Development of a small scintillation detector with an optical fiber for fast neutrons.

To investigate the characteristics of a reactor and a neutron generator, a small scintillation detector with an optical fiber with ThO(2) has been developed to measure fast neutrons. However, experimental facilities where (232)Th can be used are limited by regulations, and S/N ratio is low because the background counts of this detector are increase by alpha decay of (232)Th. The purpose of this study is to develop a new optical fiber detector for measuring fast neutrons that does not use nuclear material such as (232)Th. From the measured and calculated results, the new optical fiber detector which uses ZnS(Ag) as a converter material together with a scintillator have the highest detection efficiency among several developed detectors. It is applied for the measurement of reaction rates generated from fast neutrons; furthermore, the absolute detection efficiency of this detector was obtained experimentally.

M1 gamma strength for zirconium nuclei in the photoneutron channel.

Photoneutron cross sections were measured for 91Zr, 92Zr, and 94Zr near the neutron separation energy with quasimonochromatic gamma rays. The data exhibit some extra components around the neutron threshold. A coherent analysis of the photoneutron data for 92Zr together with the neutron capture on 91Zr based on the microscopic Hartree-Fock-Bogoliubov plus quasiparticle random-phase approximation model for the E1 strength has revealed the presence of an M1 resonance at 9 MeV. The microscopic approach systematically shows the same M1 strength in the photoneutron cross section for 91Zr and 94Zr. The total M1 strength is about 75% larger than the strength predicted by the systematics, being qualitatively consistent with the giant M1 resonance observed in the inelastic proton scattering.

Characterisation of kilo electron volt neutron fluence standard with the 45Sc(p,n)45Ti reaction at NMIJ.

We are developing a national standard of a monoenergetic kilo electron volt neutron field with the (45)Sc(p,n)(45)Ti resonance reaction. A wide resonance yields 27.4 keV neutrons at 0 degrees with respect to the proton beam. The proton energy was precisely determined in the measurement of the relative neutron yield as a function of the proton energy from the threshold energy to 2.942 MeV. Absolute measurement of the monoenergetic neutron fluence was performed using a (3)He proportional counter. Relative measurement was also carried out using a Bonner sphere calibrated at our 144 keV standard neutron field. Calibration factors were obtained between the count of a neutron monitor and the neutron fluence. A silicon-surface barrier detector with a (6)LiF foil converter was also being developed for the neutron fluence measurement. Successful results were obtained in the tests in the 144 keV standard neutron field.

Development of the fast neutron standard using a Be({alpha},n) reaction at the National Metrology Institute of Japan.

This paper describes the 8-MeV neutron field where the neutrons are generated in the (9)Be(alpha,n)(12)C reaction by bombardment of a beryllium target with a 2.4-MeV (4)He(+) beam from a Van de Graaff accelerator. The neutron field is being prepared for a new national standard on neutron fluence in Japan. Absolute measurement of the neutron fluence was taken using a proton recoil neutron detector, consisting of a silicon surface barrier detector with a polyethylene radiator. Neutron spectra were measured using a newly developed recoil proton spectrometer and a liquid organic scintillation detector. The gamma rays existing in the field were also characterised using a liquid organic scintillation detector. The ambient dose equivalents of the gamma rays were estimated to be <100 microSv at the neutron fluence of 10(7) neutrons cm(-2).

Characterization of gamma rays existing in the NMIJ standard neutron field.

Our laboratory provides national standards on fast neutron fluence. Neutron fields are always accompanied by gamma rays produced in neutron sources and surroundings. We have characterised these gamma rays in the 5.0 MeV standard neutron field. Gamma ray measurement was performed using an NE213 liquid scintillator. Pulse shape discrimination was incorporated to separate the events induced by gamma rays from those by neutrons. The measured gamma ray spectra were unfolded with the HEPRO program package to obtain the spectral fluences using the response matrix prepared with the EGS4 code. Corrections were made for the gamma rays produced by neutrons in the detector assembly using the MCNP4C code. The effective dose equivalents were estimated to be of the order of 25 microSv at the neutron fluence of 10(7) neutrons cm(-2).

