Induction of interferon-inducible protein-10 and monokine induced by interferon-gamma from human endothelial cells infected with Influenza A virus

Primary human umbilical vein endothelial cells (HUVECs) were infected with Influenza virus A/Aichi/2/68 (H3N2) in order to determine the role of endothelial cells in mediating inflammation induced upon virus infection. Structural proteins of the virus and mRNA of the M2 protein were detected in the infected cells, indicating that virus infection had occurred in HUVECs. The Influenza A virus-infected HUVECs showed elevated levels of gene expression of interferon (IFN)-inducible protein (IP)-10 and monokine induced by IFN-gamma (Mig), while heat-, formalin- and diethyl ether-inactivated viruses did not enhance the IP-10 and Mig gene expression. The results thus indicate that infection of live Influenza A virus is responsible for elevation of IP-10 and Mig gene expression. The elevation of IP-10 and Mig gene expression in infected HUVECs was not accompanied by the elevation of IFN-gamma gene expression, indicating that the elevation of IP-10 and Mig gene expression was independent of the IFN-gamma pathway.     

Down-regulation of antigen-specific antibody production by TCR antagonist peptides in vivo

The efficacy of TCR antagonist peptides in inhibition of antigen-specific antibody production and T cell responses in vivo was evaluated. Among amino acid-substituted analogs of a peptide corresponding to residues 119 - 133 of bovine beta-lactoglobulin (p119 - 133), pR124Q and pD129S, prepared by substitution of Gln and Ser for Arg(124) and Asp(129), respectively, have been shown to display TCR antagonist activity for three out of four distinct p119 - 133-specific T cell clones and for polyclonal T cells derived from p119 - 133-immunized C57BL / 6 mice. Both pD129S and pR124Q inhibited in vivo priming and subsequent activation of T cells by p119 - 133 when co-injected with p119 - 133 into mice, as shown by the decreased proliferation of T cells in response to p119-133 in vitro. pD129S significantly inhibited production of anti-p119 - 113 antibodies of IgG1, IgG2b and IgE isotype in vivo when co-injected into mice together with p119 - 133 at the time of the first immunization. However, pR124Q was totally ineffective in inhibition of the antibody responses. Anti-p119 - 133 antibodies from p119 - 133-immunized mice could bind to pR124Q but not to pD129S, suggesting that the difference in cross-reactivity is responsible for the different effect of these two peptides on specific antibody production. Our findings demonstrate that a single TCR antagonist peptide can inhibit antigen-specific polyclonal antibody production when this antagonist peptide does not cross-react with the antibody elicited in response to an antigenic peptide.     

FAMILIAL AMYLOID POLYNEUROPATHY WITH MARKED HYPERTROPHY OF THE PERIPHERAL NERVES

Autopsy findings in a 40-year-old male with heredofamilial amyloidosis and polyneuropathy are reported. He had been suffering from progressive autonomic as well as sensorimotor dysfunctions. Prominent amyloid deposit was found in the kidney, heart, thyroid, and testis, and less in the interstitium and small vessels of almost all organs. The peripheral nerves, some showing prominent hypertrophy, were most severely involved by amyloid deposit in a form of stellate mass, which ultrastructurally consisted of radially arranged amyloid filaments. In the hypertrophied nerves and ganglia, in addition to amyloid, massive accumulation of acid mucopolysaccharide (AMPS) was seen filling up the interstitial space, which was the cause of hypertrophy. Ultrastructurally, AMPS was seen as finely granular substance. An extracted amyloid from the kidney showed 8 nm filament on negative staining and was estimated of having a molecular weight of 14,000.     

Recombinant human interleukin 1 alpha is cytotoxic for and increases surface expression of HLA-A,B,C antigens of a human hepatoma cell line, PLC/PRF/5

Our study was undertaken to determine whether human recombinant interleukin 1 alpha (rIL 1 alpha) has any effect on the proliferation and expression of HLA-A,B,C antigens of human liver cell lines. The addition of rIL 1 alpha reduced the cell number of the human hepatoma cell line, PLC/PRF/5. This effect was determined to be cytotoxic, but not growth inhibitory, rIL 1 alpha did not change the number of Chang cell or SK-Hep-1 at a concentration as, high as 25,000 U/ml. rIL 1 alpha enhanced the expression of HLA-A,B,C antigens on PLC/PRF/5, but had no effect on Change cell or SK-Hep-1. Receptor binding studies showed that 125I-rIL 1 alpha bound to PLC/PRF/5 in a specific and saturable manner, but did not bind to Chang cell or SK-Hep-1. Scatchard plot analysis of the binding to PLC/PRF/5 revealed a single type of high affinity binding site with an apparent dissociation constant of approximately 5 x 10(-5) M and the presence of approximately 150 binding sites per cell. These findings suggest that IL 1 alpha may play a role in host defense against some hepatomas as cytotoxic factor and may be an enhancer of expression of HLA-A,B,C antigens on tumor cells.     

