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Biomedical subjects

K Mitani

Publications and source records attributed to K Mitani.

At least 163 records · Page 9Linked to original sources

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. The virus was recovered from the inoculated pigs for long periods. Superinfection with PRRS virus and Mhr appeared to produce more serious pneumonia than inoculation with PRRS virus alone. In this study, the presence of PRRS virus was confirmed in Japan, and the PRRS virus was considered as being the most important pathogen for Heko-Heko disease.

Animals↗

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. On the other hand, the other two cases were negative for the E2A/PBX1 fusion and one of them with ALL remains in remission. Our observations suggest that there could be heterogeneity in the molecular events among adult leukemias carrying the t(1;19) and that the E2A/PBX1 fusion formation might also be associated with an adverse treatment outcome in adult leukemias as in childhood leukemias.

Adolescent↗

[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. Even after normalization of the blood glucose level choreiform movement of the right arm and leg continued. Brain CT showed bilateral and symmetrical high density of the putamen on admission, which diminished at 32 days leaving an area of low density. This suggested that the high density was not calcification. There was no mass affect. Symmetrical high intensity of the bilateral putamen on MR T1-weighted images which was slight on admission increased in intensity after 2 months, but disappeared 4 months after the onset in association with the disappearance of choreiform movement. The abnormality in the putamen was considered to be the cause of her involuntary movements. In nonketotic hyperglycemia, high intensity basal ganglia lesions on T1-weighted MR images have previously not been reported. High intensity in the putamen on T1-weighted MR images in the present case might represent multiple petechial hemorrhages which occurred in association with metabolic disorders including nonketotic hyperglycemia.

Chorea↗

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. The induction process was largely transcriptional, as judged by the inhibition of induction by actinomycin D, but not by cycloheximide, and by increased transcription demonstrated by nuclear run-off analysis. Since CoCl2 is a potent inducer of haem oxygenase in vivo in animals, the possibility of the biosynthesis of Co-protoporphyrin was examined in human hepatoma cells by incubating them with CoCl2 and protoporphyrin, or delta-aminolaevulinate (ALA), the precursor of protoporphyrin. Both types of treatment led to a potent induction of haem oxygenase mRNA. Co-protoporphyrin formation was also spectrally demonstrated in cells incubated with the metal and ALA. The results of this study indicate that certain metals, e.g. SnCl2, may directly induce haem oxygenase mRNA, whereas with other elements, incorporation of the metal into the porphyrin macrocycle is necessary for induction. Therefore CoCl2, like haemin, may activate the haem oxygenase gene via a haem-responsive transcription factor, whereas SnCl2 may exert its effect via a metal-responsive transcription factor.

Carcinoma, Hepatocellular↗

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. We present evidence for the highly efficient gene transfer and sustained expression of human ADA in human primitive hematopoietic progenitors using retroviral supernatant with a supportive stromal layer. A stem cell-enriched (CD34+) fraction was also successfully transduced. Duchenne muscular dystrophy (DMD) is also a good model for somatic gene therapy. Two of the challenges presented by this model are the large size of the gene and the large number of target cells. Germline gene transfer and correction of the phenotype has been demonstrated in transgenic mdx mice using both a full-length and a truncated form of the dystrophin cDNA. We present here a deletion mutagenesis strategy to truncate the dystrophin cDNA such that it can be accommodated by retroviral and adenoviral vectors useful for somatic gene therapy.

Adenosine Deaminase↗

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.

Base Sequence↗

Long-term expression of retroviral-transduced adenosine deaminase in human primitive hematopoietic progenitors.

Adenosine deaminase (ADA) deficiency, a rare autosomal recessive disorder, is an ideal candidate for gene replacement therapy. By means of co-cultivation with a retroviral vector-producing cell line, we have demonstrated efficient transfer and expression of the human ADA gene into human primitive hematopoietic progenitors. At 6 weeks post-transduction in myeloid long-term bone marrow culture, approximately 50% of the clonogenic progenitors were transduced by the provirus, with ADA expression detected in 30% of transduced colonies. The ADA activity increased by 3.7-fold in the nonadherent fraction of transduced bone marrow after 9 weeks. We have also achieved efficient transduction by retroviral supernatant of normal and ADA-deficient bone marrow cells that were allowed to establish a stromal layer in long-term culture, indicating the feasibility of proceeding with attempts to perform stem cell gene therapy on patients with ADA deficiency.

