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J Mimaya

Publications and source records attributed to J Mimaya.

At least 37 records · Page 2Linked to original sources

Infantile hemangioendothelioma of the thymus with massive pleural effusion and Kasabach--Merritt syndrome: histopathological, flow cytometrical analysis of the tumor.

Infantile hemangioendothelioma of the thymus is a rare disease. We describe a patient who developed a large anterior mediastinal mass, severe thrombocytopenia and massive pleural effusion at 1 month of age. Glucocorticosteroid and irradiation therapy had no effect on either the tumor size or clinical symptoms and the tumor was resected subtotally. Three months after the subtotal resection, the remaining tumor had almost disappeared and the symptoms had resolved. The patient has now been well for 1 year after surgery without evidence of recurrence. The tumor tissue was characterized by prominent vascular endothelial proliferation intermixed with a normal thymic structure, producing a picture consistent with that of an infantile hemangioendothelioma in the thymus. Immunohistochemically, the tumor cells showed positive staining for vimentin, factor VIII and CD34. The DNA stemline and proliferative activity were examined by flow cytometry, which revealed a diploid stemline with a low growth fraction. DNA content and cell cycle analyses of the tumor tissue may be useful for predicting the biological behavior of the tumor.

DNA, Neoplasm↗

Qualitative and quantitative detection of cytomegalovirus DNA in sera by PCR as a clinical marker.

The amount of human cytomegalovirus (CMV) DNA in sera is considered to be a direct marker for CMV infection. We established conditions for nested PCR that detected one copy of CMV DNA, and for competitive PCR, which detected five or more copies of CMV DNA quantitatively. We tested 50 microl each of 16 freeze-stored and 5 fresh sera from patients, for CMV DNA. In sera obtained from the same patient at different time points, small amounts of CMV DNA were detected before the onset of CMV pneumonia. In sera from certain CMV-infected patients who were treated with the anti-CMV agent, ganciclovir, CMV DNA was not detected. Quantitative PCR detection of CMV DNA seems to be suitable for predicting early recurrent CMV infection and monitoring the efficacy of antiviral therapy. The qualitative nested PCR examination of CMV DNA in 40 cord blood plasma samples was carried out for the purpose of preventing CMV infection by cord blood stem cell transplantation, and they were all negative for CMV DNA.

AIDS-Related Opportunistic Infections↗

[Bone marrow relapse in high-risk pediatric patients with acute lymphoblastic leukemia: a comparison of relapse times and initial clinical features of patients on different protocols. Children's Cancer and Leukemia Study group (CCLSG)].

To clarify the efficacy of modern intensive chemotherapy for ALL patients with unfavorable features, we compared the time to failure and initial clinical features of children who relapsed in the bone marrow or combined sites, as documented by early CCLSG studies (H811 and H851; 1981-1987) and later studies (H874 and H/HH911; 1987-1993) concerning high-risk ALL patients. In the later studies patients outcomes with new intensive regimens employing early intensification and reinduction therapy were apparently better than those of patients in the early studies with conventional regimens. When we compared the number of relapsed patients based on duration of first remission, we found that the improved outcomes for patients in the later studies were due to a decrease in the number who relapsed 7-36 months after the start of treatment (intermediate relapse), and that the percentage of those who relapsed within the first 6 months of therapy (early relapse) was higher. Patients with high initial WBC counts tended to relapse much earlier than those with low initial WBC counts. However, in the later studies, patients with high WBC counts often relapsed after the termination of therapy (late relapse). These results suggest that the intensive chemotherapy regimens used in the later studies can prevent the development of drug resistant leukemic clones, except in extremely high-risk patients likely to relapse within the first 6 months of therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Correlation of titer of antibody to principal neutralizing domain of HIVMN strain with disease progression in Japanese hemophiliacs seropositive for HIV type 1.

