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H Sakaguchi

Publications and source records attributed to H Sakaguchi.

At least 127 records · Page 7Linked to original sources
PubMed1999

Man-made mineral fibers induce apoptosis of human peripheral blood mononuclear cells similarly to chrysotile B.

The aim of this study was to investigate whether man-made mineral fibers (MMMF) induce apoptosis of human peripheral blood mononuclear cells (PBMC), as we recently demonstrated for chrysotile B. In vitro cultivation of PBMC with various MMMF as well as chrysotile B clearly produced apoptotic cells. The alteration of the expression for apoptosis related genes at the mRNA level during in vitro cultures of PBMC with various MMMF revealed upregulation of Flice and Apaf-1 genes and down regulation of TNF receptor 1 and Bid genes. These results indicate that MMMF induce apoptosis of PBMC in a similar manner to chrysotile B. However, the process may be mediated not only by the Fas-related apoptotic pathway but also a mitochondrial pathway. Thus, one should be aware that respiratory and immunological abnormalities may occur in workers who are exposed to MMMFs.

Adult↗
PubMed1999

Expression of fibroblast growth factor and FGF-receptor family genes in human myeloma cells, including lines possessing t(4;14)(q16.3;q32. 3) and FGFR3 translocation.

Recently several chromosomal translocations involved in myeloma cases and myeloma cell lines; i.e., t(11;14)(q13;q32), t('8;14)(q24;q32), t(4;14)(q16.3;q32.3), t(6;14)(p25;q32), and t(14;16)(q32.3;q23), have been identified. These translocations are considered to dysregulate genes which may be concerned with myelomagenesis; i.e., PRAD1/cyclin D1, the c-myc oncogene, FGFR3 (fibroblast growth factor receptor 3), MMSET (multiple myeloma SET domain), MUM1 (multiple myeloma oncogene 1)/IRF4 (interferon regulatory factor 4), and the c-maf oncogene, respectively. However, the cellular biological roles of these genes have not yet been elucidated in myeloma cells. Because two of the seven human myeloma cell lines which were established at Kawasaki Medical School, Okayama, Japan, KMS-11 and KMS-18, have been proven to possess t(4;14)(q16.3;q32.3), we studied the expression levels of the FGFR3 gene in these seven cell lines and 13 primary myeloma specimens. The expression levels of 12 known FGF family genes (FGF-1 to 12) and 4 FGFR genes (FGFR1 to 4) were also examined in seven cell lines. In addition, the growth status of the KMS-11 and KMS-18 lines with FGF-1 or anti-FGF-4 neutralizing monoclonal antibody (MoAb) supplementation was investigated because FGF-1 and 4 are known as the principal ligands for FGFR3. FGFR3 overexpression was observed in both of the cell lines possessing t(4;14)(q16.3;q32.3) and in 3 of 13 case specimens. Anti-FGF-4 neutralizing MoAb caused significant growth inhibition in these two cell lines possessing t(4;14)(q16.3;q32.3). These findings indicate that t(4;14) (q16. 3;q32.3) may provide myeloma cells with a growth advantage via an autocrine mechanism between FGFR3 and FGF-4.

Aged↗
PubMed1999

[Thermo-chemotherapy using low-dose CPT-11 in a patient with local recurrence of rectal cancer].

We report a case of pelvic recurrence of advanced rectal carcinoma, presenting a favorable response with a low dose (25 mg/m2) of CPT-11 (Irinotecan) combined with topical hyperthermia for relapse after treatment with 4 cycles of high-dose (100 mg/m2) CPT-11 chemotherapy alone. This combination therapy was safely carried out on an outpatient basis. The degrees of recovery of the left lower limb pain and edema, and of serum CEA reduction were comparable to those in high-dose chemotherapy alone. No significant adverse effects were encountered in the thermo-chemotherapy attempted. Since hyperthermic treatment enhances the cytotoxic effects of CPT-11 in vitro, topical hyperthermia with low-dose CPT-11 therapy may produce a response comparable to that in high-dose CPT-11 chemotherapy alone. However, an optimal dose and comparative study with other chemotherapeutic agents would be needed. This regimen may be advantageous in the maintenance of quality of life for the palliation of postoperative pelvic recurrence since this treatment can be performed on an outpatient basis.

Adenocarcinoma↗
PubMed1999

[Interventional radiology for recurrent cancer].

