Social isolation stress augments angiogenesis induced by colon 26-L5 carcinoma cells in mice

We have previously shown that tumor necrosis factor-α (TNF-α), which is an important angiogenesis-related factor, was over-secreted in male BALB/c mice under social isolation stress as compared with the control, and closely associated with a remarkable elevation of tumor invasion and metastasis of colon 26-L5 carcinoma cells. In the present study, we explored the effect of isolation stress on the angiogenesis caused by colon 26-L5 carcinoma cells in vivo and in vitro. Social isolation lead to the enhancement of tumor growth after intrahepatic implantation with a fragment of colon 26-L5 tumor. Angiogenic response (number of vessels oriented towards tumor mass) and tumor growth (size) were significantly increased in the socially isolated mouse relative to that in the group-housed mice. Furthermore, higher protein level of hepatic TNF-α was found in the stressed mice than that in the control. Expression of mRNA for vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were also elevated in the tumor regions and liver tissues of the stressed mice in comparison with that in group-housed mice. On the other hand, hepatic sinusoidal endothelial (HSE) cells treated with TNF-α exhibited a marked promotion of the migration, invasion, expression of mRNA for matrix metalloproteinase (MMP)-9, and tube-like formation, but no cytotoxicity against the cells in vitro. The above data suggest that the social isolation stress augmented the tumor-induced angiogenesis probably by up-regulating the angiogenesis-related factors, including TNF-α, VEGF and HGF, and consequently mediating the functions of endothelial cells such as migration, invasion, and tube-like formation.     

Molecular cloning and complete nucleotide sequence of the genome of Japanese encephalitis virus Beijing-1 strain

The genomic RNA of the Japanese encephalitis virus (JEV) Beijing-1 strain was reversely transcribed and the synthesized cDNA was molecularly cloned. Six continuous cDNA clones that cover the entire virus genome were established and sequenced to determine the complete nucleotide sequence of the JEV RNA. The precise genomic size was estimated as 10,965 bases long. With flanking 95 bases at the 5 and 583 bases at the 3 non-coding regions, one long open reading frame (ORF) was revealed encoding a virus polyprotein with 3,429 amino acid residues. Because of sequence homologies observed between JEV and other flaviviruses, the genome organization of JEV appears to be identical with other flaviviruses. Genetic variation detected among flavivirus genomes is consistent with the established serological relatedness between JEV and other members of flaviviruses. The secondary structure of the JEV genome is deduced and discussed concerning its involvement in genome replication.     

HEPATITIS-ASSOCIATED APLASTIC ANEMIA WITH SYSTEMIC PLASMACYTOSIS

An autopsy case of hepatitis associated aplastic anemia was presented. A 58-year-old Japanese female with non-A, non-B hepatitis was admitted on August 2, 1983. Moderate grade of fever and hemorrhagic diathesis appeared on September 16, when hepatitis was evaluated as being under resolving. The peripheral blood and bone marrow findings were consistent with aplastic anemia. Since infection was suggested by increased levels of serum gamma-globulin and CRP, treatment with antibiotics as well as prednisolone and blood transfusion was initiated. Since September 21, gradual tenderness and edema on the right lower abdominal wall appeared. She died on October 3.
On postmortem examination, systemic plasmacytosis with lymphadenopathy and septic monilial infection was revealed. Numerous plasma cells were atypical, but were immunohistochemically proved to be polyclonal. The bone marrow showed a massive and diffuse plasma cell proliferation with extremely scarce myeloid cells and megakaryocytes. There was a large granulomatous lesion with monilial infection in the wall of the ileocecum. By these findings, systemic plasmacytosis was suspected to be due to chronic monilial infection.
The pathogenesis of systemic plasmacytosis in aplastic anemias and in other diseases were discussed with relation to the present case.     

Contractions in normal and atherosclerotic rabbit aortas

Length-tension relationships and contractile responses to agonists associated with cyclic nucleotide levels in aortas from atherosclerotic rabbits were studied. The same number of tissues from healthy rabbits was also studied. Diffuse lesions were produced by denudation of the vascular endothelium of rabbit aorta using a balloon catheter and then feeding these rabbits a high cholesterol diet for two months. Stretch-passive tension curves and length-active tension curves which developed in the presence of 60 mM KCl significantly shifted to the left. The altered length-tension relationships indicate a decreased distensibility in these strips and this is attributed to an enhanced accumulation of collagen. Dose-response curve analysis revealed a marked hypersensitivity to serotonin as indicated by greater pD2 values (negative logarithm of half maximum dose) than seen in the controls. In addition, the mean absolute values of the maximum contraction induced by serotonin and KCl were significantly higher than in the controls. Although cyclic AMP levels in the strips with a pathology were lower and cyclic GMP/cyclic AMP ratios were higher than the controls in the basal state, serotonin induced no marked alterations in the cyclic nucleotides levels in the strips from either the diseased or control rabbits. These mechanical and pharmacological alterations of atherosclerotic vessels may relate to clinical events such as coronary spasm.     

Inhibition of phytohaemagglutinin-induced autorosette formation of human peripheral blood lymphocytes by RNA or protein synthesis inhibitor.

