Shinkichi Yokoyama

Expression of erythroid‐specific genes in acute megakaryoblastic leukaemia and transient myeloproliferative disorder in Down's syndrome

Summary. Acute megakaryoblastic leukaemia (M7) and transient myeloproliferative disorder in Downs syndrome (TMD) are characterized by rapid growth of abnormal blast cells which express megakaryocytic markers. To clarify properties of the blast cells in M7 and TMD cases, we examined erythroid markers expression in blasts from six cases with M7 and seven cases with TMD in this study. Erythroid‐specific mRNAs encoding 7‐globin and erythroid 6‐aminolevulinate synthase were found to be expressed in blasts from most of these cases, indicating that majorities of the blasts in M7 and TMD cases have erythroid and megakaryocytic phenotypes. We also found that mRNAs encoding GATA‐1 and GATA‐2 are expressed in all these cases. These results suggest that M7 blasts and TMD blasts correspond to the erythroid/megakaryocytic bipotential progenitor cells.

Severe hypertension and cardiac failure associated with neuroblastoma: A case report

The authors report on 3-year-old-girl with neuroblastoma complicated by severe hypertension and cardiac failure. She had cardiomegaly and pleural and pericardial effusions. Echocardiogram showed left ventricular hypertrophy and decrease of the left ventricular ejection fraction to 0.36 (normal > .40). Abdominal computed tomographic scan indicated a 7 x 7-cm tumor in the left suprarenal area. There was a marked increase in catecholamines and metabolites in her body fluids. After hypertension was controlled with doxazosin (a long-acting alpha 1 adrenergic blocker), her cardiac function gradually improved. A tumor was surgically removed and diagnosed as a poorly differentiated ganglioneuroblastoma. Preoperative differentiation between neuroblastoma and pheochromocytoma was not possible on the basis of catecholamine analysis or imaging studies including computed tomography scan and magnetic resonance imaging. It is important to control hypertension quickly in the patients with catecholamine-induced cardiomyopathy to facilitate surgical intervention for diagnosis and treatment.

TRANSIENT ABNORMAL MYELOPOIESIS FOLLOWED BY ACUTE MEGAKARYOBLASTIC LEUKEMIA WITH EXTRAMEDULLARY TUMORS

An autopsied case of acute megakaryoblastic leukemia Is described in a 20 months old, Japanese female infant with Downs syndrome. She presented spontaneous remission of transient abnormal myelopoiesis in her neonatal period, which was followed by acute megakaryoblastic leukemia 1 year later. The clinical picture of acute megakaryoblastic leukemia was initially characterized by peripheral pancytopenia with a few blasts, the absence of hepatosplenomegaly, but ended in overt leukemia characterized by increase of blasts, marked hepatosplenomegaly, and elevated LDH. She died 6 months after the onset at 20 months of age. Autopsy findings revealed widespread leukemic infiltration comprised of megakaryoblasts and megakaryocytes, and extramedullary tumors In the left tibia, the liver, both kidneys, and the endocardium of the heart. Identification of the megakaryocytic cell line was performed in immunohistochemistry and electron microscopy. Chromosomal analyses of peripheral blood disclosed 47, XX, +21, in her neonatal period but disclosed 48, XX, +G, +G, in acute megakaryoblastic leukemia.

Severe bleeding tendency in a patient with Bernard-Soulier syndrome associated with a homozygous single base pair deletion in the gene coding for the human platelet glycoprotein Ibα

Purpose The genetic basis of Bernard-Soulier syndrome (BSS) was studied to clarify a relationship between severe clinical manifestations and gene abnormality. Patient and Methods A patient with BSS had a severe bleeding tendency that was sometimes life threatening. Flow cytometric analysis of the patients and normal control platelets was performed to study which glycoprotein (GP) was impaired in glycoprotein Ib/V/IX complex. The genes encoding GPIbα from the patients and control genomic DNA were amplified and directly sequenced. Results Flow cytometric analysis revealed a defect of GPIbα on the surface of the patients platelets. A homozygous single base pair deletion was identified in seven repeats of adenine at positions 1932 to 1938 in the GPIbα gene. This mutation, which has been previously reported, results in a frameshift and predicts a premature stop codon leading to a truncated peptide that cannot fix on the platelet membrane. Conclusion This patients severe clinical phenotype would be explained by this mutation in the GPIbα gene.

Chromosomal aberration in lipoblastoma: A case with 46,XX,ins(8;6)(q11.2;q13q27)

Chromosomal aberrations involving 8q11.2 have been reported in lipoblastoma. We report here a case of lipoblastoma with new chromosomal aberration. 46,XX,ins(8;6)(q11.2;q13q27). Cytogenetic analysis would facilitate the clinical differentiation between myxoid liposarcoma and the pathologically similar lipoblastoma and the identification of genetic loci related to cellular growth.

CD48 expression on leukocytes in infectious diseases: Flow cytometric analysis of surface antigen

Background: The function of CD48, one of the pan leukocyte cell surface antigens, is not yet well understood. CD48 was recently shown to enhance the CD40‐mediated activating signal to B lymphocytes. As CD48 is one of the activation antigens of monocytes, neutrophils and lymphocytes, a change of its expression on the cells could be expected in infectious diseases.

Novel mutations of the glutaryl‐CoA dehydrogenase gene in two Japanese patients with glutaric aciduria type I

We identified three different point mutations in the glutaryl-CoA dehydrogenase (GCDH) gene in two unrelated Japanese patients with glutaric aciduria type I (GA-I). One patient was a homozygote for Arg355His and the other a compound heterozygote for Ser305Leu and Met339Val. Arg355His and Met339Val are mutations hitherto undescribed, and all three mutations are predicted to alter the secondary structure of GCDH. Molecular analysis is useful for definite diagnosis and/or prenatal diagnosis of GA-I.

Muscular dystrophy associated with extra-abdominal desmoid tumor showing aberrant chromosome 1 [46,XX,add(1)(p36)]

We report on a 2-year-old girl with probable limb-girdle muscular dystrophy associated with an extra-abdominal desmoid tumor of the right mandible. This association is previously undescribed. The tumor was totally removed. Cytogenetic analysis of the tumor showed a clonal karyotypic abnormality: 46,XX,add(1)(p36) in 3 of 20 cells analyzed. Since an association of a neoplasm with limb-girdle muscular dystrophy has previously been reported in 3 cases, the two abnormalities are likely related causally. The chromosome abnormality in our patient may play a role in the occurrence of her desmoid tumor.