Application of breast tomosynthesis in screening: incremental effect on mammography acquisition and reading time.

OBJECTIVE: The aim of this study was to supplement the paucity of information available on logistical aspects of the application of three-dimensional (3D) mammography in breast screening. METHODS: We prospectively examined the effect on radiographers' and radiologists' workload of implementing 3D mammography in screening by comparing image acquisition time and screen-reading time for two-dimensional (2D) mammography with that of combined 2D+3D mammography. Radiologists' accuracy was also calculated. RESULTS: Average acquisition time (measured from start of first-view breast positioning to compression release at completion of last view) for seven radiographers, based on 20 screening examinations, was longer for 2D+3D (4 min 3 s; range 3 min 53 s-4 min 18 s) than 2D mammography (3 min 13 s; range 3 min 0 s-3 min 26 s; p<0.01). Average radiologists' reading time per screening examination (three radiologists reading case-mix of 100 screens: 10 cancers, 90 controls) was longer for 2D+3D (77 s; range 60-90 s) than for 2D mammography (33 s; range 25-46 s; p<0.01). 2D+3D screen-reading was associated with detection of more cancers and with substantially fewer recalls than 2D mammography alone. CONCLUSION: Relative to standard 2D mammography, combined 2D+3D mammography prolongs image acquisition time and screen-reading time (at initial implementation), and appears to be associated with improved screening accuracy. ADVANCES IN KNOWLEDGE: These findings provide relevant information to guide larger trials of integrated 3D mammography (2D+3D) and its potential implementation into screening practice.

Age-related alterations in inflammatory response during experimental autoimmune prostatitis.

Experimental autoimmune prostatitis (EAP) is an experimental model of autoimmune disease, developed in Wistar rats against prostatic components. The 12-and 18-month-old rats with EAP show a higher cellular autoimmune response and lower humoral autoimmune response compared to 3-month-old rats. The analysis of NO(.) and O(2)(-) production by peritoneal exudate cells (PECs) resulted in a higher NO(.) and O(2)(-) production in EAP rats at all ages, compared to control animals. PECs from 12- and 18-month-old rats produced more NO(.) and less O(2)(-) than PECs from 3-month-old rats. However, lipopolysacharide (LPS) did not stimulate PECs from aged rats for NO(.) production as much as in 3-month-old rats and thus, turning out in a lower index of LPS-stimulation of PECs from aged rats, compared to 3-month-old rats. Furthermore, the mast cells number in prostates of EAP rats, especially the number of degranulated cells, was higher than in control animals, but no significant differences were found between 3- and 12-month-old control rats. In conclusion, these results show that aging affects differentially the inflammation mediators during EAP.

Tear and serum soluble leukocyte activation markers in conjunctival allergic diseases.

PURPOSE: To measure markers of leukocyte activation in patients with an exclusively ocular inflammatory or bacterial disease. METHODS: Neutrophil myeloperoxidase, eosinophil cationic protein, eosinophil neurotoxin, and soluble interleukin-2 receptor were measured in serum and tears of 17 patients with allergic vernal keratoconjunctivitis, seven with atopic keratoconjunctivitis, 11 with seasonal allergic conjunctivitis, seven with giant papillary conjunctivitis, 13 with rosacea blepharokeratoconjunctivitis, seven with bacterial conjunctivitis, and 13 normal subjects as controls. RESULTS: In serum of patients with vernal and atopic keratoconjunctivitis, levels of eosinophil cationic protein, eosinophil neurotoxin, and interleukin-2 receptor were significantly increased compared with control subjects but were not correlated with the severity of ocular symptoms. In tears of patients with vernal and atopic keratoconjunctivitis and seasonal allergic conjunctivitis, as well as in the nonallergic diseases, rosacea blepharokeratoconjunctivitis and bacterial conjunctivitis, levels of eosinophil cationic protein, neurotoxin, and interleukin-2 receptor were significantly increased compared with control subjects. The highest values of these markers were found in vernal keratoconjunctivitis samples. Neutrophil myeloperoxidase was significantly increased in vernal and atopic keratoconjunctivitis, rosacea blepharokeratoconjunctivitis, and bacterial conjunctivitis. In vernal keratoconjunctivitis, tear markers were correlated to the clinical score of the disease, but not with cytology. CONCLUSIONS: Tear histamine was measured in 10 allergic patients after allergen challenge. Although none of the above markers can be considered specific to a single disease, their measurement may still be useful for the quantification of local cell activation in ocular inflammatory diseases.

