Induction of B cell costimulatory function by recombinant murine CD40 ligand

T cell-dependent regulation of B cell growth and differentiation involves an interaction between CD40, a B cell surface molecule, and the CD40 ligand (CD40L) which is expressed on activated CD4⁺ T cells. In the current study, we show that recombinant membrane-bound murine CD40L induces B cells to express costimulatory function for the proliferation of CD4⁺ Tcells. CD40L- or lipopolysaccharide (LPS)-activated, but not control-cultured B cells were strong costimulators of anti-CD3 or alloantigen-dependent T cell responses. The molecular interactions responsible for the increased costimulatory functions were examined by analyzing the activated B cells for changes in the expression of two costimulatory molecules, B7 and heat-stable antigen (HSA), as well as by the use of antagonists of B7 and HSA (CTLA4.Fc and 20C9, respectively). The expression of both B7 and HSA was enhanced on B cells activated with LPS. As observed in previous studies, the costimulatory activity of the LPS-activated B cells was dependent on both B7 and HSA and was completely inhibited in the presence of a combination of CTLA4.Fc and 20C9. In contrast, activation of B cells with CD40L induced the expression of B7 but did not enhance the expression of HSA. In addition the costimulatory activity of the CD40L-activated B cells was partially, but not completely, inhibited by the combination of CTLA4.Fc and 20C9. These results demonstrate that CD40L regulates costimulatory function of B cells in part by inducing the expression of B7 and suggest that CD40L-activated B cells express an additional costimulatory activity that is not associated with LPS-activated B cells.     

Ultrastructural and biochemical studies on the intestinal absorption of a medium-chain triglyceride (MCT), tricaprylin

The intestinal absorption of a medium-chain triglyceride (MCT) was studied by electron microscopy and biochemical analysis. In jejunal absorptive cells of rats fed tricaprylin, the smooth endoplasmic reticulum in the apical cytoplasm appeared to increase in number and contained one or two particles about 40–80 nm in diameter that were less electron dense and similar in size and profile to very low density lipoprotein. Similar particles were also observed packed in the dilated Golgi sacs and in the extended intercellular spaces. These particles were remarkably increased in number as compared with those in fasted rats. Biochemical analysis of lymph from the main intestinal lymph duct showed that caprylate was apparently demonstrated only in the lymph of rats given tricaprylin at the maximum rate 3h after oral administration. The study strongly suggests that medium-chain triglyceride is at least in part transported via lacteal, possibly in the form of very low density lipoprotein.     

Human interdigitating dendritic cells directly stimulate CD40-activated naive B cells

Human interdigitating dendritic cells (IDC) were isolated from tonsils based on their CD40⁺ lineage-negative expression in situ. Isolated IDC displayed a phenotypic profile similar to that of IDC in tonsils and spleen in situ, characterized by high-level expression of major histocompatibility complex class II, the co-stimulatory molecules B7.1 (CD80) and B7.2 (CD86), expression of the late DC maturation marker CD83, and no expression of CD1a, CD13, or CD33. IDC also showed weak nonspecific esterase staining and had the ability to induce an allogeneic mixed lymphocyte reaction. In this study, we further show that in the presence of surrogate activated T cells in the form of CD40 ligation and IL-2, IDC enhance the proliferation of naive B cells and induce their differentiation into plasma cells producing IgM. Evidence for the anatomical co-localization of naive B cells and IDC in the T cell area together with the data obtained in vitro implies a role for IDC in the initiation of the extrafollicular reaction.     

Activation induces apoptosis in Herpesvirus saimiri-transformed T cells independent of CD95 (Fas,APO-1)

Signaling via the T cell receptor (TCR)/CD3 complex of pre-activated T cells induces apoptosis. Such an activation-induced cell death (AICD) is thought to play an important role in the regulation of cellular immune responses. In this study we analyzed pathways of AICD by using human T cells transformed by Herpesvirus saimiri. These growth-transformed T cells show the phenotype of activated mature T cells and continue to express a functionally intact TCR. We show that human H. saimiri-transformed T cell clones readily undergo cell death upon signaling via the TCR/CD3 complex or via phorbol 12-myristate 13-acetate (PMA) + ionomycin. The AICD in H. saimiri-transformed T cells was detectable a few hours after activation and it was not affected by the presence of interleukin (IL)-2 or by anti-CD4 cross-linking. However, AICD required tyrosine phosphorylation, since it could be blocked by herbimycin A. Cyclosporin A (CsA) did not block the development of AICD, but other consequences of activation in H. saimiri-transformed T cells like the production of interferon-γ. Surprisingly, the development of AICD was not reduced by neutralizing antibodies to tumor necrosis factor (TNF)-α or blocking antibodies directed to CD95 (Fas, APO-1), although H. saimiri-transformed T cells were sensitive to CD95 ligation. To confirm that this form of AICD is really independent of CD95, we have established an H. saimiri-transformed T cell line from a patient with a homozygous deletion in the CD95 gene. This CD95-deficient T cell line was as sensitive to AICD as other CD95-expressing H. saimiri-transformed T cells. In conclusion, we describe here a type of AICD in H. saimiri-transformed T cells that is independent of CD95 and TNF-α, not sensitive to CsA, but requires tyrosine phosphorylation. This system should be useful for the investigation of CD95-independent forms of AICD.     

