Biomedical subjects

J Watanabe

Publications and source records attributed to J Watanabe.

At least 37 records · Page 2Linked to original sources

PubMed2003

Successful induction of immune tolerance in a patient with haemophilia B with inhibitor.

We describe successful induction of immune tolerance (IT) in a 10-month-old boy with severe haemophilia B. Urticaria developed soon after starting prophylactic treatment and was associated with an inhibitor at 7 Bethesda units mL(-1). Initially, we tried low dose factor IX therapy to induce IT with only a transient effect. The patient experienced an intracranial haemorrhage. A simple bolus dose of FIX eradicated the inhibitor. Thereafter he has been free from inhibitor and nephrotic syndrome for more than 5 years, although he receives FIX three times a week.

Drug Administration Schedule↗

PubMed2003

VEGF expression and its reguration by p53 gene transfection in endometrial carcinoma cells.

Vascular endothelial growth factor (VEGF) that activates endothelial cell growth induces angiogenesis, which is indispensable to tumor igenesis and tumor progression. On the other hand, tumor suppressor gene p53 has been considered to regulate VEGF expression, but the detailed relationship between them remains unclear. In this study, we aimed to study VEGF expression in endometrial carcinoma cells and the effect of p53 gene transfection on VEGF expression using p53-mutated endometrial carcinoma cell line, HEC-50B. Immunoblotting for detecting VEGF protein, p53 protein and beta-actin was performed using 11 endometrial carcinoma cell lines. Levels of VEGF in the cultured media were measured by Enzyme immunoassay(EIA). Transfection of wild p53 gene was carried out by SuperFect method in HEC-50B cells, which had mutant p53 gene and did not express p53 protein. The results of immunoblotting were analyzed by NIH image and expressed as values. The results of EIA were expressed as the relative value. The VEGF value was 0.8 +/- 0.3 (n = 6) in p53-wild group, whereas in p53-mutant group it was 1.6 +/- 0.8 (n = 5). VEGF expression was correlated significantly with p53 status (P < 0.05). VEGF levels in p53 gene-transfected cells and the conditioned medium were decreased in 48 hours after p53 gene transfection. VEGF expression was down-regulated by p53 in endometrial carcinoma cells.

Cell Line, Tumor↗

PubMed2003

Isolation and structural elucidation of a peptide derived from Edam cheese that inhibits beta-lactoglobulin transport.

A peptide that inhibits beta-lactoglobulin absorption in an in vitro Caco-2 cell model was isolated from Edam cheese. By 1H-NMR and N-terminal amino acid analyses, the active compound was identified as Asp-Lys-Ile-His-Pro-Phe. The sequence of the hexapeptide is the same as the amino acid sequence of residues 47-52 of beta-casein. The hexapeptide shows remarkable inhibition of beta-lactoglobulin transport at a concentration of 10(-7)M. The possibility exists that this peptide can be applied practically to the prevention of milk-sensitive allergy.

Allergens↗

PubMed2002

Paradoxical expression of cell cycle inhibitor p27 in endometrioid adenocarcinoma of the uterine corpus - correlation with proliferation and clinicopathological parameters.

p27 is regarded as a cyclin-dependent kinase inhibitor of the G1-to-S cell cycle progression by suppressing the kinase activity of cyclin/cyclin-dependent kinase complex. This study aimed to investigate p27 expression in the normal endometrium and endometrioid adenocarcinoma of the uterine corpus and the correlation of its expression with cell proliferation and clinicopathological parameters. Tissue samples of 127 endometrioid adenocarcinomas and 15 normal endometria were used in the study. Immunohistochemical staining for detecting p27 and Ki-67 was performed by the labelled streptavidin-biotin method on formalin-fixed and paraffin-embedded tissue samples. The expression was given as the labelling index, which indicates the percentage of positive nuclei. p27 staining was observed in the nuclei of the glandular cells in the functional layer of the secretory phase endometrium, whereas it was negative in those of the proliferative phase. In endometrioid adenocarcinomas, the labelling index of p27 expression paradoxically increased more significantly in the higher histological grades and was correlated with that of Ki-67. The high level of p27 expression was associated with clinicopathological parameters such as FIGO stage, lymph node metastasis, lymphovascular space involvement and myometrial invasion. High p27 expression was linked to higher grades of endometrioid adenocarcinoma, cell proliferation and some clinical prognostic factors. These results indicate that p27 might be an indicator of poor prognosis.

