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Kabuki syndrome (KS) is a congenital disorder caused by mutations in either KMT2D on chromosome 12 or KDM6A on chromosome X, encoding a lysine methyltransferase and a lysine demethylase, respectively. A 9-year-4-month-old male patient with a normal karyotype presented with KS and autism spectrum disorder. Genetic testing for KS was conducted by Sanger sequencing and episignature analysis using DNA methylation array data. The patient had a mosaic stop-gain variant in KDM6A and a heterozygous missense variant (rs201078160) in KMT2D. The KDM6A variant is expected to be deleterious. The KMT2D variant pathogenicity has been inconsistently reported in the ClinVar database. Using biobanking resources, we identified two heterozygous individuals possessing the rs201078160 variant. In a subsequent episignature analysis, the KS patient showed the KS episignature, but two control individuals with the rs201078160 variant did not. Our results indicate that the mosaic stop-gained variant in KDM6A, but not the rs201078160 variant in KMT2D, is responsible for the KS phenotype in the patient. This study further demonstrated the utility of DNA methylation information in diagnosing rare genetic diseases and emphasized the importance of a reference dataset containing both genotype and DNA methylation information., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Cardiac Resynchronization Therapy Defibrillator (CRT-D) has been one of the most important therapies for patients with cardiomyopathy over the last decades. Cardiac perforation occurs infrequently but can be fatal. The occurrence of cardiac perforation after CRT-D implantation has not been studied well. The aim of study is to investigate the occurrence, mortality and predictors of cardiac perforation in patients receiving CRT-D during the index hospitalization., Methods: Data were obtained from the National Inpatient Sample, the largest all-player inpatient dataset in the United States. Patients who received CRT-D from 2002 to 2012 were identified using ICD-9 codes. Multivariate analyses were used to identify predictors of cardiac perforation. Complications including in-hospital death and cardiac perforation were identified using ICD-9 codes., Results: A total of 77,827 patients with CRT-D implantation were included into our analysis. After the CRT-D implantation, the in-hospital and rate of cardiac perforation was between 0.24 and 0.48% and had increased significantly (p = 0.02). Although occurrence of cardiac perforation is rare (0.32%), the mortality was 10.6% among those patients with cardiac perforation. In Multivariate analysis identified female as independent risk factors for cardiac perforation (OR: 2.628, 95% CI 1.926-3.585, p < 0.0001)., Conclusion: Despite rapid progress of the tools and skills for CRT-D implantation, the occurrence of cardiac perforation has not improved. While cardiac perforation is rare, it carries the highest rate of mortality, especially in female patients. Implanting physicians should be familiar with the comorbidities and patient demographics that put them at a higher risk for complications., (Copyright © 2019. Published by Elsevier B.V.)

We present a case of critical Ebstein's anomaly with circular shunting, diagnosed in utero. The fetal cardiothoracic area ratio was elevated; tricuspid regurgitation and pulmonary regurgitation worsened with fetal hydrops. At 35 weeks 6 days of gestation, elective caesarean section delivery was performed. Planned bilateral pulmonary artery banding and pulmonary trunk ligation were performed as a palliative operation 4 hours after birth, with the infant in a stable condition. At age 5 days, we performed the Starnes operation. The postoperative course was uneventful and a bidirectional Glenn operation was performed at age 4 months., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

We report the first case of a teenage patient with chromosome 22q11.2 deletion syndrome who died of overwhelming postsplenectomy infection (OPSI) by Streptococcus pneumoniae despite appropriate prevention by pneumococcal vaccine. He had congenital heart disease and underwent several surgeries. Immunodeficiency had not been noticed clinically. Two years prior to death, splenectomy was performed for a drug-resistant idiopathic thrombocytopenic purpura and he was immunized with 23-valent pneumococcal polysaccharide vaccine (PPV23) 4 months after splenectomy. He died suddenly after a mild flu-like symptom. Autopsy was performed and OPSI was diagnosed. Blood culture was positive for S. pneumoniae. This isolated S. pneumoniae strain was serotypically un-typable by polyvalent serum agglutination test. On the contrary, multilocus sequence typing followed by DNA sequencing indicated the molecular serotype as 10A. Additional testing using monovalent and factor-specific sera confirmed the strain as serotype 10A. Ultrastructural observation of this S. pneumoniae strain showed that the polysaccharide capsule was thin and sparse. We speculate that the abnormal morphology of the capsule may have accounted for the polyvalent serum agglutination failure and may possibly be associated with severity of OPSI observed in this case. Chromosome 22q11.2 deletion syndrome is associated with certain immunodeficiency, especially susceptible to S. pneumoniae infections; however, fatal OPSI has not been reported. In addition to vaccination, prophylactic antibiotics may be necessary for these patients who are at risk of immunodeficiency., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

