Phenytoin promotes Th2 type immune response in mice

The effects of chronic administration of phenytoin, a common anticonvulsive drug, on immune responses were studied in mice. Anti-keyhole limpet haemocyanin (KLH) IgE antibody response after KLH-immunization was enhanced in phenytoin-treated mice. Proliferative responses of spleen cells induced with KLH, concanavalin A (ConA), lipopolysaccharide and anti-CD3 antibody were reduced in phenytoin-treated mice. Accessory function of spleen adherent cells on ConA-induced T cell proliferative response was reduced in phenytoin-treated mice. KLH-induced IL-4 production of spleen cells was enhanced, while IFN-gamma production was reduced in phenytoin-treated mice. In addition, production of IL-1 alpha, but not IL-6 and IL-12 by spleen adherent cells from phenytoin-treated mice was reduced. Natural killer cell activity was reduced in phenytoin-treated mice. These results suggest that phenytoin treatment preferentially induces a Th2 type response. We also observed that plasma ACTH and corticosterone levels were increased in phenytoin-treated mice, and speculated that phenytoin might act directly and indirectly, through HPA axis activation, on the immune system to modulate Th1/Th2 balance.     

Protective effect of NGF atelocollagen mini-pellet on the hippocampal delayed neuronal death in gerbils.

Very recently, contradictory results were presented as to the effects of exogenous nerve growth factor (NGF) on the hippocampal delayed neuronal necrosis following transient ischemia. In the present study, we administered a large amount of NGF with the atelocollagen mini-pellet system, measured the local NGF contents, and evaluated the effect of this neurotrophic factor on the postischemic hippocampal pyramidal cells in gerbils. We concluded that the exogenous NGF, when given continuously at sufficient concentrations, prevents pyramidal cell damage. The possible cause of discrepancy in previous studies is discussed.     

Therapeutic effect of topical administration of SN50, an inhibitor of nuclear factor-kappaB, in treatment of corneal alkali burns in mice

We evaluated the therapeutic efficacy of topical administration of SN50, an inhibitor of nuclear factor-kappaB, in a corneal alkali burn model in mice. An alkali burn was produced with 1 N NaOH in the cornea of C57BL/6 mice under general anesthesia. SN50 (10 microg/microl) or vehicle was topically administered daily for up to 12 days. The eyes were processed for histological or immunohistochemical examination after bromodeoxyuridine labeling or for semi-quantification of cytokine mRNA. Topical SN50 suppressed nuclear factor-kappaB activation in local cells and reduced the incidence of epithelial defects/ulceration in healing corneas. Myofibroblast generation, macrophage invasion, activity of matrix metalloproteinases, basement membrane destruction, and expression of cytokines were all decreased in treated corneas compared with controls. To elucidate the role of tumor necrosis factor (TNF)-alpha in epithelial cell proliferation, we performed organ culture of mouse eyes with TNF-alpha, SN50, or an inhibitor of c-Jun N-terminal kinase (JNK) and examined cell proliferation in healing corneal epithelium in TNF-alpha-/- mice treated with SN50. An acceleration of epithelial cell proliferation by SN50 treatment was found to depend on TNF-alpha/JNK signaling. In conclusion, topical application of SN50 is effective in treating corneal alkali burns in mice.     

Abnormal IgG galactosylation in MRL-lpr/lpr mice: pathogenic role in the development of arthritis

MRL-lpr/lpr (MRL/lpr) mice spontaneously develop arthritis by an increase in the incidence of agalactosylated oligosaccharides in serum IgG, similar to rheumatoid arthritis patients. However, whether this association has a pathogenic significance is still unknown. In this study, we analyzed the oligosaccharide structure of serum IgG in various MRL mice with or without arthritis, to clarify the relationship between the oligosaccharide abnormality and the development of arthritis. The level of agalactosylation in serum IgG was comparable in both arthritis-free MRL/lpr and MRL-+/+ (MRL/+) mice at 6 weeks of age. In contrast, the incidence of IgG lacking galactose markedly increased in MRL/lpr mice at 6 months of age (the age at which arthritis occurred), compared with that from age-matched MRL/+ mice without arthritis. However, the proportion of agalactosylated IgG increased similarly in anti-CD4 monoclonal antibody-treated MRL/lpr mice at 6 months of age, despite the absence of the development of arthritis, because of depletion of CD4+ T cells. These results suggest that the abnormality in IgG galactosylation of MRL/lpr mice developed in an age-dependent manner, but it did so independently of CD4+ T cell-dependent B-cell activation and is not a consequence of the development of arthritis.     

Linear antigenic regions of the structural proteins of human T-cell lymphotropic virus type I detected by enzyme-linked immunosorbent assays using synthetic peptides as antigens.