With the use of the principal neutralizing determinant (PND) peptide-based ELISA to measure anti-PND antibodies that specifically bound synthetic peptides derived from HIVIIIB, HIVMN, HIVRF, HIVSC, HIVWJM-2, HIVAf1l.con, or HIVAf2.con, type-specific antibodies to the HIVMN peptide were studied in 350 serum specimens from Japanese with hemophilia A who had been injected with known unheated factor VIII concentrates until 1985 and had been infected with HIV-1 subtype B. These antibodies were not found in any of the seronegative sera of hemophiliacs, patients with autoimmune diseases, or normal healthy controls. Further, all hemophiliacs rapidly progressing to AIDS and death among the 95 hemophiliacs in a restricted Nara area had antibody titers of less than 20 and their low levels preceded the rapid progression to the disease state. In contrast, slowly progressing hemophiliacs maintained an antibody titer of more than 100 from the initial stages of viral infection and remained asymptomatic. Sequence analysis of the V3 regions of HIV-1 indicated that the hemophiliacs who maintained a high anti-PNDMN antibody level showed a conserved MN sequence. In contrast, the HIV-infected hemophiliacs with nonreactivity in the ELISA showed sequence changes in the neutralizing epitopes of HIVMN. The dynamic of the serum anti-PNDMN antibody titer appear to be a characteristic indicator of the progression of the HIV-infected status in Japanese hemophiliacs seropositive for HIV-1.

Adult↗

Treatment outcome and prognostic factors in childhood acute myeloblastic leukemia: a report from the Japanese Children's Cancer and Leukemia Study Group (CCLSG)

Treatment outcome and prognostic factors were evaluated in 152 children with acute myeloblastic leukemia (AML) treated on three consecutive protocols (ANLL 861, 8912, 9205) of the Children's Cancer Leukemia Study Group (CCLSG, Japan). In the ANLL 9205 protocol, anthracycline was used with a continuous infusion of cytosine arabinoside, followed by an intensive sequential post remission chemotherapy of short duration. Forty-two of these 46 patients (91.3%) achieved complete remission, and 58.8% of these patients projected a 3-year disease-free survival. These results were apparently superior to those obtained with the ANLL 861 and 8912 protocols, which used conventional doses of multiple drugs followed by a moderate post remission chemotherapy of long duration. This favorable response with the ANLL 9205 protocol was attributed mainly to the high induction rate of patients with the M4 and M5 FAB subtypes, as compared to those in the previous two protocols (93.3% in ANLL 9205 vs. 57.9% in ANLL 861 + 8912; P < 0.05). The ANLL 861 and 8912 protocols, an older age (> or = 8 years), higher WBC counts (> or = 10 x 10(9)/1) and all predicted an increased risk of relapse and decreased the survival following univariate analysis (P < 0.05). An older age and high WBC count continued to predict an increased risk of relapse in multivariate analyses: patients with an age > 8 years and WBC counts > 10 x 10(9)/1 had a 4.5 times higher risk of relapse than patients without these adverse features.

Adolescent↗

Quantitative detection of human immunodeficiency virus type 1 (HIV-1) RNA by PCR and use as a prognostic marker and for evaluating antiretroviral therapy.

The amount of human immunodeficiency virus type 1 (HIV-1) genomic RNA in sera is considered to be one of the most direct markers for patient prognosis and monitoring the efficacy of antiretroviral therapy. Quantitative detection of HIV-1 RNA was performed by the dilution endpoint method and competitive PCR. Conditions for detecting one copy of HIV-1 control DNA were examined to decide the dilution endpoint exactly. PCR of the gag region by SK145/SK39 primer pair and seminested PCR by SK145/SK101 primer pair gave the best result. Conditions for competitive PCR of HIV-1 cDNA, which was reverse transcripted from HIV-1 control RNA, were also studied using a SK38/SK39 primer pair in the presence of HIV-PCR MIMIC as a competitor DNA. The detection limit of HIV-1 control DNA by competitive PCR was 10 copies but that of HIV-1 control RNA was 50 copies. Time-course quantitation of HIV-1 RNA in frozen-stored sera from an AIDS patient was carried out and traced back to 1993. The amount of serum HIV-1 RNA markedly decreased when the treatment was changed but increased again before deterioration of his clinical status. It is considered that the quantitation of serum HIV-1 RNA is useful for the prognosis of HIV-infection and the evaluation of the antiretroviral therapy.