We report the case of a female neonate born at 40 weeks' gestation with no known risk factors. On postnatal day 27, she was transferred to the pediatric intensive care unit and intubated for cardiorespiratory failure; she was diagnosed with group B streptococcus infective endocarditis. Mitral valve vegetations did not improve with antibiotic therapy. Mitral valve surgery was performed on postnatal day 36. A mechanical mitral valve with short-segment polytetrafluoroethylene skirt was inserted into the supra-annular position; gentian violet was applied to the sewing ring and skirt. She was discharged from the hospital after 6 weeks with good cardiac function and normal sinus rhythm., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Double-hit lymphoma (DHL) is defined as lymphoma with concurrent BCL2 and MYC translocations. While the most common histological subtype of DHL is diffuse large B-cell lymphoma, the present patient had leukemic follicular lymphoma (FL). A 52-year-old man was admitted to our hospital due to general fatigue and cervical and inguinal lymph node swelling. The patient was leukemic and the pathological diagnosis of the inguinal lymph node was FL grade 1. Chromosomal analysis revealed a complex karyotype including a rare three-way translocation t(8;14;18)(q24;q32;q21) involving the BCL2, MYC, and IGH genes. Based on a combination of fluorescence in situ hybridization (FISH), using BCL2, MYC and IGH, and spectral karyotyping (SKY), the karyotype was interpreted as being the result of a multistep mechanism in which the precursor B-cell gained t(14;18) in the bone marrow and acquired a translocation between der(14)t(14;18) and chromosome 8 in the germinal center, resulting in t(8;14;18). The pathological diagnosis was consistently FL, not only at presentation but even after a second relapse. The patient responded well to standard chemotherapies but relapsed after a short remission. This patient is a unique case of leukemic DH-FL with t(8;14;18) that remained in FL even at a second relapse., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aims: Excess sodium causes the development of cardiovascular diseases in conjunction with enhancing renin-angiotensin-aldosterone system (RAAS). Natriuretic peptides are sodium regulators and prevent pathological cardiac alterations by counteracting RAAS. However, it is unknown whether natriuretic peptides inhibit the sodium effect in adverse cardiac alterations. Here, we investigated whether excess salt intake could exacerbate cardiac remodeling in mice with impaired natriuretic peptide signaling., Materials and Methods: Mice lacking the gene encoding the natriuretic peptide receptor, guanylyl cyclase-A (GC-A), and wild-type mice were administered with either a vehicle substance or a subpressor dose of aldosterone (100ng/kg/min), alongside low salt (0.001% NaCl), normal salt (0.6% NaCl), or high salt diets (6.0% NaCl) for four weeks. Mice were then sacrificed and the hearts were evaluated by histology and RT-PCR., Key Findings: Salt load did not induce cardiac changes in vehicle and aldosterone groups in wild-type mice. On the other hand, cardiac hypertrophy and interstitial fibrosis were significantly exacerbated in a salt dependent manner in GC-A knockout (KO) mice administered aldosterone, and were associated with enhanced gene expression relevant to hypertrophy, fibrosis, and oxidative stress conditions. Of note, excess salt intake increased the expression of Sgk1, serum and glucocorticoid responsive kinase-1, in aldosterone-administered GC-A KO mice. These molecular changes were not observed in wild-type mice., Significance: The results of the present study demonstrate that excess salt intake induced cardiac remodeling in conjunction with aldosterone administration in GC-A KO mice, indicating that GC-A signaling attenuated the deleterious salt effect in aldosterone-induced cardiac remodeling., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Cardiac function and survival after the Damus-Kaye-Stansel (DKS) procedure are encouraging, but only limited data exist related to postprocedural semilunar valve function. We investigated postprocedural midterm to long-term outcomes and changes in semilunar valve function and identified risk factors of semilunar valve function deterioration., Methods: Between 1996 and 2012, 63 patients with a single functional ventricle underwent the DKS procedure. Of them, 50 had previously undergone pulmonary artery banding. Cardiac function was measured by catheter examination 5.3 months (interquartile range, 2.6 to 9.7) preoperatively and 1.2 years (interquartile range, 1.0 to 1.4) postoperatively. Echocardiographic examination of the semilunar valve was performed concurrently with the catheter examination and at the last follow-up (5.3 years [interquartile range, 3.1 to 9.2] postoperatively)., Results: The overall survival rate at 1, 5, and 10 years postoperatively was 0.97, 0.92, and 0.89, respectively. Aortic and pulmonary valve regurgitation grade 1 year postoperatively and at the last follow-up increased compared with the preoperative grade. There was no significant difference between regurgitation at 1 year and the last follow-up. The duration from pulmonary artery banding to the DKS procedure was longer in the group with at least mild regurgitation (n = 6) than in the group with less than mild regurgitation (n = 54)., Conclusions: Although the duration from pulmonary artery banding to the DKS procedure was associated with postoperative regurgitation, neither postprocedural aortic nor pulmonary valve regurgitation increased over time, and there were no deleterious effects on the clinical conditions., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Patients with chronic kidney disease (CKD) die of cardiovascular diseases for unknown reasons. Blood vessel formation in plaques and its relationship with plaque stability could be involved with signaling through the Flt-1 receptor and its ligands, vascular endothelial growth factor, and the closely related placental growth factor (PlGF). Flt-1 also exists as a circulating regulatory splice variant short-inhibitory form (sFlt-1) that serves as a decoy receptor, thereby inactivating PlGF. Heparin releases sFlt-1 by displacing the sFlt-1 heparin-binding site from heparin sulfate proteoglycans. Heparin could provide diagnostic inference or could also induce an antiangiogenic state. In the present study, postheparin sFlt-1 levels were lower in CKD patients than in control subjects. More importantly, sFlt-1 levels were inversely related to atherosclerosis in CKD patients, and this correlation was more robust after heparin injection, as verified by subsequent cardiovascular events. Knockout of apolipoprotein E (ApoE) and/or sFlt-1 showed that the absence of sFlt-1 worsened atherogenesis in ApoE-deficient mice. Thus, the relationship between atherosclerosis and PlGF signaling, as regulated by sFlt-1, underscores the underappreciated role of heparin in sFlt-1 release. These clinical and experimental data suggest that novel avenues into CKD-dependent atherosclerosis and its detection are warranted.

