Journal of Experimental Pathology最新文献

In the course of determining tumor profiles for wild-type and recombinant mouse polyoma viruses (MPyV's), we fortuitously discovered two types of necrotizing arterial disease in polyoma tumor-bearing C3H/BiDa mice. One type, designated BLAND, consisted of foci of necrosis unaccompanied by inflammatory reaction, in the muscular coat of aorta, pulmonary arterial trunk, and primary or occasionally secondary branches of these vessels. BLAND lesions contained MPyV capsid antigen VP1 as shown by immunocytochemistry, and appeared to be the result of viral cytolytic infection within artery walls. Lesions of the second type are designated PANoid in view of their resemblance to polyarteritis nodosa in humans. PANoid lesions had much the same distribution in the arterial tree as BLAND lesions and were also focal, but had the histologic properties of highly destructive acute inflammatory reactions. Specifically, there were dense infiltrations of polymorphonuclear leukocytes in any and often all coats of the arterial wall, acute fibrinoid necrosis, endothelial proliferations, intravascular thrombosis, and in one example, rupture of the intimal and medial coats with microaneurysm formation. In the acute phase, PANoid lesions exhibited attenuation, fragmentation, and loss of elastic laminae, and in the healing phase, intimal and medial fibrosis with varying degrees of lumenal occlusion. PANoid lesions gave negative immunocytochemical reactions for MPyV capsid antigen VP1, indicating either that the antigen was not present, or that it was masked in complexes with antibody and C3. BLAND lesions were found in 51% of 459 MPyV-infected mice, while PANoid lesions were found in 11%. There was no sex predilection for either type lesion, and practically all mice with lesions fell within ages 60-200 days. We suspect the PANoid lesions are examples of immune-complex arteritis related to persistent MPyV infection, but support for this hypothesis is presently tenuous, resting entirely on the coexistence of BLAND and PANoid lesions in MPyV-infected mice and the histological resemblance of PANoid lesions to naturally occurring and experimentally induced immune complex arteritis.

The development of monoclonal antibodies (MAb) against ras protein has made possible to study the expression of ras oncogene by immunohistochemical methods in many human solid tumors. Using the MAb RAP-5 generated against a synthetic peptide having the sequence of amino acids 10-17 of the human T24 ras gene product and the peroxidase anti-peroxidase (PAP) technique, we have observed increased level of ras p21 protein in four human hepatoma cell lines and corresponding tumors in athymic mice. The increased level of p21 is not correlated with the grade of differentiation of tumor cells, nor with the expression of HBsAg. The continuous enhanced expression of ras gene product at the cell line level and after transplantation in athymic mice suggests that the increase in p21 level may be important in the maintenance of the transformed phenotype of the hepatoma cells.

Persistent generalized lymphadenopathy during HIV infection is now a well classified syndrome featuring multiple chronic lymph node enlargement frequently associated with further symptoms (diarrhea, nocturnal sweating, loss of weight, fever): it is invariably accompanied by serious alterations of the cell-mediated immunity including lymphopenia, reduced number of helper lymphocytes in circulation, inversion of the helper/suppressor ratio, lower proliferative response in vitro and deficient delayed skin sensitivity tests. Minor opportunistic infections are also more frequent, the most widespread being chronic oral candidiasis. Whenever several of these signs are associated in a single patient, especially if the immunitary deficit is severe, an immunomodulating treatment is indicated to improve the lymphocyte functionality and finally to modify any evolutive tendency. The Authors give the preliminary results of a pilot study carried out on 12 patients with LAS/ARC treated with Thymopentin at a dosage of 50 mg by intra muscular injection on alternate days for cycles of 30 days. Compared with 14 untreated patients, the subjects receiving therapy showed a more stable immunological picture, and improvement in subjective symptoms and a better therapeutic response to minor opportunistic infections.

P(1)450 and P(3)450 are the two members of the dioxin-inducible P450 gene family, one of at least eight families in the entire P450 gene superfamily. The human P(1)450 gene has been previously sequenced. In this report the human liver P(3)450 protein is shown to migrate as a 54-kDa band on NaDodSO4-polyacrylamide gel electrophoresis. The human P(3)450 cDNA (3,064 bp) and complete P(3)450 protein (515 residues; Mr = 58,294) were determined. The human P(3)450 mRNA (3.3 kb) has an unusually long 3' nontranslated region (1,509 bp) primarily due to the inclusion of four copies of Alu repetitive sequences. Comparison of human P(3)450 cDNA with human P(1)450 cDNA and mouse (or rat) P(3)450 cDNA with mouse (or rat) P(1)450 cDNA suggests that an intra-exonic gene conversion event (in the region between 100 and 400 nucleotides from the 5' end of the translated region) most likely occurred between 20 and 80 million years ago. Analysis of 32 human X mouse and 23 human X hamster somatic cell hybrids confirm unequivocally that both P(3)450 and P(1)450 reside on human chromosome 15.

We previously described that natural autocytolytic cells (NACs) which were detected in the mesenteric lymph nodes (MLNs) of normal mice, did lyse leukocytes contained in the same lymph nodes. Discrete plaques were observed in monolayers of leukocytes prepared in wells of a microculture plate by NACs phagocytizing and lysing other leukocytes. A large NAC which was morphologically similar to macrophage was found in the middle of each plaque. The mechanisms of autocytolysis by NACs were further investigated in the present study. In contrast to various types of autocytotoxic cells reported previously, for which the incubation with fetal calf serum (FCS) was a prerequisite, the NACs showed their cytolytic activity even in serum-free medium. This excluded the possible "sensitization" by FCS proteins in vitro. The presence of the phagocytosis inhibitor cytochalasin B eliminated the autocytolysis. The peroxide scavenger thioglycollate broth had no effect on the formation of autocytolytic plaques. These results further support the previous finding that autocytolytic plaques were formed by NACs phagocytizing other leukocytes. Autologous nonadherent spleen cells and erythrocytes were also phagocytized by MLN-NACs with plastic adherent characteristics. Ia antigen was demonstrated on the surface of an approximately half population of NACs but neither Thy-1.2 antigen nor immunoglobulins. NACs may represent a subpopulation of macrophages, although the majority of adherent, phagocytic macrophages did not show the NAC activity. The endotoxin lipopolysaccharide (LPS) of Escherichia coli was apparently able to activate MLN-NACs of BALB/c mice in vivo when injected intraperitoneally at a dose of 10 micrograms/ml. A peak of the NAC activity was observed 3 days after the injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Earlier we reported that tunicamycin (TM) treatment enhances Semliki Forest virus (SFV) and encephalomyocarditis virus (EMCV) replication in Swiss mice. Interferon (IFN) mediated antiviral protection was also inhibited in mice treated with TM. The in vitro natural killer (NK) cell reactivity of mice was significantly decreased after in vivo administration of TM; however, TM treatment did not affect the response of the same cells to mitogens. TM also inhibited the boosting of NK reactivity by IFN in vivo. In this paper, we have shown that depletion of NK cells by asialo-GM1 antiserum enhances SFV/EMCV replication in mice. Both TM and anti-asialo GM1 treatment significantly inhibited the large granular lymphocyte (LGL) populations in the spleen. Similar to Swiss mice, the in vitro NK cell activity of athymic nude mice was significantly decreased after in vivo administration of TM and TM also inhibited the boosting effect on NK cells reactivity induced by IFN in vivo. TM treatment of nude mice also enhanced the SFV/EMCV in brains of infected mice and also inhibited the antiviral activity of IFN in nude mice. These results suggest that NK cells may be involved in SFV/EMCV infection and in antiviral protection afforded by IFN.