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Biomedical subjects

S Okamura

Publications and source records attributed to S Okamura.

At least 91 records · Page 5Linked to original sources

Enhanced levels of oleate-dependent and Arf-dependent phospholipase D isoforms in experimental colon cancer.

Phospholipase D (PLD) (EC 3.1.4.4) is one of the intracellar signal transduction enzymes and plays an important role in a variety of cellular functions. In order to clarify the role of PLD in proliferation and tumorigenesis of colon cancer, we investigated the activities of oleate-dependent and ADP-ribosylation factor (Arf)-dependent types of PLD in experimental colon cancer of the rat. We produced colon cancer in Wistar rats by injecting the carcinogen, dimethylhydrazine dihydrochloride (DMH). The control rats were injected with physiological saline. Mucosal scrapings from the colon were homogenized and centrifuged to obtain the microsomal or membrane fraction. We measured the two types of PLD activities in these fractions using the transphosphatidylation reaction. Both oleate-dependent and Arf-dependent PLD activities were significantly higher in the colon cancer tissue than normal colonic mucosa. The mean specific activity of oleate-dependent PLD) in colon cancers was 1.66 +/- 0.75 (SD) nmol/min/mg whereas the value for normal colonic mucosa was 0.18 +/- 0.09 nmol/min/mg (P < 0.01; Mann-Whitney U-test). On the other hand, the mean specific activity of Arf-dependent PLD in colon cancers was 76.36 +/- 29.37 pmol/min/mg whereas the value for normal colonic mucosa was 19.90 +/- 11.97 pmol/min/mg (P < 0.01; Mann-Whitney U-test). These results suggest that PLD is implicated in the proliferation and tumorigenesis of colon cancer. The present study provides the first evidence for the enhanced levels of two types of PLD in colon cancer and raises the possibility that these PLDs can be used as the potential target for the treatment of colon cancer.

1,2-Dimethylhydrazine↗

[Subsegmental transcatheter hepatic arterial embolization under balloon occlusion of the corresponding hepatic vein with SMANCS].

Recently, subsegmental transcatheter hepatic arterial embolization under balloon occlusion of the corresponding hepatic vein has been performed to treat hepatic infarction in subregion hepatocellular carcinoma (HCC). Here, we report subsegmental transcatheter hepatic arterial embolization under balloon occlusion of the corresponding hepatic vein with styrene maleic acid neocarzinostatin lipiodol (SMANCS) (SMANCS-TAE under balloon occlusion of the corresponding hepatic vein). This study included 9 patients with HCC who underwent SMANCS-TAE under balloon occlusion of the corresponding hepatic vein. In all patients, the therapeutic effects (TE) were evaluated according to the criteria of direct response to liver cancer treatment on abdominal computed tomography (CT) 3 weeks after surgery. In 7 patients who could be followed for more than one year, there was no postoperative relapse at the site of treatment. Furthermore, this procedure facilitated the detection of accumulation of SMANCS not only in the tumor but also in the subregion of the tumor in patients with HCC involving immature arterial tumor neoplastic vessels. In patients with large HCC complicated by severe heart failure showing a poor general condition, this procedure allowed treatment to be completed without complication. SMANCS-TAE under balloon occlusion of the corresponding hepatic vein, which can also embolize the portal vein by applying targeting chemotherapy with SMANCS, may cause necrosis not only in the tumor but also in noncancerous liver tissues. This procedure may be an indication for a larger number of cases than standard TAE, facilitating more complete local treatment.

Antineoplastic Agents↗

[Value of MR cholangiography in the diagnosis of pancreatic diseases compared with endoscopic retrograde cholangiopancreatography].

PURPOSE: To compare magnetic resonance cholangiography (MRCP) with endoscopic retrograde cholangiography (ERCP) in the diagnosis of pancreatic diseases. METHODS: The authors retrospectively reviewed MRCP and ERCP images obtained in 56 patients with pancreatic diseases and 192 controls. Detectability of the pancreatic duct and its branches and diagnostic usefullness were evaluated. RESULTS: MRCP was successful in almost all the patients without ascitic fluid or ileus. Findings of the main pancreatic ducts (i.e., dilation, stenosis and obstruction) were similarly demonstrated by ERCP and MRCP. The degree of ductal narrowing tends to be overestimated with MRCP. CONCLUSION: MRCP appears to be less invasive than ERCP. MRCP could provide sufficient information and play a complementary role in the diagnosis of pancreatic diseases.

Adult↗

[Lung abscess resulting from esophageal carcinoma successfully treated with intraesophageal covered self-expandable metallic stent].