Background: Little is known about the clinical and prognostic impact of early repolarization (ER) on patients with Brugada syndrome (BrS), especially those with documented ventricular fibrillation (VF)., Objective: To investigate the prevalence and prognostic significance of ER in inferolateral leads in patients with BrS and documented VF., Methods: We investigated 10 different 12-lead electrocardiograms (ECGs) recorded on different days to identify the presence of ER, which was defined as J-point elevation ≥0.1 mV in inferior (II, III, aVF) or lateral leads (I, aVL, V₄-V₆), in 49 individuals (46 men; age 46 ± 13 years) with a type 1 ECG of BrS and previous history of VF., Results: ER was observed persistently (in all ECGs) in 15 patients (31%; P group), intermittently (in at least one but not in all ECGs) in 16 patients (33%; I group), and not observed in 18 patients (37%; N group), yielding an overall ER incidence of 63% (31/49). During the follow-up period (7.7 years), recurrence of VF was documented in all 15 patients (100%) in the P group, and less in 12 patients (75%) in the I group and in 8 patients (44%) in the N group. The P group showed a worse prognosis than N group (P = .0001) by Kaplan-Meier analysis. Either persistent or intermittent ER in an inferolateral lead was an independent predictor of fatal arrhythmic events (hazard ratio 4.88, 95% confidence interval 2.02-12.7, P = .0004; and hazard ratio 2.50, 95% confidence interval 1.03-6.43, P = .043, respectively)., Conclusion: The prevalence of ER in inferolateral leads was high and an especially persistent form of ER was associated with a worse outcome in BrS patients with documented VF., (Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Brain natriuretic peptide (BNP) and amino-terminal proBNP (NT-proBNP) are useful biomarkers for diagnosis and prediction of prognosis. Both of these peptides are elevated in patients with chronic kidney disease (CKD), but there is no evidence as to which peptide is the more suitable biomarker in patients with severe renal dysfunction., Methods and Results: This retrospective cohort study evaluated patients with cardiovascular diseases (64.9±11.7 years, mean±SD). The end points were all-cause death and a composite end point of all-cause death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for severe heart failure, and initiation of hemodialysis. Baseline plasma BNP and NT-proBNP levels, expressed as log-transformed data, were closely correlated in patients with CKD stages 1-3 (n=998) (r2=0.870, p<0.001), whereas for CKD stages 4-5 (n=85) there was a significant but weaker correlation (r2=0.209, p<0.001). During follow-up periods (51.3±0.4 months), 132 patients died and 202 patients reached the composite end point. The area under the receiver operating characteristic curve (AUROC) for BNP and NT-proBNP were similar for CKD stages 1-3. However, for CKD stages 4-5, the AUC for mortality for BNP was 0.713 and that for NT-proBNP was 0.760, while the AUC for the composite end point for BNP was 0.666 and that for NT-proBNP was 0.720., Conclusions: Both BNP and NT-proBNP are useful biomarkers for mortality and cardiovascular events, but NT-proBNP may be superior to BNP for CKD stages 4-5., (Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Use of programmed electrical stimulation (PES) for risk stratification of Brugada syndrome (BrS) is controversial., Objective: To elucidate the role of the number of extrastimuli during PES in patients with BrS., Methods: Consecutive 108 patients with type 1 electrocardiogram (104 men, mean age 46 ± 12 years; 26 with ventricular fibrillation [VF], 40 with syncope, and 42 asymptomatic) underwent PES with a maximum of 3 extrastimuli from the right ventricular apex and the right ventricular outflow tract. Ventricular arrhythmia (VA) was defined as VF or nonsustained polymorphic ventricular tachycardia >15 beats. Patients with VA induced by a single extrastimulus or double extrastimuli were assigned to group SD (Single/Double), by triple extrastimuli to group T (Triple), and the remaining patients to group N., Results: VA was induced in 81 patients (VF in 71 and polymorphic ventricular tachycardia in 10), in 4 by a single extrastimulus, in 41 by double extrastimuli, and in 36 by triple extrastimuli. During 79 ± 48 months of follow-up, 24 patients had VF events. Although the overall inducibility of VA was not associated with an increased risk of VF (log-rank P = .78), group SD had worse prognosis than did group T (P = .004). Kaplan-Meier analysis in patients without prior VF also showed that group SD had poorer outcome than did group T and group N (P = .001). Positive and negative predictive values of VA induction with up to 2 extrastimuli were, respectively, 36% and 87%, better than those with up to 3 (23% and 81%, respectively)., Conclusions: The number of extrastimuli that induced VA served as a prognostic indicator for patients with Brugada type 1 electrocardiogram. Single extrastimulus or double extrastimuli were adequate for PES of patients with BrS., (Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: A high incidence of early repolarization (ER) pattern in the inferolateral leads