Disappearance of perihepatic lymph node enlargement after hepatitis C viral eradication with direct-acting antivirals.

Perihepatic lymph node enlargement (PLNE) which has been shown to be negatively associated with hepatocellular carcinoma (HCC) occurrence is frequently observed in chronic liver disease; however, changes in the state of perihepatic lymph nodes after eradication of hepatitis C virus (HCV) have not been investigated yet. We aimed to evaluate this issue. We enrolled 472 patients with chronic HCV infection who achieved viral eradication with direct-acting antivirals (DAA). We investigated whether the status of perihepatic lymph nodes changed before and after HCV eradication (primary endpoint). We also evaluated the association between PLNE and clinical findings such as liver fibrosis or hepatocellular injury before HCV eradication (secondary endpoint). Perihepatic lymph node enlargement was detected in 164 of 472 (34.7%) patients before DAA treatment. Surprisingly, disappearance of PLNE was observed in 23.8% (39 patients) of all PLNE-positive patients after eradication of HCV. Disappearance of PLNE was not associated with baseline clinical parameters or changing rates of clinical findings before and after DAA treatment. At baseline, presence of PLNE was significantly associated with a lower serum HCV-RNA level (P = .03), a higher serum AST level (P = .004) and a higher ALT level (P < .001) after adjustment for sex and age. In conclusion, PLNEs became undetectable after DAA treatment in 23.8% of PLNE-positive patients. Further study with a longer follow-up period is needed to clarify the clinical importance of this phenomenon especially in relationship with the risk of HCC development.

Free-flight measurement technique in the free-piston high-enthalpy shock tunnel.

A novel multi-component force-measurement technique has been developed and implemented at the impulse facility JAXA-HIEST, in which the test model is completely unrestrained during the test and thus experiences free-flight conditions for a period on the order of milliseconds. Advantages over conventional free-flight techniques include the complete absence of aerodynamic interference from a model support system and less variation in model position and attitude during the test itself. A miniature on-board data recorder, which was a key technology for this technique, was also developed in order to acquire and store the measured data. The technique was demonstrated in a HIEST wind-tunnel test campaign in which three-component aerodynamic force measurement was performed on a blunted cone of length 316 mm, total mass 19.75 kg, and moment of inertia 0.152 kgm(2). During the test campaign, axial force, normal forces, and pitching moment coefficients were obtained at angles of attack from 14° to 32° under two conditions: H0 = 4 MJ/kg, P0 = 14 MPa; and H0 = 16 MJ/kg, P0 = 16 MPa. For the first, low-enthalpy condition, the test flow was considered a perfect gas; measurements were thus directly compared with those obtained in a conventional blow-down wind tunnel (JAXA-HWT2) to evaluate the accuracy of the technique. The second test condition was a high-enthalpy condition in which 85% of the oxygen molecules were expected to be dissociated; high-temperature real-gas effects were therefore evaluated by comparison with results obtained in perfect-gas conditions. The precision of the present measurements was evaluated through an uncertainty analysis, which showed the aerodynamic coefficients in the HIEST low enthalpy test agreeing well with those of JAXA-HWT2. The pitching-moment coefficient, however, showed significant differences between low- and high-enthalpy tests. These differences are thought to result from high-temperature real-gas effects.

Trunk muscularity in throwers.

This study aimed to examine and compare the trunk muscularity of track and field throwers and non-athletes, and its predictive value to the physical performance of the athletes. Using a magnetic resonance imaging method, the skeletal muscle volume (SMV) of the trunk (SMV(trunk)) was determined in 19 strength trained athletes and 18 non-athletes. Also, the SMV of upper, middle and lower regions of the trunk was calculated in every 33% of the trunk length. For the athletes, the maximum weight (1RM) of squat, high clean, and deadlift, and shot forward throwing score were measured. The SMV(trunk) in the athletes was 10% greater than that of non-athletes, with a larger difference in the upper region of the trunk. Step-wise multiple regression analysis indicated that the SMV of the lower region was a significant contributor for predicting the 1RM values of the 3 tasks, as well as the shot forward throwing score. The current results indicate that, while the muscularity of the trunk in track and field throwers is characterized by predominant development in the upper region, the muscularity in the lower region is a determinant factor for the 1RM values of the squat, high clean, and deadlift and shot forward throwing score.