Effect of estrogen and antiestrogen therapy in rats bearing mesenchymal tumors.

We applied both hormonal and antiestrogen treatment in female Wistar rats to analyze the estrogen dependence of the growth of sarcomas induced with 9,10-dimethyl-1,2-benzanthracene. Animals bearing tumors of 10 mm in diameter were divided at random into five groups and submitted to different treatments during 24 weeks. The treatment with ovariectomy and tamoxifen in tumor-bearing animals resulted in tumor growth suppression and prolonged survival by a protection against the lethal tumor. On the other hand, the estrogen treatment exerted an adverse effect showing a faster growth of the tumors and a great decrease in survival. In summary, the antiestrogen treatment can have an antitumor effect in mesenchymal tumors, possibly by modifying the immunological status of the host.

Prostate cancer induction in autoimmune rats and modulation of T cell apoptosis.

In this study we present an experimental model of prostate gland cancer induced by long term hormonal treatment with testosterone in combination with a chemical carcinogenic agent in male Wistar rats with autoimmune prostatitis (AIP). This system is particularly attractive in order to study the factors involved in the transition from a non-invasive to an invasive carcinoma, decisive in the risk of human cancer. At first, autoimmune prostatitis was induced by immunization in 3 months-old male Wistar rats with autologous accessory glands. Then, rats were treated with continuous intradermal implants of testosterone propionate (TP) and with single doses of the chemical carcinogen 7, 12 dimethylbenz (alpha) anthracene (DMBA) by intraperitoneal injection. Histopathological studies of the prostate gland revealed the presence of pre-malignant lesions, particularly the so-called prostatic intraepithelial neoplasm (PIN) in 50% of animals. Moreover, we observed the development of carcinomas in 50% of treated-animals, which could be histologically discriminated in adenocarcinomas, carcinoma of epidermal origin and undifferentiated carcinoma. In autoimmune rats which did not receive any other treatment, exposure to autoantigens gave rise to an atypical hyperplasia of the prostatic gland which could be attributed to the hyperactive state of the gland. Control groups constituted by autoimmune rats treated with TP or DMBA, and normal rats which were exposed to TP and/or DMBA evidenced the presence of PINs at different degrees, but did not develop carcinomas. Moreover, serum acid phosphatase significantly increased as treatment was accomplished, reaching its maximum levels in animals with carcinoma, in which DNA content, determined by image cytometry, showed to be aneuploid. Finally, we provided biochemical and cytofluorometrical evidence of the induction of apoptosis of spleen T cells in carcinoma-bearing hosts, and to a lesser extent in animals with PIN, but not in autoimmune or normal controls, which could represent an alternative molecular mechanism for explaining host immunosuppression triggered by tumors.

Relationship between immune state and tumor growth rate in rats bearing progressive and non-progressive mammary tumors.

Impaired immune responses occur frequently in cancer patients or in tumor-bearing animals, but the mechanisms of the tumor-induced immune defects remain poorly understood. The aim of the present study was to determine the relevance of the immune system in the control of tumor growth. We have developed a model of progressive and non-progressive mammary tumor, chemically induced in female Wistar rats. In this model we evaluated the development of an immune response after immunization of rats bearing progressive and non-progressive tumors with a non-related antigen, such as sheep red blood cells. We also studied the activation state of peritoneal macrophages from animals bearing tumors by evaluating the production of free radicals. Our findings indicated that the cell-mediated immunity in rats bearing progressive tumors fails to respond to heterologous antigen in vivo, as demonstrated by a negative delayed-type hypersensitivity reaction, and is accompanied by minor nitric oxide production by peritoneal exudate cells as well as a lower capacity for macrophage activation. The study of non-progressive tumor-bearing rats indicated that the cell-mediated immune response was intact and an activated state of macrophages was found in vivo. The results described in this paper should be taken into account when therapies based on cancer vaccines are chosen for the treatment of cancer.

