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Biomedical subjects

M Harada

Publications and source records attributed to M Harada.

At least 739 records · Page 41Linked to original sources

T lymphoid/myeloid bilineal crisis in chronic myelogenous leukemia.

We describe 2 cases of "bilineal" crisis in chronic myelogenous leukemia (CML) with T cell and myeloid phenotypes. In both cases, morphocytochemically distinct myeloid and T lymphoid blast populations proliferated simultaneously in the phase of blastic crisis--myeloperoxidase (MPO)-positive, CD7+/CD33+ myeloblasts in the peripheral blood, and MPO-negative, periodic acid Schiff (PAS)-positive lymphoblasts in the lymph nodes. In each case, common karyotypes containing Ph1 translocation were demonstrated in both the peripheral blood and the lymph node samples. In Case 1, the lymph nodes were occupied by > 90% lymphoblasts, which were positive for CD2, cytoplasmic CD3 (cCD3), CD5 and CD7 and terminal deoxynucleotidyl transferase (TdT), but negative for myeloid antigens. Myeloblasts and T lymphoblasts showed an identical rearrangement of the bcr gene by Southern blotting analysis, although the clonal rearrangement of the T cell receptor (TcR)-delta gene was seen only in T lymphoblasts. In Case 2, simultaneous proliferation of myeloblasts and lymphoblasts was documented morphocytochemically in the lymph node, and a flow cytometric analysis revealed the coexistence of CD7+/CD33+ and CD7+/CD33- blast populations. Each blast population was enriched by antibody-conjugated immunomagnetic beads; the former was positive for MPO by 64% but negative for cCD3 and TdT, whereas the latter was positive for cCD3 and TdT but negative for MPO (< 1%). CD7+/CD33+ myeloblasts and CD7+/CD33- lymphoblasts showed an identical rearrangement of the bcr gene. Neither TcR-beta, TcR-gamma nor the TcR-delta gene was clonally rearranged in either population. These observations clearly indicate that T lymphoid and myeloid blasts share common Ph1-positive progenitors, and that Ph1-positive T lymphoid/myeloid progenitors are probably involved in the development of blastic transformation in some percentage of CML patients.

Adult↗

[Clinical application of cytokines in peripheral blood stem cell transplantation].

Peripheral blood stem cells (PBSC) are increased dramatically during a recovery phase after myelosuppressive chemotherapy. PBSC can be used for hematological reconstitution after marrow-ablative therapy. Autologous blood stem cell transplantation (ABSCT) has increasingly been used for the treatment of malignant diseases. Cytokines, especially hematopoietic cytokines are utilized for mobilization of PBSC, enhancement of chemosensitivity of leukemic cells having cytokine receptors and enhancement of hematologic recovery after ABSCT. We studied effects of granulocyte colony-stimulating factor (G-CSF) in these settings. In cytotoxic drug plus G-CSF mobilization of PBSC, granulocyte/macrophage and erythroid progenitor cells were significantly increased in PBSC harvests compared to cytotoxic drug-induced mobilization. When G-CSF was administered prior to the marrow-ablative conditioning before ABSCT, clinical results suggest that chemosensitivity of leukemic cells may be increased. When G-CSF was given after ABSCT, hematologic recovery from marrow aplasia was enhanced substantially. These observations clearly indicate that G-CSF is useful to mobilize PBSC and to facilitate ABSCT.

Adolescent↗

Erythropoietin production in hepatocellular carcinoma cells associated with polycythemia: immunohistochemical evidence.

Patients with hepatocellular carcinoma sometimes have erythrocytosis and high plasma erythropoietin levels. However, previous studies have not revealed direct evidence that the carcinoma cells produce the erythropoietin. To address this question, we carried out light and electron microscopic immunohistochemical studies, using a human erythropoietin antibody to the liver in three male patients with hepatocellular carcinoma and erythrocytosis. alpha-Feto-protein localization was also examined in serial liver sections by light microscopic immunohistochemistry with an antibody to alpha-fetoprotein. All three patients demonstrated high hemoglobin levels (16.7, 17.6 and 18.1 gm/dl) and high plasma erythropoietin levels (227, 266 and 280 mU/ml). In one patient the plasma erythropoietin level in the hepatic vein was significantly higher than that in the hepatic artery. The levels of plasma erythropoietin, as well as such tumor markers for hepatocellular carcinoma as serum alpha-fetoprotein and plasma des-gamma-carboxyprothrombin, were significantly reduced after treatment with an anticancer drug, cisplatin. Light microscopic immunohistochemistry showed that erythropoietin was definitely present in the cytoplasm of the hepatocellular carcinoma cells, but not in normal hepatocytes around the carcinoma lesion or in other nonparenchymal cells such as vascular endothelial cells and Kupffer cells. In electron microscopic immunohistochemistry, reaction products for erythropoietin were revealed in the cisternae of the endoplasmic reticulum in the carcinoma cells, suggesting the production of erythropoietin by these cells. Light microscopic immunohistochemistry showed that alpha-fetoprotein was localized in the hepatocellular carcinoma cells that were erythropoietin positive in the serial sections. These findings indicated that hepatocellular carcinoma cells produced erythropoietin as well as alpha-fetoprotein in these cases, leading to the complication of erythrocytosis.

