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Biomedical subjects

H Kawano

Publications and source records attributed to H Kawano.

At least 91 records · Page 5Linked to original sources
PubMed2000

Tricuspid valve replacement with the St. Jude Medical valve: 19 years of experience.

OBJECTIVE: The choice of the valve substitute in the tricuspid position remains controversial. A St. Jude Medical valve is a choice of valve substitute and its lower thrombogenicity and excellent hemodynamic performance have been reported even in the tricuspid position. However, little is known of the long-term durability of the St. Jude Medical valve in the tricuspid position. Our long-term experience of tricuspid valve replacement showed the higher thrombogenicity than we had expected, therefore, this study was done to reconsider our strategy for valve choice. METHODS: This study reviewed 23 patient who underwent 25 tricuspid valve replacements with the St. Jude Medical valves from 1980 to 1997. The mean age was 40 years. Eleven patients (48%) were men. There were four in-hospital deaths (17%). The remaining 19 patients were all alive and followed from 2.2 to 19.0 years (mean 11.8 years). RESULTS: The overall survival, including hospital mortality, was 83%, 10 and 15 years after surgery. Valve thrombosis occurred in six patients. Freedom from valve thrombosis was 78 and 70%, 10 and 15 years after surgery, respectively. The linearized rate of the valve thrombosis was 2.9%/patient-years. Six patients required reoperation. The mean interval to reoperation was 9.5 years. Freedom from reoperation was 83% and 75%, 10 and 15 years after surgery, respectively. The linearized rate of the reoperation was 2.8%/patient-years. No structural valve deterioration was found. Echocardiographic study showed that the function of the St. Jude Medical valve without valve-related complications was well maintained. CONCLUSIONS: The higher thrombogenicity of the St. Jude Medical valve in the tricuspid position altered our choice of valve substitutes from the St. Jude Medical valve to a bioprosthesis which is lack of need for anticoagulant therapy except for juvenile patients who are able to maintain potent anticoagulant therapy.

Adolescent↗
PubMed2000

Procaspase 3/p21 complex formation to resist fas-mediated cell death is initiated as a result of the phosphorylation of p21 by protein kinase A.

Caspase 3 is an essential factor for Fas-mediated cell death and exists endogenously in cells where its activation is suppressed by p21 and ILP. Inside the cell, procaspase 3 interacts with p21 on mitochondria. In the present study, we investigated the molecular basis for procaspase 3/p21 complex formation. During Fas-mediated cell death, mitochondria are damaged, accompanied by decreased mitochondrial membrane-potential and decreased intracellular ATP levels. This mitochondrial damage occurs before an estrangement of the procaspase 3/p21 complex, and we demonstrate that intracellular ATP-deprivation also initiates an estrangement of procaspase 3/p21 complex formation and accelerates Fas-mediated cell death. In addition, our current results revealed that the phosphorylated p21 by PKA interacts with procaspase 3. Here, we report that the mitochondrial role, especially for ATP synthesis, and PKA are necessary for the procaspase 3/p21 complex formation to resist Fas-mediated cell death.

Adenosine Triphosphate↗
PubMed2000

Cell death induction by CTL: perforin/granzyme B system dominantly acts for cell death induction in human hepatocellular carcinoma cells.

Cell death induction by cytotoxic T lymphocytes (CTLs) is an important thesis for the understanding of tumor immunotherapy. In the current study we investigated the molecular machinery of CTL-induced cell death in human hepatocellular carcinoma cell lines (HCC lines). CTLs prepared from human peripheral blood induced cell death in all tested HCC lines. As the CTL-induced death system, the effectiveness of Fas ligand/Fas and/or Perforin/Granzyme B systems has been suggested, whereas cell death induction by CTLs was shown independently on Fas expression in the current study. Using various tetrapeptide inhibitors for caspase and its associated factor, we additionally demonstrated that inhibitors for caspase 3 (Ac-DEVD-CHO) and caspase 8/granzyme B (Ac-IETD-CHO) suppressed CTL-induced cell death, but an inhibitor for Fas-activated serine proteinase, which acts for the caspase 3 activator, did not, suggesting that CTL-induced cell death was initiated by the Perforin/Granzyme B system, rather than the Fas ligand/Fas system. On the basis of our current results, we report here that the Perforin/Granzyme B system acts dominantly for the cell death induction of HCC lines.

