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Biomedical subjects

T Muto

Publications and source records attributed to T Muto.

At least 361 records · Page 20Linked to original sources

Augmentation of 5-fluorouracil cytotoxicity by epidermal growth factor in a newly established human signet-ring cell carcinoma of the stomach in culture.

A cell line designated TSG6 was established from a signet-ring cell gastric carcinoma developed in a 57-year-old female patient. The TSG6 cells had well preserved the features of signet-ring cell carcinoma based on morphology. The cells exhibited both epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) immunoreactivities, and also secreted EGF. Moreover, the growth of TSG6 cells was stimulated in the presence of exogenous EGF. These results suggest that the possible presence of an EGF/EGFR autocrine growth mechanism is expressed in the TSG6 cells. The simultaneous treatment with EGF and 5-fluorouracil (5-FU) produced a nearly 2.4-fold enhancement of 5-FU cytotoxicity against TSG6 cells. A bromodeoxyuridine/DNA flow cytometry analysis revealed that EGF augmented 5-FU cytotoxicity by inducing the accumulation of S phase cells which might be more susceptible to 5-FU. Moreover, we found that the incorporation of 5-FU into the TSG6 cells was increased with the addition of EGF. These data indicate that EGF may be a potent agent as a biological response modifier for 5-FU against the tumors which express the EGF/EGFR autocrine mechanism, and that the TSG6 cell line is useful in furthering our understanding of the interaction between anticancer drugs and EGF.

Carcinoma, Signet Ring Cell↗

Lysis of endothelial cells by autologous lymphokine-activated killer cells.

The mechanisms of lysis of endothelial cells derived from human umbilical vein (HUVEC) by autologous lymphokine-activated killer (LAK) cells, generated from cord blood lymphocytes of the same donor, were investigated. Freshly isolated HUVEC as well as HUVEC cultured for several passages were efficiently lysed by autologous LAK cells, and their susceptibility to the LAK cells was almost the some as that of allogenic HUVEC. Complement-depletion experiments revealed that the lysis was mainly dependent on CD16+ natural killer (NK) LAK cells. pretreatment of HUVEC with recombinant interferon gamma (rIFN gamma) for 24 h made them resistant to lysis by autologous LAK cells, while pretreatment with either rIL-1 beta. rTNF alpha, or acidic or basic fibroblast growth factor did not alter the lytic sensitivity of HUVEC. The resistance of rIFN gamma-treated HUVEC was specific to lysis by CD16+ NK LAK cells, and their lysis by CD3+ T-LAK cells was not significantly altered. Moreover, in comparison with control HUVEC or rIL-1 beta-treated HUVEC, rIFN gamma-treated HUVEC had a significantly less potent inhibitory effect on the lysis of untreated HUVEC, when used as an unlabeled target. This suggests that rIFN gamma treatment may down-regulate the recognition of some molecules on HUVEC by rIL-2-activated NK cells. These data suggest that damage of the endothelium during LAK therapy is mainly dependent on LAK cells with a NK phenotype that can specifically recognize a certain molecule on autologous endothelial cells.

CD3 Complex↗

OK432 inhibits experimental hepatic metastasis of colon adenocarcinoma ACL-15 in F344 rats.

The effect of OK432 on hepatic metastasis, induced by inoculating 1 x 10(6) ACL-15 cells from a rat colon adenocarcinoma cell line into the ileocolic vein of male F344 rats, was investigated in this study. Metastases were detected 14 days after inoculation in the control rats, however, pretreatment 3 days prior to the tumor cell inoculation with an anti-asialoGM1 antibody, which eliminates natural killer (NK) cell activity in vitro, increased the number of hepatic metastases, shortened the survival time, and decreased the NK activity of the nonparenchymal liver cells (NPC). In contrast, pretreatment with OK432 2 days prior to tumor inoculation significantly decreased the number of hepatic metastases, prolonged the survival time, and augmented the NK activity of the NPC, although treatment with OK432 3 or 7 days after inoculation did not decrease the number of hepatic metastases. Moreover, NPC from the OK432-pretreated rats had a marked antitumor effect against ACL-15 cells in the Winn's neutralization test. The results of this study indicate that pretreatment with OK432 before tumor cell inoculation inhibits hepatic metastasis in this experimental model, possibly by augmentating liver-associated NK activity.

