High Sensitivity of Late Gadolinium Enhancement for Predicting Microscopic Myocardial Scarring in Biopsied Specimens in Hypertrophic Cardiomyopathy

Background

Myocardial scarring can be assessed by cardiac magnetic resonance imaging with late gadolinium enhancement and by endomyocardial biopsy. However, accuracy of late gadolinium enhancement for predicting microscopic myocardial scarring in biopsied specimens remains unknown in hypertrophic cardiomyopathy. We investigated whether late gadolinium enhancement in the whole heart reflects microscopic myocardial scarring in the small biopsied specimens in hypertrophic cardiomyopathy.

Methods and Results

Twenty-one consecutive patients with hypertrophic cardiomyopathy who were examined both by cardiac magnetic resonance imaging and by endomyocardial biopsy were retrospectively studied. The right interventricular septum was the target site for endomyocardial biopsy in all patients. Late gadolinium enhancement in the ventricular septum had an excellent sensitivity (100%) with a low specificity (40%) for predicting microscopic myocardial scarring in biopsied specimens. The sensitivity of late gadolinium enhancement in the whole heart remained 100% with a specificity of 27% for predicting microscopic myocardial scarring in biopsied specimens. Quantitative assessments of fibrosis revealed that the extent of late gadolinium enhancement in the whole heart was the only independent variable related to the microscopic collagen fraction in biopsied specimens (β  =  0.59, 95% confident interval: 0.15 – 1.0, p  =  0.012).

Conclusions

Although there was a compromise in the specificity, the sensitivity of late gadolinium enhancement was excellent for prediction of microscopic myocardial scarring in hypertrophic cardiomyopathy. Moreover, the severity of late gadolinium enhancement was independently associated with the quantitative collagen fraction in biopsied specimens in hypertrophic cardiomyopathy. These findings indicate that late gadolinium enhancement can reflect both the presence and the extent of microscopic myocardial scarring in the small biopsied specimens in hypertrophic cardiomyopathy.     

Population Coding of Forelimb Joint Kinematics by Peripheral Afferents in Monkeys

Various peripheral receptors provide information concerning position and movement to the central nervous system to achieve complex and dexterous movements of forelimbs in primates. The response properties of single afferent receptors to movements at a single joint have been examined in detail, but the population coding of peripheral afferents remains poorly defined. In this study, we obtained multichannel recordings from dorsal root ganglion (DRG) neurons in cervical segments of monkeys. We applied the sparse linear regression (SLiR) algorithm to the recordings, which selects useful input signals to reconstruct movement kinematics. Multichannel recordings of peripheral afferents were performed by inserting multi-electrode arrays into the DRGs of lower cervical segments in two anesthetized monkeys. A total of 112 and 92 units were responsive to the passive joint movements or the skin stimulation with a painting brush in Monkey 1 and Monkey 2, respectively. Using the SLiR algorithm, we reconstructed the temporal changes of joint angle, angular velocity, and acceleration at the elbow, wrist, and finger joints from temporal firing patterns of the DRG neurons. By automatically selecting a subset of recorded units, the SLiR achieved superior generalization performance compared with a regularized linear regression algorithm. The SLiR selected not only putative muscle units that were responsive to only the passive movements, but also a number of putative cutaneous units responsive to the skin stimulation. These results suggested that an ensemble of peripheral primary afferents that contains both putative muscle and cutaneous units encode forelimb joint kinematics of non-human primates.     

Quantitative Analysis of Type IV Collagen α Chains in the Basement Membrane of Human Urogenital Epithelium

Type IV collagen is a major component of the basement membrane (BM), which consists of six genetically distinct α(IV) chains. In this study the expression of these six α(IV) chains was demonstrated immunohistochemically. In addition, the α2(IV) and α5(IV) chains were analysed quantitatively by confocal laser scanning microscopy in human urogenital epithelial BM. The α1/α2(IV) and α5/α6(IV) chains were immunoreactive in the epithelial BM, whereas, α3/α4(IV) chains were not. The quantitative analysis revealed that the amount of α2(IV) and α5(IV) chains differed in each urogenital epithelial BM. The content of α5(IV) chains in the epithelial BM of the bladder was differentially high, and that of the foreskin was differentially low. It is concluded that the elasticity of epithelial BM of the bladder may be structurally related to the high content of α5/α6(IV) chains.     

A facile preparation of gel materials from a solution of cellulose in ionic liquid

This paper reports a facile preparation of a flexible gel material from a solution of cellulose (15% w/w) in an ionic liquid of 1-butyl-3-methylimidazolium chloride by keeping it at room temperature for 7 days. Elemental analysis data indicated that the obtained gel material was composed of cellulose, the ionic liquid, and water. Both XRD and TGA results suggested that crystalline structure of cellulose was largely disrupted in the material. However, the existence of non-crystalline aggregates was assumed by the XRD data of the material. The gel material was probably obtained by the formation of cellulose aggregates in the solution, attributed to the gradual absorption of water. When the material was heated at 120 degrees C, it became soft, and converted into a fluid at 150 degrees C. By keeping the soft material at room temperature for 2 days, a gel material was regenerated, which was more transparent compared with the original material.     

