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H Harada

Publications and source records attributed to H Harada.

At least 289 records · Page 16Linked to original sources
PubMed1997

Upregulation of interferon-alpha receptor expression in hydroxyurea-treated leukemia cell lines.

BACKGROUND: Interferon-alpha (IFN-alpha) shows its antitumor effect through binding to specific cell surface receptors. A DNA synthesis inhibitor, hydroxyurea (HU), has been successfully combined with IFN-alpha to improve the efficiency of IFN therapy for chronic myelogenous leukemia (CML). To understand the mechanism of this combination effect, expression of IFN-alpha receptors on the CML cell line, K562, was studied before and after treatment with HU. METHODS: Cells were treated with HU at a dose of 0, 0.1, 0.2, or 0.4 mmol/L for 48 hours. Binding assays were performed using 125I-labeled IFN-alpha at 4 degrees C. Cell cycle analysis was carried out using flow cytometer following staining cellular DNA with propidium iodide. Northern blot analysis was performed to evaluate the inducibility of interferon regulatory factor-1 (IRF-1) gene expression by IFN-alpha. RESULTS: Hydroxyurea-treated cells showed a dose- and time-dependent increase in binding of 125I-labeled IFN-alpha (maximal 2.5-fold). The increase of binding was caused by an increase in the number of binding sites with a constant receptor affinity. Similar results were obtained in the Burkitt's lymphoma cell line, Daudi. Cell cycle analyses suggested that upregulation of the IFN receptor may have occurred as a result of the alteration in the cell cycle distribution. Furthermore, IFN-alpha induction of the IFN-inducible gene IRF-1 mRNA in HU-treated K562 cells was 2-fold higher than that in untreated cells. CONCLUSIONS: Thus, HU may have an ability to enhance the response to IFN-alpha probably because of its ability to upregulate the IFN-alpha receptors, suggesting that this may be involved in the mechanism of effective combination therapy of IFN-alpha with HU.

Antineoplastic Agents↗
PubMed1997

[All-trans retinoic acid-induced myelomonocytoid differentiation in acute promyelocytic leukemia].

A 30-year-old man with a diagnosis of acute promyelocytic leukemia (APL) was admitted. Laboratory findings were as follows: WBC 32,900/microliter with 88% promyelocytes, Hb 10.4 g/dl, platelets 2.6 x 10(4)/microliter. Coagulation tests revealed DIC. Bone marrow was hypercellular with 91.8% promyelocytes which were strongly positive for peroxidase and positive for alpha-naphthyl butyrate esterase. Cytogenetic study revealed 46, XY, t(15;17) (q22:q11). He was treated with all-trans retinoic acid (ATRA) along with hydroxyurea (HU) and low-molecular weight heparin (LMH). Because his WBC increased to 93,700/microliter on day 6 of ATRA therapy, DCMP chemotherapy was given, while ATRA was withheld. He developed enterocolitis due to myelosuppression. ATRA was restarted along with granulocyte-colony stimulating factor (G-CSF). His WBC rose to 10,400/microliter with a marked, but temporary predominance of myelomonocytes both in peripheral blood and in bone marrow. These myelomonocytoid cells were positive for specific and nonspecific esterase double stainings. Then he entered complete remission. It was of interest that myelomonocytoid differentiation of APL cells was induced by ATRA. The etiology was discussed.

Adult↗
PubMed1997

[Lung lobar volume in patients with chronic interstitial pneumonia].