Aged↗

[Evaluation of left ventricular systolic function by pulsed Doppler echocardiography in patients with acute myocardial infarction].

Left ventricular systolic function in patients with acute myocardial infarction was assessed by Doppler echocardiographic measurement of left ventricular ejection flow velocity and maximum acceleration in 20 patients with initial acute anteroseptal myocardial infarction (group A) and 15 age-matched normal subjects. All patients underwent emergency reperfusion therapy by direct percutaneous transluminal coronary angioplasty (direct PTCA). Pulsed Doppler echocardiograms were obtained from sample volume immediately below the aortic valve in the apical long-axis view. Three parameters, peak velocity, ratio of acceleration time to ejection time (AT/ET) and maximum acceleration, were measured by the Doppler analysis program. Changes in the 3 parameters from the day of admission to the 3rd post-admission day were also observed in 15 patients. Although no significant difference was observed in AT/ET in the 2 groups, peak velocity and maximum acceleration in the patient group were significantly lower than those in the normal group (peak velocity: 90.8 +/- 13.1 vs 99.4 +/- 9.7 cm/sec, p < 0.05, maximum acceleration: 2,692.4 +/- 604.5 vs 3,410.2 +/- 712.5 cm/sec2, p < 0.01, respectively). Between the admission and 3rd day, peak velocity and AT/ET did not change significantly, but maximum acceleration increased significantly (2,720.5 +/- 676.7, 1st day vs 3,313.9 +/- 947.5 cm/sec2, 3rd day, p < 0.05). These results indicate that the maximum acceleration measured by pulsed Doppler echocardiography is useful for assessing global left ventricular systolic function in acute myocardial infarction. Direct PTCA results in improved ventricular systolic function on the 3rd post-operative day.

Adult↗

[Dose escalation study of high dose etoposide in autologous hematopoietic stem cell transplantation].

Eight cases with poor prognosis hematological malignancies (non-Hodgkin lymphoma, 6 cases; acute non-lymphocytic leukemia, 2 cases) and nine cases with non-hematological malignancies were treated with high dose etoposide (VP16) containing regimen followed by autologous hemopoietic stem cell transplantation. Results were as follows; 1) all of three chemotherapy sensitive relapse patients with hematological malignancies continue complete remission without any cyto-reductive therapy 2) one of four refractory relapse patients continue remission 3) partial anti-tumor effect was noted in non-hematological malignancies, however, only two cases continue complete remission. Remission duration of other responders was not so long. The results disclosed the dose-limiting factor of high-dose VP16 therapy as reversible stomatitis with no related mortality, and maximal tolerated dose appears to be 60 mg/kg over 72 hr with 45 mg/kg as a safe and recommended therapeutic dose in future clinical trial. The clinical effect of dose escalation was not clearly demonstrated.

Adult↗

Muscle relaxant action of dantrolene sodium in rats.

The relationship between the muscle relaxant action and intramuscular concentration of unchanged dantrolene sodium [1-[5-(p-natrophenyl) furfurylidene amino] hydantoin sodium hemiheptahydrate, dantrolene] by intravenous administration of dantrolene was examined in rats. The mechanism of the muscle relaxant action of dantrolene was also examined. Dantrolene, unlike tolperisone, a centrally acting muscle relaxant, dose-dependently inhibited twitch contraction evoked by electrical stimulation of both the muscle and the phrenic nerve in the rat isolated phrenic nerve-diaphragm preparation to a similar extent (IC50: 9.5 and 6.5 x 10(-6) M, respectively). Inhibition of both twitch contractions by dantrolene (50 microM) was antagonized by 4-aminopyridine (42.5 microM) and caffeine (4 mM). The twitch contraction of the gastrocnemius muscle elicited by sciatic nerve stimulation was inhibited by intravenous administration of dantrolene in a dose-dependent manner. The effective intramuscular concentration of dantrolene producing 50% depression (ID50) was 3.4 micrograms/g tissue, equal to about 1 x 10(-5) M. We thus found a close relationship between IC50 in vitro and ID50 in situ. Furthermore, this study raised the possibility that dantrolene produces its muscle relaxant action by affecting peripheral muscular Ca2+ mobilization.

