Tyrosine phosphorylation of the proto-oncogene product Vav and its association with the adapter Grb2/Ash in a human leukemia cell line UT-7.

The vav proto-oncogene product (Vav) is expressed exclusively in hematopoietic cells and is reported to have guanine nucleotide exchange activity. Here we report that granulocyte-macrophage colony-stimulating factor, interleukin-3, and erythropoietin induce tyrosine phosphorylation of Vav in a human leukemia cell line UT-7. Tyrosine phosphorylation of Vav is rapid and transient; it occurs within 1 min of the stimulation and at physiological concentrations of the factors.

An acute myeloid leukemia gene, AML1, regulates hemopoietic myeloid cell differentiation and transcriptional activation antagonistically by two alternative spliced forms.

The AML1 gene on chromosome 21 is disrupted in the (8;21)(q22;q22) and (3;21)(q26;q22) translocations associated with myelogenous leukemias and encodes a DNA binding protein. From the AML1 gene, two representative forms of proteins, AML1a and AML1b, are produced by alternative splicing. Both forms have a DNA binding domain but, unlike AML1b, AML1a lacks a putative transcriptional activation domain.

Cardiac implications of the morning surge in blood pressure in elderly hypertensive patients: relation to arising time.

Although morning surge in blood pressure has been shown to be associated with the occurrence of myocardial ischemic events and stroke, few studies have been done regarding its pathogenesis, probably because of a lack of method for the quantitative assessment of awakening time. We conducted an echocardiographic study and ambulatory blood pressure monitoring in 23 elderly hypertensive patients to evaluate the relationship between the hypertensive cardiac change and morning surge in blood pressure. Of note was that the time of arising from bed was assessed quantitatively by an activetracer equipped with an internal acceleration sensor to monitor the physical activity.

Cerebellar ataxia in patients with Leber's hereditary optic neuropathy.

We report the cases of a mother and son with Leber's hereditary optic neuropathy (LHON), where a point mutation of mitochondria DNA from guanine to adenine on nucleotide position 11778 was verified. Both also had cerebellar ataxia and dysarthria and in both cases cerebellar atrophies were detected by computed tomography or magnetic resonance imaging. It was not possible to elucidate the relationship between LHON and the cerebellar atrophy, but it should be kept in mind that various neurological complications may occur in LHON.

Molecular analysis of the t(1;19)(q23;p13) translocation observed in adult leukemias.

We report three cases of adult leukemias with the t(1;19)(q23;p13) translocation, two with acute lymphoblastic leukemia (ALL:L2) and one with megakaryoblastic crisis of chronic myelocytic leukemia. Only one patient with ALL showed the same E2A/PBX1 fusion transcripts as those observed in childhood ALLs with the t(1;19) by RNA-based polymerase chain reaction. This patient survived for 8 months only from the time of his diagnosis.

Methylation imprinting was observed of mouse mo-2 macrosatellite on the pseudoautosomal region but not on chromosome 9.

Mouse mo-2 macrosatellites consisting of 31-bp tandem repeat units are mainly located at two loci in the C57BL/6 genome, one being at the centromere-distal telomeric region of chromosome 9 and the other at the pseudoautosomal (PA) region of chromosomes X and Y. The two clusters constitute approximately 300 kb and 150 kb, respectively. Southern analysis of a methylation-sensitive enzyme, HpaII-digested DNA showed that the mo-2 macrosatellites are detected as more than 30 polymorphic bands.

Effect of perindopril on 24-hour blood pressure levels and hemodynamic responses to physical and mental stress in elderly hypertensive patients.

This study assessed the effects of an angiotensin-converting enzyme (ACE) inhibitor, perindopril, on the 24-hour blood pressure (BP) profile and hemodynamic responses to isometric exercise and mental stress in elderly hypertensive patients. We performed ambulatory BP monitorings and echocardiographic studies during hand-grip exercises and a mental stress test before and after the 10-week administration of perindopril in 11 elderly patients (mean age, 71.8 years).

