Heavily T2-weighted imaging findings of spinal cord swelling in dogs with intervertebral disc extrusion.

ABSTRACT: This study investigated causes of attenuation of cerebrospinal fluid (CSF) signal on heavily T2-weighted (T2W) images in dogs with thoracolumbar disc extrusion. Medical records and magnetic resonance images were retrospectively reviewed. Dogs were classified into the following grades; grade 1, non-ambulatory paraparesis; grade 2, paraplegia with deep pain perception and grade 3, paraplegia without deep pain perception. The length of intramedullary T2W hyperintensity of the spinal cord, cranial/ caudal expansion of extradural compressive materials (ECM), and the CSF signal attenuation were measured. Ratios to the second lumbar vertebra (L2) were calculated for the length of intramedullary T2W hyperintensity (T2W:L2), cranial/caudal expansion of ECM (ECML:L2), and CSF signal attenuation (CSF:L2). The dogs were classified into focal or extended T2W hyperintensity groups according to the length [focal, shorter than length of L2; extended, longer than L2]. The area of EMC and the spinal canal were measured on transverse images at the lesion deriving occupancy ratio. The correlation between CSF:L2 and other data were analysed, and CSF:L2 was compared between the grades. In dogs with intramedullary T2W hyperintensity, the locations of CSF attenuation and the hyperintensity were compared if those locations were matched. Fifty-five dogs were included, 36 of which showed intramedullary T2W hyperintensity. Twenty-two of 36 dogs were considered as match of the location of the CSF attenuation and hyperintensity. CSF:L2 was significantly correlated with T2W:L2 in dogs with extended T2W hyperintensity (p = 0.0002), while CSF:L2 was significantly correlated with ECML:L2 in dogs with focal or no T2W hyperintensity (p = 0.0103 and p = 0.0364, respectively). CSF:L2 in grade 3 was significantly greater than those in patients who were grade 1 or 2 (both p < 0.001). In conclusion, higher CSF:L2, which was frequently seen in grade 3, would be most consistent with a higher T2W:L2 which might indicate spinal cord swelling.

Computed tomographic features of portal vein thrombosis in two cats with splenosystemic shunts.

Two spayed female cats presented with hepatic encephalopathy due to hyperammonaemia. On abdominal ultrasound, concurrent portal vein thrombosis and splenosystemic shunts were suspected in both cats. Computed tomographic angiography clearly detected thrombi as non-contrast enhancing intraluminal structures in the main portal vein of both cats. Additionally, splenorenal shunts were revealed in both cats. Follow-up computed tomographic angiography for portal vein thrombosis was performed in both cats, only one of whom received anticoagulant therapy. In the untreated cat, portal vein thrombosis had progressed with the development of an aberrant tortuous vessel. In the cat treated with low-molecular-weight heparin, the thrombus progressively decreased in size and disappeared on follow-up diagnostic imaging. Computed tomographic angiography might be useful for the diagnosis and follow-up of portal vein thrombosis in cats.

Two-Year Follow-Up Magnetic Resonance Imaging and Spectroscopy Findings and Cerebrospinal Fluid Analysis of a Dog with Sandhoff's Disease.

A 13-month-old female Toy Poodle was presented for progressive ataxia and intention tremors of head movement. The diagnosis of Sandhoff's disease (GM2 gangliosidosis) was confirmed by deficient ß-N-acetylhexosaminidase A and B activity in circulating leukocytes and identification of the homozygous mutation (HEXB: c.283delG). White matter in the cerebrum and cerebellum was hyperintense on T2-weighted and fluid-attenuated inversion recovery magnetic resonance images. Over the next 2 years, the white matter lesions expanded, and bilateral lesions appeared in the cerebellum and thalamus, associated with clinical deterioration. Magnetic resonance spectroscopy showed progressive decrease in brain N-acetylaspartate, and glycine-myo-inositol and lactate-alanine were increased in the terminal clinical stage. The concentrations of myelin basic protein and neuron specific enolase in cerebrospinal fluid were persistently increased. Imaging and spectroscopic appearance correlated with histopathological findings of severe myelin loss in cerebral and cerebellar white matter and destruction of the majority of cerebral and cerebellar neurons.

