Cytarabine and its effect on cerebellum of suckling mouse.

Suckling mice were injected with 30 mg/kg or 50 mg/kg body weight of cytarabine subcutaneously two, three, and four days after birth. Twenty-four hours after the final injection, these mice showed extensive necrosis of undifferentiated cells in the external granular layer of cerebellum. One or two weeks later, a new external granular layer regenerated but it did so only incompletely and regionally. The mice allowed to live longer showed impaired cerebellar function, cerebellar hypoplasia, and other malformations, including heterotopic granule cells in the molecular layer, irregularly arranged Purkinje cells, and scanty cellularity in the internal granular layer.

Changes in cell proliferation kinetics in the mouse cerebellum after total asphyxia.

This study was undertaken to investigate the effects of neonatal asphyxia on brain development, with special reference to the kinetics of neuronal proliferation by using autoradiography. For 30 minutes, two-day-old suckling mice, Jcl:ICR strain, were put into a chamber which was constantly flushed with 100% CO2 gas. After the exposure to asphyxia, 29% of the mice survived. Cell cycle studies were carried out at two days and at seven days on the external matrix cells, the precursor of the granule cells, at the external granular layer of the cerebellum from CO2-exposed and control mice by 3H-thymidine autoradiography. At two days the generation time of the control mice was about 15 hours, whereas that of the asphyxiated mice was about 17 hours. The prolongation of the generation time in the asphyxiated mice was caused mainly by a delay in the G2 phase. This prolongation was apparent for about five days and thereafter growth caught up. These results suggest that neonatal asphyxia has an adverse effect on cerebellar neuronal proliferation that may revert to normal spontaneously in older animals.

Successful allogeneic bone marrow transplantation in a case with myelodysplastic syndrome which developed following Fanconi anemia.

We report the case of a 14-year-old boy with myelodysplastic syndrome (MDS/RAEB) which developed following Fanconi anemia. The patient received BMT from an HLA-identical sister. Based on the in vitro CY-sensitivity test, 100 mg/kg of CY was administered for conditioning combined with 6 Gy TBI. Mucosal symptoms such as stomatitis, diarrhea and hematuria were severe, but manageable, and engraftment was successful. The patient has maintained normal trilineage hematopoiesis with > 90% Karnofsky score for 30 months with disappearance of a clonal chromosomal abnormality (47,XY, +i(lq)) which was detected before BMT.

Acute renal failure due to adenovirus-associated obstructive uropathy and necrotizing tubulointerstitial nephritis in a bone marrow transplant recipient.

Management of post-transplant complications caused by severe adenoviral infection remains a major therapeutic challenge. A 17-year-old male who had undergone bone marrow transplantation for the treatment of acute lymphoblastic leukemia developed complete anuria following hemorrhagic cystitis 34 days after the transplant procedure. The computed tomogram scan revealed bilateral hydronephrosis, indicating acute renal failure because of obstructive uropathy. The emergency procedure of percutaneous nephrostomy caused massive bleeding in the left kidney, which eventually required a nephrectomy. Adenovirus-positive severe necrotizing tubulointerstitial nephritis was the histopathological diagnosis. Post-transplant acute renal failure because of hydronephrosis, which could be complicated by adenovirus-induced renal parenchymal disease, is of great concern and may cause significant problems with interventional treatment.

Allogeneic Bone Marrow Transplantation for Familial Erythrophagocytic Lymphohistiocytosis, with High Dose VP16-Containing Conditioning Regimen.

A 6-month-old boy with familial erythrophagocytic lymphohistiocytosis (FEL) received allogeneic bone marrow transplantation (BMT) from an HLA-identical brother, after first achieving remission with Etoposide (VP16) and prednisone. The conditioning regimen for BMT consisted of high dose busulfan (16 mg/kg), cyclophosphamide (120 mg/kg), high dose VP16 (60 mg/kg) and intrathecal methotrexate and was well tolerated. Engraftment was achieved, and grade II GVHD was controlled with prednisone. Impaired NK activity present on admission gradually improved after BMT. The patient continues to be in complete remission more than 10 months after BMT.

Hydranencephaly in twins.

The sixth case of hydranencephaly in a twin is reported. The patient is an 11-year-old girl, and her twin was stillborn and macerated. Intrauterine disseminated intravascular coagulation may be the cause of hydranencephaly in this patient.

An autoradiographic study of new fat cell formation in adipose tissue in adult mice during malnutrition and refeeding.

The renewal of adipose cells in adult mice has been autoradiographically studied. The number of adipose cells was diminished by eighty percent during malnutrition and the same number of adipose cells proliferated during the refeeding stage. The results of our study showed that adipose tissue, which had previously been believed to be stable in cell number, has the capacity for cell proliferation according to changes in nutritional status.

[Experimental studies on the etiological mechanism of congenital microcephaly].

