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Biomedical subjects

F Hara

Publications and source records attributed to F Hara.

At least 19 recordsLinked to original sources
PubMed2005

Cyclic tensile stretch stimulates the release of reactive oxygen species from osteoblast-like cells.

It is known that the excessive generation of reactive oxygen species (ROS) is a significant factor in tissue injury observed in many disease states. To determine whether extreme levels of mechanical stress applied to osteoblasts enhances ROS synthesis, we loaded cyclic tensile stretch on osteoblast-like HT-3 cells. Cyclic tensile stretch loaded on these cells clearly enhanced ROS synthesis in a time- and magnitude-dependent fashion. Cyclic tensile stretch also enhanced superoxide dismutase (SOD) activity. The disruption of microfilaments with cytochalasin D abolished the stress-induced ROS synthesis. Rotenone, an inhibitor of the mitochondrial electron transport chain, enhanced stress-induced ROS synthesis. These data suggest that actin filament and mitochondria are involved in this action.

Actins↗
PubMed2004

Functional expression of high-affinity receptor for immunoglobulin E on mast cells precedes that of tryptase during differentiation from human bone marrow-derived CD34 progenitors cultured in the presence of stem cell factor and interleukin-6.

BACKGROUND: CD34(+) progenitor cells develop into tryptase(+), CD117(+) mast cells when cultured in the presence of recombinant human stem cell factor (rhSCF). However, spontaneous IgE receptor (FcepsilonRI) expression during human mast cell development is not well examined. OBJECTIVE: Here, the expression and function of FcepsilonRI in and on human bone marrow-derived mast cells (HBMMCs) during development were investigated. METHODS AND RESULTS: At 4 weeks of culture, predominant cells expressed high-affinity IgE receptor alpha chain (FcepsilonRIalpha) on the cell surface determined by flow cytometry, but CD117 was less expressed. Immunocytochemistry with antitryptase mAb and anti-FcepsilonRIalpha mAb revealed intracellular and surface expression of FcepsilonRIalpha at 2 weeks of culture, but tryptase was less expressed. FcepsilonRIalpha mRNA transcript preceded that of tryptase mRNA at 2 weeks of culture determined by real-time RT-PCR, and FcepsilonRIalpha, FcepsilonRIbeta, FcepsilonRIgamma, and tryptase mRNA increased along with differentiation. FcepsilonRIalpha cross-link on HBMMC and 4-week-old mast cells/mast cell precursors induced the release of IL-5 and granulocyte macrophage-colony stimulating factor, which was enhanced by rhSCF. CONCLUSION: These data indicated that HBMMC constitutively and spontaneously expressed functional FcepsilonRI subunits at the early stage of differentiation, probably because of the differences in the ability and functional property of progenitors.

Antigens, CD34↗
PubMed2004

Detection of tryptase-, chymase+ cells in human CD34 bone marrow progenitors.

BACKGROUND: Mast cells (MCs) arise from haematopoietic stem cells. We have recently reported that CD34(+) progenitors derived from human bone marrow (BM) develop into tryptase+, chymase+ MCs when cultured in the presence of recombinant human stem cell factor (rhSCF) and recombinant human IL-6 (rhIL-6). In an experiment for the expression of chymase during differentiation, chymase+ cells were detected in human BM, but tryptase+ cells were not found. OBJECTIVE: The purpose of this study was to show the appearance of chymase+ cells in CD34(+) cells with an origin different from MC differentiation. METHODS: CD34(+) cells from human BM were sorted with anti-CD117 monoclonal antibody (mAb), and cytospins of CD34(+), CD34(+)CD117(+), or CD34(+)CD117(-) were prepared. These cells were cultured with rhSCF+rhIL-6 for 12 weeks. Some of the cells were subjected to either histological stain with Wright-Giemsa or immunocytochemistry with anti-chymase mAb. Real-time RT-PCR was also performed to compare the transcriptional level of chymase from each cell preparation. RESULTS: Chymase was expressed in CD34(+) cells as well as human MCs by immunocytochemistry. Substantial CD34(+)CD117(-) cells, but not CD34(+)CD117(+) cells, were stained immunocytochemically with anti-chymase mAb. For 1 week culture with rhSCF+rhIL-6, no cells expressed chymase in any preparation. Real-time RT-PCR revealed positivity for chymase mRNA in CD34(+) cells, but it reduced at 1 week of culture, and increased as cells developed into MCs. Chymase mRNA in CD34(+)CD117(+) cells was negligible compared with that in CD34(+)CD117(-). Tryptase mRNA was below the detectable level in CD34(+) cells, and increased along with MC differentiation. After 12 weeks of culture, CD34(+)CD117(+) developed predominantly into MCs, whereas CD34(+)CD117(-) developed into monocytes/macrophages. CONCLUSION: Our findings suggested that chymase is present not only in MCs but also in CD34(+)CD117(-) BM progenitors, but that its origin is different from the MC lineage.

