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Biomedical subjects

T Ueno

Publications and source records attributed to T Ueno.

At least 199 records · Page 11Linked to original sources

Structure-activity relationships of RGD mimetics as fibrinogen-receptor antagonists.

The activities of a series of RGD mimetics, which contained a variety of cationic structures, for the inhibition of platelet aggregation and fibrinogen-receptor binding were measured. The stability of the coulombic ion-pairing complex of the model compounds with the acetate anion as a model for the receptor was calculated in terms of the ionic interaction energy. The results suggest that stability is one of the significant factors which govern the inhibitory potency of fibrinogen-receptor binding. The distance between cationic and anionic groups might also affect the potency. A compound which contained an amidinophenyl structure as the cationic moiety showed exceptionally high inhibitory activity, suggesting that some other factors, in addition to coulombic interaction and the distance, affect the potency.

Blood Platelets↗

OK-432 treatment increases matrix metalloproteinase-9 production and improves dimethylnitrosamine-induced liver cirrhosis in rats.

Kupffer cells are major matrix metalloproteinase-producing cells in the liver. The production of metalloproteinases in Kupffer cells may contribute to the improvement of liver fibrosis inducing liver cirrhosis. In this study, we examined the effect of the OK-432 (a biological response modifier) on the dimethylnitrosamine-induced liver cirrhosis in rats. Dimethylnitrosamine (10 microg/ml) was injected intraperitoneally into 20 male Wistar rats 3x/week for 4 weeks. For the subsequent 4 weeks, the animals were injected with saline (1 ml, 1x/week) (Group I, n=10) or OK-432 (1 Klinishe Einheit, 1x/week) (Group II, n=10). The control rats were injected with 1 ml saline for the initial 4 weeks and subsequent 4 weeks (Group III, n=10). The degree of hepatic fibrosis, the immunolocalization of type IV collagen, hyaluronic acid, and alpha-smooth muscle actin, and the mRNA expression by Northern blotting and the activity by gelatin zymography of metalloproteinase-9 were evaluated. Serum aminotransferase, hyaluronic acid, interleukin-1beta and tumor necrosis factor-alpha levels were measured. The deposition of á-smooth muscle actin and extracellular matrix containing type IV collagen and hyaluronic acid was markedly suppressed by OK-432. The mRNA expression and the activity of metalloproteinase-9 were markedly increased by OK-432. The serum aminotransferase and hyaluronic acid levels were decreased by OK-432. The serum interleukin-1 and tumor necrosis factor-alpha values were lower than the detectable limit in all samples from all three groups. These results indicate that OK-432 increased the production of metalloproteinase-9 and improved the rat dimethylnitrosamine-induced liver cirrhosis. OK-432 is suggested to be useful for the treatment of liver cirrhosis.

Actins↗

Various extrahepatic manifestations caused by hepatitis C virus infection.

It has been reported that hepatitis C virus (HCV) causes not only liver disease but also disorders of other organs and tissues. Previously, many HCV-related extrahepatic manifestations have been reported. In this study, we report 2 patients in whom tongue cancer was detected during the treatment of HCV-related liver disease. In one patient, tongue cancer was detected during the treatment of HCV-related liver cirrhosis, and articular rheumatism developed thereafter. The duration of HCV-related liver disease was 10 years. In the other patient, tongue cancer was detected during the treatment of HCV-related hepatocellular carcinoma. This patient had a past history of thyroid disease. The duration of HCV-related liver disease was 6 years. In these patients, the possibility that several conditions incidentally and concurrently developed cannot be denied. However, the conditions described above may be regarded as HCV-related extra-hepatic manifestations. In patients with HCV infection, it is important to examine conditions in organs other than the liver. Careful follow-up is needed.

Aged↗

Significance of thymidine phosphorylase as a marker of protumor monocytes in breast cancer.