Anti-HIV Agents↗

[Myelogenous leukemia in children. ANLL9205 study by Children's Cancer and Leukemia Study Group (CCLSG)].

Treatment results were evaluated in 45 children with acute myeloblastic leukemia (AML) treated on the ANLL-9205 protocol of the Children's Cancer Leukemia Study Group (CCLSG, Japan). In this protocol, terarubicin (THP-ADR), vincristine and continuous infusion of cytosine arabinoside (Ara C) were applied for remission induction therapy (AVC), and VP16+ high dose Ara C were used sequentially for 32 or 48 weeks. Eleven patients received stem cell transplantation. Thirty-eight out of the 43 eligible patients (88.4%) achieved complete remission, and the overall 3-year event-free survival (EFS) was 55.6% (S.E.,10%). This favorable response was attributed mainly to the high induction rate of patients with the M5, M7 FAB subtypes and higher WBC counts (> or = 10 x 10(9)/L). There was no difference in the 3-year EFS of these patients who discontinued treatment between 32 weeks and 48 weeks. Serious toxicities were not observed in this study. These findings suggest that the ANLL-9205 protocol is an effective and safe treatment regimen for childhood AML. When comparing the treatment period of 32 or 48 weeks, the difference was not statistically significant.

Antineoplastic Combined Chemotherapy Protocols↗

[Treatment results in childhood acute myeloblastic leukemia--a report of clinical trials of a past decade from the Japanese children's Cancer and Leukemia Study Group (CCLSG)].

Treatment results were evaluated in 167 children with acute myeloblastic leukemia (AML) treated on four protocols (ANLL 861, 8912, 9205, APL-ATRA) of the Children's Cancer Leukemia Study Group. In the ANLL 9205 protocol, anthracycline was used with a continuous infusion of cytosine arabinoside, followed by an intensive sequential post remission chemotherapy of short duration, 42/46 patients (91.3%) achieved complete remission, and 58.8% of these patients projected a 3-year disease free survival. These results were apparently superior to those obtained with the ANLL 861 & 8912 protocols, which used conventional doses of multi drugs followed by a moderate post remission chemotherapy of long duration. This favorable response with the ANLL 9205 protocol was attributed mainly to the high induction rate of patients with the M4 and M5 FAB subtypes, as compared to those in the previous two protocols (91.3% in ANLL 9205 vs 57.9% in ANLL 861 + 8912; p < 0.05). No significant difference in the patients outcome was found between the chemotherapy group and allogenic bone marrow transplantation group in the ANLL 9205 study. The patients with the M3 FAB subtype treated with the APL-ATRA protocol which consisted of an alternative use of all-trans retinoic acid and chemotherapy significantly prolonged event free survival as compared with the patients treated with ANLL 861/8912 protocols without all-trans retinoic acid.

Anthracyclines↗

[Cytogenetic abnormality and prognosis in childhood acute myeloblastic leukemia. Children's Cancer and Leukemia Study Group (CCLSG)].