3T3 Cells↗

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. Simultaneous mutation of the two loci was examined in 101 F1 mice. Pc-1 and Pc-2 loci showed mutation rates of 14.4 and 5.0% per gamete, respectively. Of the nine mice with a Pc-2 mutation, four carried a Pc-1 mutation at the same maternally- or paternally-derived allele. The rate of comutation was 44% (4/9), higher than the 12.2% (24/197) of Pc-1 mutation alone. This suggests that the germline mutation of the two hypervariable minisatellites may result from a common mechanism.

Alleles↗

[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. Ltd.) and ACTIVETRACER (GMS Ltd.) for detection of MS. MS was defined as a rise in BP > 50 mmHg (90% tile of 35 normotensives) during early morning (4:00 to 9:00 A.M.) compared with the lowest basal BP at night. MS was seen in 41 patients (52.6%) and was classified into two groups; MS1: BP rose steeply after waking up (27 patients) and MS2: BP started to rise gradually during sleep (14 patients). The mean age of MS1 was significantly higher than that of MS2 (72 vs. 62 years, p < 0.01). BP reached its basal value earlier in MS2 than in MS1 at night though the basal BP values were comparable between the two groups. Mean 24-hour BP and physical activity were similar between the two groups, though significantly higher incidence of cases with a correlation between SBP and activity was seen in MS1. In conclusion, there are two types of MS, the mechanisms of which may differ. MS occurring immediately after waking up was more common in older HTs, and possibly was related to augmented arousal response in BP, while MS beginning gradually during sleep was more common in younger HTs and was characterized by reaching basal BP earlier at night.

Activities of Daily Living↗

[Corticobasal degeneration: clinico-pathological studies on two cases].

We reported two patients with clinical features of corticobasal degeneration (CBD), one with autopsy observations. Their illness began in their sixties, ran progressive course and ended in death in about five years. The initial symptom was difficulty in manipulating with the left hands. Gradually the left lower limbs and the right limbs were also involved and the left became useless. They developed Parkinsonism, myoclonus, dystonia, hyperreflexia and vertical gaze palsy. They also showed the dysfunction of the fronto-parietal cortices, including grasping reflex, motor neglect, hemispatial neglect, constructional disturbance and cortical sensory loss. Dementia did not manifest until the terminal stage. Neuro-radiological studies demonstrated mild dilatation of the right central sulcus and marked reduction in cerebral blood flow in the fronto-parietal cortices, predominant in the right. Pathological examination in one of the case confirmed the the clinical diagnosis of CBD. There was a neuronal loss affecting second and third layers of the fronto-parietal cortices, especially the right parasylvian region, associated with spongiosis in these laminae and marked gliosis in deeper layers. Swollen, poorly staining (achromatic) neurons were observed in fifth layer. The hippocampus was unaffected. In the substantia nigra, there was extensive loss of pigmented cells. No Pick bodies, senile plaques, neurofibrillary tangles were observed in any region of the brain. The initial manifestations of their illness, the motor disturbances in the left upper extremities, were distinctive features in our patients. We could find no detailed description of these symptoms in the literature. We analysed these manifestations and described the results.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[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. Emergency laparotomy required hepatic resection in all and revealed hepatic vein or retrohepatic caval injuries in 9. Eighty-nine of 129 patients who survived over 24 hours of initial management underwent emergency laparotomy. Twenty-two of the 129 died thereafter. Five (3 underwent lobectomy and 2 simple suture) died of liver injury-related complications. Perihepatic packing was performed in 5 and all except for 2 of brain death were alive. Most complications except for hemobilia were well resolved. CT scan study revealed profoundly radiating injuries closed to spine in 63% and suggested existence of hepatic vein or caval injury. Especially, 20 of 31 CT studies (65%) in conservative management of liver injury showed the same findings with intact capsule. These results support that exsanguinating hemorrhage from deep injury including hepatic vein or vena cava is the most lethal but can be controlled with liver packing in a similar mechanism to liver trauma in conservative management.

Adult↗

Heme oxygenase is a positive acute-phase reactant in human Hep3B hepatoma cells.