We synthesized 46 sequential peptides 21 to 39 amino acids long over the structural protein of human T-cell leukemia virus type I (HTLV-I; the p19 and p24 gag protein and the gp46 and p20E env proteins) and tested their reactivities against antibodies in sera from HTLV-I healthy carriers and patients diagnosed as having human T-cell leukemia-lymphoma (ATLL) and myelopathy (HAM) by using an enzyme-linked immunosorbent assay. Of the 46 synthetic peptides, 18 peptides (2 corresponding to the p19 gag protein, 2 corresponding to the p24 gag protein, 8 corresponding to the gp46 env protein, and 6 corresponding to the p20E env protein) reacted with antibodies in the sera from HTLV-I healthy carriers. In particular, the peptides comprising amino acids 100 to 119 and 119 to 130 of the gag and 175 to 199, 213 to 236, 253 to 282, and 288 to 317 of the env proteins reacted with antibodies in sera from more than 30% of HTLV-I healthy carriers. These peptides also showed high reactivities to the antibodies in the sera from patients with ATLL and HAM. The results indicate that the predominant antigenic regions of the structural protein of HTLV-I were located at the C-terminal end of the p19 gag protein and the C-terminal half of the gp46 env protein, and the corresponding peptides proved to be useful antigens in detecting antibodies in the sera from individuals infected with HTLV-I.     

A NEW METHOD FOR VITAL STAINING OF CENTRAL NERVOUS TISSUES WITH NEUTRAL RED

A new vital staining method with neutral red has been established where by cerebral ganglion cells can be stained in vivo .     

Granzyme B-positive primary gastric T-cell lymphoma: gastric T-cell lymphoma with the possibility of extrathymic T cell origin

A case of primary gastric T-cell lymphoma, which was positive for granzyme B, is reported. The patient was a 47-year-old Japanese female who complained of a dull upper abdominal pain. Radiographic and endoscopic examinations revealed an ulcerative infiltrative lesion in her stomach. Following the confirmation of a high-grade malignant lymphoma, a distal gastrectomy with regional lymph nodal dissection was performed. The histology of the gastric lesion revealed a malignant lymphoma of the diffuse pleomorphic type without lymph nodal involvement. Immunohistochemistry revealed that the tumor cells were positive for LCA, CD3, TIA-1 and granzyme B, but were negative for CD4, CD8, CD56, CD30, L-26, EMA, TCR alpha/beta and TCR gamma/delta. Because the tumor cells showed T cell nature with cytotoxic activity proved by TIA-1 and granzyme B, and without evidence of further maturation of T cell, a malignant lymphoma originating from extrathymic-derived T cells was suggested.     

AN AUTOPSY CASE OF PRIMARY ANGIOSARCOMA OF THE PERICARDIUM MIMICKING MALIGNANT MESOTHELIOMA

The pathology of a rare case of primary diffuse angiosarcoma of the pericardium is reported. Grossly, the heart was entirely encased by the pericardial tumor, and the myocardium was only superficially invaded by the tumor. The tumor tissue extended directly to the mediastinum, where the great vessels were embedded in the tumor. A few minute distant metastases were found only in the bilateral lungs and pulmonary hilar lymph nodes. Microscopically, the tumor tissue was composed of malignant cells forming vascular channels admixed with solid areas. Histo- and immunohistochemically, no mesothelial characteristics were evident. Factor VHI-related antigen and Ulex'europaeus I lectin were positive, implying that the tumor was of vascular origin. Grossly, and in part microscopically, this case resembled malignant diffuse mesothelioma, indicating that pericardial angiosarcoma may sometimes mimick malignant mesothelioma. ACTA PATHOL JPN 38: 1345-1351, 1988.     

Novel Fluorinated Hybrid Polymer by Radical Polyaddition of Bis(α‐trifluoromethyl‐β,β‐difluorovinyl) Terephthalate onto Dialkoxydialkylsilanes

To develop the radical polyaddition of bisperfluoroisopropenyl esters, the reactions of bis(α‐trifluoromethyl‐β,β‐difluorovinyl) terephthalate [CF₂?C(CF₃)OCOC₆H₄COOC(CF₃)?CF₂] (BFP) with dialkoxydialkylsilane were examined to prepare fluorinated hybrid polymers bearing dialkylsilyl groups in the main chain. Prior to polyaddition, the radical addition reaction of 2‐benzoyloxypentafluoropropene [CF₂?C(CF₃)OCOC₆H₅] (BPFP) has been investigated to afford the results that diethoxydimethylsilane (DEOMS) or dimethoxydimethylsilane with BPFP initiated by oxo radical are the best combination for the preparation of polymers. The mechanism of the addition reaction was proposed. Radical polyaddition of BFP with DEOMS initiated by benzoyl peroxide or di‐tert‐butyl peroxide has yielded polymers of up to molecular weight 1 × 10⁶ with rather broad molecular weight distribution. A mechanism for the polyaddition reaction is proposed based on the radical addition reaction between BPFP and DEOMS. The step‐growth polymerization is initiated by hydrogen abstraction of DEOMS to add a perfluoroisopropenyl group, followed by a 1,7‐shift of the radical in the intermediate. The relationship between addition reaction mechanism and polyaddition mechanism was also discussed.