Animals↗
PubMed2000

Survivin promotes cell proliferation in human hepatocellular carcinoma.

Survivin is a recently described inhibitor of apoptosis. Because suppression of apoptosis is important for carcinogenesis and tumor growth, we investigated the expression and function of survivin in human hepatocellular carcinomas (HCCs). We have shown that 4 HCC cell lines and 7 out of 8 human HCC tissues expressed survivin messenger RNA (mRNA), whereas expression of survivin mRNA was not detected in normal liver and nontumor areas of these tissues using the reverse transcription polymerase chain reaction. Survivin was detected primarily in the nucleus by immunofluorescence staining of HCC cells. In addition, 14 of 20 (70%) HCC tissues showed positive nuclear staining for survivin, whereas nontumor tissues showed little detectable staining by immunohistochemistry. Survivin expression strongly correlated with the proliferation index but not significantly with the apoptosis index in HCC tissues. Therefore, we performed cell cycle analysis after survivin transfection and showed that overexpression of survivin resulted in a decrease in the G(0)/G(1) phase and an increase in the S phase in all 4 HCC cell lines. Furthermore, we have found that survivin interacted with cyclin-dependent kinase 4 (Cdk4) and overexpression of survivin released p21(WAF1/Cip1) (p21) from Cdk4. From these results, we conclude that survivin promotes cell proliferation by interacting with Cdk4 and releasing p21 from Cdk4. This may play an important role in carcinogenesis and progression of human HCCs.

Apoptosis↗
PubMed2000

Hepatocyte growth factor promotes cell survival from fas-mediated cell death in hepatocellular carcinoma cells via Akt activation and Fas-death-inducing signaling complex suppression.

The Akt/PI-3 kinase pathway is a system essential for cell survival. In the current study, we showed that hepatocyte growth factor (HGF) activates the Akt/PI-3 kinase pathway to suppress Fas-mediated cell death in human hepatocellular carcinoma (HCC; 3 lines; SK-Hep1, HLE, and Chang Liver cell lines), hepatoblastoma (1 line; HepG2), and embryonic hepatocyte (1 line; WRL). Five tested cell lines showed the resistance to Fas-mediated cell death by the pretreatment of HGF. This HGF-induced cell survival was suppressed by wortmannin (Akt/PI-3 kinase pathway inhibitor), suggesting an involvement of Akt. When cells were pretreated with HGF, Fas-mediated cell death was suppressed, followed by Akt phosphorylation at Ser473. Fas-death-inducing signaling complex (DISC) formation, especially FADD and caspase 8 interaction, was suppressed by HGF and the suppression of the Akt/PI-3 kinase pathway by transient expression of PTEN, resulting in acquisition of Fas-DISC formation and Fas-mediated cell death in HGF-treated cells. We suggest that HGF promotes cell survival in hepatocyte-derived cell lines (HCC, hepatoblastoma, and embryonic hepatocyte) from Fas-mediated cell death via Fas-DISC suppression as a result of Akt activation.

Carcinoma, Hepatocellular↗
PubMed2000

Obstruction of St Jude Medical valves in the aortic position: significance of a combination of cineradiography and echocardiography.

BACKGROUND: Obstruction of the St Jude Medical valve (St Jude Medical, Inc, St Paul, Minn) is a rare but serious complication. METHODS: Cineradiographic and echocardiographic evaluations of aortic St Jude Medical valves were simultaneously performed on 54 patients, with no signs of prosthetic valve dysfunction late after surgery. RESULTS: Although closing angles of the leaflets corresponded closely with the manufacturer data, restricted opening of the leaflets (opening angle >/= 20 degrees ) was found in 16 (group D) of the 54 patients by means of cineradiography. The opening angles were equal to or less than 14 degrees in the other 23 patients (group N) and between 15 degrees and 19 degrees in the remaining 15 (group M). Doppler-derived transprosthetic pressure gradients were significantly higher (P =.03) and the velocity index was significantly lower (P =.003) in group D than in group N. However, no significant differences were found in those values between group N and group M. Replacement of the aortic St Jude Medical valves was performed in 5 of the 16 patients, and the remaining 11 have been followed up because of relatively low pressure gradients. The cause of restricted leaflet movement was pannus formation without thrombosis in 4 patients and valve thrombosis with pannus formation in one. CONCLUSIONS: Reduced valve orifice area and restricted opening of the leaflets resulting from excess growth of pannus probably led to obstruction of the aortic St Jude Medical valves. A combination of cineradiography and echocardiography makes it possible to provide an accurate and detailed diagnosis of obstruction of the valve.

