Vortical Amplification of the Magnetic Field at an Inward Shock of Supernova Remnant Cassiopeia A.

We present an interpretation of the time variability of the x-ray flux recently reported from a multiepoch campaign of 15 years of observations of the supernova remnant Cassiopeia A by Chandra. We show for the first time quantitatively that the [4.2-6] keV nonthermal flux increase up to 50% traces the growth of the magnetic field due to a vortical amplification mechanism at a reflection inward shock colliding with inner overdensities. The fast synchrotron cooling as compared with shock-acceleration time scale qualitatively supports the flux decrease.

Impact of long-acting calcium channel blockers on the prognosis of patients with coronary artery disease with and without chronic kidney disease: a comparison of three drugs.

Calcium channel blockers (CCBs) can prevent cardiovascular events in patients with coronary artery disease (CAD). This study looked retrospectively at the prognosis of CAD in hypertensive patients with CAD who had undergone a coronary angiograph, had been given a CCB (benidipine [n = 66], amlodipine [n = 45], or long-acting nifedipine [n = 31]) on hospital discharge and were then followed up for a mean +/- SD of 5.2 +/- 2.9 years. Systolic/diastolic blood pressure for all 142 patients decreased significantly from a mean +/- SD of 137 +/- 20/74 +/- 15 mmHg to 129 +/- 20/71 +/- 12 mmHg. Major adverse cardiovascular events (MACE) occurred in 15 patients. Chronic kidney disease (CKD) was a significant risk factor for MACE (hazard ratio 2.35, 95% confidence intervals 1.45, 3.80). Benidipine was superior to nifedipine in preventing MACE in patients both with and without CKD. In conclusion, benidipine and amlodipine reduced the frequency of MACE in hypertensive patients with CAD, particularly in those with complicating CKD.

Chronic inhibition of standing behaviour alters baroreceptor reflex function in rats.

AIM: To investigate whether daily orthostatic stress during development is an important factor affecting arterial baroreceptor reflex function, we examined the effect of chronic inhibition of upright standing behaviour on the baroreceptor reflex function in rats. METHODS: Upright standing behaviour was chronically inhibited during the developmental period between 3 and 8 weeks of age in Sprague-Dawley rats and heart rate (HR) and aortic nerve activity in response to increased and decreased mean arterial pressure (MAP) was measured after the treatment period. RESULTS: The baroreceptor cardiac gain in the rats grown without standing behaviour was significantly lower than the control rats grown in a normal commercial cage (1.0 +/- 0.1 beats min(-1) mmHg(-1) vs. 1.6 +/- 0.2 beats min(-1) mmHg(-1), P < 0.05). The range of HR change in the MAP-HR functional curve was also lowered by chronic inhibition of orthostatic behaviour (56.2 +/- 5.9 beats min(-1)) compared with that of the control rats (76.8 +/- 6.9 beats min(-1), P < 0.05). However the aortic afferent function remained normal after the treatment period, indicating that the attenuated baroreceptor reflex function may be due to other mechanisms involving functional alterations in the cardiovascular centres, efferents and/or peripheral organs. Body weight and adrenal weight were not affected by the inhibition of orthostatic behaviour, suggesting that the animals were not exposed to specific stress by this treatment. CONCLUSION: These results indicate that active haemodynamic changes induced by orthostatic behaviour are an important factor for setting the basal level of reflex function during development. Moreover, our experimental model may be useful for studying mechanisms of attenuated baroreceptor reflex observed after exposure to a chronic inactive condition.

Comparison of effects of pitavastatin and atorvastatin on plasma coenzyme Q10 in heterozygous familial hypercholesterolemia: results from a crossover study.

