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Biomedical subjects

K Tanoue

Publications and source records attributed to K Tanoue.

At least 91 records · Page 5Linked to original sources
PubMed1991

Successful surgical treatment of hepatocellular carcinoma invading into biliary tree.

A 41-year-old woman was admitted to hospital with obstructive jaundice. Computed tomography showed a large mass in the right hepatic lobe and marked dilatation of the biliary tree in the left lateral segment of the liver. Angiography showed evidence of neovascularity. Percutaneous transhepatic cholangiography revealed complete obstruction of the common bile duct just below the bifurcation. The serum level of alpha-fetoprotein on admission was 1,080,000 ng/ml. These findings suggested to us a primary hepatocellular carcinoma invading the intrahepatic bile duct. Extended right lobectomy and hepaticojejunostomy for bile drainage was carried out. The patient is doing well 3 years after surgery. Hepatocellular carcinoma (HCC) invading to the portal vein is not so rare, but invasion into the bile duct is much less common. In 1947, Mallory described a single case of HCC invading the gallbladder and obstructing extrahepatic bile ducts. In 1975, Lin termed this HCC "Icteric type hepatoma". The incidence of such HCC in Japan was reported to be 1.9-9%. Obstructive jaundice is a clinical manifestation of the terminal stage in HCC. We describe here our treatment of a woman with HCC invading the common bile duct. Right extended lobectomy and reconstruction of hepaticojejunostomy were effective.

Adult↗
PubMed1991

A rat model of esophageal varices.

We have developed a new method for inducing portal hypertension and esophageal varices in rats--partial ligation of the portal vein after devascularization of the circumference of the left renal vein and complete ligation of the portal vein on the fifth day thereafter. Thirty rats were separated into groups of 10, control (sham operation), complete portal ligation only and complete portal ligation plus devascularization. Two weeks after the surgery, the presence of esophageal varices in rats with complete portal ligation plus devascularization was confirmed by portography and by the histological findings. The diameter (mean +/- SD) of the submucosal veins of the lower esophagus in the complete portal ligation plus devascularization group (219.4 +/- 86.6 microns) was significantly larger than that in the complete portal ligation group (99.8 +/- 53.4 microns) or in the control group (30.5 +/- 16.6 microns) (p less than 0.01). Vascular structures of the lower esophagus closely resembled those in humans with esophageal varices. This new technique is simple, rapid and reliable, and application can be made to various experimental studies on portal hypertension.

Animals↗
PubMed1990

Secondary signals mediated by GPIIb/IIIa in thrombin-activated platelets.

We have previously found that stimulation of aequorin-loaded platelets by thrombin produced a two-peaked increase in intracellular free calcium concentration ([Ca2+]i), and the development of the second peak of [Ca2+]i was closely related with the aggregation. In this report, we studied the interrelationship between the GPIIb/IIIa complex, aggregation, cytoskeletons and [Ca2+]i of platelets. The pretreatment of the platelets with dihydrocytochalasin B (4 microM), an actin polymerization inhibitor, did not inhibit aggregation and TXB2 production, but did inhibit both actin polymerization and the second peak of [Ca2+]i increase induced by thrombin, suggesting that actin polymerization and the second peak of [Ca2+]i are interrelated. GRGDSP (100 microM), a synthetic anti-adhesive peptide, has already been reported to inhibit platelet aggregation and the second peak of [Ca2+]i induced by thrombin. It also inhibited actin polymerization and TXB2 production, suggesting that aggregation was important for not only the generation of the second peak of [Ca2+]i but also for actin polymerization and TXB2 production. PGI2 (5 nM) did not abolish but only delayed aggregation, TXB2 production, actin polymerization and the second peak of [Ca2+]i increase. These findings suggest that the secondary signals are caused by aggregation (fibrinogen-binding to the GPIIb/IIIa) in thrombin-aggregated platelets, which results in the TXA2 production and the secondary peak of [Ca2+]i increase, and the latter was dependent on actin polymerization.

