Effect of micronized fenofibrate (Lipanthyl-200M) on cholesterol synthesis in peripheral blood lymphocytes in hyperlipidemic patients with coronary heart disease

The rate of cholesterol synthesis in peripheral blood lymphocytes and plasma lipid and lipoprotein spectra are studied in patients with isolated hypercholesterolemia and combined hyperlipidemias (IIa and IIb hyperlipidemias according to Frederickson classification).¹⁴C-acetate incorporation into cholesterol in peripheral blood lymphocytes is considerably higher in patients with type IIb hyperlipidemia. Lipanthyl-200M reduces the rate of cholesterol synthesis in lymphocytes of both groups. A direct correlation is established between serum triglyceride level and the rate of cholesterol synthesis. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 5, pp. 569–573, May, 1998     

Elevation of CD8+ CD11b+ Leu-8− T cells is associated with the humoral immunodeficiency in myeloma patients

Recurrent bacterial infections due to humoral immunodeficiency are an important cause of death in myeloma patients. Recent data indicate that CD8⁺ T lymphocytes and a reduction of T helper type 1 cells with disease progression may be involved in the regulation of polyclonal immunoglobulin secretion. In mixed lymphocyte cultures derived from peripheral blood mononuclear cells (PBMC) of 24 myeloma patients with reduced immunoglobulin serum levels we investigated the association of CD4⁺ and CD8⁺ T cell subsets and immunoglobulin-secreting B cells (ISC) upon mitogenic stimulation with pokeweed mitogen (PWM) and concanavalin A (Con A). In supernatants of cultured PBMC of myeloma patients the spontaneous secretion of the type 1 cytokine interferon-gamma was reduced. After PWM stimulation reduced numbers of polyclonal ISC were found in 79% of patients, and monoclonal ISC were observed in 12% of patients. After Con A stimulation, again formation of polyclonal ISC was reduced, but monoclonal ISC were found in 41% of patients. Elevation of monoclonal and reduction of polyclonal ISC after stimulation with Con A were associated with an increase of CD8⁺ CD11b⁺ Leu-8⁻ T cells (P < 0.05). We conclude that the elevated numbers of CD8⁺ CD11b⁺ Leu-8⁻ T cells play a role in the stimulation of monoclonal and suppression of polyclonal immunoglobulin secretion in myeloma patients.     

Production of immunoglobulins by human sIgD+ and sIgD- human blood B lymphocytes in response to stimulation with activated T cells and agonistic antibodies; effect of IL-10, IL-2 and mode of activation of T cells.

Production of IgM, IgG and IgA was induced from human blood B lymphocytes by culturing with a CD40 MoAb and IL-2 for 9 days. Replacement of IL-2 by IL-10 markedly enhanced production of all three isotypes. High levels of immunoglobulin production also occurred when activated irradiated autologous T cells replaced the CD40 MoAb, and when IL-10 replaced IL-2 in these cultures a spectacular increase in IgG production occurred. The effectiveness of the T cell stimulus depended on the mode of purification of the T cells and the nature of the stimulant used to activate them. Differences in the kinetics and level of expression of CD40L on the various T cell preparations were observed, but did not account for variations in immunoglobulin-inducing efficiency. Immunoglobulin production from sIgD+ and sIgD- B cells was investigated. IgG and IgA were found in sIgD+ cultures, indicating that some isotype switching had occurred, but the major part of the IgG and IgA secreted was from cells already committed to these isotypes. Anti-IgD or anti-IgM MoAbs enhanced the proliferation of B cells induced by anti-CD40 antibody, but immunoglobulin production was not enhanced. Factors affecting the balance of proliferation and differentiation are discussed.     

Biochemical characterization of I-Ak proteins from mutant antigen-presenting B-cell--B-lymphoma hybridomas

Chemically induced mutants of an I-Ak,d expressing antigen-presenting B-cell--B-lymphoma hybridoma have recently been generated by immunoselection in vitro and were found to possess alterations in some of their serologically and functionally defined I-Ak region dependent functions. In order to identify at the structural level the origin of the differences in serological and functional properties of these mutants, I-Ak molecules from several of these mutant hybridomas were compared biochemically to wild-type I-Ak polypeptides by two-dimensional gel electrophoresis and high-pressure liquid chromatographic tryptic peptide analyses. Two-dimensional gel electrophoresis indicated that no major structural alterations, resulting in changes in mol. wt or charge, had occurred in the Ak alpha or Ak beta polypeptides from the mutant cells. Likewise, Ak alpha peptide maps of the mutants were indistinguishable from the normal Ak alpha peptide maps. However, two of the three mutants studied did exhibit one additional peptide in their Ak beta peptide maps. These results suggest that the major deficiencies in T-cell-activating functions of these mutants are a result of a limited alteration in the Ak beta polypeptide primary structure.     

A metacognitive model of social anxiety: Implications for treatment

This article represents an attempt to clarify questions posed by evidence of varying pathways to change in social anxiety. A new perspective is developed which addresses these questions and, importantly, lays the foundation for an innovative treatment approach. Essentially, social anxiety is construed here as the product of a disorganization in which feelings and cognitions (both conscious and preconscious) about the self, about other people, and about the relations between self and others are organized. Specifically, the socially anxious client experiences others autocentrically: that is, in terms of how the other person perceives, evaluates and affects one's own self. The result is a narrowed capacity for experiencing others. The goal of treatment in the new approach advocated here is to allow the individual to understand, appreciate and share the feelings, thoughts and experience of other people. Therapy is directed toward getting clients out of themselves and into other people.     