LBH589, a deacetylase inhibitor, induces apoptosis in adult T-cell leukemia/lymphoma cells via activation of a novel RAIDD-caspase-2 pathway.

Adult T-cell leukemia/lymphoma (ATLL), an aggressive neoplasm etiologically associated with human T-lymphotropic virus type-1 (HTLV-1), is resistant to treatment. In this study, we examined the effects of a new inhibitor of deacetylase enzymes, LBH589, on ATLL cells. LBH589 effectively induced apoptosis in ATLL-related cell lines and primary ATLL cells and reduced the size of tumors inoculated in SCID mice. Analyses, including with a DNA microarray, revealed that neither death receptors nor p53 pathways contributed to the apoptosis. Instead, LBH589 activated an intrinsic pathway through the activation of caspase-2. Furthermore, small interfering RNA experiments targeting caspase-2, caspase-9, RAIDD, p53-induced protein with a death domain (PIDD) and RIPK1 (RIP) indicated that activation of RAIDD is crucial and an event initiating this pathway. In addition, LBH589 caused a marked decrease in levels of factors involved in ATLL cell proliferation and invasion such as CCR4, IL-2R and HTLV-1 HBZ-SI, a spliced form of the HTLV-1 basic zipper factor HBZ. In conclusion, we showed that LBH589 is a strong inducer of apoptosis in ATLL cells and uncovered a novel apoptotic pathway initiated by activation of RAIDD.

A case of obstructive sleep apnoea with anterior cervical osteophytes.

Osteophytes of the cervical spine are usually seen in elderly adults. When prominent, they have been blamed for dysphagia, cough, dysphonia and dyspnoea. This paper reports on an obstructive sleep apnoea (OSA) patient with cervical spinal osteophytes, one cause of airway obstruction. A 75-year-old male complained of pronounced snoring. The diagnosis was mild OSA, apnoea hypopnoea index was 9.4. Patient reported no restrictions in neck movements, experiences of neck pain or neck trauma. Previously, patient underwent a tonsillectomy due to discomfort in the pharyngeal region. A lateral cephalometric image was taken to observe airway before oral appliance therapy. The image revealed the presence of large osteophytes or sclerotic enthesopathy, lying on anterior surfaces from the fourth to seventh cervical vertebrae. A computed tomography (CT) image revealed the relationship of airway position to the spine. In the reconstructed three-dimensional (3D) image, the airway appeared displaced to the right of the craniomandiblar bone, with the hyoid bone similarly displaced in a manner to that of the airway. The spine also appeared displaced to the left side ofcraniomandiblar bone. Additionally, the 3D image revealed calcification of the stylohyoideum ligament and ligamentum nuchae. This present case highlights the necessity of CT examination for OSA patients. There were several ligament calcifications in the head and neck region. Cervical spine osteophytes, as a component of Forestier's or cervical spine disease, have been associated with dysphagia and dysphonia. It was reported that bilateral vocal cord paralysis was caused by osteophytes compressing the post-cricoid area of larynx.

Impaired circadian rhythm of gastric myoelectrical activity in patients with multiple system atrophy.

In order to evaluate gastric motility and its circadian rhythm in patients with multiple system atrophy (MSA) and healthy control subjects, we measured gastric myoelectrical activity (GMA) for 24 hours using a cutaneous electrogastrogram (EGG) recorder in 14 MSA patients and 9 age-matched controls. We analyzed six 10-minute segments of EGG before and after each meal and two 20-minute EGG segments during sleep; three parameters were used for the analysis: dominant frequency (DF), instability coefficient of dominant frequency (ICDF), and dominant power (DP). DF increased during daytime and decreased during sleep in the control, while this circadian variation was blunted in the patients with MSA. The average DF of the eight segments in the MSA patients did not differ from that of the control. Both MSA patients and control subjects did not show the circadian variation of ICDF and DP. The average ICDF of the eight segments in the patients with MSA was significantly decreased when compared with that of the control (p < 0.01). No differences were observed in DP between the two groups. This study indicates that the healthy subjects appear to have a circadian rhythm of DF, and the patients with MSA appear to have impaired circadian rhythm of DF and decreased ICDF possibly due to the degeneration of the central autonomic neurons.