The indications for the reoperative treatment for postoperative recurrence of cancer in the field of gastroenterology are usually limited. Interventional radiology (IVR), which is less invasive and effectively enhances the quality of life, will play an important role in the treatment of patients with postoperative recurrent cancer. This paper evaluate IVR as a therapeutic strategy for postoperative recurrent cancer in gastroenterology based on our experience. Metallic stents have proven useful for stenosis of the alimentary tract due to recurrence after surgery for esophageal or gastric cancer and for jejuno-biliary anastomotic stenosis caused by postoperative recurrent bile duct cancer. Segmental Lipiodol TAE is more effective and result in better cumulative survival rates than conventional TAE in the treatment of postoperative recurrence of hepatoma.

Bile Duct Neoplasms↗
PubMed1999

[Stentless aortic root bioprosthesis (freestyle) to patients of bicuspid aortic valve with abnormal positioning of the coronary ostia].

Stentless aortic root bioprosthesis (Freestyle) was implanted to two patients of bicuspid aortic valve stenosis with anatomically abnormal positioning of the coronary ostia. In a patient of LR type bicuspid valve, the left coronary artery was located at 180 degrees against the right coronary ostium. To match the Valsalva sinus of the patient with bioprosthesis, the left half of the native annulus, 23 mm in the diameter, was plicated corresponding to the one third of the Freestyle inflow, 21 mm in the diameter. In the other patient of AP type bicuspid valve, both coronary ostia were closely positioned at 90 degrees. To keep both ostia in the sinus of bioprosthesis, careful trimming and suturing were required in the narrow part of both ostia. Their postoperative courses were uneventful and no regurgitation has been observed in either case.

Aged↗
PubMed1999

[Clinical results of surgical repair for thoracic aortic aneurysms: intraoperative blood loss and morbidity].

Clinical results of 64 patients who underwent surgical repair for thoracic aortic aneurysms were studied, focusing on the relationship between intraoperative blood loss and postoperative morbidity. Operative mortality was 22% in the urgent repair group and 9% in the elective repair group. Deep hypothermia, operative death, postoperative complication were the factors which significantly correlated to the amount of intraoperative blood loss. In patients who received deep hypothermia, larger blood loss and higher incidence of mortality and morbidity were observed. There was a significant relationship between the lowest core temperature during cardiopulmonary bypass and the lowest platelet count. Intraoperative blood loss revealed as a strong risk factor to directly influence postoperative clinical outcome of thoracic aortic operation.

Aortic Aneurysm, Thoracic↗
PubMed1999

[Surgical treatment of N2 involved non-small cell lung cancer--the systematic extended lymph node dissection based on the regional lymphatic drainage].

From the study on regional lymphtic drainage, we have decided the extent of lymphadenectomy as follows; a) For the left lung cancer and the right upper lobe primary, systematic bilateral mediastinal dissection (R3 alpha) through a median sternotomy, b) For the cases with the highest mediastinal node involvement, lower half of radical neck dissection (R3 gamma) through a cervical collar incision in addition to a). The cN diagnosis by CT interpretation and pN diagnosis were compared. The under estimated rates of N were 32% of 137 patients with the left lung primary. 46 patients with pN2(+) included 14 patients (31%) with pN3 disease. As for the right upper lobe primary, 17 patients with pN2(+) included 13 patients (76%) with pN3 disease. Postoperative survival rates calculated with Kaplan-Meiermethod; 1) The five-year survival rates were 43% of 46 patients with pT1-3 N2-3 of the left lung primary. 2) As for the right upper lobe primary, the two-year survival rates were 51% of 17 patients with pT1-4 N2-3. 3) The three-year survival rates of 26 patients with pN3 gamma diagnosed as cN0-3 alpha preoperatively were 41%. These systematic extended dissection (R3 alpha, R3 gamma) would bring better prognosis in the patients with pN2-3 disease.

Carcinoma, Non-Small-Cell Lung↗
PubMed1999

[Re-coronary artery bypass grafting using a MIDCAB technique in a patient with a patent RITA-LAD graft].

In a patient with a patent RITA-LAD (right internal thoracic artery-left anterior descending artery) graft, re-CABG (re-coronary artery bypass grafting) with re-median sternotomy has been a high risk procedure. A 56-year-old male underwent 4-CABG (RITA-LAD, LITA-Dx, SVG-PL, and SVG-RCA) nine years ago. Coronary angiography showed that the RITA-LAD graft was well patent, but there was 95% stenosis distal to RITA-LAD anastomosis site. We performed re-CABG (right gastroepiploic artery-LAD; RGEA-LAD), using MIDCAB (minimally invasive direct coronary artery bypass) technique with neither re-median sternotomy nor cardiopulmonary bypass. The right gastroepiploic artery was harvested through a small upper median laparotomy and anastomosed to LAD through a small left anterior thoracotomy. The postoperative course was uneventful. This technique seems to be useful for re-revascularization of the LAD in a patient with a patent RITA-LAD graft.

