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Biomedical subjects

S Ishiguro

Publications and source records attributed to S Ishiguro.

At least 19 recordsLinked to original sources
PubMed2000

K-ras point mutation is associated with enhancement by deoxycholic acid of colon carcinogenesis induced by azoxymethane, but not with its attenuation by all-trans-retinoic acid.

The effects of deoxycholic acid (DCA) with and without all-trans-retinoic acid (ATRA) on the incidence of colon tumors induced by azoxymethane, the incidence of K-ras point mutation in colon tumors and the labeling index of colon mucosa were investigated in male Wistar rats. Rats received 5 weekly injections of 7.4 mg/kg body weight of azoxymethane. From the start of the experiment, all rats in 3 groups also received chow pellets containing 0.3% DCA with and without s.c. injections of 0.75 or 1.5 mg/kg body weight of ATRA every other day until the end of week 45. Oral administration of DCA significantly increased the incidence of colon tumors in week 45. Concomitant use of DCA and ATRA at either dose significantly attenuated the enhancement by DCA of colon tumorigenesis. Administration of DCA significantly increased the incidence of K-ras point mutation in colon tumors and the labeling index in the colon mucosa. Combined administration of DCA and ATRA significantly reduced the labeling index of colon mucosa, which was increased by DCA, but did not affect the incidence of K-ras point mutation in colon tumors. These findings suggest that DCA enhances development of colon tumors and that this enhancement is attenuated by ATRA. A possible mechanism of this enhancement is induction of K-ras point mutation. However, decreased cell proliferation in the colon mucosa may be closely related to the attenuation of DCA-enhanced colon tumorigenesis, but not suppression of K-ras point mutation.

Administration, Oral↗
PubMed2000

Pharmacologic graft protection without donor pretreatment in liver transplantation from non-heart-beating donors.

BACKGROUND: Non-heart-beating donors (NHBDs) are considered potential sources of transplant organs in an effort to alleviate the problem of donor shortage in clinical liver transplantation. We investigated the possibility of pharmacologic protection of hepatic allograft function from NHBDs without donor pretreatment. METHODS: Orthotopic liver transplantation was performed using pigs. In donors, cardiac arrest was induced by stopping the respirator. Forty-five minutes after cessation of the respirator, the liver was flushed with cold lactated Ringer's solution including heparin and with the University of Wisconsin (UW) solution, and then preserved for 8 hr at 4 degrees C in the UW solution. The pigs were divided into two groups: a control group and a treated group. In the treated group, an endothelin antagonist TAK-044 was added to the UW solutions (10 mg/L), and TAK-044 (10 mg/kg body weight) and a platelet activating factor antagonist E5880 (0.3 mg/kg body weight) were also administered to the recipients. RESULTS: TAK-044 and E5880 treatment significantly increased the 7-day survival rate of the recipients (100% vs. 17%, P<0.05). In the treated group, portal venous pressure immediately after reperfusion of the graft was significantly lower than in the control group, and postoperative increase in serum concentrations of glutamic oxaloacetic transaminase and total bilirubin was attenuated. Moreover, the energy charge and adenosine triphosphate concentration of the liver were rapidly restored after reperfusion. CONCLUSIONS: Pharmacologic modulation with TAK-044 and E5880 avoiding donor pretreatment can improve the viability of hepatic allografts procured from NHBDs.

Animals↗
PubMed2000

Vasopressin receptor subtypes on mesenteric and cremasteric arterioles in rat.

