Imaging of haemophilic arthropathy in growing joints: pitfalls in ultrasound and MRI.

The purpose of this review was to summarize the current knowledge on the utilization of magnetic resonance imaging (MRI) and ultrasound (US) for assessing arthropathy in children and adolescents with haemophilia and to recognize the limitations of each imaging modality and pitfalls in the diagnosis of soft tissue and osteochondral abnormalities. Awareness of MRI and US limitations and pitfalls in the assessment of joints in persons with haemophilia is essential for accurate diagnosis and optimal management of haemophilic arthropathy.

Increased ghrelin signaling prolongs survival in mouse models of human aging through activation of sirtuin1.

Caloric restriction (CR) is known to retard aging and delay functional decline as well as the onset of diseases in most organisms. Ghrelin is secreted from the stomach in response to CR and regulates energy metabolism. We hypothesized that in CR ghrelin has a role in protecting aging-related diseases. We examined the physiological mechanisms underlying the ghrelin system during the aging process in three mouse strains with different genetic and biochemical backgrounds as animal models of accelerated or normal human aging. The elevated plasma ghrelin concentration was observed in both klotho-deficient and senescence-accelerated mouse prone/8 (SAMP8) mice. Ghrelin treatment failed to stimulate appetite and prolong survival in klotho-deficient mice, suggesting the existence of ghrelin resistance in the process of aging. However, ghrelin antagonist hastened death and ghrelin signaling potentiators rikkunshito and atractylodin ameliorated several age-related diseases with decreased microglial activation in the brain and prolonged survival in klotho-deficient, SAMP8 and aged ICR mice. In vitro experiments, the elevated sirtuin1 (SIRT1) activity and protein expression through the cAMP-CREB pathway was observed after ghrelin and ghrelin potentiator treatment in ghrelin receptor 1a-expressing cells and human umbilical vein endothelial cells. Furthermore, rikkunshito increased hypothalamic SIRT1 activity and SIRT1 protein expression of the heart in the all three mouse models of aging. Pericarditis, myocardial calcification and atrophy of myocardial and muscle fiber were improved by treatment with rikkunshito. Ghrelin signaling may represent one of the mechanisms activated by CR, and potentiating ghrelin signaling may be useful to extend health and lifespan.

An anatomic study of the accessory anterolateral talar facet.

BACKGROUND: A small accessory facet with articular surface morphology is occasionally seen on the talus, bordering on the lateral end of the sinus tarsi. This facet has been named the accessory anterolateral talar facet. However, few anatomical studies have addressed this facet. Here we present the precise morphology of accessory anterolateral talar facet with emphasis on anatomical correlation between the presence of this facet and the angle of the infero-lateral surface of the talus (talar infero-lateral surface - TILS angle). MATERIALS AND METHODS: A total of 22 (11 male, 11 female) adult cadavers with no known pathological conditions in the talocalcaneal joints were examined during educational dissection at Nagoya City University Medical School in 2013. After exclusion of 1 joint due to the poor condition of the talus, 43 talus (22 right, 21 left) were analysed. We judged the presence of the accessory anterolateral talar facet and measured TILS angle. We performed statistical analysis on the point of laterality, gender difference and the difference in the TILS angles in tali with or without the accessory anterolateral talar facets. RESULTS: An accessory anterolateral talar facet was identified in 11 (26%) of the 43 specimens. Of the 21 cadavers with paired talar specimens, 5 displayed the facet bilaterally. CONCLUSIONS: There was no sex difference and no significant laterality, however we found that TILS angle was significantly larger in accessory anterolateral talar facet positive samples than in negative ones.

Morphological characteristics of the deep layer of articularis genus muscle.