We report on the leukemic cell karyotype of 180 children with acute myeloblastic leukemia (AML). They were treated by the protocols of chemotherapy for the Children's Cancer and Leukemia Study Group (CCLSG) in the last decade. Of 132 cases with adequate banding analysis, 24.2% had normal karyotype, 21.2% had miscellaneous clonal abnormalities and 54.6% were classified into known cytogenetic subgroups: t(8;21) (n = 35), t(15;17) (n = 23), inv (16) (n = 6), t(11q23;V) (n = 6), -7/7q-(n = 2). Each karyotype was closely correlated with a particular FAB subtype such as t(8;21) in M2, t(15;17) in M3, inv (16) in M4, t(11q23;V) in M5. In the M1+M2 group, although patients with t(8;21) had favorable clinical features such as low WBC counts and less frequent lymphadenopathy, their treatment outcome was not significantly better than those of patients with a normal karyotype (3-year EFS: 58 +/- 11% vs. 47 +/- 12%). Patients with miscellaneous chromosomal abnormalities had a significantly shorter EFS (22% +/- 10%) (p < 0.05) than those with t(8;21) or normal karyotype. In M4+M5 group, 2-year EFS of patients with inv (16) (40 + 30%) was longer than that of patients with normal karyotype (25 +/- 19%), and t(11q23;V) or miscellaneous chromosomal abnormalities (0 +/- 25%). These results suggest that cytogenetic data may be useful for risk-based treatment assignments for children with AML.

Adolescent↗

[AIDS].

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AIDS-Related Opportunistic Infections↗

[HIV infection: pathophysiology and its clinical features--clinical course and surrogate marker].

Clinical courses and several hematological and serological markers were evaluated in 34 patients with HIV infection (32 with hemophilia and 2 with homosexuality) who had been followed up at Shizuoka Prefecture Children's Hospital for 3 to 13 years, with the reference to the results observed in 1,082 patients with HIV infection registered with the Ministry of Health and Welfare Study Group, Natural History Committee. The results indicated as significant follow-up markers as (1) CD4- and CD8-positive lymphocyte count, (2) IgA, IgG and beta-2 microglobulin, (3) HIV p24 antigen and HIV culture isolation, and (4) serum HIV-RNA. Of these markers, the quantification of serum HIV-RNA seemed particularly useful for prognosis estimation, determination of therapy onset, and efficacy assessment of a given anti-HIV agent. In addition, we encountered 2 HIV-infected patients who seemed to meet the definition of long-term survivors. Factor analysis in these patients will be an important subject of investigation from a clinical point of view as well.

Biomarkers↗

Life time expectancy of hemophilia patients infected with HIV-1 with the risk of hepatocellular carcinoma after HCV infection.

1. INTRODUCTION. The latest statistics how that Japanese hemophilia patients infected with HIV-through clotting factor concentrates may survive more than 10 years after HIV-infection without showing an onset of AIDS [1]. Unfortunately, however, results of the recent surveillance have revealed that about half of hemophilia patients had also been infected with the hepatitis C virus (HCV) [2]. Therefore, some hemophilia patients might suffer from hepatocellular carcinoma triggered by HCV after some latent periods. In the present study, we computed the life time expectancy of hemophilia patients with two risks of HIV-and HCV infections. 2. METHOD. We used the Weibull hazard function h(t) for the hazard rate from AIDS after infection with HIV-1. In order to describe the hazard rate arising from hepatocellular carcinoma after HCV infection, we utilized the theoretical function c(t) with two parameters that were obtained previously by ourselves from a case-controlled study on hepatocellular carcinoma patients infected with HCV through blood transfusion [3]. Substituting necessary parameters estimated for Japanese hemophilia patients into h(t), the life time expectancy t was computed by the following integration; tau=integral of exp(-integral of h(t')+c(t¿) dt') dt, where t' means the time after HIV-infection, and t¿ is a variable composed of tU and times of HIV-and HCV infections. 3. RESULTS AND DISCUSSION. Without hepatocellular carcinoma, the life time expectancy tau of the patients infected with HIV-1 at the age of 20 was computed as 15.0 years. On the other hand, for the same patients with the risk of hepatocellular carcinoma through HCV infection at the age of 10, 15, 20 and 25 years old, values of tau were computed at 12.2, 13.3, 14.1 and 14.4 years, respectively. Especially noticeable was the reduction of tau in cases of HCV infection was prior to HIV-infection. In the present computation, the two risks from HIV-1 and HCV infections were assumed to be additive because no explicit interaction between them has been reported yet. Various long term effects have been found with the development of HIV/HCV therapies; that should also take into account the survival estimation and therapy planning for HIV-1 infected patients in the coming years.