Adolescent↗
PubMed2000

Identification of MUC5B mucin gene in human middle ear with chronic otitis media.

OBJECTIVES: To identify the mucin gene and its expressing cells in the middle ear mucosa with chronic otitis media (COM), and to study the correlation between infiltration of inflammatory cells in the submucosa and expression of the mucin gene in the mucosal epithelium with COM. STUDY DESIGN: Middle ear mucosal specimens removed from the inferior promontory area of 19 patients undergoing middle ear surgery for COM were studied. METHODS: Sections were stained with H&E, Alcian blue-periodic acid Schiff (AB-PAS), polyclonal MUC5B antibody, and specific MUC5B riboprobe for histological, histochemical, immunohistochemical, and mucin mRNA analyses. RESULTS: H&E staining revealed pseudostratified epithelia in 18 of the middle ear specimens with COM and cuboidal secretory epithelia in one. AB-PAS staining of epithelia revealed abundant secretory cells and their products (glycoconjugates). In situ hybridization and immunohistochemistry studies demonstrated that the secretory cells of the middle ear mucosa with COM expressed MUC5B mucin mRNA and its product MUC5B mucin. CONCLUSIONS: The MUC5B mucin gene and its product were identified in the middle ear secretory cells of patients with COM. Its expression was extensive in pseudostratified mucosal epithelia and related to infiltration of inflammatory cells in the submucosa of the middle ear cleft with COM, suggestive that inflammatory cell products are involved in the production of MUC5B.

Adolescent↗
PubMed2000

Insulin resistance and endothelial dysfunction in smokers: effects of vitamin C.

Cigarette smoking impairs endothelial function and is one of the major risk factors for atherosclerosis and coronary heart disease. Insulin resistance is associated with major risk factors for atherosclerosis. We examined the effects of vitamin C on insulin sensitivity and endothelial function by measuring steady-state plasma glucose (SSPG) and flow-mediated dilation (FMD) of the brachial artery. We studied 16 current smokers with normal glucose tolerance, 15 nonsmokers with impaired glucose tolerance (IGT), and 17 nonsmokers with normal glucose tolerance as controls. Both SSPG and FMD were blunted in smokers and nonsmokers with IGT compared with controls. In smokers, vitamin C decreased SSPG (P < 0.01 by ANOVA) with decreasing plasma thiobarbituric acid-reactive substances (TBARS) (P < 0.05 by ANOVA) and improved FMD (P < 0.05 by ANOVA). Furthermore, vitamin C improved both SSPG (P < 0.005 by ANOVA) and FMD (P < 0.05 by ANOVA) in nonsmokers with IGT. SSPG, FMD, or TBARS in controls did not change after vitamin C infusion. There was a significant correlation between SSPG and FMD both in smokers and nonsmokers with IGT, whereas no correlation was observed in controls. In conclusion, both insulin sensitivity and endothelial function were impaired in smokers and nonsmokers with IGT and were improved by vitamin C. Thus increased reactive oxygen species play an important role in the pathogenesis of insulin resistance as well as endothelial dysfunction in smokers and nonsmokers with IGT.

Analysis of Variance↗
PubMed2000

Angiotensin II enhances integrin and alpha-actinin expression in adult rat cardiac fibroblasts.