Adenocarcinoma↗

The macroscopic diagnosis of lymph node metastasis from early gastric cancer.

As the proportion of early gastric cancers (EGC) has been steadily increasing, modifications of the "radical lymphadenectomy" approach to stomach cancer have been attracting considerable attention; however, accurate pre- and intraoperative evaluations of tumor extent are essential for the successful application of this method. We examined the reliability of macroscopically diagnosing node involvement by reviewing the operative and pathological records of 522 patients with EGC. Of 59 patients histologically diagnosed as node-positive (n+), only 19 (32%) had been macroscopically diagnosed as node-positive (N+). In contrast, of 61 N+ patients, 42 (69%) were in fact n-. Metastases from histologically diffuse type carcinomas were less accurately diagnosed than those from intestinal type tumors. In 44% of the false-positive (N+/n-) patients, the tumor had been preoperatively diagnosed as advanced, which seemed to have lead to intraoperative overdiagnosis. These results suggest that lymph node metastases from EGC cannot be reliably diagnosed during surgery. The indications for a modified radical operation should thus be decided according to preoperative tumor evaluation based on the depth of invasion.

Humans↗

Computer-aided 3-dimensional visualization of abdominal aortic aneurysms from CT images.

A new method for elucidating the process of abdominal aortic aneurysm enlargement is presented herein. First, 3-dimensional (3-D) reconstructed images were used to precisely evaluate the size of an aneurysm, after which reconstruction and a volume analysis of images were performed with a personal computer system using serial computed tomographic films. The evolution of an aneurysm was examined by the detailed reconstruction, and an estimation of size was achieved by accurately measuring the figure reconstructed from the angle perpendicular to the axis of the contour. In quantifying the enlargement of an aneurysm, an exact evaluation of volume changes and morphological changes can be performed using the 3-D reconstruction method from the film series obtained at follow-up studies. The volume analysis proved especially useful for evaluating the axial expansion of aneurysms with stable maximum diameters.

Aortic Aneurysm, Abdominal↗

Chronic esophagitis and subsequent morphological changes of the esophageal mucosa in Barrett's esophagus: a histological study of esophagectomy specimens.

Chronic esophagitis and the subsequent morphological changes of the esophageal mucosa were histologically studied in esophagectomy specimens from 15 patients with Barrett's esophagus. Basal layer hyperplasia with papillary elongation, intraepithelial eosinophils, and intraepithelial neutrophils were found in the squamous epithelium of all (100%), 7 (46.7%), and 14 (93.3%) of the 15 specimens, respectively. Moreover, a specialized type of Barrett's mucosa was found in the metaplastic columnar lining of all the specimens. The muscularis mucosae appeared intact beneath the squamous epithelium lining the proximal esophagus in 13 specimens (86.7%), while it became thick and "dual" beneath the metaplastic columnar epithelium lining the distal esophagus in 14 specimens (93.3%). This dual muscularis mucosae, as well as the metaplastic columnar epithelium, particularly the specialized type, may be part of the specific histological changes characteristic of Barrett's esophagus.

Aged↗

Pancreatic carcinoma accompanied by pseudocyst: report of two cases.

