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Biomedical subjects

H Harada

Publications and source records attributed to H Harada.

At least 199 records · Page 11Linked to original sources
PubMed1999

Activation of the transcription factor ISGF3 by interferon-gamma.

The interferon-stimulated gene factor 3 (ISGF3) transcription factor has been extensively studied in the context of the type I interferon (IFN-alpha/beta)-mediated antiviral response; it consists of the major DNA-binding component p48, and the signal transducers and activators of transcription (Stat)1 and Stat2. We show here that type II IFN (IFN-gamma) can also invoke the activation of ISGF3 in mouse primary embryonic fibroblasts. In fact, the two Stat proteins were tyrosine phosphorylated in IFN-gamma stimulated cells. Our present findings reveal an additional mechanism by which these two distinct types of cytokines, IFN-alpha/beta and -gamma, can commonly elicit antiviral activities.

Animals↗
PubMed1999

Evaluation and design of a small portable EMG amplifier with potential RMS output.

The present study attempted to design and evaluate a small portable electromyogram (EMG) amplifier that can output enhanced EMG and its root mean square (RMS) value. The production and design were of a laboratory scale without any special or high cost circuit construction. The designed amplifier was actually innovated according to the actual working conditions based on physiological anthropology. The present amplifier was compared with commercially available products and proved to be of practical use. The device was installed with a sufficiently small body depicting 8-channel variable gain AC amplifier and variable time-window RMS-to-DC converter. The prototype was battery-driven and well-shielded to minimize external noise interference.

Amplifiers, Electronic↗
PubMed1999

Transition of polycythemia vera to chronic neutrophilic leukemia.

Two cases of polycythemia vera (PV) had transition to a hematological condition compatible with chronic neutrophilic leukemia (CNL) 17 and 8 years after diagnosis, respectively. One patient was treated with carboquone followed by hydroxyurea (HU) and the other with HU during PV phase. On transition, both had neutrophilia with white blood cell count above 40,000/microl, elevated neutrophil alkaline phosphatase activity, splenomegaly, normal karyotype without bcr-abl rearrangement. Busulfan was temporally effective in controlling the neutrophil count. However, one patient progressed to the so-called spent phase and the other subsequently had multiple transitions between PV and CNL. These cases may represent a form of uncommon evolution of PV and support the contention that CNL is a type of myeloproliferative disorder and that at least some CNL cases have derangement at the hematopoietic stem cell level.

Busulfan↗
PubMed1999

[Comparative studies on immunogenicity of Chinese hamster ovary cell drived HB vaccine and plasma drived HB vaccine].

Chinese Hamster Ovary cell drived HB vaccine (CDV) and plasma drived HB vaccine (PDV) were separately given to two groups of 113 and 112 medical staff subjected, and the anti-HBs responses were observed for five years from the initial injection. The anti-HBs positive rate at 7 months was 96.9% (mean geometric anti-HBs concentration 588 IU/L) in CDV group and 77.8% (83 IU/L) in PDV group, and the positive rate and mean titer of anti-HBs were always higher for 5 years in CDV group. Those differences were remarkable in the subjects aged over 40 years. The decreasing curves of anti-HBs titer in the two groups were parallel from 7th. month to 60th. month. Thus, the protective efficacy was estimated to be far longer in CDV than PDV. Also, the rate of non-responder was less lower in CDV group (2.8%) than PDV group (15.2%). Above results show that CDV has a higher immunogenicity than PDV.

Animals↗
PubMed1999

[Preoperative inoculation of CTLA4Ig combined with allogeneic dendritic cells prolongs rat renal allograft survival in a donor-specific fashion].

