Search PubMed⌕ Search

Biomedical subjects

T Itoh

Publications and source records attributed to T Itoh.

At least 55 records · Page 3Linked to original sources

Impact of caveolin-1 expression on prognosis of pancreatic ductal adenocarcinoma.

Caveolin-1 is a major component of caveolae and plays a regulatory role in several signalling pathways. Caveolin-1 was recently identified as a metastasis-related gene in prostate cancer. The clinical effects of caveolin-1 expression in pancreatic carcinoma, however, remain unknown. In this study, we have investigated the relationship between caveolin-1 expression and the clinicopathologic variables and clinical outcome in 79 patients with pancreatic adenocarcinoma undergoing surgical resection. Caveolin-1 expression was determined by immunohistochemistry, using a polyclonal anti-caveolin-1 antibody. Patients were divided into two groups based on the extent of caveolin-1 expression: a negative expression group (immunoreactivity in less than 50% of cells) and a positive expression group. Positive caveolin-1 immunostaining was detected in 32 cases (40.5% of total), while non-neoplastic ductal epithelium showed little or no staining. Positive caveolin-1 expression was correlated with tumour diameter (P=0.0079), histopathologic grade (P=0.0272) and poor prognosis (P=0.0008). Upon multivariate analysis with Cox's proportional hazards model, positive caveolin-1 expression was shown to be an independent negative predictor for survival (P=0.0358). These results suggest that caveolin-1 overexpression is associated with tumour progression, thereby indicating a poor prognosis for certain patients undergoing surgical resection for pancreatic carcinoma.

Adenocarcinoma↗

N-acetylgalactosaminyl transferase-3 is a potential new marker for non-small cell lung cancers.

N-acetylgalactosaminyl transferase-3 (GalNAc-T3) is an enzyme involved in the initial glycosylation of mucin-type O-linked proteins. In the present study, we used immunohistochemistry to examine GalNAc-T3 expression in 215 surgically resected non-small cell lung cancers. We analysed the biological and clinical importance of GalNAc-T3 expression, especially with regard to its potential as a prognostic factor. We found that normal bronchial epithelial cells, bronchial gland cells, and alveolar pneumocytes showed cytoplasmic immunostaining for GalNAc-T3. Low expression of GalNAc-T3, observed in 93 of 215 tumours (43.4%), was found more frequently in tumours from smokers than those from nonsmokers (P=0.001), in squamous cell carcinomas than nonsquamous cell carcinomas (P<0.0001), and in moderately and poorly differentiated tumours than well differentiated tumours (P=0.0002). Multivariate logistic regression analysis showed that an association of low GalNAc-T3 expression with squamous cell carcinomas was the only one significant relationship of GalNAc-T3 expression with various factors (P<0.0001). Moreover, tumours losing GalNAc-T3 expression had a significantly higher Ki-67 labelling index than tumours retaining GalNAc-T3 expression (P=0.0003). Patients with low GalNAc-T3 expression survived a significantly shorter time than patients with high GalNAc-T3 expression in 103 pStage I non-small cell lung cancers (5-year survival rates, 58% and 78%, respectively; P=0.02 by log-rank test) as well as in 61 pStage I nonsquamous cell carcinomas (5-year survival rates, 63% and 85%, respectively; P=0.03). Low GalNAc-T3 expression was an unfavourable prognostic factor in pStage I non-small cell lung cancers (hazards ratio, 2.04; P=0.03), and in pStage I nonsquamous cell carcinomas (hazards ratio, 2.70; P=0.03). These results suggest that GalNAc-T3 is a new marker of non-small cell lung cancers with specificity for histology and prognosis.

Aged↗

Cimetidine modulates the antigen presenting capacity of dendritic cells from colorectal cancer patients.

