Systematic Review of Clinical and Pathophysiological Features of Genetic Creutzfeldt–Jakob Disease Caused by a Val-to-Ile Mutation at Codon 180 in the Prion Protein Gene

Genetic Creutzfeldt–Jakob disease (gCJD) is a subtype of genetic prion diseases (gPrDs) caused by the accumulation of mutated pathological prion proteins (PrP^Sc). gCJD has a phenotypic similarity with sporadic CJD (sCJD). In Japan, gCJD with a Val to Ile substitution at codon 180 (V180I-gCJD) is the most frequent gPrD, while the mutation is extremely rare in countries other than Japan and Korea. In this article, we aim to review previously elucidated clinical and biochemical features of V180I-gCJD, expecting to advance the understanding of this unique subtype in gCJD. Compared to classical sCJD, specific clinical features of V180I-gCJD include older age at onset, a relatively slow progression of dementia, and a lower positivity for developing myoclonus, cerebellar, pyramidal signs, and visual disturbance. Diffuse edematous ribboning hyperintensity of the cerebral cortex, without occipital lobes in diffusion-weighted magnetic resonance imaging, is also specific. Laboratory data reveal the low positivity of PrP^Sc in the cerebrospinal fluid and periodic sharp wave complexes on an electroencephalogram. Most patients with V180I-gCJD have been reported to have no family history, probably due to the older age at onset, and clinical and biochemical features indicate the specific phenotype associated with the prion protein gene mutation.     

Absorption saturation mechanism in short-period GaAs/AlAs superlattice self-electro-optic effect devices based on Wannier-Stark localization

We have studied absorption saturation characteristics in short-period GaAs/AlAs superlattice self-electro-optic effect devices based on Wannier-Stark localization. The disappearance of negative differential resistances due to absorption saturation was observed under high optical excitation intensities. To understand the mechanism, we measured the time-resolved photocurrent and time-resolved photoluminescence. Results revealed that the absorption saturation is caused by electric field screening originating from the space-charge of remaining holes due to effective mass filtering.     

Increase in adhesion molecules on CD4+ cells and CD4+ cell subsets in synovial fluid from patients with rheumatoid arthritis

OBJECTIVE: To elucidate the role of adhesion molecules in the pathogenesis of rheumatoid arthritis (RA). METHODS: We evaluated their expression and that of an activation marker on CD4+ cell populations and CD4+ cell subsets in specimens of peripheral blood (PB) and synovial fluid (SF) obtained from 10 patients with RA and 7 with osteoarthritis (OA). A 2 or 3-color immunofluorescent method was used for analysis. RESULTS: The SF from both groups of patients showed a greater density of adhesion molecules including LFA-1 alpha, LFA-1 beta, CD2, VLA-4 alpha and VLA-5 alpha on CD4+ cells, and a higher percentage of CD4+HLA-DR+ cells compared with their PB. IN PB-CD4+ cell subsets from the arthritic and healthy subjects, the CD4+CD45RO+ cell population showed an increased expression of adhesion molecules compared with CD4+CD45RA+ cell population. The expression of adhesion molecules on circulating CD4+ cell population and CD4+ cell subsets from the patients with RA and OA was comparable to that from healthy subjects. SF from both groups of patients showed a higher percentage of CD4+CD45RO+ cells and a lower percentage of CD4+CD45RA+ cells. In SF-CD4+ cell subsets from patients with RA, the CD4+CD45RO+ cell population had an increased expression of VLA-4 alpha compared to the CD4+CD45RA+ cell population; however, there was no significant difference in other adhesion molecule expression and the percentage of HLA-DR+ cells between the 2 cell subsets. Furthermore, the expression of VLA-4 alpha on the CD4+CD45RO+ cell population in SF from patients with RA was significantly higher than that in matched PB. In CD4+CD45RA+ cell population from both groups of patients, SF showed an enhanced expression of adhesion molecules and an increased percentage of HLA-DR+ cells compared with matched PB. CONCLUSION: Our results suggest that increased expression of adhesion molecules and increased percentage of HLA-DR+ cells on CD4+ cells in SF may be responsible for cellular interactions between these cells and synovial cells or extracellular matrix.     

Histiocytic sarcoma of the spleen associated with hypoalbuminemia, hypo gamma-globulinemia and thrombocytopenia as a possibly unique clinical entity--report of three cases

The organization and nucleotide sequence of the capsular gene cluster involved in the biosynthesis of the type 33F capsular polysaccharide of Streptococcus pneumoniae have been determined. The complete type 33F operon (cap33f) is composed of 14 potential open reading frames where the last ten genes are group-specific. Putative functions have been assigned to several gene products by sequence comparison with the proteins included in the databases. A functional promoter located immediately upstream from the first gene of the cap33f gene cluster has been demonstrated. A 20 kb DNA fragment containing the cap33f genes and the operon promoter was sufficient to transform a S. pneumoniae type 3 unencapsulated mutant to the type 33F capsule.     