Clearance rates of cerivastatin metabolites in a patient with cerivastatin-induced rhabdomyolysis.

We report on a patient who developed acute rhabdomyolysis after taking cerivastatin. A 74-year-old hypercholestrerolaemic woman taking cerivastatin (0.15 mg/day) for 22 days complained of general muscle weakness and muscle pain. Her serum creatinine phosphokinase level was 19,190 IU/L. Serum myoglobin was over 3000 ng/mL. Serum concentration of cerivastatin at 6 h after taking the last dose (0.15 mg) was 8062.5 ng/L, which was almost 5.7 times higher than that of normal persons. The serum concentration of cerivastatin showed that the half-life of cerivastatin in this patient was 22.4 h, compared with 2.4 h for normal controls. Cerivastatin is catabolized by cytochrome P450, 3A4 and 2C8 to M-1, and by 2C8 to M-23. The ratio of M-23 to M-1 in her serum was much lower than that of control persons (0.64 vs. 2.08). She had previously taken simvastatin which is metabolized by CYP3A4, without any sign and symptoms of rhabdomyolysis. These results suggest that the slowed clearance of cerivastatin in this patient might have been compounded by cytochrome P450, 2C8 dysfunction.

Organotropic chemopreventive effects of n-3 unsaturated fatty acids in a rat multi-organ carcinogenesis model.

Organotropic chemopreventive effects of n-3 unsaturated fatty acids were studied using a multi-organ carcinogenesis model in male rats. Rats were treated with diethylnitrosamine (DEN), N-methyl-N-nitrosourea (MNU), N-butyl-N-4-hydroxybutylnitrosamine (BBN), 1,2-dimethylhydrazine (DMH) and dihydroxy-di-n-propylnitrosamine (DHPN) during the first 7 weeks, and then given unsaturated fatty acid (UFAs), docosahexaenoic acid (n-3, C(22:6)) (DHA), eicosapentaenoic acid (n-3, C(20:5)) (EPA), linoleic acid (n-6, C(18:2)) (LA) or oleic acid (n-9, C(18:1)) (OA) at a dose of 1.0 ml/rat, 3 times a week by gavage for the consecutive 30 weeks. All rats were fed a low LA basal diet throughout the experiment and a calorie-restricted basal diet during the period of UFAs feeding administration. DHA significantly reduced tumor size and numbers in the large intestine as compared to OA treatment. Furthermore, DHA showed a tendency to inhibit carcinogenesis in the small intestine and lung. EPA also showed a tendency to inhibit intestinal carcinogenesis. On the other hand, LA showed a tendency to inhibit lung carcinogenesis, but to promote large intestinal carcinogenesis. However these UFAs did not influence preneoplastic and neoplastic lesion development in the liver, kidney, and urinary bladder. Levels of the administered fatty acids were clearly increased in the serum and organs. In contrast, arachidonic acid (AA) levels in the large and small intestines and liver were markedly decreased by treatment with DHA and EPA. Decreased levels of AA in the large intestine correlated well with tumor incidence, although the number of glutathione S-transferase-positive (GST-P(+)) foci showed an inverse correlation with AA levels. The data thus provide evidence that an organotropism exists with regard to the influence of UFAs on carcinogenesis, which correlates with reduction of tissue AA levels in the target organs.

Seasonal and diurnal patterns of soil water potential in the rhizosphere of blue oaks: evidence for hydraulic lift.

