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T Sawai

Publications and source records attributed to T Sawai.

At least 37 records · Page 2Linked to original sources

Effects of paclitaxel on cultured synovial cells from patients with rheumatoid arthritis.

BACKGROUND: Proliferation of synovial cells is considered to play a key role in rheumatoid arthritis (RA). Using paclitaxel, a unique antineoplastic agent known to suppress collagen-induced arthritis, we conducted an in vitro study of cell kinetics on cultured synovial cells from patients with RA. METHODS: Alterations of the cell cycle of cultured fibroblast-like synovial cells (FLSs) from patients with RA were studied using flow cytometry and laser scanning cytometry. Apoptosis and accumulation of cyclin concerning effects of paclitaxel were detected. RESULTS: Paclitaxel induced arrest of the cell cycle at G2/M phase and apoptosis in FLSs. The late stage of apoptosis was determined by the positivity of terminal deoxynucleotidyl transferase assay. Morphological observation by combined usage of both annexin V and propidium iodide on FLSs on a slide glass showed early apoptotic changes in detail. FLSs arrested at G2/M phase showed marked accumulation of cyclin B1. The effects of paclitaxel decreased on FLSs, which diminished proliferative activity. CONCLUSIONS: These data indicate that paclitaxel induces cell arrest at G2/M phase followed by apoptosis in human FLSs, which have high proliferative activity, and possible therapeutic effects of paclitaxel on RA.

Adult↗

Characterization of the active-site residues asparagine 167 and lysine 161 of the IMP-1 metallo beta-lactamase.

The roles of lysine at position 161 and asparagine at position 167 in IMP-1 metallo beta-lactamase were studied by site-directed mutagenesis. These residues are highly conserved in metallo beta-lactamases and are thought to be present in the active-site cavity. Mutant enzymes with alanine or aspartic acid at position 167 showed almost the same properties as the wild-type enzyme. Kinetic parameters for the mutant enzymes differing at position 161 indicated that the positive charge of lysine 161 is required for electrostatic interaction with the carboxyl moiety of the substrate, i.e. C-3 of penicillins or C-4 of cephalosporins.

Asparagine↗

Pancreatectomy combined with superior mesenteric-portal vein resection for adenocarcinoma in pancreas.

The aims of this study were to investigate morbidity, mortality, and survival of patients with ductal adenocarcinoma of the pancreas who underwent pancreatectomy without (group 1) or with (group 2) en bloc portal vein resection and to study the degree of carcinoma invasion of the portal vein in group 2. The medical records of 46 and 28 patients in groups 1 and 2, respectively, were reviewed. In addition, the degree of invasion of the wall of the portal vein was categorized histologically into three types: type I, transmural invasion involving the intima; type II, invasion of the wall of the vein without intimal involvement; and type III, compression of the wall of the vein by surrounding carcinoma without true invasion. The morbidity and mortality in group 1 (26% and 4%) were not different from those in group 2 (32% and 4%). Similarly, there was no difference in survival between the two groups. Survival tended to vary directly with the depth of invasion of the wall of the portal vein: type I 6.8 +/- 1.9 months; type II 15.3 +/- 6.4 months; type III 20.6 +/- 13.0 months. These findings suggest that en bloc resection of the pancreas and the portal vein does not increase mortality and morbidity after pancreatectomy; survival after en bloc resection was similar to that of patients not requiring portal vein resection. Combined resection of the pancreas with the portal vein could be an option in the treatment of pancreatic cancer with direct invasion of the portal vein.

Adenocarcinoma↗

The effect of phospholipids and fatty acids on tight-junction permeability and bacterial translocation.

