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Biomedical subjects

K Mitani

Publications and source records attributed to K Mitani.

At least 55 records · Page 3Linked to original sources

[Progressive limb-kinetic apraxia with myoclonus focal atrophy in the postcentral gyrus and the supplementary motor area].

We report a 70-year-old right handed man with a 5-year history of slowly progressive clumsiness of his left hand. A neurological examination disclosed mild rigidity and myoclonus in his left hand. He showed limb-kinetic apraxia, but neither ideational apraxia nor ideomotor apraxia was present. Aphasia and agnosia were also absent. He was thought to have the primary progressive limb-kinetic apraxia clinically. Brain CT and MRI revealed focal atrophy in the right postcentral gyrus and the supplementary motor area. A positron emission tomography (PET) study showed diffuse decrement of cerebral blood flow, predominantly in the right hemisphere. The decrease in the uptake of [18F]-Fluoro-deoxyglucose also revealed glucose hypo-metabolism, especially in the right frontal and parietal lobe. Striatal [11C]NMSP and [18F]FDOPA uptake were also reduced in an asymmetric pattern. These findings suggest that our patient is likely to have corticobasal degeneration. Transcranial magnetic stimulation using double pulse paradigm revealed a decrease in the level of cortico-cortical inhibition in the motor cortex on the affected side. Our results indicate increase in the excitability of motor cortical neurons in primary progressive limb-kinetic apraxia, likely due to a decreased excitability of cortico-cortical inhibitory mechanism as a result of focal degeneration of cortical neurons.

Aged↗

Frequent false-positive results of Aspergillus latex agglutination test: transient Aspergillus antigenemia during neutropenia.

BACKGROUND: Two serologic assays, Aspergillus latex agglutination testing (LA) and plasma (1-->3)-beta-D-glucan (BDG) measurement, are used when invasive pulmonary aspergillosis (IPA) is suspected. Despite the high specificity of these assays, false-positive results are frequent for neutropenic patients. This study was conducted to evaluate the efficacy of LA and BDG and to investigate the cause of the false-positive results. METHODS: Eighty-eight consecutive patients with hematologic malignancies who underwent intensive chemotherapy were tested weekly with LA and BDG. RESULTS: Sixteen of 88 patients were diagnosed as having IPA. The sensitivity, specificity, and positive predictive values were 23%, 98%, and 64% for LA and 27%, 88%, and 52% for BDG, respectively. Of 11 patients who became positive for LA only during neutropenic periods, 2 patients developed IPA. In contrast, six of eight patients who became positive for LA during nonneutropenic periods developed IPA. Transient Aspergillus antigenemia was more frequently encountered during neutropenia (2.9%) than during nonneutropenic periods (0.2%). The plasma BDG concentration increased at the nadir of neutropenia in 36 of 45 patients who had no signs of IPA, and it exceeded the level of 20 pg/mL in 2 patients. CONCLUSIONS: Both BDG and LA have a low sensitivity and a high specificity for IPA. However, the false-positive rate of LA increases during neutropenic periods. Caution should be exercised in interpreting the results of these blood tests, especially when patients are neutropenic.

Adolescent↗

Transcriptional inhibition of p53 by the MLL/MEN chimeric protein found in myeloid leukemia.

The t(11;19)(q23;p13.1) translocation is frequently found in adult myeloid leukemia. In the MLL/MEN fusion protein generated by this translocation, most of the coding region of the MEN protein, an RNA polymerase II elongation factor, is fused to the N-terminal third of the MLL protein, a possible transcriptional regulator. However, the molecular mechanism of leukemogenesis by the fusion protein remains unclear. We investigated the effects of the fusion protein on p53 function using luciferase assays. Overexpression of the fusion protein suppressed the transactivation ability of p53. This negative effect of the fusion protein on p53 function was dependent on the region derived from MEN. Moreover, p53 coimmunoprecipitated with MLL/MEN as well as MEN, suggesting that the fusion protein binds to p53 through the MEN region. We found that MEN binding to p53 was mediated by its N-terminal region and repression of p53 transcriptional activity was mediated by its C-terminal region. We also found that these two functional regions were essential for the transformation of Rat1 cells mediated by MEN. Although we could not demonstrate a functional difference between MLL/MEN and MEN in this study, these data suggest that the MLL/MEN chimeric transcriptional regulator may exert its oncogenic activity by inhibiting the function of the p53 tumor-suppressor protein by binding to it. Our findings provide a novel insight into the leukemogenic mechanism exerted by the t(11;19)(q23;p13.1) translocation.

Adult↗

TT virus in bone marrow transplant recipients.

