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H Fujiwara

Publications and source records attributed to H Fujiwara.

At least 217 records · Page 12Linked to original sources
PubMed1999

CD9 is expressed on the cell surface of human granulosa cells and associated with integrin alpha6beta1.

The CD9 molecule is a 24-27 kDa cell surface glycoprotein which is reported to be involved in cell adhesion and migration. Recently, CD9 was shown to be associated with beta1-related integrins. We have previously found that integrin alpha6beta1 is expressed on human granulosa cells (GC) and regulates luteinization of GC in concert with its ligand laminin. In this study, we examined the expression of CD9 in human ovary and the relationship between CD9 and integrin alpha6beta1 in GC. By immunohistochemistry, CD9 was detected on GC in a small antral follicle of <1 mm in diameter. In growing follicles, CD9 was moderately expressed on both GC and theca interna cells (TI). The expression intensity of CD9 on GC increased in preovulatory follicles. In the early luteal phase, CD9 was expressed in both luteinizing GC and TI. The expression intensity on large luteal cells decreased in the mid-luteal phase. In the corpus luteum (CL) of pregnancy, CD9 continued to be expressed on large luteal cells, but not on small luteal cells. By flow cytometry, CD9 was detected on the cell surface in approximately 90% of the isolated GC from patients undergoing in vitro fertilization. The molecular weight of CD9 in the isolated GC was shown to be 26.5 kDa by Western blotting. CD9 mRNA was also detected in the isolated GC and CL by reverse transcription-polymerase chain reaction (RT-PCR). The proteins purified from GC by immunoaffinity chromatography using anti-integrin alpha6 monoclonal antibodies were shown by Western blotting to include CD9 as well as integrin beta1. These findings suggest that CD9 is a differentiation-related molecule of GC and TI and that it is associated with integrin alpha6beta1 on the cell surface of GC, suggesting that CD9 is implicated in the function of human GC in cooperation with integrin alpha6beta1.

Adult↗
PubMed1999

Human granulosa cells express integrin alpha2 and collagen type IV: possible involvement of collagen type IV in granulosa cell luteinization.

Previously, it has been shown that integrin alpha6beta1 expressed on human granulosa cells regulates luteinization in co-operation with its ligand, laminin. In this study, integrin alpha2 was immunohistochemically demonstrated to be expressed on granulosa and large luteal cells. It was also detected on luteinizing theca interna cells after ovulation. Immunoreactive collagen type IV, which is one of the ligands for integrin alpha2beta1, was detected around granulosa cells in the pre-ovulatory follicles and its expression was rapidly increased during ovulation. By flow cytometry, collagen type IV was detected on the cell surface of luteinizing granulosa cells isolated from pre-ovulatory follicles, confirming the physiological interaction between granulosa cells and collagen type IV. Collagen type IV in follicular fluid was positively related with progesterone concentration. In 4-day cultures of granulosa cells, collagen type IV in the media was significantly increased by human chorionic gonadotrophin (HCG). The progesterone production was significantly attenuated when granulosa cells were cultured on collagen type IV-coated dishes, suggesting that collagen type IV suppresses granulosa cell luteinization. These findings show that collagen type IV, a ligand for integrin alpha2beta1, is rapidly produced around luteinizing granulosa cells during ovulation, probably under the control of luteinizing hormone (LH) and suggest that collagen type IV is a new parameter and/or regulator of granulosa cell luteinization in the periovulatory phases.

Antigens, CD↗
PubMed1999

Induction of apoptosis by gallic acid in lung cancer cells.

The apoptosis-inducing effect of gallic acid (3,4,5-trihydroxybenzoic acid) was investigated in four human lung cancer cell lines, SBC-3 (small cell carcinoma), EBC-1 (squamous cell carcinoma), A549 (adenocarcinoma) and SBC-3/CDDP (cisplatin-resistant subclone of SBC-3). Gallic acid induced apoptosis in a dose-dependent manner as evidenced by analyses of DNA fragmentation, changes in cell morphology and loss of viability. Fifty percent inhibitory concentration (IC50) values of gallic acid on the cell viability of SBC-3, EBC-1 and A549 were around 10, 20 and 60 microg/ml, respectively. The IC50 value for SBC-3/CDDP cells was almost the same as that of SBC-3, suggesting that susceptibility of cells to gallic acid-induced apoptosis is not altered by the acquisition of cisplatin resistance. The apoptotic process was effectively triggered by 30 min exposure to gallic acid. A caspase inhibitor and alpha-tocopherol effectively prevented the gallic acid-induced apoptosis, indicating the involvememt of caspase activation and oxidative processes during the course of apoptosis in gallic acid-treated cancer cells. These findings suggest the possible applicability of gallic acid in lung cancer therapy, especially to circumvent resistance to anti-cancer drugs.