Age estimation using microfocus X-ray computed tomography of lower premolars.

The dental pulp, like other parts of the body, shows age-related changes. The aim of this study was to develop an age estimation method based on the ratio of the three-dimensional volume of the pulp chamber compared to the total tooth. Pulp chamber volumes were calculated using microfocus X-ray computed tomography (SMX-130CT, Shimadzu, Co., Kyoto, Japan) of the three-dimensional digital radiographic images of teeth. The specimens used in this study were 50 lower first and 50 lower second premolar teeth without caries or other abnormalities, obtained from patients in six 10-year age groups (age range 20-78 years). Each specimen was imaged by a micro-CT to reconstruct the three-dimensional structure. Using the reconstructed images, the tooth and pulp volumes at four levels (crown area (L(1)); coronal one third (L(2)); midroot (L(3)), and apical one third of the root (L(4))) were measured. Mean values of the pulp-tooth volume ratio (PTVR(1-4)) were compared between the six age groups and these values were used as the variables for the multiple regression analysis. The coronal one third of the root (L(2)) showed the greatest ratio values, followed by L(3), L(4) and L(1) in all age groups. Morphological changes of the pulp cavity in different age groups were observed. PTVR gradually reduced in value with increasing age, with the steepest reduction occurring in the 20-50 age range, and most noticeably at the L(2) level. The coefficients of determination by multiple regression analysis for four variables were 0.635 for lower first and 0.703 for lower second premolars. Among the variables used for estimating age by this method, only PTVR(2) showed a significant correlation at P<0.001. To determine the variables with the most significant contribution and to optimize the models, stepwise regression method was applied with inclusion level at P<0.05. Only the variable of PTVR(2) contributed significantly to the fit for lower first premolar whereas the two variables of PTVR(1) and PTVR(2) for lower second premolars. The coefficients of determination for the chosen variables were 0.625 for lower first and 0.698 for lower second premolars. Pulp-tooth volume ratio is an age-dependent variable that can be used to estimate age with reasonable accuracy.

Effects of 6 months of walking training on lower limb muscle and tendon in elderly.

The purpose of this study was to investigate the effects of 6 months of walking training on muscle strength, muscle thickness and tendon stiffness on various parts of the lower limbs in the elderly. Subjects were assigned to training (n=35) and control (n=10) groups. Maximal isometric torque (MVC) and muscle thickness for knee extensors (KE), knee flexors (KF), dorsi flexors (DF) and plantar flexors (PF) were measured. Tendon stiffness for KE and PF was measured using ultrasonography while subjects performed isometric contraction. No significant changes occurred in any measured variables in the control group. In the training group, muscle thickness increased significantly for KF and DF, but not for PF. For KE, significant increases of muscle thickness at the proximal and medial sides were observed, although mean relative increase of the eight measured sites for KE was not significant. MVC increased significantly for KF, DF, and PF, but not for KE. In addition, tendon stiffness for KE and PF did not change after training. These results indicated that walking training brought about increments of muscle thickness and strength in most of the lower limbs in the elderly, but it did not result in any changes in tendon stiffness.

Component analysis of dental porcelain for assisting dental identification.