TT virus (TTV) is a newly discovered transfusion-transmissible DNA virus, which may cause posttransfusion hepatitis. The virus was detected in 12% of Japanese blood donors. The aim of the study is to investigate the prevalence and clinical influence of TTV in bone marrow transplant (BMT) recipients. Sera from 25 BMT recipients obtained 6 to 12 weeks after the transplant were examined for TTV-DNA by the seminested polymerase chain reaction. Serial samples were additionally analyzed in patients with TTV-DNA. Fifteen of 25 recipients (60%) were positive for TTV-DNA after transplant, whereas it was detected in only two of 20 BMT donors (10%). In patients positive for TTV-DNA before BMT, the amount of TTV-DNA decreased to an undetectable level during the myelosuppressed period after BMT. We also found that there was a novel group of TTV, G3, classified by the nucleotide sequences. The median peak alanine aminotransferase (ALT) levels were 135.0 IU/L and 116.5 IU/L (normal range, 4 to 36 IU/L) in TTV-positive and TTV-negative recipients, respectively. In one of the seven TTV-positive patients who developed hepatic injury (ALT > 150 IU/L), a serial change in the serum TTV titer showed a good correlation with the ALT level. We concluded that (1) the prevalence of TTV is high in BMT recipients, (2) TTV might be replicated mainly in hematopoietic cells, (3) transfusion-transmitted TTV may cause persistent infection, (4) a novel genetic group of TTV, G3, was discovered, and (5) TTV does not seem to frequently cause hepatic injury, although one patient was strongly suggested to have TTV-induced hepatitis.

Adolescent↗

Unilateral papilledema after bone marrow transplantation.

We describe a patient who developed unilateral papilledema after allogeneic BMT. This is a rare manifestation of pseudotumor cerebri, which results from elevated intracranial pressure caused by cyclosporin A. The papilledema usually involves the fundi bilaterally, but unilateral involvement has been described. Congenital anomalies, compression and adhesion of the optic nerve sheath are its causes. In this patient, the right optic fundus was spared although leukemic infiltration was present on this side and high-dose irradiation (72 Gy) was given. Although papilledema is a sensitive marker of elevated intracranial pressure, this sign may be masked by constriction of the optic sheath in patients who suffer from leukemic infiltration of the central nervous system and receive high doses of cranial irradiation.

Adult↗

Ki-67 positive fractions in benign and malignant thyroid tumours: application of flow cytometry.

We investigated the DNA ploidy pattern, cell cycle and the percentage of Ki-67 positive fractions in fresh surgical material from 17 benign and 33 malignant thyroid tumours using flow cytometry. DNA aneuploidy was not seen at all in benign tumours, but was seen in 3 out of 33 malignant tumours, suggesting that detection of DNA aneuploidy indicates malignancy, although the detection sensitivity was low. Regarding the cell cycle, there was no difference in the percentage of S-phase fractions (SPF) or G2 plus M phase fractions (G2M) between benign and malignant tumours. However, the percentage of Ki-67 positive fractions in malignant tumours (39.9 +/- 3.9%) was significantly higher than that in benign tumours (9.4 +/- 2.1%), indicating that malignant thyroid tumours contained a large population of G phase cells. When a cut-off value of 20%, was used for Ki-67 positive fractions, sensitivity was 82%, specificity was 88% and accuracy was 84% for the diagnosis of malignant tumours. Although this study was carried out on surgically derived materials, it is possible that flow cytometric analysis of fine needle aspiration-derived materials may have a place in preoperative histopathological assessment of thyroid tumours.

Adenocarcinoma, Follicular↗

Frequency and stability of chromosomal integration of adenovirus vectors.

One of the limitations of adenovirus vectors is the lack of machinery necessary for their integration into host chromosomes, resulting in short-term gene expression in dividing cells. We analyzed frequencies of integration and persistence of gene expression from integrated adenovirus vectors. Both E1-substituted and helper-dependent adenovirus vectors achieved similar integration efficiencies of approximately 10(-3) to 10(-5) per cell, with the helper-dependent vector showing slightly higher efficiencies. In stable cell pools, gene expression of the integrated vector persisted for at least 50 cell divisions without selection. However, some stable cell clones showed changes in gene expression, which were accompanied by structural changes in the integrated vector DNA.

3T3 Cells↗

Early diagnosis of central nervous system aspergillosis with combination use of cerebral diffusion-weighted echo-planar magnetic resonance image and polymerase chain reaction of cerebrospinal fluid.

We treated a patient diagnosed as central nervous system (CNS) aspergillosis with the combined use of cerebral diffusion-weighted echo-planar magnetic resonance imaging (DWI) and polymerase chain reaction of the cerebrospinal fluid (CSF-PCR). DWI, a cutting-edge imaging modality to reveal the earliest changes of cerebral infarction, detected cerebral fungal embolization when the conventional computed tomographic scan and magnetic resonance imaging failed to reveal it. CSF-PCR demonstrated the presence of Aspergillus-specific DNA in the specimen, when the conventional examination and culture of CSF were nonspecific or negative. These diagnostic methods could be useful in the early diagnosis of CNS aspergillosis.

Aspergillosis↗

Increased serum soluble Fas ligand associated with recurrent B-cell non-Hodgkin's lymphoma after autologous peripheral blood stem cell transplantation.

