The Japanese journal of experimental medicine最新文献

The resident peritoneal macrophages from untreated mice develop potent microbicidal activity against amastigotes of Leishmania major and Leishmania donovani after in vitro exposure to lymphokines (LK) from mitogen stimulated spleen cells. However, to the best of our knowledge, the response of L. donovani infected peritoneal macrophages from already infected/treated animals to LK has not been investigated. Therefore in the present study, the effect of LK on infected macrophages from BALB/c mice following specific infection and subsequent treatment with sodium stibogluconate has been investigated. As the infection progressed, a decrease in percent microbicidal activity was noticed. An attempt was also made to treat the animals on different post infection days and reinfect them in vitro. Infection could not be produced in vitro in late treatment groups when the treatment was given on 14 days and 21 days post infection. Whereas, macrophages obtained from animals treated on 7 days post infection (early treatment) could be infected in vitro. However, only 50% of the cells got infection. This infection was eliminated when the cells were exposed to LK for 72 hours.

Serum levels of several markers for liver fibrosis were measured utilizing three groups of human subjects related with schistosomiasis mansoni in northeast Brazil; (1) 20 Schistosoma mansoni egg-positives, who have never been administered with anti-schistosomal drugs, (2) 29 egg-negative inhabitants in the endemic area of schistosomiasis, and (3) 23 egg-negative Japanese immigrants in the non-endemic area. None of these sera were positive for antibody to the surface antigen of human hepatitis B (HBs) and circulating HBs antigen. There was no significant difference in the serum levels of N-terminal peptide of procollagen type-III between the egg-positive subjects and either of the egg-negative Brazilian or Japanese immigrants, whereas the mean value of serum laminin significantly increased in the egg-positive subjects. A significantly higher concentration of serum immunoreactive beta-subunit of prolyl 4-hydroxylase (IR beta PH) was also observed in the egg-positive subjects only in comparison with that of the egg-negative Brazilian. Serum laminin and IR beta PH concentrations of the egg-positive subjects did not correlate with the absorbance of enzyme-linked immunosorbent assay (ELISA) which utilized crude antigens isolated from schistosome adults or eggs. No significant difference in these two parameters was observed between two subgroups of the egg-negative Brazilian or Japanese immigrants divided according to the serological data by ELISA. These findings suggest that serum laminin and IR beta PH levels are worth further evaluation for their usefulness as the marker for liver fibrosis in schistosomiasis.

In this study the long term effects of vasectomy on serum lipid profile, in vitro platelet aggregability and the risk of developing acute myocardial infarction have been elucidated in a monkey model. Four groups were made viz. (I) atherogenic diet fed vasectomised, (II) atherogenic diet fed control, (III) stock diet fed vasectomised and (IV) stock diet fed control. The respective diets were fed for first 6 months and then half of the atherogenic and stock diet fed monkeys were bilaterally vasectomised. The remaining monkeys were sham-vasectomised. At the end of one year, norepinephrine infusion was given to all the monkeys each day for 2 hrs, for 3 consecutive days and animals sacrificed after 96 hrs. Although serum lipids were not altered following vasectomy, platelet aggregation response was significantly enhanced in atherogenic diet fed animals. ECG changes were suggestive of acute myocardial ischaemia in 4 monkeys, 2 each from gp. I and II. Histopathology of heart revealed patchy myocardial necrosis and haemorrhage only in one monkey of gp. I, while others had fuchsinorrhagia indicating ischaemic change. These findings are in contrast to those seen in vasectomised human subjects.

The incidence of the lethal growth of 10(1) L1210 murine leukemia cells in mice was higher in intraperitoneal (i.p.) (97%) than in intradermal (i.d.) (17%) inoculation, and survival time of mice was shorter in i.p. than i.d. inoculation. It was supposed that resident peritoneal cells (PC) enhanced tumor progression. I.d. inoculation of 10(1) L1210 cells mixed with 10(6) PC induced a lethal tumor growth at higher incidence than that of 10(1) L1210 cells alone or the mixture of 10(1) L1210 cells and 10(4) peripheral blood mononuclear cells (PBM) did. Furthermore, co-inoculation of a tumorigenic number of L1210 cells (10(3] with 10(6) PC resulted in marked shortening of median survival time of mice. Similar growth enhancing effect of PC was observed in Meth 1 fibrosarcoma. Meth A fibrosarcoma and colon carcinoma 26 (C26). Further study showed that PC, intact or X-rayed, helped the in vitro tumor growth under the conditions in which L1210 alone did not grow at all, whereas PBM had no enhancing effect to L1210 growth. We characterized the cells involved in tumor growth enhancement by the in vivo and in vitro tests. Plastic dish adherent cells of PC which were Mac-1 positive, large in size and resistant to X-ray, enhanced L1210 growth, whereas non-adherent cells which were Mac-1 negative and small in size, did not. These data suggest that the cells responsible for enhancing activity of tumor progression in the peritoneal cavity were macrophages (M phi).

