Analysis of DNA copy number aberrations in hepatitis C virus-associated hepatocellular carcinomas by conventional CGH and array CGH.

To clarify the genetic aberrations involved in the development and progression of hepatitis C virus-associated hepatocellular carcinoma (HCV-HCC), we investigated DNA copy number aberrations (DCNAs) in 19 surgically resected HCCs by conventional CGH and array CGH. Conventional CGH revealed that increases of DNA copy number were frequent at 1q (79% of the cases), 8q (37%), 6p (32%), and 10p (32%) and that decreases were frequent at 17p (79%), 16q (58%), 4q (53%), 13q (42%), 10q (37%), 1p (32%), and 8p (32%). In general, genes that showed DCNAs by array CGH were usually located in chromosomal regions with DCNAs detected by conventional CGH analysis. Increases in copy numbers of the LAMC2, TGFB2, and AKT3 genes (located on 1q) and decreases in copy numbers of FGR/SRC2 and CYLD (located on 1p and 16q, respectively) were observed in more than 30% of tumors, including small, well-differentiated carcinomas. These findings suggest that these genes are associated with the development of HCV-HCC. Increases of MOS, MYC, EXT1, and PTK2 (located on 8q) were detected exclusively in moderately and poorly differentiated tumors, suggesting that these alterations contribute to tumor progression. In conclusion, chromosomal and array CGH technologies allow identification of genes involved in the development and progression of HCV-HCC.     

Cytoplasmic architecture of the axon terminal: filamentous strands specifically associated with synaptic vesicles

Cytoplasmic architecture of axon terminals in rat central nervous tissue was examined by quick-freeze deep-etch method to determine how synaptic vesicles and their associated cytoplasmic environment are organized in the terminal and to know how these structures participate in the mechanism for neurotransmitter release. The axoplasm is divisible into two domains: one occupied by mitochondria in the middle of the terminal, called the mitochondrial domain, the other situated in the periphery and exclusively filled with spherical synaptic vesicles, 50-60 nm in diameter, the synaptic vesicle domain. The most characteristic feature of the mitochondrial domain was the appearance of many microtubules connected with mitochondria by filamentous strands. Large vesicles, 80-100 nm in diameter, were preferentially associated with the mitochondrial domain, and linked with microtubules wherever they appeared. The cytoplasmic matrix of the synaptic vesicle domain showed a more fibrillar texture than that of the mitochondrial domain because of the distribution of filamentous strands associated with synaptic vesicles. These strands were significantly thicker and longer (mean 11.7 nm thick and 42.7 nm long) than those linking membrane-bound organelles to microtubules (mean 8.3 nm thick and 23.0 nm long), and connected vesicles to one another or to the plasma membrane, making a complicated network around the vesicles. Further, both strands were significantly different in dimension from actin filaments (mean 9.9 nm thick and 73.5 nm long) showing 5-nm axial periodicity. These strands, especially synaptic vesicle-associated ones including their network, were readily broken down in the most part by detergent treatment or chemical fixation, indicating that they are very delicate in nature. Granular materials, which are spherical and vary in size (6-20 nm in diameter), are also more conspicuous in the synaptic vesicle domain than in the mitochondrial domain. More fibrillar and granular cytoplasmic structure of the synaptic vesicle domain may be crucial for synaptic vesicles to perform an essential role in releasing the transmitter.     

Structure-acute toxicity relationship of aromatic hydrocarbons in mice

The structure-acute toxicity relationship of aromatic hydrocarbons was examined in mice. In all test compounds, the acute toxicity was determined under 2 conditions: control LD₅₀ (LD₅₀-cont) and carbon tetrachloride (CCl₄)-pretreated LD₅₀ (LD₅₀-CCl₄). The CCl₄-pretreatment was done in order to evaluate the toxic potency of compound itself without the influence of metabolism. Both log (1/LD₅₀-cont) and log (1/LD₅₀-CCl₄) were functions of the log P, n-octanol/water partition coefficient, i.e., log (1/LD₅₀-cont) = 0.080 log P − 1.532 and log (1/LD₅₀-CCl₄) = −0.040(log P)² + 0.157 log P − 1.373. Both equations were statistically significant (P < 0.01). The ratio of LD₅₀-cont/LD₅₀-CCl₄ indicated that metabolic activation is more evident in hydrophobic compounds than in hydrophilic compounds. The results suggest that hydrophobicity of the aromatic hydrocarbons plays an important role in determining their acute toxicity.     