Time-course study of cellular immune response and testosterone metabolism in an autoimmune model for chronic prostatic inflammation.

PURPOSE: Little is known of the etiology and pathogenesis of chronic inflammatory prostate diseases of noninfectious origin. In our experimental autoimmune rat model for chronic prostatic inflammation (CPI) we evaluated, in a time-course study, the specific cellular immune response to male accessory glands (MAG) and metabolic activity in the prostate gland. Results obtained in CPI rats were compared with data from rats immunized with kidney homogenate as well as from non-treated rats. MATERIALS AND METHODS: Specific cellular immune response against MAG antigen(s) was studied by delayed type hypersensitivity (DTH) and lymphocyte proliferation tests. The prostate 5alpha-reductase activity was studied in prostate homogenates by thin layer chromatography (TLC). RESULTS: DTH values were positive in MAG treated rats sacrificed at days 7 and 28 after first immunization (FI) (p < or = 0.05) in relation to kidney treated and non-treated rats. When we analyzed the proliferative responses to MAG antigen(s), an antigen specific proliferation, as shown by the mean [3H]thymidine uptake (cpm), was observed in rats sacrificed on days 14 and 28 (p < or = 0.05) after FI. The metabolic studies indicated that the 5alpha-reductase activity decreased slightly in MAG treated groups at day 14 after FI and diminished significantly at the end of CPI development. CONCLUSION: These data reveal that the prostatic endocrine cell destruction during CPI could be a consequence of immune/inflammatory cell mediated processes.

Procollagens and inflammatory cytokine concentrations in tarsal and limbal vernal keratoconjunctivitis.

To quantify the presence of inflammatory/fibrogenic cytokines and procollagens type I (PICP) and III (PIIIP) in active and non-active tarsal and limbal forms of vernal keratoconjunctivitis (VKC), tear and blood samples were collected from 27 VKC patients (20 active and 7 non-active) and 15 normal subjects. Upper tarsal conjunctival biopses were obtained from 8 controls and 8 tarsal VKC patients. From biopses of 4 tarsal VKC, fibroblasts were cultured in F12 medium with 10% FCS. TGF-beta 1, IL-1 alpha, IL-1 beta, IL-6 and TNF-alpha, PICP and PIIIP were measured in: (1) tears, (2) homogenized conjunctival tissues, (3) serum, (4) supernatants of tissue cultures at 24 hr, and fibroblast primary passage cultures. Results showed: (1) in tears, TGF-beta 1 and TNF were identified in several active VKC patients without significant differences between the tarsal and the limbal forms. IL-1 beta (27 +/- 51 pg ml-1, P = 0.03) and IL-6 (28 +/- 43 pg ml-1, P = 0.006) were significantly increased in tarsal VKC compared to controls. Both control and non-active VKC tear samples had undetectable levels of all of the above cytokines. PICP and PIIIP were significantly increased in tarsal VKC compared to both limbal VKC and controls. Non-active VKC levels were similar to controls. (2) In homogenized VKC tissues, TGF-beta 1 and IL-6 were both significantly increased compared to controls (P < 0.01) while no increases were observed in IL-1 and TNF-alpha. (3) In serum, IL-1 alpha, IL-1 beta and TNF-alpha were higher in VKC patients compared to controls. (4) In vitro fibroblasts from VKC patients showed an increased production of TGF-beta 1, IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, PICP, and PIIIP over time. Increased levels of TGF-beta 1, IL-1 and IL-6 in VKC tissues and tears indicate a local production of these cytokines in active VKC. Collagen hyperproduction occurs only in active tarsal VKC and may be related to high levels of TGF-beta 1, IL-1 and IL-6. Increased serum levels of IL-1 and TNF-alpha suggests that systemic immunological changes occur in VKC. Cell culture can be used as a model to further study the pathogenesis of VKC and its characteristic local fibroblast activation.