Adenocarcinoma↗
PubMed1999

Optimal target site for slow AV nodal pathway ablation: possibility of predetermined focal mapping approach using anatomic reference in the Koch's triangle.

INTRODUCTION: Although a variety of ablation techniques have been developed in the treatment of atrioventricular nodal reentrant tachycardia (AVNRT), there have been few reports discussing the location of the optimal target site. Based on our early experiences, we hypothesized that radiofrequency (RF) current applied around the upper margin of the coronary sinus ostium (UCSO) results in the most effective and safe treatment of AVNRT. METHODS AND RESULTS: To confirm our hypothesis, the efficacy of RF currents applied around the UCSO guided by local electrograms in 59 patients (group B: predetermined focal mapping approach) were compared with the outcomes in 60 other patients previously treated with the standard electrogram-guided mapping method starting around the lower margin of the coronary sinus ostium (group A). The precise location of ablation catheters at successful sites (S) was also evaluated. All the patients were successfully treated without complications. Significantly fewer RF pulses and lower energies were needed in group B patients (mean RF applications: 4.3 vs 1.4 applications, mean total energy delivered: 4,699 vs 2,236 J in groups A and B, respectively, P < 0.01). Detailed analyses of the anatomical locations of S using CS venography in group B patients who received only a single RF application (46 patients) revealed that the distance between His and S varied according to the length of Koch's triangle, while that between S and UCSO was relatively constant. In 85 % of these 46 patients, S was located within 5 mm above and below the level of the UCSO. CONCLUSION: RF applications around the UCSO guided by local electrograms yielded excellent outcomes in AVNRT patients with wide varieties in the size of Koch's triangle. The optimal target site was located within 5 mm above and below the level of UCSO along the tricuspid annulus.

Atrioventricular Node↗
PubMed1999

Apoptosis and overexpression of bax protein and bax mRNA in smooth muscle cells within intimal hyperplasia of human radial arteries : analysis with arteriovenous fistulas used for hemodialysis.

There is a type of arteriosclerosis with remodeling of middle-size arteries in which intimal hyperplasia of smooth muscle cells (SMCs) plays the main role, and there are few macrophages, T lymphocytes, and foam cells. It is unknown whether apoptosis and the expression of Bax, an inducer of apoptosis, are increased according to the progression of this type of human arteriosclerosis, which is different from so-called atherosclerosis. Bax heterodimerizes with Bcl-2, an inhibitor of apoptosis, and the ratio of Bax to Bcl-2 determines cellular apoptosis or survival. Thus, we investigated apoptosis and the expressions of Bax, bax mRNA, and Bcl-2 in human arteriovenous (AV) fistulas used for hemodialysis, a representative of arteriosclerosis of the aforementioned type. The material was 20 radial arteries obtained from 20 patients with chronic renal failure undergoing AV shunt surgery. SMCs, macrophages, and T lymphocytes were immunohistochemically identified at the light microscopic (LM) level. Apoptosis was detected by in situ terminal deoxynucleotidyl transferase (TdT)-mediated digoxigenin-dUTP nick end labeling (TUNEL) at both the LM and electron microscopic (EM) level. Cell proliferating activity was estimated by proliferating cell nuclear antigen (PCNA). Bax and Bcl-2 were detected by immunohistochemistry and Western blot analysis. Expression of bax mRNA was detected by in situ hybridization. LM TUNEL-positive cells in both the intima and media were significantly increased according to the percent stenosis of the vessels. EM analysis revealed that ultrastructures of apoptotic SMCs were seen in both synthetic and contractile phenotypes. Their frequency of occurrence in the intima and media were greater in those vessels with >50% stenosis than in those with <50% stenosis (5.2+/-0.7% versus 1.0+/-0.3% in the intima and 2. 1+/-0.5% versus 0.2+/-0.1% in the media). The proportion of apoptotic SMCs with ruptured plasma membranes was greater than that of apoptotic SMCs with intact membranes in the intima of the former (4.1+/-0.6% versus 1.1+/-0.1%). Only those SMCs with apoptotic ultrastructures had TUNEL-positive nuclei with moderate or marked accumulation of immunogold particles at the EM level. However, ultrastructures of oncosis (primary necrosis) were not observed. Immunohistochemical analyses showed significant positive correlations between percent stenosis of vessels and the percentage of either PCNA-positive intimal cells or Bax-positive areas in the intima and media. Bcl-2-positive cells were not observed in the intima but mainly in the outer media. The percentage of Bcl-2-positive medial cells was definitely decreased at an early stage after formation of the AV fistula but did not change according to the duration of hemodialysis or the progression of arteriosclerosis. Western blot analysis of Bax or Bcl-2 and in situ hybridization of bax mRNA confirmed the immunohistochemical data. Thus, regulation of cellularity in intimal hyperplasia of SMCs in human arteriosclerosis with remodeling is mediated by proliferation and apoptosis but not oncosis. The apoptosis is probably induced by an increase in the Bax to Bcl-2 ratio.