Homozygous loss of the cyclin-dependent kinase 4-inhibitor (p16) gene in human leukemias.

Recently, it has been shown that the homozygous deletion of the cyclin-dependent kinase-4 inhibitor (CDK4I;p16) gene, which is mapped to chromosome 9p21, is frequently observed in a wide spectrum of human cancers, including leukemias. Therefore, the CDK4I gene is thought to be a putative tumor-suppressor gene. We report here that both alleles of the CDK4I gene were completely or partially deleted in human leukemia cells derived from both patients and established cell lines.

Evi-1 raises AP-1 activity and stimulates c-fos promoter transactivation with dependence on the second zinc finger domain.

Evi-1 is a gene, encoding a zinc finger protein, associated with a common viral integration site in murine leukemias. It is suggested that Evi-1 plays important roles in embryogenesis and transformation of myeloid cells. To elucidate mechanisms by which Evi-1 induces such biological effects, we analyzed the relationship between Evi-1 and AP-1 which could regulate cellular proliferation and differentiation.

Transduction of human bone marrow by adenoviral vector.

Recombinant adenoviral vectors have been shown to be potential new tools for a variety of human gene therapy protocols. We examined the effectiveness of an adenovirus vector for gene transfer into human bone marrow (BM). Mononuclear cells from one adenosine deaminase (ADA)-deficient and two normal human BM samples were transduced by an E1-defective adenoviral vector encoding human ADA and kept in myeloid long-term culture.

Isolation of porcine reproductive and respiratory syndrome (PRRS) virus from Heko-Heko disease of pigs.

Porcine reproductive and respiratory syndrome (PRRS) virus was isolated at high frequency from the sera and lungs of pigs affected with Heko-Heko disease. In addition, a considerable amount of Mycoplasma hyorhinis (Mhr) was also isolated from the lungs. Inoculation of gnotobiote pigs with the first isolate of PRRS virus resulted in the reproduction of proliferative and interstitial pneumonia.

Characterization of diazepam-insensitive [3H]Ro 15-4513 binding in rodent brain and cultured cerebellar neuronal cells.

Experiments were performed to characterize diazepam-insensitive [3H]Ro 15-4513 binding sites in discrete regions of rodent brain and cultured rat cerebellar granule cells. Scatchard analysis of [3H]Ro 15-4513 binding in the presence of 10 microM diazepam revealed that diazepam-insensitive binding sites in the rat brain were most abundant in the cerebellum, followed by the hippocampus, cerebral cortex and olfactory bulb. Diazepam-insensitive sites represented approximately 80% of the total [3H]Ro 15-4513 binding sites in the membranes of cultured rat cerebellar granule cells.

Marked and reproducible increase in trilineage blood cell counts by administration of granulocyte colony-stimulating factor in a patient with refractory anaemia with excess blasts in transformation.

We report a patient with refractory anaemia with excess blasts in transformation (RAEB-t) who presented with severe pancytopenia and received four intermittent series of granulocyte colony-stimulating factor (G-CSF) treatment over 1.5 years. In addition to the increase in mature neutrophils, platelet count and haemoglobin level were dramatically increased.

Generation of the AML1-EVI-1 fusion gene in the t(3;21)(q26;q22) causes blastic crisis in chronic myelocytic leukemia.

The t(3;21)(q26;q22) translocation, which is one of the consistent chromosomal abnormalities found in blastic crisis of chronic myelocytic leukemia (CML), is thought to play an important role in the leukemic progression of CML to an acute blastic crisis phase. The AML1 gene, which is located at the translocation breakpoint of the t(8;21)(q22;q22) translocation found in acute myelocytic leukemia, was also rearranged by the t(3;21)(q26;q22) translocation. Screening of a cDNA library of the t(3;21)-carrying leukemic cell line cells (SKH1) resulted in the isolation of two potentially complete AML1-EVI-1 chimeric cDNAs of 6 kb.

[Chorea-ballism associated with nonketotic hyperglycemia and presenting with bilateral hyperintensity of the putamen on MR T1-weighted images--a case report].