Actins↗
PubMed1990

Localization of von Willebrand factor and thrombin-interactive domains on human platelet glycoprotein Ib.

Platelet membrane glycoprotein Ib (GPIb) functions as receptors for thrombin and von Willebrand factor (vWF) in the presence of ristocetin. To precisely locate the domains on GPIb interacting with vWF and thrombin, we prepared several peptides that have amino acid sequences analogous to that of the GPIb alpha-chain and examined their effects on ristocetin-induced (vWF-dependent) and thrombin-induced platelet aggregations. A peptide extending from residues Asp235 to Lys262 showed the strongest inhibitory effect on ristocetin-induced platelet agglutination, and a group of overlapping peptides composed of 24-28 amino acid residues representing sequences extending from Phe216 to Asp274 was found to inhibit platelet aggregation induced by thrombin. Other peptides did not inhibit platelet aggregations. Moreover, the binding to platelets of the monoclonal anti-GPIb antibody (TM60) which had been shown to inhibit both ristocetin- and thrombin-induced platelet aggregations was strongly inhibited by a peptide extending from Asp249 to Asp274. These data demonstrate that the vWF-binding domain exists in a small region between residues Asp235 and Lys262; the thrombin-interacting domain, in contrast, is located between residues Phe216 and Ala274, with a possible center of interaction in the sequence from Phe216 to Thr240 on the GPIb alpha-chain, and thrombin binding requires a relatively strict conformation in this domain.

Antibodies, Monoclonal↗
PubMed1990

Localization of adhesive proteins in two newly subdivided zones in electron-lucent matrix of human platelet alpha-granules.

Platelet alpha-granules have been reported to consist of two zones, nucleoid and electron-lucent matrix, with different densities under electron microscopy. When washed human platelets were prepared by a rapid freeze-substitution method using liquid helium, we found that the electron-lucent matrix could be further subclassified into two zones having different densities: the intermediate and the light zones. The light zone was located at the periphery opposite the most dense nucleoid and contained several tubular structures with diameters of about 20 nm. The intermediate zone often laid between the nucleoid and light zone. By careful inspection, intermediate and light zones could even be identified in the platelets embedded in Lowicryl K4M, which where then used to localize several adhesive proteins in these two zone by immunocytochemical studies using the respective polyclonal antibodies. Fibrinogen, thrombospondin, and fibronectin were detected only in the intermediate zone. In contrast, von Willebrand factor (vWF) was localized only in the light zone, suggesting an association between vWF and the tubular structures in the light zone. In the nucleoid, none of these adhesive proteins were detected. Glycoprotein IIb/IIIa, a receptor for these adhesive proteins on the platelet surface, was detected not only on the outer surface of the cell membranes but also on the inner surface of the alpha-granule membrane. These data indicate that two zones with different densities in electron-lucent matrix and functions exist in the platelet alpha-granules.

Blood Coagulation Factors↗
PubMed1990

Localization of fibrinogen during ADP- or thrombin-induced aggregation of washed rabbit platelets.

In contrast to human platelets, which aggregate poorly in response to ADP unless fibrinogen is present in the external medium, washed rabbit platelets form large aggregates in response to ADP without fibrinogen in the suspending medium. Addition of fibrinogen to the suspending medium of rabbit platelets frequently has little or no effect on the extent of ADP-induced platelet aggregation. We examined washed rabbit platelets by immunocytochemistry during ADP-induced aggregation and deaggregation and during thrombin-induced aggregation when the external medium did not contain added fibrinogen to determine if (a) fibrinogen was expressed on the surface of rabbit platelets that could support aggregation when the platelets were stimulated, or (b) fibrinogen secreted from the alpha granules supports platelet aggregation. Glutaraldehyde-fixed samples were prepared at different times after addition of ADP or thrombin, embedded in Lowicryl K4M, sectioned, incubated with sheep anti-rabbit fibrinogen, washed, reacted with gold-labeled anti-sheep IgG, and prepared for electron microscopy. The alpha granules of rabbit platelets were heavily labeled with immunogold; the platelet membrane was not labeled. During platelet aggregation and deaggregation in response to ADP, fibrinogen was not detectable on the platelet surface. In response to thrombin, large aggregates formed before fibrinogen was secreted from the alpha granules; fibrinogen was detectable focally at sites of granule discharge by 30-60 sec and fibrin formed by 3 min. Therefore, stimulated washed rabbit platelets can adhere to each other without large amounts of fibrinogen taking part in the close platelet-to-platelet contact, since aggregation occurs before detectable secretion, and large areas where the platelets are in contact are devoid of fibrinogen between the adherent membranes. Adhesion mechanisms not involving fibrinogen may support the aggregation of washed rabbit platelets.