Adult↗
PubMed1999

Synthesis and pharmacological activity of 4-amino-5-chloro-2-methoxy-N-[(2S,4S)-1-ethyl-2-hydroxymethyl-4- pyrrolidinyl]benzamide (TKS159) and its optical isomers.

Of 4-amino-5-chloro-2-methoxy-N-(1-ethyl-2-hydroxymethyl-4- pyrrolidinyl)benzamide, four optical isomers, (2S,4S)-1 (TKS159), (2S,4R)-25, (2R,4S)-26 and (2R,4R)-27, were prepared from optically active 4-amino-1-ethyl-2-hydroxymethylpyrrolidine di-p-toluenesulfonate [(2S,4S)-14, (2S,4R)-17, (2R,4S)-20 and (2R,4R)-23, respectively]. The requisites, (2S,4S)-14, (2S,4R)-17, (2R,4S)-20 and (2R,4R)-23, were prepared from a commercially available trans-4-hydroxy-L-proline. The absolute configurations of (2S,4S)-1 (TKS159), (2S,4R)-25, (2R,4S)-26 and (2R,4R)-27 were spectroscopically determined. Of the benzamide derivatives, four optical isomers, (2S,4S)-1, (2S,4R)-25, (2R,4S)-26 and (2R,4R)-27, showed a relatively potent affinity for 5-hydroxytryptamine 4 (5-HT4) receptors in a radioligand binding assay ([3H]GR113808). The activities of 25-27 were less effective than that of 1 for the gastric emptying of a phenol red semisolid meal in rats. All this suggests that the most potent of the isomers was 4-amino-5-chloro-2-methoxy-N-[(2S,4S)-1-ethyl-2- hydroxymethyl-4-pyrrolidinyl]benzamide (1).

Animals↗
PubMed1999

[The application of the endotoxin test for globulin and other blood products].

The application of the endotoxin test for globulin and other blood products were investigated by two different limulus amebocyte lysate (LAL) test methods, colorimetric and kinetic turbidimetric methods, using two endotoxin-specific reagents. By the dilution of the blood products in 40 times or more, spiked endotoxin in the products was recovered accurately showing neither inhibition nor enhancement. The definite difference was not shown between the results obtained by the two LAL test methods. According to the method of the endotoxin test described under General Tests of The Japanese Pharmacopeia (thirteenth edition), JPXIII, the maximum valid dilution (MVD) for these products will be calculated to be 40 or more, so it is capable to measure the endotoxin limit for each product. This study indicates that the endotoxin test is applicable to measure the endotoxin content in globulin and other blood products as an alternative method for the rabbit pyrogen test.

