AZT plus AMK was 20.0%. Efficacy rates in different types of infections were 53.2% for sepsis and suspected sepsis, 78.9% for pneumonia and respiratory tract infection, 93.1% for fever of undetermined origin and 55.6% for other infections. The efficacy rate was 71.3% in 94 patients in whom causative organisms were not identified and 50.0% in 10 patients in whom causative organisms were identified. Most of infections in which causative organisms were identified were caused by Gram-negative pathogens. The response rate among infections caused by Gram-negative bacilli was 50.0%. A combination of AZT and CMZ or PIPC was effective in 3 (100.0%) out of 3 patients in whom Escherichia coli was the causative organism. Efficacies classified according to different neutrophil counts were 59.3% for less than or equal to 100/microliters, 78.6% for 101-500/microliters and 82.4% for greater than or equal to 501/microliters. No significant adverse reactions were observed. These results indicated that combination of AZT and 2nd generation cephalosporins or penicillins were well tolerated and effective for infections complicated with accompanying hematologic disorders and solid tumors.

Adolescent↗
PubMed1989

The oxygen dependency of the redox state of heme and copper in cytochrome oxidase in vitro.

The oxidation-reduction state of cytochrome oxidase in isolated mitochondria at low oxygen concentrations was measured by the use of leghemoglobin as an oxygen indicator. P50 a + a3 varied with energy state as well as the respiratory rate. In contrast to heme a + a3, copper was slower to reduce than heme a + a3. The P50Cu of 8 x 10(-8)M in State 4 and 7.4 x 10(-8)M in State 3 was independent of both the energy state and the respiratory rate.

Aerobiosis↗
PubMed1989

[Changes in hemopoietic and immunohematologic parameters with various modes of treatment in children with congenital pure red cell aplasia].

Clinical course, response to various modes of treatment and changes in in vitro marrow culture assay were studied in two patients with congenital pure red cell aplasia (Diamond-Blackfan syndrome) who were followed up for a long period. Patient 1, whose diagnosis was made at 8 months of age, was refractory to prednisolone and anabolic steroid. Bolus methylprednisolone, cyclophosphamide, ALG and high-dose intravenous immunoglobulin were given but none were effective. Particularly, hemolysis occurred during high-dose intravenous immunoglobulin therapy. In colony assay, CFU-E and BFU-E were found to be extremely decreased throughout the course, and colony formation was not corrected by adding prednisolone to the assay system. However, coculture of normal bone marrow cells with the patient's peripheral mononuclear cells resulted in reduction in CFU-E and BFU-E colonies. It was interesting that CFU-E and BFU-E were normalized after high-dose intravenous immunoglobulin therapy. Patient 2, whose diagnosis was made at 3 months of age, responded to prednisolone treatment at the early phase but became dependent on it thereafter. Thus, bolus methylprednisolone and high-dose intravenous immunoglobulin were given, without effect. Unlike patient 1, bolus methylprednisolone therapy induced reticulocytosis once. During high-dose intravenous immunoglobulin therapy, hemolysis was also observed. In colony assay, CFU-E and BFU-E decreased during the course, but were not corrected by adding prednisolone to the assay system. These findings suggest that in vitro colony assay is not always correlated with response to various therapies, and congenital pure red cell aplasia seems to be a heterogeneous disorder. The indication for high-dose intravenous immunoglobulin therapy for this disorder is limited because of hemolysis complicating the therapy.

Colony-Forming Units Assay↗