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Biomedical subjects

M Naya

Publications and source records attributed to M Naya.

At least 19 recordsLinked to original sources
PubMed2006

Allogeneic stem cell transplantation in children with acute lymphoblastic leukemia after isolated central nervous system relapse: our experiences and review of the literature.

The prognosis of patients with acute lymphoblastic leukemia (ALL) and central nervous system (CNS) relapse has historically been very poor. Although chemo-radiotherapy has improved outcomes, some patients still have a poor prognosis after CNS relapse. Therefore, allogeneic hematopoietic stem cell transplantation (allo-SCT) has recently become an option for treatment of CNS leukemia; however, information, particularly on the long-term outcome of transplant recipients, is limited. We performed allo-SCT in eight pediatric patients with ALL (n=7) or T-cell type non-Hodgkin's lymphoma (n=1), who had isolated CNS relapse. All patients survived for a median of 70.5 (range, 13-153) months after SCT. Sequelae developed late in some patients: mental retardation (IQ=47) in one patient, severe alopecia in two patients, limited chronic graft-versus-host-disease in three patients, and amenorrhea and/or hypothyroidism in three patients. Except for a pre-school child with post transplant CNS relapse, six out of seven patients show normal school/social performance. Our results clearly indicate a high cure rate of isolated CNS relapse by allo-SCT in pediatric lymphoid malignancies; however, there needs to be further studies to determine which are the appropriate candidates for transplantation and what is the best transplant regimen to achieve high cure rate and maintain good quality of life.

Adolescent↗
PubMed2004

Adenoviral infection in hematopoietic stem cell transplantation: early diagnosis with quantitative detection of the viral genome in serum and urine.

Early diagnosis and prompt introduction of effective therapy are imperative to manage systemic, often fatal adenoviral (AdV) disease following hematopoietic stem cell transplantation (SCT). We evaluated the usefulness of real-time polymerase chain reaction (PCR) in the diagnosis of AdV disease in SCT recipients. Seven SCT recipients, including three with AdV disease, were retrospectively evaluated for AdV genome detection. In serum specimens, the AdV genome was detected at >10(3) copies/ml in the pre-SCT period in two of the five recipients studied. These two patients subsequently developed AdV disease. The three patients with AdV disease had high levels of >10(5) copies/ml during the 4-6 weeks post-SCT period. In none of these patients was the AdV genome detected in urine specimens in pre-SCT period. However, three recipients with detectable urinary levels during the period 1-2 weeks post-SCT subsequently developed AdV disease. Regarding the outcome, two of the three patients with AdV disease died of progressive renal failure. Our results suggest that quantitative determination of the AdV genome in serum and urine is useful to identify patients at high risk of developing AdV disease. Prospectively applied, these measures are expected to improve the dismal outcome of AdV disease in SCT recipients.

Adenovirus Infections, Human↗
PubMed2001

Risk factors for cytomegalovirus retinitis following bone marrow transplantation from unrelated donors in patients with severe aplastic anemia or myelodysplasia.

Two cases of cytomegalovirus (CMV) retinitis following bone marrow transplantation (BMT) from unrelated donors are reported. 1 patient had been treated for severe aplastic anemia (SAA) and the other for hypoplastic myelodysplastic syndrome (MDS). Because first line therapy with antithymocyte globulin (ATG) and cyclosporin A (CsA) had failed, BMT was performed following a conditioning regimen of ATG, cyclophosphamide, and total lymphoid irradiation. Treatment for CMV retinitis was successfully carried out with gancyclovir (systemic and intraocular injection), foscarnet, and photocoagulation (Case 1) and gancyclovir and foscarnet (Case 2). Both patients also developed Epstein-Barr virus-associated lymphoproliferative disease (EBV-LPD). We compared these 2 cases with 14 SAA patients who did not develop CMV retinitis after BMT using marrow from either HLA-identical siblings (n = 9) or from unrelated donors (n = 5). Unlike the retinitis patients, the latter 5 patients received ATG only once. The retinitis patients had significantly lower CD4+ T-cell levels in their peripheral blood than the 14 patients who did not develop CMV retinitis. We believe that repeated treatment with ATG and transplantation from unrelated donors may lead to immune dysfunction that could increase the likelihood of CMV retinitis, as well as LPD. For such BMT patients, regular ophthalmic examinations and careful testing for CMV antigenemia are recommended.