磷脂酰胆碱抗氧化效应及对遗传损伤的保护作用

磷脂酰胆碱５００ｍｇ／ｋｇ灌胃２０日可使Ｏ_３环境中的小鼠超氧化物歧化酶（ＳＯＤ）活性显著增强，血浆丙二醛（ＭＤＡ）含量及外周血正染红细胞（ＮＣＥ）微核率明显下降。结果提示：磷脂酰胆碱具有抗氧化作用及拮抗自由基造成遗传的损伤。进一步证实了自由基在微核形成中具有重要意义。     

Potent depressant effects of adenosine analogs on hippocampal slow-wave activity in the unanesthetized rat

Summary Adenosine and its analogs have previously been shown to exert a depressant effect on several measures of hippocampal excitability in the hippocampal slice and intact anesthetized preparation. In the present report, we examined the effects of intraventricular injections of adenosine analogs on hippocampal slow-wave activity in the freely moving rat. Each of three adenosine analogs— 5-N-ethylcarboxamidoadenosine (NECA) and N⁶-(phenylisopropyl) adenosine (L- and D-PIA) — were found to strongly suppress hippocampal electroencephalographic (EEG) activity. For instance, low doses of NECA (0.5 g) produced an 80–90% decrease in the amplitude of the hippocampal EEG. NECA was approximately 20-fold more potent than L-PIA, and L-PIA was twice the potency of D-PIA. In separate experiments in the anesthetized rat, NECA and L-PIA were found to block completely the activation of the hippocampal theta rhythm elicited with brainstem stimulation. The effects of adenosine analogs on both the hippocampal EEG and theta rhythm were very effectively reversed with methylxanthine, 8-para-sulphophenyl-theophylline (8-PSPT). The present findings demonstrate that adenosine analogs exert a powerful depressant effect on the hippocampal EEG in the natural unanesthetized state, and suggest that changes in the levels of endogenous adenosine may play a significant role in modulating the normal activity and function of the hippocampus.This work was supported in part by National Science Foundation grant BNS-8403544 to RPV     

MMPI, personality dysfunction and the dexamethasone suppression test in major depression

In this study we examined the relationship of psychopathology and personality dysfunction to neuroendocrine functioning. MMPI profiles were examined for 30 psychiatric inpatients with major depression who were suppressors (60%) and nonsuppressors (40%) on the dexamethasone suppression test. There were no differences between suppressors and nonsuppressors on any of the MMPI scales or on DSM-III Axis-II diagnosis. When subdivided according to T-score elevations above 70 on MMPI scales 4 and 6, or 4 and 9, 30% of the sample, however, met criteria for personality dysfunction. Furthermore, a significantly higher proportion of suppressors (50%) evidenced personality dysfunction than did the nonsuppressors (8%). This suggests that certain MMPI scales are able to identify a subgroup of depressed patients with personality disturbances who also have a hypothalamic-pituitary-adrenal dysfunction.     

Immunochemical characterization of mouse brain-associated theta (Thy-1) antigen.

The Thy-1 antigens or rat brain and thymus have been isolated and chemically characterized, but those of mice have not been identified. Moreover, it is uncertain whether the antigens are glycolipids or glycoproteins. This study with highly purified preparations of gangliosides GM₁, ¹GD_1a, GD_1b and GT_1b from bovine brain and several ganglioside fractions from mouse brain showed that Thy-1 activity does not reside in gangliosides, but rather in the chloroform-methanol-insoluble residue of brain remaining after extraction of gangliosides. The antigen could be solubilized from this residue with a non-ionic detergent. The antigenic activity of the solubilized preparation was heat-labile but resistant to periodate. The chemical properties of the Thy-1 antigen of mouse brain are discussed.     

Providing Interdisciplinary Geriatric Team Care: What Does It Really Take?

We concur with Speer and Schneider's arguments (2003 ; this issue) that more psychologists should offer mental health services to older adults and that the primary care system is a good focus of such efforts. Three issues deserve more prominence in their review. First, their argument that older adults are averse to mental health services seems incorrect, given research indicating that older adults prefer psychotherapy to medication for treatment of depression. Second, psychologists working in primary care need to be aware of new Current Procedural Terminology (CPT) codes that allow documentation of psychological work in medical settings. Third, Speer and Schneider allude to interdisciplinary team functioning, but provide little information about models of team care or issues in developing a well-functioning interdisciplinary team; this commentary expands on those topics.     

基于自适应小波神经网络的心电图检测法

自适应小波神经网络检测法就是利用小波函数取代通常神经网络中隐层的作用函数来实现的，通过网络的学习自适应地调整尺度参数和时移因子，提高了特征提取能力，因此，该网络可提高心电信号的检测率和可靠性。