We measured lung lobar volume by using helical computed tomography (HCT) in 23 patients with idiopathic interstitial pneumonia (IIP), 7 patients with chronic interstitial pneumonia associated with collagen vascular disease (CVD-IP), and 5 healthy volunteers. HCT scanning was done at the maximal inspiratory level and the resting end-expiratory level. To measure lung lobar volume, we traced the lobar margin on HCT images with a digitizer and calculated the lobar volume with a personal computer. The lower lobar volume and several factors influencing it in chronic interstitial pneumonia were studied. At the maximal inspiratory level, the lower lobar volume as a percent of the whole lung volume was 46.8 +/- 4.13% (mean +/- SD) in the volunteers, 39.5 +/- 6.19% in the patients with IIP, and 27.7 +/- 7.86% in the patients with CVD-IP. The lower lobar volumes in the patients were significantly lower than in the volunteers. Patients with IIP in whom autoantibody tests were positive had lower lobar volumes that were very low and were similar to those of patients with CVD-IP. These data suggest that collagen vascular disease may develop in patients with interstitial pneumonia. The patients with IIP who had emphysematous changes on the CT scans had smaller decreases in total lung capacity and lower ratios of forced expiratory volume in one second to forced vital capacity than did those who had no emphysematous changes, those two groups did not differ in the ratio of lower lobar volume to whole lung volume. This suggests that emphysematous change is not factor influencing lower lobar volume in patients with chronic interstitial pneumonia. We conclude that chronic interstitial pneumonia together with very low values for lower lobar volume may be a pulmonary manifestation of collagen vascular disease.

Chronic Disease↗
PubMed1997

[A clinical investigation of Bentall's operation for annuloaortic ectasia in the elderly].

Although Bentall's operation has become a routine procedure for annuloaortic ectasia (AAE), few reports on its effects on operative mortality in elderly patients have been published. The results of Bentall's operation for AAE on 4 elderly patients were reviewed. There were two males and two females in the series. The ages ranged 71 to 77 years with an average of 73. The etiology of aneurysms was syphilitic in three and arteriosclerotic in one patients. All patients had AAE, aortic regurgitation and ascending aortic aneurysms. Of all these patients, 1 had a subacute Type A dissecting aneurysm, 1 had a proximal arch aneurysm and 1 had an aortic arch aneurysm plus a sacciform descending aortic aneurysm. All patients had composite graft replacement with coronary reimplantation. Three patients received the concomitant operative procedures including aortic arch replacement and CABG to right coronary artery with saphenous vein graft. All patients survived operation. Postoperative CTR and NYHA classification showed remarkable improvement and serious complications were not found in spite of old age. In the late postoperative period, all patients were alive and well from 4 to 6 years after operation. Bentall's operation can be performed in elderly patients with AAE.

Age Factors↗
PubMed1997

Clinicopathologic manifestations of Epstein-Barr virus-associated cutaneous lymphoproliferative disorders.

OBJECTIVE: To elucidate clinicopathologic manifestations of cutaneous lymphoproliferative disorders associated with Epstein-Barr virus (EBV) infection. DESIGN: Retrospective survey of case series. SETTING: University hospital medical center. PATIENTS: Sixty-five patients with cutaneous lymphomas and related disorders. MAIN OUTCOME MEASURES: Detection of EBV genes and EBV-encoded small nuclear RNAs. RESULTS: Evidence of latent EBV infection was demonstrated in 15 patients: 3 had malignant lymphoma with clinical features mimicking cytophagic histiocytic panniculitis, 6 had facial vesiculopapular eruptions mimicking hydroa vacciniforme, 4 had angiocentric lymphoma, 1 had histiocytoid lymphoma associated with hemophagocytosis, and 1 had plasmacytoma. Hypersensitivity to mosquito bites was noted in a patient with hydroa vacciniforme-like eruptions and another with histiocytoid lymphoma. Angiocentric infiltration of atypical lymphoid cells was a common histological feature in the patients with hydroa vacciniforme-like eruptions and angiocentric lymphoma. No evidence of EBV infection was apparent in 19 patients with mycosis fungoides or Sézary syndrome, 7 with adult T-cell leukemia or lymphoma, 3 with lymphomatoid papulosis (type A), and 2 with lymphocytoma cutis. CONCLUSION: Patients with EBV-associated cutaneous lymphoproliferative disorders present with unique and diagnostic clinicopathologic features distinct from those of mycosis fungoides or Sézary syndrome.

Adolescent↗
PubMed1997

[Blast crisis accompanied by severe DIC of Ph negative chronic myeloid leukemia showing t(9;16) and positive M-BCR/ABL rearrangement].