Donor dendritic cells (DCs) within allografts initiate the induction of allospecific T cell response, while abortive alloantigen presentation by DCs may induce allospecific unresponsiveness. It thus seems important to determine if preoperative transfusion of donor DCs in conjunction with CTLA4Ig would prolong graft survival, in a donor-specific manner. Rats treated with donor DCs (2 x 10(6)/rat i.v.) on the preoperative day 9 rejected allografts in an accelerated manner (5.0 +/- 2.2 vs. 8.2 +/- 1.6 days in the control group). Preoperative transfusion of DCs pulsed with CTLA4Ig, a procedure which suppresses an allogeneic mixed lymphocyte reaction (MLR), also provoked accelerated rejection (5.6 +/- 1.7 days). When DCs and CTLA4Ig (500 mg/rat i.p. on days -9, -7, and -5) were concomitantly inoculated, allograft survival was significantly prolonged (> 38.8 +/- 38.3 days); preoperative inoculation of CTLA4Ig alone failed to do so (7.5 +/- 1.2 days). Postoperative CTLA4Ig alone prolonged graft survival (> 68.1 +/- 39.0 days). Long-term graft survivors tolerated skin grafts from the donor but not those from a third party. There were no cellular infiltrates into the transplanted kidneys in the long-term survivors. The serum cytokine profiles were almost identical between the experimental groups of long-term survivors; that is the relative predominance of IL-4 and IL-10 in the early and late phases of the graft enhancement, respectively. The above collective evidence suggests that as preoperative treatment with donor DCs in combination with CTLA4Ig prolongs graft survival, and supports the notion that abortive alloantigen presentation by DCs conveys allospecific unresponsiveness.

Abatacept↗
PubMed1999

Role of dipyridamole myocardial scintigraphy in abdominal aortic aneurysm repair.

BACKGROUND: We evaluated the usefulness of preoperative dipyridamole myocardial scintigraphy (DMS) under low-level exercise in predicting postoperative cardiac problems in patients undergoing elective abdominal aortic aneurysm (AAA) repair. METHODS EXPERIMENTAL DESIGN: retrospective comparison of patients who did and did not undergo the investigation preoperatively. SETTING: at the Keio University Hospital and the Kawasaki City Hospital. PATIENTS: eighty-five patients who had abdominal aortic aneurysm repair consecutively from 1986 to 1990 without undergoing dipyridamole myocardial scintigraphy preoperatively were compared with 118 patients who underwent the repair consecutively from 1991 to 1997 after having had preoperative scintigraphy. MEASUREMENTS: postoperative occurrences of myocardial infarction and angina pectoris in the two groups of patients were compared statistically. RESULTS: In the group not having scintigraphy, cardiac events occurred in 12 patients (14.1%) after repair. Ten patients had a myocardial infarction; six died within 30 days of operation and four died after the 31st postoperative day. The other two patients had angina pectoris; both survived. In the group having scintigraphy, there were no postoperative cardiac events (p<0.001). Seventeen patients had positive results on preoperative scintigraphy. Seven of them had undergone coronary artery bypass grafting and five coronary angioplasty before the repair. In the five other patients, scintigraphy, was found to have yielded false positive results. CONCLUSIONS: Dypiridamole myocardial scintigraphy is an accurate predictor of postoperative myocardial infarction and angina pectoris in patients being evaluated for elective abdominal aortic aneurysm repair and should be used routinely.

Aged↗
PubMed1999

[Functions and the regulation of cytokines and growth factors in the thrombotic event of arteries and veins].

Recent progress of molecular biology has elicited the pathogenesis of arterial and venous thrombosis at the cellular level. The pathogenesis, as well as the etiology of the sequelae, has become clear to be closely relevant to inflammatory cytokines and growth factors such as tumor recrosis factor (TNF) alpha, interleukin-1 beta, or vascular endothelial growth factor (VEGF). From this point of view, the anti-cytokine or the anti-growth factor therapy including the use of some proteins, antibodies, drugs, and gene delivery systems has every possibility of improving the therapeutic outcome for the thrombosis.

Cytokines↗
PubMed1999

[A case of mediastinal myelolipoma].