Adenocarcinoma↗

PubMed2002

Expression of cyclin A in endometrial adenocarcinoma and its correlation with proliferative activity and clinicopathological variables.

PURPOSE: Cyclin A is known as an S- and G2-M phase regulatory protein and its abnormal expression has been reportedly implicated in cellular proliferation. This study was designed to investigate the correlation of cyclin A expression with tumorigenesis of the endometrium and clinicopathological variables. METHODS: Immunohistochemical staining using labeled streptavidin-biotin complex was performed on formalin-fixed, paraffin-embedded tissue of normal endometrium (15 cases), endometrial hyperplasia (23 cases), and endometrial adenocarcinoma (endometrioid type) (112 cases). RESULTS: Immunohistochemistry showed that the nuclei of the cells were positive for cyclin A. In normal endometrium, only proliferative phase was focally positive for cyclin A. Cyclin A was also positive for endometrial hyperplasia. Its expression in hyperplasia was significantly more frequent than that of proliferative phase and less than that of endometrioid adenocarcinoma. The labeling index (LI) of cyclin A in endometrioid adenocarcinoma was 16.3+/-6.9 in well-differentiated, 18.3+/-8.8 in moderately differentiated, and 30.2+/-11.8 in poorly differentiated adenocarcinoma, respectively. Cyclin A expression increased significantly more in high histological grades. The area of squamous metaplasia in endometrioid adenocarcinoma was negative for cyclin A. The LI of cyclin A was positively correlated with that of Ki-67 and cyclin-dependent kinase 2. Cyclin A expression was significantly associated with carcinoma without coexisting endometrial hyperplasia and lymphovascular space involvement (LVSI), but not with FIGO stage, myometrial invasion, lymph node metastasis, estrogen receptor, progesterone receptor, and menopause as well as recurrence. CONCLUSIONS: Cyclin A expression was involved in the progression to malignancy of the endometrium and was correlated with proliferative activity and prognostic features including histological grade, without coexisting endometrial hyperplasia and LVSI.

Adenocarcinoma↗

PubMed2002

Impact of respiratory syncytial virus infection as a cause of lower respiratory tract infection in children younger than 3 years of age in Japan.

BACKGROUND: Respiratory syncytial virus (RSV) is the most important viral pathogen for lower respiratory tract infection (LRI) in infants and children. An RSV-specific monoclonal antibody has been developed to provide prophylaxis against RSV associated LRI (RSV-LRI). The objective of this study was to determine the impact of RSV as a cause of LRI in children younger than 3 years of age to provide data to aide in the implementation of forthcoming prophylaxis against RSV. METHODS: We analyzed the viral etiology of LRI in hospitalized Japanese children younger than 3 years of age admitted to Shizuoka Red Cross Hospital from July, 1997 to June, 2000. RESULTS: A total of 535 patients younger than 3 years of age were hospitalized with LRI at Shizuoka Red Cross Hospital from July 1, 1997 to June 30, 2000. Of these, a positive diagnosis of RSV infection was made in 168 patients (31.4%). Most of the patients with RSV infection had been well and had had no underlying disease that was defined as risk factor of RSV infection (94.0%). The peak incidence of LRI was observed in the winter each year and the number of LRI was strongly associated with the epidemic of RSV (r=0.700, P<0.0001). The number of patients with LRI younger than 6 months of age was 116 (21.7%). Of these 116 patients younger than 6 months with LRI, 55 patients (47.4%) were confirmed to have RSV infection. The proportions of RSV infection to total LRI was greatest in early infants younger than 6 months (P<0.0001). The number of patients with which RSV infection was detected in LRI patients younger than 3 years was highest during the first five months of life and there was a dramatic decrease in incidence of RSV infection with increasing age thereafter. CONCLUSIONS: The incidence of LRI hospitalization is highly affected by RSV infection epidemic. The proportion of RSV infections among early infants younger than 6 months is greater than that of older patients. The prophylaxis against RSV will be needed to be toward early infants.

Age Factors↗

PubMed2002

Interaction of iodine with 2-hydroxypropyl-alpha-cyclodextrin and its bactericidal activity.