Fas-ligand (FasL) is a member of the tumor necrosis factor family and transmits apoptotic cell death signal by binding to its receptor, Fas. FasL is expressed on the cell surface of activated T-cell and natural killer (NK) cell. It has been shown that the FasL can be released from the cell surface by metalloproteinase. The serum soluble FasL (sFasL) is increased in some patients with NK cell lymphoma/large granular lymphocytic leukemia. We have recently seen a patient with recurrent B-cell lymphoma accompanied with an increased serum sFasL level after autologous peripheral blood stem cell transplantation. The sFasL was markedly decreased with the tumor regression induced by the chemotherapy. We present here the first case of an elevated serum sFasL level associated with B-cell lineage malignancy and discuss the possible clinical value of sFasL.

Adult↗

[Reduction of forehead integrated EMG and integrated alpha wave through mechanical chair vibration using progressive relaxation by Mitani method].

An experiment was conducted to investigate the effects of respondent revised progressive relaxation by Mitani Method (new PR) on left frontal (Fpl) electromyogram (EMG) and electroencephalogram (EEG) alpha waves. 20 subjects, 10 males, 10 females, mean age = 29, SD = 10.05, were divided into the experimental group and the control group. The experimental group received the respondent new PR. Intermittent two minutes vibrations and five minutes rests, namely DV 15-9-4.5. V vibration were given at shoulder and leg. The Fpl integrated EMG, integrated alpha wave and time of alpha wave appearance were measured by Mitani System. Results showed that only the experimental group showed significant integrated EMG reduction at Fpl. Alpha waves tended to appear more frequently. Integrated alpha wave, however, decreased significantly. Combined mean of integrated EMG and integrated alpha wave also decreased significantly. These results suggest the quick reduction of energy expenditure or entering into a deep relaxation of neuro-muscle circuit by the mechanical respondent New PR. As for operant New PR, experiment including such EEG data is not yet performed.

Adult↗

Mutations of the WT1 gene in childhood nonlymphoid hematological malignancies.

The Wilms' tumor gene WT1, whose loss of function accounts for the genesis of about 10% of Wilms' tumors, is expressed in hematopoietic stem cells and leukemia. By analogy with the relationship between the kidney stem cell and Wilms' tumor, it is probable that WT1 is mutated in leukemia. WT1 mutations have been found in only eight cases of primary leukemia, mainly in acute myeloid leukemia (AML) and rarely in acute lymphoblastic leukemia. However, two other studies have demonstrated the absence of WT1 mutations in leukemia. To determine if WT1 mutations are associated with leukemias, we screened childhood nonlymphoid malignancies for WT1 mutation. WT1 mutations were found in 6 of 46 (13%) AMLs, but not in other nonlymphoid hematological malignancies. In addition, the presence of WT1 mutations in AML caused by chromosomal translocations suggests that mutations of WT1 may lead to the progression of leukemia.

Child↗

Molecular characterization of the genomic breakpoints in a case of t(3;21)(q26;q22).

The t(3;21)(q26;q22) is a recurring chromosomal abnormality in blastic crisis of chronic myelogenous leukemia (CML) and in therapy-related myelodysplastic syndrome and acute leukemia. In order to clarify the genetic recombination mechanism underlying the t(3;21), we molecularly cloned the breakpoints and determined their nucleotide sequence in a case of CML in blastic crisis with t(3;21). Near the breakpoint on chromosome 21, three homopyrimidine (CT)-rich sequences were found. We also identified a sequence homologous to the topoisomerase II binding and cleavage consensus sequence surrounding the breakpoint on chromosome 3, and two topoisomerase II binding and cleavage consensus sequences near the breakpoint on chromosome 21. In addition, around the breakpoint on chromosome 21, four chi-like sequences, potential consensus signals for activating recombination, were found. There were no Alu sequences or antigen receptor gene-like heptamer/nonamer signal sequences within the breakpoints on chromosomes 3 and 21. The breakpoints were found adjacent to the topoisomerase II binding and cleavage consensus sequence or the homopyrimidine-rich sequence. Furthermore, the chi-like sequences and the homopyrimidine-rich sequence were detected on chromosome 21 but not on chromosome 3. Genes Chromosomes Cancer 26:92-96, 1999.

Amino Acid Sequence↗

[A case report of pure micrographia progressing over 5 years--an early sign of "pure akinesia"?].

We report a 68-year-old man who have had only slowly progressive micrographia in both hands over the past 5 years without rigidity, tremor, bradykinesia, and festination or freezing in walking. The fine finger movements were normal. PET studies suggested the diagnosis of progressive supranuclear palsy or pure akinesia. Administration of L-DOPA and L-threo-DOPS did not improve his micrographia. Festination and freezing in writing may contribute to the genesis of micrographia in this case. We postulate that "pure micrographia" is an early atypical sign of pure akinesia.

Aged↗