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Biomedical subjects

Y Nagashima

Publications and source records attributed to Y Nagashima.

264 records · Page 15Linked to original sources

Occurrence of tetrodotoxin-related substances in the nontoxic puffer Takifugu xanthopterus.

Instead of tetrodotoxin, significant amounts of tetrodotoxin-related substances with no mouse lethality were detected in the nontoxic liver specimen of puffer fish, Takifugu xanthopterus. The tetrodotoxin-related substances, which were demonstrated to be tetrodotoxin derivatives by gas chromatography-mass spectrometry analysis, were similar to tetrodonic acid in HPLC but distinguishable from it in electrophoresis. Our results suggest that nontoxic puffer fish contains nontoxic tetrodotoxin derivatives as precursors or metabolites of tetrodotoxin.

Animals↗

Specific expression of PP5/TFPI2 mRNA by syncytiotrophoblasts in human placenta as revealed by in situ hybridization.

Placental protein 5 (PP5) is a placenta-derived glycoprotein with serine proteinase-inhibiting activity. To date its physiological functions have not been well elucidated. Recently, cDNA sequence analysis revealed that PP5 belongs to the Kunitz-type proteinase inhibitor family and it is identical to tissue factor pathway inhibitor-2 (TFPI-2), homologous to TFPI. Northern blot analysis demonstrated that placental tissue is extremely rich in the transcripts. This study localized PP5/TFPI-2 mRNA in placental tissues at three different gestational periods using in situ hybridization. PP5/TFPI-2 mRNA was specifically detected in syncytiotrophoblast at any gestational period examined, suggesting that syncytiotrophoblast is the principal production site of PP5/TFPI-2 in developing placental tissues. This mRNA expression pattern of PP5/TFPI-2 is quite different from that of TFPI, which is mainly found in vascular endothelial cells. The results indicated possible roles of PP5/TFPI-2 in the trophoblast differentiation and in the maintenance of intervillous blood flow. Also, Northern analysis demonstrated no or little expression of PP5/TFPI-2 in four choriocarcinoma cell lines, in contrast to its abundant expression in syncytiotrophoblast.

Adult↗

Detachable coils for occlusion of patent ductus arteriosus in 2 dogs.

OBJECTIVE: To describe the use of a detachable coil for transcatheter closure (TCC) of patent ductus arteriosus (PDA) in 2 dogs. STUDY DESIGN: Clinical study. ANIMALS: Two female Pembroke Welsh Corgi dogs with PDA. METHODS: Using fluoroscopic guidance, an 8-mm-diameter coil stent with 5 loops (detachable coils for PDA closure) was inserted via catheterization of the femoral artery. The catheter was passed through the PDA into the pulmonary artery. The coil was withdrawn so that 1.5 loops remained on the pulmonary side of the orifice of the ductus. The rest of the loops were pushed out from the catheter into the ductus. After confirming the correct placement of the coil and the effectiveness of the occlusion, the delivery wire was detached from the coil. RESULTS: Insertion of the coil was easily performed, even without previous experience. Immediate and marked decrease of the cardiac murmur was auscultated. Only slight residual flow was detected by angiography conducted 3 months' postoperatively. The dogs experienced quick and uneventful recovery after coil placement and required minimal postoperative care. Follow-up evaluation of the dogs showed no functional clinical signs of PDA, and no cardiac abnormalities were detected on electrocardiographic, phonocardiographic, and echocardiographic examination. In dog 1, the residual flow had disappeared on the color-flow Doppler echocardiographic examination at 18 months' postoperatively. CONCLUSION: TCC using a detachable coil was easy, safe, and effective in 2 dogs with PDA. The minimal residual shunting observed only by echocardiography seemed hemodynamically insignificant. CLINICAL RELEVANCE: This method can be used as an alternative to traditional surgical methods.

Animals↗

Subcellular localization of PP5/TFPI-2 in human placenta: a possible role of PP5/TFPI-2 as an anti-coagulant on the surface of syncytiotrophoblasts.

Placental protein 5 (PP5)/tissue factor pathway inhibitor-2 (TFPI-2), a serine proteinase inhibitor, is homologous to tissue factor pathway inhibitor (TFPI) and commonly found in peripheral blood of pregnant woman. Although TFPI is well known to be synthesized primarily in endothelium and to play an important role in regulation of the extrinsic pathway of blood coagulation, the function of PP5/TFPI-2 remains unclear. Our previous report demonstrated that PP5/TFPI-2 expression is ubiquitous and extremely high in growing placental tissue. Using newly generated polyclonal anti-PP5/TFPI-2 antibody, and by immunohistochemistry and immunoelectromicroscopy, we examined precise localization of PP5/TFPI-2 in placenta especially in syncytiotrophoblasts, which had been shown to produce PP5/TFPI-2 mRNA by our previous study using in situ hybridization. Immunoelectromicroscopy revealed PP5/TFPI-2 localizing on the surface of the microvilli and the membrane of endoplasmic reticulum of syncytiotrophoblasts. To confirm the cell surface association of PP5/TFPI-2, placental villi were incubated with heparin and resultant soluble fraction was analysed by Western blotting. Heparin liberating PP5/TFPI-2 from villi suggested that PP5/TFPI-2 might be retained on the microvilli surface through the binding to membrane-anchored proteoglycans such as glypican and/or syndecan family members. We also examined the relationship between the presence of cell layer of syncytiotrophoblasts and the coagulation using clinical specimens, and revealed that the fibrin depositions were specifically observed on the regions lacking syncytiotrophoblasts cell layer in placental villi. Therefore, it is likely that during pregnancy PP5/TFPI-2 may be retained on the surface of placental villi via proteoglycans, and may play an important role to maintain intervillous blood flow and the patency of microvasculature in feto-maternal blood system mediated by the inhibition of serine proteinases involved in the blood coagulation.