The fluorescence of porcelain crowns recovered from the mouth of an unknown murder victim, and several control porcelain samples, were examined by fluorescent examination lamps. The fluorescence from two of the control samples was quite similar to that from the porcelain crowns recovered from the victim. To increase the objectivity of the results by quantitative analysis, the composition of each porcelain crown and control sample was also evaluated by wave dispersion X-ray microanalyser. The elements detected from the porcelain crowns of the victim matched those of two of the porcelain samples. Later, the antemortem dental records and radiographs of the victim were obtained through a dentist, who had recognized the name of the porcelain manufacturer in a postmortem dental information request placed on the Japanese Dental Association web page. Although component analysis of dental porcelain may be an effective means of assisting dental identification, a more rapid and non-destructive analysis for detecting the elements is required. The energy dispersive X-ray fluorescence (EDXRF) spectrometer was used for a pilot study of identification of porcelain composition.

Allele frequencies of dinucleotide repeat marker loci on the X chromosome in the Japanese population.

The allele frequencies of 18 dinucleotide repeat marker loci on the X chromosome have been analyzed in 130 Japanese individuals living in Kanagawa by means of multiplex PCR and the ABI PRISM Linkage Mapping Set MD 10 Panel 28, followed by capillary electrophoresis using the ABI PRISM 310 Genetic Analyzer.

Immunocytochemical demonstration of the gap junction proteins connexin 43 and connexin 45 in the musculature of the rat small intestine.

The immunohistochemical localization of connexin (Cx) 43 and Cx 45 in the musculature of the rat small intestine was studied at the ultrastructural level, with special reference to the interstitial cells of Cajal in the deep muscular plexus region (ICC-DMP). Cx 43 was localized at gap junctions formed between every group of cells, i.e., smooth muscle cell~smooth muscle cell, smooth muscle cell--ICC-DMP and ICC-DMP--ICC-DMP. In contrast, Cx 45 immunoreactivity was only detected at gap junctions between ICC-DMP--ICC-DMP. Since different types of Cx molecules have different properties for electrical and chemical coupling of cells, it is suggested that the homotypic network of ICC-DMP connected with Cx 45 gap junctions may function as an independent compartment segregated from the whole cellular network including the smooth muscle cells connected with Cx 43 gap junctions. It is further speculated that the ICC-DMP of the rat small intestine communicate with each other and with smooth muscle cells via the passage of messenger molecules through Cx 43, but they may use an additional mechanism, as yet unknown, for communications restricted to other ICC-DMP.

The vasorelaxation of cerebral arteries by carbon monoxide.

Carbon monoxide (CO) is known to increase cerebral blood flow, but the effect of CO on the vascular tone of large cerebral arteries is uncertain. We tested whether CO affects cerebral artery tone by measuring tension generated by ex vivo segments of dog basilar artery upon exposure to CO. In cerebral artery segments contracted with either KCl or prostaglandin F(2alpha), CO caused a concentration-related relaxation beginning with a concentration of 57 microM. Relaxation did not occur if CO was administered in the presence of bubbling carboxygen (95% O(2):5% CO(2)), which reduces greater than 99% of CO from the solution. Furthermore, the CO-induced relaxation of cerebral artery segments was reduced in the presence of the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 microM)or the potassium channel blocker tetraethylammonium (TEA, 1 mM). Neither ODQ nor TEA completely eliminated the relaxation caused by CO and there was no additive effect if ODQ and TEA were administered together. These results suggest that cerebral arteries are directly relaxed by CO and that this relaxation depends upon the activation of guanylyl cyclase and the opening of potassium channels.

Vasospasm in monkeys resolves because of loss of and encasement of subarachnoid blood clot.