We studied the effects of a selective vasopressin V(1A) receptor antagonist [1-(1-(4-(3-acetylaminopropoxy)benzoyl)-4-piperidyl)-3, 4-dihydro-2(1H)-quinolinone (OPC-21268)] and a selective vasopressin V(2) receptor antagonist [5-dimethylamino-1(4-(2-methylbenzoylamino)benzoyl)-2,3,4, 5-tetrahydro-1H-benzazepine (OPC-31260)] on vasopressin-induced contraction of mesenteric and cremasteric arterioles in urethane-anaesthetized rats. Vasopressin was infused intravenously for 60 min or applied topically to arterioles directly. Vasopressin infusion (50, 100 or 500 ng/kg/min) decreased the diameter of both mesenteric and cremasteric arterioles. Vasopressin (500 ng/kg/min)-induced vasoconstriction was antagonized by OPC-21268 (0. 2, 1.0 and 5.0 mg/kg, i.v.), dose-dependently, but not by OPC-31260. Topically applied vasopressin (4.6x10(-10)-4.6x10(-8) M) dose-dependently constricted both microvessels. Pre-administration of OPC-21268 (5.0 mg/kg, i.v.) completely inhibited topically applied vasopressin-induced vasoconstriction in both microvessels, and OPC-31260 partially inhibited it in cremasteric arterioles. These results suggest that vasopressin induces vasoconstriction in rat mesenteric and cremasteric arterioles mainly by stimulating vasopressin V(1A) receptors, while vasoconstriction in cremasteric arterioles is partly associated with stimulation of vasopressin V(2) receptors.

Animals↗
PubMed2000

K-ras point mutation in the nerve plexuses around the superior mesenteric artery in resectable adenocarcinoma of the pancreatic head: distribution pattern and related factors.

BACKGROUND: Adenocarcinoma of the pancreas is likely to spread into the nerve plexuses around the superior mesenteric artery (SMA) at a microscopic level. Since there has been no detailed report on how minute cancer invasion is distributed among the peri-SMA plexuses or which cases are more vulnerable to such an event, it has long been controversial how to treat this area when resecting the pancreatic head cancer. HYPOTHESIS: The K-ras mutation assay is more sensitive than the conventional histologic diagnosis in detecting minute cancer invasion around the SMA. DESIGN: Prospective consecutive series. SETTING: Cancer center hospital. PATIENTS AND METHODS: The entire circle of the peri-SMA tissues was obtained from 24 patients who had received an extended pancreatectomy for adenocarcinoma of the pancreatic head. They were divided into right and left hemicircular samples (48 samples), and each sample was used for both histologic and genetic diagnoses. Since all patients' primary tumors were positive for point mutation at codon 12 of the K-ras gene, the presence or absence of the mutation was determined for the peri-SMA plexuses using the mutant allele specific amplification method. RESULTS: Compared with results of the histologic examination, the K-ras mutation assay was more sensitive in detecting positive findings in the peri-SMA plexuses (12 samples from 9 patients). According to the distribution of the K-ras mutation into the right- and left-half samples, 24 patients were classified into the following 4 patterns (right/left): negative/negative in 15 patients; positive/negative in 6 patients; positive/positive in 3 patients; and negative/positive in 0 patients. In 3 patients who showed a positive/positive pattern in the genetic diagnosis, their right-half samples included more cancer cells that were detectable by routine microscopy. There was no relation between K-ras mutation and lymphatic invasion, while K-ras mutation was particularly related with the invasion of portal vein (P =.04) and posterior peripancreatic tissues (P =.002). All 3 patients with K-ras mutation in bilateral plexuses were classified by the TNM staging system as T4 using Union Internationale Contre le Cancer classification. CONCLUSIONS: The K-ras mutation (at codon 12) assay indicated a simple and regular pattern of cancer extension into the nerve plexuses around the SMA from adenocarcinoma of the pancreatic head: (1) The left half of the plexus was unlikely to be involved by cancer in cases in which the right half was intact. (2) Cancer extension into the peri-SMA plexuses occurred after the posterior confine of the pancreas had been involved by direct invasion from the primary pancreatic tumor. (3) The left half was not involved in cancerous tumors classified as T1 to T3 but was occasionally involved in those classified as T4 tumors. These data seem to provide a useful indicator of some additional treatments (resection, irradiation, etc) for the peri-SMA region when a locally advanced pancreatic head cancer is treated with a curative intent.

Adenocarcinoma↗
PubMed2000

Expression of hepatocyte growth factor and c-met in ulcerative colitis.

