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Biomedical subjects

K Tanoue

Publications and source records attributed to K Tanoue.

At least 55 records · Page 3Linked to original sources
PubMed1995

Platelets with 10% of the normal amount of glycoprotein VI have an impaired response to collagen that results in a mild bleeding tendency.

Platelet glycoprotein VI (GPVI), a 62kD membrane protein, has been identified as one of the platelet receptors for collagen, since GPVI-deficient platelets exhibit abnormal responses to collagen and an abnormal bleeding tendency. We report a female patient with a mild bleeding history whose platelets expressed 10% GPVI of normal platelets. Shape change, aggregation and ATP release of the patient's platelets were completely absent in response to 1-5 micrograms/ml collagen but present normally in response to ADP and Ca2+ ionophore A23187. Adhesion of the patient's platelets to coated collagen was mildly affected (40-60% of normal platelets) in spite of only 10% expression of GPVI. Flow cytometrical studies revealed that the patient's platelets expressed normal amounts of the GPIa/IIa complex. These results suggest that platelet GPVI is less involved in adhesion to collagen than shape change and aggregation induced by collagen.

Adenosine Diphosphate↗
PubMed1995

Cellular and molecular mechanisms of gastric ulcer healing. Is the quality of mucosal scar affected by treatment?

BACKGROUND: Ulcer healing, i.e. the reconstruction of the mucosal architecture, is an active process of filling the mucosal defect with proliferating and migrating epithelial cells and connective tissue. METHODS: This article represents a summary of histologic and ultrastructural assessment of the cellular events occurring during healing of experimental gastric ulcer. RESULTS: Mucosa adjacent to the ulcer crater forms a 'healing' zone. The gastric glands in this zone dilate and the epithelial cells lining these glands de-differentiate, express epidermal growth factor receptor, and proliferate. The latter is the result of local activation of genes encoding for EGF and its receptors. At the ulcer margin, proliferating and dividing epithelial cells migrate onto the granulation tissue to cover (re-epithelialize) the ulcer and bud into granulation tissue to reconstruct glandular structures within the ulcer scar. Re-epithelialization and reconstruction of epithelial structures is under control of epidermal growth factor (EGF) and related peptides which are produced locally by regenerating cells. Under control of fibroblast growth factors, granulation connective tissue grows extensively supplying (a) microvessels for restoration of the microvascular network and (b) connective tissue cells for restoration of the lamina propria within the mucosal scar. The final outcome of the healing process reflects a dynamic interaction between the epithelial component for the 'healing' zone at the ulcer margin and the connective tissue component (including microvessels) originating from the granulation tissue. Depending on these interactions, mucosal scar can be of good quality (restoration close to normal) or poor quality. While a number of pharmacologic agents affect gastric ulcer healing, it is unknown whether these drugs affect the quality of mucosal architecture reconstruction. In previous studies, we demonstrated that sucralfate exerts a trophic effect on gastric mucosa and, compared with omeprazole, improves the quality of restored mucosal structures within the scar of healed gastric ulcers. In the most recent studies, we demonstrated that treatment with sucralfate activates genes for EGF, bFGF, and their receptors, significantly increasing (vs placebo and omeprazole) expression of EGF and its receptor in ulcerated gastric mucosa. CONCLUSION: Thus, the superior quality of ulcer healing by sucralfate (versus omeprazole) is most likely based on its capacity to induce and stimulate expression of EGF, bFGF, and their receptors.

Animals↗
PubMed1995

Prognostic significance of hepatic vein waveform by Doppler ultrasonography in cirrhotic patients with portal hypertension.

OBJECTIVE: We prospectively evaluated the prognostic value of the flat hepatic vein waveform, measured by Doppler ultrasound, in cirrhotic patients with portal hypertension. METHODS: The Doppler pattern of right and left hepatic veins in a series of 120 consecutive cirrhotic patients with portal hypertension but without hepatocellular carcinoma was examined, together with clinical and biochemical parameters. RESULTS: Flat waveform of the right hepatic vein was recognized in nine patients and that of the left hepatic vein was seen in 13. After a mean follow-up of 13.6 +/- 9.7 months, 17 patients died, all from liver failure. In the univariate analysis, variable significantly associated with the duration of survival were age, etiology of the liver cirrhosis, upper gastrointestinal bleeding after start of the study, Child-Pugh score, ascites, encephalopathy, prothrombin index, bilirubin, albumin, and flat Doppler waveform in the right and left hepatic veins. Multivariate analysis showed that flat Doppler waveform in the right hepatic vein, bilirubin, and prothrombin index were independently related to survival. CONCLUSIONS: The prognostic accuracy in cases of cirrhosis with portal hypertension is significantly improved with acquisition of information obtained from hepatic vein waveform by Doppler ultrasound.

