Interleukin (IL)-10 regulates immune responses, acting as a suppressive cytokine by inhibiting the synthesis of Th1 cytokines, such as IL-2 and interferon (IFN)-gamma. It also strongly down-regulates major histocompatibility complex (MHC) class II determinants on antigen presenting cells (APC). On the other hand, long-term tolerance is well correlated with the persistence of a peripheral microchimerism. In this study, we investigated the synergistic effect of human IL-10 (huIL-10) and hematopoietic microchimerism for the induction of long-term tolerance. Irradiated Balb/c mice (H-2d) were used as recipients (fetal liver stem cells [FLSC], skin and heart) and C57BL/6 (H-2b) mice were used as donors of FLSC, skin and heart. Recipients were simultaneously transplanted with the heart, the skin and with huIL-10 gene-transduced FLSC. Microchimerism was checked using fluorescent flow cytometry, huIL10 production using enzyme-linked immunosorbent assay (ELISA), and graft survival was evaluated by daily observation. Significant level of huIL10 (up to 900 pg/mL) was detected for more than 2 weeks in the serum of mice that underwent transplantation. Four weeks after the FLSC injection, microchimerism was identified in the recipient lymphoid organs (spleen, thymus, and bone marrow) by the presence of donor cells (H-2b). Finally, in the group of mice treated with huIL-10 gene-transduced FLSC, skin allografts survived for 18.9 +/- 1.8 days compared with 9.5 and 9.6 days in the groups of mice treated with nontransduced FLSC or huIL-10 alone, respectively. The same pattern for heart allograft survival was observed. HuIL-10 transduction of donor hematopoietic stem cells resulted in production of huIL-10, cell engraftment, and chimerism. Although full tolerance was not obtained, specific and highly significant (P < .001) prolongation of the survival of donor heart allografts with (more than 2-fold compared with nontreated groups) was observed. The infiltration of the transplanted heart and its late rejection demonstrate that stem cells transduced with huIL-10 gene induce "prope" tolerance in this model.

Animals↗

PubMedDate not supplied

Study of cyclooxygenase-2 in renal ischemia-reperfusion injury.

The pathogenesis of ischemia-reperfusion (I/R) injury is known to involve cytokines and particularly surface adhesion molecules, the expression of which initiates the attachment of inflammatory cells. Cyclooxygenase (COX)-1 and COX-2 catalyze the initial key enzymatic steps in the metabolism of arachidonic acid. COX-1 is constitutively expressed in most tissues, whereas COX-2 is induced in response to proinflamamatory cytokines and stress. In this study we examined the expression of COX-1 and COX-2 in the rat after 90 minutes of warm-I/R injury. Rats were sacrificed at 0, 1.5, 3, 5, 12, and 24 hours after reperfusion. COX-2 expressions were analyzed by immunohistochemical staining, which was graded on a scale of 0 to 4. All results are presented as the mean values +/- SD. Data analyses used analysis of variance. COX-2 expression was most intense on endothelial cells at 3 and 5 hours after reperfusion. From 12 to 24 hours after reperfusion COX-2 expression on endothelial cells gradually became weaker. COX-2 expression scores were significantly higher at 1.5, 3, 5, 12, and 24 hours after reperfusion than at 0 hours. However, there were no differences in COX-1 expression after reperfusion. Several hours after the maximum of COX-2 expression the maximum renal I/R injury was observed. These results suggest a relationship between COX-2 expression and renal I/R injury.

Animals↗

PubMedDate not supplied

NKT cells as nonspecific immune-regulator inducing tolerance in mouse model transplantation.

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Animals↗

PubMedDate not supplied

A hybrid bioartificial liver composed of multiplated hepatocyte monolayers.

Monolayer cultures of hepatocytes were shown to have good function when compared with suspended cells. The authors manufactured a new hybrid artificial liver containing hepatocyte monolayers and evaluated its function. Hepatocytes isolated from an adult dog liver were cultured on collagen coated borosilicated glass (10 X 20 X 0.04 cm). A long-stroke artificial liver module was constructed by stacking 200 glass plates bearing hepatocytes, which were viable and functioned well during 4 weeks in perfusion culture; glyconeogenesis = 110 ng/micrograms DNA/min, urea synthesis = 3.6 ng/micrograms DNA/min and albumin synthesis = 29 micrograms/10(6) cells/day at the 5th day of perfusion. The levels were maintained for 2 weeks. The new device was applied to anhepatic dogs (Group 3) and compared with untreated (Group 1) and plasma exchange dogs (Group 2). The survival times were 21.3 +/- 5.6 hours in Group 1 (N = 6), 27.8 +/- 4.0 hours in Group 2 (N = 3), and 55.0 +/- 10.3 hours in Group 3 (N = 4). The longest survival was 65 hours. Serum ammonia increased to over 2,000 micrograms/dl after 12 hours in Groups 1 and 2, but remained under 400 micrograms/dl in Group 3. This new type of hybrid system may be a pilot design for the complete artificial liver.

Animals↗

PubMedDate not supplied

Estradiol receptors and ovalbumin in adenocarcinoma of hens.

The origin of adenocarcinomas in 10 hens was studied using an assay for estradiol receptors (ERs) and ovalbumin. ERs were found in nine tumors, and ovalbumin was present in eight tumors. Hormonal regulation of this cancer is indicated, and it is suggested that the origin of the tumor is probably the glands of the oviduct.

Adenocarcinoma↗

PubMedDate not supplied

Cytologic studies of nipple discharges.

Cytologic findings of nipple discharges from 71 histologically confirmed breast cases (29 malignant and 42 benign) were analyzed. Papillary clusters composed of more than 30 ductal cells were found in the discharges from 18 of the malignant cases (62%) and 6 of the benign cases (14%); all 6 benign cases with papillary clusters were papillomas. Erythrocytes were detected in the discharges from 15 of the malignant cases (52%) and 5 of the benign cases (12%); 4 of the 5 benign cases with bloody discharge were papillomas. Both erythrocytes and papillary clusters were observed in the discharges from 14 of the malignant cases (48%) and 2 of the benign cases (5%).

Breast↗

PubMedDate not supplied

Aspiration cytology of breast cysts.

A cytologic evaluation was made of 57 samples of fluid aspirated from cystic breast masses during the past 12 years in our hospital. The cytologic diagnosis of the cyst aspirates from 17 cancer cases was positive in 10 cases, suspicious in 2 and negative in 5. No false-positive cytologic diagnosis was made in 40 cases of benign cystic disease. Blood-tinged aspirates were observed in 14 of the 17 cases of malignant cystic disease but in only 2 of 40 benign cases. Ductal cell clusters were detected in aspiration smears from 16 of the cases of malignant cystic disease and 15 of the cases of benign cystic disease. Apocrine cells were seen in the aspiration smears from 12 of the cases of benign cystic disease but in none of the aspirates from the 17 cancer cases.

Breast Diseases↗