Adolescent↗
PubMed2001

Collaborative study on rat sperm motion analysis using CellSoft Series 4000 semen analyzer.

A collaborative study was conducted to determine useful and sensitive rat sperm motion parameters in a CellSoft Series 4000 semen analyzer to detect the effects of compounds on sperm motion. The effects on the sperm motion parameters were investigated using alpha-chlorohydrin, boric acid, ethinylestradiol, ethyl methanesulfonate, nitrazepam, nitrobenzene, ornidazole, sulfasalazine or valproic acid which are well known to induce reproductive or testicular toxicities. All compounds used in this study decreased percentage of motile sperm (% motile). Curvilinear velocity (VCL), maximum and mean amplitude of lateral head displacement (ALH max and ALH mean) were decreased by treatment with all compounds except for valproic acid. Treatment with alpha-chlorohydrin, ornidazole or sulfasalazine under mid-dosage regimens decreased only these parameters. Beat cross frequency (BCF) was increased by treatment with sulfasalazine. There were some treatments which caused either decreased or increased changes irrespective of dosage regimen in linearity, average radius, percentage of circular-swimming sperm out of motile sperm (circular/motile) and percentage of circular-swimming sperm out of all sperm (circular/all). Based on these results, we concluded that % motile, VCL, ALH max and ALH mean are considered useful and sensitive parameters for evaluating the effects of compounds on sperm motion. A parameter of BCF can be useful to detect the effects of specific compounds on sperm motion. Linearity, average radius, circular/motile and circular/all are not considered useful or sensitive indicators to detect the effects of compounds on sperm motion.

Animals↗
PubMed1999

Effects of maternal acetazolamide treatment on body weights and incisor development of the fetal rat.

The incisor development of fetal rats on gestation day 19 was well correlated with their fetal weights. The number of odontoblasts in the mandibular incisors, an index of incisor development, increased more than that of the maxillary incisors with increase in fetal body weights. Maternal acetazolamide treatments were observed to suppress the mean fetal weight and to retard incisor development. A smaller incisor size, a thinner predentin layer, and fewer odontoblasts were characteristic of the acetazolamide group. There was also a good correlation between the fetal weights and the number of odontoblasts in the acetazolamide group. From these results, we postulated that the retarded incisor development of the fetal rats caused by the maternal acetazolamide treatment was related to their suppressed fetal weights. However, the regression coefficient of the fetal weights and the number of odontoblasts in the acetazolamide group was smaller than that of the vehicle control group. It may indicate that retarded incisor development in response to maternal acetazolamide treatment is to some extent independent of suppressed fetal weight.

Acetazolamide↗
PubMed1999

[Relapse of acute lymphoblastic leukemia as a retro-orbital mass].

A 16-year-old girl who had been treated for B-precursor acute lymphoblastic leukemia (ALL) presented with a mass in the left orbit as an isolated relapse. Five years earlier, she had undergone chemotherapy that promptly resulted in a complete remission. For prophylaxis of central nervons system leukemia, the patient received cranial radiotherapy (18 Gy) with shielding of the orbit and 15 cycles of intrathecal MTX and prednisolone. Cerebrospinal fluid analysis did not detect infiltration during the treatment course. Exophthalmos of the eft eye and hyperemia of the conjuctiva developed 15 months after therapy. Computed tomography showed a retro-orbital mass behind the left eye. Though bone marrow aspiration was negative, biopsy specimens from the mass disclosed the infiltration of CD10-positive leukemic blasts. After 8 courses of chemotherapy, 5 cycles of intrathecal MTX, and orbital irradiation (24 Gy), the mass disappeared. All relapse as an isolated retro-orbital mass is very rare, and only 3 cases have been reported to date.

Adolescent↗
PubMed1998

[Post-transplant EBV-associated lymphoproliferative disorders--report of two cases].