To obtain an effective iodine solution, the use of 2-hydroxypropyl-alpha-cyclodextrin (2-HP-alpha-CD) as solubilizer was examined in comparison with alpha-cyclodextrin (alpha-CD), beta-cyclodextrin (beta-CD), potassium iodide (KI), and polyvinylpyrrolidone (PVP). The stability constants for inclusion of iodine with cyclodextrin and KI were ascertained by the solubility method. The apparent stability constants increased in the following order: KI < beta-CD < alpha-CD < 2-HP-alpha-CD. This order was nearly in accordance with that of the stabilization ability. The largest volatile depression effect was exhibited by 2HP-alpha-CD. The measurement of the minimum inhibitory concentration (MC) using Escherichia coli NIH-J-2 and Staphylococcus aureus FDA209P suggested that the bactericidal activity of the iodine/2-HP-alpha-CD system was the same as that of the iodine/alpha-CD, iodine/beta-CD, and iodine/PVP systems. The present results suggest that the combination of 2-HP-alpha-CD and iodine is useful for a stable and effective iodine solution.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed2002

Activation of adenosine-receptor-enhanced iNOS mRNA expression by gingival epithelial cells.

A series of reports has revealed that adenosine has a plethora of biological actions toward a large variety of cells. In this study, we investigated the influence of adenosine receptor activation on iNOS mRNA expression in human gingival epithelial cells (HGEC) and SV-40-transformed HGEC. HGEC expressed adenosine receptor subtypes A1, A2a, and A2b, but not A3 mRNA. Ligation of adenosine receptors by a receptor agonist, 2-chloroadenosine (2CADO), enhanced iNOS mRNA expression by both HGEC and transformed HGEC. In addition, the adenosine receptor agonist enhanced the production of NO(2)(-)/NO(3)(-), NO-derived stable end-products. An enhanced expression of iNOS mRNA and NO(2)(-)/NO(3)(-) was also observed when SV40-transformed HGEC were stimulated with CPA or CGS21680, A1- or A2a-selective adenosine receptor agonists, respectively. These results provide new evidence for the possible involvement of adenosine in the regulation of inflammatory responses by HGEC in periodontal tissues.

Adenosine↗

PubMed2001

The spin temperature of NH3 in Comet C/1999S4 (LINEAR).

A high-dispersion spectrum of Comet C/1999S4 (LINEAR) was obtained in the optical region with the high-dispersion spectrograph on the Subaru telescope when the comet was 0.863 astronomical units from the Sun before its disintegration. We obtained high signal-to-noise ratio emission lines of the cometary NH2 bands from which an ortho-to-para ratio (OPR) of 3.33 +/- 0.07 was derived on the basis of a fluorescence excitation model. Assuming that cometary NH2 mainly originates from ammonia through photodissociation, the derived OPR of NH2 molecules should reflect that of ammonia, which provides information on the environment of molecular formation or condensation and of the thermal history of cometary ices. Assuming that the OPR of ammonia in comets was unchanged in the nucleus, the derived spin temperature of ammonia (28 +/- 2 kelvin) suggests that a formation region of the cometary ammonia ice was between the orbit of Saturn and that of Uranus in the solar nebula.

Ammonia↗

PubMed2001

Early identification of impaired myocardial reperfusion with serial assessment of ST segments after percutaneous transluminal coronary angioplasty during acute myocardial infarction.

To evaluate the relation between ST-segment analysis and microvascular reperfusion in patients with acute myocardial infarction (AMI), we studied 51 patients with first AMI who were successfully treated by percutaneous transluminal coronary angioplasty (PTCA). The lead showing the greatest ST-segment elevation on the 12-lead electrocardiogram (ECG) was serially investigated until 24 hours after PTCA. Successful reperfusion was determined by technetium-99m tetrofosmin single-photon emission computed tomography. Impaired reperfusion (group 1: < 4 change in the sum of the defect score from before to immediately after PTCA) was observed in 24 patients, and successful reperfusion (group 2) was observed in 27 patients. Although ST-segment elevation was reduced significantly at 30 minutes after PTCA in group 2 (2.2 +/- 1.4 to 1.7 +/- 1.3 mm, p = 0.01), there was no significant change in group 1 (1.9 +/- 1.9 to 2.4 +/- 1.7 mm). Ten of 14 patients (71%) with persistent ST-segment elevation (DeltaST > 0 mm change in ST segment from before to 30 minutes after PTCA > 0) were in group 1, whereas 23 of 37 patients (62%) with ST-segment resolution (DeltaST < or = 0) were in group 2. The sensitivity and specificity of persistent ST-segment elevation for predicting impaired microvascular reperfusion were 42% and 85%, respectively. Thus, persistent ST-segment elevation 30 minutes after primary PTCA was a highly specific electrocardiographic marker of impaired reperfusion in patients with AMI.