Angiotensin II (Ang II) plays an important role in cardiac remodeling through stimulation of proliferation and extracellular matrix (ECM) production in cardiac fibroblasts. Integrins are a family of transmembrane receptors that mediate the attachment of cells to ECM. We hypothesized that Ang II regulation of integrins further contributes to its role in cardiac remodeling. We cultured adult rat cardiac fibroblasts with and without Ang II (100 nmol/L) to determine the effects on mRNA and protein levels of integrins, as well as alpha-actinin and other cytoskeletal proteins that link to integrins at the site of focal adhesions. Ang II was also added in the presence of irbesartan (10 micromol/L), a specific Ang II type 1 (AT(1)) receptor antagonist, or PD 123319 (10 micromol/L), a specific Ang II type 2 receptor antagonist. To investigate the function of these integrins, we determined the effects of blocking antibodies on Ang II-induced adhesion to ECM. We also treated spontaneously hypertensive rats (SHR) with an AT(1) receptor blocker, losartan, or with hydralazine to investigate integrin and alpha-actinin expression in treated and untreated SHR. Ang II enhanced alpha(v), beta(1), beta(3), and beta(5) integrins; osteopontin; and alpha-actinin mRNA and protein levels in cardiac fibroblasts. All of these effects were inhibited by irbesartan but not by PD 123319. Pretreatment of cardiac fibroblasts with Ang II enhanced cell attachment to ECM proteins and induced focal adhesion kinase phosphorylation. Blocking antibodies to beta(3) and alpha(v)beta(5) attenuated Ang II-induced adhesion. In SHR, ventricular alpha(v) and beta(5) integrin expression and alpha-actinin were increased compared with those in Wistar-Kyoto rats. Although both losartan and hydralazine lowered mean arterial pressure and decreased peripheral vascular resistance, only losartan attenuated the increased integrin, alpha-actinin, fibronectin laminin, and osteopontin expression and the increased left ventricular mass (as determined with echocardiography). Hydralzine had none of these effects. Although both agents attenuated beta-myosin heavy chain expression, a marker of hypertrophy, losartan had a greater effect. These results suggest that integrins and alpha-actinin are upregulated by Ang II and in left ventricular hypertrophy and that the block of expression of these proteins through inhibition of the AT(1) receptor is associated with attenuation of the hypertrophic response. Ang II induces integrin and alpha-actinin expression in cardiac fibroblasts that is associated with adhesion and left ventricular hypertrophy and blocked through inhibition of the AT(1) receptor.

Actinin↗
PubMed2000

Developmental changes in cerebrospinal fluid concentrations of monoamine-related substances revealed with a Coulochem electrode array system.

The relationship between age and cerebrospinal fluid concentrations of monoamine-related substances, including kynurenine, were investigated using a Coulochem electrode array system, to clarify developmental changes in monoamine-related substances in the human central nervous system. In neurologically normal children, significant inverse correlations with age were observed for the cerebrospinal fluid concentrations of 5-hydroxytryptophan, 5-hydroxyindole-acetic acid, kynurenine, homovanillic acid, 3-methoxy-4-hydroxyphenyl glycol, and 3-O-methyl-dopamine. The concentrations of their precursors, tryptophan and tyrosine, were not related to age. This is the first comprehensive study revealing developmental changes in monoamine-related substances including their precursors and metabolites.

Age Factors↗
PubMed2000

The plasma levels of dehydroepiandrosterone sulfate are decreased in patients with chronic heart failure in proportion to the severity.

Dehydroepiandrosterone sulfate (DHEAS) is the major secretory steroid of the human adrenal glands. The secretion of DHEAS decreases with aging. The incidence of heart failure also rises in the elderly population. We measured the plasma levels of DHEAS and cortisol in 49 patients with chronic heart failure (CHF) and 32 age-matched controls and assessed its relation to plasma levels of A-type natriuretic peptide and B-type natriuretic peptide, biochemical markers of heart failure. Plasma levels of DHEAS were significantly lower in patients with CHF than in controls, whereas there was no significant difference in plasma levels of cortisol between the two groups. In stepwise regression analysis, the plasma level of DHEAS was significantly and independently correlated with age (beta = -0.451; P < 0.0001) and the plasma level of B-type natriuretic peptide (beta = -0.338; P < 0.001), and the plasma cortisol/DHEAS ratio was significantly and independently correlated with the plasma levels of A-type natriuretic peptide (beta = 0.598; P < 0.0001) and thiobarbituric acid-reactive substances (a marker of oxidative stress; beta = 0.252; P < 0.01) and age (beta = 0.171; P < 0.05). These results indicate that the plasma levels of DHEAS are decreased in patients with CHF in proportion to its severity and that oxidative stress is associated with decreased levels of DHEAS in patients with CHF.