Adenosine Diphosphate↗
PubMed1989

Neutralizing monoclonal antibody specific for alpha-bungarotoxin: preparation and characterization of the antibody, and localization of antigenic region of alpha-bungarotoxin.

We prepared an alpha-bungarotoxin-specific monoclonal antibody that neutralizes the biological activity of the toxin in vivo. The antigenic determinant combining specifically with this antibody was determined on the basis of cross-reaction experiments using three other long neurotoxins and peptide fragments of alpha-bungarotoxin. The antigenic determinant was located on the peptide fragment containing S34-S35-R36-G37-K38, which forms a part of the expected site that binds to the acetylcholine receptor proteins.

Amino Acid Sequence↗
PubMed1989

Calcium ions and the conformation of glycoprotein IIIa that is essential fibrinogen binding to platelets: analysis by a new monoclonal anti-GP IIIa antibody, TM83.

Using a newly developed murine monoclonal antibody (MoAb), TM83, against glycoprotein IIIa (GPIIIa) of human platelets, we have analyzed the relationship between platelet fibrinogen binding and conformational changes in GPIIIa under EDTA treatment. Crossed radioimmunoelectrophoresis demonstrated that TM83 reacted with only the GPIIb/IIIa complex but also with GPIIIa alone. TM83 dose-dependently inhibited both thrombin-induced aggregation and fibrinogen binding to activated platelets. 125I-TM83 bound to an average of 20,890 +/- 1,600 (mean +/- SE, n = 12) sites on a resting platelet, with Kd = 2.06 nmol/L in the presence of Ca2+. When platelets were incubated in 2 nmol/L EDTA-containing medium, pH 7.4, at 22 degrees C for 30 minutes, binding of TM83 decreased to 70% of the control level. The decreased binding was fully recovered to the control level when the platelets were resuspended in Ca2+-containing medium. These platelets retained their aggregability. In contrast, when platelets were incubated in 2 mmol/L EDTA-containing medium, pH 7.4, at 37 degrees C for 30 minutes, TM83 binding to the platelets markedly decreased to 7% of the control, which could only be recovered to 40% of the control by replacing the medium with calcium-containing medium; these platelets lacked thrombin-induced aggregability. These findings suggest that the epitope for TM83 may be located near the fibrinogen binding site on GPIIIa and that its conformation is dependent on Ca2+ ions.

Antibodies, Monoclonal↗
PubMed1989

Autoantibody against platelet glycoprotein IIb/IIIa in a patient with non-Hodgkin's lymphoma.

An autoantibody to platelet glycoprotein (GP) II b/III a was produced in a 38 year-old woman who had a previous history of the malignant lymphoma of the stomach. The aggregations of the patient's platelets showed losses of the primary waves in response to ADP and epinephrine and marked hypoaggregation in response to collagen, while agglutination by ristocetin was normal. Crossed immuno-electrophoresis (CIE) of her platelets solubilized by 1% Triton X-100 revealed an abnormal biphasic precipitate line of GP II b/III a complex. Nine months later, she developed severe thrombocytopenia along with a relapse of the lymphoma in the cervical lymph nodes. The patient's IgG, which was collected during her thrombocytopenic period and purified, inhibited ADP-, epinephrine- and collagen-induced aggregations of normal platelets. In CIE, the 125I-labelled IgG of the patient, inserted into the intermediate gel, was incorporated into the precipitation line of the GP II b/III a complex of normal platelets. Radiation treatment to the cervical lymph nodes dramatically normalized both the function and the count of the patient's platelets. From these findings, it is suggested that an autoantibody to the GP II b and/or III a was produced by the lymphoma cells.