4-Aminopyridine↗

[Autologous blood stem cell transplantation].

Autologous blood stem cell transplantation (ABSCT) has been increasingly used, as the third generation of hemopoietic stem cell transplantation next to allogeneic and autologous bone marrow transplantation (allo-BMT and ABMT), in the treatment of malignant diseases. As to the principle of treatment, ABSCT is identical to ABSCT. However, ABSCT has some advantages over ABMT as follows: 1) a rapid engraftment, 2) no requirement of general anesthesia for harvesting hemopoietic stem cells, and 3) possibility of less contamination of tumor cells. Accordingly, ABSCT will take place of ABMT in the strategy of cancer treatment and improved results will be expected.

Adult↗

[Cytomegalovirus antigenemia in the differential diagnosis of pulmonary infiltrates after allogeneic bone marrow transplantation].

For the differential diagnosis of pulmonary infiltrates after bone marrow transplantation, cytomegalovirus (CMV) antigenemia was evaluated in 9 episodes of pneumonia which developed in 7 allogeneic marrow transplant patients between 9 and 495 days after transplant. The diagnosis of lung infiltration was made based on clinical findings including histological, cytological or microbiological examinations using bronchoalveolar lavage fluid specimens, sputum or lung tissue. The CMV antigen-positive leukocytes were detected with a direct immunoperoxidase technique using a peroxidase-labeled monoclonal antibody (HRP-C7) against CMV immediate early antigen. The episodes included 2 CMV pneumonias, 1 pneumocystis carinii pneumonia, 1 adenovirus pneumonia, 1 bacterial pneumonia, 1 bacterial and fungal pneumonia, 2 idiopathic pneumonias and 1 capillary leak syndrome associated with hyper acute GVHD. The CMV antigenemia became positive only in two patients with CMV pneumonia and the number of CMV antigen-positive leukocytes exceeded 10 per 50000 WBCs. The CMV antigenemia test required only 24 hours to obtain results. These observations suggest that the detection of CMV antigenemia is of great value in the differential diagnosis of pulmonary infiltrates in marrow transplant patients.

Adult↗

[A case report of acute mid-graft occlusion of the left internal mammary artery to the left anterior descending artery after PTCA].

A 66 year-old woman underwent coronary artery bypass grafting for postinfarction angina. A left internal mammary artery graft was joined to the left anterior descending artery. Coronary and graft angiography revealed a 90% stenosis in the anastomotic site of the left internal mammary artery. During PTCA with a 2.0 mm balloon catheter, acute occlusion of the graft body occurred. Intragraft injection of isosorbide dinitrate failed to dilate the graft. Thus, careful consideration should be given to several complications such as acute occlusion of the graft when PTCA for anastomotic site of the graft is performed.

Acute Disease↗

Cyclosporine combined with methylprednisolone or methotrexate in prophylaxis of moderate to severe acute graft-versus-host disease.

To evaluate the efficacy of cyclosporine (CYA) regimens in preventing moderate to severe acute graft-versus-host disease (GVHD), 25 patients received immunosuppressive therapy consisting of either CYA and methylprednisolone or CYA and methotrexate (MTX) and the incidence and severity of acute GVHD was compared. These patients had leukemia or myelodysplastic syndrome (MDS) and received bone marrow transplants (BMT) from genotypically HLA-identical siblings. The incidence of grade I-IV acute GVHD in patients on the CYA/methylprednisolone regimen was 64% (7 of 11) compared with 50% (7 of 14) in those on the CYA/MTX regimen. Five of 11 patients with the CYA/methylprednisolone regimen developed moderate to severe acute GVHD (grade II-IV), fatal in 3 cases. No patient on the CYA/MTX regimen developed moderate to severe acute GVHD. Engraftment was faster in the CYA/methylprednisolone group than in the CYA/MTX group. The incidence of toxicity observed soon after BMT was comparable between groups. The CYA/MTX regimen may be superior to the CYA/methylprednisolone regimen for preventing moderate to severe acute GVHD.

Acute Disease↗

[Changes in plasma and urinary calcium levels during cardiopulmonary bypass].

