CD3-associated alpha/beta and gamma/delta heterodimeric receptors are expressed by distinct populations of CD4- CD8- thymocytes.

Immature double negative (DN) CD4-8- thymocytes expressing the CD3 molecular complex can be subdivided into two distinct subsets based on expression of the B2A2 antigen. Thus, B2A2+ CD3+ DN thymocytes express CD3-associated 35 kDa and 45 kDa polypeptide chains characteristic of a gamma/delta T cell receptor, whereas B2A2- DN thymocytes express predominantly 38 to 43 kDa CD3-associated structures typical of alpha/beta TCR. At the mRNA level, B2A2+ DN thymocytes express full length gamma and delta transcripts but no alpha message and only short (1 kb) B transcripts.

T-cell receptor V beta use predicts reactivity and tolerance to Mlsa-encoded antigens.

T lymphocytes reactive with the product of the Mlsa-allele of the minor lymphocyte stimulating (Mls) locus use a predominant T-cell receptor beta-chain variable gene segment (V beta 6). Such V beta 6-bearing T cells are selectively eliminated in the thymus of Mlsa-bearing mice, consistent with a model in which tolerance to self antigens is achieved by clonal deletion.

Lovastatin (mevinolin) in the treatment of heterozygous familial hypercholesterolemia. A multicenter study.

Study Objective: To evaluate the efficacy and tolerability of lovastatin under controlled conditions in heterozygous familial hypercholesterolemia.

Design: Randomized, double-blind, placebo-controlled, multicenter trial.

Setting: Five lipid clinics with a central laboratory and coordinating center.

Developmentally regulated expression of T cell receptor beta chain variable domains in immature thymocytes.

A minor subset of immature (CD4-,8-) thymocytes that lack expression of the B2A2 antigen was found to express low levels of surface TCR protein as detected by mAbs F23.1 and KJ16 (reacting with protein products of the V beta 8 gene family). Interestingly, F23.

Accumulation of native and methylated low density lipoproteins by healing rabbit arterial wall.

To determine whether healing arterial wall accumulation of low density lipoproteins (LDL) is mediated by the high affinity LDL receptor, normocholesterolemic rabbits were injected with 125I-LDL, 99mTc-LDL, or the reductively methylated analogs of these compounds (125I-MeLDL, 99mTc-MeLDL), 1 month after balloon catheter deendothelialization of the abdominal aorta. If the mechanism of accumulation requires interaction with the LDL receptor, reductively methylated lipoproteins which do not bind to the receptor should not accumulate in healing arterial wall. Twenty-four hours after injection of labelled lipoproteins, each animal was injected with Evans blue dye, in order to distinguish reendothelialized from deendothelialized aorta.

T cell antigen receptor expression in athymic (nu/nu) mice. Evidence for an oligoclonal beta chain repertoire.

The expression of T cell antigen receptors (TCR) in congenitally athymic (nude) mice has been investigated. Lymph node T cells from 4-5-mo-old athymic mice expressed full-length transcripts for the TCR alpha and beta chains at a level two-to three-fold lower than normal littermate (nu/+) controls. Low levels of expression of TCR protein at the surface of a proportion of nude T cells was demonstrated by staining with monoclonal antibodies KJ16-133 and F23.

Immunologic studies of subjects with asthma exposed to formaldehyde and urea-formaldehyde foam insulation (UFFI) off products.

There has been concern in recent years as to the health hazards of exposure to potentially carcinogenic or immunotoxic substances in the environment. This study was done to determine the effects of exposure to urea-formaldehyde foam insulation (UFFI) off products on various hematologic and immunologic parameters in subjects with asthma: complete blood count and differential, erythrocyte sedimentation rate, lymphocyte subpopulations (E-rosetting, T3, T4, T8, B73.1, and Fc receptor positive lymphocytes and large granular lymphocytes), lymphocyte response to phytohemagglutinin and formalin-treated red blood cells (Form-RBC), serum antibody against the Thomsen-Friedenreich RBC antigen and against Form-RBC, and natural killer (NK), interferon (IFN)-boosted NK (IFN-NK), and antibody-dependent cell-mediated cytotoxicity.

Abnormal expression of T cell receptor genes in Lyt-2- L3T4- lymphocytes of lpr mice: comparison with normal immature thymocytes.

The autoimmunity and lymphoproliferation characteristic of lpr mice are age and thymus dependent. The accumulating Lyt-2- L3T4- T cells express only minimal cell-surface antigen receptor. After stimulation with phorbol myristic acetate (PMA) and interleukin 2, essentially normal levels of surface antigen receptor were expressed by the lpr Lyt-2- L3T4- subpopulation but remained undetectable in the corresponding normal immature thymocyte population.

A case-control study of lung cancer relative to domestic radon exposure.

Public concern was expressed regarding the possibility of adverse health effects with the disposal of radioactive waste in Port Hope, Ontario. A case-control study was carried out to estimate the relative importance of domestic radon gas exposure in the causation of lung cancer in the town over a ten-year period. Twenty-seven cases met the entry criteria.

Adrenal imaging with technetium-99m-labelled low density lipoproteins.