Development of a fast neutron spectrometer composed of silicon-SSD and position-sensitive proportional counters.

A new fast neutron spectrometer has been developed. The spectrometer is composed of a silicon surface barrier detector and three position-sensitive proportional counters with methane gas working as counting gas and a radiator. A collimated incident neutron interacts with a hydrogen atom in the methane gas to generate a recoil proton. The position information on the path of the recoil proton obtained from the three position-sensitive proportional counters gives the recoil angle. In the meanwhile, the energy of the recoil protons is measured with the three proportional counters and the silicon surface barrier detector. The characteristics of the spectrometer were evaluated with a monoenergetic neutron beam. The best energy resolution was 1.8% for 5.0 MeV neutrons.

Development of a tiny neutron probe with an optical fibre for BNCT.

We have developed a tiny neutron probe detector as a monitor of a thermal neutron flux for boron neutron capture therapy. The detector consists of an optical fibre and a small neutron probe. We have used a film-like ZnS(Ag) scintillator and a 6LiF neutron converter for the neutron probe. In order to improve the gamma-neutron discrimination ability, vacuum evaporation of 6LiF onto the ZnS(Ag) film has been done. In order to improve the neutron detection efficiency, we made use of a wavelength-shifting fibre as the probe material. The characteristics of the above two types of fibre probe detector have been evaluated experimentally.

[Twenty-one cases of Sebastian platelet syndrome].

We report a Japanese family with Sebastian platelet syndrome. Twenty-one thrombocytopenic patients exhibited giant platelets and inclusion bodies in their granulocytes. They were thought to be related because they bore the same surname and lived within a localized area. None of them had additional clinical findings peculiar to Fechtner syndrome. Ultrastructural studies of the granulocytes were performed on four patients. The inclusion bodies in the granulocytes were different from those found in May-Hegglin anomaly, and consisted of ribosome clusters and rough endoplasmic reticula.

[Acute myelocytic leukemia with ins(21;8)(q22;q13q22) presenting with AML1/MTG8 chimeric mRNA].

We report a case of acute myelocytic leukemia (AML) showing a chromosomal abnormality, ins(21;8), with AML1/MTG8 chimeric mRNA. The patient, a 73-year-old woman, was admitted to our hospital because of AML relapse. Bone marrow aspiration showed 44% blasts and ins(21;8)(q12;q13q22) by cytogenetic study. Moreover, the size of chimeric AML1/MTG8 mRNA detected by RT-PCR in this case was shorter than that of previously reported. The patient was diagnosed as having relapse of AML (M2), but achieved complete remission with DCP therapy. Four months later, extramedullary relapse occurred, and this was followed five months later by bone marrow relapse. However, the patient again achieved complete remission. Most cases of AML1/MTG8 fusion gene are caused by t(8;21), and only very rarely by ins(21;8). In this case, the AML1/MTG8 fusion gene is thought to have been involved in the onset of leukemia.

[Treatment outcome in elderly patients with aggressive non-Hodgkin's lymphoma].

Seventy-one patients aged 61-84 years with previously untreated aggressive non-Hodgkin's lymphoma were treated with a doxorubicin-containing regimen and evaluated retrospectively. The patients comprised 49 men and 22 women with a median age of 68 years. The median observation period was 544 days. Histological examination revealed 17 cases of diffuse small cleaved, 11 cases of diffuse mixed, 40 cases of diffuse large, and 3 cases of immunoblastic lymphoma, classified according to the International Working Formulation. When the patients were divided according to the age-adjusted international index, group A (61-64 years; n = 21) comprised 5 low (L)-, 4 low-intermediate (LI)-, 7 high-intermediate (HI)-, and 5 high (H)-risk patients. The corresponding numbers in group B (> or = 65 years; n = 50) were 14, 12, 16, and 8, respectively. The overall three-year survival rate was 50%, being 78% in group A and 36% in group B (P = 0.02), and 77% for L + LI patients and 34% for HI + H patients (P = 0.003). The respective three-year survival rates for L + LI and HI + H patients were 100% and 67% in group A, and 68% and 16% in group B. HI + H patients in group B showed shorter survival than L + LI patients in group B (P = 0.002) and HI + H patients in group A (P = 0.03). The cause of death in most group B HI + H patients was lymphoma, although the dose intensity of doxorubicin, cyclophosphamide and vincristine did not differ significantly from that in the other groups. Thus, HI + H patients aged 65 and over had an essentially poor prognosis.