has been reported in patients with idiopathic ventricular fibrillation (IVF). Brugada syndrome (BS) is characterized by J-point or ST-segment elevation in the right precordial leads and ventricular fibrillation, and some patients with BS also have ER in the inferolateral leads., Objective: To compare the clinical characteristics and effects of sodium-channel blockade on ER between IVF patients with ER (early repolarization syndrome [ERS]) and BS patients with or without ER., Methods: Fourteen patients with ERS and 21 patients with BS were included in this study. ER was defined as an elevation of at least 0.1 mV from baseline in the QRS-T junction in the inferorolateral leads. Provocative tests with sodium-channel blockers were conducted in all patients with ERS to distinguish ERS from BS., Results: In the ERS group, all patients were male and most patients experienced ventricular fibrillation during sleep or low activity (79%). ER was attenuated by sodium-channel blockers in most patients with ERS (13/14, 93%) and BS (5/5, 100%), whereas ST-segment elevation was augmented in the right precordial leads in the BS group. The rates of positive late potentials were significantly higher in the BS group (60%) than in the ERS group (7%) (P <.01)., Conclusions: Some similarities were observed between ERS and BS, including gender, arrhythmia triggers, and response of ER to sodium-channel blockers. Unlike the ST segment in the right precordial leads in BS, ER was attenuated in patients with both ERS and BS, suggesting a differential mechanism between ER in the inferolateral leads and ST elevation in the right precordial leads., (Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Dual-source computed tomography (DSCT) has enabled us to non-invasively visualize coronary artery stenosis, but its ability to characterize coronary atherosclerotic plaques (ASPs) has not been evaluated. Intravascular optical coherence tomography (OCT) provides tissue images of coronary artery wall that are validated by pathohistological studies. We studied the diagnostic accuracy of DSCT in the characterization of coronary ASPs, especially lipid-rich ASP with thin fibrous cap (TCFA), in comparison with OCT., Methods: DSCT and OCT were used to image non-stenotic ASPs in non-culprit coronary arteries of 17 acute coronary syndrome (ACS) patients, and 162 coronary regions were enrolled., Results: The mean CT values of fibrous ASP, ASP with lipid core, and ASP with calcium deposit were 77.5, 28.9, and 515.9 HU, respectively (P<0.0001). ASP with calcium deposit was detected with a sensitivity of 88.9% and a specificity of 98.6%, while ASP with lipid core was detected by DSCT with a relatively low sensitivity of 73.1% and a high specificity of 94.0%. In TCFA, cross-sectional areas of both ASP and lipid core were significantly larger, mean CT value of ASP was significantly lower, and concomitant calcification was more frequently observed compared with lipid-rich ASP with thick fibrous cap (ThCFA). The combination of these CT parameters seems to be a useful index for the differentiation of TCFA from ThCFA., Conclusion: DSCT is useful for non-invasive evaluation of calcified and fibro-fatty tissue characters in coronary artery plaque, but it is still not able to differentiate TCFA, one of the features of vulnerable plaque., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Background: Coronary spasm (CS) plays an important role in the pathogenesis of many types of ischemic heart disease, but morphological appearance of non-stenotic coronary segments with CS is not fully understood. We evaluate the morphological characteristics of coronary arteries in patients with coronary spastic angina (CSA) using intravascular optical coherence tomography (OCT)., Methods: We evaluated 37 patients with resting chest pain whose coronary angiograms did not reveal significant stenosis. These patients underwent an acetylcholine (ACh) provocation test. OCT was performed after complete dilatation of coronary arteries, and additionally during ACh-induced CS in four patients., Results: Based on the ACh test, 23 patients were diagnosed as having CSA, and the remaining 14 patients without CS were referred to as CS-negative. OCT study revealed that coronary segments with ACh-induced CS had homogeneous intimal thickening, and quantitative analysis showed that CS-positive segments had a significantly greater intima area as compared with corresponding CS-negative segments without lipid or calcium content. By contrast, CS-positive segments had a significantly smaller intima area as compared with CS-negative segments with lipid or calcium deposit. During ACh-induced CS, lumen and total vascular areas were significantly decreased, whereas intima area did not change in comparison with complete vasodilatation. The luminal surface of the intima formed a markedly wavy configuration during CS., Conclusions: Coronary artery segments involved in CS are characterized by diffuse intimal thickening without lipid or calcium content. High-resolution coronary OCT imaging could make it possible to analyze the vascular pathophysiology in patients with CS., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