Adult↗

Diagnostic clinical application of two-color fluorescence in situ hybridization that detects chromosome 1 and 17 alterations to direct touch smear and liquid-based thin-layer cytologic preparations of endometrial cancers.

We performed two-color fluorescence in situ hybridization (FISH) on direct touch smears and liquid-based thin-layer (ThinPrep) cytological preparations of endometrial tumors to detect alterations of chromosome 1 and 17 that present with high incidence in endometrial cancers. The DNA probes used for two-color FISH analysis were a combination of the probes designed for 17cen (cCI 17-321) and 17p13.3 (D17S34), and a combination of the probes designed for 1q12 (D1Z1) and 1p36 (cCI1-5335). Numerical or structural alterations of chromosome 1 and/or 17 were detected in 95% (19 of 20 cases) of the direct touch smears obtained from endometrial cancer, while these alterations were also detected in 93% (12 of 13 cases) of samples obtained from grade 1 endometrioid adenocarcinoma cases, including three cases that could not be diagnosed as positive by conventional Papanicolaou cytopathologic staining. Using ThinPrep cytopathologic preparations, numerical or structural abnormalities were found in 26 (90%) and five (100%) cases, respectively, of samples obtained transcervically from 29 endometrial cancer and five atypical endometrial hyperplasia cases. Therefore, two-color FISH may be a useful diagnostic method for endometrial adenocarcinoma and premalignant lesions that demonstrate only slight cellular atypia in conventional cytopathologic preparations.

Adenocarcinoma↗

Stimulation of motility of human renal cell carcinoma by SPARC/Osteonectin/BM-40 associated with type IV collagen.

SPARC is known to be important in development and tissue remodelling. Here, we examined the effects of SPARC (secreted protein, acidic and rich in cysteine; osteonectin) derived from a rat osteosarcoma cell line on migration of renal cell carcinoma (RCC) by a Boyden chamber assay. YCR RCC cells migrated through type IV collagen-coated filters without stimuli (basal level). SPARC in the lower compartment stimulated chemotactic activity to 120% of the basal level, whereas premixing of YCR with purified SPARC before inoculation reduced their migration to 72% of the basal level. Furthermore, SPARC mixed with type IV collagen more efficiently stimulated their migration in a concentration-dependent manner (up to 170% of the basal level). This suggests that SPARC bound to type IV collagen plays a role in tumor invasion.

Animals↗

Beneficial effect of hyperbaric oxygen therapy on liver regeneration after 90% hepatectomy in rats.

BACKGROUND/AIMS: Hyperbaric oxygen therapy (HBOT) has been reported to augment oxygen delivery to ischemic tissues and improve the liver dysfunction in clinical cases. HBOT was performed after 90% hepatectomy in rats to determine its effect on the regeneration of remnant liver. METHODS: After 90% hepatectomy was performed in 8-week-old male Wistar rats, the animals were subdivided into an HBOT (2 atm abs., 80% O2, 1 h/day, 3 days) group and a non-HBOT group. Members of both groups were sacrificed, usually every 4 h until a maximum of 50 h after hepatectomy, and the liver regeneration rate, the proportion of PCNA-positive cells and the ATP volume in the remnant tissues were examined. RESULTS: In the HBOT group, the liver regeneration rate at 36 h and 50 h after operation and the proportion of PCNA positive cells at 8 h was significantly increased compared with the non-HBOT group. The ATP volume in the remnant livers in the HBOT group was also significantly increased at 12 h. CONCLUSION: HBOT augmented liver regeneration after hepatectomy by stabilization of energy metabolism induced by oxygen delivery in rats.

Animals↗

Role of nitric oxide in human gastric cancer cells treated with 5-fluorouracil.

We examined whether 5-fluorouracil (5-FU) induces nitric oxide (NO) production and evaluated the role of NO in antitumor activity in human gastric cancer cells. MKN-1 gastric cancer cells were treated with the IC50 of 5-FU in the presence of interferon-gamma (IFN-gamma). In addition, s-methylisothiourea (an antagonist of inducible nitric oxide synthase) or anti-TNF-alpha antibody was added to the culture medium. Production of NO was measured by nitrite assay, TNF-alpha was measured by enzyme-linked immunoabsorbent assay, antitumor activity was evaluated by 3-[4,5-dimethylethiazol-2-yl]-2,5-dipheniltetrasolium bromide (MTT) assay. After 5-FU treatment in the presence of IFN-gamma, NO and TNF-alpha were produced and anti-tumor activity was enhanced. In contrast, s-methylisothiourea abolished the antitumor activity of 5-FU treatment. Anti-TNF-alpha antibody inhibited NO production and decreased the antitumor activity. 5-FU induces NO production by gastric cancer cells, and NO participates in antitumor activity in gastric cancer cells. These effects may be mediated by TNF-alpha production.