Antigens, CD34↗
PubMed2003

Cyclic tensile stretch loaded on bovine chondrocytes causes depolymerization of hyaluronan: involvement of reactive oxygen species.

OBJECTIVE: We have previously demonstrated that reactive oxygen species (ROS) are involved in cartilage degradation. Decreased size of hyaluronan (HA), the major macromolecule in synovial fluid, to which it imparts viscosity, is reported in patients with arthritis. The purpose of this study was to determine the alteration in the molecular weight range of HA as a result of mechanical deformation loaded on the chondrocytes, as well as the involvement of ROS in this action. METHODS: ROS were generated via the oxidation of hypoxanthine by xanthine oxidase. Cyclic tensile stretch was loaded using a vacuum-operated instrument. Levels of HA were measured using a sandwich enzyme-binding assay. Superoxide dismutase (SOD) activity and ROS were measured using water-soluble tetrazolium and a chemiluminescent probe, respectively. RESULTS: ROS depolymerized HA molecules. Cyclic tensile stretch depolymerized HA and induced ROS. SOD inhibited not only ROS induction but also HA depolymerization caused by the mechanical stress. CONCLUSION: ROS play an important role in mechanical stress-induced HA depolymerization.

Animals↗
PubMed2003

[Pulmonary adenocarcinoma of the fetal lung type; report of a case].

An asynptomatic 58-year-old male was admitted to the hospital because of an abnormal nodule in the left lung field on screening chest X-ray. Chest computed tomography (CT) showed a tumor shadow mass in the left lower lobe. Open biopsy was performed to diagnose the mass. The cytological diagnosis was low-grade malignant adenocarcinoma, underwent left lower lobectomy. The histological diagnosis was pulmonary adenocarcinoma of the fetal lung type which was one of pulmonary blastoma (PB). Recently, the concept of pulmonary blastoma has changed. It will be useful to investigate the old PB's case reports to classify new concept.

Adenocarcinoma↗
PubMed2001

Cyclic tensile stretch inhibition of nitric oxide release from osteoblast-like cells is both G protein and actin-dependent.

Recent reports indicate the alteration of nitric oxide (NO) synthesis with mechanical stress loaded on the osteoblast and NO is considered to have a significant role in mechanotransduction. We found the involvement of guanine-nucleotide-binding regulatory proteins (G proteins), especially Gi, in stress-inhibited NO release of osteoblast-like cells (JOR:17;593-597, 1999). To determine further the mechanism involved in this process, we measured c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) activity under cyclic tensile stretch loaded on osteoblast-like cells. Cyclic stretch significantly enhanced JNK/SAPK activity and pertussis toxin clearly reversed stress-enhanced JNK/SAPK activity. Cytochalasin D, actin microfilament disrupting reagent, also abolished the stress activation of JNK/SAPK. We propose a model for signaling events induced by cyclic tensile stretch, namely a transmembrane mechanosensor which couples Gi-protein, actin cytoskeleton and finally activates JNK/SAPK activity of osteoblasts.

Actins↗
PubMed2001

[A case of advanced hepatocellular carcinoma with portal invasion resected after treatment by continuous intra-arterial chemotherapy with cisplatin and 5-fluorouracil].