Adult↗
PubMed1989

Involvement of platelet membrane glycoprotein Ib and glycoprotein IIb/IIIa complex in thrombin-dependent and -independent platelet aggregations induced by tumor cells.

Involvement of platelet membrane glycoproteins (GP) in interactions between platelets and tumor cells was studied by using two human tumor cell lines and two monoclonal antibodies against platelet membrane GP. HMV-I cells derived from vaginal melanoma induced platelet aggregation in heparinized plasma, which was not followed by coagulation. M7609 cells derived from colon adenocarcinoma also induced platelet aggregation in heparinized plasma, which, on the contrary, was followed by coagulation. Aggregating activities of the HMV-I cells were abolished by pretreatment with neuraminidase or trypsin, but M7609 activity was not labile to these enzymes. Aggregations induced by M7609 were inhibited by hirudin or MD805, while those by HMV-I were not. M7609 cells dose dependently shortened the recalcification time of normal as well as Factor IX-deficient plasmas, while they were not effective in shortening the time of Factor II- or Factor VII-deficient plasmas. The procoagulant activity of HMV-I cells was 1000 times less than M7609 on the basis of cell numbers. When human platelets were preincubated with monoclonal anti-GPIb or anti-GPIIb/IIIa complex antibodies, neither cell line could cause aggregations. These findings suggest that both GPIb and the GPIIb/IIIa complex on the platelet surface are involved in the thrombin-dependent and -independent platelet aggregations induced by tumor cells.

Adenocarcinoma↗
PubMed1989

Ca2+ influx and platelet membrane glycoproteins.

When aequorin-loaded platelets were stimulated with thrombin, the luminescence of aequorin showed two peaks. From experiments with 1 mM external Ca2+ or 1 mM EGTA, both one-half of the first peak and the entire second peak reflected the influx of Ca2+ from the external medium, and the remaining half of the first peak reflected the mobilization of Ca2+ from its storage site. A monoclonal antibody (TM83), that recognizes the GPIIb/IIIa complex which has binding sites for fibrinogen, and synthetic peptide GRGDSP are known to inhibit fibrinogen binding and platelet aggregation. Both of them eliminated the second peak of intracellular free calcium. Similar effects were observed during activation by collagen, but not by TPA. Also dihydrocytochalasin B inhibited the second peak of Ca2+ influx by thrombin, suggesting that the signal, which was caused by fibrinogen-binding to GPIIb/IIIa (aggregation) in thrombin-activated platelets, is transferred to the inner sites of GPIIb/IIIa complex and induces the cytoskeletal reorganization such as actin polymerization. This in turn, induces the secondary increase in [Ca2+] i of platelets. It is interesting that ticlopidine inhibited the Ca2+ influx through the GPIIb/IIIa complex. This result suggests the importance of such kinds of antiplatelet drugs to prevent thrombus formation.

Blood Platelets↗
PubMed1988

Autoradiographic observation of platelets in cerebrovascular injuries induced by arachidonic acid and its prevention by ticlopidine.

The behavior of circulating 111In-labeled platelets in cerebrovascular injuries induced by arachidonic acid injection was studied. Fourteen rabbits were pretreated with the antiplatelet agent ticlopidine, and 10 rabbits were used for controls. Arachidonic acid (AA, 0.7 mg/kg) was injected into the internal carotid artery. Prior to the injection, platelets labeled with 111Inoxine were injected for autoradiography of the brain. Evans blue was injected as an indicator of blood-brain barrier disturbance. Nine control animals showed marked blue staining, and one showed slight blue staining. Seven out of the 14 pretreated animals showed slight or no staining, while 7 showed intensive staining. The distributions of the blue staining and the radioactivity showed high correlation. In the rabbits whose platelet aggregability was depressed by ticlopidine, lower blue staining as well as lower radioactivity was observed. Our findings suggest that activated platelets have an important role in the genesis of cerebrovascular injuries.