Cimetidine, a H(2) receptor antagonist, has been reported to improve survival in gastrointestinal cancer patients. These effects have largely been attributed to the enhancing effects of cimetidine on the host's antitumour cell-mediated immune response, such as inhibition of suppressor T lymphocyte activity, stimulation of natural killer cell activity and increase of interleukin-2 production from helper T lymphocytes. We conducted an in vitro study on the effects of cimetidine on differentiation and antigen presenting capacity of monocyte-derived dendritic cells from advanced colorectal cancer patients and normal controls. As a result, an investigation of expression of surface molecules associated with dendritic cells by flow cytometric analyses showed that cimetidine had no enhancing effect on differentiation of dendritic cells from cancer patients and normal controls. An investigation of [(3)H]thymidine incorporation by allogeneic mixed lymphocyte reactions revealed that cimetidine increased the antigen presenting capacity of dendritic cells from both materials. Moreover, a higher antigen presenting capacity was observed in advanced cancer patients compared to normal controls. These effects might be mediated via specific action of cimetidine and not via H(2) receptors because famotidine did not show similar effects. Our results suggest that cimetidine may enhance the host's antitumour cell-mediated immunity by improving the suppressed dendritic cells function of advanced cancer patients.

Adult↗

Isolation and characterization of a homologue of mammalian prolactin-releasing peptide from the tilapia brain and its effect on prolactin release from the tilapia pituitary.

In the tilapia (Oreochromis mossambicus), as in many teleosts, prolactin (PRL) plays a major role in osmoregulation in freshwater. Recently, PRL-releasing peptides (PrRPs) have been characterized in mammals. Independently, a novel C-terminal RF (arginine-phenylalanine) amide peptide (Carrasius RF amide; C-RFa), which is structurally related to mammalian PrRPs, has been isolated from the brain of the Japanese crucian carp. The putative PrRP was purified from an acid extract of tilapia brain by affinity chromatography with antibody against synthetic C-RFa and HPLC on a reverse-phase ODS-120 column. The tilapia PrRP cDNA was subsequently cloned by polymerase chain reaction. The cDNA consists of 619 bp encoding a preprohormone of 117 amino acids. Sequence comparison of the isolated peptide and the preprohormone revealed that tilapia PrRP contains 20 amino acids and is identical to C-RFa. Incubation of the tilapia pituitary with synthetic C-RFa (100 nM) significantly stimulated the release of two forms of tilapia PRL (PRL188 and PRL177). However, the effect of C-RFa was less pronounced than the marked increase in PRL release in response to hyposmotic medium. The ability of C-RFa to stimulate PRL release appears to be specific, since C-RFa failed to stimulate growth hormone release from the pituitary in organ culture. In contrast, rat and human PrRPs had no effect on PRL release. C-RFa was equipotent with chicken GnRH in stimulating PRL release in the pituitary preincubated with estradiol 17beta. Circulating levels of PRL were significantly increased 1 h after intraperitoneal injection of 0.1 microg/g of C-RFa in female tilapia in freshwater but not in males. These results suggest that C-RFa is physiologically involved in the control of PRL secretion in tilapia.

Amino Acid Sequence↗

Acute and chronic alterations in calcium homeostasis in 3-nitropropionic acid-treated human NT2-N neurons.

3-Nitropropionic acid (3-NP), an irreversible inhibitor of succinate dehydrogenase, induced ATP depletion and both necrosis and apoptosis in human NT2-N neurons. Necrosis occurred predominantly within the first two days, and increased in a dose-dependent fashion with the concentration of 3-NP, whereas apoptosis was observed after 24 h or later at a similar rate in 0.1 mM and 5 mM 3-NP. We focused our efforts on intracellular calcium homeostasis during the first 48 h in 1 mM 3-NP, a period during which 10% of the neurons died by necrosis and 3% by apoptosis. All NT2-N neurons showed a stereotyped [Ca(2+)](i) rise, from 48+/-2 to 140+/-12 nM (mean +/-S.E.M.), during the first 2 h in 3-NP. Despite severe ATP depletion, however, [Ca(2+)](i) remained above 100 nM in only 17% and 25% of the NT2-N neurons after 24 and 48 h in 3-NP, respectively, indicating that most neurons were able to recover from acute [Ca(2+)](i) rise, and suggesting that chronic [Ca(2+)](i) dysregulation is a better indicator of subsequent necrosis. Blockade of N-methyl-D-aspartate-glutamate receptor by MK-801 substantially ameliorated 3-NP-induced ATP depletion, subsequent chronic [Ca(2+)](i) elevation, and survival. Moreover, xestospongin C, an inhibitor of endoplasmic reticulum Ca(2+) release, enhanced the capacity of NT2-N neurons to maintain [Ca(2+)](i) homeostasis and resist necrosis while subjected to sustained energy deprivation. As far as we know, this report is the first to employ human neurons to study the pathophysiology of 3-NP neurotoxicity.