Aged↗

PubMed2001

Heart rate recovery immediately after treadmill exercise and left ventricular systolic dysfunction as predictors of mortality: the case of stress echocardiography.

BACKGROUND: An attenuated heart rate recovery after exercise has been shown to be predictive of mortality. In prior studies, recovery heart rates were measured while patients were exercising lightly, that is, during a cool-down period. It is not known whether heart rate recovery predicts mortality when measured in the absence of a cool-down period or after accounting for left ventricular systolic function. METHODS AND RESULTS: We followed 5438 consecutive patients without a history of heart failure or valvular disease referred for exercise echocardiography for 3 years. Heart rate recovery was defined as the difference in heart rate between peak exercise and 1 minute later; a value </=18 beats per minute was considered abnormal. Patients assumed the left lateral decubitus position after exercise. An abnormal heart rate recovery was present in 805 patients (15%); during follow-up, 190 died. An abnormal heart rate recovery was predictive of death (9% versus 2%, hazard ratio [HR] 3.9, 95% CI 2.9 to 5.3, P<0.0001) and predicted death whether or not left ventricular systolic dysfunction (ejection fraction </=40%) was present. After adjusting for age, sex, exercise capacity, left ventricular systolic function, presence or absence of myocardial ischemia, and other confounders, an abnormal heart rate recovery remained predictive of death (adjusted HR 2.09, 95% CI 1.49 to 2.82, P<0.001). CONCLUSIONS: Even in the absence of a cool-down period and even after accounting for left ventricular systolic function, heart rate recovery is a powerful and independent predictor of death.

Adult↗

PubMed2001

Aspirin use and all-cause mortality among patients being evaluated for known or suspected coronary artery disease: A propensity analysis.

CONTEXT: Although aspirin has been shown to reduce cardiovascular morbidity and short-term mortality following acute myocardial infarction, the association between its use and long-term all-cause mortality has not been well defined. OBJECTIVES: To determine whether aspirin is associated with a mortality benefit in stable patients with known or suspected coronary disease and to identify patient characteristics that predict the maximum absolute mortality benefit from aspirin. DESIGN AND SETTING: Prospective, nonrandomized, observational cohort study conducted between 1990 and 1998 at an academic medical institution, with a median follow-up of 3.1 years. PATIENTS: Of 6174 consecutive adults undergoing stress echocardiography for evaluation of known or suspected coronary disease, 2310 (37%) were taking aspirin. Patients with significant valvular disease or documented contraindication to aspirin use, including peptic ulcer disease, renal insufficiency, and use of nonsteroidal anti-inflammatory drugs, were excluded. MAIN OUTCOME MEASURE: All-cause mortality according to aspirin use. RESULTS: During 3.1 years of follow-up, 276 patients (4.5%) died. In a simple univariable analysis, there was no association between aspirin use and mortality (4.5% vs 4.5%). However, after adjustment for age, sex, standard cardiovascular risk factors, use of other medications, coronary disease history, ejection fraction, exercise capacity, heart rate recovery, and echocardiographic ischemia, aspirin use was associated with reduced mortality (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.51-0.87; P =.002). In further analysis using matching by propensity score, 1351 patients who were taking aspirin were at lower risk for death than 1351 patients not using aspirin (4% vs 8%, respectively; HR, 0.53; 95% CI, 0.38-0.74; P =.002). After adjusting for the propensity for using aspirin, as well as other possible confounders and interactions, aspirin use remained associated with a lower risk for death (adjusted HR, 0.56; 95% CI, 0.40-0.78; P<.001). The patient characteristics associated with the most aspirin-related reductions in mortality were older age, known coronary artery disease, and impaired exercise capacity. CONCLUSION: Aspirin use among patients undergoing stress echocardiography was independently associated with reduced long-term all-cause mortality, particularly among older patients, those with known coronary artery disease, and those with impaired exercise capacity.

Aspirin↗

PubMed2001

Gene expression and in situ localization of diacylglycerol kinase isozymes in normal and infarcted rat hearts: effects of captopril treatment.