Maffucci’s syndrome associated with spindle cell hemangioendothelioma

 The case of a 49-year-old man with Maffucci’s syndrome, who developed multiple spindle cell hemangioendotheliomas, is presented. The case provides support for recent reports suggesting an association between this peculiar vascular lesion and skeletal enchondromatosis.     

Reconstruction of the distal foot dorsum with a distally based extensor digitorum brevis muscle flap.

We have successfully applied a reverse flow island flap of extensor digitorum brevis muscle for coverage of tissue defects in the distal portion of the foot dorsum in 2 patients. This flap covered the metatarsophalangeal area well with cadaver limb dissection and seems useful to cover the defect in the distal foot dorsum.     

Periodic alternating nystagmus and rebound nystagmus in spinocerebellar ataxia type 6.

We report on a family with ataxia type 6 (SCA6) showing peculiar oculomotor symptoms. The proband presented with periodic alternating nystagmus (PAN), and her 2 brothers had rebound nystagmus and gaze-evoked nystagmus. They carried the identical mutation (the number of expanded CAG repeat, 24) in the CACNA1A gene. The intrafamilial variability of oculomotor symptoms may be ascribed to factors other than CAG repeat expansion size in SCA6.     

Early seizures after acute ischemic stroke]

In order to determine predictive factors of early seizures (ES) after acute stroke and to estimate prognosis, we retrospectively examined clinical data of 1,743 consecutive patients with acute ischemic stroke. The subjects were divided into two groups; an ES group (19 patients) and a non-ES group (1,724 patients). Multivariate statistical analysis revealed that the NIH-Stroke Scale score on admission (/10, OR, 1.1: 95% CI 1.04 to 1.13) and positive past history of cerebrovascular disease or brain injury (OR, 3.85: 95% CI 1.49 to 9.95) are significant factors to predict ES. There was no significant difference in the outcome between the two groups. A recurrence of seizures, after follow up for 4 to 40 months, was observed only in one patient with a history of ES.     

Technique of intramedullary fixation for arthrodesis of the wrist in rheumatoid arthritis.

We did 18 arthrodeses of the wrist in 16 patients with rheumatoid arthritis using an intramedullary fixation technique. There were 15 women and one man, whose ages at operation ranged from 47 to 71 years (mean 58). Follow up ranged from 13 to 68 months (mean 27). The operative technique consists of a combination of intramedullary placement of two Kirschner (K)-wires and an autogenous bone graft. At follow up bony union was apparent in all cases. K-wires came out of the metacarpal joints in two cases. Paraesthesiae in the median nerve distribution occurred in two cases which both recovered within three months.     

Antibodies to beta 2-microglobulin, the light-chain component of class I histocompatibility molecules, provide an activation signal to human lymphocytes

Antibodies to beta 2-microglobulin (beta 2m), the light-chain component of class I histocompatibility antigens, provide a strong co-stimulatory signal to human lymphocytes in the presence of phorbol ester. This activation signal requires a high concentration of antibody, whereas the effect on responses to a mitogenic lectin is exclusively inhibitory over a broad dose range. A rabbit polyclonal and a mouse monoclonal antibody to beta 2m were similarly co-stimulatory. Antibody to beta 2m was co-stimulatory with phorbol ester, but not calcium ionophore, suggesting that class I antigens play a role in the initiation of the 'first' signal of a recently described two-signal model of lymphocyte activation.