Antimetabolites, Antineoplastic↗

Changes in clinicopathological findings after portal vein embolization.

BACKGROUND/AIMS: Portal vein embolization is becoming more common as a method of preventing hepatic failure after an extended hepatectomy but its mechanism is not well understood. This clinicopathological study focused on its mechanism. METHODOLOGY: Thirty patients who underwent extended hepatectomy after portal vein embolization were evaluated. Liver volume was measured before and after portal vein embolization, and histological studies were performed to examine morphological changes, morphometric parameters and apoptosis of hepatocytes. RESULTS: The mean volume of the non-embolized lobe grew significantly from 392 to 462 mL after portal vein embolization (P < 0.0001). The hypertrophy ratio of the non-embolized lobe (100 x volume change during portal vein embolization/volume before portal vein embolization, %) was correlated closely with the volume of the non-embolized lobe before portal vein embolization (r = -0.65, P < 0.0001). Histological study showed the embolized lobe hepatocytes to be atrophic, partly necrotic and apoptotic. In the non-embolized lobe, the mean hepatocyte volume was 8686 micron 3 (control: 6544 micron 3) and the mean hepatocyte count was 109 x 10(6)/mL (control: 122 x 10(6)/mL). CONCLUSIONS: The enlargement of the non-embolized lobe was caused by hypertrophy rather than hyperplasia suggesting hyperfunction. The resection of the atrophic embolized lobe, leaving the hypertrophic non-embolized lobe was thought to be less surgically stressful than hepatectomy without portal vein embolization.

Aged↗

Correlation of immunohistochemical p53 labeling index with inhibition rate in chemosensitivity test in gastric and colon cancer.

To determine whether the expression of p53, p21, bcl-2 or Ki-67 in cancer cells is predictive of chemosensitivity, immunohistochemical examination of these factors and chemosensitivity assays were performed on colon and gastric cancer specimens. Chemosensitivity tests were performed using CDDP, 5-FU, MMC, or ADR and inhibition rate (IR) was calculated by MTT assay. Before exposure to anticancer drugs, the samples were investigated immunohistochemically for expression of the above factors and after anticancer drug exposure by TUNNEL staining, for the presence of apoptotic cells. With 5-FU and MMC, the apoptotic index was well correlated with IR, so their effects were related to apoptosis. Moreover, with these two agents, the p53 labeling index (LI) was inversely correlated with IR and p21-LI showed a good correlation with IR. We therefore concluded that immunohistochemical studies for p53 and p21 were useful for predicting the chemosensitivities of colon and gastric cancer to MMC and 5-FU.

Antineoplastic Agents↗

Pancreatic trauma in patients with pancreatobiliary anomaly.

One patient with a choledochal cyst and anomalous pancreaticobiliary junction had pancreatic transection causing bile peritonitis. Intraoperative cholangiopancreatography revealed this anomaly. In another patient with pancreas divisum, cannulation of the minor papilla (ERCP) demonstrated focal stenosis of the dorsal pancreatic duct, corresponding to the site of the minor laceration. The possibility of a coexisting pancreatobiliary anomaly should be considered in the diagnosis of pancreatic trauma, particularly in terms of the interpretation of pancreatograms.

Adult↗

Continuous hyperthermic peritoneal perfusion for peritoneal dissemination of gastric cancer.

BACKGROUND/AIMS: We investigated the histological and clinical effectiveness of continuous hyperthermic peritoneal perfusion (CHPP) for treating peritoneal dissemination (therapeutic CHPP) and for the prevention of peritoneal recurrence (prophylactic CHPP). METHODOLOGY: In 5 patients with gastric cancer and peritoneal dissemination, the apoptosis index of the cancer cells on in situ end-labeling for detection of apoptotic cells was 3.0+/-1.2% before CHPP, and had increased to 52.9+/-8.3% after CHPP. The survival curve of the therapeutic CHPP group was significantly better than that of the control group. The therapeutic CHPP group was classified as miliary type or nodular type. The survival curve in the miliary type was significantly better than that in the nodular type. RESULTS: In prophylactic CHPP, there was no improvement in prognosis, but a prophylactic effect against peritoneal recurrence was demonstrated in the patients who were n4 negative when the mean intraperitoneal temperature during CHPP (MIT) was maintained above 42 degrees C. CONCLUSIONS: These results indicated that an improved prognosis can be expected after therapeutic CHPP in patients with peritoneal spread. The beneficial effects are especially marked in patients with the miliary type. Moreover, prophylactic CHPP exerts a prophylactic effect against peritoneal recurrence in patients with n4 negative, providing that the MIT can be maintained above 42 degrees C.

Apoptosis↗