An 82-year-old man was admitted to our hospital with high fever and back pain. He already suffered from esophageal carcinoma and expandable metallic stent had been inserted because of esophageal stenosis. A chest x-ray film obtained on admission showed infiltrative shadows in the right lower lung filled. The diagnosis of lung abscess was made on the basis of aspirate findings. Despite closed drainage, antibiotic treatment, and fasting therapy, progressive pulmonary infiltrates developed. Esophagography and esophagoscopy revealed that an esophageal fistula due to an advanced esophageal carcinoma had caused the lung abscess. An additional covered self-expandable metallic stent (EMS) was placed on the surface of the esophageal carcinoma, close to the esophageal fistula. This promptly resolved the lung abscess. Our conclusion was that the covered-EMS can be effective for the palliation of esophagorespiratory fistulas.

Aged↗

Effect of the chimeric soluble granulocyte colony-stimulating factor receptor on the proliferation of leukemic blast cells from patients with acute myeloblastic leukemia.

The biological roles of the soluble granulocyte colony-stimulating factor (G-CSF) receptor, which arises as a result of alternative RNA splicing, are as yet unknown. In this study, we examined the in vitro effect of a chimeric protein composed of the extracellular region of a murine G-CSF receptor and the human IgG1 Fc region because a human natural soluble G-CSF receptor was not available. First, we found that this chimeric soluble G-CSF receptor could inhibit the biological activity of G-CSF on normal bone marrow colony formation. Because G-CSF also plays an important role in the proliferation of leukemic blast cells, we next examined the effect of the soluble G-CSF receptor on leukemic blast colony formation in 10 acute myeloblastic leukemia cases. Although G-CSF stimulated the proliferation of leukemic progenitor cells to form leukemic blast colonies, the chimeric soluble G-CSF receptor completely inhibited this stimulatory effect. Furthermore, the chimeric soluble G-CSF receptor also inhibited spontaneous leukemic blast colony formation in two cases. Because a high concentration of G-CSF was observed in the supernatants of leukemic blast cells from these two cases, it seems likely that the soluble G-CSF receptor cut off the autocrine growth mechanism of leukemic blast cells mediated by G-CSF. These findings suggest the possibility that the soluble G-CSF receptor could be used in a clinical application for acute myeloblastic leukemia patients in the future.

Animals↗

Increased phospholipase D activity in human breast cancer.

Phospholipase D is believed to play an important role in cell proliferation and tumorigenesis. One of its major functions is to cause a sustained activation of protein kinase C through the primary production of phosphatidic acid from phosphatidylcholine by the enzyme, followed by dephosphorylation forming diacylglycerol. Protein kinase C is known to be activated or translocated in some tumors including breast tumors. In order to examine phospholipase D activity in breast tumors, surgical specimens of human breast tumors were obtained by mastectomy or wide excision, and their phospholipase D activities were assayed by determining the formation of phosphatidylethanol from phosphatidylcholine and ethanol. Phospholipase D activity was predominantly localized in the microsomal fraction of the tumor tissue and markedly stimulated by oleic acid. We observed a significant increase in phospholipase D activity in 17 out of 19 spontaneous human breast tumors as compared to adjacent histologically normal breast tissue. The mean specific activity in the tumors was 52.9 +/- 41.8 (SD) pmol min-1 mg protein-1 whereas the value for the normal breast tissue was 34.0 +/- 36.2 (SD) pmol min-1 mg protein-1 (P < 0.01; paired Wilcoxon's rank-sum test). The mean tumor/normal activity ratio was 2.37. Among prognostic factors, the nuclear grade, evaluated according to Schnitt et al., was found to be correlated with the activity ratio. Our results suggest a role for phospholipase D in human breast tumors. An elevation in phospholipase D activity is useful as a potential marker for malignant disease in the breast.

Adult↗

Jejunal pouch and interposition reconstruction after total gastrectomy for cancer.

The authors modified the operative procedures used in pouch and interposition (PI) reconstruction in an attempt to improve the surgical results after total gastrectomy, because a randomized controlled trial had revealed that the clinical assessment of PI was quite poor, even though it is a physiological route. In most of the treated patients, the gastric emptying test revealed delayed emptying, and an X-ray video film showed folding and twisting of the jejunal conduit between the pouch and duodenum, which disturbed the transmission of nutrition. Modified PI (m-PI) was performed by decreasing the length of the jejunal conduit and widening the mesenteric pedicle to preserve the blood and nerve supply. This procedure was retrospectively compared with the previously used PI reconstruction by evaluating the postprandial symptoms, food intake, body weight, serum nutritional parameters, and emptying time of the gastric substitute. The m-PI group (n = 6) showed a lower incidence of symptoms, a greater food intake, and a greater weight recovery than the PI group (n = 6). The gastric emptying test also revealed an acceptable degree of emptying. We thus conclude that the m-PI reconstruction is more useful for improving the postoperative quality of life than the previously used method of PI reconstruction.