An open, randomized, four-phased crossover study using 4 mg of pitavastatin or 20 mg of atorvastatin was performed to compare their efficacy and safety, especially regarding plasma levels of coenzyme Q10 (CoQ10) in 19 Japanese patients with heterozygous familial hypercholesterolemia. Pitavastatin and atorvastatin caused significant and almost comparable reductions in serum levels of total cholesterol (-35.4 vs. -33.8%), low-density lipoprotein cholesterol (-42.8 vs. -40.7%), and triglyceride (-26.1 vs. -29.4%), and significantly increased serum levels of high-density lipoprotein cholesterol (12.1 vs. 11.4%). Under these conditions, plasma levels of CoQ10 were reduced by atorvastatin (-26.1%, P=0.0007) but not by pitavastatin (-7.7%, P=0.39), although no adverse events or abnormalities of liver and muscle enzyme were observed after either statin treatment. It remains to be seen whether the observed changes in CoQ10 levels are related to the long-term safety of this drug.

Complete atrioventricular block associated with lymphocytic myocarditis of the atrioventricular node in two young adult dogs.

A histological investigation of the atrioventricular (AV) conduction system was performed in two young adult dogs with complete AV block. In both cases, infiltration of lymphocytes and plasma cells into the AV node and loss and disappearance of the conduction fibres were observed. Such inflammatory lesions of the AV conduction system were associated with complete AV block. The aetiology of these changes and the cause of its location at the AV node were not elucidated.

Reactive lymphoid hyperplasia of the liver in a patient with multiple carcinomas: a case report and brief review.

A rare case of reactive lymphoid hyperplasia (RLH) of the liver in a 75-year-old woman admitted to hospital for surgical treatment of gastric, caecal and colon carcinomas is described here. Two nodular lesions in the left and right lobes of the liver were clinically diagnosed as metastatic tumours by computed tomography of the abdomen. A demarcating grey-white mass of size 1.4 cm was observed in a partially resected liver specimen. On examining the lesion microscopically, it was found to be composed of hyperplastic lymphoid follicles, lymphocytes, plasma cells, other inflammatory cells and interlaced hyalinised fibrous tissues. In the portal tracts around the lesion, chronic inflammatory cell infiltrates were seen, but no interface hepatitis or lymphoid follicle was observed. No evidence of monoclonality was observed by immunohistochemistry for B and T cell markers, in situ hybridisation for kappa and lambda light chains, and polymerase chain reaction analysis of immunoglobulin heavy chains or T cell receptor beta and gamma gene rearrangements. Bcl-2 immunoreactivity was not observed in the germinal centre. Epstein-Barr virus (EBV) antigen (latent membrane protein-1) and EBV-encoded small RNAs were not detected. A proliferation neither of myofibroblasts nor of cells positive for follicular dendritic cell markers was observed. RLH, formerly known as pseudolymphoma, has been reported of the liver in only 14 cases and is considered to be a differential diagnosis of small nodular lesions of the liver. That RLH has an inflammatory reactive nature, not a neoplastic disposition, and that EBV does not participate in the pathogenesis of RLH is supported by this case.

Composite large cell neuroendocrine carcinoma and adenocarcinoma of the common bile duct.

Large cell neuroendocrine carcinoma (LCNEC) is a high grade type of neuroendocrine tumour with an aggressive clinical course. This report describes the first case of LCNEC combined with an adenocarcinoma component in the common bile duct. A 68 year old man presented with jaundice. Severe stenosis of the bile duct was revealed by endoscopic retrograde cholangiography, and adenocarcinoma cells were detected by brush cytology. Pancreaticoduodenectomy was performed, and the patient died of disease three months after surgery. A tumour measuring 2.0 cm in diameter was located in the intrapancreatic portion of the bile duct. Histologically, the tumour consisted of a LCNEC component and a well differentiated adenocarcinoma component. There were transitional areas between the two components. Immunohistochemically, LCNEC cells were reactive for neuroendocrine markers, but no specific hormonal expression was found. Chromogranin A positive cells were found in some areas of the adenocarcinoma component. These findings are consistent with the theory that both of the carcinoma components originated from a common pluripotent stem cell.

Oxidative stress by glutathione depletion induces osteonecrosis in rats.