In a 3-year study, seasonal and daily soil water fluctuations in a California blue oak woodland were investigated by measuring soil water potential (Ψs) at hourly intervals. Soil water potential remained relatively high well into the annual summer drought, with values above -0.5 MPa until June even in a dry year. As drought progressed, Ψs (at 25, 50, 75, and 100 cm depth) decreased to less than -3 MPa, providing evidence for continued blue oak root activity throughout the summer. We observed diurnal Ψs fluctuations (gradual increase at night and rapid decrease during daytime) characteristic of hydraulic lift, a process by which plant roots redistribute water from wet to dry soil layers. These diurnal fluctuations were observed at all four soil depths and began to appear when Ψs reached approximately -0.3 MPa. When Ψs reached approximately -3 MPa, fluctuations became "offset" from those typical of hydraulic lift. These offset fluctuations (apparent at low water potentials when temperature fluctuations were large) closely followed diurnal fluctuations in soil temperature. We propose that these offset patterns resulted from a combination of hydraulic lift cessation and an over-correction for temperature in the model used to calculate Ψs from raw sensor data. The appearance and disappearance of hydraulic lift fluctuations seemed to depend on Ψs. While soil temperatures and dates at which hydraulic lift appeared (and disappeared) were significantly different between wet and dry years, Ψs values associated with hydraulic lift appearance were not significantly different. Hydraulic lift occurred too late in summer to benefit annual forage grasses. However, water released by blue oak trees at night could slow the rate of soil water depletion and extend blue oaks' growing season.

A new analytical method for the detection of anti-tumor promoters using flow cytometry.

Flow cytometry analysis was applied to the measurement of Epstein-Barr virus (EBV) induction which is used as a short term assay for anti-tumor promoters. The data obtained by measurement with flow cytometry were parallel with those of the fluorescence microscopic method. Flow cytometry is rapid, quantitative and should be applicable for the EBV activating test.

Phorbol ester-induced production of prostaglandin E2 from phosphatidylcholine through the activation of phospholipase D in UMR-106 cells.

To determine the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) on phospholipase D (PLD) activity in osteoblast-like UMR-106 cells, we used cells prelabeled with [3H] myristic acid or [3H] arachidonic acid, which were preferentially incorporated to phosphatidylcholine. The treatment of [3H] myristate-labeled cells with TPA in the presence of 1% ethanol caused a dose-dependent formation of [3H] phosphatidylethanol (PEt), a product specific to PLD, suggesting an activation of this enzyme. Pretreatment of the cells with protein kinase C (PKC) inhibitors (GF109203X, staurosporine or H-7) abolished the TPA-dependent formation of PEt. The PEt formation in response to TPA treatment was not observed after the pretreatment of the cells with TPA to downregulate PKC. These results suggest the involvement of PKC in the TPA-induced activation of PLD. With [3H] arachidonate-labeled cells, TPA treatment in the absence of ethanol resulted in the liberation of [3H] arachidonic acid, which was gradually converted to prostaglandin E2 (PGE2), but the accumulations of [3H] phosphatidic acid (PA) and [3H] diacylglycerol (DAG) were very small and temporary. In contrast, PA was linearly accumulated following TPA treatment, when the cells were pretreated with an inhibitor of phosphatidate phosphohydrolase (PAP), propranolol, with no accumulation of either DAG or arachidonic acid. The TPA treatment of the cells pretreated with a DAG lipase inhibitor, RHC-80267, caused the generation of DAG after a lag period of approximately 5 min, with a very small and temporary accumulation of PA. The TPA treatment of cells pretreated with a cyclooxygenase (COX) inhibitor, indomethacin, blocked the PGE2 production. The TPA-induced PGE2 production was not affected by the pretreatment of cells with a phospholipase A2 inhibitor, p-bromophenacylbromide, or with a phospholipase C inhibitor, D-609. TPA also stimulated PGE2 production in osteoblastic cells that were enzymatically isolated from adult rat calvaria, and the experiments with lipid metabolizing enzyme inhibitors gave the same profile of inhibition of TPA-induced PGE2 production as was observed in UMR-106 cells. These results suggest that PA formed as a consequence of the activation of PLD by TPA is rapidly converted to arachidonic acid via a PAP/DAG lipase pathway, followed by a gradual conversion of arachidonic acid to PGE2 by COX in both UMR-106 cells and isolated adult osteoblastic cells, and that neither phospholipase A2 nor phospholipase C is involved in the TPA-induced PGE2 production. To the best of our knowledge, this is the first report that shows that the activation of PKC in osteoblastic cells leads to the production of PGE2 via a PLD/PAP/DAG lipase/COX pathway.