The effects of human interleukin-6 (hIL-6), the major acute-phase inducer, on the level of the transcript of microsomal heme oxygenase (HO) were examined in a human hepatoma cell line, Hep3B. Messenger RNAs (mRNAs) encoding HO and haptoglobin (Hpt) increased after hIL-6 treatment in a time- and dose-dependent manner. hIL-6 had no effect on the induction of heat-shock protein 70 (hsp70) mRNA, suggesting that the induction of HO by hIL-6 is regulated by a different mechanism from that which mediates the heat-shock induction of this enzyme. The hIL-6-mediated induction of HO mRNA was completely abrogated by simultaneous treatment of cells with actinomycin D, but not with cycloheximide, suggesting that the induction occurs at the level of transcription. A nuclear factor was shown both in untreated, and in the hIL-6-treated Hep3B cells that binds specifically to the IL-6-responsive element (IL6-RE) of the human HO gene. These findings suggest that HO is a positive acute-phase reactant in this human liver-derived cell line, and that the nuclear factor specific to the IL6-RE may be involved in the activation of the HO gene after hIL-6 treatment.

Acute-Phase Proteins↗

Differential induction responses of delta-aminolevulinate synthase mRNAs during erythroid differentiation: use of nonradioactive in situ hybridization.

Expression of mRNAs encoding the erythroid-specific delta-aminolevulinate synthase (ALAS-E) and the nonspecific delta-aminolevulinate synthase (ALAS-N) were examined in murine Friend virus-transformed erythroleukemia (MEL) cells using nonradioactive in situ hybridization. Following dimethyl sulfoxide (DMSO) treatment, ALAS-E mRNA increased markedly, while ALAS-N mRNA did not increase in wild-type MEL cells. In contrast, in a DMSO-resistant clone of MEL cells, ALAS-E was not detectable before and after DMSO treatment. These findings suggest that ALAS-E and ALAS-N mRNAs are under separate controls and that the expression of ALAS-E mRNA is a critical event in erythroid differentiation.

5-Aminolevulinate Synthetase↗

Serum erythropoietin titers in hematological malignancies and related diseases.

Serum erythropoietin (Epo) titers in patients with various hematological malignancies and related diseases were determined by radioimmunoassay. Serum Epo titer was inversely correlated with hemoglobin concentration in iron deficiency anemia, aplastic anemia, myelodysplastic syndromes (MDS), acute leukemia, malignant lymphoma, multiple myeloma and myelofibrosis, but there was no correlation between serum Epo titer and hemoglobin concentration in chronic myelogenous leukemia or polycythemias. Serum Epo titers in aplastic anemia were much higher than those in iron deficiency anemia. Serum Epo titers in MDS, malignant lymphoma and multiple myeloma differed considerably among patients. Serum Epo titers in untreated polycythemia vera were significantly lower than in treated polycythemia vera or secondary polycythemia.

Anemia↗

Evaluation of enzyme immunoassay using a recombinant envelope protein expressed in insect cells for serological confirmation of HTLV-I infection.

A recombinant human T-lymphotropic virus type I (HTLV-I) envelope protein expressed in insect cells using a recombinant baculovirus was employed as the antigen in an enzyme immunoassay (renvEIA). Peripheral blood samples were obtained from asymptomatic carriers or healthy individuals. Plasma was tested for HTLV-I antibody by renvEIA, particle agglutination, and Western immunoblot (WB), and lymphocyte DNA was tested for HTLV-I proviral DNA amplification by polymerase chain reaction (PCR). Of 61 people aged 9 months or older, 23 were positive (gag+, env+) and 19 others were in the "indeterminate" category (gag+, env-) when their WB results were interpreted according to the WHO-proposed criteria. Thirty-seven cases, including all of the WB+ cases and 14 of 19 WB indeterminate cases, were positive by renvEIA. In 34 of 37 renvEIA-positive cases, the presence of long terminal repeat (LTR) and tax/rex region of HTLV-I proviral DNA was detected by polymerase chain reaction (PCR) and following Southern blot hybridization. Thus, renvEIA would be a useful supplemental assay to confirm the presence of HTLV-I antibody in HTLV-I asymptomatic carriers.

Adolescent↗