Plasma total protein, total calcium, ionized calcium and urinary calcium were measured in six patients scheduled for open heart surgery, and the effect of the administration of calcium during and after cardiopulmonary bypass (CPB) was studied. After the initiation of CPB, plasma total protein decreased significantly from 5.47 +/- 0.50 g.dl-1 to 2.55 +/- 0.23 g.dl-1 (P < 0.01). Total calcium also decreased from 2.14 +/- 0.29 mmol.l-1 to 1.38 +/- 0.07 mmol.l-1 (P < 0.01), and remained depressed during CPB. However, ionized calcium was not decreased and showed normal value during CPB because total protein concentration was decreased by hemodilution. Urinary calcium excretion increased gradually during CPB from 0.18 +/- 0.17 mmol.h-1 to 0.87 +/- 0.38 mmol.h-1 (P < 0.01) and the increase continued after CPB. Fractional excretion of filtered calcium increased from 0.85 +/- 0.63% to 54.16 +/- 36.52% (P < 0.05) accompanied with hypothermia. From these findings, reabsorption of the calcium in the kidney was thought to be inhibited by the influence of hypothermia at the early phases after weaning from CPB. When total protein returned to normal value after weaning from CPB, percentage of ionized calcium is predicted to diminish. We conclude that after weaning from CPB, administration of calcium is required because of the prolonged increase of urinary calcium excretion, particularly if blood containing citrate is given.

Aged↗

Idiopathic retroperitoneal fibrosis: a case of unilateral lesion.

Here we report a case of idiopathic retroperitoneal fibrosis, a unilateral case, which resulted in remission by ureterolysis with intraperitonealization. A 24-year-old female was hospitalized because of hydronephrosis. Many examinations were performed with the suspicion of malignant disease, but no apparent cause was detected. We suspected idiopathic retroperitoneal fibrosis and performed surgical exploration. The pathological diagnosis was retroperitoneal fibrosis. Ureterolysis with intraperitonealization of the ureter was performed. Six months later, marked improvement of the right hydronephrosis was observed without steroid therapy.

Adult↗

[Establishment and characterization of a cell line (H-1) from squamous cell carcinoma of human gingiva--effect of temperature].

We established a cell line (H-1) from human oral cancer. It was derived from a biopsy specimen of squamous cell carcinoma in the lower gingiva of a japanese man. The cell line has now been growing in vitro for more than 86 passages. The cells had an epithelial morphology and grew as adherent monolayers. PAS stain was positive and activity of ALP also was positive. They had a doubling time of 37 hours and colony formation of 32%. Chromosomal numbers ranged from 49 to 75 and the modal number was 61. The cell line was tumorigenic in nude mice, its histologic examination showed identification with that from the original tumor. The cells were sensitive to hyperthermia.

Animals↗

Bone marrow microenvironment of patients with systemic lupus erythematosus.

In an attempt to clarify the hematologic abnormality in systemic lupus erythematosus (SLE), we studied the bone marrow microenvironment of 8 women with this disease. The number of fibroblast colonies was similar to that of healthy control individuals. Culture supernatants of monocytes obtained from the patients with SLE showed a diminished production of the hemopoietic growth factor required to stimulate bone marrow fibroblasts. As the activity of the humoral factor released from SLE monocytes was diminished, such a reduction may play a role in the pathogenesis of the hematologic abnormality seen in SLE.

Bone Marrow↗

[A case of multiple ureteral polyps treated with ureteroscopy].

We report a case of multiple ureteral polyps treated with a rigid ureteroscope in a 27-year-old man with the chief complaint of left lower abdominal pain. The patient, who had left renal stones pointed out on his plain film, was referred for further examination and treatment of left hydronephrosis as suggested by drip infusion pyelography (DIP). DIP and retrograde pyelography (RP) revealed left hydronephrosis and a filling defect in the upper third of ureter. An ureteroscopic inspection and biopsy was conducted. The pathological diagnosis was fibroepithelial polyps of the ureter, so we performed an ureteroscopic polypectomy for the treatment. The postoperative course has elapsed favorably, without ureteral stricture or recurrence of the polyps. Ureteroscopic procedures are considered to be useful for the preoperative diagnosis and treatment of ureteral polyps.

Adult↗

Dynamic MR imaging of hepatoma treated by transcatheter arterial embolization therapy. Assessment of treatment effect.

The effect of transcatheter arterial chemo-embolization therapy (TACE) for hepatoma was evaluated with dynamic MR imaging with Gd-DTPA in 37 patients (44 tumors). TACE was performed using Lipiodol/cis-platinum and gelatin sponge (or microspheres) as an embolic material. All patients were examined with dynamic CT and MR imaging before and after treatment. On conventional spin echo images, changes of signal intensity after treatment varied regardless of presence of Lipiodol. Dynamic MR imaging revealed changes of tumor vascularity before and after treatment. On histologic correlation, areas of persistent tumor enhancement on dynamic MR imaging corresponded to areas of viable tumor cells while areas of non-enhancement corresponded to areas of necrosis. Dynamic MR imaging was superior in contrast resolution and was not influenced by the presence of Lipiodol compared with dynamic CT, and therefore residual viable tumors were better defined by dynamic MR imaging.

Adult↗