Adult↗
PubMed2000

Molecular analysis of external genitalia formation: the role of fibroblast growth factor (Fgf) genes during genital tubercle formation.

The molecular mechanisms underlying the development of the external genitalia in mammals have been very little examined. Recent gene knockout studies have suggested that the developmental processes of its anlage, the genital tubercle (GT), have much in common with those of limb buds. The Fgf genes have been postulated as regulating several downstream genes during organogenesis. Fgf8 was expressed in the distal urethral plate epithelium of the genital tubercle (GT) together with other markers such as the Msx1, Fgf10, Hoxd13 and Bmp4 expressed in the mesenchyme. To analyze the role of the FGF system during GT formation, an in vitro organ culture system was utilized. It is suggested that the distal urethral plate epithelium of GT, the Fgf8-expressing region, regulates the outgrowth of GT. Ectopic application of FGF8 beads to the murine GT induced mesenchymal gene expression, and also promoted the outgrowth of the GT. Experiments utilizing anti-FGF neutralizing antibody suggested a growth-promoting role for FGF protein(s) in GT outgrowth. In contrast, despite its vital role during limb-bud formation, Fgf10 appears not to be primarily essential for initial outgrowth of GT, as extrapolated from Fgf10(-/-) GTs. However, the abnormal external genitalia development of Fgf10(-/-) perinatal mice suggested the importance of Fgf10 in the development of the glans penis and the glans clitoridis. These results suggest that the FGF system is a key element in orchestrating GT development.

Animals↗
PubMed2000

Different recognition by peroxisome proliferator structures in rat peroxisomal induction: application of sandwich ELISA using monoclonal antibody against rat peroxisomes.

A novel assay for a peroxisomal beta-oxidation enzyme by sandwich ELISA using a monoclonal antibody (RPX-5) against purified rat liver peroxisomes was developed. Immunoblot analysis revealed that RPX-5 recognized a 78 Kd protein, which is a peroxisomal bifunctional enzyme (PBE) in the beta-oxidation pathway. Immunoprecipitation by RPX-5 and the resulting reduction of PBE activity were dependent on RPX-5 concentrations. Sandwich ELISA using RPX-5 could be used to assay PBE in the range of 30 to 2000 ng protein/ml. In rat hepatocyte cultures, the PBE amount by this assay correlated well with PBE activity, with correlation coefficients of 0.965. Studying the mechanisms of peroxisomal induction, patterns of peroxisomal induction were examined by co-treatment of rat hepatocytes with various peroxisome proliferators (PxPs). Treatment with clofibrate and bezafibrate resulted in neither an additive nor synergistic effect on PBE level. On the other hand, co-treatment with either bezafibrate-Wy-14,643 or clofibrate-MEHP(mono(2-ethylhexyl)phthalate) both resulted in an additive effect. From these results, it is suggested that PxPs of the fibrate group may exert their functions via a common process, and non-fibrate PxPs via a different process in hepatocytes. The cognition site for peroxisome proliferators, therefore, might not involve a single site for inducing peroxisomal enzymes.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed2000

Analysis of plasma cell clonality in localized AL amyloidosis.

AL amyloidosis is characterized by fibrillar tissue deposits composed of monoclonal immunoglobulin light chains(IgLs). It has been speculated that clonal expansion of plasma cells may occur locally and produce amyloidogenic IgLs. Both immunohistochemistry and molecular genetics are useful for examining plasma cell clonality from paraffin-embedded tissue sections, which are easy to obtain. We evaluated plasma cell clonality in 16 biopsy cases of localized AL amyloidosis using these two methods. A clonal excess of plasma cells was detected in 6 (37.5%) cases immunohistochemically, in 10 (62.5%) cases molecularly, and in 13 (81.3%) cases by at least one of the two methods. These results support local synthesis of the light chain proteins in localized AL amyloidosis.

Adult↗
PubMed2000

Atherosclerotic plaques composed of a large core of foam cells covered with thin fibrous caps in twice-injured carotid arterial specimens obtained from high cholesterol diet-fed rabbits.