Coronary Artery Bypass↗
PubMed1999

Significant role of apoptosis in type-1 autoimmune hepatitis.

We used the terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling (TUNEL) method to detect apoptosis, and immunohistochemical staining for molecules related to apoptosis, a marker of cell proliferation, and surface markers of lymphocytes to examine 20 patients with autoimmune hepatitis (AIH). Confluent hepatic necrosis was frequently found, in which rosette formation of hepatocytes and ductular proliferation were common. TUNEL staining and staining for Lewis Y antigen, Bax protein, and Fas antigen were found in biliary epithelial cells in bile ducts and proliferating atypical bile ductules in regions of confluent necrosis with severe lymphocytic infiltration. TUNEL staining and staining for Lewis Y antigen and Bax protein were found in rosette-forming hepatocytes. Many hepatocytes in lobules without injury were stained for proliferating cell nuclear antigen (PCNA). bcl-2 oncoprotein was found in many lymphocytes surrounding proliferating atypical bile ductules and rosette-forming hepatocytes in regions of confluent necrosis, in which CD20 and OPD 4 were found. Apoptosis of both hepatocytes in rosette arrangement and biliary epithelial cells in bile ducts and proliferating atypical bile ductules may play a role in progression of AIH as well as confluent hepatic necrosis.

Adult↗
PubMed1998

Biologic implications of the expression of vascular endothelial growth factor subtypes in ovarian carcinoma.

BACKGROUND: Vascular endothelial growth factor (VEGF) has been identified as an important factor for tumor angiogenesis, which is essential for the growth, invasion, and metastasis of solid tumors. This study examines the clinical significance of VEGF subtypes in ovarian carcinoma. METHODS: Tumor specimens from 128 patients with ovarian carcinoma were evaluated for VEGF and its mRNA expression. The expression of VEGF, especially its subtypes, was determined by Western blot analysis with a sandwich enzyme immunoassay in ovarian carcinomas and reverse transcription-polymerase chain reaction and Southern blot analysis in normal ovaries that served as controls, and the relation between VEGF expression and the histologic types and clinical stages of ovarian carcinomas was analyzed. RESULTS: Among the four subtypes of VEGF, the populations of VEGF165 and VEGF121 were dominant in normal ovaries and ovarian carcinomas. The levels of VEGF and VEGF165 mRNA in ovarian carcinomas were significantly higher than in normal ovaries (P < 0.05). On the other hand, there was no significant difference in the levels of VEGF and VEGF165 mRNA among ovarian carcinomas classified according to histopathologic type or clinical stage. CONCLUSIONS: This analysis suggests that VEGF165 may be elevated in all stages of ovarian carcinoma via angiogenic activity, regardless of histopathologic type.

Adult↗
PubMed1998

Expressions of vascular endothelial growth factor (VEGF) and its mRNA in uterine endometrial cancers.

To know the potential of growth, invasion and metastasis of uterine endometrial cancer associated with neovascularization, the expressions of VEGF and its mRNA, especially their subtypes, in uterine endometrial cancers and normal uterine endometria as controls were determined by Western blot analyses with a sandwich enzyme immunoassay and RT-PCR-Southern blot analysis, respectively, and the relation between their expressions and histological grades, grades of myometrial invasion and clinical stages of uterine endometrial cancers was analyzed. The levels of VEGF (VEGF165 and VEGF121) protein and mRNA were in a wide range and higher in normal uterine endometria than in the malignant counterparts. The levels of VEGF protein were higher in order of histopathological differentiation (normal uterine endometrium > well-differentiated (G1) > moderately differentiated (G2) and poorly differentiated (G3)) and those of VEGF protein and VEGF121 mRNA were lower in order of the advance of clinical stages (normal uterine endometrium > stage I > stage II > stages III and IV). There was, however, no significant difference in their levels among uterine endometrial cancers classified according to grades of myometrial invasion. This suggests that VEGF is downregulated during uterine endometrial cancer progression with dedifferentiation. Namely, VEGF in some endometrial cancers might contribute to the early process of advancing of malignancy via angiogenic activity.

Adult↗
PubMed1998

The very low- and intermediate-density lipoprotein fraction isolated from apolipoprotein E-knockout mice transforms macrophages to foam cells through an apolipoprotein E-independent pathway.