Colorimetry↗
PubMed1999

Radiofrequency catheter ablation for sinoatrial node reentrant tachycardia: electrophysiologic features of ablation sites.

The aim of this study was to investigate catheter ablation of sino-atrial reentrant tachycardia (SART) and the electrophysiologic characteristics of the ablation sites. From January 1990 to October 1997, 651 patients with supraventricular tachycardia were referred and 11 patients were found to have SART. Ablation was successful in all cases with a mean number of 3.3 radiofrequency (RF) current pulses. SART terminated during 22 of 36 RF pulses. In spite of prompt termination, tachycardia could be re-induced in 3 of 11 patients with its earliest activation site shifted. At effective ablation sites, the electrograms during tachycardia were characterized as fractionated (75+/-17 ms), and 38+/-16 ms prior to surface P wave, and 42+/-18 ms prior to the high right atrium. Unipolar electrograms revealed a sharp negative unipolar deflection, so called QS pattern, in 15 of 20 sites during SART and 15 of 15 sites during sinus rhythm. During effective applications, atrial premature beats (APB) with activation sequences identical to sinus rhythm appeared in 14 of 22 cases. Effective ablation sites of SART showed fractionated electrograms during tachycardia and sinus rhythm. Unipolar electrogram with a QS pattern and APB during energy application could be an indicator of the optimal ablation sites.

Adenosine Triphosphate↗
PubMed1999

Membrane-bound cell surface peptidases in reproductive organs.

Membrane-bound cell surface peptidases including aminopeptidase-N (EC 3.4.11.2), dipeptidyl peptidases IV (EC.3.4.14.5), carboxypeptidase-M (EC 3.4.17.12), neutral endopeptidase (EC 3.4.24.11) and endothelin converting enzyme-1 (EC 3.4.23) were shown to be differently expressed on human ovarian granulosa, theca interna and luteal cells and on endometrial epithelial and stromal cells. These peptidases have their catalytic sites extracellularly and can metabolize biologically active peptides at the cell surface, serving as local regulators of peptide concentrations. In the ovary and endometrium, numerous peptides are considered to be locally produced and play an important role in the follicular growth, ovulation, corpus luteum function, endometrial differentiation and embryo implantation in an autocrine and/or paracrine fashion. The inhibition of aminopeptidase activity by bestatin affected murine follicular growth, steroidogenesis by porcine ovarian cells and progesterone-induced decidualization of human endometrial stromal cells in vivo or in vitro. These findings suggest that membrane-bound peptidases are important regulators of the function and differentiation of the ovarian cells and endometrial cells including embryo. In the near future, the physiological roles of these peptidases will be clarified and clinical use of peptidase inhibitors may be applied to the various reproductive disorders.

Animals↗
PubMed1999

Fifteen-year follow-up of a heterozygous Fabry's disease patient associated with pre-excitation syndrome.

A 47-year-old woman with heterozygous Fabry's disease with pre-excitation syndrome has been followed up for 15 years. Diagnosis was confirmed by the typical electron microscopic feature of the endomyocardial specimen and a decreased plasma alpha-galactosidase activity. As the disease progressed, the interventricular septum thickened from 11 to 17 mm as measured by echocardiography, while the AH interval was prolonged from 80 to 140 msec. In Fabry's disease, the PR interval has been reported to be variable from short PR to AV block. Therefore, this case may be helpful to understand the time course in the AV conduction abnormalities with the progression of Fabry's disease.

Biopsy↗
PubMed1999

Long-term maintenance combination chemotherapy with OPEC/MPEC (vincristine or methotrexate, prednisolone, etoposide and cyclophosphamide) or with daily oral etoposide and prednisolone can improve survival and quality of life in adult T-cell leukemia/lymphoma.