BACKGROUND: The articularis genus muscle pulls the suprapatellar pouch upwards when the knee joint is extended, preventing mechanical impingement of the joint capsule which theoretically could cause anterior knee pain. However, few anatomical studies have addressed this muscle. Here we present the precise morphology of articularis genus. MATERIALS AND METHODS: A total of 22 (13 male and 9 female) adult cadavers with no pathological conditions in the knee joints were examined during educational dissection at Nagoya City University Medical School in 2012. After exclusion of 4 joints due to their flexion contracture, 40 knee joints (18 right and 22 left) were analysed. We performed statistical analysis on anatomical laterality and the difference of sizes among lateral, medial and central branches and studied the correlation of the length and area of the articularis genus muscle to the lengthand cross-section area of the femur. RESULTS AND CONCLUSIONS: The average number of branches of the deep layer of the articularis genus muscle was 2.7 ± 0.5, the mean length of all brancheswas 5.4 ± 1.3 cm and the mean area of all branches was 5.5 ± 2.6 cm². There was no significant correlation between the length and area of the articularis genus muscle to the length and cross-section area of the femur. There was no significant laterality in central, medial and lateral branches; however we found that the medial branch was statistically longer and larger than the lateral branchon either knee. This could be contributing to prevention of lateral dislocation of the patella.

The co-existence of an aberrant origin of the right subclavian artery and a coronary myocardial bridge.

We encountered the co-existence of an aberrant origin of the right subclavian artery and a myocardial bridge on the left anterior descending coronary artery in the cadaver of an 80-year-old Japanese woman during the course of educational dissection at Nagoya City University Medical School. We document the precise gross anatomical findings with some morphometric measurements. Neither an aberrant origin of the right subclavian artery nor the cardial myocardial bridge is a very rare anomaly, but a case of both anomalies being found in the same body is very rare. We believe this is the first report of the simultaneous occurrence of these two anomalies.

Gap junctional communication between the satellite cells of rat dorsal root ganglia.

Many studies have described the ultrastructure of the dorsal root ganglia in various embryonic and adult animals, but in spite of the efforts of many investigators the functional role of the satellite cells in this tissue is not clearly understood. In this study, we discuss the function of this cell type based on the concept of cell-to-cell interaction through gap junctions. Five male 60 day-old Wistar strain rats were used. All animals were anesthetized with pentobarbital and perfused with glutaraldehyde fixative, then the dorsal root ganglia in levels L4, L5 and L6 were taken from each rat. After postosmication, the specimens were prepared for observation by transmission electron microscopy. All nerve cells were completely surrounded by satellite cell cytoplasmic expansions. The boundaries between adjacent nerve cells and satellite cells were complicated due to the presence of perikaryal projections of nerve cells. Gap junctions which showed the typical trilamellar structure of plasma membranes were found mainly between satellite cell processes belonging to the same nerve cell. On the other hand, some gap junctions were found between the satellite cell projections belonging to different nerve cells. The size of the gap junctions ranged from 300 to 400 nm. No gap junctions were associated with the plasma membrane of any nerve cell. In conclusion, only satellite cells can share free transcellular exchange of cytoplasmic molecules such as ions, amino acids, sugars and several second messengers including cAMP and inositol 1,4,5-triphosphate by way of gap junctions in dorsal root ganglia.

Effects of hydrocortisone on the formation of gap junctions and the abnormal growth of cilia within the rat anterior pituitary gland: possible role of gap junctions on the regulation of cell development.

We investigated the effects of hydrocortisone on the formation of gap junctions in and the growth of cilia on folliculo-stellate cells. The male rats of experimental groups were given daily intraperitoneal injections of 5 mg/kg of hydrocortisone from Day 20 to 60. Five rats were killed at ages 10, 20, 30 and 40 days after initiation of injections, and the pituitary gland was removed from each rat. Then, the specimens were prepared for observation by transmission electron microscopy. A delay in the formation of gap junctions between folliculo-stellate cells was observed in hydrocortisone treated rats compared with control rats on Day 30, 40 and 50. Another finding in the present study was the increase of ciliated follicles on Day 40 and 50 in the hydrocortisone treated groups, simultaneous with the delay in gap junction formation. The results suggest that hydrocortisone has a suppressive effect on the gap junction formation between folliculo-stellate cells, and loss of intercellular communication by way of gap junctions may lead to alteration of morphological development of the cell.