Tumor-associated monocytic cells (TAMs) are a major component of the stroma responsible for tumor formation. TAMs generate various kinds of mediators for their function, one of which is thymidine phosphorylase (TP). TP is an angiogenic enzyme that is known to be up-regulated in tumor tissues. Here, we focused on the clinical implication of TP expression in TAMs by studying 229 primary breast carcinoma tissues. Immunohistochemical analysis demonstrated that monocytic TP+ tumors had a significantly worse prognosis than did monocytic TP- tumors (P < 0.01, log-rank test). A multivariate analysis confirmed that monocytic TP status provided an independent prognostic value (P < 0.0001). Furthermore, of interest was that monocytic TP status could categorize the CD68+ patients, who had an extensive accumulation of CD68+ TAMs, into two subgroups with strikingly contrasting prognoses: a good prognostic monocytic TP- group and a poor prognostic monocytic TP+ group. This indicates that there are both antitumor and protumor types of TAM. Subanalysis showed that microvessel density was significantly increased in CD68+/monocytic TP+ tumors compared with CD68+/monocytic TP- tumors. Experimentally, TAMs are known to function in diverse manners, antitumor and protumor; however, little is known about clinically recognizable markers to characterize the TAMs in histological sections. TP might be such a marker, which would be useful for identifying the character of TAMs, particularly the protumor phenotype.

Adult↗

[A case of type 4 gastric cancer with peritoneal dissemination treated with intra-aortic chemotherapy].

A 45-year-old woman was admitted to our hospital because of lower abdominal pain and anorexia. A barium gastrography and gastroscopy showed a type 4 gastric cancer in the upper gastric body. Histologic study on biopsy specimens from the tumor revealed poorly differentiated adenocarcinoma. Computed tomography revealed bilateral hydronephrosis, and barium enema showed diffuse stenosis of the sigmoid colon because of peritoneal dissemination. This patient was treated by intra-aortic infusion therapy with sequential MTX and 5-FU. After five courses of the administration, barium enema revealed reexpansion of the lumen of sigmoid colon with normalization of the tumor markers. The patient was discharged without symptoms. Intra-aortic infusion therapy with sequential MTX and 5-FU was considered an effective treatment for unresectable gastric cancer.

Adenocarcinoma↗

The herbal medicine Dai-Kenchu-Tou stimulates upper gut motility through cholinergic and 5-hydroxytryptamine 3 receptors in conscious dogs.

BACKGROUND: The herbal medicine Dai-Kenchu-To, composed of zanthoxylum fruit, ginseng root, and dried ginger rhizome, is clinically effective for uncomplicated postoperative adhesive intestinal obstruction. We investigated the effect of Dai-Kenchu-To and each ingredient on upper gastrointestinal motility and its mechanism of action. METHODS: Five mongrel dogs were equipped with 4-strain gauge-force transducers on the gastric body, antrum, duodenum, and jejunum to measure contractile activity of the circular muscle. Dai-Kenchu-To (1.5 g) or the separate ingredients zanthoxylum fruit, ginseng root, or dried ginger rhizome (1.0 g each) were administered by bolus into the gastric lumen. The effect of atropine, hexamethonium, phentolamine, propranolol, and ondansetron on intragastric Dai-Kenchu-To-induced contractions was studied. RESULTS: Intragastric Dai-Kenchu-To induced phasic contractions in the antrum, duodenum, and jejunum. Zanthoxylum fruit elicited phasic contractions mainly in the duodenum and jejunum, whereas dried ginger rhizome induced phasic contractions in the antrum. Ginseng root had no effect. Phasic contractions induced by intragastric Dai-Kenchu-To were inhibited by atropine and hexamethonium at all sites, although ondansetron inhibited these contractions in the antrum and duodenum. CONCLUSIONS: Intragastric Dai-Kenchu-To stimulates upper gastrointestinal motility through cholinergic and 5-hydroxytryptamine 3 receptors.

Animals↗

Circulating soluble Fas concentration in breast cancer patients.