We report two cases of Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPD) after allogenic bone marrow transplantation which were conditioned with regimens including antithymocyte globulin (ATG). The first case was a 31 year-old man which severe aplastic anemia who was transplanted from HLA-matched unrelated donor conditioned with total lymphoid irradiation (TLI)/ cyclophosphamide/ATG and prophylactic administration of ganciclovir Grade I acute GVHD improved in response to cyclosporine (CsA). LPD as a polyclonal epipharyngeal mass developed at day +53 and spontaneously regressed along with the withdrawal of CsA. Second case was a 11 year-old boy with acute myelomonocytic leukemia (FAB:M4E). He was transplanted from HLA B locus mismatched mother conditioned with total body irradiation (TBI)/busulfan/L-PAM/ATG. He showed grade IV acute GVHD, which was controlled by steroids and FK-506. LPD as a monoclonal intestinal lymphoma was diagnosed at day +82, and he was unsuccessfully treated with ganciclovir, acyclovir, chemotherapy and transfusions of EBV-specific cytotoxic lymphocytes in addition to discontinuation of immunosuppressants, and died at day +18 due to sepsis and multiple cerebral infarction. Early detection and introduction of appropriate treatment for post bone marrow transplantation LPD is necessary.

Adult↗
PubMed1997

Unsuccessful CTL transfusion in a case of post-BMT Epstein-Barr virus-associated lymphoproliferative disorder (EBV-LPD).

A patient with AML (FAB M4Eo) developed EBV-LPD 1.5 months after allogeneic BMT from his one locus-mismatched mother, the diagnosis being confirmed on day +82. Attempts to eradicate the monoclonally proliferating LPD using chemotherapy (VP16/dexamethasone) followed by two doses of EBV-specific CTL and one dose of unstimulated donor leukocytes were not successful. We assume delay of infusions (day +100, +107) and insufficient CTL cell doses (total 9.2 x 10(6)) may have been responsible for the poor outcome in this case.

Bone Marrow Transplantation↗
PubMed1997

Chimerism analysis on mononuclear cells in the CSF after allogeneic bone marrow transplantation.

To evaluate the chimeric status of mononuclear cells in the CSF after allogeneic BMT, cells were analyzed by FISH using satellite DNA probes for human X and Y chromosomes. CSF cells were obtained from five pediatric ALL patients who received BMT from sex-mismatched donors. All patients received TBI-containing conditioning regimens. We found that CSF cells showed complete donor type in 19-97 days after BMT, when complete donor type hematopoiesis was observed. The rapid entry of the donor leukocytes into the brain may exert beneficial effects to eradicate the residual CNS leukemic cells and prevent a CNS relapse in ALL patients after BMT.

Bone Marrow Transplantation↗
PubMed1997

A flow cytometric analysis of cytotoxic effects of nitrobenzene on rat spermatogenesis.

Cytotoxic effects of nitrobenzene (NB) on spermatogenesis of mature Sprague-Dawley (Crj:CD) rats were analyzed by measuring the DNA content distribution and testicular weight at 1, 2, and 3 weeks of daily oral dose of NB (60 mg/kg/day). Rats at the age of 9 weeks were used because the ratios of 1C, 2C, S, 4C to total testicular cells were stabilized after the age of 52 days. Within a week of administration, a large number of 1C cells were lost but 2C cells proliferated, resulting in little change of testicular weight. In another week that followed, the number of 1C cells and testicular weight were decreased, but the ratio of S-4C cells was increased, indicating that an appreciable number of 2C cells could progress to the 4C compartment. The data indicated that (1) 1C cells were destroyed, and (2) meiosis of secondary spermatocytes was suppressed, but (3) NB had little effect on the spermatocytes prior to the early pachytene stage. This interpretation was reinforced by the observation that (4) the ratio of 1C cells returned to a nearly normal level during a recovery period of 2 weeks. In conclusion, flow cytometry could offer an efficient method for the quantitative analysis of male reproductive toxicity.

Animals↗
PubMed1996

Secondary lymphoid malignancy in two children with neuroblastoma.

