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Biomedical subjects

H Nishihira

Publications and source records attributed to H Nishihira.

At least 37 records · Page 2Linked to original sources
PubMed1997

Microscopic intraosseous extension of osteosarcoma: assessment on dynamic contrast-enhanced MRI.

OBJECTIVE: This study investigated whether dynamic MRI could determine microscopic intraosseous invasion in osteosarcoma. PATIENTS: Six patients with osteosarcoma who underwent total resection of the tumor after chemotherapy were studied. DESIGN: The steepest slope value of the time-intensity curve was calculated on the basis of the first-pass method on dynamic MRI performed after chemotherapy. Slope value modified log = [100.(SIb - SIa)/(Tb - Ta)/SIa], where SIa and SIb represent the signal intensity at time points Ta and Tb when the steepest slope started and ended, respectively. The slope value was correlated with the histological findings of the surgical specimens. The findings on conventional MRI were also reviewed. RESULTS AND CONCLUSIONS: In five of six patients microscopic tumor invasion ranging from 1 to 3.5 cm in depth was pathologically proven. The slope value within the microscopic invasion (-0.052 +/- 0.267) was significantly greater than that of tumour-free marrow (-0.609 +/- 0.220) and less than that in areas showing macroscopic tumor invasion (0.595 +/- 0.483) (P < 0.001). Histological examination disclosed the dilatation of small vessels within the macroscopic and microscopic invasion. Findings on conventional MRI varied among patients; microscopic invasion was not detected in one, underestimated in two, and overestimated in two. It is concluded that calculation of the slope value on dynamic MRI can discriminate regions of microscopic invasion from tumor-free marrow in patients with osteosarcoma after chemotherapy.

Adolescent↗
PubMed1997

Aggressive natural killer (NK) cell lymphoma: report of a pediatric case and review of the literature.

We report a rare pediatric case of aggressive natural killer (NK) cell lymphoma, characterized by acute onset hepatosplenomegaly and respiratory distress, and infiltration by large granular lymphocytes with the phenotype of CD3-CD16-CD56+. The patient has remained in complete remission after short-pulse intensive chemotherapy, and myeloablative therapy followed by allogeneic bone marrow transplantation. We compare our case with 7 other children with NK cell leukemia reported from other institutions.

Adolescent↗
PubMed1997

[Present state of cord-blood stem cell transplantation].

Allogeneic bone marrow transplantation (BMT) can cure some hematologic and solid malignancies, but its success depends on the prompt identification of a suitable donor and the avoidance of severe graft-versus-host (GVH) disease. Transplantation using hematopoietic stem cells from umbilical cord blood may overcome these problems. Over the past several years, cord blood transplantation (CBST) from siblings and unrelated donors has been performed in more than 300 patients. The probability of event-free survival was almost similar to that for BMT. This review described the recent status of CBST in USA, Europe and Japan, and the outlook for CBST.

Child, Preschool↗
PubMed1996

A nude mouse Wilms' tumor line (KCMC-WT-1) derived from an aniridia patient with monoalleleic partial deletion of chromosome 11p.

BACKGROUND: A candidate tumor suppressor gene, WT-1, is believed to have an important role in the pathogenesis of Wilms' tumor, especially that occurring in patients with congenital aniridia. METHODS: To obtain a stable tumor line to work with, Wilms' tumor tissue was serially transplanted in athymic nude mice. Biopsied Wilms' tumor tissue, derived from an aniridia patient, was transplanted subcutaneously to an athymic nude mouse, and then transplanted serially. Histopathologic and molecular biologic studies were performed on the xenotransplants. RESULTS: The aniridia patient showed partial deletion in one short arm of chromosome 11, which bears the WT-1 gene. The tumor was successfully transplanted in the nude mouse. Although the tumor contained blastemic, organoid, and stromal histologic elements, the organoid element began to decrease after more than 20 passages. Cytogenetic analysis revealed an additional abbreviation of one long arm of chromosome 6. Dot blot analysis showed that the copy number of WT-1 gene was decreased to half the amount in the tumor, in spite of the WT-1 transcript with normal size detected by Northern blotting. CONCLUSIONS: The tumor is expected to bear one WT-1 gene with minute abnormalities as well as one congenitally deleted gene. This tumor line is useful when examining the effect caused by introduction of WT-1 gene to Wilms' tumor in vivo.