Evaluation of adrenal cortical function by external imaging is currently accomplished by injection of radiolabelled analogs of cholesterol. Although the adrenals do utilized exogenous cholesterol for steroid hormone synthesis, the cholesterol is delivered to the glands not as free cholesterol but through the uptake of low density lipoproteins (LDL), which are subsequently degraded within the adrenal cortical cells to provide cholesterol. Thus, we sought to assess the use of 99mTc-labelled LDL injected into rabbits to obtain external images of the adrenal glands.

Local variation in arterial wall permeability to low density lipoprotein in normal rabbit aorta.

Normal rabbits were injected intravenously with horseradish peroxidase (HRP) and 125I-labeled human low density lipoprotein (LDL), and the aortas were perfusion-fixed. Subsequent visualization of HRP in the aortas was produced by reaction of the tissue with diaminobenzidine and hydrogen peroxide. The luminal surface of the aortas showed many small punctate foci of brown reaction product to the HRP, which represented penetration of the HRP into the vessel wall.

High and low affinity IL 2 receptors: analysis by IL 2 dissociation rate and reactivity with monoclonal anti-receptor antibody PC61.

In this report we characterize two classes of interleukin 2 (IL 2) binding sites on the basis of their differential IL 2 dissociation rate and of their reactivity with PC61, a monoclonal anti-IL 2 receptor (IL 2-R) antibody. PC61 inhibited the binding of IL 2 to both classes of receptor, but IL 2 did not inhibit the binding of PC61. This indicates that PC61 recognizes a determinant that is distal to the actual IL 2 binding site of the receptor.

Cell surface glycoproteins involved in the stimulation of interleukin 1-dependent interleukin 2 production by a subline of EL4 thymoma cells. II. Structure, biosynthesis, and maturation.

In the present study, we examined the biosynthesis and the maturation of two distinct membrane glycoproteins detected by two monoclonal antibodies (RL388 and RL119), which were selected on the basis of their ability to stimulate the production of interleukin 2 by a subline of the murine EL4 thymoma. RL388 detected a disulfide-linked heterodimer complex (Mr = 130,000) composed of a glycosylated heavy (Mr = 86,000) and a nonglycosylated light (Mr = 39,000) subunit. The unglycosylated precursor of the heavy chain was a polypeptide of Mr = 57,500, which was converted upon maturation into a Mr = 73,000 core-glycosylated intermediate, and then into the Mr = 86,000 surface-expressed molecule.

Cell surface glycoproteins involved in the stimulation of interleukin 1-dependent interleukin 2 production by a subline of EL4 thymoma cells. I. Functional characterization by monoclonal antibodies.

Three rat monoclonal antibodies (MAb) capable of stimulating interleukin 2 (IL 2) production by a variant subline of EL4 thymoma cells (EL4-6.1) have been produced. The stimulatory capacity of these MAb (designated RL73, RL119, and RL388) was originally found to be dependent on the presence of irradiated peritoneal exudate cells; however, this requirement could be replaced by the cellfree supernatant of the "macrophage-like" cell line P388D1 or by biochemically purified human interleukin 1 (IL 1).

Arsenic, syphilis, and cancer of the prostate.

A study was conducted to investigate the association of cancer of the prostate with historical records of previous venereal disease and treatment with arsenical drugs. Eighty-three cancer cases were each age matched with two male controls--one with benign prostatic hypertrophy and one other non-cancer patient. Analysis from pooled data showed a statistically significant difference for syphilis infection between cases and controls at p less than 0.

Technetium-99m low density lipoproteins: preparation and biodistribution.

The focal uptake by human atherosclerotic lesions of 125I bound to low density lipoproteins (LDL) can be demonstrated by external imaging. However, 125I has poor imaging characteristics. Therefore, we have developed a technique for labeling LDL with technetium.

Evaluation of aortic stenosis by spectral analysis of the murmur.

A relation between the peak transaortic pressure gradient and the frequency content of the murmur (r = 0.79) was demonstrated in a prospective "test" set of 50 patients with the clinical diagnosis of aortic stenosis. After heart sounds were recorded and digitized, three segments of the systolic murmur were isolated and analyzed by fast Fourier transform technique.

Simultaneous therapy with antiplatelet and anticoagulant drugs in symptomatic cardiovascular disease.

Twenty of approximately 1000 patients attending the arteriosclerosis clinic at MIT during a 13 year period were treated simultaneously with aspirin and warfarin for symptomatic atherosclerotic (19) or rheumatic (1) heart or vascular disease. The average duration of therapy was 5.8 years.

Mutant EL-4 thymoma cells polyclonally activate murine and human B cells via direct cell interaction.

In this report we show that three mutagenized sublines of (murine) EL-4 thymoma cells can constitutively activate human and/or murine B cells via an MHC-nonrestricted cell-cell interaction. The activation signal is not by itself mitogenic but renders B cells capable of proliferating in response to interleukin 2 (IL 2). In addition, one of the mutant EL-4 sublines can constitutively respond by release of IL 2 in the presence of IL 1-containing macrophage (P388D1) supernatant.