The activity of phospholipase A2 (PLA2) is elevated in the intestinal epithelia of patients with inflammatory bowel disease (IBD). We recently reported that PLA2 mediates hydrolysis of phosphatidylcholine (PC) to lysophosphatidylcholine (L-PC) when both are applied to the apical surface of cultured EC monolayers, resulting in increased bacterial translocation (BT) and decreased transepithelial electrical resistance (TEER). Free fatty acids (FFA) are the other products of this reaction, however, their effect on Caco-2 cell permeability has not been reported. In addition to PC, other luminal phospholipids are present at the surface of the enterocyte. PLA2 may also mediate the hydrolysis of luminal phospholipids other than PC. The aim of this study was to examine the effects of phospholipids other than PC and common FFA on intestinal epithelial permeability and BT. Human Caco-2 enterocytes were grown to confluence on porous filters in the apical chamber of a two-chamber cell-culture system. Monolayer integrity and tight-junction permeability were measured as TEER. First, common FFA released by PC hydrolysis were determined using thin-layer chromatography (TLC). In separate experiments, monolayers were treated with phosphatidylethanolamine (PE), lysophosphatidylethanolamine (L-PE), or palmitoleic acid, oleic acids, linoleic acids, and arachidonic acid solubilized in solution with PC. The magnitude of BT was determined 2 h after treatment by adding Escherichia coli C25 to the apical chamber followed by quantitatively culturing basal-chamber samples. Statistical analysis was by the Kurosaki-Wallis test. TLC of PC samples incubated with PLA2 on the apical surface of Caco-2 monolayers demonstrated the production of palmitoleic acid, oleic acids, linoleic acids, and arachidonic acid. L-PE significantly decreased TEER compared to controls, but to a lesser degree than L-PC alone. L-PE had no effects on BT. Palmitoleic acid and oleic acid likewise significantly decreased TEER compared to controls, however, less than L-PC. All FFA tested had no effect on BT. Phospholipids applied to the apical surface of enterocytes, such as those found in vivo in mucus, can be hydrolyzed by the enzyme PLA2 resulting in lysophospholipid and FFA species that can alter enterocyte monolayer permeability. However, FFA and L-PL, other than L-PC, appear to have no effect to stimulate BT. This observation may have clinical implications in the pathogenesis and treatment strategies for IBD patients in whom enterocyte PLA2 activity has been shown to be elevated.

Bacterial Translocation↗

Effect of secretory immunoglobulin A on bacterial translocation in an enterocyte-lymphocyte co-culture model.

Intestinal secretory immunoglobulin A (sIgA) plays an important role in gut mucosal immunity in vivo; however, in-vitro enterocyte models for studying the mechanisms of these effects are lacking. This study utilizes a cell-culture model to investigate the effect of sIgA on bacterial translocation (BT) across human enterocytes co-cultured with human lymphoid cells (Raji cells). This model is intended to mimic in-vivo enterocyte/lymphocyte interactions found in intestinal follicle-associated epithelia. Human Caco-2 enterocytes were grown to confluence on porous filters in the apical chamber of a two-chamber cell-culture system. After differentiation, human B lymphoid cells (Raji cells) were added to the basolateral surface of Caco-2 monolayers for 3 days' co-culture, followed by washing away of unincorporated Raji cells. Transepithelial electrical resistance (TEER) was used to measure tight-junction permeability. Monolayers were treated with or without sIgA, IgG (negative control), or mannose (positive control). BT across the cell monolayer was determined 1.5 h after addition of Escherichia coli. Statistical analysis was by the Kruskal-Wallis test, P below 0.05 considered significant. In co-culture monolayers treated with sIgA, IgG, or mannose, there was no significant effect on TEER; however, the magnitude of BT across cells treated with sIgA (1.3 +/- 0.4 log10CFU/ml) and mannose (1.6 +/- 1.1 log10CFU/ml) was significantly decreased compared to PBS (3.9 +/- 0.4 log10CFU/ml) and IgG (2.9 +/- 0.6 log10CFU/ml) controls (P < 0.05). sIgA BT inhibition was dose-dependent. BT inhibition by sIgA and mannose was additive (0.5 +/- 1 log10CFU/ml). Inhibition of BT was negated when sIgA and mannose were removed by washing prior to E. Coli addition (3.6 +/- 0.5 log10CFU/ml), suggesting that both inhibitors act through bacterial binding.

Bacterial Translocation↗

Circulating sialyl Lewis(x), sialyl Lewis(a), and sialyl Tn antigens in colorectal cancer patients: multivariate analysis of predictive factors for serum antigen levels.