Alleles↗
PubMed1996

Measurement of endogenous plasma granulocyte colony-stimulating factor in patients with acquired aplastic anemia by a sensitive chemiluminescent immunoassay.

Endogenous plasma granulocyte colony-stimulating factor (G-CSF) concentrations were serially measured in 68 patients with acquired aplastic anemia (AA). A very sensitive chemiluminescent immunoassay (CLEIA) was used to measure the plasma G-CSF concentration. The minimum detection limit of this assay (0.5 pg/mL) was sufficient for the determination of G-CSF concentrations in patients and normal subjects. The plasma G-CSF concentrations were significantly higher in 51 AA patients without signs of infection as compared with healthy control subjects. In AA patients with signs of infection, the G-CSF concentrations appeared to increase during the acute phase. There was a significant negative correlation between plasma G-CSF concentrations and absolute neutrophil counts (ANC) in AA patients without signs of infection. Although a decrease in the plasma G-CSF concentration was observed in all patients who achieved self-sustaining hematopoiesis following bone marrow transplantation (BMT) or immunosuppressive (IS) therapy, it was lower in patients undergoing BMT as compared with those receiving IS therapy for any given degree of neutropenia. Plasma G-CSF concentrations were higher in patients responding to IS therapy than in nonresponders. This study demonstrated the negative feedback regulation of G-CSF that plasma G-CSF concentrations may be useful in predicting the clinical response to IS therapy.

Adolescent↗
PubMed1996

Fusion of an ETS-family gene, EIAF, to EWS by t(17;22)(q12;q12) chromosome translocation in an undifferentiated sarcoma of infancy.

EIAF is a newly isolated ETS-family gene that is located on 17q21 and codes for the adenovirus EIA enhancer-binding protein. In our chromosome analysis of 18 of the Ewing family of tumors and undifferentiated sarcomas, we found t(17;22)(q12;q12) in an MIC2 antigen-positive undifferentiated sarcoma of infancy. On Southern blot analysis, EWS and EIAF cDNA probes hybridized to the same rearranged band, indicating that an EWS-EIAF fusion gene was formed in the tumor. Further Southern blot analysis using four EIAF cDNA probes of different sizes showed that the breakpoint lies in the region upstream to the ETS domain of the EIAF gene. EIAF may be the fourth ETS-family gene to be identified forming a fusion gene with EWS. We assume that the RNA binding domain of EWS may have been replaced by the DNA binding domain of EIAF in the EWS-EIAF fusion protein as in other fusion proteins previously characterized in Ewing sarcoma and other types of sarcomas.

Adenovirus E1A Proteins↗
PubMed1996

Successful engraftment of sibling cord-blood stem cell transplantation in a child with acute promyelocytic leukemia.

Cord blood stem cell transplantation (CBSCT) was performed on a patient with acute promyelocytic leukemia. The patient was a boy 3 years and 8 months old, who had shown complete remission following treatment with intensive chemotherapy. However, after the final course of consolidation chemotherapy, chromosome analysis of his bone marrow aspirates revealed 46XY, t(15,17)(q22;q21), and a PML-RAR alpha fusion gene was detected by the reverse transcriptase-polymerase chain reaction test. All-trans retinoic acid diminished the chromosomal abnormality, but the PML-RAR alpha fusion gene remained. The patient was then treated with CBSCT from an HLA-matched sibling donor. The number of nucleated cells in the cord blood was 2.2 x 10(7)/kg of body weight, and that of granulocyte-macrophage colony-forming units 0.6 x 10(4)/kg. Methotrexate was given, on days 3 and 6, as prophylaxis against graft-versus-host disease (GVHD). The neutrophil count rose to above 500/microliters on day 22. The platelet count exceeded 50,000/microliters on day 48. Platelet transfusions were given 12 times after CBSCT, the last one on day 36. Grade I acute GVHD was treated with steroids. The patient was well and discharged on day 103, without symptoms or laboratory data suggestive of relapse. Following this experience we instituted a project of the Kanagawa Cord Blood Bank, which is scheduled for expansion nationwide.

