Glycyrrhizin enhances interleukin-10 production by liver dendritic cells in mice with hepatitis

Background Glycyrrhizin (GL), an aqueous extract of licorice root, is known to have various immune-modulating and biological response-modifier activities. GL is used in patients with hepatitis to reduce the activity of liver inflammation; however, the mechanism underlying the anti-inflammatory activity of GL is poorly understood. As antigen-presenting dendritic cells (DC) in the tissue play a major role in the regulation of the inflammatory mucosal milieu during tissue inflammation, we studied whether the function of liver DC was altered by GL therapy in a murine model of concanavalin-A (Con A)-induced hepatitis.Methods Liver DC were propagated from control mice or mice with Con-A-induced hepatitis, and the effect of GL on liver DC was evaluated in vivo and in vitro.Results The levels of interleukin (IL)-10 produced by liver DC were significantly lower in mice with Con-A-induced hepatitis compared with control mice. However, treatment with GL caused increased production of IL-10 in mice with Con A-induced hepatitis. The increased production of IL-10 by mice with Con A-induced hepatitis was also confirmed in vitro by culturing liver DC with GL.Conclusions This study indicates that increased production of IL-10 by liver DC due to GL administration may be involved in downregulation of the levels of liver inflammation in mice with Con A-induced hepatitis.     

Cardiac glands hyperplastic polyp of the stomach

Reported herein is a very rare polyp in the gastric cardia of a 49-year-old man. He was referred because of a polyp detected by upper gastrointestinal examination in an affiliated hospital. Endoscopic examination revealed a polyp-like submucosal tumor. Endoscopic ultrasonography revealed minute cystic dilatations and thickening of the submucosal layer. Accordingly, a preliminary diagnosis of cardiac gland hyperplasia was made. The lesion was removed successfully by snare polypectomy. Observed macroscopically, the polyp was 30 mm in diameter and covered with normal gastric mucosa. Examined histologically, the polyp comprised a hyperplastic submucosal cardiac gland.     

Insulin resistance in nondiabetic patients is associated with expansive remodeling in coronary arterial lesions

OBJECTIVE: Insulin resistance has been implicated as an important initiating factor in coronary atherosclerosis. However, associations between insulin resistance and specific morphologic features of atherosclerotic coronary arteries remain unclear. We ultrasonographically evaluated the morphologic features of atherosclerotic coronary arteries in nondiabetic patients with insulin resistance. METHODS: Before intervention, 90 patients with 105 culprit lesions underwent intravascular ultrasound examination through which vessel area, lumen area and plaque area were evaluated. Expansive remodeling (lesion vessel area more than 5% greater than at the proximal reference segment) and constrictive remodeling (lesion vessel area more than 5% less than at the distal reference segment) were also evaluated. Insulin resistance was determined by homeostasis model assessment and defined as values above the 75th percentile (that is, 1.71). RESULTS: Insulin-resistant patients numbered 23, while nonresistant patients numbered 67. Culprit lesions in the insulin-resistant group showed larger vessel area (18.16 +/- 6.94 compared with 13.64 +/- 4.28 mm, P = 0.0001) and plaque area (16.64 +/- 6.78 compared with 12.05 +/- 4.12 mm, P = 0.0001) and more frequently showed expansive remodeling (56% compared with 14%, P < 0.0001) and calcific plaque (33% compared with 12%, P = 0.01). Multivariable logistic regression analysis identified only insulin resistance (odds ratio, 4.9, P = 0.008) as an independent predictor of expansive remodeling. CONCLUSIONS: Insulin resistance independently predicted expansive remodeling, underscoring the importance of insulin resistance in coronary atheroscrelosis.     

Atorvastatin slows the progression of cardiac remodeling in mice with pressure overload and inhibits epidermal growth factor receptor activation.

The aim of this study was to investigate whether atorvastatin inhibits epidermal growth factor receptor (EGFR) activation in cardiomyocytes in vitro and slows the progression of cardiac remodeling induced by pressure overload in mice. Either atorvastatin (5 mg/kg/day) or vehicle was orally administered to male C57BL/6J mice with transverse aortic constriction (TAC). Physiological parameters were obtained by echocardiography or left ventricular (LV) catheterization, and morphological and molecular parameters of the heart were also examined. Furthermore, cultured neonatal rat cardiomyocytes were studied to clarify the underlying mechanisms. Four weeks after TAC, atorvastatin reduced the heart/body weight and lung/body weight ratios (8.69+/-0.38 to 6.45+/-0.31 mg/g (p<0.001) and 10.89+/-0.68 to 6.61+/-0.39 mg/g (p<0.01) in TAC mice with and without atorvastatin, respectively). Decrease of LV end-diastolic pressure and the time constant of relaxation, increased fractional shortening, downregulation of a disintegrin and metalloproteinase (ADAM)12, ADAM17 and heparin-binding epidermal growth factor genes, and reduction of the activity of EGFR and extracellular signal-regulated kinase (ERK) were observed in the atorvastatin group. Phenylephrine-induced protein synthesis, phosphorylation of EGFR, and activation of ERK in neonatal rat cardiomyocytes were all inhibited by atorvastatin. These findings indicated that atorvastatin ameliorates cardiac remodeling in mice with pressure overload, and its actions are associated with inhibition of the EGFR signaling pathway.     