Preoperative serum levels of sialyl Lewis(a) (CA 19-9), sialyl Lewis(x) (SLX), and sialyl Tn (STN) antigens in colorectal cancer patients were examined to establish predictive factors for serum levels of these antigens compared with carcinoembryonic antigen (CEA). A total of 308 patients who underwent resection for a colorectal cancer were divided into low and high antigen groups (higher or lower than a selected diagnostic-based cutoff value). The cutoff values were 37 U/ml for CA19-9, 38 U/ml for SLX, 45 U/ml for STN, and 2.5 ng/ml for CEA. The American Joint Committee on Cancer Classification and Stage grouping was used to classify the tumors. Statistical tests were conducted using univariate and multivariate logistic regression analyses. For CA19-9, 81 patients (26.3%) were assigned to the high antigen group: for SLX, 39 (12.7%); for STN, 33 (10.7%); and for CEA, 133 (43.2%). Multivariate logistic regression analysis revealed that predictive factors associated with high antigen levels were female sex (odds ratio [OR], 1.78 vs male sex), T4 (OR, 3.26 vs T1/T2), and M1 (OR, 3.35 vs M0) for CA19-9; M1 (OR, 6.40 vs M0) for SLX; mucinous carcinoma (OR, 8.45 vs well differentiated adenocarcinoma) and M1 (OR, 8.24 vs M0) for STN; and mucinous carcinoma (OR, 7.21 vs well differentiated adenocarcinoma), T3/T4 (OR, 3.84/4.18, respectively, vs T1/T2), and M1 (OR, 6.39 vs M0) for CEA. In conclusion, high serum levels of CA19-9, SLX, and STN are strongly associated with distant metastasis. In addition, high serum levels of CA19-9 may be an independent predictor for female gender and T4, and high serum levels of STN may be an independent predictor for mucinous carcinoma.

Aged↗

Minilaparotomy wound edge protector (Lap-Protector): a new device.

Laparoscopic-assisted or minimally invasive surgery involving minilaparotomy is occasionally complicated by infection of the minilaparotomy wound caused by intestinal bacteria. Furthermore, when this procedure is performed to excise colorectal or gastric cancer, tumor recurrence may develop in the minilaparotomy wound. In an attempt to minimize the risk of these complications, we developed a new, easy-to-use device which we named the "Lap-Protector." Minilaparotomy was performed using the Lap-Protector in 28 patients with colon cancer and eight patients with early gastric cancer who underwent minimally invasive surgery between January and September, 1999. During a median follow-up period of 15.9 (range 12.4-21.0) months, none of the 36 patients showed any sign of wound infection or tumor recurrence in the minilaparotomy wound. These results indicated that the Lap-Protector is a safe and useful device that may help to prevent infections and cancer cell contamination of the minilaparotomy wound.

Aged↗

Surgical treatment and subsequent outcome of patients with carcinoma of the splenic flexure.

Extended resection, comprising extended right hemicolectomy, splenectomy, and distal pancreatectomy, has been advocated for carcinoma of the splenic flexure because the lymphatic drainage at this site is variable. The present study addresses the problems associated with selecting the most appropriate operative procedure to achieve cure of splenic flexure cancers. We conducted a retrospective review of 27 patients with splenic flexure cancer who underwent curative resection. Left partial colectomy was performed in 20 patients and partial resection of the transverse/descending colon was performed in 7 patients. The combined resection of adjacent organs due to tumor adherence was performed in three patients. The spleen and distal pancreas were the organs most frequently resected among a collective total of six adjacent organs. The median duration of follow-up was 60.9 months after resection for splenic flexure cancer. No patient developed local recurrence. There was no significant difference in 5-year survival between patients with splenic flexure cancers and those with colon cancers at other sites. In conclusion, splenic flexure cancer resected by left partial colectomy or partial resection of the transverse/descending colon without routine extended resection was not associated with a worse prognosis than colon cancers at other sites.

Adenocarcinoma↗

Colectomy for colon cancer via a 7-cm minilaparotomy.

We herein describe our technique for performing a colectomy to resect colon cancer via a 7-cm minilaparotomy using conventional surgical techniques and instruments. By moving the minilaparotomy wound laterally as well as either caudad or cephalad, the mobilization of the relevant segment of the bowel loop was thus made possible. To ensure an adequate visualization of the operative field during a dissection of the lymph nodes, an Omni-Tract retractor system was used. The division of the colonic mesentery, transection of the affected bowel, and bowel anastomosis were performed extracorporeally or at the level of the incision. This same operation was successfully performed in 102 patients with colon cancer. We conclude that a colectomy for colon cancer via a 7-cm minilaparotomy is an attractive alternative to a conventional full laparotomy in selected patients.

Colectomy↗

Prognostic factors in hepatic metastases of colorectal carcinoma: immunohistochemical analysis of tumor biological factors.

The present study was designed to provide a systemic analysis of prognosis in 62 patients who underwent hepatic resection for colorectal liver metastasis. The analyzed factors included microvessel counts stained by CD34 and expression of two adhesion molecules, E-cadherin and CD44 variant exon 6-(v6) in these tumors. No significant factors related to recurrence were identified and only negative expression of CD44v6 tended to correlate with recurrence (P = 0.075). A short disease-free period to recurrence was noted in patients with high CEA levels (>10 ng/ml) and H2/3 classification. A short surgical margin, H2/3 classification, high microvessel counts (>60/field, x200), and negative expression of CD44v6 and E-cadherin tended to be associated with poor prognosis. A high microvessel count was the most significant prognostic factor by multivariate Cox proportional hazards regression model. Hepatic resection without tumor exposure and a careful follow-up in cases identified with poor prognostic factors are necessary.