OBJECTIVE AND DESIGN: This study was designed to determine if the hepatocyte growth factor (HGF)-Met system is involved in the repair process of inflamed mucosa of ulcerative colitis (UC) and in the development of UC-associated colorectal cancer. MATERIALS AND METHODS: HGF and c-met gene expressions were quantified in colonic mucosal specimens from healthy control subjects, patients with UC and patients with UC-associated colorectal cancer, using the competitive reverse transcription-polymerase chain reaction. Expression of HGF protein was determined by immunoblot analysis. Expression of c-Met protein was analyzed immunohistochemically. RESULTS: HGF and c-met gene expressions were increased in inflamed mucosa of UC, compared with control subjects. Gene expression of HGF was also increased in the surrounding inflamed mucosa of UC-associated cancers. In cases in which the HGF gene expression was increased, an apparent increase in protein levels of HGF in inflamed mucosa of UC were observed by immunoblot analysis. The c-met gene was overexpressed in UC-associated cancers and a high level of immunoreactivity of the c-Met protein was immunohistochemically detected within the cancer cells. CONCLUSION: We showed that HGF and c-met expression is increased in the inflamed mucosa of UC and that c-met is overexpressed in UC-associated colorectal cancers. These observations suggest HGF-Met system is involved in the repair process of the inflamed mucosa of UC and provide further support for the view that the inappropriate expressions of both HGF and c-met genes predispose to the development of colorectal cancer in patients with UC.

Adult↗
PubMed2000

Diagnosis of the extent of gastric cancers by a new endoscopic ultrasonic tactile sensor.

BACKGROUND: Because gastrointestinal cancers are generally firm, the presence and extent of a tumor can be assessed by touch during surgery. However, an objective scale for evaluating tissue hardness does not exist. We developed a new instrument, the endoscopic ultrasonic tactile sensor, that allows objective evaluation of hardness. In this study the usefulness of this device for diagnosis of the extent of gastric cancers was evaluated. METHODS: Twenty-three patients with depressed or ulcerated early gastric cancers and 7 patients with active or healed gastric ulcers underwent endoscopic examination with the ultrasonic tactile sensor before gastrectomy. RESULTS: Gastric cancers were significantly harder than normal mucosa or gastric ulcers. The histologic type of gastric cancer and the presence of ulceration did not affect tumor hardness and mucosal cancers could not be differentiated from submucosal or deeper cancers. CONCLUSIONS: This new ultrasonic tactile sensor was useful for endoscopic diagnosis of the extent of gastric cancers.

Endosonography↗
PubMed2000

Increased expression of S100A6 at the invading fronts of the primary lesion and liver metastasis in patients with colorectal adenocarcinoma.

Two members of the S100 gene family, S100A6 and S100A4 have been suggested to be associated with cancer invasion and metastasis. To study their involvement in the malignancy of human colorectal adenocarcinoma, we examined the protein expression levels of S100A6 and S100A4 in the primary colorectal adenocarcinoma (T) and paired adjacent normal colorectal mucosa (N) from 12 cases, quantitatively by Western blot analysis. In 11 of 12 and seven of 12 cases, S100A6 and S100A4 expression levels were higher in T than in N, respectively. Average S100A6 level in T was significantly higher than in N (about x 2.3;P = 0.001), whereas average S100A4 level in T was not. When S100A6 expression levels in three sets of matched samples of primary colorectal adenocarcinoma (T) and liver metastasis (M) were examined, S100A6 levels were higher in M than in T in two of three cases. Immunohistochemical analysis using monoclonal anti-S100A6 antibody showed that 23 of 42 (55%) primary colorectal adenocarcinoma and 15 of 16 (94%) liver metastasis specimens were positively stained. S100A6 immunostaining of primary colorectal adenocarcinomas was significantly more intense in the invading fronts with structural atypia than in central portions with glandular structure (P< 0.0001), whereas Ki-67 staining (a growth marker) was similar in these two portions. Interestingly, S100A6 and Ki-67 immunostaining patterns in liver metastases were also the same as in primary lesions. These results suggest that S100A6 is involved in the invasive process of human colorectal adenocarcinomas and that S100A6 expression levels decrease when carcinoma cells form glandular structure again at the central portions of metastatic nodules.

Adenocarcinoma↗
PubMed2000

Endoscopic piecemeal resection with submucosal saline injection of large sessile colorectal polyps.

