Piperine, a Bioactive Component of Pepper Spice Exerts Therapeutic Effects on Androgen Dependent and Androgen Independent Prostate Cancer Cells.

Prostate cancer is the most common solid malignancy in men, with 32,000 deaths annually. Piperine, a major alkaloid constituent of black pepper, has previously been reported to have anti-cancer activity in variety of cancer cell lines. The effect of piperine against prostate cancer is not currently known.

Activation of human peripheral blood T cells does not lead to increased P-glycoprotein expression.

The expression of P-glycoprotein (Pgp) on normal human lymphocytes, and its drug exclusion capacity, implies that Pgp might be involved in cytokine secretion. We used two-color flow cytometry to detect simultaneously Pgp expression and IL-2 accumulation in resting and mitogen-activated human lymphocytes. Among resting lymphocytes from five healthy donors less than 1% were Pgp+ as determined by reactivity with the anti-Pgp monoclonal antibody (mAb) 4E3.

L-Canavanine modulates cellular growth, chemosensitivity and P-glycoprotein substrate accumulation in cultured human tumor cell lines.

L-Canavanine (L-CAV) is a naturally occurring L-arginine analog that induces the formation of non-functional proteins in a variety of organisms. Previous studies have shown that L-CAV is cytotoxic for several human tumor cell lines. In this study, we have evaluated the cytotoxicity of L-CAV for both parental and multi-drug resistant (MDR) human tumor cells.

Impairments in immune cell function in B cell chronic lymphocytic leukemia.

B cell chronic lymphocytic leukemia (B-CLL) is a common clonal B cell leukemia that is often accompanied by a multitude of immune abnormalities. Each immune defect may be linked to several of the common complications affecting B-CLL patients. Furthermore, the combined abnormalities constitute a significant immunodeficiency for each patient.

Indirect examination of exocrine pancreatic function in vivo by determination of chymotrypsin activity in animal intestine using a synthetic substrate.

Using the substrate N-acetyl-L-tyrosyl-p-aminobenzoic acid, we determined chymotrypsin activity in the small intestine of calf, pig, and poultry. Orally administered N-acetyl-L-tyrosyl-p-aminobenzoic acid is enzymatically cleaved in vivo, and the released p-aminobenzoic acid is determined by HPLC. We found that the p-aminobenzoic acid concentration in plasma and urine was significantly influenced by the feeding of soya flour.

cAMP accumulation in T-cells inhibits anti-CD3 monoclonal antibody-induced actin polymerization.

The results presented in this report offer a novel explanation for how stimulation of the beta-adrenergic receptor (beta AR) inhibits the ability of T cells to proliferate after interaction with immobilized anti-CD3 monoclonal antibody (mAb). Accordingly, T cells binding to immobilized anti-CD3 mAb but not anti-CD4 mAb undergo time-dependent F-actin assembly with concomitant formation of pseudopodia. This process is completely inhibited in the presence of isoproterenol (ISO) indicating that stimulation of the beta AR on T cells interferes with the biochemical processes responsible for the assembly of actin.

Induction of cAMP-dependent protein kinase (PKA) activity in T cells after stimulation of the prostaglandin E2 or the beta-adrenergic receptors: relationship between PKA activity and inhibition of anti-CD3 monoclonal antibody-induced T cell proliferation.

Recently, we have shown that T cells exposed to concentrations of prostaglandin E2 (PGE2) or the beta-adrenergic receptor agonist isoproterenol (ISO) that elicit equimolar levels of cAMP accumulation do not inhibit anti-CD3 monoclonal antibody-induced T cell proliferation to the same extent. This report extends these studies by investigating the induction of cAMP-dependent protein kinase (PKA) in T cells stimulated with PGE2 or ISO. The kinetics of PKA activity induced by PGE2 or ISO in T cells are similar but PGE2 induces more PKA activity.

Costimulatory signals modulate the antiproliferative effects of agents that elevate cAMP in T cells.

Stimulation of highly purified human T cells with immobilized anti-CD3 monoclonal antibody (mAb) in the presence of cAMP-inducing agents results in inhibition of proliferation by these T cells. In the present study, experiments were performed to determine how costimulatory signals modulate the inhibitory effects of cAMP-elevating agents on proliferation and interleukin 2 (IL-2) secretion by anti-CD3 mAb-stimulated T cells. Accordingly, the level of anti-CD3 mAb-induced T cell proliferation was determined in the presence or absence of accessory cells, anti-CD28 mAb, or phorbol myristic acid (PMA) in the presence of the adenylyl cyclase (AC)-linked receptor agonists prostaglandin E2 (PGE2), or isoproterenol (ISO) as well as the AC activator forskolin (FSK) or the cAMP analog dibutyryl-cAMP (dB-cAMP).

Modulation of T cell proliferation by stimulation of the beta-adrenergic receptor: lack of correlation between inhibition of T cell proliferation and cAMP accumulation.

The presence of beta-adrenergic receptors on T cells suggests the potential for modulating T cell function upon binding of an appropriate agonist. Utilizing highly purified human T cells we assessed the proliferative capacity of T cells upon stimulation with immobilized anti-CD3 monoclonal antibody (mAb) in the presence of the beta-adrenergic agonist isoproterenol (ISO). The proliferative response of T cells and their CD4+, CD8+, or CD45RO+ subsets to anti-CD3 mAb was inhibited in a dose-dependent manner by ISO.

Dominant exudative vitreoretinopathy: a sporadic case with a normal platelet aggregation study.

Case report of a woman with the characteristics of dominant exudative vitreoretinopathy. These anomalies are however unilateral and the family study is not very contributive. A platelet aggregation study carried out on the patient and 3 family members is normal.