OBJECTIVE: We recently implicated in vivo oxidative stress in the development of osteonecrosis in a steroid-induced osteonecrosis model in the domestic rabbit. In the present experiment we devised a new non-traumatic model using the rat to investigate the relationship between oxidative stress and the development of osteonecrosis. METHODS: Seven 24-week-old male Wistar rats were subcutaneously injected with the pro-oxidant buthionine sulphoximine (BSO) 500 mg/kg for 14 consecutive days (group B) and eight rats received injections of vehicle (physiological saline; group N). The rats in both groups were killed after 14 days, and their bilateral femurs were examined histopathologically. Blood levels of reduced glutathione (GSH), total cholesterol (T-cho) and triglycerides (TG) were also determined. RESULTS: GSH was significantly decreased in group B compared with group N (P < 0.01). No significant differences were found in T-cho or TG. Osteonecrosis was not detected in any animal in group N in contrast to five of seven animals in group B (P < 0.05). CONCLUSION: BSO is an inducer of oxidative stress, in particular interfering with the synthesis of GSH in vivo. In the present study, GSH levels were markedly reduced by BSO, whereas neither T-cho nor TG was significantly changed. The high rate of osteonecrosis noted in group B suggests that oxidative stress alone may be sufficient to promote the development of osteonecrosis at certain sites.

Relationship of lipoprotein lipase and hepatic triacylglycerol lipase activity to serum adiponectin levels in Japanese hyperlipidemic men.

OBJECTIVE: The aim of this study was to determine how lipoprotein lipase (LPL) and hepatic triacylglycerol lipase (HTGL) activity relate to serum adiponectin levels. RESEARCH DESIGN AND METHODS: Fifty-five hyperlipidemic Japanese men were recruited for this study. LPL and HTGL activity in post-heparin plasma (PHP) was measured using Triton X-100 emulsified-[14C] triolein. The remaining activity in the presence of 1M NaCl was defined as HTGL activity. Serum adiponectin levels were determined by an enzyme-linked immunosorbent assay system. RESULT: LPL activity had a positive relationship with HDL2, but had no relation with HDL3, while HTGL had positive relationship with HDL3, but had no relationship with HDL2. LPL activity showed a positive relationship [r = 0.345, p = 0.010] to serum adiponectin levels, while and HTGL activity showed an inverse relationship [r = - 0.365 p = 0.006]. Multiple regression analysis with LPL and HTGL as dependent variables and age, BMI, serum adiponectin and the homeostasis model assessment of insulin resistance (HOMA-IR) as independent variables showed LPL and HTGL's association to adiponectin did not persist after adjustments for these covariants. However, the association of LPL activity to HOMA-IR was found to persist after adjustments of age, BMI, and serum adiponectin. CONCLUSIONS: There was a co-linearity between insulin sensitivity and adiponectin as well as insulin sensitivity and LPL/HTGL activity.

A histological study of the cardiac conduction system in a heifer with complete atrioventricular block.

A case of complete atrioventricular (AV) block of congenital origin in a 16-month-old Holstein heifer was studied histologically with serial sectioning of the cardiac conduction system. The heart was enlarged and showed moderate dilatation of the left and right ventricles. Histologically, the abnormally placed and poorly formed AV bundle was observed in association with abnormality in the tricuspid extension of the central fibrous body, suggesting that the pathological state of the AV bundle had been responsible for the complete AV block. This type of anatomical fault in the AV bundle is considered to be part of an embryological, developmental malformation of the central fibrous body.

Effects of spaceflight on postnatal development of arterial baroreceptor reflex in rats.