Animals↗
PubMed1988

Platelet adenine nucleotides in patients with primary glomerular disease.

Total platelet adenosine diphosphate (ADP) and adenosine triphosphate (ATP) contents and amounts of ADP and ATP released from platelets by 3 micrograms/ml of collagen were studied in 20 patients with primary glomerular disease (PGD) to examine the metabolism of these platelet substances in the disease. ADP and ATP were measured by Holmsen's firefly luciferase method. The patients had significantly lower total platelet ATP compared with controls and total platelet ATP was significantly lower in nephrotic patients than in patients whose serum albumin levels were normal. Releasable platelet ADP and ATP were both significantly decreased in patients. Releasable ADP: total ADP ratio and releasable ATP: total ATP ratio were both significantly lower in patients' platelets than in normal platelets. There was no significant difference in platelet counts between patients and controls. Platelet aggregation induced by ADP and adrenaline were significantly higher in patients compared with controls. We conclude that total ATP content and the amount of ADP and ATP released by collagen are decreased in PGD patients' platelets.

Adenosine Diphosphate↗
PubMed1988

Immunocytochemical localization of fibrinogen on washed human platelets. Lack of requirement for fibrinogen during adenosine diphosphate-induced responses and enhanced fibrinogen binding in a medium with low calcium levels.

The association of fibrinogen with washed human platelets was examined by immunocytochemistry during aggregation induced by adenosine diphosphate (ADP) and during deaggregation. The platelets were suspended either in a medium containing 2 mmol/L Ca2+ or in a medium containing no added Ca2+ (20 mumol/L Ca2+). Platelets were fixed at several times during aggregation and deaggregation, embedded in Lowicryl K4M, sectioned, incubated with goat antihuman fibrinogen, washed, reacted with gold-labeled antigoat IgG, and prepared for electron microscopy. To determine whether the method detected fibrinogen associated with the platelets, the platelets were pretreated with chymotrypsin (10 U/mL) and aggregated by fibrinogen; gold particles were apparent not only in the alpha granules but on the platelet surface and between adherent platelets as well. In the medium with 2 mmol/L Ca2+, ADP caused extensive aggregation of normal platelets in the presence of fibrinogen (0.4 mg/mL), and gold particles were evident between the adherent platelets and on the platelet surface; when the platelets deaggregated, gold was no longer present on the surface. In a medium without added Ca2+, ADP caused extensive aggregation in the presence of fibrinogen, and large numbers of gold particles were on the platelet surface and even more between adherent platelets. In this medium, the platelets did not deaggregate, and by five minutes, the granules appeared to be swollen or fused. In the absence of external fibrinogen, ADP caused the formation of small aggregates, and fibrinogen was not detected between adherent platelets. Thus, the association of fibrinogen with the platelet surface enhances platelet aggregation but is not essential for the ADP-induced formation of small aggregates. The association of fibrinogen with platelets is greater under conditions in which platelets release their granule contents and do not deaggregate because both endogenous and exogenous fibrinogen take part in aggregation.

Adenosine Diphosphate↗
PubMed1988

Thrombin-induced membrane depolarization of platelets and its inhibition by cetiedil.

When 50 microM cetiedil alone was added to a platelet suspension, increase in Na+ content, decrease in K+ content, and depolarization of platelet membrane were observed without change in the intracellular concentration of free Ca2+ ([Ca2+]1) or in the morphology of platelets. The cetiedil-induced depolarization was attenuated by the reduction of extracellular sodium concentration, while sodium transport inhibitors such as procaine and tetrodotoxin failed to modify the depolarization. On the other hand, thrombin caused such changes in platelets as increases in Na+ content, 22Na space and [Ca2+]1, decrease in K+ content, and membrane depolarization. All these changes caused by thrombin were inhibited by cetiedil. It is suggested that cetiedil brought the increased ion transport and subsequent partial depolarization, which might lead to modification of the reaction of platelet membrane induced by thrombin.

Azepines↗