Lymphopenia in acute nitrofurantoin pleuropulmonary reactions

Each of 5 patients with acute nitrofurantoin pleuropulmonary reactions had profound lymphopenia and 4 had eosinophilia developing early in the clinical course after the drug was withdrawn. The 2 patients tested had only one third of the normal numbers of E rosettes (T lymphocytes) in the peripheral blood during recovery. Lymphoblastic transformation tests with purified nitrofurantoin were done in 3 patients and all of them were negative; responses to phytohemagglutinin, concanavalin A, and pokeweed were decreased but still normal. The diagnosis of various nitrofurantoin hypersensitivity reactions relies on clinical data. The mechanisms of these reactions presently remain unclear.     

Generation of the eosinophil chemotactic factor (ECF) from various cell types by melittin

The peptide melittin, the main constituent of bee venom is a potent stimulus for the generation of an eosinophil chemotactic factor (ECF) from human polymorphonuclear neutrophils, rat mast cells and rat peritoneal cells depleted in mast cells. Optimal EFC induction required a sublytic activation of the cells. With each cell type the kinetics of ECF generation were similar in that after an early rise in activity a steep fall off occurred at later times of incubation suggesting a mechanism of inactivation. The induction of ECF by melittin is increased in the presence of calcium. The polar portion of the melittin molecule (aminoacids 20–26) is responsible for the generation of the chemotactic activity. Other peptides of honey bee venom such as the mast cell degranulating peptide (MCD) or apamine do not initiate ECF release. It appears that melittin leads to ECF induction via the phospholipase A₂-arachidonic acid dependent pathway of cell activation. Our data suggests that the lipid mediator ECF can be obtained from phagocytes and mast cells thus indicating the interdependence of inflammatory reactions.     

儿童铁缺乏对血清IgG亚类及PnPs特异性IgG亚类抗体的影响

本文测定铁缺乏症患儿血清IgG亚类(47例)和PnPs特异性IgG_1、IgG_2抗体(18例)。发现47例缺铁儿童中28例伴IgG亚类缺陷,各亚类缺陷检出率依次为:IgG_4 27.66％(13/47)、IgG_1 21.28％(10/47)、IgG_2 14.89％(7/47)、IgG_2 2.13％(1/47)。与同龄正常儿童比较,缺铁组血清IgG_4和IgG_1均值以及PnPs特异性IgG_1、IgG_2抗体水平明显降低;缺铁患儿外周血CD~+_4细胞百分率及CD~+_4/CD~+_8细胞比值降低,IL-6活性、T淋巴细胞增殖反应减低。缺铁时反复呼吸道感染率(占63.83％)亦明显增高。提示缺铁不仅致T细胞功能受损,B细胞功能亦明显障碍。     

Separation of human basophils into two fractions with different density and histamine content

We designed experiments in this study to test the hypothesis suggested by recent purification data that blood basophils comprise two populations of different density, which circulate in numbers characteristic for each human subject. Basophils were separated into two density bands by single step centrifugation on a discontinuous Percoll gradient. Band 1 cells were at the interface between plasma and Percoll of density 1.070 gm/ml. Band 2 cells were at the Percoll 1.070 to 1.080 interface. When the number of band 1 basophils was expressed as a percentage of the total in bands 1 and 2, this relative amount generally remained in a narrow range for blood obtained from the same donor on 3 successive days but differed markedly in different individuals. In a series of leukapheresis experiments, we demonstrated that the percentage of band 1 basophils in postleukapheresis venous blood was strikingly similar to the preleukapheresis value. If basophils that repopulated the leukapheresis-depleted circulation came from the bone marrow, we can conclude that blood levels of basophils in bands 1 and 2 are under physiologic control and that the two types of basophils are released in amounts characteristic for each human subject. Additional evidence for two distinct blood basophil populations was provided by histamine measurements. The histamine content per basophil was consistently higher in cells from band 1 than from band 2, the mean difference between pairs of values for 30 subjects being 0.3 +/- 0.04 pg or about 27% of the band 1 basophil histamine content of 1.1 pg.     

Effect of intravenous immunoglobulin treatment on the Th1/Th2 balance in women with recurrent spontaneous abortions

PROBLEM: The way by which intravenous immunoglobulin (IvIg) acts to prevent immunlogically mediated recurrent spontaneous abortions (RSA) has not been clarified. In the present study, a possible effect of IvIg on the T helper cell (Th1/Th2) balance was investigated in abortions of either alloimmune or autoimmune abnormalities. METHOD OF STUDY: The study included 21 women treated with IvIg before conception because of a history of RSA characterized by alloimmune abnormalities (n = 15) or associated with anti-phospholipid antibodies (APA) (n = 6). Peripheral blood samples, collected before and 5 days after the first IvIg infusion, were stimulated, and Th1 and Th2 cells were detected by flow-cytometric analysis using a combination of monoclonal antibodies against T-cell surface markers and intracellular interferon (IFN)-gamma and interleukin (IL)-4. The percentage of IFN-gamma-producing (Th1) and IL-4-producing (Th2) cells and the Th1/Th2 ratio were compared between pre- and post-infusion samples. RESULTS: A decrease of Th1 percentage in 66.6% of the cases and a concurrent Th2 percentage increase (47.61%) resulted in a decrease in the Th1/Th2 ratio in most of the cases (76.1%) (p < 0.01). Similar results were found in Group A (Th1/Th2 decreased in 60% of the cases, p < 0.05), while in Group B the effect of IvIg was not clear (Th1/Th2 increased in three and decreased in another three cases). CONCLUSION: Our finding suggests that IvIg administration in women with alloimmune RSA enhances Th2 polarization. This is not always the case with APA-associated abortions.