A 66-year-old woman complained of chest discomfort in January 1995. In March the accelerated phase of chronic myeloid leukemia (CML) was diagnosed. Chromosomal analysis demonstrated negative Ph and positive t(9;16) (q34;p11) with positive major BCR/ABL chimeric mRNA. Administration of hydroxycarbamide was initiated, but in May she developed high fever and severe left hypochondralgia. Her WBC was 62,100/microliter (blast 64%), and LDH was 3,590 IU/l. Bone marrow examination showed 78.6% blasts, with a nucleated cell count of 74 x 10(3)/microliter. Blasts were negative for esterase stain and partially positive for both peroxidase stain and PAS reaction. Surface marker analysis revealed that blasts were positive for CD13, CD19, CD33, CD34, and HLA-DR. A diagnosis of blast crisis was made and she was treated with the VDS-CP regimen with heparin for DIC. After temporary improvement her disease recurred rapidly with severe DIC. Treatment with low molecular weight heparin and fresh frozen plasma failed to control DIC and she died of subarachnoid hemorrhage on the 48th hospital day. This is the first veprted of case Ph-negative, M-BCR/ABL-positive CML with t(9;16) accompanied by severe DIC.

Aged↗
PubMed1996

Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L)

Extracellular survival factors alter a cell's susceptibility to apoptosis, often through posttranslational mechanisms. However, no consistent relationship has been established between such survival signals and the BCL-2 family, where the balance of death agonists versus antagonists determines susceptibility. One distant member, BAD, heterodimerizes with BCL-X(L) or BCL-2, neutralizing their protective effect and promoting cell death. In the presence of survival factor IL-3, cells phosphorylated BAD on two serine residues embedded in 14-3-3 consensus binding sites. Only the nonphosphorylated BAD heterodimerized with BCL-X(L) at membrane sites to promote cell death. Phosphorylated BAD was sequestered in the cytosol bound to 14-3-3. Substitution of serine phosphorylation sites further enhanced BAD's death-promoting activity. The rapid phosphorylation of BAD following IL-3 connects a proximal survival signal with the BCL-2 family, modulating this checkpoint for apoptosis.

14-3-3 Proteins↗
PubMed1996

Characterization of inhibition by chronic treatment with lithium ion on nerve growth factor-induced neuronal differentiation of rat PC12 pheochromocytoma cells.

To understand the mechanism underlying the neurotoxicity of lithium ion, we investigated the inhibition of the nerve growth factor-induced neuronal differentiation of rat PC12 pheochromocytoma cells induced by treatment with LiCl. Incubation with 0.1-3 mM LiCl from 30 min before nerve growth factor (NGF) treatment attenuated neurite outgrowth. Moreover, incubation with 3 mM LiCl from 24 h before strongly reduced the neurite out-growth. The chronic pretreatment inhibited the NGF-caused induction of acetyl-cholinesterase activity known to be elevated by NGF in transcription-dependent processes, and inhibited expression of c-fos proto-oncogene mRNA. This pretreatment also inhibited the NGF-induced formation of inositol phosphates, accompanied by the significant accumulation of inositol monophosphate. These observations, that chronic treatment with LiCl inhibits the NGF-induced neuronal differentiation in a transcription-dependent manner and inhibits phosphoinositide metabolism, suggest a possible causal relationship between these two events.

Acetylcholinesterase↗
PubMed1996

Identification of the lysyl oxidase gene as target of the antioncogenic transcription factor, IRF-1, and its possible role in tumor suppression.

The transcriptional activator IFN regulatory factor 1 (IRF-1) and its antagonistic repressor IRF-2 are regulators of the IFN system. IRF-1 also manifests tumor suppressive activity, and its inactivation could contribute to the development of human hematopoietic malignancies. Here, we report the identification of the lysyl oxidase gene as a target gene of IRF-1. An IRF response element was identified in the lysyl oxidase gene promoter. We also demonstrate that the transformed phenotype of ras-expressing embryonic fibroblasts with a null mutation in the IRF-1 allele could be suppressed by the expression of the lysyl oxidase cDNA, implicating its potential role in tumor suppression. Thus, the regulation of the lysyl oxidase gene by IRF-1 could contribute to the multistep process of malignant transformation.