Fas/Fas ligand (FasL) system, a major regulator of apoptosis, is involved in cancer cell death induced by the immune system and anticancer drugs. Fas is a cell-surface receptor that exists in two forms, transmembrane and soluble. The former induces apoptosis by ligation of FasL or agonistic anti-Fas antibody, whereas the latter inhibits Fas-mediated apoptosis by neutralizing its ligand. In this study, we examined circulating soluble Fas (sFas) concentration in 118 healthy people, 162 primary and 71 recurrent breast cancer patients by ELISA. In the healthy group, men showed higher sFas concentrations than women (P<0.001). In both sexes, sFas levels increased with age, and the age-matched cutoff value was determined. The median sFas concentration in primary and recurrent cancer patients was 0.815 and 1.510 ng/ml, both of which were higher than in normal female controls (0.580 ng/ml; P = 0.024 and P<0.001, respectively). Among primary cancer patients, although no significant correlation was found between sFas concentration and clinical parameters other than menopausal status, high-sFas patients had a worse prognosis than low-sFas patients for both overall and disease-free survival (P = 0.013 and P = 0.032, respectively). The multivariate analysis confirmed that circulating sFas concentration was an independent prognostic indicator (P = 0.020 for overall survival, P = 0.025 for disease-free survival). We looked at the recurrent cancer patients, and sFas levels were higher in patients with liver metastasis compared with those with other recurrent sites (P = 0.010), and high-sFas patients showed a worse prognosis than low-sFas patients (P = 0.037). Our data demonstrate that, compared with healthy female controls, breast cancer patients, especially those with liver metastases, have higher circulating sFas levels. sFas may be useful once these results are confirmed by larger studies.

Adult↗

Treatment of cholecystoduodenal fistula by laparoscopy.

We describe a patient with cholecystoduodenal fistula treated by a laparoscopic approach. Use of a flexible videoscope, flexible retractor, and endoscopic transecting stapler allows for laparoscopic treatment of cholecystoenteric fistulae.

Biliary Fistula↗

Laparoscopic distal pancreatectomy with preservation of the spleen.

We describe a case of chronic pancreatitis treated by laparoscopic distal pancreatectomy with conservation of the spleen involving the resection of the splenic vessels. A proximal ligation of the splenic artery and vein was performed, followed by transection of the body of the pancreas. Retroperitoneum was dissected to the left by mobilizing the stump of the transected pancreas. The entire distal pancreas was freed posteriorly. The distal splenic artery and vein were ligated and divided individually adjacent to the tail of the pancreas at the hilum of the spleen. The points of this operation were to ligate the splenic artery and vein at both sides of the resected pancreas and to save the spleen with the blood supply continuing through the short gastric vessels and the splenocolic ligament. This operation with splenic preservation is more suitable for a patient who is a candidate for laparoscopic distal pancreatectomy, which will minimize the operation time, preserve the useful immunologic role of the spleen, and obtain the intact resected specimen. Furthermore, this procedure is useful in chronic pancreatitis patients because it avoids the difficult dissection of the posterior pancreas off of the splenic vessels.

Aged↗

Hydroxyl radical-induced cross-linking of thymine and lysine: identification of the primary structure and mechanism.

Hydroxyl radical-induced formation of a cross-link of thymine (Thy) and lysine (Lys) in the gamma-radiolysis of N2O-saturated aqueous solution was studied. A Thy-Lys cross-link (I) of the formal structure that OH radical and 4-carbon-centered Lys radical added respectively to C(5) and C(6) positions of Thy was isolated by a preparative HPLC and identified by a FAB-HRMS. The primary cross-link I was dehydrated by treatment with HCl at 120 degrees C to yield the secondary structure (II) possessing a C(5)-C(6) double bond in the Thy moiety: the latter structure II was reported previously (Dizdaroglu, M.; Gajewski, E. Cancer Res. 1989, 49, 3463-3467). A pulse radiolysis study with a redox titration method indicated that 4-carbon centered Lys radical intermediate was of neutral redox reactivity in contrast to reducing reactivity of 5-hydroxy-5,6-dihydrothymin-6-yl radical intermediate. The cross-link I could be formed by a conventional radical recombination mechanism, but not by an ionic recombination mechanism involving a redox reaction between the radical intermediates.