Diacylglycerol (DG) kinase (DGK) terminates signaling from DG, which serves as an activator of protein kinase C (PKC), by converting DG to phosphatidic acid. DGK is thus regarded as an attenuator of the PKC activity. In rats, five DGK isozymes have been cloned, but little is known about their role in the heart. In this study, the spatiotemporal expression of DGK isozymes was investigated in rat hearts under a normal condition and after myocardial infarction (MI) by in situ hybridization histochemistry and immunohistochemistry. In normal left ventricular myocardium, DGKalpha, DGKepsilon, and DGKzeta mRNAs were expressed evenly throughout the myocardium, although the DGKalpha expression was very low. In infarcted hearts, the expression of DGKzeta was enhanced in the peripheral zone of the necrotic area and at the border zone 3 and 7 days after MI, and to a lesser extent in the middle layer of the granulation tissue 21 days after MI. The enhanced DGKzeta expression in the infarcted and border areas could be attributed to granulocytes and macrophages. In contrast, the expression of DGKepsilon in the infarcted and border areas was lower than that in the viable left ventricle (LV) throughout the postoperation period. Furthermore, DGKepsilon expression in the viable myocardium 21 days after MI decreased significantly compared with left ventricular myocardium in the sham-operated rats and was completely restored by treatment with captopril. Our results demonstrate that three DGK isozymes are expressed in the heart and that each isozyme might have different functional characteristics in the healing and LV remodeling after MI.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2001

FULL-malaria: a database for a full-length enriched cDNA library from human malaria parasite, Plasmodium falciparum.

FULL-malaria is a database for a full-length-enriched cDNA library from the human malaria parasite Plasmodium falciparum (http://133.11. 149.55/). Because of its medical importance, this organism is the first target for genome sequencing of a eukaryotic pathogen; the sequences of two of its 14 chromosomes have already been determined. However, for the full exploitation of this rapidly accumulating information, correct identification of the genes and study of their expression are essential. Using the oligo-capping method, we have produced a full-length-enriched cDNA library from erythrocytic stage parasites and performed one-pass reading. The database consists of nucleotide sequences of 2490 random clones that include 390 (16%) known malaria genes according to BLASTN analysis of the nr-nt database in GenBank; these represent 98 genes, and the clones for 48 of these genes contain the complete protein-coding sequence (49%). On the other hand, comparisons with the complete chromosome 2 sequence revealed that 35 of 210 predicted genes are expressed, and in addition led to detection of three new gene candidates that were not previously known. In total, 19 of these 38 clones (50%) were full-length. From these observations, it is expected that the database contains approximately 1000 genes, including 500 full-length clones. It should be an invaluable resource for the development of vaccines and novel drugs.

Animals↗

PubMed2001

Recombination and gene conversion-like events may contribute to ABO gene diversity causing various phenotypes.

We identified five different alleles, tentatively named ABO*O301, *0302, *R102, *R103, and *A110, in Japanese individuals possessing the blood group O phenotype. These alleles lack the guanine deletion at nucleotide position 261 which is shared by a majority of O alleles. Nucleotide sequence analysis revealed that *0301 and *0302 had single nonsynonymous substitutions compared with *A101 or *A102 responsible for the A1 phenotype. Analysis of intron 6 at the ABO gene by polymerase chain reaction-single-strand conformation polymorphism and direct sequencing revealed that *R102 and *R103 had chimeric sequences of A-02 and B-02, respectively, from exons 6 to 7. In the analysis of five other chimeric alleles detected in the same manner, we identified a total of four different recombination-breakpoints within or near intron 6. When 510 unrelated Japanese were examined, the frequency of the chimeric alleles generated by recombination in intron 6 or exon 7 was estimated to be 1.7%. In addition, we found that *O301, *A110, *C101, *A111, and 35% of *A102 had a unique A-B-A chimeric sequence at intron 6, presumed to originate from a gene conversion-like event. We had previously established that *A110 also had an A-O2-A chimeric sequence around nucleotide position 646 in exon 7. Thus this allele has an A-B-A-O2-A chimeric sequence from intron 6 to exon 7 probably generated by two different gene conversions. Similar patchwork sequences around nucleotide position 646 in exon 7 were observed in two other new alleles responsible for the Ax and B3 phenotypes. Thus, the site is presumably a hotspot for gene conversion. These results indicate that both recombination and gene conversion-like events play important roles in generating ABO gene diversity.