The induction of autorosette forming cells (ARFC) with phytohaemagglutinin (PHA) in human peripheral blood lymphocytes (PBL) was examined. After 24 h of incubation with PHA, the level of ARFC in PBL was markedly increased but subsequently decreased to about one-third of the peak level at 96 h of culture. When PBL were pre-treated with actinomycin D, or cultured with puromycin, the induction of ARFC was completely blocked. Pre-treatment of PBL with mitomycin C (MMC) had no effect on induction of ARFC, whereas DNA synthesis was completely blocked. These data indicate that the generation of autologous red blood cell receptors is a relatively early event in PHA activated PBL, and that it is independent of DNA synthesis but dependent on RNA and protein synthesis.     

Accumulation of filamentous tau in the cerebral cortex of human tau R406W transgenic mice

Missense mutations of the tau gene cause autosomal dominant frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), an illness characterized by progressive personality changes, dementia, and parkinsonism. There is prominent frontotemporal lobe atrophy of the brain accompanied by abundant tau accumulation with neurofibrillary tangles and neuronal cell loss. Using a hamster prion protein gene expression vector, we generated several independent lines of transgenic (Tg) mice expressing the longest form of the human four-repeat tau with the R406W mutation associated with FTDP-17. The TgTauR406W 21807 line showed tau accumulation beginning in the hippocampus and amygdala at 6 months of age, which subsequently spread to the cortices and subcortical areas. The accumulated tau was phosphorylated, ubiquitinated, conformationally changed, argyrophilic, and sarcosyl-insoluble. Activation of GSK-3beta and astrocytic induction of mouse tau were observed. Astrogliosis and microgliosis correlated with prominent tau accumulation. Electron microscopic examination revealed the presence of straight filaments. Behavioral tests showed motor disturbances and progressive acquired memory loss between 10 to 12 months of age. These findings suggested that TgTauR406W mice would be a useful model in the study of frontotemporal dementia and other tauopathies such as Alzheimer's disease (AD).     

Effects of ISI and stimulus probability on event-related go/nogo potentials after somatosensory stimulation

The present study investigated the characteristics of the middle-latency negative potential of event-related potentials (ERPs) using somatosensory go/nogo tasks. We manipulated interstimulus interval (ISI) in Experiment 1 and stimulus probability in Experiment 2 and analyzed the subtracted difference waveform resulting from subtraction of the ERP evoked by the go stimulation from that evoked by the nogo stimulation. In Experiment 1, the peak latency of negativity became significantly longer as the ISI increased, but the peak amplitude was unchanged. The reaction time (RT) was longer with increasing ISI. In Experiment 2, manipulation of the stimulus probability yielded an increase in peak amplitude with decreasing probability of the nogo stimulus, but did not affect the latency. The RT increased as the probability of a nogo stimulus rose. Because manipulation of the ISI and stimulus probability elicited different brain activities, we hypothesized that manipulation of the ISI elicited a delay of the stimulus evaluation process including response inhibition, and that stimulus probability significantly affected the strength of the response inhibition process.     

Infective endocarditis caused by Granulicatella elegans originating in the oral cavity

We studied the pheno- and genotypes of an oral Granulicatella elegans strain in comparison with those of a blood-derived isolate which caused infective endocarditis. The two isolates exhibited identical biochemical characteristics and had the same drug MICs. Their genotypes were indistinguishable, indicating that these were from the same clone. The transmission of G. elegans from the oral cavity thus should be noted as a possible cause of infective endocarditis.     

Expression and function of X chromosome-linked inhibitor of apoptosis protein in Sjögren's syndrome

Apoptotic cell death in acinar and ductal epithelial cells is thought to play an important role in the development of salivary gland dysfunction in patients with Sjogren's syndrome (SS). We examined the expression of anti-apoptotic molecules in salivary glands from patients with SS. The labial salivary glands from six human T-cell leukemia virus (HTLV)-I-seronegative and eleven HTLV-I-seropositive SS patients were analyzed by immunohistochemistry. In vitro experiments were performed with a human salivary gland cell line (HSG cells). Immunohistologic analyses revealed that Bcl-2 and Bcl-x were preferentially expressed in salivary infiltrating mononuclear cells more than acinar and ductal epithelial cells. In contrast, strong X chromosome-linked inhibitor of apoptosis protein (XIAP) expression was evident in both acinar and ductal epithelial cells. The pattern of expression of these anti-apoptotic molecules was similar in both HTLV-I-seropositive and HTLV-I -seronegative SS patients. Western blot analysis confirmed expression of XIAP in cultured HSG cells. The expression of XIAP in HSG cells was increased by IL-1beta, TGF-beta1, or IL-10. However, XIAP expression was down-regulated by TNF-alpha, which induced apoptotic cell death of HSG cells with an increase in caspase-3 activity. These effects of TNF-alpha in HSG cells were antagonized by IL-1beta, TGF-beta1, or IL-10. Our results suggest that XIAP is important in regulating apoptotic cell death of acinar and ductal epithelial cells in patients with SS.