Enhancing effect of 17 beta-estradiol on human NK cell activity.

The in vitro effect of 17 beta-estradiol on NK activity was studied. The proliferation and NK activity of YT-N17 (a human NK-like cell line) were enhanced by 17 beta-estradiol (E2), and the enhancement was blocked by tamoxifen (Tx), an antagonist of E2. On the contrary, other steroid hormones such as Tx, progesterone, and testosterone had no effect. YT-N17 contained 11.8 fmol/mg protein of estrogen receptor (mean of two independent assays), a value which was 5-10-fold higher than that of other hematopoietic cell lines. An enhancement of NK activity by E2 was also seen in large granular lymphocytes obtained from normal subjects, and it was again suppressed by Tx. These data suggest that E2 is one of the activating factors for NK/LGL cells.

Detection of adult T-cell leukemia-derived factor/human thioredoxin in human serum.

Adult T-cell leukemia (ATL)-derived factor (ADF), originally defined as an inducer of interleukin-2 receptor/alpha-chain (IL-2R/p55) of human T-lymphotropic virus type I (HTLV-I) positive T cells, is a human homologue of redox-active coenzyme thioredoxin (Trx) of Escherichia coli. In this study, an enzymatic assay system based on the dithiol-dependent insulin-reducing activity of ADF/Trx was established (insulin-reducing assay) to determine the amount of ADF/Trx in human serum using NADPH and Trx reductase purified from human placenta. Insulin-reducing activity was detected in all of the serum samples from healthy volunteers (n = 30) screened by this assay, with a mean +/- SD of 10.9 +/- 2.4 U/l. This mean value corresponds with the concentration of 223 ng recombinant ADF/Trx (rADF/Trx)/ml. Human serum is known to contain several redox-active proteins with ADF/Trx motifs. To differentiate the contribution of these proteins and ADF/Trx to the insulin-reducing activity, the anti-rADF/Trx monoclonal antibody (mAb)-conjugated affinity column-depleted sera obtained from an identical source was used for analysis. The affinity column-depleted sera demonstrated a loss of over 99% of the original activity, while control column depleted sera lost less than 4%. Furthermore, the amount of affinity-purified ADF/Trx molecules eluted from the same column almost corresponded with the amount estimated by the insulin-reducing activity.(ABSTRACT TRUNCATED AT 250 WORDS)

HLA-DQ-specific autoreactive T cell clone with helper and cytotoxic functions.

To clarify the existence and the possible function of DQ-specific autoreactive T cells, we established a novel autoreactive T cell clone (28B8) responding to self-DQ molecules from an unimmunized normal subject. Blocking studies with monoclonal antibodies (mAbs) to HLA class II antigens and alloreactive response of the clone revealed that the clone recognized DQ molecules defined by a DR1-DQw5 haplotype. Clone 28B8 markedly induced autologous B cells to produce immunoglobulins, and was also cytotoxic against autologous lymphocytes, as well as against allogeneic lymphocytes with a DR1-DQw5 haplotype. These findings indicate that DQ antigens are involved in autoreactivity and stimulate autologous T cells that may have potent immunoregulatory functions.

Induction and function of Fc epsilon RII on YT cells; possible role of ADF/thioredoxin in Fc epsilon RII expression.

The regulation of low-affinity Fc receptor for IgE (Fc epsilon RII) and the characteristics of both membrane and soluble forms of Fc epsilon RII were studied using YT cell line. We found that YT cells, a human NK like cell line, expressed Fc epsilon RII after IL-1 stimulation. Cross-linking of Fc epsilon RII on IL-1-stimulated YT cells as well as the transfectant of Fc epsilon RII-cDNA (YTSER) resulted in the up-regulation of IL-2R alpha (p55/Tac). A 59 kDa protein phosphorylated at tyrosine residues was co-immunoprecipitated with Fc epsilon RII from YTSER lysate using H107 anti-Fc epsilon RII mAb. YTSER not only expressed Fc epsilon RII on their surface but also secreted soluble form of Fc epsilon RII (sFc epsilon RII/sCD23; IgE binding factor). Affinity purification revealed that sFc epsilon RII released from YTSER is heterogeneous and consisted of several proteins differing in molecular weight. Both EBV+ B cells and HTLV-1+ T cells are high producers of ATL derived factor (ADF)/thioredoxin (TRX) and express Fc epsilon RII and IL-2R alpha respectively. To clarify the mechanism of Fc epsilon RII and IL-2R alpha induction by ADF/TRX, we examined the effect of ADF/TRX on the bindability of nuclear factor kappa B (NF-kappa B), which is known to regulate IL-2R alpha gene expression. In the gel shift assay, ADF/TRX was shown to enhance the bindability of NF-kappa B to its responsive element.

An information network for community medical care.

An information network for community medical care was established by the Himeji Medical Association in 1987. The network interconnects through public telephone a central computer located at the office of the Medical Association with personal computers installed in the offices of members of the Association. An overview of the network, which is in full operation, is given, and current problems and future directions are discussed.

Cardiac sarcoidosis.

The present report describes a patient with cardiac sarcoidosis who developed complete right bundle branch block, complete atrioventricular block and subsequent congestive heart failure. The patient demonstrated no clinical evidence of systemic sarcoidosis. Upon postmortem examination, the myocardium showed extensive noncaseating granuloma with numerous multinucleated giant cells. An initial routine microscopic examination of the lung revealed no evidence of granulomatous lesions. However, an extensive microscopic examination of the lung using serial sections demonstrated inconspicuous granulomatous lesions with giant cells. Thereby, a diagnosis of sarcoidosis was made. All other organs were free of granulomatous inflammation in spite of an extensive microscopic examination through serial sections. The present case suggests that a careful and extensive microscopic examination of the other organs may be necessary to establish a diagnosis of cardiac sarcoidosis.

Portal hypertension associated with anticardiolipin antibodies in a case of systemic lupus erythematosus.

A 26-year-old man with systemic lupus erythematosus (SLE) and a history of acute myocardial infarction developed portal hypertension accompanied by abnormal liver function and esophageal varices. As his clinical course suggested the possibility of antiphospholipid syndrome, a titer of anticardiolipin antibody (aCL) was serially measured using an enzyme immunoassay with beta 2-glycoprotein I as a cofactor. The titer of aCL increased with the development of portal hypertension, and promptly decreased with the improvement of liver function just after corticosteroid therapy. The long-term course in this case suggests that aCL may cause portal hypertension associated with SLE.