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Biomedical subjects

M Toshima

Publications and source records attributed to M Toshima.

At least 19 recordsLinked to original sources

Identification of myelodysplastic syndrome-specific genes by DNA microarray analysis with purified hematopoietic stem cell fraction.

Myelodysplastic syndrome (MDS) is a slowly progressing hematologic malignancy associated with a poor outcome. Despite the relatively high incidence of MDS in the elderly, differentiation of MDS from de novo acute myeloid leukemia (AML) still remains problematic. Identification of genes expressed in an MDS-specific manner would allow the molecular diagnosis of MDS. Toward this goal, AC133 surface marker-positive hematopoietic stem cell (HSC)-like fractions have been collected from a variety of leukemias in a large-scale and long-term genomics project, referred to as "Blast Bank," and transcriptome of these purified blasts from the patients with MDS were then compared with those from AML through the use of oligonucleotide microarrays. A number of genes were shown to be expressed in a disease-specific manner either to MDS or AML. Among the former found was the gene encoding the protein Delta-like (Dlk) that is distantly related to the Delta-Notch family of signaling proteins. Because overexpression of Dlk may play a role in the pathogenesis of MDS, the disease specificity of Dlk expression was tested by a quantitative "real-time" polymerase chain reaction analysis. Examination of the Blast Bank samples from 22 patients with MDS, 31 with AML, and 8 with chronic myeloid leukemia confirmed the highly selective expression of the Dlk gene in the individuals with MDS. Dlk could be the first candidate molecule to differentiate MDS from AML. The proposal is made that microarray analysis with the Blast Bank samples is an efficient approach to extract transcriptome data of clinical relevance for a wide range of hematologic disorders.

DNA↗

A member of Forkhead family transcription factor, FKHRL1, is one of the downstream molecules of phosphatidylinositol 3-kinase-Akt activation pathway in erythropoietin signal transduction.

The phosphatidylinositol 3-kinase (PI3K) signaling pathway is important for the regulation of a number of cellular responses. Serine/threonine kinase Akt (protein kinase B; PKB) is downstream of PI3K and activated by growth factors. This study found that erythropoietin (EPO) induced tyrosine phosphorylation of Akt in a time- and dose-dependent manner in EPO-dependent human leukemia cell line UT-7/EPO. In vitro kinase assay using histone H2B and glucose synthase kinase as substrates demonstrated that Akt was actually activated by EPO. EPO-induced phosphorylation of Akt was completely blocked by a PI3K-specific inhibitor, LY294002, at 10 micromol/L, indicating that activation of Akt by EPO is dependent on PI3K activity. In addition, overexpression of the constitutively active form of Akt on UT-7/EPO cells partially blocked apoptosis induced by withdrawal of EPO from the culture medium. This finding suggested that the PI3K-Akt activation pathway plays some role in the antiapoptotic effect of EPO. EPO induced phosphorylation of a member of the trancription factor Forkhead family, FKHRL1, at threonine 32 and serine 253 in a dose- and time-dependent manner in UT-7/EPO cells. Moreover, results showed that Akt kinase activated by EPO directly phosphorylated FKHRL1 protein and that FKHRL1 phosphorylation was completely dependent on PI3K activity as is the case for Akt. In conjunction with the evidence that FKHRL1 is expressed in normal human erythroid progenitor cells and erythroblasts, the results suggest that FKHRL1 plays an important role in erythropoiesis as one of the downstream target molecules of PI3K-Akt.

DNA-Binding Proteins↗

All-trans-retinoic acid treatment for chemotherapy-resistant acute adult T-cell leukemia.

We report a case in which treatment with all-trans-retinoic acid (ATRA) improved the clinical features of a 47-year-old female patient with acute adult T-cell leukemia (ATL). The patient was first treated several times with combination chemotherapy. but the number of ATL cells increased and other clinical manifestations progressed. ATRA 60 mg was then administered daily. ATRA treatment dramatically improved the patient's clinical features. In vitro examination revealed that ATRA inhibited the growth of ATL cells from the patient. These findings suggest that ATRA may be a useful treatment for patients with chemotherapy-resistant acute ATL.

Acute Disease↗

Primary duodenal MALT lymphoma.

Primary duodenal MALT lymphoma (MALToma) is a very rare neoplasm arising from the mucosa-associated lymphoid tissue of the duodenum. We report a 55-year-old woman with MALToma located in the descending duodenum and accompanying Helicobacter pylori infection of the stomach. We performed operative resection due to involvement of the papilla of Vater and submucosal tumor infiltration. Despite wide mucosal spreading, postoperative examination revealed only a small amount of MALToma cells infiltrating into the submucosa. No invasion into the adjacent structure or metastasis to regional lymph nodes was confirmed, suggesting the disease could have been controlled by eradication of Helicobacter pylori.