Adult↗

Volar melanotic macules in a Japanese man with histopathological postinflammatory pigmentation: the volar counterpart of mucosal melanotic macules.

BACKGROUND: Volar melanotic macules are asymptomatic light-brown or tannish-grey macules usually found on the palms and/or soles of blacks, although they have also been reported on the volar surfaces of whites. Similar lesions have not been reported before in Japanese people. Since the cause is as yet unknown, it remains to be discussed whether they are a distinct entity. METHODS: In this report, a 52-year-old Japanese man with volar melanotic macules is reported with the clinical and histopathological findings. RESULTS: A 52-year-old Japanese man presented with many light-brown macules on his bilateral soles. He had a 20-year history of tinea pedis. Histopathological examination revealed melanophages and inflammatory infiltrates in the superficial dermis. There was a slight increase in melanin granules around the acrosyringium. Fontana-Masson stain revealed a slight increase in melanin granules in the basal layer including the acrosyringium and superficial dermis. These changes corresponded with postinflammatory pigmentation. CONCLUSIONS: This is the first report of volar melanotic macules in Japanese people. We suggest that volar melanotic macules is not an independent entity but a clinicopathological one that includes postinflammatory pigmentation, and that the condition is the volar counterpart of mucosal melanotic macules.

Foot↗

Use of minilaparotomy in the treatment of colonic cancer.

BACKGROUND: The feasibility and safety of a minilaparotomy approach for curative resection of colonic cancer have not been fully elucidated. The purpose of this study was to compare outcomes utilizing this alternative technique with those of conventional laparotomy. METHODS: Eighty-four patients scheduled to undergo resection for colonic cancer via minilaparotomy between 1997 and 1999 were studied prospectively. The minilaparotomy involved complete resection performed through a skin incision less than 7 cm in length. Sixty-nine patients who underwent a similar resection via a conventional laparotomy between 1994 and 1996 served as the control group. RESULTS: The minilaparotomy approach was successful in 72 of 84 patients. Colectomy type, operating time and histopathological features of tumours were similar between cases and controls, whereas operative blood loss in the control group was significantly greater (P = 0.002). Postoperative times to standing, walking, passage of flatus and urinary catheter removal were significantly shorter in the minilaparotomy group (P = 0.007, P = 0.003, P = 0.03 and P = 0.006 respectively), and analgesic requirements were significantly lower (P = 0.001). At a median follow-up of 24.8 months there have been no tumour recurrences at the minilaparotomy incision sites. CONCLUSION: A minilaparotomy approach to the curative resection of colonic cancer is an attractive alternative to conventional laparotomy in selected patients.

Adult↗

Evaluation of pancreatic secretion after administration of secretin: application of magnetic resonance imaging.

BACKGROUND: To evaluate pancreatic exocrine function, we measured the changes in T2 enhanced hydrograhic intensity on magnetic resonance (MR) images of the pancreas following an injection of secretin, which is representative of the changes in duodenal fluid volume. METHODS: The subjects were 10 patients with normal pancreatic function (N > 70% detected by using a pancreatic function diagnostant test) and 12 patients with hypo-function, including those with mild hypo-function (MH, 50-70%, six patients) and severe hypo-function (SH < 50%, six patients). RESULTS: In the N group, T2 enhanced intensity of the pancreas increased to a maximum value (more than 10% compared with baseline) within 5 min of stimulation, then gradually decreased. No significant difference in the response was observed between the head and body of the pancreas. Changes in the MH group were similar to those of the N group. In contrast, significantly lower changes in T2 enhanced intensity were observed in SH group, relative to both the N and MH group (P < 0.05). The amount of secretin-induced increase in duodenal fluid after 16 min was not significantly different among the three groups. Furthermore, an evaluation of the residual pancreatic tissue after a pancreatoduodenectomy was also feasible. CONCLUSIONS: Our results indicate that the MR-secretin test is useful for the evaluation of severe pancreatic exocrine dysfunction. The diagnostic test is simple, direct and non-invasive.

Adult↗

Comparison of the expression of ABH/Lewis-related antigens in polypoid and non-polypoid growth types of colorectal carcinoma.