Pregnant mice were injected intraperitoneally on different gestational day with either one or three successive doses of 30 mg/kg of cytosine arabinoside (ara-C), which has been known to interfere with DNA synthesis. Some of them were injected intraperitoneally with tritiated thymidine (3H-TdR) consecutively. The fetuses and the youngs were sacrificed at various hours and days after treatment. Pyknotic nuclei or nuclear debris were observed at the matrix layer three hours after the injection of single dose of ara-C. Nuclear debris were increased as time elapse and they were most prominent 12 hours after treatment. However, 24 hours later, new matrix layer was regenerating. Twenty-four hours after treatment with two successive doses of ara-C, labeling index in the matrix layer was about one third of that of control. Cerebral hemispheres of the treated youngs were reduced in size. The youngs, treated with three successive doses of ara-C on day 13, 14 and 15 of gestation, showed most severe microcephalus. Cytoarchitecture in the cortices of these microcephalic mice was characterized by irregular arrangement of the pyramidal neurons and their dendritic branches. Autoradiographic study revealed that cortical neurons which were produced at the regenerated matrix layer after ara-C treatment migrated to the surface of the cortex.

[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.

[AML(M7) associated with t(16;21)(p11;q22) showing relapse after unrelated bone marrow transplantation and disappearance of TLS/FUS-ERG mRNA].

A 3-year-old boy with poorly prognostic acute megakaryoblastic leukemia (AML M7) showing t(16;21)(p11;q22) karyotype underwent unrelated bone marrow transplantation (U-BMT) during his first hematological remission. The conditioning regimen consisted of BU, VP-16 and L-PAM. Engraftment was smooth, but the patient developed grade I acute GVHD. During hematological remission before U-BMT, the TLS/FUS-ERG chimeric transcript of t(16;21)(p11;q22) was consistently detectable as minimal residual disease (MRD) by RT-PCR. However, after U-BMT it soon became undetectable. There was no detectable MRD until 7 months after U-BMT, but bone marrow relapse occurred 10 months after U-BMT. We consider that U-BMT is a promising treatment for t(16;21)(p11;q22) AML. However, an intensified conditioning regimen or modification of GVHD prophylaxis is needed.

Cytosine arabinoside-induce transplacental dysgenetic hydrocephalus in mice.

Pregnant mice were injected with 30 mg of cytosine arabino side/kg body weight on 13-1/3 and 14 days of gestation. Within six hours after the first injection, pyknotic nuclei and nuclear debris were found at the matrix layer surrounding the lateral ventricles of the embryonic brain. Autoradiographic studies using tritiated thymidine revealed that most of the matrix cells exposed to cytosine arabinoside during DNA synthesis were killed by this dose of the drug. Twenty-four hours after the second injection, most of the matrix cells had disappeared. When experimental animals were examined after birth, they showed marked dilation of the lateral ventricles. The dilatation of the lateral ventricles was more pronounced in the parieto-occipital region. The young showed rapid enlargement of the cranial vault and subsequently died by 35 days of age.

Muscular changes in Engelmann's disease.

In a case of Engelmann's disease in an 11-year-old Japanese boy the muscular changes were studied in detail. Muscle weakness was maximal about the pelvic girdle. Muscle biopsy showed the selective atrophy of type II fibres, and no degenerative change could be seen histologically, histochemically, or electron-microscopically. Although the distribution of muscular weakness in Engelmann's disease is similar to that of a progressive muscular dystrophy, the disease does not seem to be a myopathy.

Multicystic encephalomalacia in liveborn twin with a stillborn macerated co-twin.

Computed tomography showed multiple cystic lesions in the brains of three infants with cerebral palsy. Each patient was the product of a twin pregnancy with a stillborn, macerated co-twin. In two patients angiography was performed and suggested that the cystic lesions were multicystic encephalomalacia due to perinatal arterial occlusion.

Values for urinary beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase in normal healthy infants.

BACKGROUND: Measuring urinary beta 2 microglobin (B2M) and N-acetyl-beta-D-glucosaminidase (NAG) excretion is widely used as a valuable clinical tool in assessing renal tubular lesions. However, few data are available on normal values for urinary excretion of B2M and NAG in infancy. METHODS: Urinary B2M and NAG were measured in healthy infants. The logarithmic values of urinary B2M, NAG, B2M/creatinine ratio and NAG/creatinine ratio were distributed almost normally and reference ranges were calculated from the logarithms of the observed values. RESULTS: The levels of urinary B2M and B2M/creatinine ratio were highest in the 1-month-old group, followed by a decrease during the first 3 months. Urinary B2M excretions in the 3-month-old group showed rather lower levels than those of the 12-month-old and 36-month-old groups. Although urinary NAG excretions were almost constant throughout all groups, urinary NAG/creatinine ratio decreased gradually until 3 years of age. CONCLUSIONS: We suggest that these reference ranges are of importance in evaluating tubular damage due to a variety of renal diseases in infancy.