Adult↗
PubMed1995

Recurrent rectal bleeding from portal hypertensive colopathy in a patient with hemorrhoids.

In a 62-yr-old woman who complained of recurrent rectal bleeding, hemorrhoids with mucosal prolapse were found. Virus-related cirrhosis also was present. Colonoscopy revealed spontaneous bleeding from two rectal ectasias (portal hypertensive colopathy) located 9 cm from the anus. Endoscopic hemostasis was achieved with a heater probe, and there has been no recurrent hemorrhage. Colonoscopy is important in ruling out hemorrhage from portal hypertensive colopathy when rectal bleeding occurs in the presence of portal hypertension.

Angiodysplasia↗
PubMed1995

Portal venous blood flow unaltered in cirrhotic patients given metoclopramide injections.

The effects of metoclopramide on blood flow in portal and left gastric veins and cardiovascular haemodynamic variables were studied in 30 patients with both liver cirrhosis and oesophageal varices. Measurements were made under baseline conditions and after the intravenous administration of saline, metoclopramide 10 mg, and metoclopramide 20 mg. Portal haemodynamics, including portal and left gastric veins were studied using pulsed Doppler ultrasound. In all groups, the blood flow and the maximal diameter of portal and left gastric veins, and heart rate remained unchanged. However, metoclopramide 10 mg significantly decreased the mean arterial pressure 15 minutes after administration while metoclopramide 20 mg decreased it 30, 45 and 60 minutes after administration. Therefore, metoclopramide apparently does not alter the blood flow of the portal venous system in these patients.

Adult↗
PubMed1995

[Shear-induced platelet aggregation (SIPA) monitoring of hemostatic effect during platelet transfusion in a patient with Glanzmann's thrombasthenia: a comparison between SIPA and conventional platelet aggregation].

Shear-induced platelet aggregation (SIPA) in a patient with Glanzmann's thrombasthenia was examined during platelet infusion therapy. Prior to platelet infusion, SIPA measured with the modified cone-and-plate type viscometer, as well as ADP-and collagen-induced platelet aggregation measured with the conventional platelet aggregometer, were absent. The patient's SIPA after multiple infusions of platelet, in parallel with the bleeding time and the clinical hemostatic effect, improved to the normal level, while ADP-and collagen-induced platelet aggregation remained abnormal. These observations imply that SIPA is physiologically more relevant than the conventional agonist-induced platelet aggregometry in this type of the disease.

Adenosine Diphosphate↗
PubMed1995

Heterogeneous expression of glycoprotein Ib, IX and V in platelets from two patients with Bernard-Soulier syndrome caused by different genetic abnormalities.

Bernard-Soulier syndrome (BSS) is a rare inherited bleeding disorder, which is caused by deficiency or decrease of the platelet GPIb/IX/V complex. Analysis of two patients with BSS by flow cytometry of the blood revealed different expression patterns of the components of the GPIb/IX/V complex. In case 1, GPIX was completely absent but residual amounts of GPIb alpha and GPV were detectable; in case 2, GPIb alpha was completely absent. We amplified the coding regions of GPIb alpha, GPIb beta, GPV, and GPIX from the patients' genomic DNA with the polymerase chain reaction (PCR) and sequenced the PCR products. in case 1, we identified a point mutation in the GPIX coding region that changes the codon for tryptophan-126 (TGG) to a nonsense codon (TGA). In case 2, we found a deletion of nucleotide within seven adenine repeats at the position of 1932 to 1938 in the coding region of GPIb alpha, which causes a frame shift that results in 58 altered amino acids and a premature stop codon. These genetic changes alter the transmembrane domain of GPIX or GPIb alpha and, therefore, would prevent proper insertion of the proteins in the plasma membrane. Thus, abnormality of a single component protein (GPIX or GPIb alpha) alters the assembly of the GPIb/IX/V complex and causes heterogeneous surface expression of GPIb alpha, GPV and GPIX.