Apolipoprotein E (apoE)-knockout mice develop severe atherosclerosis associated with high levels of very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) in plasma. To investigate the atherogenic role of VLDL and IDL, the lipoprotein fraction containing both VLDL and IDL (apoEko-VLDL/IDL) was isolated from plasma of apoE-knockout mice by ultracentrifugation, and its interaction with macrophages was studied. When peritoneal macrophages obtained from apoE-knockout mice were incubated with apoEko-VLDL/IDL, the level of cellular cholesteryl esters (CE) increased with the concentration of apoEko-VLDL/IDL. The level of cellular cholesteryl [3H]oleate formed reached 15.1 nmol/mg of cell protein upon incubation with 50 microg/mL apoEko-VLDL/IDL for 18 h, which was an 8.4-fold increase over the corresponding level induced by low-density lipoprotein (LDL). The cellular CE mass was also significantly increased by apoEko-VLDL/IDL. Morphologically, after exposure to apoEko-VLDL/IDL, macrophages became strongly stained with Sudan black B. The total binding of [125I]apoEko-VLDL/IDL to macrophages was effectively replaced by more than 80% by an excess of the unlabeled ligand. Specific binding, calculated by subtracting the nonspecific binding from the total binding, exhibited a saturation pattern. Similar results were obtained with cell association and degradation experiments. In addition, the endocytic degradation of [125I]apoEko-VLDL/IDL was partially inhibited by LDL, whereas acetyl-LDL did not show any effect. These results indicated that apoEko-VLDL/IDL in its unmodified form produced significant CE accumulation in macrophages through a specific and apoE-independent pathway. This pathway may explain, in part, the mechanisms of foam cell formation in arterial walls and the subsequent development of atherosclerosis in apoE-knockout mice.

Animals↗
PubMed1998

Antiatherogenic effects of the antioxidant BO-653 in three different animal models.

Antioxidants have been proposed to have antiatherogenic potential by their inhibition of low density lipoprotein (LDL) oxidation. Here, we report an antioxidant, BO-653 (2,3-dihydro-5-hydroxy-2, 2-dipentyl-4,6-di-tert-butylbenzofuran), designed to exhibit antioxidative potency comparable to that of alpha-tocopherol, but yet possess a high degree of lipophilicity comparable to that of probucol. BO-653 exhibits a high affinity for LDL and is well distributed in aortic vessels in vivo. In atherosclerosis models of rabbits and mice, BO-653 has been shown to be able to suppress the formation of atherosclerotic lesions without untoward side effects. Specifically, there was no reduction of high density lipoprotein levels. This antioxidant provides additional evidence in support of the oxidized-LDL hypothesis, and itself is a promising candidate antioxidant for clinical use.

Animals↗
PubMed1998

Expression of platelet-derived endothelial cell growth factor (PD-ECGF) and its mRNA in uterine endometrial cancers.

To determine the potential of growth, invasion and metastasis of uterine endometrial cancer cells associated with neovascularization, the expressions of platelet-derived endothelial cell growth factor (PD-ECGF) and its mRNA in uterine endometrial cancers and in normal uterine endometria as controls were determined and the relationship between their expressions and histological grades, grades of myometrial invasion and clinical stages of uterine endometrial cancers was analyzed. The levels of PD-ECGF were significantly higher in uterine endometrial cancers of well-differentiated grade (G1) with invasion to < or =1/2 myometrium (B) and of stage 1 than in those of moderately and poorly differentiated grades (G2 and G3, respectively) limited to endometrium (A) and with invasion to >1/2 myometrium (C) and of stages II and III/IV and in normal uterine endometria. There was no significant difference in the levels between uterine endometrial cancers of G2 and G3, A and C, or stages II and III/IV and normal uterine endometria. Therefore, the active availability of PD-ECGF might contribute to the acceleration of angiogenic activity in the early process of invasion of well-differentiated uterine endometrial cancers.

Adult↗
PubMed1998

Unique inhibitory action of the synthetic compound 2-[N-(2-aminoethyl)-N-(5-isoquinolinesulfonyl)] amino-N-(4-chlorocinnamyl)-N-methylbenzylamine (CKA-1306) against calcium/calmodulin-dependent protein kinase I.