Enhanced expansion of the thymic CD8+ cell subset as a potential mechanism for the generation of enhanced antitumor cytotoxicity by thymocytes from low-dose melphalan-treated MOPC-315 tumor bearers.

We have previously shown that thymocytes from low-dose melphalan (L-phenylalanine mustard)-treated MOPC-315-tumor-bearing mice (melphalan TuB) are able to generate an enhanced level of anti-MOPC-315 cytotoxicity, as compared to thymocytes from untreated MOPC-315-tumor-bearing mice or thymocytes from untreated or low-dose melphalan-treated normal mice, upon in vitro stimulation with MOPC-315 tumor cells in the presence of a low concentration of recombinant interleukin-2 (rIL-2). Here we show that the generation of enhanced anti-MOPC-315 cytotoxicity by melphalan TuB thymocytes depends on the ability of the thymocytes to proliferate. In addition, the ability of melphalan TuB thymocytes to generate an enhanced level of anti-MOPC-315 cytotoxicity correlated with their ability to proliferate more readily than thymocytes from untreated tumor-bearing mice and thymocytes from untreated or melphalan-treated normal mice in response to stimulation with MOPC-315 tumor cells plus a low concentration of rIL-2.

Presence of an enlarged pool of MOPC-315-specific cytotoxic T lymphocyte precursors in the thymuses of mice that eradicated a large MOPC-315 tumor as a consequence of low-dose melphalan therapy.

We have previously shown that, as a consequence of low-dose melphalan (L-phenylalanine mustard) treatment, thymocytes from mice bearing a large, day-10 MOPC-315 tumor, but not thymocytes from normal mice, acquire the ability to generate an enhanced level of antitumor cytotoxicity upon in vitro stimulation with MOPC-315 tumor cells plus low concentrations (9.0-90 IU/ml) of exogenous interleukin-2 (IL-2). Here we show that the time interval between tumor inoculation and low-dose melphalan therapy as well as the magnitude of tumor burden at the time of the chemotherapy are important for the ability of the drug to render thymocytes more responsive to in vitro stimulation with MOPC-315 tumor cells plus low concentrations of recombinant IL-2 (rIL-2).

[Association of the CHARGE syndrome and imperforation of the lacrymal ducts].

Clinical description of a 12-year-old girl with a number of congenital abnormalities including retarded growth and an asymmetric facies. All the clinical features observed are compatible with the CHARGE association. Ocular anomalies are important bilateral colobomata associated with nystagmus and strabismus.

Interleukin 2 requirement for the in vitro generation of antitumor cytotoxicity by thymocytes from melphalan-cured MOPC-315 tumor bearers.

We have previously shown that enhanced antitumor cytotoxicity is generated when thymocytes from melphalan (L-phenylalanine mustard; L-PAM)-treated MOPC-315 tumor bearers, but not thymocytes from normal mice, are added to the immunization culture of syngeneic normal spleen cells and MOPC-315 tumor cells (Bartik et al., Cancer Res., 47: 4848-4855, 1987).

Melphalan-induced enhancement of antitumor immune reactivity in thymocytes of adult BALB/c mice bearing a large MOPC-315 tumor.

At no stage of tumor growth are thymocytes from MOPC-315 tumor bearers capable of bringing about the generation of enhanced antitumor cytotoxicity when added to immunization cultures of syngeneic normal spleen cells and "autochthonous" tumor cells. However, by Day 7 after low-dose melphalan [L-PAM (L-phenylalanine mustard)] therapy of mice bearing a large (greater than or equal to 20 mm) s.c.

Porcine aortic versus bovine pericardial valves: a comparative study of unimplanted and from patient explanted bioprostheses.

This extensive morphological study (macroscopy, x-ray, histology, histochemistry and electron microscopy) compares two types of bioprosthetic valves, porcine aortic (PAV) and bovine pericardial (BPV) of various models, both unimplanted (five) and explanted (229). There were 197 PAV and 32 BPV explanted from the mitral, aortic and tricuspid positions, with a mean duration of implantation of 70.3 and 13.

Melphalan-induced appearance of potent antitumor immune reactivity in tumor bearer lymphocytes co-expressing the Lyt 2 and the L3T4 antigens.

We have previously shown that Sephadex G-10-adherent spleen cells from mice bearing a large MOPC-315 tumor can suppress the in vitro generation of a primary anti-MOPC-315 cytotoxic response. Here we show that following low dose melphalan (L-phenylalanine mustard; L-PAM) therapy of such tumor bearing mice their Sephadex G-10-adherent spleen cells no longer suppressed but actually brought about the generation of enhanced antitumor cytotoxicity when added to the immunization culture of normal spleen cells and MOPC-315 tumor cells. This immunopotentiating activity of the Sephadex G-10-adherent spleen cells from L-PAM treated MOPC-315 tumor bearers was attributed to T-cells which co-express the Lyt 2 and the L3T4 antigens based on results of experiments employing negative selection.

Use of Ac-L-Tyr-PAB for estimating the activity of chymotrypsin in rats.

Pancreatic secretion in rats was assessed by measuring the amounts of p-aminobenzoic acid (PABH) excreted in urine after oral administration of Ac-L-Tyr-PAB, and by determination of enzyme activity in pancreas and faeces. 3 groups of 7 rats were kept on diets with casein as the main source of nitrogen without (control K0) or with two levels of trypsin inhibitor (K1 and K2). Two other groups were fed diets with 40 and 80% of casein substituted by raw soya bean protein and having trypsin inhibitor contents equivalent to those in diets K1 and K2.