Myelolipoma is a benign tumor composed of mature adipose tissue and hematopoietic tissue. It was mainly found in the adrenal grand, but there have been reports of extra-adrenal locations. Only 7 cases of mediastinal myelolipoma have been reported ever. We have experienced a case of mediastinal myelolipoma surgically resected from a 55-year-old-man. He has visited our department because of chest pain. Chest X-ray showed typical pneumothorax, but abnormal mediastinal shadow was remarked. Chest CT showed a well circumscribed mass with fat and soft-tissue attenuation in posterior mediastinum. Lung bullectomy and mediastinal tumor resection under VATS was performed. A blue-red tumor 4 cm in diameter was resected en bloc. Pathological examination showed its composition of mature adipose tissue and hematopoietic tissue. Diagnosis was extra-adrenal myelolipoma. No recurrent nor abnormality was found in 8 months since surgery.

Endoscopy↗
PubMed1999

[Onset of acute eosinophilic pneumonia after resumption of smoking].

We report a case of acute eosinophilic pneumonia (AEP) apparently caused by the resumption of smoking. A 38-year-old woman was admitted to our hospital because of dry cough, high fever and chest pain. Arterial blood gas analysis revealed pronounced hypoxemia and chest X-ray film disclosed diffuse bilateral infiltrate throughout all lung fields. Eosinophils (43.7%) were significantly increased in bronchoalveolar lavage fluid (BALF). The patient was treated with pulse therapy consisting of methylprednisolone and improved quickly. AEP was diagnosed on the basis of BALF findings and the patient's clinical course. Prior to and after her illness, the only noteworthy change in the patient's environmental setting or habits was the resumption of smoking, 3 days after which the symptoms had appeared. We reasoned that the onset of AEP in this patient was strongly related to the resumption of smoking.

Adult↗
PubMed1999

[Progress of the laboratory supporting system of the ordering system].

University hospitals and large public hospitals introduced a first-generation ordering system, which mainly involved an integrated system developed by each institution. This type of system considerably improved the efficiency of hospital jobs, but clinically increased the burden of data-input handling of hospital staffs because the software used was unique to the respective unit. Later, the development of both network technology and package software for the ordering system allowed construction of an easy, low-cost and high-performance ordering system. Most of the recent ordering systems are a type of distributed system which is referred to as a client-server system. In this system the terminal was replaced by personal computer loaded with widely distributed Windows OS, resulting in better performance of multi-tasks. In February 1998, our hospital information system was changed from an intensive host-type to a client-server system, in which the laboratory ordering system was also reconstructed. The laboratory ordering system mainly utilizes EG Main for Windows, package software by Fujitsu Co. Ltd., and has reduced the handling of laboratory ordering jobs with Graphical User Interface and better construction of screen images. In addition to extra-laboratory tests, ordering into this system allowed the database of all the laboratory tests ordered in our hospital to be unified. The previous laboratory ordering system supported laboratory data, especially those of laboratory tests and samples conducted within the last 10 years, and the new system will also provide this function. The new laboratory ordering system is further expected to support reference image-data from physiological tests as well as to allow consultation concerning laboratory test data. These clinical job-supporting systems will likely lead to further progress of the total laboratory system.

Clinical Laboratory Information Systems↗
PubMed1999

[Actual situations and problems of patients receiving home IVH--trial use of an assessment chart for outpatients].

In order to improve the quality of life (QOL) and continue nursing, we used an assessment chart to investigate the actual situations and problems of the patients receiving home intravenous hyperalimentation (IVH). From January, 1997 to June, 1999, we investigated 20 patients with home IVH. To 7 patients among them, we asked questions using Kurihara's assessment chart for QOL, plus our original questions concerning IVH. The mean age of the patients was 61 years old, and 19 of them had advanced cancers. Forty percent of the patients maintained the IVH all by themselves and 10% of the patients needed the support of their family. The remaining 50% of the patients left all to their family. There were 9 incidents of trouble during the maintenance of the IVH. Almost all patients from whom informed consent had been received were satisfied with the home IVH. On the contrary, all patients who had not given informed consent were not satisfied with the home IVH. According to the results of the assessment chart, even if the total points were low, the points for the IVH were high in the patients had given informed consent. The main reason for lower QOL was pain. The points for the families were lower than those for the patients. They sometimes complained of uneasiness and dissatisfaction with the support they received. We conclude that therapies to improve symptoms and mental state are necessary to satisfy the patients, and that it is important to support not only the patients but also their families.