Acute leukemia and lymphoma varieties of adult T-cell leukemia/lymphoma (ATL) usually carry a poor prognosis. While etoposide is generally useful for treating ATL, especially as a daily oral maintenance regimen, etoposide has not proven effective in severe types of ATL efficient in some patients. Of 87 ATL patients whom we have treated, 51 had acute leukemia, 22 lymphoma and 14 progressive chronic leukemia. Seventy-nine patients were treated with a long term maintenance combination protocol, OPEC/MPEC (weekly doses of vincristine, 0.7 mg/m2 or methotrexate, 14 mg/m2; prednisolone, 20 mg/m2; etoposide, 70 mg/m2 and cyclophosphamide, 200 mg/m2). The other 8 patients, 3 with acute leukemia, 2 with lymphoma and 3 with progressive chronic leukemia, were treated with daily oral administration of 25 mg of etoposide and 10 mg of prednisolone (DOEP). The dose administered was modified in individual cases to maintain the granulocyte count and reduce the number of ATL cells. Considering both protocols, a complete response and a partial response were achieved in 31.0% and 58.6% patients, respectively. Median survival times (MST) of all patients and, acute leukemia, lymphoma and progressive chronic leukemia types were 7.5, 6.7, 9.6 and 12.4 months, respectively. Respective MST of patients treated with OPEC/MPEC or DOEP protocols were 7.1 and 18.0 months. Relatively normal WBC counts, lower lactate dehydrogenase concentration and normal calcium concentration, limited numbers of anatomic sites involved, good performance status and good response to chemotherapy were significantly associated with long survival time. Drug toxicity was not apparent, and about half of patients were treated in an outpatient setting.

Administration, Oral↗
PubMed1999

[Management of mycobacteriosis in general hospital without isolation ward for tuberculosis patients. 2. The problems of management of the patients diagnosed pulmonary tuberculosis after admission to the respiratory ward of university hospital having no an isolation ward for the tuberculous patients].

The management of 28 patients, diagnosed pulmonary tuberculosis by bacteriological or pathologic findings after the administration to the Koshigaya Hospital of Dokkyo university school of Medicine from January 1994 through September 1997, which had no an isolation ward for tuberculosis patients was analyzed. The mean age of the patients was 50.6 +/- 16.7 (18-85), and the number of male and female patients was 22 and 6 respectively. The underlying diseases found in 10 patients were gastric cancer, breast cancer, osteochondrosarcoma, collagen disease, diabetes mellitus, liver cirrhosis, pneumoconiosis, and bronchial asthma. Two patients were complicated by a lung cancer. Six of 28 patients showed smear-positive and culture-positive specimens and 22 of 28 patients showed smear-negative and culture-positive specimens. The detection of mycobacterial DNA in the samples after amplification by the polymerase chain reaction (PCR) used in 15 patients and was positive for 7 of 15 patients. The pathological study of the specimens obtained by Transbronchial lung biopsy was performed for 14 patients. The pathological findings were compatible with tuberculosis in 7 of 14 patients. The chief complaints of the 11 patients admitted to the hospital with in 3 days after first visit, were fever in all patients and in 5 patients with pleural effusion. A few patients showed smear-negative and PCR positive specimens and complicated by lung cancer or other malignancy, were treated in non isolation ward in the particular case of emergency evacuation before admission, careful examination such as a tuberculin test, bacterial examination, and PCR of sputum should be performed in the patients suspected of having pulmonary tuberculosis. The patients isolating tubercule bacilli after administration should be transferred to the hospital with isolated ward for tuberculosis or isolated room in general hospital in the particular case of emergency evacuation with the greatest care.

Adolescent↗
PubMed1999

[A case report of coronary artery bypass grafting using hypothermic circulatory arrest technique for the severely calcified ascending aorta].

Severe calcification of the ascending aorta makes coronary artery bypass grafting (CABG) complicated since aortic cross-clamping may induce cerebral embolization of aortic debris or aortic dissection. Furthermore, there are problems that the distal aortic occlusion becomes incomplete and proximal anastomosis between the ascending aorta and saphenous veins becomes impossible. CABG for a 56 year-old male with severely calcified ascending aorta was successfully conducted using hypothermic circulatory arrest technique. His right internal thoracic artery was bypassed to LAD under fibrillatory arrest and then his right gastroepiploic artery was bypassed to the distal portion of RCA under hypothermic circulatory arrest. There was no complication and left ventricular ejection fraction improved from 16% to 38% postoperatively.

Aorta↗
PubMed1999

A synergistic effect of serotonin transporter gene polymorphism and smoking in association with CHD.