Offshore Dolly Varden charr (<Emphasis Type="Italic">Salvelinus malma</Emphasis>) in the North Pacific

Many studies have investigated the ecology of charrs in freshwater, however, little is known about charrs in the ocean. This study examined the distribution, seasonal abundance, and some biological features of Dolly Varden (Salvelinus malma) in the Pacific Ocean. An analysis of by-catch data of Japanese offshore salmon monitoring showed that Dolly Varden were distributed across a wide range in the offshore waters of the Pacific Ocean, including the Japan Sea, Bering Sea, and Okhotsk Sea. The catch per unit effort showed a sharp increase from May to August, followed by a sharp decrease in September. Offshore areas served as an important summer habitat for anadromous Dolly Varden.     

Altered expression of connexin43 contributes to the arrhythmogenic substrate during the development of heart failure in cardiomyopathic hamster

Heart failure is known to predispose to life-threatening ventricular tachyarrhythmias even before compromising the systemic circulation, but the underlying mechanism is not well understood. The aim of this study was to clarify the connexin43 (Cx43) gap junction remodeling and its potential role in the pathogenesis of arrhythmias during the development of heart failure. We investigated stage-dependent changes in Cx43 expression in UM-X7.1 cardiomyopathic hamster hearts and associated alterations in the electrophysiological properties using a high-resolution optical mapping system. UM-X7.1 hamsters developed left ventricular (LV) hypertrophy by ages 6 approximately 10 wk and showed a moderate reduction in LV contractility at age 20 wk. Appreciable interstitial fibrosis was recognized at these stages. LV mRNA and protein levels of Cx43 in UM-X7.1 were unaffected at age 10 wk but significantly reduced at 20 wk. The expression level of Ser255-phosphorylated Cx43 in UM-X7.1 at age 20 wk was significantly greater than that in control golden hamsters at the same age. In UM-X7.1 at age 10 wk, almost normal LV conduction was preserved, whereas the dispersion of action potential duration was significantly increased. UM-X7.1 at age 20 wk showed significant reduction of cardiac space constant, significant decrease in conduction velocity, marked distortion of activation fronts, and pronounced increase in action potential duration dispersion. Programmed stimulation resulted in sustained ventricular tachycardia or fibrillation in UM-X7.1. LV activation during polymorphic ventricular tachycardia was characterized by multiple phase singularities or wavebreaks. During the development of heart failure in the cardiomyopathic hamster, alterations of Cx43 expression and phosphorylation in concert with interstitial fibrosis may create serious arrhythmogenic substrate through an inhibition of cell-to-cell coupling.     

Quantitative analysis of type IV collagen alpha chains in the basement membrane of human urogenital epithelium

Type IV collagen is a major component of the basement membrane (BM), which consists of six genetically distinct (IV) chains. In this study the expression of these six (IV) chains was demonstrated immunohistochemically. In addition, the 2(IV) and 5(IV) chains were analysed quantitatively by confocal laser scanning microscopy in human urogenital epithelial BM. The 1/2(IV) and 5/6(IV) chains were immunoreactive in the epithelial BM, whereas, 3/4(IV) chains were not. The quantitative analysis revealed that the amount of 2(IV) and 5(IV) chains differed in each urogenital epithelial BM. The content of 5(IV) chains in the epithelial BM of the bladder was differentially high, and that of the foreskin was differentially low. It is concluded that the elasticity of epithelial BM of the bladder may be structurally related to the high content of 5/6(IV) chains.     

Progesterone-dependent and -independent expression of the multidrug resistance type I gene in porcine granulosa cells

A primary role of plasma membrane P-glycoprotein (P-gp), encoded by multidrug resistance type I (MDR1), is to protect against naturally occurring xenotoxics. Progesterone (P₄) profoundly influences MDR1 expression in granulosa cells and luteal cells. Here, P₄ regulation of MDR1 expression was investigated in porcine granulosa cells using the P₄-mediated promoter activity assay and a P4 receptor (PR) antagonist (RU-486). The promoter activity was measured chronologically for 48 h in cells transfected with the PR response element-containing pGL3. LH could stimulate the promoter activity through endogenous P4, with a maximum activity at 5 h. MDR1 mRNA level was highly maintained at 24–36 h. Conversely, exogenous P4 prolonged the promoter activity to further 10 h, and the high level of MDR1 mRNA was maintained even at 48 h. RU-486 completely inhibited the promoter activity, but the level of MDR1 mRNA rapidly increased in the presence of RU-486. The granulosa cells may become susceptible to RU-486 as a xenotoxic to rapidly express MDR1 for protection against it. These results indicate that MDR1 is expressed in porcine granulosa cells through P4-dependent and -independent regulations.