BACKGROUND AND PURPOSE: We studied in monkeys why vasospasm resolves after subarachnoid hemorrhage (SAH). METHODS: Monkeys underwent angiography and right (n=17) or bilateral (n=8) SAH. Animals with bilateral SAH underwent angiography 1, 3, 5, and 7 days later. Animals with right SAH underwent angiography 7 days later. The clot was then not removed (n=5), removed and replaced with fresh clot (n=7), or removed and not replaced (n=5). At the same time on day 7, the removed clot (n=12) or fresh clot (n=5) was placed on the left side. Angiography was repeated every 2 days until day 14. RESULTS: SAH caused significant vasospasm on day 7 that resolved by day 14. Removal of clot on day 7 resulted in more rapid resolution of vasospasm. Placement of fresh clot onto arteries that had already been exposed to clot for 7 days produced vasospasm that persisted without resolving for an additional 7 days. Placement of 7-day-old clot from the right onto previously unexposed left arteries or of clot from blood removed from an animal 7 days after SAH caused significantly more rapid onset of vasospasm compared with de novo vasospasm. Microscopic examination of the clots showed they were surrounded by macrophages 7 days after SAH. Arterial compliance and contractility were reduced in relation to duration of the exposure of arteries to clot. CONCLUSIONS: Vasospasm resolves because of loss of subarachnoid blood clot. We hypothesize that reduced spasmogen release from the clot contributes to resolution of vasospasm. There was no response in the cerebral arteries that rendered them less responsive to the subarachnoid clot.

Properties of gastric smooth muscles obtained from mice which lack inositol trisphosphate receptor.

Membrane potential recordings, made from the circular smooth muscle layer of the gastric antrum taken from mutant mice which lacked the inositol trisphosphate (InsP3) type 1 receptor, were compared with those obtained from the stomach of control (wild-type) mice. Immunostaining of gastric muscles indicated that the distribution and form of c-kit positive cells were similar in wild-type and mutant mice. Smooth muscles from wild-type mice generated slow waves that in turn initiated spike potentials, while those from mutant mice were either quiescent or generated irregular bursts of spike potentials. In the presence of nifedipine, slow waves with reduced amplitude were generated in wild-type mice, while all electrical activity was abolished in mutant mice. Acetylcholine depolarized and sodium nitroprusside hyperpolarized the membrane in muscles from both types of mice, being more effective in wild-type mice. Noradrenaline produced similar hyperpolarizations in both types of mice. Transmural nerve stimulation evoked inhibitory junction potentials (IJPs) in both wild-type and mutant mice. In wild-type mice, the IJPs were reduced in amplitude by nitroarginine and converted to a cholinergic excitatory junction potential (EJP) by apamin. In mutant mice, the IJPs were unaffected by nitroarginine or atropine but were abolished by apamin. It is concluded that in antral smooth muscle, the expression of InsP3 type 1 receptors may be causally related to the generation of slow waves but not to the generation of action potentials. A lack of InsP3 receptors attenuates cholinergic excitatory and nitrergic inhibitory responses but does not alter the response to noradrenaline.

Ultrastructural observations of fibroblast-like cells forming gap junctions in the W/W(nu) mouse small intestine.

The ultrastructure of the wild-type (+/+) mice small intestine was compared with c-kit mutant (W/W(nu)) mice which only have few interstitial cells of Cajal (ICC) associated with Auerbach's plexus, in order to elucidate whether the specialized membrane contacts are general features of so-called fibroblast-like cells that are widely distributed in the tunica muscularis of the alimentary tract. Fibroblast-like cells in the Auerbach region were found in approximately equal number in W/W(nu) mice as in +/+ mice, while ICC associated with Auerbach's plexus (ICC-AP) could not be demonstrated in W/W(nu) mice in the present investigation. Fibroblast-like cells were characterized by cytoplasm of moderate to high electron density, well developed rough endoplasmic reticulum and nuclei with thick peripheral accumulations of heterochromatin. There were no basal lamina and caveolae along the cell membrane. It was observed that single fibroblast-like cells formed probable small gap junctions with muscle cells of both circular and longitudinal layers. Fibroblast-like cells with the same features were also observed in the region of the deep muscular plexus in both +/+ and W/W(nu) mice. The present observation, together with our previous studies on rats and guinea-pigs, suggest the common presence of gap junctions or gap junction-like structures on fibroblast-like cells in the gastrointestinal musculature and their involvement in the regulatory system of gastrointestinal motility by passing electrical or molecular signals to influence the state of muscle tonus.