A 67-year-old male diagnosed as having inoperable advanced hepatocellular carcinoma with portal invasion was able to undergo resection after continuous intra-arterial chemotherapy with 5-fluorouracil (5-FU) and cisplatin (CDDP). These were continuously administered for 24 hours at doses of 5-FU of 250 mg and CDDP of 5 mg/day, from day 1 to day 5 in a week, repeated 6 times. In additions to the reductions of the levels of AFP and PIVKA-II from 212.6 ng/ml and 16,100 mAU/ml to 11.8 ng/ml and 12 mAU/ml, respectively, the volume of the tumor and the portal invasion were diminished remarkably. As a result, a left extended hepatectomy could be performed. No sign of recurrence was seen during 16 months of follow-up after the operation. Given the above results, continuous intra-arterial chemotherapy with 5-FU and CDDP therapy may be effective for patients with hepatocellular carcinoma.

Aged↗
PubMed2001

[A case of Coxiella burnetii pneumonia in an adult].

A 49-year-old man visited our hospital complaining of a continuous high-grade fever and cough which had appeared during his stay in Indonesia. He was admitted on the same day because his laboratory data showed marked inflammatory changes and his chest radiograph revealed an infiltrative shadow in the right upper lung field. Initial treatment with beta-lactams was not effective and both his symptoms and his chest radiograph worsened. However, treatment with erythromycin clearly had an effect. Then, we carried out several tests for detection of atypical pathogens including Mycoplasma and Chlamydia. Finally, the case was diagnosed as one of Coxiella burnetii pneumonia because the DNA of C. burnetii was detected from his sera and seroconversion of C. burnetii--specific antibody was observed among paired serum samples. C. burnetii is one of the most commonly recognized pathogens among community-acquired pneumonias in Western countries, but in Japan, reports of community-acquired C. burnetii pneumonia have been rare. This difference may be due to the features of Q fever, in which there are large differences in frequency and form from country to country and among areas of the same country. Surveillance of C. burnetii pneumonia in Japan and different area will be required.

Anti-Bacterial Agents↗
PubMed2000

A child with adrenocortical adenoma accompanied by congenital hemihypertrophy: report of a case.

We report herein the findings of a 7-year-old male child with a ruptured adrenocortical adenoma and congenital hemihypertrophy which was incidentally detected after suffering a trauma. A review of 21 pediatric cases of adrenocortical neoplasms in the literature was made. The patient showed precocious puberty such as pubis and advanced bone age, but an endocrinological examination revealed no definite abnormalities. The right adrenal tumor with hematoma was resected after these evaluations. Adrenocortical adenoma is considered to occur more frequently in female children. However, the incidence of adrenocortical tumors accompanied by congenital hemihypertrophy does not differ between males and females. The outcomes were relatively good, although the observation periods were short in some patients. A large number of patients presented with a tumor and hemihypertrophy on the same side. This finding is of interest when considering the possible association between hemihypertrophy of the organs and tumor proliferation. However, their association in terms of development was unclear. It is necessary for patients with hemihypertrophy to have regular examinations for the possible development of malignant tumors, especially in the kidney, adrenal gland, and liver.

Adrenal Cortex Neoplasms↗
PubMed2000

[A case report of pneumococcal pneumonia diagnosed by urinary antigen].

Using a kit for the rapid detection of Streptococcus pneumoniae, we examined 3 clinical cases, clearly diagnosed as pneumococcal pneumonia. Case 1 was a 63-year-old man hospitalized for right middle lobular pneumonia. Streptococcus pneumoniae was detected by blood culture initiated on the day of admission. His urine sample was found to have Streptococcus pneumoniae antigen at hospital day 4, and positive test results were observed 3 times thereafter. The other 2 cases had negative sputum and blood cultures, but they were positive for urine antigen, with clinical courses consistent with those of pneumococcal pneumonia. The kit used was determined to provide a test result within 15 min for each urine sample, and it was easy to perform. Thus, this kit is expected to serve as a very useful clinical tool.

Antigens, Bacterial↗
PubMed1999

Pertussis toxin-sensitive G proteins as mediators of stretch-induced decrease in nitric-oxide release of osteoblast-like cells.

