Immune Abnormalities Induced by Human Endogenous Retroviral Peptides: With Reference to the Pathogenesis of Systemic Lupus Erythematosus

P15E is a specific sequence among the envelope gene (env)-encoded transmembrane proteins of exogenous and endogenous retroviruses. A synthetic peptide (CKS-17) that shows homology to this p15E region in several species of retrovirus is known to induce immune abnormalities. In this study, we examined the effect of a synthetic peptide derived from a region of human endogenous retrovirus (HERV) clone 4-1 ( 4-1) similar to sequences of CKS-17 on the induction of systemic lupus erythematosus (SLE)-related immune abnormalities. Our results indicated that this peptide could induce T-cell activation and anergy in normal peripheral blood mononuclear cells, and the peptide could also promote the production of interleukins IL-6 and IL-16. These phenomena are representative immune abnormalities observed in SLE patients. Thus, our findings support the possibility that HERV acts as a pathogen in human SLE.     

The effect of jogging on P300 event related potentials

Physical exercise has beneficial effects not only on cardiovascular system and fat metabolism, may also directly effect the cognitive process. We studied the effect of physical exercise on cognitive processes by measuring the P300 event related-potential (ERP) after jogging. Seven well-trained joggers were enrolled in this study and the P300 potentials using auditory oddball paradigm. ERPs were measured before and after 30 minutes of jogging. The amplitude of the P300 significantly increased after jogging compared to values recorded before jogging. These findings suggest that jogging has the effect of facilitating cognitive processes involved in generation of the P300.     

Anti-allergic activities of a new benzopyranopyridine derivative Y-12,141 in rats.

Passive cutaneous anaphylaxis (PCA) mediated in rats by IgE-like antibodies against egg albumin or the benzylpenicilloyl determinant was inhibited in a dose-dependent manner by intravenous treatment with Y-12,141; the ED50 was 0.09--0.2 mg/kg. The inhibitory effect of Y-12,141 ON PCA was about 5 times as potent as that of disodium cromoglycate (DSCG). Oral treatment with Y-12,141 resulted in the inhibition of PCA, showing an ED50 of 2.5 mg/kg. This action of Y-12,141 on PCA was considered to be due to the inhibition of the release of allergic mediatros from mast cells in a manner similar to DSCG. The results suggest that Y-12,141 may have an anti-allergic activity.     

Appearance of prolactin-releasing peptide-producing neurons in the area postrema of adrenalectomized rats

Prolactin-releasing peptide (PrRP) was found to be a novel hypothalamic peptide that stimulates prolactin release in vitro and in vivo. In the normal adult rat brain, PrRP neurons are known to be located in only three areas, i.e. the dorsomedial hypothalamic nucleus, ventrolateral reticular formation; and nucleus of the tractus solitarius in the medulla oblongata. These PrRP neurons project neurites into various brain areas, including regions such as the paraventricular nucleus, supraoptic nucleus, and bed nucleus of the stria terminalis. Both PrRP nerve fibers and a high level of PrRP receptor, UHR-1, mRNA are observed in the area postrema (AP),but no PrRP neurons are detected in the AP of normal rats. In this study, we clearly demonstrated that PrRP-producing cells newly appeared in the AP of adrenalectomized rats by in situ hybridization and immunocytochemistry. Our results suggest that PrRP may have some important roles in the AP of adrenalectomized rats. This is the first report demonstrating the appearance of PrRP-positive cells in the AP.     

Granulocyte-macrophage colony-stimulating factor enhances the production of eosinophil chemotactic lymphokine by egg-associated granulomas of Schistosoma japonicum-infected mice.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) produced by splenic lymphocytes obtained from Schistosoma japonicum-infected mice was partially purified by a combination of DEAE anion-exchange chromatography, concanavalin A-Sepharose affinity chromatography, and high-pressure liquid chromatography. When this partially purified GM-CSF was added to the culture of isolated intact granulomas, eosinophil chemotactic factor (ECF) lymphokine production by granulomas was significantly enhanced. The partially purified GM-CSF also enhanced ECF lymphokine production by granuloma T cells cocultured with syngeneic macrophages and specific antigen. The partially purified GM-CSF itself had neither ECF activity nor a synergistic effect with ECF lymphokine. When normal splenic macrophages were preincubated with the partially purified GM-CSF, they potentiated the ECF production by granuloma T cells under the presence of specific antigen. Augmentation of ECF lymphokine production by partially purified GM-CSF was further confirmed by using T-cell clones that were established from granuloma T cells. These results suggest that T-cell-derived GM-CSF primarily activate macrophages so that these activated macrophages can cooperate more effectively with T lymphocytes to produce ECF. Such potentiation of macrophage-T-cell interaction by GM-CSF may be important in the mechanisms of granuloma formation during an acute stage of schistosomiasis.     