We attempted to find atherosclerotic plaques including a large lipid core and thin fibrous cap in twice-injured arterial specimens obtained from high cholesterol diet (HCD) fed rabbits. Rabbits fed a HCD were subjected to carotid artery injury using a balloon catheter. After 2 or 4 weeks of cholesterol feeding, a second mild injury was induced in the same region as the first injury. The rabbits were given a standard diet for 2 weeks after the second injury. Typical atherosclerotic plaques with a fibrous cap formed by smooth muscle cells and extracellular matrix overlying a core formed by macrophage foam cells were observed in the lesion. Gelatin proteolytic activities were found in homogenates containing either media or intima from the injured artery, and activated matrix metalloproteinase-2 (MMP2) was detected. With prolongation of the HCD feeding period (interval between injuries) from 2 weeks to 4 weeks, typical plaque was observed more frequently. Furthermore, the neointimal area and the macrophage foam cells area increased, as did gelatin-proteolytic activity. Since the typical atherosclerotic plaques observed in the present study have some histopathological and pathogenic characteristics in common with unstable atherosclerotic plaque, we expect that the typical atherosclerotic plaque found in the present study will be useful for basic studies of plaque stabilization and prevention of acute coronary syndromes.

Animals↗
PubMed2000

Rapid change of platelet aggregability in acute hyperglycemia. Detection by a novel laser-light scattering method.

We examined the alteration of platelet aggregability in acute hyperglycemia during 75-gram oral glucose tolerance tests (OGTT). Twenty subjects underwent 75-gram OGTT and venous blood samples were obtained before (0 min), 60, 120 and 180 min postload. Platelet aggregability shown as the number of small platelet aggregates was measured with a novel laser-light scattering (LS) method. Platelet aggregability increased in parallel with both glucose and immunoreactive insulin (IRI) levels. The number of mean small aggregates at 60 min (12.30 +/- 1.10 X 10(4)) was significantly higher than the one at 0 min (8.32 +/- 0.88 x 10(4), p <0.001), 120 min (10.63 +/- 0.98 x 10(4), p <0.05) and 180 min (8.28 +/- 0.84 x 104, p <0.001) (mean +/- SEM). Small aggregates correlated positively with plasma glucose levels at 60 min postload (r = 0.67, p = 0.001) while not with IRI. It might be important to suppress transient hyperglycemia for preventing the onset of acute coronary syndromes that could be closely related to platelet hyperaggregability.

Acute Disease↗
PubMed2000

[A case report of neovascular glaucoma due to carotid artery occlusive disease--diagnosis of neovascular glaucoma and histological characteristics].

PURPOSE: The methods of diagnosing neovascular glaucoma were evaluated in a case with carotid artery occlusive disease. A trabeculectomy specimen taken from this patient was examined histologically to find the characteristic picture of this slowly progressive neovascular glaucoma. MATERIALS AND METHODS: The left eye of a 48-year old man with neovascular glaucoma due to carotid artery occlusive disease had been previously diagnosed as uveitis with ocular hypertension. His left eye was examined by fluorescein fundus and gonioangiography. Trabeculectomy was performed because of uncontrolled intraocular pressure and the trabeculectomy specimen was examined histologically including immunohistochemistry with antibodies against von Willebrand factor antigen. RESULTS: The characteristic picture of fluorescein fundus angiography was filling delay in the choroid and stained walls of the retinal arteries and veins. Fluorescein gonioangiography using a fundus camera clearly demonstrated new vessels in the pupil and angle with intense fluorescein leak in spite of faint neovascularization in those areas when observed by slit lamp with gonioscopy. Histological examination of the trabeculectomy specimen revealed proliferation of new vessels in the spaces of the trabecular meshwork and focal occlusion of Schlemm's canal. CONCLUSION: Fluorescein fundus angiography and gonioangiography by fundus camera is very useful for diagnosis of neovascular glaucoma due to carotid artery occlusive disease. Neovascular proliferation in the trabecular meshwork with slight of peripheral anterior synechia and focal occlusion of Schlemm's canal may be peculiar to such slowly progressive neovascular glaucoma.

Carotid Stenosis↗