Effect of a spider toxin (JSTX) on excitatory postsynaptic current at neuromuscular synapse of spiny lobster

1. We studied the blocking properties of a spider (Nephila clavata) toxin (JSTX) purified from venom on the spiny lobster neuromuscular junction. 2. When a small amount of JSTX was applied to the neuromuscular junction, the excitatory postsynaptic potential (EPSP) was partially suppressed. The amplitude of EPSPs remained at a steady level for several hours during the washing of the preparation, showing that the action of JSTX is irreversible. 3. We recorded the excitatory postsynaptic current (EPSC) from synaptic site using a macro-patch electrode. The amplitude of EPSC increased linearly with hyperpolarization of the membrane potential in the presence and absence of JSTX. 4. The decay phase time constant of EPSC and spontaneous EPSC was decreased by hyperpolarizing the membrane potential both in the absence and in the presence of JSTX. The relationship between the decay time constant and the membrane potential was not modified by JSTX. 5. It is suggested that JSTX irreversibly blocks EPSC by acting on the site that is apart from the ionic channel of the glutamate receptor molecule.     

Dynamic characteristics of carotid sinus pressure-nerve activity transduction in rabbits

The dynamic characteristics of the baroreflex neural arc from pressure input to efferent sympathetic nerve activity (SNA) reveal derivative characteristics in the frequency range of 0.01 to 0.8 Hz (i.e., the baroreflex gain augments with increasing frequency) and high-cut characteristics in the frequency range above 0.8 Hz (i.e., the baroreflex gain decreases with increasing frequency) in rabbits. The derivative characteristics accelerate the arterial pressure regulation via the baroreflex. The high-cut characteristics preserve the baroreflex gain against pulsatile pressure by attenuating the high-frequency components less necessary for arterial pressure regulation. However, to what extent the carotid sinus baroreceptor transduction from pressure input to afferent baroreceptor nerve activity (BNA) contributes to these characteristics remains unanswered. To test the hypothesis that the carotid sinus pressure-BNA transduction partly explains the derivative characteristics but not the highcut characteristics, we examined the dynamic BNA response to pressure input in the frequency range from 0.01 to 3 Hz by using a white noise analysis in 7 anesthetized rabbits. The transfer function from pressure input to BNA showed slight derivative characteristics in the frequency range from 0.01 to 0.3 Hz with approximately a 1.7-fold increase in dynamic gain, but it showed no high-cut characteristics. In conclusion, the carotid sinus baroreceptor transduction partly explained the derivative characteristics but not the high-cut characteristics of the baroreflex neural arc. The present results suggest the importance of the central processing from BNA to efferent SNA to account for the overall dynamic characteristics of the baroreflex neural arc.     

Epidermoid Cyst Derived from an Accessory Spleen in the Pancreas

A rare case of splenic epidermoid cyst (SEC) of the pancreas discovered in a 32-year-old Japanese female is reported. The lesion, 5x6cm in size including caseous material and serous fluid in the lumen, was discovered by ultrasonography and computed tomography at the tail of the pancreas and was easily removed. Histopathologically, the cystic wall consisted of three components: the inside was lined by mature squamous epithelium with keratinization, the middle layer consisted of splenic pulp with a sinus structure, and the peripheral layer was dense fibrous connective tissue in which some involutional pancreatic ducts and islets were recognized. The literature about SEC of the pancreas is discussed in comparison with other types of epidermoid cyst including lymphoepithelial cyst and dermoid cyst in the pancreas. Acta Pathol Jpn 41: 916 921, 1991.     

Atypical Glomus Tumor in the Mediastinum: A Case Report with Immunohistochemical and Ultrastructural Studies

A case is reported of atypical glomus tumor occurring in the posterior inferior mediastinum of a 26-year-old woman complaining of severe back pain. The tumor was composed of atypical small, round tumor cells with scattered mitotic figures. In addition to sheet-like, diffuse proliferation of the tumor cells, some areas of the tumor contained small “glo-moid” cells arranged in organoid and hemangiopericytoma-like patterns. Immunohistochemically, many tumor cells were positive for muscle-type actins and a few cells were focally positive for desmin. Ultrastructural studies revealed smooth muscle features of tumor cells, that is, pinocytotic vesicles, external laminas, dense plaques, and occasional thin filaments with dense bodies. The patient remained well for 5 years and 4 months after the operation without additional radiation and chemotherapy. The tumor was diagnosed as an atypical, or low-grade malignant, glomus tumor morphologically. It seems important to recognize the presence of this type of tumor in sites other than extremities and to differentiate it from other malignant small, round cell tumors.     

Retinoblastoma protein prevents staurosporine-induced cell death in a retinoblastoma-defective human glioma cell line.

OBJECTIVE: To investigate the mechanism of staurosporine-induced glioma cell death and cell cycle arrest using adenovirus-mediated gene transfection, as well as the function of retinoblastoma (Rb) and genetic instability induced by staurosporine. METHODS: Cell cycle regulation, cell death and nuclear abnormalities induced by staurosporine were examined using an adenovirus vector expressing Rb, p16 or p21 genes in human glioma cell lines. RESULTS: The Rb-defective SF-539 cell line was resistant to staurosporine compared with cell lines expressing intact Rb. SF-539 glioma cells exposed to staurosporine became multinucleated and then died. Multinucleation was prevented in SF-539 cells transfected with the Rb gene, thus decreasing the death rate of these cells. CONCLUSIONS: These results imply that enforced Rb expression protects cells from genomic instability induced by staurosporine regardless of its upstream molecular effects.