Clinical evaluation of pneumonia-associated rhabdomyolysis with acute renal failure

This study aims to evaluate the clinical features, diagnosis, and treatment efficacy in patients with pneumonia-associated rhabdomyolysis and acute renal failure. The subjects included six patients who had presented with rhabdomyolysis and acute renal failure due to bacterial or viral pneumonia on admission to our university hospital and the Yokohama Social Insurance Central Hospital between 2004 and 2005. The causative organisms were identified as Legionella pneumophila (N = 1), Staphylococcus epidermidis (N = 2), Staphylococcus aureus (N = 1), and Unknown (N = 2). For anuric or oliguric patients (N = 4), a blood purification therapy was performed, while conservative therapy was administered to those with a normal urine volume (N = 2). The patient suffering from L. pneumophila pneumonia did not survive, while the other patients regained full kidney function. It is important to identify, evaluate, and treat patients with bacterial or viral pneumonia-associated rhabdomyolysis and acute renal failure.     

Bone lesions in elderly multiple myeloma

We investigated the incidence of bone lesions in elderly cases of multiple myeloma (MM) and the course of those lesions, and also evaluated the relationships of skeletal symptoms with prognostic factors, and prognosis. The subjects were 146 patients, aged 65 years or more (median age 74, range 65-97 year), who were admitted to 11 institutions between January, 1988 and December, 1997. They consisted of 64 men and 82 women. The disease type was IgG type in 88 patients, IgA type in 37 patients, Bence-Jones (BJ) type in 17 patients, IgD type in three patients, and non-secretory type in one patient. Bone lesions in elderly MM patients were compared with those in 65 non-elderly MM patients. Skeletal symptoms were noted in 104 patients, and bone pain in 75 patients at the time of diagnosis. The bone lesions were evaluated as only osteolytic lesions in 26 patients, osteolytic lesions + osteoporosis in 23 patients, only osteoporosis in 2 patients and pathologic bone fractures in 53 patients. The occurrence rate of osteoporosis plus osteolytic lesion was higher in elderly patients (63.5%) than that in non-elderly patients (NE-MM group) (28.3%) (p < 0.0001). The bone lesions were most often observed in lumbar vertebrae (58.7%), cranial bone (56.7%), thoracic vertebrae (40.4%) and ribs (27.9%). The occurrence rate of bone lesion in lumbar vertebrae was higher in elderly patients (58.7%) than that in non-elderly patients (22.6%) (p < 0.0001). The life activities were limited in 71 patients because of the bone lesions. The relationship between the prognostic factors of MM and bone lesions was evaluated. There was a significant difference in the serum Ca level between patients with and without bone pain (P < 0.0001) and between those with and without pathologic bone fracture (P < 0.01). There was a significant difference in the appearance rate of plasma cells in the bone marrow between the patients with and without bone lesions (P < 0.05), between those with and without bone pain (P < 0.01), and between those with and without pathologic fracture (P < 0.05). There was a significant difference in the serum beta 2-microglobulin level between the patients with and without bone pain, and between those with and without pathologic fracture. There were no significant differences in survival times between elderly MM patients with and without bone lesions, bone pain and pathological bone fractures, while significant differences of survival times were found between non-elderly MM patients with and without bone lesions, bone pain and pathological bone fractures (P < 0.05, each). These data suggest that there are some differences in bone lesions between elderly and non-elderly MM patients.     