Duodenal Neoplasms↗

[Tricuspid valve replacement in a patient with idiopathic tricuspid regurgitation].

Tricuspid regurgitation is often seen but is rarely categorized as "idiopathic". A 66-year-old man suspected of idiopathic tricuspid regurgitation underwent tricuspid valve replacement. With right heart failure over twenty years, his CTR increased to eighty six (86) per cent. During operation, no abnormal findings were observed except for the dilated tricuspid valve ring. Then a stented porcine xenograft (Carpentier-Edwards 33 mm) was inserted in the tricuspid valve annulus. Seven years after replacement, he died. Autopsy demonstrated myocardial hypertrophy of the right ventricle and dilatation of the right heart, supporting the diagnosis of idiopathic tricuspid regurgitation.

Aged↗

A new method for right ventricular endomyocardial biopsy via the femoral veins: a novel approach employing a right ventriculography catheter (Nishiya type).

We have devised a new method for right ventricular endomyocardial biopsy, in which the use of a right ventriculography catheter (Nishiya Type) allows us to ensure the introduction of a guiding sheath (Cordis, right-angled long sheath) to the apical portion of the right ventricle by way of the femoral vein. With this method, we have biopsied the endomyocardium in 52 patients during the last 4 years. In each case, it only took us several minutes to complete the biopsy procedure. Neither failed applications nor significant complications were seen. We believe that this technique provides a clinically beneficial means as it enables us to readily and safely achieve right ventricular endomyocardial biopsy.

Adolescent↗

Oculomotor nerve invasion of acute myelogenous leukemia demonstrated by magnetic resonance imaging.

A 53-year-old male was diagnosed as having acute myelogenous leukemia (M2, FAB). He complained of double vision and right blepharoptosis after receiving remission induction chemotherapy. Magnetic resonance imaging (MRI) showed enlargement of the bilateral oculomotor nerves. Intrathecal injections of methotrexate and cytosine arabinoside were partially effective and repeated MRI showed shrinkage of the enlarged oculomotor nerves, after therapy. This case shows the importance of MRI in the early diagnosis of CNS leukemia.

Cranial Nerve Neoplasms↗

[Retrospective analysis of elderly patients > or = 60 years of age with acute leukemia].

A retrospective analysis was performed on 76 consecutive elderly patients with acute leukemia aged 60 years or more (48 men, 28 women). Forty patients were 60-69 years old, 28 were 70-79 years old and 8 were > or = 80 years old. There were 55 patients with acute myelogenous leukemia (AML), 13 acute lymphoblastic leukemia (ALL) and 8 AML from myelodysplastic syndrome (MDS/AML). Patients were treated with the JALSG protocol, CAG regimen, or low-dose Ara-C regimen for AML, and DVP/M-CHOP protocol for ALL. The complete remission (CR) rates were 52.7% (29 of 55) in AML, 61.5% (8 of 13) in ALL, and 0% in MDS/AML. The median CR durations were 226, 85, 0 days, and the median survivals were 204, 177, 99 days, respectively. CR rates were 65.3% for the JALSG protocol, 62.5% for the CAG regimen and 25.0% for low-dose Ara-C regimen. According to age, CR was obtained 62.5% in patients aged 60-69 years and 33.3% in patients over 70 years old. Our results indicated that patients aged 60-69 years should be treated with intensive chemotherapy.

Aclarubicin↗

[A case of mediastinal teratoma discovered availing of pneumonia].

A 42-year-old woman was admitted to our hospital with hemosputum and an abnormal shadow on chest X-ray. Although her hemosputum disappeared after the treatment of pneumonia, the abnormal shadow was not improved. Chest CT showed a mediastinal mass. She underwent thoracotomy and the tumor, measuring 6 x 5 x 5 cm in size, was resected. Pathological diagnosis was a mature type teratoma with direct invasion to the lung. We have to take mediastinal teratoma into consideration as one of the causes of pneumonia.

Adult↗

[A case of anastomotic aneurysm-enteric fistula].

We successfully performed circulation reconstructive surgery and repair of a small intestine resection, primarily at an anatomical position, for perforation of a pseudoaneurysm in the small intestine, which occurred in an anastomosis site of the right leg of a Y graft of an artificial blood vessel and internal iliac artery graft on a patient, at the remote time of 18 years after she had received a Y-type artificial blood vessel. The patient's life was saved. The results suggest that it is important to make a definitive diagnosis quickly after the occurrence of symptoms and to select an appropriate surgical technique according to the findings of infection adjacent to the perforation site.

Aged↗

Effect of gamma knife irradiation on relaxation and contraction responses of the common carotid artery in the rat.