Oxidative stress-related parameters in prostate of rats with experimental autoimmune prostatitis.

BACKGROUND: Oxidative stress in tissues can be provoked by an augmented metabolic rate, which may sometimes be combined with a decrease in the antioxidant capacity. METHODS: In this study we examined the primary enzymatic defense mechanisms against the damage caused by reactive oxygen species (ROS): the superoxide dismutase (SOD) and catalase activities and glutathione content, as well as the levels of total thiobarbituric acid-reactant substances (TBARS), indicative of lipid peroxidation. These studies were made in prostate homogenates of rats with experimental autoimmune prostatitis (EAP) and of control rats treated with complete Freund's adjuvant (CFA) or nontreated. RESULTS: The evaluation of antioxidant defenses revealed a significant diminution of the catalase activity in autoimmune rats without changes in SOD activity and glutathione content. TBARS levels evidenced a significant increase in prostate homogenates from autoimmune rats in relation to control rat samples. CONCLUSIONS: The results suggest that in EAP, a marked diminution of catalase activity associated with an enhanced oxidative metabolism of inflammatory macrophages might lead to oxidative damage in this autoimmune disease.

Non-obese diabetic (NOD) mice are genetically susceptible to experimental autoimmune prostatitis (EAP).

Rodents develop inflammatory, non-infectious, prostatitis upon autoimmuniz-ation with male accessory gland (MAG) extracts in complete Freund's adjuvant (CFA). Although there appears to be differences among strains, with respect to susceptibility to induction, specific details are not known about the genetic bases of such differences. Because NOD mice have inherited a genetic predisposition to autoimmune lesions affecting, apart from the islets of Langerhans, a large array of secretory glands such as salivary glands, thyroid, parathyroids and adrenal cortex, we selected this strain to assess the influence of inherited genes upon experimentally-induced autoimmune prostatitis (EAP). Indeed, MAG extracts injected into young NOD males in association with CFA cause a severe inflammatory reaction in the prostate, accompanied by a humoral and T cell-mediated response. NOD mice develop a more aggressive form of EAP than Wistar rats, the strain of reference used to establish the model. In NOD mice, disease begins earlier, affects 100% of the animals, does not require boosting and leads to florid infiltrates circumscribed to lateral and dorsal prostatic lobes. Immune mice develop a T cell-mediated response to MAG assessed by in vitro proliferation and accompanied by the release of IFN-gamma, whereas IL-4 is not detectable in the same culture super-natants. To assess the influence of the NOD background genes upon EAP susceptibility, we tested C57BL/6.H2(g7) mice in parallel. NOD mice are considerably more susceptible to EAP induction than congenic C57BL/6.H2(g7) mice. Both strains demonstrate a detectable humoral and cell-mediated response against MAG, but the histopathological manifestations are considerably more dramatic in NOD than in the C57BL/6.H2(g7) strain. Our results thus support the notion that NOD mice have background genes which favour severe autoimmune manifestations, irrespective of the target tissue.

Inflammatory cells and MHC class II antigens expression in prostate during time-course experimental autoimmune prostatitis development.