The effect of IL-2 on the expression of the mouse zinc-fingers and homeoboxes 1 (ZHX1) gene was investigated in a mouse cytotoxic T cell line, CTLL-2 cells. IL-2 specifically induced the expression of ZHX1 mRNA. The level of ZHX1 mRNA was decreased in the absence of IL-2. These alterations were in parallel with the status of cell proliferation. The signaling pathways involved in the induction were examined. AG-490, wortmannin, and LY294002 blocked the induction by IL-2. Nuclear run-on assays and a mRNA stability analysis revealed that the half-life of ZHX1 mRNA but not the transcription rate of the gene was increased by IL-2. Thus, we conclude that IL-2 induces the expression of the mouse ZHX1 gene in CTLL-2 cells, that both Janus kinase 3/signal transducer and activator of transcription 5 and phosphoinositide 3-kinase pathways are involved in the induction, and that the increased mRNA stability results in the induction.

The rat enhancer of split- and hairy-related protein-2 (SHARP-2) is a basic helix-loop-helix transcription factor. The hepatic expression of SHARP-2 mRNA was investigated under various conditions. The level was decreased in the regenerating rat liver and malignant hepatoma cells. In contrast, the expression of SHARP-2 mRNA was induced in rat livers by feeding a high-carbohydrate diet. To analyze the molecular mechanism involved in the regulation of the rat SHARP-2 gene expression, the gene was cloned. It was approximately 6-kb in length and consists of five exons and four introns. To investigate the transcriptional regulatory region of this gene, SHARP-2/firefly luciferase reporter plasmids were transfected into hepatoma cells. A functional analysis of 5(')-deletion constructs revealed that two E box sequences between -160 and -144 are mainly responsible for promoter activity. Although upstream stimulatory factors (USFs) bound to the element in vitro, USF2 failed to stimulate promoter activity from the element using the co-transfection experiment. Therefore, other E box-binding transcription factors differing from USF proteins or USF-associated proteins are necessary for transcriptional stimulation of the rat SHARP-2 gene.