Mechanical loading plays an important role in regulating bone remodeling, and nitric oxide may be one regulator of this process. To determine how mechanical stress modulates osteoblast function, we loaded cyclic tensile stretch on osteoblast-like cells and measured levels of nitric oxide in the medium. High frequency of stretch at any magnitude inhibited release of nitric oxide; however, low frequency of stretch enhanced its release from the static control. To examine the involvement of G protein (guanine nucleotide-binding regulatory protein) in stress-inhibited release of nitric oxide, we added pertussis toxin, a specific inhibitor of the Gi class, and found that it completely reversed the stress-inhibited release. These data support the idea that pertussis toxin-sensitive G protein is activated in the presence of cyclic tensile stretch.

Bone Remodeling↗
PubMed1999

The cyclin-dependent kinase inhibitor p27 as a prognostic factor in advanced non-small cell lung cancer: its immunohistochemical evaluation using biopsy specimens.

The expression of p27, which is known as a cyclin-dependent kinase inhibitor, on surgically resected specimens has considerable value for the prognosis of non-small cell lung cancer (NSCLC) patients. We immunohistochemically investigated the expression of the p27 protein in the biopsy specimens taken from 69 advanced NSCLC patients and assessed its clinical value. There was no significant correlation between p27 positivity and clinical parameters, including sex, age, histological type, clinical stage, smoking index and performance status. Furthermore, p27 positivity was not associated with response to chemotherapy. However, the Kaplan-Meier curve demonstrated that low p27 expression was significantly related to poor prognosis (P = 0.0019, by the log-rank test). Using multivariate analysis, p27, age and serum total protein level were found to be the independent prognostic parameters. The p27 positivity in the biopsy specimens of advanced NSCLC appears to be a useful prognostic marker.

Aged↗
PubMed1999

Effects of granisetron in children undergoing high-dose chemotherapy: a multi-institutional, cross-over study.

The efficacy of granisetron hydrochloride 20 microg/kg and 40 microg/kg were compared using a cross-over method to determine the optimal dose in children with solid tumors receiving high-dose chemotherapy. Granisetron controlled the onset of vomiting in 17 of 23 patients (73.9%) who were given 40 microg/kg of granisetron, while 8 of 21 patients (38.1%) were free of vomiting in the 20 microg/kg group. The average frequency of vomiting was 7.22 times in the 20 microg/kg dose versus 4.44 times in the 40 microg/kg dose. No safety problems were associated with either dose. The 40 microg/kg dose of granisetron appears to be more optimal.

Adolescent↗
PubMed1999

[Palliation for a recurrent lung cancer patient with superior vena cava syndrome by arterial infusion of CDDP through the implantable port system--a case report].

A case of lung cancer with superior vena cava syndrome treated with internal thoracic arterial infusion of anti-cancer drugs by the implantable port system was reported with our technique. In this case, blood supply was mainly from internal thoracic artery. A trans-catheterial contrast enhanced helical CT was very helpful to identify the routes of blood supply to the lung cancer.

Aged↗
PubMed1998

[Primary liposarcoma of the anterior mediastinum--case report and review of literature].

A 76-year-old male with anterior mediastinal tumor was admitted to our hospital. He had undergone mediastinal lipoma surgery 3 years earlier. The tumor was excised surgically. Microscopic sections of the tumor showed liposarcoma composed of myxoid tissue. Further examination of prior specimens taken from this patient proved this case to be a recurrence of liposarcoma. Poorly differentiated tumors, which pathologically tend to be more cellular with less fat per cell component, are likely to have high CT numbers. But CT number is not sufficient to distinguish well-differentiated liposarcoma from benign lipoma.

Aged↗
PubMed1998

Protein kinase C modulates the synthesis of nitric oxide by osteoblasts.

To determine the involvement of protein kinase C (PKC) in nitric oxide (NO) synthesis of osteoblast, a combination of proinflammatory cytokines (tumor necrosis factor-alpha, interferon-gamma, bacterial lipopolysaccharide) were added on rat osteoblast-like cells. Results show that these cytokines clearly enhanced the synthesis of NO. The activation of PKC with phorbol ester also resulted in the stimulation of NO synthesis in these cells. These cytokines activated PKC and increased the levels of intracellular Ca2+. In addition, the cytokine-induced synthesis of NO was blocked by PKC inhibitors. Findings suggest the involvement of PKC in the synthesis of NO by rat osteoblasts.

Animals↗