ABO Blood-Group System↗

PubMed2001

Immunohistochemical study on VEGF expression in endometrial carcinoma--comparison with p53 expression, angiogenesis, and tumor histologic grade.

OBJECTIVE: Vascular endothelial growth factor (VEGF)--that activates endothelial cell growth--has been considered to induce angiogenesis, which is indispensable to tumor-genesis and progression. In this study, an immunohistochemical analysis was carried out to clarify the correlation of VEGF expression with angiogenesis, p53 expression--of which the wild-type is considered to suppress VEGF expression--and histologic grade in endometrial carcinoma. STUDY DESIGN: Immunohistochemical staining for detecting VEGF protein, factor VIII-related antigen of endothelial cells, and p53 protein was performed by the labeled streptavidin-biotin method on the formalin-fixed and paraffin-embedded tumor tissue of 104 patients with endometrial (endometrioid) carcinoma, including 69 with well-differentiated, 25 with moderately differentiated, and ten with poorly differentiated adenocarcinoma. RESULTS: The labeling index of p53 expression was 19.9+/-28.8% in the high VEGF group, whereas in the low VEGF group it was 12.2+/-17.0%, showing that VEGF expression was significantly correlated with p53 expression (P<0.05). VEGF expression, however, was not correlated with either the number of microvessels in the tumor area or tumor histologic grade. CONCLUSION: VEGF expression was not a single specific indicator of angiogenesis in endometrial carcinoma, whereas it was significantly correlated with p53 expression.

Adenocarcinoma↗

PubMed2001

Comparison of antimycobacterial activity of grepafloxacin against Mycobacterium avium with that of levofloxacin: accumulation of grepafloxacin in human macrophages.

The bactericidal activity of two new quinolones, grepafloxacin and levofloxacin, against five strains of Mycobacterium avium was investigated in vitro. The minimum inhibitory concentrations (MICs) of these two quinolones, determined by the broth microdilution method, were comparable for all strains tested. In contrast, grepafloxacin suppressed the intracellular growth of all the strains in monocyte-derived macrophages more strongly than levofloxacin, when the cells infected with these strains were incubated for 7 days in the presence of various concentrations of the two new quinolones. To find the reason for the strengthened intracellular killing activity of grepafloxacin, we determined the ratio of the concentration of the new quinolones in the cells to that in the medium (C/M concentration ratio). The C/M concentration ratio of grepafloxacin was increased to 34.7 by 7 days, whereas that of levofloxacin at 7 days was only 12.3. These data suggested that a higher level of intraphagocytic accumulation of grepafloxacin endows it with greater mycobactericidal activity.

Anti-Infective Agents↗

PubMed2001

Increased von Willebrand factor in the endocardium as a local predisposing factor for thrombogenesis in overloaded human atrial appendage.

OBJECTIVES: We investigated immunoreactive von Willebrand factor (vWF), a platelet adhesion molecule, in the endocardial endothelium and its relationship to thrombogenesis in the human atrial appendage. BACKGROUND: Intra-atrial thrombogenesis is generally thought to be induced by blood stasis in the atrial appendage involved with atrial fibrillation (AF). Little attention has been paid to alterations of the endocardial endothelium on which the thrombus develops. METHODS: Atrial appendage tissue was obtained at heart surgery or at autopsy from AF and non-AF cardiac patients and from noncardiac patients. Immunohistochemistry for endothelial cell markers including vWF, CD31, CD34 and endothelial nitric oxide synthase (eNOS) and platelet glycoprotein Ib/IX or IIb/IIIa was performed and semiquantitatively graded. RESULTS: In contrast to the apparent immunostaining for CD31, CD34 and eNOS, only focal or little immunoreactive vWF was seen in the endocardium of noncardiac patients. Immunoreactive vWF in the endocardial endothelium was increased in most cardiac patients, particularly in the left, but not in the right, atrial appendage of patients with mitral valvular disease, irrespective of whether AF was present. Platelet adhesion/thrombus formation in the endocardium was found in limited sites in which the overlying endothelium was deficient in eNOS and CD34. When warfarin-treated cases were excluded, there was a significant correlation between the immunohistochemical grade for vWF and the degree of platelet adhesion/thrombus formation in the endocardium. CONCLUSIONS: Immunoreactive vWF in the endocardial endothelium was increased in overloaded human atrial appendage, which may be a local predisposing factor for intraatrial thrombogenesis.

Adult↗