Adult↗
PubMed1995

The role of extracellular matrix in injury to gastric mucosa by indomethacin.

The extracellular matrix components fibronectin, collagen IV, and laminin provide structural support for the gastric mucosal cells and influence cell migration, attachment, differentiation, and proliferation. Because little is known about the effect of indomethacin on the extracellular matrix, we studied the expression and distribution of extracellular matrix components in the gastric mucosa before and sequentially during indomethacin injury. A total of 32 male Sprague-Dawley rats were treated with placebo or indomethacin 100 mg intraperitoneally. One, 4, and 18 h later, stomachs were excised and gastric specimens were immunostained with specific antibodies against fibronectin (FN), collagen IV (CIV), laminin (LM), fibronectin receptor (FNR), and vimentin (VM). Gross necrosis, quantitative histology, and expression of FN, CIV, LM, FNR, and VM were analyzed using a videoimage analysis system. In the mucosa treated with indomethacin, the expression of VM and LM was decreased by 54% (p < 0.01) and 52% (p < 0.01), respectively, within 1 h vs. control mucosa. The former reflected damage to endothelial cells. Expression of FN, FNR, and CIV was decreased by 50, 25, and 50%, respectively, at 1 h after indomethacin, reflecting significant damage to the extracellular matrix. However, at 1 h, no gross necrosis and no histologic damage were seen in the gastric mucosa. We conclude that expression of extracellular matrix components in the gastric mucosa is significantly reduced during indomethacin injury and that damage to extracellular matrix and microvascular endothelium precedes injury of glandular epithelial cells.

Animals↗
PubMed1994

Platelet glycoprotein IV (CD36) deficiency is associated with the absence (type I) or the presence (type II) of glycoprotein IV on monocytes.

Platelet membrane glycoprotein (GP) IV (also called CD36 and GPIIb) deficiency is associated with N(aka)-negative platelets. Using flow-cytometric analysis of cells stained with the monoclonal anti-GPIV antibody OKM5, we have studied the expression of GPIV on the monocytes from 16 healthy Japanese individuals whose platelets were deficient in GPIV. GPIV was absent on the surface of monocytes from 2 platelet GPIV-negative donors (type I), whereas it was present on the monocytes from the remaining 14 platelet GPIV-negative donors (type II). The fluorescent intensity of OKM5-stained type II monocytes was significantly (P < .05) lower than that of normal monocytes derived from platelet GPIV-positive donors, suggesting that the expression of GPIV on the type II monocytes is also abnormally regulated as compared with that on normal monocytes. OKM5 induced an oxidative burst in the type II monocytes as well as in the normal monocytes, but it failed to induce it in the type I monocytes. Because the 2 individuals with the type I deficiency have been healthy and exhibited no immunologic problems, GPIV appears to be not essential for the normal physiologic functions of monocytes. An anti-GPIV antibody was detected in the serum from one of the type I GPIV-deficient women, who had never received any blood transfusions but had given birth to three apparently healthy children. These results suggest that type I GPIV-deficient individuals may be at risk of developing an anti-GPIV isoantibody upon blood transfusion or pregnancy.

Antibodies↗
PubMed1994

Portal and gastric mucosal hemodynamics in cirrhotic patients with portal-hypertensive gastropathy.

Controversy exists as to the nature of gastric perfusion in portal-hypertensive gastropathy. To investigate portal hemodynamics and gastric mucosal perfusion in cirrhotic patients with and without portal-hypertensive gastropathy, we subjected 56 cirrhotic patients with portal hypertension to portal vein catheterization, pneumatic pressure sensor technique, duplex sonography and laser Doppler flowmetry. Thirteen patients had portal-hypertensive gastropathy: In 10 it was mild, and in 3 it was severe. The presence of portal-hypertensive gastropathy seemed to be independent of age, sex, cause of cirrhosis or grade of esophageal varices. Portal venous pressure, esophageal variceal pressure, portal venous flow and congestion index in patients with portal-hypertensive gastropathy were not significantly different from the values in those without portal-hypertensive gastropathy. However, portal-variceal pressure gradient (subtracting esophageal variceal pressure from portal venous pressure) (p < 0.01) and the incidence of palisading-type esophageal varices on portography (p < 0.05) was increased in patients with portal-hypertensive gastropathy significantly more than in those without portal-hypertensive gastropathy. In the fundus, gastric mucosal blood flow was significantly higher in patients with portal-hypertensive gastropathy than in those without portal-hypertensive gastropathy, whereas in the corpus and the antrum the values were not significantly different. We suggest that the mucosa of the upper stomach in patients with portal-hypertensive gastropathy is congestive and highly perfused. The pathogenesis of portal-hypertensive gastropathy may be related to both congestion and hyperemia in the upper stomach.