A newly synthesized compound, 2-[N-(2-aminoethyl)-N-(5-isoquinolinesulfonyl)]amino-N-(4-chlorocinnamyl )-N-methylbenzylamine (CKA-1306), was found to inhibit cyclic AMP-dependent protein kinase (PKA) and Ca2+/calmodulin-dependent protein kinase I (CaMK I) with IC50 values of 1.6+/-0.14 and 2.5+/-0.16 microM, respectively. In contrast, the established PKA inhibitors H-8 and H-89 inhibited CaMK I with relatively high IC50 values of >100 and 24.4+/-3.2 microM, respectively. An additional inhibitor, KN-62, against Ca2+/calmodulin-dependent protein kinase II (CaMK II) did not inhibit either PKA or CaMK I at the concentrations tested. In our library of many isoquinolinesulfonamide derivatives, only CKA-1306 inhibited CaMK I to a satisfactory degree, suggesting a unique mode of action. Indeed, the inhibition of CaMK I by CKA-1306 was competitive in every respect to Mg2+/ATP, peptide substrate (syntide-2), and Ca2+/calmodulin. This phenomenon may be understood from the context of the recently determined structure of the enzyme in its autoinhibited state. Such kinetic analysis was also extended to cases using a phosphorylated and activated enzyme at Thr177 or a constitutively active, COOH-terminal truncated mutant at Gln293. CKA-1306 still competed with Mg2+/ATP for the two enzymes, but it no longer achieved any competitive advantage over syntide-2. These results may reflect some differences in the active conformation of CaMK I. However, the compound should be constant in its recognition of an Mg2+/ATP-binding site of the enzyme. Though CKA-1306 is not specific to CaMK I, the compound will be useful in studying the enzyme further under limited conditions.

Animals↗
PubMed1998

Expression of platelet-derived endothelial cell growth factor (PD-ECGF) and its mRNA in ovarian cancers.

The potential of growth, invasion and metastasis of ovarian cancer cells associated with neovascularization, and the expression of platelet-derived endothelial growth factor (PD-ECGF) and its mRNA in ovarian cancers were determined. The relationship between their expression and histopathological types and clinical stages of ovarian cancers was also analyzed. The levels of PD-ECGF and its mRNA were higher in ovarian cancers than in normal ovaries. Furthermore, some endometrioid carcinomas and serous cystadenocarcinomas of the ovary and some ovarian cancers in stages III and IV expressed remarkably high levels of PD-ECGF and its mRNA. Therefore, in some ovarian cancers, PD-ECGF might be related to advanced stages of ovarian cancers associated with neovascularization.

Adult↗
PubMed1998

Long-term benefits of internal thoracic artery-coronary artery bypass in Japanese patients.

OBJECTIVES: This study sought to determine the effects of grafting the internal thoracic artery (ITA) to the left anterior descending coronary artery (LAD) on long-term (10-year) survival, the cardiac death-free rate, and on the cardiac event-free rate in Japanese patients. BACKGROUND: The use of ITA grafts has been reported to enhance postoperative survival and to decrease the occurrence of cardiac events in the Western literature. However, the survival benefits in Japanese patients, who may have different prognoses with coronary artery disease and a different fate of a saphenous vein graft, have not yet been determined. SUBJECTS AND METHODS: A total of 954 consecutive patients who underwent coronary artery bypass graft operations (CABG) during the last 12 years at the Nara Medical University were followed and evaluated. Of these, 713 patients underwent ITA-CABG to at least the LAD (ITA group), and 241 patients received a saphenous vein graft (SVG) to the LAD (SVG group). At the time of operation, no significant difference was found between these two groups in age, sex ratio left ventricular ejection fraction, left ventricular end-diastolic pressure, cardiac index, incidence of unstable angina, or in the necessity for an emergency operation. However, those patients who received ITA-CABG had significantly higher incidences of diabetes mellitus, hyperlipidemia, and left main coronary artery disease. RESULTS: The 10-year cumulative graft patency rate for the LAD was 23% higher in the ITA group (90.3%) compared to the SVG group (67.0%), (p < .0001). Despite increased preoperative risk factors, patients in the ITA group showed significant improvements in their 5- and 10-year cumulative survival rates as well as in their cardiac death-free and event-free rates. Furthermore, this study demonstrated that ITA grafts improved the prognoses of patients with diabetes mellitus or left ventricular dysfunction and lowered both the long-term postoperative cardiac-death rate and the cardiac-event rate. CONCLUSIONS: The use of ITA grafts was effective in improving both the postoperative survival and cardiac event-free rates, and should be recommended in patients with diabetes mellitus or left ventricular dysfunction. ITA grafting to the LAD should be a routine operation in almost all categories of such patients.

Aged↗