Intraluminal thrombosis and growth-mechanism of giant intracranial aneurysms

12 giant intracranial aneurysms were studied by MRI. Intraluminal thrombosis was observed in 9 aneurysms. Thrombosis was found more frequently in larger aneurysms. Thrombi were formed posteriorly or inferiorly in the lumen of 4 among 5 IC-cavernous aneurysms. Location of the neck of the aneurysms and stagnation of blood flow influenced by gravity may be causative factors determining the location of thrombi. In 6 aneurysms intraluminal thrombi were inhomogeneous on MRI, suggesting that the thrombi had been formed at different times. New thrombi were formed between the aneurysmal wall and the old thrombus in 3 cases. Dissection of the aneurysmal wall by residual blood flow in the lumen or hemorrhage in the aneurysmal wall may be one of the growth mechanisms of giant intracranial aneurysms.     

Glucose consumption and rate constants for 18F-fluorodeoxyglucose in human gliomas.

To investigate the value of direct measurement of the rate constants by performing 18F-labeled fluorodeoxyglucose (FDG) studies of glucose consumption in human gliomas in vivo, a kinetic method with 3- and 4-parameter rate constant models for FDG uptake was used to analyze data from dynamic scans obtained by positron emission tomography after injection of FDG into 14 patients with glioma. The results were compared with those obtained by the autoradiographic method using 3- and 4-parameter rate constant models. There were no significant differences in the glucose consumption calculated by the four different methods both in the gliomas and in the contralateral intact cortex. It was found that the rate constant k4* could be neglected in calculation of glucose consumption in gliomas as well as in the contralateral intact cortex. The rate constant k3*, an index of hexokinase function, was higher in malignant gliomas than in benign gliomas and was close to that in the contralateral cortex. This study indicates that the 3-parameter autoradiographic method, which is the most common one used in clinical practice, is reliable for the calculation of glucose consumption in human gliomas. Furthermore, direct measurement of the regional rate constants for FDG by the kinetic method was found to be useful for evaluation of the biochemical and physiological characteristics of human gliomas in vivo.     

Significance of deposits and abnormalities of the glomerular basement membrane in tissue injury accompanying IgA nephropathy.

The glomerular injuries in 129 cases of IgA nephropathy (IgA-N) were examined ultrastructurally with special reference to the glomerular basement membrane (GBM) deposits and capillary loop abnormalities, and the correlation between these findings and the clinicopathological data was analyzed. The following results were obtained. 1) The degree of daily excretion of urine protein (UP) and creatinine clearance (Ccr) revealed a significant correlation with the degree of mesangial hypercellularities and the frequency of segmental lesions. 2) All sites of GBM deposits, and discontinuity and/or splitting among the GBM abnormalities showed a significant relation to the severity of proliferation and segmental lesions. 3) The GBM deposits, discontinuity and splitting showed a significant relation to the degree of UP and Ccr. We speculate therefore that capillary loop deposits and/or capillary loop discontinuity and splitting could represent histological prognostic factors for an unfavorable outcome in IgA nephropathy.     

Pyoderma gangrenosum associated with ulcerative colitis and subcutaneous and splenic abscesses

Pyoderma gangrenosum is a rare, chronic, inflammatory ulcerative skin disease of unknown etiology and pathogenesis. It is often associated with systemic disease. We describe a patient with pyoderma gangrenosum associated with ulcerative colitis and aseptic abscesses of the subcutis and spleen, which have been rarely reported previously. These manifestations were cleared by combined therapy with minocycline hydrochloride and diaphenylsulfone.     

Polyglutamine aggregates stimulate ER stress signals and caspase-12 activation

Accumulation of unfolded and malfolded proteins causes endoplasmic reticulum (ER) stress, stimulating unfolded protein response (UPR) and c-Jun N-terminal kinase (JNK) activation and activating caspase-12 located on the ER. Little is known about the relationship between the ER stress and polyglutamine [poly(Q)] aggregates. Poly(Q)72 repeats [poly(Q)(72)] induced the stimulation of ER stress signals such as JNK activation, upregulation of Grp78/Bip and caspase-12 activation in C2C5 cells. We prepared antiserum against the cleavage site of mouse caspase-12 at D(318) (anti-m12D318), and showed that poly(Q)(72) with perinuclear aggregates, cytoplasmic inclusions and nuclear inclusions stimulated JNK activation and anti-m12D318 immunoreactivity, but poly(Q)(72) with dispersed aggregates and small nuclear aggregates showed a significantly less effect. Poly(Q)(72) and poly(Q)(11) dispersed in cytoplasm did not. Anti-m12D318-positive cells showed apoptotic features. Unlike anti-m8D387 immunoreactivity, the anti-m12D318 immunoreactivity was not coaggregated with poly(Q). Ac-IETD-fmk (caspase-8 inhibitor) and Ac-DEVD-CHO (caspase-3 inhibitor) did not prevent the anti-m12D318 immunoreactivity induced by poly(Q)(72) aggregates. Anti-m12D318 immunoreactivity was detected in caspase-8(-/-) and caspase-3(-/-) mouse embryonic fibroblasts expressing poly(Q)(72) aggregates. Thus, caspase-12 was activated by poly(Q)(72) aggregates via a pathway independent of caspase-8 and caspase-3 activation, and caspase-12 activation was closely associated with poly(Q) aggregate-mediated cell death. Stimulation of ER stress signals may be involved in the pathogenesis of neurodegenerative disorders with poly(Q) expansion.     

Camostat mesilate attenuates pancreatic fibrosis via inhibition of monocytes and pancreatic stellate cells activity

Camostat mesilate (CM), an oral protease inhibitor, has been used clinically for the treatment of chronic pancreatitis in Japan. However, the mechanism by which it operates has not been fully understood. Our aim was to evaluate the therapeutic efficacy of CM in the experimental pancreatic fibrosis model induced by dibutyltin dichloride (DBTC), and we also determined the effect of CM on isolated monocytes and panceatic stellate cells (PSCs). In vivo, chronic pancreatitis was induced in male Lewis rats by single administration of 7 mg/kg DBTC and a special diet containing 1 mg/g CM was fed to the DBTC+CM-treated group from day 7, while the DBTC-treated group rats were fed a standard diet. At days 0, 7, 14 and 28, the severity of pancreatitis and fibrosis was examined histologically and enzymologically in both groups. In vitro, monocytes were isolated from the spleen of a Lewis rat, and activated with lipopolysaccharide stimulation. Thereafter, the effect of CM on monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) production from monocytes was examined. Subsequently, cultured rat PSCs were exposed to CM and tested to see whether their proliferation, MCP-1 production and procollagen alpha1 messenger RNA expression was influenced by CM. In vivo, the oral administration of CM inhibited inflammation, cytokines expression and fibrosis in the pancreas. The in vitro study revealed that CM inhibited both MCP-1 and TNF-alpha production from monocytes, and proliferation and MCP-1 production from PSCs. However, procollagen alpha1 expression in PSCs was not influenced by CM. These results suggest that CM attenuated DBTC-induced rat pancreatic fibrosis via inhibition of monocytes and PSCs activity.