Postnatal development of synovial capillaries of rats with special reference to permeability.

The size of a substance is a major factor determining whether it can permeate the wall of synovial capillaries. The maximum diameter of particles that can move across the synovial capillary wall has generally been thought to be 50 nm. We studied the permeability of the synovial capillaries of the rat between day 20 and 30 after birth using a polystyrene particle whose diameter was 240 nm. In addition using lecithin-coated polystyrene particles, we studied the maturation of the barrier function supported by endothelial and peripheral cells against foreign bodies. Lecithin-coated particles were found within the fibroblast-like synovial cells near the capillary in the 20 day-old rats, while non-coated particles remained in the endothelial wall and in the peripheral cells of capillaries. In the 30 day-old rats, lecithin-coated particles were present in the peripheral cells and the neighboring synovial cells; however, the non-coated particles were never found in the synovial or perisynovial cells. The present study shows that the size of the transportable substance by transcytosis may be larger than previously thought. Furthermore, the synovial capillaries functionally changed between day 20 and 30 suggesting that active movement of the joint led to the functional maturation of the synovial capillaries.

Ultrastructural study of cells at the synovium-cartilage junction: response of synovial cells of the rat knee joint to intra-articularly injected latex particles.

To study phagocytosis in synovial cells at the synovium-cartilage junction, we used polystyrene latex spheres which induced no infiltration of inflammatory cells into the synovial tissues and observed them for a long term period. The latex bead suspension was injected into the knee joint cavities of 60 day-old male Wistar rats. The animals were then sacrificed at 1, 4, 7, 14, 28 and 56 days after the injections and their synovial tissues including the patellar cartilage were resected for subsequent examination with the transmission electron microscope. On day 1, particles were phagocytised intensively by both type A (macrophage-like) and type B (fibroblast-like) cells. Particles were more numerous in the cytoplasm of type A rather than type B cells. The number of synovial cells containing particles and the number of particles present in these cells decreased remarkably on day 4. By day 7, particles were also observed in the tendon. On day 14, particles were observed in the cytoplasm of chondrocyte. It was noted that particle density within cells began to increase again after day 28. On day 56, numerous particles were observed in type A and type B cells and moreover within the intercellular matrix. Even tendon cells actively engulfed the particles. The results of the present study suggest that both type A and B synovial cells, chondrocytes and tendon cells possess the ability to phagocytise foreign materials. Moreover, the possibility is proposed that the synovium-cartilage junction is the point where the synovial fluid exits and particles drain via the blood circulation.

A possible barrier function of the articular surface.

Since MacConaill first reported the existence of a thin additional layer of the articular cartilage and named it the lamina splendens, there have been various opinions as to the role of this layer in the lubrication of the articular surface. We studied the superficial portion of the articular cartilage in the 20 day-old and 30 day-old rats using light and transmission electron microscopy. Furthermore, we studied the articular cartilage of the rat whose "cover layer" had been removed mechanically. Also, intraarticular latex beads injection, intraarticular dye injection using lithium carmine and supravital staining experiments were performed. On day 20, dye injected intraarticularly was clearly observed by light microscopy in chondrocytes situated in the deeper layers. The dye injected in the 30 day-old rats, however, was not seen in the chondrocytes but was found only in the superficial layer. Dye was found in the chondrocytes when supravital staining was performed in the articular cartilage of 30 day-old rats after mechanical removal of the cover layer. By transmission electron microscopy, a superficial layer consisted of fine filamentous structures was observed on the articular surface of the 30 day-old rats. The cover layer was destroyed by intraarticular injected latex beads in 30 day-old rats. These findings strongly support the idea that the cover layer acts as a barrier against substances which invade from the surface of the articular cartilage. The development period of the cover layer coincides with the initiation of weight bearing, and joint cartilage debris and pressure changes might further promote maturation.