Ca2+-induced excess capacitance fluctuation studied by phase-sensitive detection method in exocrine pancreatic acinar cells

A phase-sensitive detection method in combination with whole-cell voltage-clamp was applied to exocrine pancreatic acinar cells from rat. The results have shown that cell-aialysis with a solution containing 5×10^–7 M Ca²⁺ induces stp-wise changes in cell capacitance. The size distribution of increasing and decreasing capacitance steps is compatible with the idea that these capacitance steps are the results of individual granular fusion and retrieval events. This method may enable experiments studying the exo-and endo-cytotic mechanisms in morphologically polarized secretory cells.     

Immunohistochemical localization of glomerular basement membrane antigens in various renal diseases

Summary The immunofluorescent localization of glomerular basement membrane (GBM) antigens was examined in 52 specimens from normal kidneys and in various renal diseases using antisera to human GBM HGBM), IV type collagen (IV Col) and P3 antigen, a rat nephritogen. Anti-HGBM serum normally stained the GBM and the mesangium in a restrictive pattern, anti-IV Col serum stained the GBM and the mesangium in a wider pattern and anti-P3 serum stained only the GBM. In mesangial proliferative glomerulonephritis, including IgA nephropathy pathy and Henoch-Schönlein nephritis, the widened mesangial areas were stained with anti-HGBM and anti-IV Col sera. In membranous nephropathy, the punched-out lesions of thickened GBM were demonstrated with the three antisera in moderate cases and a double linear distribution with fine granulation with anti-HGBM and anti-IV Col sera were revealed in one severe case. In membranoproliferative glomerulonephritis, the expanded mesangium and thickened capillary walls were stained with anti-HGBM and anti-IV Col sera, while the outer line of glomerular capillary walls was only positive with anti-P3 serum. In crescentic glomerulonephritis, the collapsed glomerular tufts were stained normally with anti-HGBM and anti-P3 sera and weakly with anti-IV Col serum. In diabetic nephropathy, anti-HGBM serum stained the GBM in a double linear distribution without reacting with the expanded mesangium; anti-IV Col serum stained the mesangium and the GBM in a less clear double linear fashion while anti-P3 serum stained the GBM as single line. Thin membrane disease and Alport's syndrome had normal reactivity with all antisera. However, in one case of Alport's syndrome anti-HGBM and anti-P3 sera stained the GBM in a focal and segmental pattern, while normal staining with anti-IV Col serum was found. In lesions with adhesions and crescents the staining was positive for HGBM and IV Col and negative for P3; obsolescent glomeruli were stained with anti-HGBM and anti-P3 sera, and had diminished staining with anti-IV Col serum.The identification of the various structural glomerular antigens is useful in the classification of certain types of glomerular diseases. Further insight into the mechanisms underlying these conditions may be obtained in this way.     

Dendritic cells in the murine dermis in delayed-type contact hypersensitivity. An ultrastructural and immunocytochemical study

Dendritic cells within the dermis in the later stages of delayed-type contact hypersensitivity were examined ultrastructurally and immunohistochemically. The immunohistochemical observations were done using monoclonal antibody M1-8, which reacts specifically with murine Langerhans cells and interdigitating cells. Seventeen hours after challenge, infiltrating cells in the dermis included dendritic cells, possibly so-called indeterminate cells, monocytoid cells and Langerhans cells. Immunohistochemically, the indeterminate cells and some monocytoid cells were M1-8-positive. These findings suggest that indeterminate cells are intimately related to Langerhans cells, and that they belong to the mononuclear phagocyte system. M1-8 is a very useful marker for studies on the kinetics of Langerhans cells or indeterminate cells.