Two cases of pancreatic cancer accompanied by pseudocyst are reported. Case 1 was a 60-year-old man who was admitted to our hospital complaining of left lower abdominal discomfort. A cystic lesion, about 3 cm in diameter, was found in the pancreatic tail by ultrasonography (US) and computed tomography (CT). No signs of chronic pancreatitis were found. At operation, an elastic, hard, white tumor, about 1 cm in diameter, was felt adjacent to the cystic lesion on the duodenal side. Histologically, this tumor was a duct cell carcinoma with an adjacent pseudocyst upstream of the pancreas. Case 2 was a 57-year-old man who complained of back pain and loss of body weight. US and CT examination revealed a cystic lesion, 11 x 7 cm in size, in the tail of the pancreas. Histological examination of the resected specimen revealed both a duct cell carcinoma, 3 cm in size, in the body of the pancreas and a pseudocyst, 9 cm in size. Pseudocysts accompanying carcinoma are thought to develop from obstruction of the pancreatic duct by the carcinoma, followed by intraductal high pressure and disruption of ductules upstream of the pancreas. Thus, we should pay careful attention to pseudocyst of the pancreas, especially when signs of diffuse chronic inflammation cannot be found, to help identify duct cell carcinoma in the early stage. Further detailed examinations of the cyst fluid or pancreatic juice, such as cytology, tumor marker determinations, or establishment of K-ras codon 12 mutation, are needed.

Carcinoma, Ductal, Breast↗

Intracellular action of an exogenous low-molecular-weight synthetic protease inhibitor, E3123, in cerulein-induced acute pancreatitis in rats.

The intracellular distribution and action of a new synthetic protease inhibitor, E3123, were studied in cerulein-induced acute pancreatitis in rats. Acute pancreatitis was induced by a 4-h iv infusion of a supramaximal dose of cerulein, and was treated by prophylactic (pretreatment) or therapeutic (posttreatment) continuous administration of E3123. Pancreatic edema and hyperamylasemia were ameriolated only by prophylactic treatment. A subcellular fractionation study showed that the activities of cathepsin-B and trypsin in the zymogen granule-enriched fraction of the cerulein-pancreatitis group were remarkably increased. Both prophylactic and therapeutic treatment significantly prevented the elevation of these enzyme activities. These effects were accompanied by amelioration of pancreatic histopathological features, including intracellular vacuolization and fat necrosis. A microscopic autoradiographic study using 3H-labeled E3123 showed diffuse intracellular distribution of E3123, and the radioactivity of 3H-E3123 in the posttreatment group was three times greater than that in the pretreatment group. This study provides the first experimental evidence that, even when administered therapeutically, exogenous protease inhibitors are transported into pancreatic acinar cells, thereby reducing the severity of early intracellular alterations in cerulein-induced acute pancreatitis.

Acute Disease↗

Positional change of the hyoid bone at maximal mouth opening.

The positional change of the hyoid bone in both closed and maximal mouth-opening positions of the mandible was investigated by cephalometric measurements. The following results were obtained: (1) With the increase in mouth opening the hyoid bone moved downward and backward. At maximal mouth opening the head posture changed posteriorly compared with that of occluded mouth position. (2) By superimposing films of the S-N plane, it became apparent that the hyoid bone was displaced downward by sagittal opening movement of the mandible and backward by the posterior change of the head posture. (3) Significant correlations were found between the degrees of sagittal rotation of the mandible and the position of the hyoid bone. (4) These results suggest that the posterior change of the head posture and inferior shift of the hyoid bone with mouth opening are important factors in obtaining maximal mouth opening.

Adult↗

Effects of fibroblast growth factors and related peptides on food intake by rats.

The effects of acidic fibroblast growth factor (aFGF), basic FGF (bFGF), and related peptides, such as aFGF fragments, on food and water intake were investigated. Infusion of aFGF and bFGF into the third cerebral ventricle significantly suppressed food intake. The potency of aFGF was 1.5 that of bFGF in food intake inhibition. Both FGFs also suppressed water intake. Infusion of a carboxyl-terminal fragment of aFGF, aFGF-(114-140), did not affect food intake, whereas an amino-terminal fragment of aFGF, aFGF-(1-15), was significantly inhibitory. Other amino-terminal fragments, aFGF-(1-20) and aFGF-(1-29), did not affect food intake. However, [Ala16]aFGF-(1-29), in which the cysteine residue at position 16 was replaced with alanine, significantly suppressed food intake. Infusions of functional antagonists for FGFs, anti-aFGF, anti-bFGF, and anti-aFGF-(1-15) IgGs, into the lateral hypothalamus significantly increased food intake. The results suggest that: aFGF, bFGF, and some amino-terminal peptides of aFGF participate in the central regulation of food intake; the lateral hypothalamus is involved in their feeding suppression actions; and these peptides may function as physiologically relevant substances in the adult central nervous system, other than as neurotrophic factors.