Adult↗

Effect of (-)-epigallocatechin gallate on leukemic blast cells from patients with acute myeloblastic leukemia.

Information on the anti-carcinogenic effect of EGCG, the main constituent of the polyphenols present in Japanese green tea leaves, has recently been accumulating. In this report, we evaluate the effect of EGCG on leukemic blast cells from AML patients. The results showed that EGCG inhibited the proliferation of AML cells in all cases examined. Since AML cells might proliferate by autocrine or paracrine growth mechanisms, we also examined the effect of EGCG on the production of GM-CSF from AML cells. Although EGCG did not directly inhibit the production of GM-CSF, it did inhibit the effect of TNF-alpha or TPA, both of which stimulated AML cells to produce GM-CSF. On the other hand, the modulation of receptors for growth factors might play a role in the proliferation or carcinogenesis of AML cells. We also found that EGCG inhibited the modulation of c-kit, a receptor for stem cell factor, on leukemic cells. These findings suggested that EGCG might be available as a new therapeutic tool for AML patients.

Blast Crisis↗

Revascularization with split duro-encephalo-synangiosis in the pediatric moyamoya disease--surgical result and clinical outcome.

Dural arteries are potential donor arteries for cortical revascularization. In this report, a technique of indirect anastomosis using a split dura is presented. At surgery, the dura near the branches of the middle meningeal artery was split into outer and inner layers, and the split surface of the outer layer was attached to the cortical surface (split duro-encephalo-synangiosis; split DES). This procedure, combined with standard encephalo-duro-arterio-synangiosis, was applied to 25 hemispheres in 18 patients with pediatric Moyamoya disease (mean age, 6 years). Postoperative superselective angiograms demonstrated effective cortical revascularization through the dural arteries in addition to the supply from the scalp arteries. All the patients were symptom free by 1.5 years after surgery. Postoperative reversible ischemic neurological deficit and infarction were seen in three (12%) and one (4%), respectively. The follow-up period ranged from 1 to 12 years (mean, 6.5 years). Thirteen of 16 (81%) patients led normal lives and three were mildly handicapped due to mental retardation that existed preoperatively. The split DES is a useful technique to extend the area of revascularization of ischemic hemispheres in Moyamoya disease.

Adolescent↗

Interleukin-10 inhibits the autocrine growth of leukemic blast cells from patients with acute myeloblastic leukemia.

The effect of interleukin-10 (IL-10) on the growth of leukemic blast cells from patients with acute myeloblastic leukemia (AML) is in need of clarification. We therefore examined the effect of IL-10 on AML cells obtained from 10 patients. Although granulocyte colony-stimulating factor (G-CSF) and/or granulocyte/macrophage colony-stimulating factor (GM-CSF) was able to stimulate the growth of AML progenitor cells to form leukemic blast colonies, IL-10 itself demonstrated no leukemic blast colony-forming activity and no synergistic stimulating activity with other cytokines. However, leukemic blast colonies were formed without the addition of exogenous cytokines in four cases and IL-10 suppressed these spontaneous colony formations in two of the four cases. Since the production of G-CSF and GM-CSF was observed in these two cases, the presence of an autocrine growth mechanism mediated by these cytokines was suggested. When serial concentrations of IL-10 were added, the production of G-CSF and GM-CSF was dramatically inhibited in a dose-dependent manner. These findings suggested that IL-10 could suppress the autocrine growth of AML cells by inhibiting their production of G-CSF and/or GM-CSF. In addition, the administration of IL-10 may be harmless to normal hematopoiesis because IL-10 did not suppress the growth of normal hematopoietic progenitor cells. Our study provides experimental support for the clinical application of IL-10 in patients with AML.

Autocrine Communication↗

Two short peptide sequences repeated three times in carrot beta-tubulin.

There are two repeated peptides, [S,T,Y]QQ[Y,M] and MFR[R,X][V,K], which appear three times each in the region corresponding to the third exon of carrot beta-tubulins. The former peptide is flanked on both sides by a pair of identically charged groups and the latter includes two or three basic amino acids in it. The sequences are generally conserved well among the eukaryotes except for fungi, in which one of the peptides, SQQY, does not exist.