The long-term results of percutaneous isolated hepatic perfusion for patients with advanced hepatocellular carcinoma

We studied the long-term outcome of percutaneous isolated hepatic perfusion (PIHP) for patients with hepatocellular carcinoma. This study included 31 patients with Stage IVA and 5 with IVB disease treated by PIHP until December, 1997. The mean age and tumor diameter were 55 and 7.7 cm, respectively. Twenty-two had portal vein invasion, 13 had hepatic vein invasion, and all patients had multiple intrahepatic metastases of more than 5 tumor foci. The PIHP with adriamycin or cisplatin was undertaken in a total of 50 treatments in these 36 patients. CR was observed in 6 and PR in 13 with an overall response rate of 59%, excluding 4 patients who were not evaluable. Five of 6 patients with CR remain free of disease at 7 to 54 months after the first treatment. The overall survival rate was 67% at 1 year and 32% at 5 years. The survival rates of Stage IVA patients (1-year = 71%, 5-year = 36%) were higher than Stage IVB patients (1-year = 20%, 5-year = 0%). The 5-year survival rates of patients with vascular invasion (Vp1-3 = 23%, Vv1-3 = 8%) were lower than those without it (Vp0 = 47%, Vv0 = 51%). These results indicated that PIHP achieved a 5-year survival rate of approximately 40% in patients with multiple advanced hepatocellular carcinoma in the absence of distant organ metastases and marked vascular invasion, and yielded complete long-term remission in some of these patients.     

Screening for APC mutations based on detection of truncated APC proteins

Mutation of the adenomatous polyposis coli (APC) gene is frequently found in colorectal tumors from both familial adenomatous polyposis (FAP) and non-FAP patients. Analysis of APC mutation is time-consuming and costly due to the large size of the APC gene. As the majority of APC mutations result in the truncation of gene products, the detection of truncated APC proteins may be used as a screening method for APC mutations. The aim of this study is to establish a practical method of detecting truncated APC proteins for the screening of APC mutations. APC proteins in human colorectal cancer cell lines were analyzed by western blotting. Truncated APC proteins were expressed in all of the colorectal cancer cell lines studied. Two species of truncated APC proteins were expressed in two cell lines. Western blotting is a rapid, reliable screening method for APC mutations and provides information on both alleles.     

Prostaglandin E1 from the tip of an intraaortic balloon catheter for lower limb ischemia

A method to treat lower limb ischemia associated with the insertion of an intraaortic balloon catheter is herein reported. A low dose of prostaglandin E1 was administered into the descending aorta continuously from the tip of the intraaortic balloon catheter. Immediately after the administration of prostaglandin E1 in patients whose lower limbs were ischemic due to obstruction with the catheter, the peripheral circulation of the ischemic limbs recovered with minimal changes in the systemic arterial blood pressure. This method is simple and noninvasive and was found to induce a satisfactory effect.     

Magnetic resonance imaging and pathologic studies on lateral fluid percussion injury as a model of focal brain injury in rats

In this study, morphologic changes in brain lesions initiated by moderate lateral fluid percussion injury in rats were investigated chronologically using high-resolution magnetic resonance imaging (MRI) and histopathologic methods. Rats were subjected to moderate fluid percussion injury (average 2.80 +/- 0.48 atmospheres) over the exposed dura overlying the right parietal cortex. MRI obtained in vivo were compared with corresponding pathologic findings at 1, 6, and 24 h and at 3, 6, 14 and 80 days after injury. T2-weighted images showed scattered low-signal intensity in the injured cortex within a few hours after injury, whereas histologic findings revealed intraparenchymal hemorrhages. T2-weighted images of the ipsilateral cerebral cortex and/or corpus callosum showed a high-signal-intensity area 4 h after injury. The high-signal-intensity area became largest in size between 6 and 24 h, then declined gradually, and almost disappeared 14 days after injury. Histologic examination revealed pyknosis, retraction of the cell body of neurons with vacuolated neuropil in the corresponding regions 6 and 24 h after injury, and cystic necrosis 14 days after injury. The location and extent of these pathologic changes were depicted accurately by MRI in vivo. In the hippocampus, pyknosis and retraction of the cell body of pyramidal neurons were observed on the injured side 24 h after injury, and the number of neurons in the CA1 and CA2-CA3 regions decreased significantly on the same side by 14 days after injury. It is concluded that morphologic changes in the brain following experimental traumatic brain injury in rats are detectable in vivo by high-resolution MRI, and that MRI may be useful for the evaluation of treatment effects in experimental brain injury.