Abnormal lipoprotein and apolipoprotein pattern in lipoprotein glomerulopathy.

Recently, two cases of renal disease were observed in which there was an abnormal accumulation of lipids, "lipoprotein thrombi," in the glomerular capillary lumen. This disease has been designated as lipoprotein glomerulopathy. Four other cases have been diagnosed independently by renal histology in other clinical laboratories. All six patients showed proteinuria (1.6 to 10 g/d), normal lecithin-cholesterol acyltransferase (LCAT) activity, type III hyperlipoproteinemia-like lipoprotein profiles, and significantly (P less than 0.01) higher levels of plasma apolipoprotein (apo) E (greater than 10 mg/dL) compared with the control patients with hyperlipidemic nephrotic syndrome without lipoprotein thrombi and type IIb hyperlipoproteinemia without renal disease. Lipoprotein glomerulopathy is not familial type III hyperlipoproteinemia (dysbetalipoproteinemia), because apolipoprotein E3 is present. Apo E isoforms were all rare: five cases of E2/3 and one case of E4/4. These results suggest that excessive apo E is associated with apo E isoform and lipoprotein metabolic derangement in such a renal disease. Further studies are needed on the relationship between the apo E hyperlipoproteinemia and the formation of lipoprotein thrombi.

Effect of taurine administration on serum lipid and biliary lipid composition in man.

The effect of oral administration of taurine (3.2 g/day, 2 weeks) on the metabolism of lipids and bile acids was studied with healthy humans. Four male subjects were fed taurine. Another five male subjects were administered 1 g of cholesterol daily for two weeks and, at intervals of two weeks, cholesterol and taurine simultaneously. Serum lipoprotein and duodenal bile were analyzed. Oral administration of taurine resulted in the increase of taurine-conjugated bile acids. However, neither serum lipid nor biliary lipid composition was altered. Addition of taurine with cholesterol administration showed elevation of both the serum low density lipoprotein cholesterol level and the lithogenic index in bile. The ratio of glycine-to taurine-conjugated bile acids was changed from 4.1 to 0.63. The ratio of cholic acid/chenodeoxycholic acid was augmented from 0.57 to 0.81. The percentage of taurocholic acid, taurochenodexycholic acid and taurodeoxycholic acid were increased about 4-fold, 2.5-fold and 3-fold, respectively. Our results suggested that taurine administration alone did not influence the serum lipid level although taurine-conjugated bile acids were increased. The taurine intake would increase serum low density lipoprotein cholesterol and biliary cholesterol levels when excessive cholesterol is administered simultaneously.

Appearance of multidisperse low density lipoprotein and altered lipoprotein composition in non-insulin-dependent diabetes with type IIa hyperlipoproteinemia.

The purpose of the present study is to elucidate the characteristics of lipoprotein disorders in diabetes mellitus. By analytical ultracentrifugation, non-insulin-dependent diabetic patients (NIDDM) with type IIa hyperlipoproteinemia (HLP) showed significantly higher incidence of multidisperse low density lipoprotein (LDL) than non-diabetics with type IIa HLP. Furthermore, LDL multidispersity in diabetic subjects seemed to be directly related to neither triglyceride (TG) levels in very low density lipoprotein (VLDL) nor the degree of glycemic control. Diabetics with multidisperse LDL had a lipoprotein profile that was different from the subjects with paucidisperse LDL as follows: (1) enrichment in the cholesterol content of VLDL, (2) TG-rich LDL with small flotation coefficient, (3) low cholesterol levels in high density lipoprotein2 along with enrichment in TG, and (4) high plasma concentrations of apoprotein B. Although the underlying mechanism behind the prevalence of multidisperse LDL in NIDDM with type IIa HLP remains unknown, it seems important that lipoprotein disorders in diabetics with multidisperse LDL were potentially atherogenic.