The degree of lymphocytic infiltration alongside the phenotype of the infiltrating cells and MHC class II expression were studied in rats during a time-course experimental autoimmune prostatitis (EAP) development. Inflammatory foci per square millimeter were scarce at day 7 after first immunization (FI) and were composed of few mononuclear cells. The number of inflammatory foci per square millimeter increased at day 14 and remained with slight variations at days 21 and 28 after FI. The number of mononuclear cells per square millimeter increased on day 14, diminished slightly on day 21 and reached the highest level on day 28. All these infiltrates were constituted by CD4 and CD8 T cells whereas only few macrophages were present. Mast cells were also present reaching maximum levels on day 7 after FI and then decreased. MHC class II antigens were found in epithelial cells during EAP development. IA showed a similar pattern in all periods analyzed whereas IE showed a modulating behavior, reaching the highest expression on day 21 after FI. In this experimental model, the differential expression of MHC class II antigens could modulate the immune response during EAP development.

Production of reactive nitrogen intermediates (RNI) by peritoneal macrophages from rats with experimental autoimmune prostatitis (EAP).

Peritoneal macrophages from experimental autoimmune prostatitis (EAP) rats were examined for their capacity to secrete reactive nitrogen intermediates (RNI), measured by the release of nitrite (NO2-). Under basal conditions, there was a significant increase of NO2- secretion by cells from autoimmune rats in relation to resident cells. After stimulation in vitro with lipopolysaccharide (LPS), the NO2- production was higher in cells from autoimmune rats compared to treated and nontreated controls. The NO2- production was dependent upon the presence of L-arginine in the culture medium. The addition of L-NG-monomethyl arginine, an inhibitor of nitric oxide synthesis, to the medium reduced the amount of measurable NO2-. Kinetic studies in cells from EAP rats showed that in basal conditions there was an significant release of NO2- at day 7 of immunization that was maintained during the whole period studied. After LPS stimulation, there was a similar behavior and maximum values were reached at day 28 of immunization. These results, together with the lesion observed in the prostate gland, suggest that RNI may be of pathogenic importance in the development of early tissue inflammation and autoimmune disease of the prostate.

Time course of reactive oxygen intermediates release and histopathological findings during experimental autoimmune prostatitis development.

Spontaneous and stimulated reactive oxygen intermediates (ROI) release by peritoneal exudate cells (PEC) and histopathological findings in the prostate gland were assessed during experimental autoimmune prostatitis (EAP) development. Results in EAP rats were compared with data from rats immunized with kidney homogenate, BSA, and CFA, as well as nontreated rats. At 28 days of first immunization (FI), EAP rats spontaneously released significantly more ROI than occurred in the cells from control rats. A similar response was found when ROI release was analyzed after in vitro stimulus. In time course studies, an increased spontaneous O2- production was observed at day 7 after FI, and remained the same during all period studied, (14, 21, and 28 days after FI). The stimulated O2- production showed elevated levels at 7 days after FI and fell afterward to levels similar to those of nontreated rats and increased again at 28 days. Spontaneous or stimulated H2O2 release showed a progressive increase during the study periods. ROI release was correlated with infiltrate formation in the prostate gland. This differential responsiveness could indicate that, during the autoimmune process, the autoantigen(s) amplify the inflammatory response triggered by them.

Chronic restraint attenuates the immunosuppressive response induced by novel aversive stimuli.

The exposure to a novel aversive event, such as foot shock, induced a decrease in the percentage of T lymphocytes and a clear reduction in the delayed-type hypersensitivity reaction (DTH). This immunosuppressive response to an acute stressor was absent in rats that were previously exposed to a chronic immobilization stress regime (2 h daily during 7 consecutive days), but was still present in animals with prior exposure to only one or three restraint sessions. No stress effect was observed in other immunologic parameters, such as the percentage of B lymphocytes or the hemagglutinin titer, in any of the experimental treatments. The possible involvement of central adaptive mechanisms in the attenuation of the immunosuppressive response induced by an acute stress is discussed.

Exposure to physical and psychological stressors elevates plasma interleukin 6: relationship to the activation of hypothalamic-pituitary-adrenal axis.