Adult↗
PubMed1996

Reference intervals for serum granulocyte colony-stimulating factor levels in children.

OBJECTIVE: To determine age-adjusted reference intervals for children for serum granulocyte colony-stimulating factor (G-CSF) levels. DESIGN: We determined the serum G-CSF levels of 168 disease-free children who were term neonates to 15 years of age with a highly sensitive chemiluminescent enzyme immunoassay. RESULTS: The lowest values (5 ng/L) exceeded the detectable limit (1 ng/L) of this assay technique. The G-CSF levels were highest on the day of birth (mean +/- SD 147 +/- 146 ng/L); thereafter values decreased to 46 +/- 33 ng/L in the early neonatal period and to 23 +/- 10 ng/L in the late neonatal period. The G-CSF levels both on the day of birth and in the early neonatal period were significantly higher than in all older age groups. No significant differences were found among any of the age groups after 4 weeks of age. The G-CSF values were correlated with both blood leukocyte counts (r = 0.496, p < 0.0001) and neutrophil counts (r = 0.547, p < 0.0001). In children older than 4 weeks of age (n = 128), the 95% reference interval for G-CSF values was 5 to 42 ng/L. CONCLUSIONS: Our study in disease-free children revealed that change in serum G-CSF levels are age dependent and are correlated with neutrophil counts. Determination of reference intervals for the neonatal period requires further study.

Adolescent↗
PubMed1996

Growth of macroscopic human megakaryocyte colonies from cord blood in culture with recombinant human thrombopoietin (c-mpl ligand) and the effects of gestational age on frequency of colonies.

We investigated the effects of recombinant human thrombopoietin (rhTPO) on the growth of megakaryocytic (MK) colony derived MK progenitors from human cord blood (CB) in vitro and the effects of gestational age on the number of MK colonies. The results demonstrated that rhTPO alone supports the growth of MK colonies and induces not only proliferation but also differentiation of MK progenitors. CB shows a high frequency of MK colonies; most of which are very large and equivalent to high proliferative potential colony-forming unit-megakaryocyte. The colonies could be macroscopically observed as white spots in the culture dish. Preterm neonates showed greater numbers of MK progenitors than term neonates and there was an inverse correlation between gestational age and concentration of MK progenitors of CB. The effects of gestational age was an important factor on the proliferative capacity of MK progenitors and on the response to rhTPO.

Cell Culture Techniques↗
PubMed1996

[Detection of early cardiac dysfunction in patients with transfusion-dependent aplastic anemia and chronic iron overload in childhood. Stress-velocity relation as a sensitive index by echocardiography].

In order to detect early-stage left ventricular dysfunction, we examined a load-independent index, that is, the stress-velocity relation, by echocardiography in 13 patients with aplastic anemia including pure red cell anemia. Even when left ventricular contractility and pump function were within the normal range, its afterload had a tendency to increase in transfusion-dependent patients. The patients who had impairment of cardiac pump function died of congestive heart failure within one year after abnormal findings in stress-velocity relation were detected. Therefore, the stress-velocity relation is a sensitive, useful and noninvasive index for detecting asymptomatic myocardial dysfunction in patients with transfusion-dependency and chronic iron overload. It is necessary for these patients to undergo examinations of echocardiography at regular intervals. In case of abnormally in the stress-velocity relation, treatment for afterload mismatch and more effective chelation should be recommended to reduce the burden on the heart. Thereby, the heart is kept in better condition and the prognosis of these patients will be improved.