Acquired Immunodeficiency Syndrome↗

Detection of antibody IgG to HIV-1 in urine by ultrasensitive enzyme immunoassay (immune complex transfer enzyme immunoassay) using recombinant p24 as antigen for diagnosis of HIV-1 infection.

Anti-HIV-1 IgG in urine was detected by an ultrasensitive enzyme immunoassay (immune complex transfer enzyme immunoassay) using recombinant p24 gag protein (p24) of HIV-1 as antigen and beta-D-galactosidase from Escherichia coli as label. Anti-HIV-1 IgG in urine was reacted simultaneously with 2,4-dinitrophenyl-bovine serum albumin-recombinant p24 conjugate and recombinant p24-beta-D-galactosidase conjugate. The complex formed, consisting of the three components, was trapped onto polystyrene balls coated with affinity-purified (anti-2,4-dinitrophenyl group) IgG, eluted with epsilon N-2,4-dinitrophenyl-L-lysine, and transferred to polystyrene balls coated with affinity-purified (anti-human IgG gamma-chain) IgG. Bound beta-D-galactosidase activity was assayed by fluorometry. This assay was at least 3,000-fold more sensitive than conventional methods. The lowest signal among 49 asymptomatic carriers was 3.1-fold higher than the highest nonspecific signal among 100 seronegative subjects. The sensitivity and specificity were both 100%. The positivity could be confirmed by preincubation of urine samples with excess of the antigen. Thus, this assay would be a powerful tool for detecting IgG antibody to HIV-1 in urine.

Adolescent↗

Detection of antibody IgG to HIV-1 in urine by sensitive enzyme immunoassay (immune complex transfer enzyme immunoassay) using recombinant proteins as antigens for diagnosis of HIV-1 infection.

For diagnosis of HIV-1 infection, attempts were made to detect anti-HIV-1 IgG in urine by sensitive enzyme immunoassay (immune complex transfer enzyme immunoassay) using recombinant reverse transcriptase (RT) and p17 as antigens. Anti-HIV-1 IgG in urine was reacted simultaneously with 2,4-dinitrophenyl-bovine serum albumin-recombinant protein conjugate and recombinant protein-enzyme conjugate. The enzymes used as labels were horseradish peroxidase for RT and Escherichia coli beta-D-galactosidase for p17. The complex formed, consisting of the three components, was trapped onto polystyrene balls coated with affinity-purified (anti-2,4-dinitrophenyl group) IgG, eluted with epsilon N-2,4-dinitrophenyl-L-lysine and transferred to polystyrene balls coated with affinity-purified (anti-human IgG gamma-chain) IgG. Finally, bound enzyme activity was assayed by fluorometry. Urine samples were collected from 100 seronegative subjects and 70 seropositive subjects. The sensitivity and specificity were both 100% with unconcentrated urine samples. The positivity was confirmed by preincubation of urine samples with excess of the antigens. The positivity and negativity with one of the two antigens could be confirmed with the other antigen. The positivity with low signals could be confirmed by concentration of urine samples. Detection of anti-HIV-1 IgG in urine by the immune complex transfer enzyme immunoassay using different antigens would make diagnosis of HIV-1 infection possible.

Adolescent↗

Phase I/II trial of didanosine (2',3'-dideoxyinosine) in hemophiliac patients with AIDS or AIDS-related complex.