A 55-year-old woman was admitted to our hospital with abrupt onset of chorea-ballism in the right arm and both legs. She had thirst before admission. The blood glucose level was 976 mg/dl, the serum osmolality was 335 mOsm/l, and there was slight ketonuria on admission.

Abnormal cytoskeletal pathology peculiar to corticobasal degeneration is different from that of Alzheimer's disease or progressive supranuclear palsy.

An autopsy case of clinically diagnosed "corticobasal degeneration (CBD)" was investigated. In addition to status spongiosus and neuronal achormasia around the central sulcus, cortical pyramidal neurons and thread-like structures were densely stained by Gallyas stain and tau immunohistochemistry, but apparent fibrillary structures like Alzheimer's disease neurofibrillary tangle were absent. Bodian, methenamine-Bodian, Congo red, thioflavin S, or Bielshowsky stains failed to visualize these structures.

[The relation between blood pressure variation and daily physical activity in early morning surge in blood pressure].

Morning rise in blood pressure (morning surge; MS) has been shown to be associated with the occurrence of myocardial ischemic events and stroke. This study aimed to elucidate the incidence and the mechanism of MS in hypertensive patients (HT). We monitored ambulatory blood pressure (BP) and physical activity in 68 untreated HTs using TM2421 (A & D Co.

Detection of the PML/RAR alpha fusion gene in acute promyelocytic leukemia with a complex translocation involving chromosomes 15, 17, and 18.

We report a case with typical clinical features of acute promyelocytic leukemia (APL) carrying an atypical chromosomal aberration involving chromosomes 15, 17, and 18. Molecular analysis using Southern blot hybridization and reverse transcriptase-polymerase chain reaction (RT-PCR) proved the creation of the PML/RAR alpha fusion gene in this case. These findings support the notion that this fusion is of crucial importance to leukemogenesis of APL.

Two mouse hypervariable minisatellites: chromosomal location and simultaneous mutation.

Pc-1 and Pc-2 hypervariable minisatellites of the mouse show a structural similarity and hence have been compared in terms of chromosomal location and mutability. Polymorphisms of the Pc-2 locus detected by analyses of Southern blotting and polymerase chain reaction were used for typing 61 backcross mice that were obtained by mating (C57BL/6 x MSM)F1 females to MSM males. Segregation patterns indicated that the Pc-2 locus maps to the 60 cM region of chromosome 6, while that of Pc-1 maps to chromosome 4.

[The surgical management of blunt liver trauma].

One hundred and sixty-six consecutive patients with closed hepatic injury admitted to Osaka University Hospital from 1966 to 1990 were reviewed to evaluate the surgical procedures for injured liver. Of the 166 patients, 37 died within 24 hours of initial management. Thirteen (35%) of the 37 died related to exsanguinating hemorrhage of liver injury.

The role of inorganic metals and metalloporphyrins in the induction of haem oxygenase and heat-shock protein 70 in human hepatoma cells.

The role of inorganic metals and metalloporphyrins in the induction of mRNAs for haem oxygenase and heat-shock protein 70 (hsp70), the two heat-shock proteins, was examined in human HepG2 and Hep3B hepatoma cells. SnCl2, but not Sn-protoporphyrin, was found to be a potent inducer of both haem oxygenase and hsp70 mRNAs. In contrast, CoCl2, ZnCl2 and FeCl2 caused little induction of haem oxygenase and hsp70 mRNAs, whereas the porphyrin complexes of these metals strongly induced haem oxygenase mRNA, without influencing the level of hsp70 mRNA.

Gene transfer therapy for heritable disease: cell and expression targeting.

Gene therapy is defined as the delivery of a functional gene for expression in somatic tissues with the intent to cure a disease. Different gene transfer strategies may be required to target different tissues. Adenosine deaminase (ADA) deficiency is a good gene therapy model for targeting a rare population of pluripotent hematopoietic stem cells capable of self-renewal.