Secondary lymphoid malignancy, particularly acute lymphoblastic leukemia (ALL), is rare. We report one case of ALL and another case of mediastinal lymphoblastic lymphoma developed after treatment for neuroblastoma. The secondary ALL characterized by short latency period and an 11q23 translocation apparently was induced by etoposide treatment. The pathogenesis of the secondary lymphoma is less certain and may be related to previous treatment with cyclophosphamide and radiotherapy, host susceptibility, or chance occurrence. One child died of progressive lymphoma and the other remains in remission 1 year following allogeneic bone marrow transplantation. Additional studies are needed to determine the risk, pathogenesis, and optimal treatment for secondary lymphoid malignancy.

Child↗
PubMed1993

[Intensive chemotherapy for alveolar soft part sarcoma with lung metastasis in a child].

Alveolar soft part sarcoma (ASPS) is one of the soft tissue sarcomas characterized by metastasis early in the course of the disease, regardless of slow tumor growth. The ultimate clinical outcome is, therefore, very poor. To date, the efficacy of combination chemotherapy for this tumor has not been confirmed. We present a case of ASPS in an 8-year-old boy with bilateral pulmonary metastasis who received systemic combination chemotherapy (CPM/IFO/ACD/ADR/CD DP/VP-16 as induction, and VCR/ACD as maintenance therapy) for eleven months. The result showed that despite the prevention of tumor progression, such intensive chemotherapy could not cure the disease. Besides refinement of chemotherapy regimens, immunotherapy might be considered for ASPS.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Effects of phorone and/or buthionine sulfoximine on teratogenicity of 5-fluorouracil in mice.

Embryotoxicity and teratogenicity of 5-fluorouracil (5-FU) and modulation of its effect by the depletors of glutathione (GSH) were evaluated in mice. Pregnant ICR mice were intraperitoneally (i.p.) injected with 25 mg/kg of 5-FU on day 11 of gestation (vaginal plug = day 0). Mice were pretreated i.p. with 250 mg/kg of phorone, a GSH depleting agent and/or 200 mg/kg of buthionine sulfoximine (BSO, an inhibitor of GSH biosynthesis) 4 hours before dosing with 5-FU. Dams were killed on day 17 of gestation. Fetuses were examined for external malformations, especially limb malformations. Pretreatment with phorone or BSO decreased fetal weight and increased the frequency and severity of oligodactyly induced by 5-FU, as well as the reduction of maternal GSH levels. Combined use of 125 mg/kg phorone and 100 mg/kg BSO i.p. augmented growth retardation induced with 5-FU. Cotreatment with exogenous GSH, at a dose of 300 mg/kg injected intravenously, could not suppress the augmentative effects of phorone and/or BSO on 5-FU teratogenicity under these experimental conditions. These results indicate that the level of endogenous GSH is one of the factors which significantly affects teratogenicity of 5-FU.

Animals↗
PubMed1990

Effects of L-2-oxothiazolidine-4-carboxylate, a cysteine pro-drug, on teratogenicity of 5-fluorouracil in mice.

Embryotoxicity and teratogenicity of 5-fluorouracil (5-FU) and modulation of its effect by L-2-oxothiazolidine-4-carboxylate (OTC), a cysteine pro-drug, were evaluated in mice. Pregnant ICR mice were intraperitoneally (i.p.) injected with 25 mg/kg of 5-FU on day 11 of gestation (vaginal plug = day 0). Mice were pretreated i.p. with 950 mg/kg of OTC 4 hours before dosing with 5-FU. Dams were killed on day 17 of gestation. Fetuses were examined for external malformations, especially limb malformations. Pretreatment with OTC decreased the frequency and severity of oligodactyly induced by 5-FU, although the differences were not significant statistically. There was little difference in either liver glutathione levels, or body weight gain during gestation of dams between the 5-FU group and the 5-FU plus OTC group. Fetal mortality and fetal weight of the group treated with 5-FU alone were comparable with those of the group pretreated with OTC. In the present study, teratogenicity of 5-FU seemed to be slightly mitigated with OTC pretreatment.

Animals↗