This report concerns a pilot study of the short- and long-term effects of gamma knife radiosurgery on vascular responses. The investigation was carried out on male Sprague-Dawley rats, and the relaxation and contraction responses of the right common carotid artery (CCA) were assessed following irradiation (100 Gy). The non-treated CCA of the same animals served as internal controls. Non-irradiated rats were used to control the effect of normal aging on vascular function. Isometric tension was determined on in vitro preparations of arterial rings. Acetylcholine-mediated, endothelium-dependent relaxation was impaired one month after radiosurgery, as was endothelium-independent relaxation induced by sodium nitroprusside, but the effect on the latter was minimal. The irradiated CCA was also impaired with respect to contraction responses induced by norepinephrine, endothelin-1 or phorbol dibutyrate. This impairment appeared to be biphasic, as it was evident one day after radiosurgery, followed by a partial recovery one week later, and again manifest after one month. At the light microscope level, the carotid arteries appeared to be well preserved throughout the experiment. However, obvious ultrastructural changes were noted in endothelial and smooth muscle cells of specimens obtained three months after radiosurgery. The present data indicate that high dose gamma knife radiosurgery affects the functions of both, the vascular endothelium and the vascular smooth muscles in an apparent time-dependent fashion. Because of its increasing application to patients, there is the need for studying the effects of gamma knife radiosurgery on cerebral arteries, since functional vascular changes may occur in the absence of obvious histological alterations. Our results on CCAs point to the feasibility of such experimental investigations.

Animals↗

[Thrombotic complication in the course of aplastic anemia-paroxysmal nocturnal hemoglobinuria syndrome; possible involvement of dysplasminogenemia (plasminogen Tochigi) in the pathogenesis of thrombosis].

A 44-year-old Japanese man having aplastic anemia (AA)-paroxyamal nocturnal hemoglobinuria (PNH) syndrome was referred to our hospital because of purpuras due to thrombocytopenia in July 1994. He suffered from pneumonia after admission, complicated with cerebral, splenic, and left renal infarction. Pulmonary infaction was also confirmed by perfusion lung scan. He had a plasma plasminogen (PLG) functional activity of 54.4% with a normal level of PLG antigen. The gel isoelectrofocusing pattern of the plasminogen derived from the patient showed 10 normal bands and 10 additional doublet bands with slightly higher isoelectric points than the normal components. Abnormal PLG is converted by urokinase to an inactive two-chain plasmin molecule. These findings were similar to those of a case with dysplasminogenemia (PLG Tochigi) reported by Aoki et al. He was given warfarin for the prevention of thrombosis in December 1994. As of October 1995, these was no recurrence of thrombosis. The cause of thrombosis in the present case have been the association with PNH, predisposition to PLG Tochigi, or the complication of pneumonia. This is the first report of AA/PNH syndrome associated with dysplasminogenemia.

Adult↗

Treatment of labyrinthine fistula with interruption of the semicircular canals.

Evaluation of postoperative hearing acuity and equilibrium was performed in eight patients with labyrinthine fistula caused by cholesteatoma, in which at least one of the semicircular canals (five cases, lateral; one case, superior; one case, posterior; and one case, both lateral and superior) was interrupted during eradication of the matrix and granulations from the semicircular canals. The interrupted semicircular canals were obliterated firmly with autologous materials such as fascia, perichondrium, bone chips, and cartilage. The observation period ranged from 9 months to 3.3 years. Postoperative hearing was unaltered or improved in seven patients, and decreased by 12 dB in one patient. Postoperative disequilibrium lasting more than 2 weeks was experienced in two patients and disappeared at the second and fifth postoperative months, respectively. Relief from fistula symptoms was complete after surgery, indicating adequacy of this procedure in one-stage open-method tympanoplasty. The present study indicates that manipulation of the semicircular canal with awareness can be conducted without damaging the cochlear function, and that the treatment of labyrinthine fistulas should be performed very carefully but not so conservatively as to lead to future problems. In some cases of deep fistulas of the semicircular canals, interruption and/or obliteration of the semicircular canals can be the most proper procedure.

Adult↗

[Cavernostomy and muscle plombage with the pedicled latissimus dorsi and serratus anterior flap for recurrent large bullae with infection: a case report].

A 70-year-old male, who suffered from infection by MRSA and Aspergillus of the recurrent large bullae, was operated on cavernostomy for space sterilization. About three months later he underwent muscle plombage with the pedicled latissimus dorsi and serratus anterior flap. These muscles are ideal to place in open wound in the thorax because of the following reasons: These have the ability to eliminate local infection, a sufficient length and volume to obliterate an open cavity. And transposition of these muscles cause minimal functional upper extremity disability. Therefore, we considered that this technic was useful for the case of an infectious intrathoracic cavity with many bronchial fistulas.

Aged↗