Forty-three hemophiliacs with AIDS or ARC received a daily dose of 334 or 500 mg didanosine (2',3'-dideoxyinosine or ddI) orally in 2 divided doses in phase I/II, open-label clinical trial conducted in Japan. Twenty-eight patients completed 6 months of therapy. There was an increase in circulating CD4(+) cells in 19 valuable patients from 91 +/- 25 (mean +/- SE) at entry to 131 +/- 38 at 24 weeks of therapy P = 0.01; Wilcoxon signed rank). Fourteen of 37 patients met the criteria for CD4 rise >/= 50/mm3 rise or >/= 50% increase from entry values) for more than 4 consecutive weeks. Twenty patients were p24 positive at entry. Nine out of the 10 evaluable patients (90%) showed a decline in p24 antigen at weeks 20-24 (P = 0.02). Thirty-five patients had symptoms related to HIV-1 infection at entry. Twenty-seven patients reported improvements in constitutional symptoms during therapy. Nine patients presented with possible drug-related adverse effects, and didanosine was discontinued in 6 patients (one each with edema; abdominal pain with anorexia; hematuria with edema and rash; sense of abdominal distension with anorexia; diarrhea and abdominal pain; and irritability). One patient had a transient increase in serum amylase level to twice the upper limit of normal, but he continued to receive the drug. These data suggest that didanosine was generally well tolerated in hemophiliacs with AIDS or ARC, and its administration correlated with improvement in constitutional symptoms and laboratory findings. The adverse effects of didanosine seen in this population were moderate to mild, and no complications related to hemorrhagic diathesis were observed, although the relative risk of acute pancreatitis in this population (while not seen in the present study to date) requires more study.

Journal Article↗

Immunological abnormalities in HIV-free haemophiliacs.

Since some haemophiliacs manifest profound immunodeficiency with no evidence of human immunodeficiency virus type 1 (HIV) infection, we measured the circulating immune complex (CIC) level in sera obtained from haemophiliacs and addressed the question of whether viral infection is associated directly or indirectly with enhanced CIC production. While more than 90% of HIV-positive individuals had a high level of CIC, around 60% of seronegative ones also showed CIC levels comparable to those of seropositive patients. These sera activated fresh complement in vitro. The patients infected with either HIV or Hepatitis C virus (HCV) or both showed higher frequency and concentration of serum CIC than those free of either pathogens. It is worth noting, however, that 64% of patients with no evidence of infection with HIV or HCV produced significant amounts of CIC. Among the infectious viruses examined, parvovirus is considered as one of the pathogens associated with CIC synthesis, since all the haemophiliacs including the HIV-free patients who had been supplied with heated coagulation factors for several years from birth carried antibodies to parvovirus B19. Strikingly, 60% of the children in this category were positive for CIC, suggesting the possible contribution of parvovirus infection to CIC formation.

Adolescent↗

[Isolation of HIV-1 and its correlation with various HIV-markers in Japan].

In Japan, the isolation rate of HIV-1 has increased in recent years, and has become as high as 36.7% in 1991. In order to evaluate the onset of AIDS, we have collected various HIV markers, which were obtained from surveillance committee of Natural History. These data include a total of 1991 specimens (actual number 556 individuals) from Japanese hemophiliacs and non-hemophiliacs since 1985. The data analysed CDC stage, leucocyte counts, lymphocyte counts, CD4+ cell counts, CD8+ cell counts, CD4/CD8 ratio and immunoglobulins (IgA, IgG, IgM). The results indicate that in HIV-isolation positive patients, leucocyte counts, lymphocyte counts, CD4+ cell counts, CD8+ cell counts and CD4/CD8 ratio were significantly lower than those of HIV-isolation negative patients in both hemophiliacs and non-hemophiliacs. IgA value of the positive patients was significantly higher than that of the negative patients, while the IgM value showed converse results to the IgA, in hemophiliacs only. In general, the difference of each HIV marker in non-hemophiliacs was more conspicuous than those in hemophiliacs.

Acquired Immunodeficiency Syndrome↗