Predictive factors for central nervous system involvement in non-Hodgkin's lymphoma: significance of very high serum LDH concentrations.

Factors predictive for central nervous system (CNS) involvement at presentation were investigated in 152 patients with non-Hodgkin's lymphoma (NHL) except for lymphoblastic cell lymphoma and small noncleaved cell lymphoma. Twelve patients developed CNS involvement during their disease course. The incidence was 7.9% of all the patients studied and 17.0% of the patients with serum LDH concentration > or = two times the upper limit of normal (2N). By univariate analysis, stage IV disease (P = .023), a serum LDH concentration > or = 2 N (P = .009), and bone marrow involvement (P = .016) were risk factors for CNS involvement. Multivariate logistic regression analysis identified a serum LDH concentration > or = 2 N (P = .032) as an independent predictor for CNS involvement. All 12 patients who developed CNS involvement were among the 126 patients with diffuse lymphoma, whereas none of the 17 patients with follicular lymphoma developed CNS involvement, although the difference was not statistically significant. The median survival of the patients with CNS involvement was only 4.5 months. We conclude that a serum LDH concentration > or = 2N at presentation is a significant predictive factor for CNS involvement for NHL patients without lymphoblastic lymphoma and small noncleaved cell lymphoma. Therefore, we would suggest that CNS prophylaxis should be considered for patients with a serum LDH concentration > or = 2N at presentation and diffuse lymphoma once a complete remission is achieved.

[CD16+ CD56- indolent, NK cell-lineage granular lymphocyte proliferative disorder with autoimmune hemolytic anemia].

A 64-year-old man was given a diagnosis of CD16+ CD56- natural killer cell-lineage granular lymphocyte proliferative disorder (NK-GLPD) with Coombs-negative autoimmune hemolytic anemia (AIHA). Two courses of 1,000 mg intravenous methylprednisolone for 3 days were transiently effective for both AIHA and NK-GLPD. On the recurrence of AIHA, NK-GLPD also re-appeared. The same treatment was effective in controlling both diseases again. This was a rare case of NK-GLPD combined with autoimmune disease.

Chronic myelomonocytic leukemia with t(1;3)(p36;q21) and a synchronous gastric cancer.

The translocation t(1;3)(p36;q21) has been reported previously in patients with the myelodysplastic syndrome and with acute nonlymphocytic leukemia. It has been reported in only 5 cases of chronic myelomonocytic leukemia and t(1;3)(p36;q21). We observed a case of chronic myelomonocytic leukemia with t(1;3)(p36;q21) complicated by a gastric cancer at the time of diagnosis.

Strong inverse correlation between serum TPO level and platelet count in essential thrombocythemia.

Serum thrombopoietin (TPO) levels in 50 essential thrombocythemia (ET) patients were measured using a highly sensitive sandwich ELISA. In nine cases, TPO levels were measured at two points with different platelet counts. ET patients showed significantly higher serum TPO levels (n = 59, 2.70 +/- 2.74 fmol/mL, P < 0.0001) than those of normal individuals (n = 29, 0.83 +/- 0.36 fmol/mL). Twenty-three previously untreated ET patients also showed significantly higher serum TPO levels (1.33 +/- 0.75 fmol/mL, P = 0.0066) than normal individuals. Extremely high serum TPO levels (5.46 +/- 3.68 fmol/mL) were observed in ET patients with normal platelet counts. Furthermore, a strong inverse correlation was found between serum TPO levels and platelet counts in ET patients (R = -0.729, P < 0. 0001). This inverse correlation also held for each of nine cases with two-point TPO measurements. In the clinical course of ET, megakaryocyte mass may parallel the platelet mass before and after chemotherapy. Although it is unknown whether overproduction of TPO exists or not in ET, total platelet and megakaryocyte mass, i.e., the total number of c-Mpl, may play a role to regulate serum TPO levels.