A geometrical-dynamical model has been designed with the aim to reproduce the early phases of ventricular aneurysms formation. Possible deleterious forces within a solidary-dynamic structure start when a partial or localized loss of contractility arises. A following important aspect is related to the compressive effects of those altered cells over the normally contracting neighborhood. An abnormal packing of elements within a cyclic-dynamic structure has taken place and consequently new abnormal forces of compression between altered and normal cells will result in a longitudinal course of progression. When this circle crosses itself, a ventricular aneurysm will be completed. The process could be ascribed to an elastic phenomenon activated by a compressive stress. The chain of events included in this model has been matched with usual pathological findings of ventricular aneurysms, i.e. wavy and broken fibres neatness of aneurysmatic borders, and apical outstanding incidence of aneurysms etc. The proposed geometrical-dynamical model admits the possibility of an interruption in the 7 steps process of ventricular aneurysm formation by means of a "barrier effect". This effect has been related to the fibrous extracellular matrix with its differences in amount and quality of scar formation, which is possible to be observed in ischemic heart disease and chronic Chagas' cardiomyopathy and in some other illustrative entities. An analysis of this particular aspect of scar formation on diverse aneurismogenic entities with different reactions of collagen and particularly different figures of incidence of aneurysmatic formation, show a high correlation with possible alternatives disclosed by this geometrical-dynamical model.

The production of primary human specific antibody against an exogenous antigen by in vitro system was achieved in this study. Human lymphocytes were prepared from the lymphocytes of human spleen (SPL), tonsil (TL), and peripheral blood (PBL). These lymphocytes were stimulated by sheep red blood cells (SRBC) co-cultured with the appropriate number of allogeneic lymphocytes or fractionated T cells. Significant numbers of plaque forming cells (PFC) against SRBC were obtained. A major population of PFC responded to the stimulator RBC and a minor population of PFC responded to both SRBC and bovine red blood cells (BRBC). The culture of allogeneic combination of whole SPL or TL stimulated with SRBC produced PFC, but not that of whole PBL. Reconstitution of equal numbers of allogeneic separated B cells and T cells from PBL was required for a significant response. These specific antibody forming cells (AFC) were immortalized by Epstein Barr virus (EBV) infection and culture supernatant containing antigen-specific antibodies (anti-SRBC: Forssman antibody) were obtained after repeated cloning.

Humoral and cell mediated immune responses were studied in control, infected and immunized-infected mice at different time intervals. The levels of antiporin antibodies were found to be higher throughout the study period in immunized-infected group in which 87.5% protection was observed by mouse potency test. A significant increase in stimulation index of lymphocyte blast transformation as well as delayed type hypersensitivity response was observed in the same group as compared to infected and control group when porins were used as antigens. Using nonspecific mitogens like PHA and Con A the lymphocyte proliferation was maximum in control group whereas a significant depression was observed in infected mice. It is indicated from this study that porins are excellent antigens interacting efficiently with both arms of the host immune systems which could play a role in providing protection against the disease.

An increase of ceramide, which is the major component of sphingolipids, was found in the ischemic human brain of an acute case of internal carotid artery occlusion. Amide-linked fatty acids in the ceramide isolated from the ischemic human brain were mostly non-hydroxy fatty acids, such as stearic acid (66.9%) and palmitic acid (20.2%). Other long-chain fatty acids, C24:0 and C21:1, were rare components in the ceramide. The ceramide contained C-20 sphingosine, and the ratio of C-20 to C-18 was 0.13. These findings indicate that an ischemic insult accelerates the degradation of gangliosides and causes an accumulation of ceramide in the ischemic human brain.