Cross-Linking Reagents↗

Inhibitory effect of OPC-15161, a component of fungus Thielavia minor, on proliferation and extracellular matrix production of rat cultured hepatic stellate cells.

A component of fungus Thielavia minor, OPC-15161, has been shown to inhibit the proliferation and extracellular matrix production of extracellular matrix-producing mesangial cells in the kidney in vivo. In this study, we examined the effects of OPC-15161 on the proliferation and extracellular matrix production of rat cultured hepatic stellate cells (HSCs). To determine the effect of OPC-15161 on proliferation of HSCs, the cell number and the uptake of [3H]thymidine were investigated in the presence and absence of interleukin-1beta (IL-1beta). IL-1beta significantly increased the uptake of [3H]thymidine in the HSCs, and the addition of OPC-15161 inhibited the uptake in a dose-dependent manner. The cell number of HSCs was also increased by IL-1beta, which was inhibited by OPC-15161. Production of extracellular matrix by OPC-15161 was studied by the production of [3H]-hydroxyproline in the presence and absence of transforming growth factor-beta1 (TGF-beta1). TGF-beta1 significantly increased the production of [3H]-hydroxyproline in the cells, whereas the addition of OPC-15161 inhibited this effect dose dependently. We also investigated the effects of OPC-15161 on Ca2+ mobilization and measured D-myo-inositol 1,4,5-triphosphate (IP3) in the HSCs. IL-1beta induced the increase of intracellular Ca2+ and IP3 concentrations in the HSCs, which were decreased by OPC-15161. Based on these results, we conclude that OPC-1 5161 inhibited the proliferation and production of hydroxyproline in cultured rat HSCs, and thus, it may have a role in prevention of liver fibrosis in vivo.

Animals↗

Noninvasive measurement of pulsatile intracranial pressure using ultrasound.

The present study was designed to validate our noninvasive ultrasonic technique (pulse phase locked loop: PPLL) for measuring intracranial pressure (ICP) waveforms. The technique is based upon detecting skull movements which are known to occur in conjunction with altered intracranial pressure. In bench model studies, PPLL output was highly correlated with changes in the distance between a transducer and a reflecting target (R2 = 0.977). In cadaver studies, transcranial distance was measured while pulsations of ICP (amplitudes of zero to 10 mmHg) were generated by rhythmic injections of saline. Frequency analyses (fast Fourier transformation) clearly demonstrate the correspondence between the PPLL output and ICP pulse cycles. Although theoretically there is a slight possibility that changes in the PPLL output are caused by changes in the ultrasonic velocity of brain tissue, the decreased amplitudes of the PPLL output as the external compression of the head was increased indicates that the PPLL output represents substantial skull movement associated with altered ICP. In conclusion, the ultrasound device has sufficient sensitivity to detect transcranial pulsations which occur in association with the cardiac cycle. Our technique makes it possible to analyze ICP waveforms noninvasively and will be helpful for understanding intracranial compliance and cerebrovascular circulation.

Brain↗

[Acute ventricular septal perforation in a patient with autoimmune hemolytic anemia].

A 71-year-old woman with autoimmune hemolytic anemia underwent an emergency endocardial patch repair for ventricular septal perforation after acute myocardial infarction. Use of washed red blood cells was effective in averting hemolytic crisis throughout perioperative period. In spite of improvement of her hemodynamics, liver dysfunction which had been present preoperatively deteriorated after the operation. Finally she died of hepatic failure on the 21st postoperative day. Deterioration of liver function could not be associated with autoimmune hemolytic anemia. To date, little information is available concerning the influence of cardiopulmonary bypass on hemolysis in patients with autoimmune hemolytic anemia. Therefore, prudent management and use of washed red blood cells transfusion would prevent hemolytic aggravation even in open heart surgery.