AIM: It has been reported that spaceflight attenuates the arterial baroreceptor reflex. As this reflex function changes dramatically during postnatal development, we hypothesized that space flight depresses the developmental changes of the reflex system. To test this hypothesis, we evaluated the baroreceptor reflex function in rats, which were exposed to a microgravity environment on a space shuttle 9-25 days after birth. METHODS: Baroreceptor reflex sensitivity and the afferent sensitivity were evaluated by measuring heart rate (HR) and aortic nerve activity (ANA) changes in response to an increase in mean arterial pressure (MBP) derived by phenylephrine injection (20-50 microg kg(-1)) under urethane-anaesthesia. RESULTS: Baroreceptor reflex sensitivity (% change of HR/% change of MBP) was lower in the flight group (FLT: -0.19 +/- 0.04, n = 4) than either the asynchronous ground control group (AGC: -0.47 +/- 0.06, n = 6, P < 0.01) or the vivarium group (VIV: -0.41 +/- 0.07, n = 6, P < 0.05). This was similar to the differences of the afferent sensitivity (% change of ANA/% change of MBP) between FLT (2.07 +/- 0.30) and the control groups (AGC: 2.71 +/- 0.22, n.s.; VIV: 3.00 +/- 0.32, P < 0.05). At the end of 30 days of recovery under normal gravity conditions, however, there were no significant group differences in these parameters. conclusion: These results suggest that the space environment attenuates the postnatal development of the arterial baroreceptor reflex function in rats, which may be partially because of a depression of the postnatal development of the baroreceptor afferents. These functional alterations, however, recover to their normal level on re-exposure to the Earth's gravity.

DNA oxidation injury in bone early after steroid administration is involved in the pathogenesis of steroid-induced osteonecrosis.

OBJECTIVE: Using a rabbit model, we investigated the DNA oxidation injury occurring in bone following steroid administration and focused on the relation between DNA oxidation injury and osteonecrosis. METHODS: Japanese white rabbits weighing about 3.5 kg were injected with a single intramuscular dose of methylprednisolone 4 mg/kg and divided into groups consisting of 10 rabbits each, which were killed after 3, 5 and 14 days (groups A, B and C respectively). As a control, five untreated rabbits (group N) were also studied. An immunohistochemical study of the diaphysis of the proximal femur was conducted using the monoclonal antibody N45.1, which is a highly specific antibody against 8-hydroxy-2'-deoxyguanosine, an index of DNA oxidation injury. Also, using NIH Image freeware, the positive area (8-OHdG %PA) of each group was calculated and the four groups were compared. RESULTS: Osteonecrosis was detected only in group C (70%). N45.1 positivity was noted in bone marrow haematopoietic cells and was particularly marked in groups B and C. 8-OHdG %PA was 1.6 +/- 0.2% in group N, 2.2 +/- 0.4% in group A, 4.8 +/- 0.4% in group B and 5.1 +/- 0.5% in group C, with significantly greater oxidation injury found in groups B and C (P < 0.001). CONCLUSION: Oxidative injury was demonstrated soon after the administration of methylprednisolone in a rabbit model prior to the development of osteonecrosis. This finding may suggest new strategies to prevent steroid-induced osteonecrosis, such as the optimally timed (early) administration of antioxidant agents.

Spaceflight alters the fiber composition of the aortic nerve in the developing rat.

Hydrostatic pressure gradients due to the gravitational force in blood vessels disappear under conditions of microgravity during spaceflight, and the ability of the baroreceptor reflex to control arterial pressure and blood distribution may be altered. We hypothesized, on the basis of the results obtained in our previous experiments using the head-down tilt method in rats and rabbits, that the range of increase in arterial pressure caused by animal behavior narrows under conditions of microgravity, affecting the development of high-threshold unmyelinated fibers in the rat aortic nerve which sends signals from baroreceptors located in the aortic wall to the reflex center. We verified this hypothesis using 9-day-old rat neonates housed with their dams for 16 days on the space shuttle Columbia in outer space (STS-90, Neurolab Mission). Age-matched neonatal rats with the dams remained on the ground as controls. After breeding was carried out in the three experimental groups (FLT, spaceflight; AGC, asynchronous ground control; VIV, vivarium ground control), specimens of the 25-day-old rats were excised and five left aortic nerves in each group were examined by electron microscopy. The number of aortic unmyelinated fibers was significantly less in the FLT group than in each ground control (mean+/-S.D.; 139+/-37 in the FLT, 207+/-36 in the AGC, 283+/-121 in the VIV; P<0.05), which may be related to the weakness of the baroreceptor reflex under conditions of microgravity in space. This result may contribute to understanding of the several cardiovascular issues which occur under microgravity and after reexposure to gravity in human.

P-glycoprotein expression is associated with FDG uptake and cell differentiation in patients with untreated lung cancer.