Acute minimally differentiated myeloid leukemia (M0) with inv(3)(q21q26).

We describe a 55-year-old Japanese man with acute minimally differentiated myeloid leukemia (M0) with an inversion in the long arm of chromosome 3, i.e., inv(3)(q21q26). Patients with this chromosomal abnormality usually show normal or elevated platelet counts. However, our case had a low platelet count with megakaryocytic dysplasia at diagnosis. Furthermore, the 3q21q26 aberration is generally detected in patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome. To the best of our knowledge, it has also been reported in two cases of AML-M0 with 3q21q26 and this is the third case of AML-M0 with 3q21q26. Thus it is suggested that there is some relationship between this type of karyotype abnormality and leukemogenesis and/or thrombopoiesis.

[p53 tumor suppressor gene mutation and prognosis in 105 cases of bladder cancer--the relationship between mutation of the p53 gene with clinicopathological features and smoking].

PURPOSE: Alterations of the p53 tumor suppressor gene are the most common genetic change detected in human cancers. The incidence of p53 gene mutation in bladder tumor patients were studied and were compared with clinicopathological findings, smoking history and prognosis. MATERIALS AND METHODS: Polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) was used for analysis from exon 4 to 9 of p53 gene in 105 cases of primary bladder tumors. RESULT: p53 matations were detected in 38 or 105 patients (36.2%). Kaplan-Meier Survival curves fo groups wit or without p53 gene mutation show a statistically significant difference (p = 0.0098). The mutation of p53 gene in stages pT 1 pT 1. pT 2, pT 3, pT 4 was found in 2 of 12 (16.7%), 8 of 32 (25.0%), 10 of 25 (40.0%), 12 of 20 (60.0%), 6 of 16 (37.5%) and in grades I, II, III, was noted in 1 of 17 (5.9%), 16 of 49 (32.7%), 21 of 39 (53.8%) cases, respectively. Significant differences were found for groups with grade I and grade II-III (p = 0.0045) cancers and in cases of superficial (stage pTa-1) and muscle-invasive (pT 2-4) tumors (p = 0.0148). However, mutation of p53 was not related to either age or sex in 105 patients. Recurrence rates in stage pTa-1 superficial tumor group with or without p53 mutation showed a statistically significant difference (p = 0.0419). No statistically significant difference was noted between p53 mutation and habitual smoking as well as durations of smoking. CONCLUSIONS: p53 mutations occur more commonly in higher grades and later stages of bladder tumors. Our results suggest that the prognostic factor is linked to not only histological findings but also to the presence of p53 mutation. The mutations of the p53 gene may be involved in the late events of tumorigenesis and might be used as good molecular markers for prognosis in bladder tumor.

Residual leukemic cell counts in the bone marrow at the end point of intensive induction therapy may be a prognostic factor for acute myeloblastic leukemia in adults.

Between January 1990 and May 1994, 59 previously untreated adult patients with acute myeloblastic leukemia (AML) were treated with a combination of behenoyl-cytosine-arabinoside (BHAC), daunorubicin (DNR), 6-mercaptopurine (6-MP) and prednisolone (PSL). Forty one patients (69.5%) achieved complete remission (CR). The Kaplan-Meier analysis revealed an actuarial probability for remaining in remission of 36% in patients who achieved remission and a survival of 29% in all patients at 5 years. A favorable factor relative to achieving CR was performance status (P=0.04). In addition the presence of 300 cells/microl or less of residual leukemic cell counts in the bone marrow at the end point of induction therapy tended to favor remission (P=0.06) using the multivariate analysis with a multiple logistic regression model. In addition the residual leukemic cells counts of less than 300/microl in the bone marrow at the end point of induction therapy was the most significant factor for durable remission (P=0.05) by the Cox's proportional hazard model. We concluded that residual leukemic cells counts in the bone marrow at the end point of intensive induction therapy is a valuable prognostic factor for adults receiving response-oriented individualized induction therapy for AML.