Serotonin induces vasoconstriction in the presence of atherosclerotic lesions. Platelets acquire serotonin from the extracellular space by serotonin transporter and release it following aggregation. There is a functional polymorphism in the serotonin transporter (5-HTT) gene promoter associated with transcriptional efficacy and plasma serotonin levels. To examine whether the polymorphism is associated with coronary heart disease (CHD) in the Japanese, we analyzed 144 male CHD patients with an onset age before 65 and 222 apparently healthy men. The L allele was observed significantly more frequently in the CHD patients (26%) than in the control subjects (19%); the odds ratio was 1.48 (p <0.03). A significant interaction between the polymorphism and smoking was observed for CHD (p = 0.03), suggesting that the two have a synergistic effect on CHD. Odds ratio of the combination of the L allele and smoking was 1.95 (p <0.003). The 5-HTT gene promoter polymorphism may play a role in susceptibility to CHD, particularly when it is combined with smoking.

Adult↗
PubMed1999

[Angiography of occlusive vascular disease].

Angiography is still "the gold standard" of diagnosis of arterial and venous disease. With improvement of equipment, materials and contrast media, angiography has become less invasive and increased its image quality. Because the resolution of digital subtraction angiography (DSA) has been improved and the size of image intensifier has become large enough, DSA is being substituted for conventional angiography. Rotational DSA and stepping DSA have made it possible to evaluate a vessel from multi-direction or the whole lower extremity with one injection of contrast media. Improvement of catheter, guide wire and contrast media has reduced complications and made angiography less invasive examination. Progress of angiography contributes to interventional radiology, which uses the technique of angiography for therapy.

Angiography↗
PubMed1999

Clinical application of adoptive immunotherapy and IL-2 for the treatment of advanced digestive tract cancer.

BACKGROUND/AIMS: We investigated the clinical efficacy of systemic and locoregional adoptive immunotherapy (AIT) with or without interleukin-2 (IL-2) against solid metastatic lesions from digestive tract cancer, which are refractory to conventional chemotherapy or radiotherapy. METHODOLOGY: Seven of 18 patients received hepatic arterial infusion (HAI) of lymphokine-activated killer (LAK) cells with or without IL-2 against metastatic liver tumors (local therapy group). The remaining 11 patients received systemic transfer of LAK cells with IL-2 against metastatic lesions located in organs other than the liver (systemic therapy group). RESULTS: Three of the 7 local therapy group patients showed clinically significant tumor regressions and this was evaluated as being equivalent to partial response (PR) (response rate: 43%). Two of the 11 systemic therapy group patients showed tumor regression which was evaluated as being equivalent to either complete response (CR) or PR (response rate: 18%). These 2 effective cases in the systemic therapy group were esophageal cancer patients. CONCLUSIONS: Locoregional AIT with or without IL-2 against liver metastases of digestive tract cancer could be an effective therapeutic modality in some patients who are refractory to conventional therapies. However, clinical efficacy of systemic AIT with IL-2 against metastases of digestive tract cancer would not be an effective modality except for the metastases of esophageal cancer.

Adult↗
PubMed1999

[Therapeutic efficacy of intra-peritoneal infusion of cisplatin and continuous intravenous infusion of 5-fluorouracil in gastric cancer patients with peritoneal metastasis].

A combination chemotherapy with intra-peritoneal infusion of CDDP and continuous intravenous infusion of 5-FU was used with a total of 16 gastric cancer patients with peritoneal metastasis (P 2 or P 3). Infuse A-port was inserted at the time of operation, CDDP 70 mg/m2 was administered intra-peritoneally at day 1, and 5-FU 700 mg/m2 was continuously administered intravenously at day 1-5. This treatment was repeated twice. Toxicity was evaluated according to the criteria from JCOG. Major toxicities of this regimen were anemia, leukocytopenia and nausea/vomiting. Except for one patient with Grade 3 venous thrombosis, all toxicities were less than Grade 2 and well tolerable. Median survival time was 343 days, but, one patient has survived more than 6 years. According to the multivariate analyses, depth of invasion was selected as an independent prognostic factor for this treatment. This therapy is considered to be a safe and effective treatment modality for gastric cancer patients with peritoneal metastasis.

Adult↗