Amino Acid Sequence↗

Alterations in lymphocyte subsets and pituitary-adrenal gland-related hormones during fasting.

We investigated changes in the immunoendocrine system during fasting. Ten hospitalized patients aged 14-46 y with psychosomatic disorders fasted for 7 or 10 d. Blood samples were collected before and on days 3 and 7 of the 7-d fasts. When fasting continued to 10 d, an additional sample was taken on day 10. We measured blood cellularity (white blood cells and total lymphocytes), the total number and percentage of lymphocyte subsets (CD2, CD3, CD4, CD8, and CD19), natural killer (NK) cell activity, cytokines (interleukin 1 beta, interleukin 2, interleukin 6, granulocyte-macrophage colony stimulating factor, tumor necrosis factor alpha, and interferon gamma), and soluble interleukin 2 receptors. Corticotropin, cortisol, and dehydroepiandrosterone sulfate (DHEAS) concentrations were also determined. Although the total number of lymphocytes decreased during fasting, NK cell activity increased significantly. Plasma cortisol and DHEAS concentrations also increased significantly whereas changes in corticotropin concentrations were not significant. The total number and percentage of CD4 cells decreased significantly during fasting but no other lymphocyte subsets changed significantly. The percentage of CD4 cells was negatively correlated with cortisol concentrations during fasting. No detectable changes occurred in cytokines or soluble interleukin 2 receptors during the study. All measured immunoendocrine values that changed during fasting returned to prefasting values during the refeeding period. These findings indicate that fasting affects immune variables such as T cell subsets and NK cell activity at least in part through changes in adrenal gland-related hormones.

Adolescent↗

Characterization of the carrot beta-tubulin gene coding a divergent isotype, beta-2.

Four different beta-tubulin clones were isolated from carrot genomic and cDNA libraries. Their nucleotide sequences were determined 1 and their predicted amino acids were compared with each other. The predicted amino acid composition of the C-terminal region of three of them (beta-1, 3, 4) resembled one another, but that of one isotype (beta-2) was divergent. The beta-2 tubulin included two hydroxyl amino acids, serine and threonine, and consisted of a lower number of negatively charged amino acids than the others in the C-terminal region. The predicted hydrophobicity profile of the beta-2 tubulin around the residue 200 is less hydrophobic than beta-1, but it is still more hydrophobic than those of animal and fungal beta-tubulins. The beta-2 gene was transcribed in cultured cells and flowers, while the beta-1 gene was ubiquitously transcribed in cultured cells, roots, shoots and flowers. When the predicted amino acids of plant tubulin were compared with those of other organisms, substitutions from non-polar amino acids to those with hydroxyl group were conspicuous in the region corresponding to the third exon in the plant genes.

Amino Acid Sequence↗

[Jejunal pouch and interposition reconstruction after a total gastrectomy for cancer].

The authors modified the operative procedures used in pouch and interposition (PI) reconstruction in an attempt to improve the surgical results after a total gastrectomy, because a randomized controlled trial had revealed that the clinical assessment of PI was quite poor, even though it is a physiological route. In most of the treated patients, the gastric emptying test revealed delayed emptying, and an X-ray video film showed folding and twisting of the jejunal conduit between the pouch and duodenum, which disturbed the transmission of the nutrition. Modified PI (m-PI) was performed by decreasing the length of the jejunal conduit and widening the jejunal pedicle to preserve the blood and nerve supply. The m-PI group showed a lower incidence of symptoms, a greater food intake, and a greater weight recovery than the PI group. The gastric emptying test also revealed an acceptable degree of emptying. We conclude that the m-PI reconstruction is more useful for improving the postoperative quality of life than the previously used method of PI reconstruction.

Anastomosis, Surgical↗

Effects of granulocyte colony-stimulating factor on the hemostatic system in healthy volunteers.

We previously identified a receptor for granulocyte colony-stimulating factor (G-CSFR) on platelet membranes, and reported that G-CSF enhanced ADP-induced platelet aggregation. Here, we investigated the priming effect of G-CSF on the hemostatic system in healthy volunteers given G-CSF. Following the administration of rhG-CSF (10 micrograms/kg for 30 min div) to 10 healthy volunteers, we found a significant elevation in the maximum platelet aggregation rate induced by ADP or collagen, thromboxane B2 level and amount of thrombin-antithrombin III complex. The D-D dimer and plasminogen activator inhibitor-1 showed no significant changes. These observations indicate that G-CSF administration may induce hypercoagulability in susceptible subjects. Therefore, patients or donors at risk of thrombosis or hypercoagulable state should be followed carefully after G-CSF administration.

Adenosine Diphosphate↗