Animals↗

Perioperative changes in coagulative and fibrinolytic function during surgical treatment of abdominal aortic aneurysm and arteriosclerosis obliterans.

To determine the factors which influence perioperative coagulative and fibrinolytic function, we studied 41 patients who underwent surgical repair of unruptured abdominal aortic aneurysm (AAA) and 30 patients who underwent arterial reconstruction for arteriosclerosis obliterans (ASO). In patients with AAA, the levels of fibrin/fibrinogen degradation products (FDP) (11.4 +/- 20.1 micrograms/ml), thrombin-antithrombin III complex (TAT) (22.0 +/- 21.8 micrograms/l), plasmin-alpha 2 plasmin inhibitor complex (PIC) (2.6 +/- 2.9 micrograms/ml) and d-dimer of cross-linked fibrin degradation products (D-D) (8.4 +/- 10.8 micrograms/ml) were elevated, particularly when the AAAs had a large mural thrombus surface area or were accompanied by aneurysm of the iliac or femoral artery. In arterial aneurysms, blood coagulability and secondary fibrinolytic activity were believed to be enhanced. In patients with ASO, the level of TAT (17.2 +/- 24.8 micrograms/l) was so elevated that they were considered to show chronic hypercoagulability. Among the ASO patients with aorto-iliac lesions, those with concomitant graft occlusion or anastomotic aneurysm had significantly elevated levels of TAT. Proximal arterial occlusion or accompanying aneurysm in the ASO patients was associated with increased levels of PIC and D-D. Postoperative fluctuations in conventional hematological variables did not differ significantly among the surgical procedures. Conventional markers showed a transient decrease due to consumption during surgery, and a subsequent recovery or an actual increase within several days after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

The position of the mandibular condyle at maximal mouth opening in normal subjects.

PURPOSE: To investigate the position of the mandibular condyle at maximal mouth opening in individuals 19 to 30 years of age with no functional disorders of the masticatory system. PATIENTS AND METHODS: Measurements were made in 153 subjects (99 men, 54 women), and 41 men and 44 women had transcranial radiographs taken of their right and left temporomandibular joints in the closed and maximal opening positions. RESULTS: In all subjects the condyle moved forward beyond the summit of the articular eminence, and in more than half the subjects the condyle was located inferior to the eminence at maximal opening. CONCLUSION: The correlation between maximal opening and anterior shift of the condyle from the summit of the eminence was significant, but the correlation with vertical shift of the condyle was not significant. The correlation between the form of the glenoid fossa (length and depth) and anterior or vertical shift of the condyle from the summit of the eminence also was not significant.

Adult↗

An objective assessment of intermittent claudication by near-infrared spectroscopy.

Changes in tissue oxygenation in the calf muscle were measured by near-infrared spectroscopy (NIRS) in 62 patients who complained of intermittent claudication in the calf during a treadmill test. Three distinctive patterns of oxygenated and deoxygenated haemoglobin were observed. None of the type 0 cases were severe (i.e., unable to walk for more than 5 minutes), while 37 and 82% of the type 1 and type 2 cases were severe, respectively. The mean maximum walking distance of type 1 was significantly longer than that of type 2 (179 +/- 70 m and 109 +/- 46 m, respectively; p < 0.005), while the mean ankle-brachial pressure index at rest of type 1 was not significantly different from that of type 2 (0.68 +/- 0.19 and 0.61 +/- 0.23, respectively). Our results indicate that NIRS can be used to accurately assess the severity of intermittent claudication.

Adult↗

Clinical implications of cervical lymph node metastasis patterns in thoracic esophageal cancer.