Adolescent↗
PubMed1995

Treatment combined with bone marrow transplantation for advanced neuroblastoma: an analysis of patients who were pretreated intensively with the protocol of the Study Group of Japan.

One hundred and ten patients with advanced neuroblastoma were treated with the protocol of the Study Group of Japan between January 1985 and March 1991. Patients received six cyclic courses of regimen A1, consisting of cyclophosphamide (1,200 mg/m2), vincristine (1.5 mg/m2), tetrahydropyranyl adriamycin (40 mg/m2), and cisplatin (90 mg/m2). Primary tumors and regional lymph node metastases were removed some time during the first six cycles of regimen A1. After six cycles of A1, the patients were divided into three groups. Patients in group 1 received alternating treatment with regimen B (cyclophosphamide and ACNU) and intensified A1, and those in group 2 were treated with alternating administration of regimen C (cyclophosphamide and DTIC) and intensified A1. Patients in group 3 were treated with supralethal therapy and bone marrow transplantation (BMT). Event-free survival rates at five years were 38.8% in the chemotherapy group (groups 1 and 2) and 50.0% in the transplant group (group 3). Because of the study design that was not in truly randomized fashion and because of the small number of patients in each risk group, it is indicated, though not concluded, that the transplant group had a better prognosis than the chemotherapy group in the cases with stage III disease or with amplified N-myc oncogene, based on the statistical calculations. Differences in survival rates for patients who underwent BMT when complete remission (CR) was achieved and for those who achieved CR but who did not undergo marrow transplant were statistically insignificant. BMT-related death occurred in 3 of 31 cases (9.7%) undergoing marrow transplant, and the causes of the death included hemorrhagic pneumonia, myocardial disturbance and hemorrhagic uremia.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

What is the benefit of aggressive chemotherapy for advanced neuroblastoma with N-myc amplification? A report from the Japanese Study Group for the Treatment of Advanced Neuroblastoma.

In 1985, a nationwide single protocol (cyclophosphamide, vincristine, tetrahydropyranyl Adriamycin, and cisplatin) for the treatment of advanced neuroblastoma was begun in Japan and was found to significantly increase the 3-year survival rate--to 70% for stage III, and to 45% for stage IV. In this study, the authors investigated the efficacy of this protocol for advanced neuroblastoma with or without N-myc amplification. In 159 of the 233 patients with advanced neuroblastoma treated with this protocol (between January 1985 and March 1993), genomic amplification of N-myc was determined. These 159 patients were divided into two groups according to the number of N-myc copies, ie, those with fewer than 10 copies (105 patients) and those with 10 or more copies (54 patients). The survival curves for the two groups were significantly different. The 5-year survival rate for patients with 10 or more copies was 43.9%; this is surprisingly high in comparison to results of previous studies in which no survivors were expected in cases of advanced neuroblastoma with highly amplified N-myc. Persistent bone marrow suppression was common, but there were no deaths attributable to drug side effects. Five patients with fewer than copies of N-myc amplification died more than 3 years after initial treatment. Three of the five had tumors with an unfavorable Shimada classification, and two had diploid nuclear DNA content. The authors conclude that the protocol resulted in dramatic improvement in the patients with advanced neuroblastoma, even with high N-myc amplification.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Immunocytochemical detection of bone marrow-invasive neuroblastoma cells.

We evaluated the utility of an immunocytochemical technique employing the commercially available anti-CD56 monoclonal antibody, NKH 1. The utility and sensitivity of this technique in the detection of invasive neuroblastoma (NB) cells in the bone marrow were compared with those of Wright-Giemsa staining. The correlation coefficient for the percent NB cells detected using Wright-Giemsa staining with the percent NKH 1 immunoreactive cells was 0.78. In the analysis of specificity, this monoclonal antibody showed slight cross-reactivity with normal bone marrow cells, including macrophages, lymphocytes and osteoblasts. In the evaluation of the sensitivity of the NKH 1 immunocytochemical technique, SK-N-DZ and SK-N-SH NB cell lines were added to morphologically normal bone marrow mononuclear cells from patients without NB to the final NB cell line at concentrations of 2%, 1% and 0.1%. NB cells at the final concentration of 0.1% could be detected by the immunocytochemical technique. We conclude that the NKH 1 immunocytochemical staining technique is useful in the detection of metastatic NB cells in bone marrow.