Ephrin-B2 controls PDGFRβ internalization and signaling

B-class ephrins, ligands for EphB receptor tyrosine kinases, are critical regulators of growth and patterning processes in many organs and species. In the endothelium of the developing vasculature, ephrin-B2 controls endothelial sprouting and proliferation, which has been linked to vascular endothelial growth factor (VEGF) receptor endocytosis and signaling. Ephrin-B2 also has essential roles in supporting mural cells (namely, pericytes and vascular smooth muscle cells [VSMCs]), but the underlying mechanism is not understood. Here, we show that ephrin-B2 controls platelet-derived growth factor receptor β (PDGFRβ) distribution in the VSMC plasma membrane, endocytosis, and signaling in a fashion that is highly distinct from its role in the endothelium. Absence of ephrin-B2 in cultured VSMCs led to the redistribution of PDGFRβ from caveolin-positive to clathrin-associated membrane fractions, enhanced PDGF-B-induced PDGFRβ internalization, and augmented downstream mitogen-activated protein (MAP) kinase and c-Jun N-terminal kinase (JNK) activation but impaired Tiam1–Rac1 signaling and proliferation. Accordingly, mutant mice lacking ephrin-B2 expression in vascular smooth muscle developed vessel wall defects and aortic aneurysms, which were associated with impaired Tiam1 expression and excessive activation of MAP kinase and JNK. Our results establish that ephrin-B2 is an important regulator of PDGFRβ endocytosis and thereby acts as a molecular switch controlling the downstream signaling activity of this receptor in mural cells.     

Epilepsy in patients with advanced Fukuyama congenital muscular dystrophy

BackgroundRecent advances in respiratory management have improved survival for patients with Fukuyama congenital muscular dystrophy (FCMD), characterized by congenital muscular dystrophy and brain malformation. Previous studies reported that more than half of patients exhibit seizures in childhood. However, little is known about epilepsy after childhood.MethodsTo elucidate the long-term clinical course of epilepsy, we retrospectively reviewed all medical records in nine patients (6 males, mean age 20.7 years) with FCMD diagnosed between 1981 and 2019.ResultsThe follow-up periods ranged from 6 to 30 years (mean 18.4 years). A total of 75 EEG recordings were available from nine patients. In some patients, EEGs were normal during early childhood but tended to show paroxysmal discharges with age. Overall, epileptic seizures were observed in six patients. Except for one presenting with afebrile seizure at one year of age, the remaining five patients developed epilepsy between 13 and 22 years of age. The most common seizure type was focal impaired awareness seizure. After adolescence, four patients exhibited status epilepticus. Their convulsive movements of the seizures became less prominent with progression of the disease. At the last evaluation, most patients (5/6) had uncontrolled seizures.ConclusionsDespite presence of distinct brain malformation, epileptic seizures may develop after childhood in FCMD patients. Our experience suggests that clinicians should be careful not to overlook epileptic seizures, especially in advanced-stage patients who had profound muscle weakness.     

Intraosseous leiomyosarcoma arising in the epiphysis of the distal femur

Herein, we present a rare case of intraosseous leiomyosarcoma arising in the epiphysis of the distal femur and showing unusual radiographic features. A 44-year-old man presented with a pain in the left knee joint. Computed tomography revealed an intraosseous lesion with slightly increased attenuation and a thin marginal sclerotic rim in the femoral medial condyle. The signal of the lesion was hypointense on T1-weighted magnetic resonance (MR) images and hyperintense on fat-suppressed T2-weighted MR images. After gadolinium administration, the signal of the lesion was moderately and diffusely enhanced. The histological diagnosis of leiomyosarcoma was made based on a preoperative core biopsy specimen. Microscopic examination of the resected specimen revealed an ill-defined intraosseous tumor composed of proliferated atypical and mildly pleomorphic smooth muscle cells permeating among the bone trabeculae with only focal destruction of the bone trabeculae and low mitotic activity, indicating low grade leiomyosarcoma. The bone trabeculae at the periphery of the tumor were mildly thickened and anastomosed with a rim of an increased number of osteoblasts. Systemic examination showed no tumorous lesions in other anatomical sites. Leiomyosarcomas rarely present in the bone as a diffuse intertrabecular growth, even in low grade tumors.     

An anatomic study of the inferior oblique nerve with high-resolution magnetic resonance imaging

Objective

To investigate anatomic features of the inferior oblique nerve (IObN) by high-resolution magnetic resonance (MR) imaging and cadaveric dissection.

Methods

This study enrolled 100 consecutive outpatients, who underwent 3.0 T MR imaging equipped by the 32-channel head coil. The T2-weighted imaging data of IObN were extracted for analysis and compared with the findings of microsurgical dissection in 14 orbits.

Results

50 male and 50 female subjects allotted to the imaging study were aged from 11 to 78 years. In 94 % sides, the IObN was found to separate from the inferior rectus muscle (IRM) at the level just behind to the posterior pole of the bulb. At the midpoint of the IObN part coursing along the orbital floor and above or adjacent to the infraorbital nerve and artery complex, the mean distance from the lateral margin of the IRM was 1.0 mm on the right and 0.9 mm on the left. The IObN showed upward direction change just below the belly of the inferior oblique muscle and innervated to it at the equator level in 78 sides on the right and 89 on the left. Dissected specimens revealed the consistent morphological findings of the IObN.

Conclusions

The IObN seems to be a relatively consistent structure. Anatomic information on the IObN and surrounding structures that are provided by high-resolution MR imaging can be a help for safe surgery.