BACKGROUND: Because endoscopic en bloc resection of large, sessile colorectal polyps is technically difficult, they are usually resected piecemeal. However, piecemeal resection makes it difficult to evaluate the completeness of the resection histopathologically. In this study the efficacy of endoscopic piecemeal resection of large, sessile colorectal polyps was investigated after follow-up greater than 1 year. METHODS: We removed 56 sessile colorectal polyps 2 cm or greater in diameter in 56 patients by using an endoscopic submucosal saline injection technique. Endoscopic examinations were repeated at 3, 6, and 12 months and longer after initial endoscopic resection. If no residual tumor was found endoscopically and histologically, the patient was considered to be "cured." RESULTS: Of the 56 polyps, 14 (25%) were resected en bloc, and 42 (75%) were resected piecemeal. Of the 42 patients treated with piecemeal resection, 23 (55%) required additional endoscopic or surgical interventions. In patients followed 1 year or longer after initial treatment, the cure rate by en bloc resection was 100% (14 of 14) and that by piecemeal resection was 83% (35 of 42). Arterial bleeding occurred in 4 patients (7%) during or after endoscopic resection. In 3 of them, bleeding was stopped by endoscopic clipping, but 1 patient required emergent laparotomy. CONCLUSIONS: Endoscopic piecemeal resection after submucosal saline injection with an intensive follow-up program is a safe and effective treatment for large, sessile colorectal polyps.

Adult↗
PubMed2000

Effectiveness of the near-infrared electronic endoscope for diagnosis of the depth of involvement of gastric cancers.

BACKGROUND: Near-infrared light penetrates deeply into tissue but is not visible with a conventional endoscope. We developed a new infrared electronic endoscope system and evaluated its usefulness for assessing the depth of involvement of gastric cancers. METHODS: A total of 61 patients with depressed or ulcerated gastric cancers underwent infrared endoscopy after intravenous injection of indocyanine green. RESULTS: Intramucosal cancers were observed as tumors with or without a homogeneous tumor stain, whereas submucosal or deeper cancers were observed as tumors with an inhomogeneous stain or with pooling of the dye. Histologic examination showed staining properties of gastric cancers were significantly correlated with the characteristics of the vascular bed. The accuracy for depth of cancer invasion was 89% for mucosal cancers and 89% for submucosal or deeper cancers. CONCLUSION: Our new infrared electronic endoscope system was useful for distinguishing mucosal cancers from submucosal or deeper cancers either with or without ulcerative changes.

Adult↗
PubMed2000

Percutaneous balloon fenestration in a case of traumatic abdominal aortic dissection with lower extremity ischemia.

A 38-year-old man was involved in a traffic accident and experienced a heavy blow to the abdomen. He had traumatic abdominal aortic dissection with right lower extremity ischemia. He underwent percutaneous balloon fenestration, which is safe and minimally invasive, for relief of right lower extremity ischemia. He has been working for 2 years without any signs of vascular compromise. Percutaneous balloon fenestration is one of the few treatments for traumatic abdominal aortic dissection.

Abdominal Injuries↗
PubMed2000

RPT2. A signal transducer of the phototropic response in Arabidopsis.

The blue light receptor NPH1 (for nonphototropic hypocotyl) has been considered to be the only UV-A/blue light receptor that induces a phototropic response by the hypocotyl and root of Arabidopsis. By analysis of root phototropism (rpt) mutants, we show, however, the involvement of another blue light receptor as well as the existence of two separate signaling pathways working downstream of these receptors in the phototropic response. A newly isolated gene, RPT2, controls one of these pathways. The RPT2 gene is light inducible; encodes a novel protein with putative phosphorylation sites, a nuclear localization signal, a BTB/POZ domain, and a coiled-coil domain; and belongs to a large gene family that includes the recently isolated NPH3 gene. From genetic, physiological, and biochemical evidence, we propose a genetic model of the signaling pathways that induce the phototropic response in Arabidopsis.

Amino Acid Sequence↗
PubMed2000

Bcl-2 expression in cholangiocellular carcinoma is inversely correlated with biologically aggressive phenotypes.

bcl-2 is known to play a crucial role in modulating carcinoma progression as well as in inhibiting apoptosis. However, its expression and clinical significance for cholangiocellular carcinoma (CCC) remains unclear. In the present study, we immunohistochemically investigated bcl-2 expression in 41 CCC. Thirteen cases (31.7%) were classified as bcl-2 positive, because more than 10% of the carcinoma cells expressed bcl-2. The expression of bcl-2 was inversely related to lymph node metastasis, vascular invasion, perineural invasion, the Ki-67 labeling index, aberrant p53 expression and the incidence of apoptotic cells. Furthermore, well or moderately differentiated carcinoma more frequently expressed bcl-2. These results suggest that downregulation of bcl-2 expression is strongly linked to highly biologically aggressive phenotypes of CCC.