Adult↗
PubMed1994

Metoclopramide inhibits development of esophageal varices in rat model.

We examined the preventive effect of metoclopramide on the development of esophageal varices in a rat model. Thirty rats were divided into three groups: metoclopramide (7.5 mg/kg twice a day, intraperitoneally), control group I (saline 2 ml/kg twice a day, intraperitoneally), and control group II (incised lower esophageal sphincter and metoclopramide 7.5 mg/kg twice a day, intraperitoneally). On the 14th postoperative day, lower esophageal sphincter pressure in the metoclopramide group (8.6 +/- 1.4 cm H2O) increased more than in the control groups (5.4 +/- 0.5, 5.0 +/- 0.5 cm H2O, P < 0.01). Development of small collateral vessels from the spleen to the retroperitoneum was evident only in the metoclopramide group, as seen on the portography (P < 0.01). Histologically, the variceal area of the horizontal cross section of the esophagus in the metoclopramide group (0.62 +/- 0.26 mm2) was significantly smaller than in the controls (2.67 +/- 0.95, 2.78 +/- 0.82 mm2), determined using an image processor-analyzer for photographing histological specimens (P < 0.01). We also investigated the effect of metoclopramide on smooth muscle cells in the rat portal vein, using isometric-tension recording. Metoclopramide relaxed the smooth muscle precontracted with norepinephrine, in a concentration-dependent manner. Thus, metoclopramide inhibits the development of esophageal varices in this rat model due to both an increase in resistance of the lower esophagus and to development of small collaterals.

Animals↗
PubMed1994

Redistribution of alpha-granule membrane glycoprotein IIb/IIIa (integrin alpha IIb beta 3) to the surface membrane of human platelets during the release reaction.

Treatment of human washed platelets with 5 mM EDTA at 37 degrees for 60 min irreversibly dissociated glycoprotein (GP) IIb/IIIa complex (alpha IIb beta 3 integrin) on the surface membrane, since transmission immunoelectron microscopy studies demonstrated that these EDTA-pretreated platelets in the presence of added Ca2+ ion could not bind P2, an anti-GPIIb/IIIa complex-specific monoclonal antibody, to their surface membrane. The treatment, however, had no effect on the GPIIb/IIIa complex on the alpha-granule membrane. At 30 sec after the EDTA-pretreated platelets were activated with 0.1 U/ml of thrombin, alpha-granules fused with each other or with the surface-connected canalicular system (SCCS) to form swollen SCCS, the membrane of which was found to have the intact GPIIb/IIIa complex detectable by P2. In addition, at this time the intact GPIIb/IIIa complex reappeared on the surface membrane. At 5 min, the intact GPIIb/IIIa complex increased on the surface membrane with a reciprocal decrease or disappearance on the membrane of the swollen SCCS. The observation under scanning immunoelectron microscopy also confirmed the same translocation of the intact GPIIb/IIIa complex. These results indicate that alpha-granule membrane GPIIb/IIIa is redistributed to the surface membrane via the membrane of SCCS during the release reaction.

Blood Platelets↗
PubMed1994

Hemodynamic study of splenic artery aneurysm in portal hypertension.