Diagnostic value of hemostatic parameters in bone marrow transplant-associated thrombotic microangiopathy.

We investigated hemostatic parameters in a prospective study of 16 patients who received bone marrow transplants (BMT). We found a significant rise in the levels of fibrinogen, plasmin-alpha2 antiplasmin inhibitor complex, tissue-plasminogen activator.plasminogen activator inhibitor complex (t-PA.PAI), von Willebrand factor antigen, and thrombomodulin on day 14 after transplant compared with values before transplant. Protein C and thrombin-antithrombin III levels did not change significantly. No significant changes in prothrombin time ratio, activated partial thromboplastin time, or protein S were detected. Patients who had grades II-IV graft-versus-host disease (GVHD) (n = 6) showed a significantly higher level of t-PA.PAI on day 14 compared with those with grades 0-I GVHD (n = 10) (P = 0.0062). Three patients with grades II-IV GVHD developed thrombotic microangiopathy (TMA) on days 19, 19 and 62. In these patients, we noted significantly lower levels of fibrinogen (P = 0.0383), and significantly higher levels of t-PA.PAI (P = 0.0008) and thrombomodulin (P = 0.0001) on day 14 compared with those patients who did not develop TMA. These results suggest that prothrombotic states and endothelial damage may be caused by the conditioning regimen and/or acute GVHD during BMT; thrombomodulin values on day 14 post BMT may be useful in surveillance for TMA because of endothelial cell injury.

Variant of intron 22 inversions in the factor VIII gene in severe hemophilia A.

Recurrent DNA inversions, which disrupt the factor VIII (FVIII) gene, generally occur between a region of intron 22 (int22h) and one of two homologous copies of this region, located 300 to 400 kb telomeric to the FVIII gene. This report describes a patient with severe hemophilia A and a high level inhibitor with atypical hybridization patterns. A Bcl I Southern blot assay was altered to 17.5, 16, and 14 kb. His mother and two out of four aunts tested had normal and abnormal restriction patterns which led to a total of five different fragments, suggesting that they were carriers. The Xba I plus Kpn I restriction fragment-length polymorphism in intron 22 by Southern blotting using the same probe (probe a) yielded the 6.2 kb polymorphic band, with a clearly separated 6.6 kb band from the non-factor VIII region; an alternative int22h hybridization probe (probe x) detected no additional fragment. These results suggest that probe a as well as probe x could recognize an intron-22-sized fragment. This report shows a variation in the number of int22h copies although we could not find the inversion junction.

The evidence of clonal evolution with monosomy 7 in aplastic anemia following granulocyte colony-stimulating factor using the polymerase chain reaction.

We present here the case of a Japanese female patient with aplastic anemia who developed monosomy 7 and clonal evolution following a treatment with recombinant human granulocyte colony-stimulating factor (rhG-CSF). At the onset of aplastic anemia, cytogenetic analysis was 46, XX and X-inactivation/methylation analysis revealed a polyclonal pattern. After 4 months of administration of rhG-CSF, she had 45, XX, -7 and a clonal pattern, although there were no morphological evidence of a myelodysplastic syndrome or leukemia. The ratio of monosomy 7 to normal analyzed by fluorescence in situ hybridization decreased after discontinuation of rhG-CSF and there were still no dysplastic changes and/or increased numbers of blasts. These results indicate that the acquisition of monosomy 7 following rhG-CSF treatment dose not always cause clonal evolution to induce hematological malignancies.