OBJECTIVE: The authors attempt to clarify the clinical implications of cervical lymph node metastases from thoracic esophageal cancers. SUMMARY BACKGROUND DATA: Cervical lymph node metastases from thoracic esophageal cancer have been considered to be incompatible with curative resection. However, recent studies have demonstrated that cure is achievable in patients with such metastases. METHODS: Patterns of esophageal cancer metastasis to the cervical nodes and long-term results after tumor resection were investigated in 23 patients undergoing bilateral cervical lymphadenectomy for treatment of thoracic esophageal cancer. RESULTS: The number of positive nodes per patient was significantly greater (p < 0.05) in lower esophageal cancers (median: 15) than in upper or mid esophageal cancers (median: 2.5). Simultaneous metastases to three nodal regions (the neck, mediastinum, and abdomen) were significantly more common (p < 0.001) in lower esophageal tumors (88.9%) than in upper and mid esophageal lesions (7.1%). Although the overall 5-year survival rate was 16.5%, long-term survival was achieved only in patients with upper or mid esophageal cancer.

Adult↗

Lower incidence of K-ras codon 12 mutation in flat colorectal adenomas than in polypoid adenomas.

In order to clarify genetic changes in flat adenomas, K-ras codon 12 point mutations were examined in 56 flat adenomas, 81 polypoid adenomas and 42 cancers of colon and rectum. The mutation frequency in flat adenomas was 23% (13/56), significantly lower than that in polypoid adenomas (67%: 54/81) and cancers (76%: 32/42). Even mildly dysplastic adenomas or small (less than 5 mm) adenomas showed higher mutation incidence in polypoid type (62%, 57%) than in flat type (23%, 19%). Among flat adenomas, flat elevated lesions exhibited relatively higher mutation frequency than completely flat or depressed ones. As for cancers, 14 tumors (33%) contained mutations only in a minor tumor cell population, indicating that these mutations occur at a late stage of tumorigenesis. These results suggest that the adenoma-carcinoma sequence through flat adenomas may be different from that through polypoid adenomas, and genetic changes may be heterogeneous in colorectal carcinogenesis.

Adenoma↗

Different clinicopathologic findings in two histologic types of carcinoma of papilla of Vater.

The aim of this study was to investigate the differences between the clinicopathological findings in two histologic types of carcinoma of the papilla of Vater. We histologically classified carcinoma of the papilla into two types: 1) an intestinal type that resembles tubular adenocarcinoma of the stomach or colon, and 2) a pancreaticobiliary type that is characterized by papillary projections with scant fibrous cores. We examined 53 cases of resected carcinoma of the papilla. The intestinal-type carcinomas were similar to the intestinal mucosa in that they had lysozyme-containing, Paneth or argyrophil cells, as demonstrated by the immunohistochemically positive stainings for the anti-lysozyme antibody. Although both the sizes of the two types of carcinomas and the age distributions of cases with the two types of carcinoma were almost the same, the prognosis of the cases with the intestinal type was much better than that of the cases with the pancreaticobiliary type. Histological lymph node metastasis was found significantly more often in the pancreaticobiliary type. This result was supported by the fact that small carcinomas of the intestinal type showed little or no invasion into the surrounding interstitium, as opposed to the pancreaticobiliary type, which had a strong infiltrative tendency. The pathogenesis of carcinoma of the papilla of Vater should be further evaluated, taking into consideration the existence of these two histologic types.

Adult↗

Structure, expression and chromosome assignment of the human catenin (cadherin-associated protein) alpha 1 gene (CTNNA1).

We have isolated the human alpha-catenin gene (CTNNA1), which encodes a cadherin-associated protein, and have determined its primary structure and chromosomal localization. The transcript of CTNNA1 is 3.4 kb long and consists of 16 coding exons encoding 906 amino acids and at least one 5' noncoding exon. The 102-kDa predicted protein is the same size as the murine homolog, and the amino acid sequences of the two proteins are 99.2% homologous. Analysis by reverse transcription-PCR revealed that this gene is expressed ubiquitously in normal tissues. It was mapped to chromosome band 5q31 by fluorescent in situ hybridization.

Amino Acid Sequence↗