In vitro studies demonstrated that the accumulation of 2-deoxy-D-glucose was reduced in multidrug resistant cell lines. In animal study, it has been suggested that 2-[18F]fluoro-2-deoxy-D-glucose (FDG) may be a marker for multidrug resistance (MDR). The aim of this clinical study was to compare MDR characteristics by immunohistochemical assay with FDG uptake and investigate whether FDG is a marker for MDR in patients with untreated lung cancer. Forty-seven patients with 49 untreated lung cancers, who had undergone both preoperative FDG PET imaging and thoracotomy, were enrolled in this study. Before surgery, FDG PET was performed 40 min after injection, and standardized uptake values (SUVs) were obtained. Patients were classified into low-SUV (< or = 5) and high-SUV (> 5) groups. After surgery, the expression of P-glycoprotein (Pgp) was investigated by immunohistochemistry, and the lung cancer FDG uptake was analysed for possible association with Pgp expression. The strong intensity of Pgp immunoreactivity was seen only in the low-SUV group. The percentage of the Pgp positive area was significantly lower in the high-SUV group (21.7 +/- 13.4%) than in the low-SUV group (44.1 +/- 29.7%) (P = 0.015). In the high-SUV group, the percentage of Pgp positive area did not exceed 50%. In lung adenocarcinoma, the intensity of Pgp immunoreactivity and the percentage of Pgp positive area increased with degree of cell differentiation, while FDG uptake decreased with degree of cell differentiation. Bronchioloalveolar carcinoma, in particular, showed overexpression of Pgp and modest uptake of FDG. In conclusion, Pgp expression was found to be inversely related to FDG uptake in untreated lung cancer. Pgp expression correlated with the degree of cell differentiation in adenocarcinomas, whilst FDG uptake was inversely related to cell differentiation. FDG may be an in vivo marker for MDR in patients with untreated lung cancer.

Cardiac myxoma of the tricuspid valve in a dog.

A case of cardiac myxoma arising from the tricuspid valve is described in an 8-year-old dog that had suffered intermittent episodes of syncope. At surgical operation, a large, irregular, gelatinous mass was found attached to the septal leaflet of the tricuspid valve. The excised tumour, measuring 5x4x3.5 cm, had a grey-to-yellow, friable, mucoid, multilobulated and polypoid appearance, with focal haemorrhage. Histologically, the tumour consisted of a hypocellular mass of a myxoid matrix, rich in acid mucopolysaccharides, with a supporting structure of spindle-like, elongated or stellate cells scattered in an abundant stroma. The surface of the mass was covered by a single layer of endothelial-like cells. Immunohistochemistry revealed that the surface cells of the mass were positive for the endothelial marker CD34 and the constituent cells within the mass reacted positively and uniformly with antibodies to vimentin and alpha-smooth muscle actin. The dog died 36 h after the operation and, at necropsy, wide dissemination of myxomatous embolization to the intrapulmonary arteries was found.

Primary malignant mixed mesenchymal tumour of the heart in a dog.

A case of primary malignant mixed mesenchymal tumour of the heart in an 8-year-old golden retriever is described. The cardiac tumour, measuring 2.5 x 3 x 5 cm, was located in the posterior part of the atrial septum, extending into the surrounding region. Histologically, the tumour was composed of multiple mesenchymal elements of fibrosarcoma, rhabdomyosarcoma, liposarcoma and chondrosarcoma. No previous reports of such a tumour occurring in the heart of the dog were found in the literature.

Lack of effects of oxolinic acid on spermatogenesis in young adult and aged Wistar rats.