Background: Some patients with univentricular hearts who are candidates for Fontan operation may develop ventricular outflow tract obstruction after pulmonary artery banding (PAB) or Fontan. However, the indication for Damus-Kaye-Stansel (DKS) operation for these patients has not been clear. To clarify the indication, the changes in the diameter of ventricular outflow tract and the feasibility of DKS operation before or with Fontan were investigated., Methods: Among the patients with univentricular heart who underwent PAB, 21 patients had probable ventricular outflow obstruction with an aorta arising from the morphologic right ventricle. Diameter of ventricular outflow tract was measured before and after PAB, Glenn, and Fontan operations with or without DKS, and indexed by normal value (%VOT)., Results: Six patients died after PAB. In the surviving 15 patients, %VOT decreased significantly from 103% (median, range 75%-153%) to 75% (range 52%-153%) after PAB. Four with very small %VOT (52% to 63%) after PAB needed DKS with bidirectional Glenn or central shunt operation, and 5 with moderately small %VOT (67% to 109%) after PAB needed DKS concomitantly with Fontan. A patient with %VOT of 117% before Fontan required DKS after Fontan. A patient with %VOT of 153% underwent Fontan without DKS and obstruction did not develop after Fontan. The remaining 4 patients were under consideration for Glenn or Fontan operation., Conclusions: The diameter of the ventricular outflow tract decreased after PAB and Fontan operations. DKS operations might be indicated before Fontan if the indexed diameter of ventricular outflow tract after PAB was below 70% and concomitantly with Fontan if it was below 120%.