Acute Disease↗

Prediction of vertebral artery compression in patients with hemifacial spasm using oblique sagittal MR imaging.

To discriminate between the various compressing vessels of the facial nerves in patients with hemifacial spasm, pre-operative oblique sagittal gradient-echo MR imaging was performed. Forty-two patients underwent pre-operative MR imaging and microvascular decompression. The MR images were divided according to findings into three groups as follows: Group A, a thick and/or long high-intensity line along the root exit zone (REZ) of the facial nerve; Group B, a thin and/or short high-intensity line along the REZ; and Group C, an unreliable image around the REZ. Fifteen images were classified as Group A, 19 as Group B, and 8 as Group C. In Group A, vertebral artery (VA) compression was confirmed intra-operatively in 12 cases and posterior inferior cerebellar artery (PICA) or anterior inferior cerebellar artery (AICA) compression in 3. In Group B, PICA or AICA compression was confirmed intra-operatively in all cases. In Group C, PICA or AICA compression was confirmed intra-operatively in 7 cases and no compression in one. In all cases of VA compression of the facial nerve, the oblique sagittal gradient-echo images demonstrated a thick and/or long high intensity line along the REZ. Oblique sagittal gradient-echo MR imaging is a useful preoperative planning aid, which can predict the possibility of VA compression prior to microvascular decompression for hemifacial spasm.

Facial Nerve↗

Repair of left ventricular diverticulum with ventricular bigeminy in an infant.

Surgical repair of left ventricular diverticulum usually is not required in infancy even though it combines with other anomalies. In addition to prevention of rupture of the diverticulum and thrombus formation, treatment of combined ventricular tachycardia is thought to be an indication for resection of the diverticulum. We describe a successful repair performed by excising the isolated left ventricular diverticulum under cardiopulmonary bypass in a 9-day-old infant. The combined ventricular bigeminy has disappeared 9 months after the operation.

Cardiopulmonary Bypass↗

Off-pump coronary bypass using interposed radial artery graft.

We describe a patient with severely diseased ascending aorta and small internal mammary arteries, who underwent off-pump coronary artery bypass to the left anterior descending coronary artery and right coronary artery using composite arterial grafts consisting of the pedicled proximal internal mammary artery and interposed radial artery graft. The interposed radial artery graft provides advantages, such as making coronary anastomosis on the beating heart easier and to increasing the flow potentiality of the internal mammary artery.

Aged↗

Influence of FK506 on experimental atherosclerosis in cholesterol-fed rabbits.

To investigate the role of activated T lymphocytes in the formation of atherosclerotic lesions, we studied the influence of FK506, an immunosuppressant, on the development of atherosclerosis in cholesterol-fed rabbits. New Zealand White rabbits fed on a 1.5% cholesterol diet were administered FK506 at 0.05 mg/kg (n = 12), 0.1 mg/kg (n = 12) or isotonic saline (as the control, n = 12) intramuscularly three times a week for 12 weeks. Although FK506 treatment did not affect plasma lipid levels, it caused an increase in the development of atherosclerotic lesions in a dose-dependent manner. Immunohistochemical analysis of the aorta after 8 weeks on the diet revealed that the ratio of T lymphocytes to the total number of cells in the plaques decreased significantly in the FK506 treated rabbits compared to the control rabbits. In culture, FK506 did not affect smooth muscle cell proliferation and cholesteryl ester formation in the macrophages. In contrast, culture medium from lymphocytes stimulated by concanavalin A decreased the accumulation of cholesteryl ester in the macrophages. This effect was inhibited by the culture medium in the presence of FK506. These findings suggest that activated T lymphocytes may inhibit intracellular cholesterol accumulation in atherosclerotic plaque.

Animals↗