3T3 Cells↗
PubMed1996

Cystic mesothelioma of the peritoneum.

We report a case of cystic mesothelioma of the peritoneum (CMP), a rare tumor. The magnetic resonance imaging (MRI) findings and the histochemical features were studied. The patient was an 18-year-old women who presented with upper abdominal pain. Abdominal ultrasonography and computed tomography showed a well defined cystic mass with a solid papillary projection in its lumen. MRI of the cyst showed high intensity on T2- and proton weighted images and low intensity on T1-weighted images, and the solid projection showed low intensity on T2- and proton-weighted images and slight low intensity on T1-weighted images, on which it was well enhanced. The lesion was suspected to be a benign cyst, such as a hemangioma, lymphangioma, or a splenic or pancreatic cyst. Complete surgical resection was performed. The resected specimen consisted of a unilocular cystic mass, with a solid projection, weighing 260 g and measuring 10 cm in diameter. The final diagnosis, arrived at by histopathological examination, was low-grade malignant CMP. The tumor cells were strongly positive for keratin, weakly positive for vimentin, and negative for epithelial membranous antigen. The patient is now well and symptom-free with no recurrence 19 months after operation. CMP is a rare tumor; only 12 cases have previously been reported in Japan.

Adolescent↗
PubMed1996

Outcome of major hepatectomy with pancreatoduodenectomy for advanced biliary malignancies.

In patients with advanced biliary malignancies a chance of curability is obtained by performing only major hepatectomy with concomitant pancreatoduodenectomy. This aggressive procedure carries two major risks: hepatic failure and pancreatic anastomotic leakage. Ten patients with advanced biliary malignancies were treated by major hepatectomy with pancreatoduodenectomy. Nine patients underwent right portal venous embolization before hepatectomy. Complete external drainage of pancreatic juice followed by second-stage pancreatojejunostomy was performed in five patients. Three of these five underwent concomitant resection of the hepatic artery, portal vein, or both. Pancreatogastrostomy was chosen for five patients who required no concomitant vascular resection. There were no hospital deaths or hepatic failures. Leaks from pancreatogastrostomy occurred in two patients. In five patients who underwent external drainage of pancreatic juice, there were no complications related to the pancreatic stump, although one had ischemic necrosis of the jejunal segment and laparotomy was repeated. Mean survival time was 31.8 months (range 13-59 months). Portal venous embolization and complete external drainage of pancreatic juice followed by late stage pancreatojejunostomy are recommended surgical procedures for patients undergoing major hepatectomy with pancreatoduodenectomy, especially when concomitant vascular resection is required for curative resection of the tumor in patients with a soft pancreatic parenchyma and thin pancreatic duct.

Adult↗
PubMed1996

The significance of epidermal growth factor receptor and matrix metalloproteinase-3 in squamous cell carcinoma of the oral cavity.

Surgical specimens from 65 patients with squamous cell carcinoma (SCC) of the oral cavity were examined immunohistochemically. The clinicopathological significance of the expression of epidermal growth factor receptor (EGFR) and matrix metalloproteinase-3 (MMP-3) was assessed. Among the 65 tumours, 20(30.8%) and 37(56.9%) tested positively for EGFR and MMP-3, respectively. A positive correlation between the expression of EGFR and MMP-3 was found. The expression of EGFR in oral SCCs was associated with an advanced T stage of the primary tumour, an advanced pathological stage, and a high incidence of neck metastasis. In addition, MMP-3 was primarily expressed at the advancing front of cancer with a diffuse invasive mode. Thus, overexpression of MMP-3 was associated with an advanced pathological stage, a diffuse invasive mode, and a high incidence of neck metastasis. The analysis of MMP-3 expression is useful to evaluate the pathological status of tumours. Because EGFR-overexpressed tumour should produce larger amounts of MMP-3 in vivo, a close examination of oral SCC for expression of EGFR and MMP-3 should be helpful to predict their malignant potential.