BACKGROUND AND AIMS: Colorectal tumors can be classified based on their growth pattern into the polypoid growth-type (PG-type) and non-polypoid growth-type (NPG-type). To ascertain whether there is any relationship between the expression of particular blood group-related antigens (A, B, H, Lewis (Le)a, sialyl Le(a), Le(x), sialyl Le(x)) in a colorectal tumor, and a tumor having polypoid or non-polypoid growth, we examined 78 PG-type and NPG-type colorectal cancers. METHODS: Fourteen PG-type and 64 NPG-type colorectal carcinomas were subjected to immunohistochemical analyses by using monoclonal antibodies against A, B, H, Le(a), sialyl Le(a), Le(x) and sialyl Le(x). RESULTS: The patients with NPG-type carcinomas had a significantly younger age of onset, significantly smaller maximal tumor diameter, significantly higher rate of lymph node metastasis and significantly worse prognosis than those with PG-type carcinomas. Among the 32 tumors of patients with blood type A or AB, isoantigen A was expressed in a significantly larger percentage of NPG-type carcinomas than PG-type carcinomas (95.8 vs 62.5%, respectively; P=0.014). Among all 78 tumors, sialyl Le(x) antigen was expressed in a significantly larger percentage of NPG-type than PG-type carcinomas (90.6 vs 64.3%, respectively; P=0.010). Multivariate analysis using the logistic regression model revealed that isoantigen A and sialyl Le(x) expression were independent predictive risk factors for the development of NPG-type colorectal carcinoma. CONCLUSIONS: These data suggest that the expression of isoantigen A and sialyl Le(x) in a colorectal carcinoma partially determines whether the tumor will have polypoid or non-polypoid growth.

ABO Blood-Group System↗

Measurement of serum hyaluronic acid level during the perioperative period of liver resection for evaluation of functional liver reserve.

BACKGROUND AND AIM: The serum hyaluronic acid (HA) concentrations reflect the degree of hepatic fibrosis and sinusoidal endothelial cell damage. The HA concentrations were examined to evaluate liver damage during the perioperative period of hepatectomy. METHODS: The HA level of serum samples from 79 patients who underwent a hepatectomy was measured, and the results were compared to conventional liver function tests, the degree of fibrosis, liver regeneration and complications. RESULTS: Hyaluronic acid concentrations correlated with the severe fibrosis or histological activity index, and also correlated with liver function tests including transaminase level, platelet counts, prothrombin time activity, indocyanine green retention rate at 15 min (ICG R15), liver activity at 15 min by technetium-99m galactosyl human serum albumin scintigraphy (LHL 15), and portal pressure. The HA level postoperatively correlated with liver function, especially with total bilirubin. Hyaluronic acid levels at day 28 postoperatively correlated with ICG R15 and LHL 15. The hyaluronic acid level before surgery and at day 28 postoperatively correlated with the regeneration of remnant liver in major hepatectomy. The HA levels were significantly higher in patients with hepatic failure or prolonged ascites. CONCLUSION: Our results indicate that the measurement of the HA level is useful for monitoring liver damage or predicting complications associated with liver surgery.

Adult↗

Pre-operative serum levels of sialyl Tn antigen predict liver metastasis and poor prognosis in patients with gastric cancer.

AIMS: To clarify the prognostic value of preoperative serum levels of sialyl Tn antigen (STN) for survival of gastric cancer patients. METHODS: Pre-operative serum levels of STN, sialyl Lewis(a)antigen (CA19-9) and carcinoembryonic antigen (CEA) were examined in 180 patients who underwent resection of gastric cancer. Patients were divided into high and low antigen groups on the basis of a selected diagnostic-based cut-off value. Correlation between high antigen serum levels, established clinicopathologic factors and prognosis was examined by univariate and multivariate analysis. RESULTS: Twenty-eight patients (15.6%) were classified as high STN; 37 (20.6%) as high CA19-9; and 33 (18.3%) as high CEA. The survival time of the high STN, CA19-9 or CEA group was shorter than that of the respective low-antigen group (P<0.0001, P=0.0008 or P=0.0002, respectively). Patients with stage III/IV tumours with high STN had a shorter survival time that those with low STN (P=0.0004). Cox's regression with multiple covariates showed that high serum STN is an independent factor predicting a worse outcome in gastric cancer patients. Multiple logistic regression analysis revealed that high serum STN is an independent predictor for the development of liver metastasis. CONCLUSIONS: Pre-operative high serum levels of STN predict both liver metastasis and poor prognosis after resection for gastric cancer.

Aged↗