Prolonged treatment with oxolinic acid is known to elevate serum luteinizing hormone (LH) levels, resulting in induction of Leydig cell tumors in rats. In a carcinogenicity study of the compound, tubular atrophy of the testis was also increased, suggesting that oxolinic acid might affect spermatogenesis. The present study was therefore performed using rats of different ages with a particular focus on seminiferous tubule alteration and its relation to Leydig cell proliferation. Young adult (7 weeks of age) and aged (52 weeks of age) males of the Wistar strain were administered oxolinic acid at dietary concentrations of 0 (basal diet), 300, 1000 or 3000 ppm for 4 (all groups), 13 (0 and 3000 ppm groups), 26 (0 and 3000 ppm groups), or 52 weeks (0 and 3000 ppm groups of aged rats). Serum LH levels were elevated in both young adult and aged animals treated with 3000 ppm at most examined time points. While testosterone levels were also increased at the early time points in young adult, this was not the case in older animals. Elevation of the incidences of foci and/or focal hyperplasia of Leydig cells was noted but was only slight limited to aged rats treated with 3000 ppm after 26 weeks. Furthermore, it did not appear to be related to seminiferous tubular alteration. No treatment-related histopathological abnormalities could be detected in any treatment group, and morphometrical stage analysis of spermatogenesis conducted for the control and 3000 ppm-treated groups demonstrated no lesions. These results provide strong evidence that prolonged oxolinic treatment does not directly induce testicular toxicity or altered spermatogenesis in either young adult or aged rats, except for slight increase of Leydig cell proliferative lesions caused by elevated serum LH levels. Aged rats might have higher sensitivity than young adults to the effects of oxolinic acid on proliferative lesions of Leydig cells.

Myocardial hamartoma of the right atrium in a dog.

A myocardial hamartoma of the right atrium is described in an 8-year-old dog that died from pneumonia. At necropsy, a firm, mottled, dark-brown right atrial appendage, of normal shape but slightly enlarged, was found incidentally. On section, the right atrial appendage was composed of a grey-tan, solid mass. Histological features of the mass were as follows: the component cells were mature cardiac muscle cells; the mass contained all of the components of the normal heart wall (i.e., epicardium, myocardium and endocardium), but the arrangement of the component tissues was disorganized; growth of the mass was non-invasive, and continuity of the component cells with adjacent normal myocardial cells was evident, suggesting a congenital origin. This appears to be the first report of congenital myocardial hamartoma in any animal other than man.

Expression of multidrug resistance protein and messenger RNA correlate with (99m)Tc-MIBI imaging in patients with lung cancer.

UNLABELLED: In vitro studies have shown that (99m)Tc-sestamibi (MIBI) is a transport substrate for the P-glycoprotein (Pgp) pump and the multidrug resistance-associated protein (MRP) pump. However, whether MRP and lung resistance protein (LRP) affect tumor accumulation and efflux of (99m)Tc-MIBI in lung cancer is not known. In this study, we explored whether Pgp and the other pumps, MRP and LRP, affect tumor accumulation and efflux of (99m)Tc-MIBI in lung cancer. METHODS: Thirty-four lung cancer patients who underwent surgery were examined. Before surgery, (99m)Tc-MIBI SPECT was performed 15 min and 180 min after injection, and early uptake, delayed uptake (L/Nd), and washout rate (L/Nwr) of (99m)Tc-MIBI were obtained. Pgp, MRP, and LRP expression were investigated by immunohistochemistry. The messenger RNA (mRNA) level of Pgp, MRP, and LRP was determined by real-time reverse-transcription polymerase chain reaction. The lung cancer (99m)Tc-MIBI images were correlated with protein and mRNA expression. RESULTS: The mean L/Nd of the Pgp (-) group was significantly higher than that of the Pgp (++) group (P = 0.0324). The Pgp (++) group had a higher L/Nwr than did the Pgp (-) group (P = 0.0269). The mean L/Nd of the Pgp mRNA low-expression group was significantly higher than that of the Pgp mRNA high-expression group (P = 0.0127). The Pgp mRNA high-expression group had a higher L/Nwr than did the Pgp mRNA low-expression group (P = 0.0825). No appreciable correlation was found between the lung cancer (99m)Tc-MIBI images and the expression of MRP or LRP on the level of protein or mRNA. CONCLUSION: These data suggest that an increased level of Pgp expression correlates with a low accumulation on delayed scans and a high L/Nwr of (99m)Tc-MIBI in lung cancer. Neither MRP nor LRP expression on the level of either protein or mRNA correlated significantly with tumor accumulation or efflux of (99m)Tc-MIBI in lung cancer.