Bile Duct Neoplasms↗
PubMed2000

Captopril increases the affinity of bradykinin receptor binding sites in bovine coronary arterial endothelial cells.

In a radioligand binding study using bovine coronary artery endothelial cell membranes, captopril changed a single bradykinin (BK) binding site (Kd = 1.77 nM, Bmax = 60.2 fmol/mg protein) to high- (Kd = 0.68 pM, Bmax = 17.7 fmol/mg protein) and low- (Kd = 1.00 nM, Bmax = 72.5 fmol/mg protein) affinity binding sites. This effect was reversed by GppNHp. Captopril also enhanced BK-induced endothelium-dependent relaxation in saponin-treated coronary rings, and GppNHp partially suppressed this enhancement. These results suggest that captopril may affect BK receptors that couple to G-proteins.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Expression of Fas and Fas ligand reflects the biological characteristics but not the status of apoptosis of intrahepatic cholangiocellular carcinoma.

Although intrahepatic cholangiocellular carcinoma (CCC) is the second most common of hepatic malignancies, there have been few studies evaluating its biological characteristics. We therefore decided to investigate the status of apoptosis and of Fas and Fas ligand expression in this carcinoma. We performed immunohistochemistry for Fas and Fas ligand in 40 CCC cases and evaluated the apoptotic index (AI) by counting the number of morphologically apoptotic cells per 1000 cells. AI was higher in cases with poor differentiation, lymph node metastasis and high Ki-67 labeling index (LI). Fas expression in CCC cells decreased in cases with poor differentiation and high Ki-67 LI. Fas ligand expression in the stromal infiltrating mononuclear cells did not correlate with any clinicopathological features of CCC, but was directly related to Fas expression in CCC cells. Fas ligand was also expressed in CCC cells in 27.5% of the cases and more frequently observed in cases with moderate or poor differentiation and high Ki-67 LI. None of these three parameters correlated with AI. These findings indicate that, in CCC, i) cases showing rapid growth characteristics are less likely to die of Fas-mediated apoptosis and more likely to display counterattack to lymphocytes via Fas ligand expressed by carcinoma cells; ii) stromal mononuclear cells express Fas ligand in response to Fas expression in carcinoma cells; iii) Fas and Fas ligand expression are not related to the status of apoptosis.

Apoptosis↗
PubMed2000

Increased expression of S100A6 (Calcyclin), a calcium-binding protein of the S100 family, in human colorectal adenocarcinomas.

The expression of S100A6 (also known as Calcyclin/2A9/ 5B10/PRA) in surgically resected human colorectal adenocarcinomas was examined to investigate whether S100A6 plays a role in the malignancy of human tumor cells. Western blot analysis using the lysates from colorectal adenocarcinomas and adjacent normal mucosa from 10 patients revealed that the average S100A6 level of adenocarcinomas was significantly higher (about 2.4-fold) than that of normal mucosa. Immunohistochemical analysis using formalin-fixed paraffin-embedded surgical specimens and monoclonal anti-S100A6 antibody (mAbA6) demonstrated that 2(5%) of 42 normal mucosa and 6 (46%) of 13 adenoma specimens were mAbA6-positive and showed granular staining localized at the supranuclear regions of epithelial cells, whereas 23 (55%) of 42 adenocarcinomas and 13 (100%) of 13 carcinoma cells that metastasized to the liver were mAbA6-positive and showed diffuse cytoplasmic staining. A significant correlation between S100A6 expression and Dukes' tumor stage or lymphatic permeation but not with other clinicopathological factors was shown. S100A6 was stained more intensely in peripheral portions than in central portions of adenocarcinomas, whereas Ki-67 (a growth marker) was stained equally in these two portions. These results suggest that S100A6 may be involved in the progression and invasive process of human colorectal adenocarcinomas.

Adenocarcinoma↗