Ultrastructural characterization of the interstitial cells of Cajal.

Recent studies on the interstitial cells of Cajal (ICC) have determined ultrastructural criteria for the identification of these previously enigmatic cells. This review deals with the electron microscopic findings obtained by the author's research group in different tissue regions of the gut in mice, rats and guinea-pigs, comparing these with reports from other groups in different species and in humans. ICC are characterized by the following morphological criteria: numerous mitochondria, abundant intermediate filaments and large gap junctions which connect the cells with each other and with smooth muscle cells. Due to their location in the gut and the specific species, the ICC are markedly heterogeneous in appearance, ranging from cells closely resembling smooth muscle cells to those similar to fibroblasts (Table 1). Nevertheless, the above-mentioned morphological features are shared by all types of ICC and serve in identifying them. Recent discoveries on a significant role of c- kit in the maturation of the ICC and their specific immunoreactivity to anti-c-Kit antibody have confirmed the view that the ICC comprise an independent and specific entity of cells. This view is reinforced by the findings of the author's group that the ICC characteristically possess vimentin filaments and are stained with the zinc iodide-osmium tetroxide method which provides a staining affinity similar to methylene blue, the dye used in the original work by Cajal, (1911). Developmental studies indicate that the ICC are derived from a non-neuronal, mesenchymal origin. This paper further reviews advances in the physiological studies on the ICC, in support of the hypothesis by THUNEBERG (1982) that they function as a pacemaker in the digestive tract and a mediator transmitting impulses from the nerve terminals to the smooth muscle cells.

Comparative morphology of interstitial cells of Cajal: ultrastructural characterization.

The shape, distribution, and ultrastructural features of interstitial cells of Cajal (ICC) of different tissue layers and organs of the rat and guinea-pig digestive tract were described and compared with the corresponding cells in other species including mice, dogs, and humans, as reported in the literature. By light microscopy, the best marker for ICC appeared to be immunoreactivity for c-Kit. Ultrastructurally, ICC were characterized by the presence of many mitochondria, bundles of intermediate filaments, and gap junctions, which linked ICC with each other. However, ICC were morphologically heterogeneous and had particular features, depending on their tissue and organ location and species. ICC in the deep muscular plexus of the small intestine and in the submuscular plexus of the colon were the most like smooth muscle cells, and had a distinct basal lamina and numerous caveolae. In contrast, ICC of Auerbach's plexus at all levels of the gastrointestinal tract were the least like smooth muscle cells. They most closely resembled unremarkable fibroblasts. ICC within the circular muscle layer were intermediate in form. In addition to the tissue specificity, some organ and species specificity could be distinguished. The structural differences between ICC may be determined by their microenvironment, including the effects of mechanical force, type of nerve supply, and spacial relationship with smooth muscle cells.

Ultrastructure of intramural ganglia in the striated muscle portions of the guinea pig oesophagus.

The ultrastructure of the myenteric plexus located in the striated muscle portion of the guinea pig oesophagus was examined and compared with that of the plexus associated with the smooth muscle portion of the rest of the digestive tract. The oesophageal ganglia had essentially the same architecture as those of the smooth muscle portion, such as a compact neuropil without the intervention of connective tissue and blood vessels. Some features, however, were particular to the striated muscle part of the oesophagus. It was clearly demonstrated that myelinated fibres, probably sensory terminals of vagal origin, join the myenteric ganglia. Synapses and terminal varicosities are sparsely distributed within the ganglia and fewer morphological types of axon varicosities could be distinguished compared with other regions. Glial cells are well developed in the oesophageal myenteric ganglia. These cells outnumber the ganglion cells, having a higher ratio than in the lower digestive tract, and form numerous cytoplasmic lamellar processes. The lamellar processes, located at the surface of the ganglia, considerably reduce the area of neuronal membrane which directly contacts the basal lamina. The role of these lamellar processes in the oesophageal ganglia is discussed.