Background: Change in apoptosis in gastric glands after eradication of Helicobacter pylori has never been reported., Aims: The purpose of this paper is to investigate the change in apoptosis in gastric glands after eradication of Heliobacter pylori., Patients and Methods: We studied 23 Heliobacter pylori-positive patients with duodenal and gastric ulcers, who were monitored for 6-12 months after eradication, and eight controls. Biopsies were taken from the antrum and body. Apoptosis was evaluated immunohistochemically using anti-single stranded DNA antibody. Apoptotic index was calculated by counting immunostained cells in surface epithelial and glandular cells., Results: In the surface epithelium, Apoptotic indexes were significantly higher in patients than in controls. In the upper portion of fundic glands, apoptotic indexes were significantly higher in patients with gastric ulcers (14.2% (9.3, 17.8)) (median (1st quartile, 3rd quartile)) than in controls (8.0% (2.0, 9.0), p < 0.01) and decreased significantly after eradication (3.4% (2.0, 5.3)), p < 0.01). In pyloric glands, apoptotic indexes were no different between patients and controls. In the lower portion of fundic glands, apoptotic indexes were very low, both in patients and in controls., Conclusions: Our results showed that apoptosis, not only of surface epithelial cells but also of glandular cells in the upper portion of fundic glands, increased in Heliobacter pylori-positive patients with gastric ulcers and decreased to normal levels after eradication of Heliobacter pylori.

Zinc-fingers and homeoboxes 1 (ZHX1) is a protein that interacts with the activation domain of the A subunit of nuclear factor-Y. The function of ZHX1, as a transcription factor, was characterized and their domains were mapped. To determine the nuclear localization signal, expression vectors, in which various truncated forms of ZHX1 were fused to the C-terminal of green fluorescence protein (GFP), were transfected into human embryonic kidney (HEK) 293 cells. All GFP-ZHX1 fusion proteins including an arginine-rich region that corresponds to the amino acid sequence between 734 and 768 were localized in the nuclei. A dimerization domain of the ZHX1 was also mapped using protein-protein interaction assays. The homeodomain (HD) 1 consisting of the amino acid sequence between 272 and 432 of ZHX1 was necessary and sufficient for dimerization. Lastly, the transcriptional activity of ZHX1 was examined using a mammalian one-hybrid system. ZHX1, fused to the C-terminal of the GAL4 DNA-binding domain, was co-transfected with luciferase reporter plasmids with or without five copies of the GAL4-binding site into HEK293 cells. The luciferase activity was decreased in both concentration- and GAL4-binding site-dependent manner. The acidic region corresponding to the amino acid sequence between 831 and 873 was a repressor domain and dimerization was prerequisited for full repressor activity.

We studied vascular endothelial growth factor (VEGF) mRNA synthesis by peripheral blood mononuclear cells (PBMCs) in 30 patients with acute myocardial infarction (AMI) and 20 healthy individuals. PBMCs were isolated from all patients on days 3 and 14 after the onset of aMI, and from all of control individuals. To prepare samples containing identical amounts of GAPDH cDNA, competitive PCR was performed by co-amplifying serial dilutions of GAPDH mutant templates. Next, to measure VEGF cDNA quantitatively in the samples containing identical amounts of GAPDH, we also used competitive PCR by co-amplifying mutant templates of VEGF. The serum VEGF concentrations on day 14 in patients with aMI were measured by an ELISA method. Higher levels of VEGF mRNA in PBMCs were present on day 14 than either on day 3 or in the control group. Serum VEGF concentrations correlated with the VEGF mRNA levels of PBMCs on day 14. Peak serum CK levels correlated well with VEGF mRNA levels of PBMCs on day 14. The present findings suggest that PBMCs may be one of the candidates responsible for elevated circulatory VEGF protein following aMI. In addition, VEGF mRNA may be overexpressed in PBMCs in response to cardiac muscle damage.

We examined serial changes in serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) measured by ELISAs in 45 patients with acute myocardial infarction (AMI) who received heparin intravenously for 3 to 5 days after the onset and in 30 control subjects with an old myocardial infarction. To evaluate the effect of heparin on these serum levels, heparin was administered intravenously in 10 patients with AMI on day 21. Blood samples were obtained from all AMI patients on days 1, 2, 3, 7, 14, 21, and 28 and from 10 AMI patients before and 1 h after heparin administration. Serum VEGF level was significantly reduced after heparin administration (P<0.001). Serum samples from day 1 to 3 were therefore excluded from the subsequent analysis. Serum VEGF level in AMI patients was significantly higher on day 7 than in the control subjects (P<0.0001), and then decreased over time (P<0.0001). The serum VEGF level on day 7 was independently associated with the peak serum CK level (P<0.05). The serum bFGF level did not differ significantly between the AMI patients and the control subjects. In conclusion, the serum VEGF level may be selectively elevated during the healing process after AMI.