Adenosine Triphosphate↗

Successful allogeneic blood stem cell transplantation for aplastic anemia in a patient with renal insufficiency requiring dialysis.

A 27-year-old man with aplastic anemia and renal insufficiency requiring dialysis underwent allogeneic PBSCT. The preparative regimen consisted of melphalan, ATG and TLI. GVHD prophylaxis consisted of cyclosporine and prednisolone. He was dialyzed prior to administration of melphalan and at 24 and 72 h after it. Otherwise, the dialysis schedule was unchanged, at three times a week. Engraftment was rapid. Regimen-related toxicity was minimal. Pharmacokinetic parameters of melphalan were not significantly altered with its plasma half-life 1.5 h. Patients with renal failure can receive allogeneic HSCT, and a combination of melphalan, ATG and TLI may serve as an alternative to CY and ATG.

Adult↗

The possible involvement of micro-organisms other than Helicobacter pylori in the development of rectal MALT lymphoma in H. pylori-negative patients.

It remains unclear whether lymphoma of the mucosa-associated lymphoid tissue (MALT) in the extragastric organs is related to Helicobacter pylori infection or not. This report describes three patients with rectal MALT lymphoma negative for H. pylori infection, all of whom showed disease regression after being treated with antibiotics. One patient had MALT lymphoma in both the descending colon and the rectum; the other two patients had rectal disease only. None of the patients had chronic gastritis which was detectable either endoscopically or histologically and H. pylori infection was completely ruled out by various methods, including a urease breath test. These patients received antibiotic therapy. In all the patients, regression of MALT lymphoma was observed endoscopically and histologically, and polymerase chain reaction revealed that a previously observed rearranged band of immunoglobulin heavy chain had also disappeared after antibiotic treatment. These cases therefore suggest involvement of micro-organisms other than H. pylori in the development of rectal MALT lymphoma.

Adult↗

Epidural cooling for regional spinal cord hypothermia during most or all of descending thoracic or thoracoabdominal aneurysm repair.

PURPOSE: Hypothermia has some protective effect against ischemia of the spinal cord in thoracoabdominal aneurysm repair. Its method is divided into systemic or regional cooling. Several experimental studies of the regional cooling of the spinal cord have been performed, however, clinical reports are few. The purpose of this study is to evaluate the effect and safety of perfusion cooling of the epidural space during thoracic or thoracoabdominal aortic replacement. METHODS: Between January 1998 to June 2001 37 patients (True aneurysm: 18 patients, type B aortic dissection: 19 patients) underwent thoracic or thoracoabdominal aortic replacement with an aid of epidural perfusion cooling. The age ranged from 23 to 78 years old with a mean age of 61 years old. Separate perfusion of upper and lower body was used in all cases. Temperature was lowered to around a 31 degrees C or 32 degrees C. In cases where proximal cross-clamping was danger, deep hypothermic circulatory arrest was used. RESULTS: Ten patients underwent most or all of descending thoracic aneurysm repair with no spinal cord injury and hospital death. Number of patients of the Crawford type I, type II, and type III were 14, 8 and 5 patients, respectively. One Crawford type II patients was complicated with postoperative spinal cord injury (2.7%). There was one hospital death (2.7%) in Crawford type III. The mean epidural cooling time was 150 minutes, and mean infusion volume of cold saline was 981 cc. The mean lowest cerebrospinal fluid (CSF) temperature was 24.3 degrees C, and mean temperature differences between nasopharynx and CSF was 6.3 degrees C. CONCLUSION: Perfusion cooling of the epidural space during most or all of the descending thoracic or thoracoabdominal aneurysm repair was effective in reducing postoperative spinal cord injury and a safe method in clinical situations.

Adult↗

Regression of fundic gland polyps following acquisition of Helicobacter pylori.