Interleukin 6 (IL-6) is a pleiotropic cytokine produced by the cells of immune and nonimmune origin. Increased production of IL-6 is associated with disturbances of homeostasis, such as trauma, sepsis, or inflammatory diseases. Endotoxemia, tissue injury, or immune inflammatory reactions as well as physical or psychological stress are known to cause increased production of IL-6. We have confirmed this by showing that rats exposed to electric footshock, physical restraint, or a conditioned aversive stimulus have increased levels of plasma IL-6. Interestingly, the kinetics of the increase in plasma IL-6 resembled that of increase in plasma corticosterone. As no detectable endotoxin was found in the plasma samples from stressed and nonstressed rats and there is no evidence of tissue damage and inflammation in situations of restraint or conditioned aversive stimulus, a nonimmune origin of IL-6 is possible. Thus, the releasing of IL-6 into plasma may be under the regulation of neural and endocrine responses to stress. This hypothesis is supported by the decreased production of IL-6 in cultures of splenic cells and peripheral blood mononuclear cells from stressed animals. Furthermore, substantial attenuation of increased plasma IL-6 was achieved by adrenalectomy but not by pretreatment with the beta-receptor antagonist propranolol. The important role of the adrenal gland in the IL-6 response to stress suggests that increased plasma IL-6 may be part of the hormonal responses to stress. As IL-6 induces acute-phase proteins along with glucocorticoids from the adrenal, and regulates the secretion of various hormones from neuroendocrine and endocrine tissues, it is possible that stress-induced increase in plasma IL-6 contributes to the maintenance of homeostasis.

Seven-day variable-stress regime alters cortical beta-adrenoceptor binding and immunologic responses: reversal by imipramine.

Rats were submitted daily to a variable stressor for 1 week with or without concurrent imipramine (IMI) administration. One day after the last injection or stressful event, binding of cortical beta-adrenoceptors was determined in all experimental groups. Another group of chronically stressed animals with or without concurrent IMI administration were sacrificed 24 h following the last stress or injection treatment, and several immunologic parameters were evaluated. Chronically stressed rats showed an enhanced number of cortical beta-adrenergic sites without changes in their affinity. This effect was not present following concurrent administration with the antidepressant. In addition, a decreased percentage of T lymphocytes and a reduced delayed-type hypersensitivity reaction was also observed in stressed animals. Both responses were no longer evident when stressed rats were previously administered IMI. A possible link between behavioral, neurochemical, and immunologic alterations due to the stress regime is discussed.

Experimental autoimmune prostatitis (EAP): enhanced release of reactive oxygen intermediates (ROI) in peritoneal macrophages.

The metabolic state of peritoneal macrophages is defined quantitatively for spontaneous ROI release and compared with those produced after cell contact with phorbol myristate acetate (PMA) or zymosan (OZ) particles. Peritoneal exudate cells (PEC) from EAP animals spontaneously released significantly more ROI than cells from controls rats, indicating that mononuclear phagocytes from autoimmune rats were more activated than populations cells arising from rats injected with BSA, with CFA or non-injected. These findings could indicate an in vivo activation state in PEC from autoimmune rats different from that obtained with heterologous antigens or CFA immunization procedures. The release of ROI induced after in vitro stimulus was, in general, higher in cells from autoimmune than in BSA or CFA treated rats. This differential responsiveness between the MAG, BSA and CFA injected macrophage populations could indicate that during the autoimmune process the autoantigen/s could amplify the inflammatory response triggered by them. Although release of oxygen metabolites represents only one of many potential mechanisms of tissue injury, this together with the lesions observed in the prostate gland indicate that oxygen radicals could be involved in this autoimmune disease.

[Continuous sinusoid systemic Fudr infusion in advanced colorectal carcinoma. Preliminary experience]. / Infusione sistemica continua sinusoidale di Fudr nel carcinoma colorettale avanzato. Esperienza preliminare.