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

Although transaortic patch repair under cardiopulmonary bypass is a suitable procedure for aortopulmonary window, another method without cardiopulmonary bypass may be the only one for an infant with extremely low birth weight. We describe a successful repair of an infant with extremely low birth weight (758 g) by closing the window with a clip through a left thoracotomy. Cardiac catheterization 7 months after the operation showed no residual shunt and no stenosis of ascending aorta, pulmonary artery, or coronary arteries in the patient, whom we believe to be one of the smallest with successful repair.

Surgical atrial septostomy using a special atriotomy knife without cardiopulmonary bypass in patients with obstruction of the left-sided atrioventricular valve and complex cardiac anomalies is described. This procedure is effective, safe, and economical for patients in the acute stage after intracardiac repair, and available for patients with a closed fossa ovalis.

To elucidate the effect of interleukin-6 (IL-6) on bone and bone marrow (BM), human IL-6 transgenic mice (hIL-6 tgm) were produced. Their bone and BM were examined histologically, radiologically, histomorphometrically, and hematologically on a temporal basis. hIL-6 tgm showed histologically evident neutrophilia in BM. Increase in precursors of granulocytes and monocytes in hIL-6 tgm was demonstrated by an assay for colony forming unit in culture (CFU-C) of BM cells. Decrease in osteoblasts and osteoid and suppression of primary spongiosa formation were predominantly observed in hIL-6 tgm at 14 weeks old, the terminal stage of life for hIL-6 tgm. An assay for colony forming unit in fibroblastic (CFU-F) of BM cells revealed a decrease in osteoblast precursor (with regard to alkaline phosphatase-positive colonies) in hIL-6 tgm at 15 weeks old. Histomorphometry demonstrated a decrease of both osteoclast number and bone resorption in hIL-6 tgm. These results suggested that enhanced granulocytic hematopoiesis, suppressed bone turnover, and alteration of cellular population in stromal cells in BM occurred in hIL-6 tgm. Thus we provide new findings that facilitate understanding of cellular interrelationships among hematopoietic cells, osteoblasts, and osteoclasts mediated by stromal cells in BM.

A program for calculating the total concentrations of ligands and metals at any temperature, ionic strength and pH for solutions with a controlled metal concentration was written in Quick-Basic. For the calculation, the absolute stability constants of ligands and the proton activity coefficient were corrected for temperature and ionic strength.

A program for calculation of the proton activity coefficient at any given ionic strength and temperature was written in Quick Basic. The calculation of proton activity coefficient was confirmed by titration of HEPES buffer.

The release of digoxin and its simultaneous conversion to digoxigenin bisdigitoxoside, digoxigenin monodigitoxoside, and digoxigenin in a USP dissolution test medium were followed by high-pressure liquid chromatography. Two products, Tablets A and B, were manufactured by solvent deposition and simple blending methods, respectively. Tablet A released digoxin faster than Tablet B in distilled water and in artificial intestinal juice, and no decomposition was observed. In the USP dissolution test medium, the rate of hydrolysis to digoxigenin bisdigitoxoside was almost equal to that of hydrolysis to digoxigenin monodigitoxoside, and a comparatively large formation rate of digoxigenin was observed. Concentrations of digoxin and its decomposition products were described by differential equations that included dissolution rates of digoxin (rapidly dissolving digoxin and digoxin crystals) and an apparent hydrolysis rate. In the earlier stage of dissolution, hydrolysis was rate determining; in the later stage, dissolution became the rate-determining step for overall digoxin degradation. To suppress digoxin hydrolysis in the USP dissolution test medium, a developmental formulation study was performed. The incorporation of magnesium oxide and magnesium hydroxide-aluminum hydroxide in the tablet formulations inhibited digoxin hydrolysis by 15.3 and 14.5%, respectively, after dissolution for 30 min without serious delay of drug release.