The prevalence of Helicobacter pylori infection is very low in patients with fundic gland polyps (FGPs) of the stomach. We report here two cases with multiple FGPs that regressed following new H pylori acquisition. Patient Nos I and II had multiple FGPs in normal fundic mucosa without inflammatory changes or atrophy. Both were not infected with H pylori. Following acquisition of H pylori infection however, all FGPs in both patients completely disappeared except for one FGP in patient No I. Although the size of the remaining polyp in patient No I was greatly reduced after H pylori acquisition, it became enlarged again after eradication. Interestingly, in the remaining polyp, we found an activating beta-catenin gene mutation whereas no such mutations were detected in FGPs of patient No II. Thus H pylori infection may have an inhibitory effect on the development of FGPs.

Adult↗

Correlation between age and vital organ function following deep hypothermic circulatory arrest.

BACKGROUND: We investigated the correlation bet-ween perioperative variables such as patients' age and vital organ function after operation on thoracic aorta using deep hypothermic circulatory arrest (DHCA). METHODS: Ninety-five patients who underwent replacement of thoracic aorta under DHCA for acute or chronic aortic dissection and aortic aneurysm, and survived more than 10 days were divided into group I (age less than 60, n=17), group II (between 60 and 69, n=39), and group III (over 70, n=39). Concomitant procedures such as aortic root replacement and coronary artery bypass grafting were performed in 9, 4, and 1 patients in group I, II, and III, respectively. Postoperative pulmonary, renal, and hepatic function within 10 days were compared. Correlation between other perioperative variables and organ function was also investigated among all 95 patients. RESULTS: Postoperative pulmonary, renal, and hepatic function in group III was not significantly inferior to those in groups I and II. The operation time, and amount of red blood cells and fresh frozen plasma used during operation, were significantly greater in group I, which showed an intimate correlation to significant elevation of hepatic enzymes. CONCLUSIONS: Although lower functional reserve of vital organs in the elderly patients was predicted, they showed an acceptable functional recovery after operation with DHCA. Other perioperative variables such as operation time and blood transfusion showed a negative impact on postoperative hepatic function.

Age Factors↗

[Blood conservation in thoracic aortic surgery with total cardiopulmonary bypass].

BACKGROUND: In thoracic aortic surgery, a large number of homologous transfusions sometimes cause systemic inflammatory response, which may lead to pulmonary dysfunction, renal dysfunction and brain edema. To predict the need for homologous blood transfusion in aortic surgery, we use blood transfusion index (preoperative Ht x body weight) to predict the magnitude of homologous transfusion. PATIENTS AND METHODS: From Dec 1997 to May 2000, 59 consecutive patients were underwent thoracic aortic graft replacement with total cardiopulmonary bypass. These patients were divided in 2 groups, who were underwent graft replacement without blood transfusions, and who needed blood transfusions. Each group was compared in age, sex, emergency, Ht, CPB time, blood transfusion index and operative mortality. RESULTS: Forty patients (67.7%) did not required blood transfusion. In elective cases (32 cases), 84.3% were underwent operation without blood transfusion. There was no significant difference between 2 groups in terms of age and mean bypass duration. Blood transfusion index was significantly higher in transfusion group (2,320 +/- 784) compared with that in not transfusion group (1,445 +/- 706). CONCLUSION: Blood transfusion index was useful preoperative parameter to predict the need for homologous transfusion.

Aged↗

[Combined carotid endarterectomy and off-pump coronary artery bypass grafting].

Patients with angina undergoing carotid endarterectomy have a high mortality. A 74-yaer-old man who has severe carotid stenosis was performed combined carotid endarterectomy and off-pump coronary artery bypass grafting successfully. At first, carotid endarterectomy was performed with Jamieson's specially designed dissector, which allow simultaneous dissection and removal blood from the surgical field. Secondly, then off-pump CABG was performed. Skeletonized internal mammary artery was harvested with ultrasound dissector. The advantage of that the dissected artery is not only long and greater blood flow, but also less damage to sternal blood flow which prevent infection and complications. Then internal mammary artery was anastomosed to left anterior discending artery with Octopus II stabilizer. After the operation, he recovered uneventfully without neurological complication. Combined single staged carotid endarterectomy and off-pump CABG appears to be a safe method.