In our ongoing studies on the hemodynamics of splenic artery aneurysms (SAA) in portal hypertension, 32 patients with portal hypertension were examined by duplex sonography and angiography. Four out of 32 (12.5%) had SAA, and SAA(+) and SAA(-) groups were formed. On duplex sonography, splenic venous blood flow in the SAA(+) group (1058 +/- 211 ml/min) increased more than in the SAA(-) group (423 +/- 173 ml/min, p < 0.01), but there was no significant difference in portal venous flow. On angiography, there were significant differences in the diameters of the splenic arteries between the SAA(+) group (7.5 +/- 0.5 mm) and the SAA(-) group (5.6 +/- 1.0 mm, p < 0.01). All patients (100%) in the SAA(+) group had prominent portosystemic shunts, while 8 out of 28 (28.6%) in the SAA(-) group had these shunts (p < 0.05). Thus, there seems to be a splenic hyperkinetic state in patients with SAA and portal hypertension, a finding which may closely relate to the pathogenesis of SAA.

Adult↗
PubMed1994

Analysis of hepatic vein waveform by Doppler ultrasonography in 100 patients with portal hypertension.

OBJECTIVES: We classified the Doppler waveform seen in patients with portal hypertension and examined the associations of the waveform type with the diagnosis of Budd-Chiari syndrome and severity of the liver cirrhosis. METHODS: The Doppler pattern of right and left hepatic veins in 100 consecutive Japanese patients with portal hypertension and esophagogastric varices was classified into six types: I, triphasic waveform; II, biphasic waveform without reversed flow; III, decreased amplitude of phasic oscillations; IV, flat waveform with fluttering; V, completely flat waveform with fluttering; VI, no waveform. All patients underwent computed tomography and magnetic resonance imaging. Patients in whom hepatic vein waveform showed type IV, type V, or type VI, positively underwent hepatic venography and inferior vena cavography. RESULTS: Type I was seen in 31 of 100 patients, type II in 35, type III in 17, type IV in eight, type V in four, and type VI in five. Types I-IV waveform indicated no lesion in hepatic veins and inferior vena cava, type V indicated stenosis of hepatic veins or occlusion of inferior vena cava, and type VI, occlusion of hepatic veins. For one patient with type V hepatic veins, balloon angioplasty was done, and the waveform changed from type V to type II. Examining the relationship between hepatic vein waveform and the Child-Pugh score, liver function of type IV cases was worse than that of type I cases in 66 cirrhotic patients without hepatocellular carcinoma (p < 0.05). There was no clear relationship between hepatic vein waveform and portal venous perfusion, as based on Nordlinger's grade. CONCLUSIONS: Our classification of hepatic vein waveform in Doppler ultrasonography is useful in diagnosing Budd-Chiari syndrome, in judging the efficiency of treatment for hepatic vein lesions, and in assessing severe liver function in cirrhotic patients.

Adult↗
PubMed1993

Activated platelets induce superoxide anion release by monocytes and neutrophils through P-selectin (CD62).

Activated platelets expressing P-selectin in their surfaces are known to adhere to monocytes and neutrophils. We examined the possibility that the leukocytes are functionally modified by their adhesion to activated platelets. We used human peripheral blood monocytes and neutrophils and measured superoxide anion generation by these cells cultured with platelets. The levels of superoxide anion production were found to be markedly elevated when thrombin-activated platelets were used. The extent of this enhancement was much smaller when leukocytes were cultured with resting platelets than activated platelets. The increase depended on incubation time and platelet concentration. The membranes prepared from activated platelets also induced superoxide anion production, but the culture supernatant of activated platelets did not. The enhanced superoxide anion production was inhibited by anti-P-selectin antibody, anti-sialyl-Lewis X antibody, or a soluble recombinant P-selectin fusion protein. These results indicate that the adhesion of activated platelets to the leukocytes through P-selectin was a crucial step for the activation of leukocyte function, and support the idea that activated platelets are actively involved in inflammation processes.

Base Sequence↗
PubMed1993

In situ capture of mu-calpain activation in platelets.

In situ detection of calpain activation in intact cells has not been possible to date. Here we present the first direct evidence, employing a novel approach, that mu-calpain is rapidly activated at cell membranes in platelets upon a rise in intracellular calcium concentration. Immunoelectron microscopy using antibodies capable of distinguishing between the pre- and postautolysis forms of mu-calpain revealed that treatment of platelets with calcium ionophore causes the preautolysis form of the protease to translocate from cytosol to membranes, where it becomes activated by autolysis. This indicates that proteins associated with membranes serve as primary substrates for calpain in cells.

Blood Platelets↗