Adult↗
PubMed1999

[A case of stiff-man syndrome with head retraction like reflex myoclonus and jerky myoclonus of bilateral lower extremities which responded well to removal of mediastinal carcinoma].

A 58-year-old male presented with reflex myoclonus and stiffness of the left facial, tongue, shoulder, and lower limbs muscles. Muscle stiffness and gait progressively worsened, leading to frequent falls. Acoustic and cutaneous stimuli of head precipitated reflex myoclonus like head retraction. Cutaneous of lower extremities precipitated jerky myoclonus of bilateral lower extremities. CSF analysis were unremarkable. No anti GAD antibody or anti amphiphysin antibody was detected in the serum and CSF. On surface EMG the spasms initiated with 4-5 short burst discharges at intervals between 59 and 84 ms, followed by a tonic decrescendo activity up to 3 s. After diazepam treatment, stiffness and reflex myoclonus of lower extremities were disappeared and head retraction like reflex myoclonus was improved but remained. CT of the chest revealed a mediastinal tumor. Biopsy of the tumor revealed undifferential carcinoma. The patient further improved after the resection of the tumor. These findings suggest that this stiff-man syndrome may occur as an autoimmune paraneoplastic syndrome of CNS.

Autoimmunity↗
PubMed1998

Downbeat nystagmus in two siblings with spinocerebellar ataxia type 6 (SCA 6).

We report two siblings with spinocerebellar ataxia type 6 (SCA 6), both showing downbeat nystagmus (DBN) as a predominant clinical feature. Familial hemiplegic migraine (FHM), episodic ataxia type 2 (EA-2) and SCA 6 are allelic disorders, and interestingly, the occasional presence of DBN in EA-2 was reported. Our observations suggest that common molecular mechanisms might underlie DBN in FHM, EA-2 and SCA 6. Then, these disorders should be kept in mind in diagnosing patients with DBN.

Adult↗
PubMed1998

Methylation of the 5' CpG island of the FHIT gene is closely associated with transcriptional inactivation in esophageal squamous cell carcinomas.

Previous studies suggested that the FHIT (fragile histidine triad) gene on 3p14.2 might be involved in the development of esophageal squamous cell carcinomas, but the mechanisms for inactivating the gene have not been fully revealed. In the present study, we examined aberrations of the FHIT gene in 23 esophageal squamous cell carcinoma cell lines and 35 primary tumors. We detected aberrant expression in seven cell lines (30%), including a shorter transcript in two cell lines and loss of apparent transcript in five cell lines. Genomic PCR or cDNA sequencing analysis revealed a single exon deletion in two cell lines with a shorter transcript and one cell line without expression, but no structural alterations were found in the other 20 cell lines, including transcriptionally repressed four cell lines. Next we examined methylation of the 5' CpG island of the FHIT gene by bisulfite genomic sequencing. Hypermethylation of the 5' CpG island of the FHIT gene was observed in three of four structurally unaltered but transcriptionally repressed cell lines. The remaining cell line harbored a point mutation upstream of exon 1. All methylated cell lines exhibit re-expression of the FHIT gene and demethylation in the CpG island after treatment with demethylating agent 5-aza-2'-deoxycytidine. Hypermethylation was also found in 5 of 35 (14%) primary tumors, whereas corresponding normal tissue shows no methylation. These findings suggest that methylation of the 5' CpG island of the FHIT gene is closely associated with transcriptional inactivation and might be involved in tumor development of the esophagus.

Acid Anhydride Hydrolases↗
PubMed1998

Twin helical undulator beamline for soft X-ray spectroscopy at SPring-8.