Aged↗

RCAS1 as a tumour progression marker: an independent negative prognostic factor in gallbladder cancer.

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) induces apoptosis in immune cells bearing the RCAS1 receptor. We sought to determine RCAS1 involvement in the origin and progression of gallbladder cancer, and also implications of RCAS1 for patient survival. RCAS1 expression was examined immunohistochemically in 110 surgically resected gallbladder specimens. The gallbladders represented 20 cases of cholecystitis with no associated pancreaticobiliary maljunction; 23 cases of cholecystitis with pancreaticobiliary maljunction; 14 cases of adenomyomatosis; 7 adenomas; and 46 cancers. High expression of RCAS1 (immunoreactivity in over 25% of cells) was observed in 32 of the 46 cancers (70%), but not in other diseases, including pre-cancerous conditions. RCAS1 immunoreactivity was associated with depth of tumour invasion (P = 0.0180), lymph node metastasis (P = 0.0033), lymphatic involvement (P = 0.0104), venous involvement (P = 0.0224), perineural involvement (P = 0.0351) and stage by the tumour, nodes and metastases (TNM) classification (P = 0.0026). Thus, RCAS1 expression may be a relatively late event in gallbladder carcinogenesis, possibly promoting tumour progression. Cox regression multivariate analysis demonstrated RCAS1 positivity to be an independent negative predictor for survival (P = 0.0337; risk ratio, 12.690; 95% confidence interval, 1.216-132.423). High expression of RCAS1 significantly correlated with tumour progression and predicted poor outcome in gallbladder cancer.

Adult↗

The role of the cAMP-PKA system in the short-term regulation of striatal [(14)C]-2-deoxyglucose uptake in freely moving rats.

The cyclic adenosine monophosphate (cAMP)-protein kinase (PK) A system has been shown to have stimulatory effects on glucose utilization in various tissues in vitro. However, little is known about the influence of cAMP on glucose utilization in vivo. In the present study, we examined how cAMP-related compounds affected [(14)C]-2-deoxyglucose (DG) uptake in the striatum of freely moving rats. An intrastriatal injection of dibutyryl-cyclic adenosine monophosphate (db-cAMP), although increasing local cerebral blood flow, was found to decrease the uptake of [(14)C]-2-DG in the striatum. This decrease of [(14)C]-2-DG uptake in the striatum was completely blocked by pretreatment with Rp-adenosine-3',5'-cyclic monophosphorothioate triethylamine (Rp-cAMPS). Moreover, intrastriatal infusion of Rp-cAMPS alone produced a striking increase of [(14)C]-2-DG uptake in the striatum. These results strongly suggest that transient activation of the cAMP-PKA system can depress the glucose phosphorylation process of the rat brain in vivo.

Animals↗

Reversible inhibition of hypoxia-inducible factor 1 activation by exposure of hypoxic cells to the volatile anesthetic halothane.

Volatile anesthetics modulate a variety of physiological and pathophysiological responses including hypoxic responses. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that mediates cellular and systemic homeostatic responses to reduced O(2) availability in mammals, including erythropoiesis, angiogenesis, and glycolysis. We demonstrate for the first time that the volatile anesthetic halothane blocks HIF-1 activity and downstream target gene expressions induced by hypoxia in the human hepatoma-derived cell line, Hep3B. Halothane reversibly blocks hypoxia-induced HIF-1alpha protein accumulation and transcriptional activity at clinically relevant doses.

Anaerobiosis↗

Diminished corneal angiogenesis in gelatinase A-deficient mice.

The goal of the present study was to define the role of gelatinase A in angiogenesis. We performed corneal micropocket assays in gelatinase A-deficient mice and their age-matched wild-type littermates. The corneal neovascular area in gelatinase A-deficient mice (0.15+/-0.14 mm(2)) was significantly less than that of wild-type littermates (0.53+/-0.35 mm(2); P<0.01). Similarly, aortic ring assays showed significant reduction of endothelial outgrowth in gelatinase A-deficient mice (0.26+/-0.14 mm(2)) as compared to wild-type littermates (0.44+/-0.06 mm(2); P<0.05). These results suggest that gelatinase A may play an important role in the regulation of corneal angiogenesis.

Animals↗