Sinusoidal circadian continuous infusion with a maximal flow rate in the afternoon (3-9 pm) reduces Fudr toxicity. In order to estimate if the reported lower toxicity is merely due to the quasi-intermittence of the daily dose or to the circadian rhythm of infusion. Ten patients with widespread cancer (9 colorectal and 1 renal) underwent sinusoidal continuous iv Fudr infusion with the peak level in antiphase (ie 68% of the dose from 3 to 9 am) as compared with the Römeling shape. An initial dose of 0.15 mg/kg/d for 14 days monthly has been given, escalating it every cycle by 0.025 mg/kg/d increments until toxicity. Mean (+/- SD) number of cycles has been 4.1 +/- 2.1 (range 2-8), maximal dose given has been 0.2 mg/kg/die in 5 patient and mean dose intensity of 0.570 +/- 0.04. Gastrointestinal toxicity consisted of nausea/vomiting WHO grade 1 in one patient and diarrhoea grade 1 in two, grade 2 and 3 in one and one case. Toxicity and dose intensity of both sinusoidal infusion seem to be similar and allow higher dose of Fudr than continuous constant infusion. Some other studies have to be done to include pharmacokinetics evaluation in order to estimate chronobiologic implication in continuous Fudr infusion.

Chronic variable stress facilitates tumoral growth: reversal by imipramine administration.

The present study was conducted to examine whether a chronic variable stress procedure (CVS)--an animal model of depression--facilitates tumor growth, and whether this effect can be modified by concurrent administration of the antidepressant imipramine (IMI). Unstressed rats, with or without previous administration of the immunosuppressive agent cyclosporine (CS), were inoculated with 5 x 10(6) cells of a sarcoma. Another group of rats was inoculated with tumoral cells and later exposed to the CVS procedure with or without concurrent administration of IMI (10 mg/kg, i.p.). An additional group of animals was treated with CS and later given daily injections of IMI (10 mg/kg, i.p.) without stress manipulation. A lack of tumoral development was observed in unstressed animals without previous injections of CS, whereas, prior injections of this immunosuppressive agent increased tumoral growth in unstressed animals. Exposure to the CVS procedure facilitated tumoral growth even in animals without CS injections. This effect was clearly attenuated when chronically stressed rats were concurrently given IMI. These findings support the notion that the development of a tumoral process is facilitated when a state of experimental depression is induced and that the reversal of such a state by antidepressant treatment results in the inhibition of tumor development.

Activation of cytotoxic cells by syngeneic prostate antigens in experimental autoimmune vesiculo-prostatitis.

In our experimental model of autoimmune vesiculo-prostatitis, obtained by immunization with syngeneic male accessory glands (MAG) and complete Freund's adjuvant, the presence of specific autoreactive cells with cytotoxic activity against prostate antigens was studied. The specific cytotoxicity generated in MAG immunized rats was tested using 51Cr labelled syngeneic prostate cells or labelled chicken erythrocytes coated with specific antigens (MAG homogenate or chromatographic fractions from prostate homogenate) which were used as target cells in a medium free of complement. The addition of spleen sensitized cells to prostate cells suspension produced a significant release of 51Cr in regard to normal effector cells (11.87 +/- SE 1.12 versus 1.5 +/- 0.75). Similar results were obtained when MAG-coated erythrocytes were used as target cells (10.87 +/- SE 0.62 versus 1.50 +/- 0.25). Depletion of T but no B or adherent-cells was shown to abolish the lytic effect indicating that MAG immunization provides determinants which are recognized by sensitized T-cells on cells of the prostate gland where the most severe tissue alterations were previously observed. Erythrocytes coated with chromatographic fractions obtained from prostate homogenate were used to identify the antigens triggering the lytic effect. It was demonstrated that two fractions (FI and FII) functioned as in vivo sensitizing antigens as well as in vitro activating antigens for themselves. The restimulation in vitro of sensitized cells with purified prostate fractions induces an additional lytic effect suggesting that an expansion of effector cells may take place after contacting the antigens at the prostate site.(ABSTRACT TRUNCATED AT 250 WORDS)