Adult↗
PubMed1996

Clinical manifestations of hypertrophic cardiomyopathy with mutations in the cardiac beta-myosin heavy chain gene or cardiac troponin T gene.

Introduction of molecular genetics has improved our understanding of HCM substantially, but has simultaneously raised further important questions. Studies on HCM are revealing a more complex picture than might have been expected on clinical grounds. Further extensive studies are warranted to elucidate the pathogenesis and pathophysiology of HCM, and to establish therapeutic strategies to cure or prevent the development of the disease.

Adult↗
PubMed1996

Epithelial-myoepithelial carcinoma--report of a case arising in the nasal cavity.

We present an extremely rare case of epithelial-myoepithelial carcinoma (EMC) arising in the nasal cavity. The patient was a 56-year-old Japanese male with a polypoid tumour arising from the nasal septum. Histopathological examination revealed the tumour to consist of a solid proliferation of clear-cells and, in some areas, small or elongated duct structures with a double-layered arrangement of inner cuboidal cells and outer clear-cells. Dual differentiation toward myoepithelial and ductal cells were confirmed immunohistochemically. The occurrence of EMC in the nasal cavity is possible and this entity should be generally recognized by surgical pathologists, not only those engaged in head and neck surgery.

Carcinoma↗
PubMed1996

Coherence analysis of EEG changes during odour stimulation in humans.

In a pilot study, EEG changes during odour administration were evaluated by coherence analysis. Ten normal adults were studied. Simultaneous recordings of 16 EEG channels with, and without, odour administration were stored on magnetic tape for further processing. EEG signals were analysed using a signal analyser. Coherence spectra were calculated between all possible channel pairs on the scalp. The amount of data was reduced by extracting broad band coherence values for five frequency bands: delta (2-3.9 Hz), theta (4-7.9 Hz), alpha 1 (8-9.9 Hz), alpha 2 (10-12.9 Hz), and beta 1 (13-17.9 Hz). Coherence values extracted from the control EEG recordings and those during odour administration were compared to evaluate the presence of any significant differences. The results demonstrated significant changes in the EEG coherence between the two control recordings (control before and control after) in the theta and beta 1 bands. These frequency bands were therefore excluded from the examination. During odorant stimulation with methyl-cyclopentenolone, the coherence in the delta band decreased in the frontal region, while that in the alpha 1 and alpha 2 bands increased in the temporal region. During odorant stimulation with scatol, the coherence in the delta band decreased in the frontal region, while that in the alpha 1 and alpha 2 bands increased between the longitudinal electrode locations. It was suggested that EEG coherence mapping may provide the basis for the development of an objective test of olfactory function in humans.

Adult↗
PubMed1996

Essential and non-redundant roles of p48 (ISGF3 gamma) and IRF-1 in both type I and type II interferon responses, as revealed by gene targeting studies.

BACKGROUND: Interferons (IFNs) are a class of cytokines which confer cellular resistance against viral infections. Type I (IFN-alpha and -beta) and type II (IFN-gamma) IFNs utilize distinct receptors, the stimulation of which results in the induction of downstream target genes. These target genes usually contain within their promoter region an IFN responsive element, termed ISRE (IFN stimulated response element) which binds a heterotrimeric transcription factor, ISGF3 (IFN-stimulated gene factor 3) consisting of p48 (ISGF3 gamma), Stat1 (Signal transducers and activators of transcription-1; alpha or beta), and Stat2. The ISRE sequence overlaps with that of IRF-E which binds another IFN-inducible factor, IRF-1 (IFN regulatory factor-1). RESULTS: We generated mice lacking p48 by gene targeting. We show that p48 plays an essential role in both type I and type II IFN responses; activation of IFN-inducible genes and establishment of the antiviral state by IFN-alpha or -gamma are both severely impaired, and ISRE-binding activities induced by both IFNs are absent in the p48-negative embryonic fibroblasts (EFs). Furthermore, we generated mice deficient for both p48 and IRF-1 and found that at least one IFN-inducible gene is dependent on both factors. CONCLUSIONS: p48 and IRF-1 do not perform redundant functions in the cell, but rather complement one another in both type I and II IFN responses.

Animals↗