Antibodies, Monoclonal↗
PubMed1994

Gonadal mixed germ cell tumor combined with a large hemangiomatous lesion in a patient with Turner's syndrome and 45,X/46,X, +mar karyotype.

In this report, we describe bilateral gonadal tumors with characteristic histopathological findings in a patient with Turner's syndrome who had 45,X/46,X, +mar mosaicism. The left gonad contained a gonadoblastoma and a remnant of streak gonad. The right gonad was entirely replaced by a 15x11x7-cm solid and cystic tumor, which was revealed to be a combination of a mixed germ cell tumor and a cavernous hemangiomatous lesion. The latter occupied approximately half of the entire tumor volume, and there was an incomplete boundary between it and the mixed germ cell tumor lesion. To our knowledge, this is the first reported case of Turner's syndrome with a combination of a mixed germ cell tumor and a hemangiomatous lesion in the gonad.

Adolescent↗
PubMed1993

[Clinical study of recombinant human granulocyte-colony stimulating factor (KW-2228) in pediatric field. 1. Effectiveness on neutropenia by various causes and safety].

The effect of KW-2228, a derivative of recombinant human granulocyte colony stimulating factor, on neutropenia in children was studied in 23 cases of aplastic anemia, 13 cases of chronic benign neutropenia, 6 cases of congenital neutropenia (Kostmann type), 2 cases of cyclic neutropenia, 2 cases associated with glycogenosis type Ib and 1 cases associated with immune deficiency. KW-2228 was administered at 1-8 micrograms/kg subcutaneously and at 2-16 micrograms/kg intravenously. As a principle, the administration was started at low doses and continued for 7-28 days increasing the doses in the cases who didn't respond to the treatment well. The response rate of all the cases by the physicians in charge was 81. 8% (36/44). The mean absolute neutrophil count was increased from 304 to 1,300/microliters in aplastic anemia, from 204 to 3,027/microliters in chronic benign type, from 125 to 2,193/microliters in Kostmann type, and from 360 to 2,007 microliters in others. KW-2228 did not induce any noteworthy serious side effects. These results indicated that KW-2228 is a useful drug to treat neutropenia in children.

Adolescent↗
PubMed1993

[Clinical study of recombinant human granulocyte-colony stimulating factor (KW-2228) in pediatric field. 2. Effectiveness on neutropenia associated with administration of anticancer agent and safety].

The effect of KW-2228, a derivative of recombinant human granulocyte colony stimulating factor, on neutropenia associated with chemotherapy was studied in pediatric patients with malignant tumor. To patients repeatedly treated with the same chemotherapy, KW-2228 was administered subcutaneously at 1 microgram/kg or intravenously at 2 micrograms/kg once a day in the 2nd course of the chemotherapy. During the administration term of KW-2228, the nadir of neutrophils went up, and the duration of neutrophil count under 500/microliters as well as the interval for recovery of the count to 500/microliters were remarkably shortened, compared with those during the observation term. Further, the duration of fever in patients and the administration days of antibacterial agent were also reduced. The effective rate judged by attending doctors was as high as 78.9%, consisting of 83.3% in 42 cases of subcutaneous administration and 73.5% in 34 cases of intravenous administration. Side effects such as slight skeletal pain and slight fever in one case each (2.3% in total) were improved without treatment. It is concluded that KW-2228 may be a useful drug for treatment of neutropenia associated with chemotherapy in pediatric patients with malignant tumor.

Adolescent↗