A very high resolution soft X-ray beamline, BL25SU, has been designed and is under construction at SPring-8. Completely right or left circularly polarized light is supplied on a common axis of a newly designed twin helical undulator. A helicity modulation up to 10 Hz can be performed using five kicker magnets. The fundamental radiation covers the region 0.5-3 keV. Higher-order radiation is rather weak on the axis. A monochromator with varied-line-spacing plane gratings is installed to cover the region below 1.5 keV. A very high resolution beyond 10(4) is expected for the whole energy region.

Journal Article↗
PubMed1998

Expression of a knocked-in AML1-ETO leukemia gene inhibits the establishment of normal definitive hematopoiesis and directly generates dysplastic hematopoietic progenitors.

The t(8;21)-encoded AML1-ETO chimeric product is believed to be causally involved in up to 15% of acute myelogenous leukemias through an as yet unknown mechanism. To directly investigate the role of AML1-ETO in leukemogenesis, we used gene targeting to create an AML1-ETO "knock-in" allele that mimics the t(8;21). Unexpectedly, embryos heterozygous for AML1-ETO (AML1-ETO/+) died around E13.5 from a complete absence of normal fetal liver-derived definitive hematopoiesis and lethal hemorrhages. This phenotype was similar to that seen following homozygous disruption of either AML1 or CBFbeta. However, in contrast to AML1- or CBFbeta-deficient embryos, fetal livers from AML1-ETO/+ embryos contained dysplastic multilineage hematopoietic progenitors that had an abnormally high self-renewal capacity in vitro. To further document the role of AML1-ETO in these growth abnormalities, we used retroviral transduction to express AML1-ETO in murine adult bone marrow-derived hematopoietic progenitors. AML1-ETO-expressing cells were again found to have an increased self-renewal capacity and could be readily established into immortalized cell lines in vitro. Taken together, these studies suggest that AML1-ETO not only neutralizes the normal biologic activity of AML1 but also directly induces aberrant hematopoietic cell proliferation.

Animals↗
PubMed1998

Solution structure of the IRF-2 DNA-binding domain: a novel subgroup of the winged helix-turn-helix family.

BACKGROUND: The transcription of interferon (IFN) and IFN-inducible genes is mainly regulated by the interferon regulatory factor (IRF) family of proteins, which recognize a unique AAGTGA hexamer repeat motif in the regulatory region of IFN genes. A DNA-binding domain of approximately 100 amino acids has been commonly found in the IRF family of proteins, but it has no sequence homology to known DNA-binding motifs. Elucidation of the structures of members of the IRF family is therefore useful to the understanding of the regulation and evolution of the immune system at the structural level. RESULTS: The solution structure of the DNA-binding domain of interferon regulatory factor-2 (IRF-2) has been determined by NMR spectroscopy. It is composed of a four-stranded antiparallel beta sheet and three alpha helices, and its global fold is similar to those of the winged helix-turn-helix (wHTH) family of proteins. A long loop (Pro37-Asp51) is found immediately before the HTH motif, which is not found in other wHTH proteins. The NMR signals of residues in this long loop, as well as the second helix of the HTH motif, are strongly affected upon the addition of the hexamer repeat DNA, suggesting that these structural elements participate in DNA recognition and binding. CONCLUSIONS: The structural similarity of the DNA-binding domain of IRF-2 with those of proteins in the wHTH family shows that the IRF proteins belong to the wHTH family, even though there is no apparent sequence homology among proteins of the two families. The sequential structure alignment program (SSAP) shows that IRF-2 has a slightly different structure from typical wHTH proteins, mainly in the orientation of helix 2. The IRF family of proteins should therefore be categorized into a subfamily of the wHTH family. The evidence here implies that the evolutional pathway of the IRF family is distinct from that of the other wHTH proteins, in other words, the immune system diverged from an evolutional stem at an early stage.

Amino Acid Sequence↗