Identification of integrin alpha(M)beta(2) as an adhesion receptor on peripheral blood monocytes for Cyr61 (CCN1) and connective tissue growth factor (CCN2): immediate-early gene products expressed in atherosclerotic lesions.

Cysteine-rich 61 (Cyr61, CCN1) and connective tissue growth factor (CTGF, CCN2) are growth factor-inducible immediate-early gene products found in blood vessel walls and healing cutaneous wounds. We previously reported that the adhesion of endothelial cells, platelets, and fibroblasts to these extracellular matrix-associated proteins is mediated through integrin receptors. In this study, we demonstrated that both Cyr61 and CTGF are expressed in advanced atherosclerotic lesions of apolipoprotein E-deficient mice.

Novel tocotrienols of rice bran inhibit atherosclerotic lesions in C57BL/6 ApoE-deficient mice.

We are studying novel tocotrienols, which have a number of activities that might interfere with the formation of atherosclerotic plaques, including hypocholesterolemic, antioxidant, anti-inflammatory and antiproliferation effects. This study compared the effects of alpha-tocopherol, the tocotrienol-rich fraction (TRF(25)) and didesmethyl tocotrienol (d-P(25)-T3) of rice bran on the pathogenesis of atherosclerotic lesions in C57BL/6 apolipoprotein (apo)E-deficient (-/-) mice. These mice are an excellent model because they become hyperlipidemic even when they consume a low fat diet and they develop complex atherosclerotic lesions similar to those of humans.

Alcohol inhibits the progression as well as the initiation of atherosclerotic lesions in C57Bl/6 hyperlipidemic mice.

Background: Evidence that a moderate consumption of alcohol is associated with a reduced incidence of and mortality due to coronary artery disease continues to accumulate. Despite recent evidence that substances in red wine confer resistance to coronary artery disease, it is clear that at least a substantial proportion of the protective effect is due to the alcohol content of the beverage. We have previously shown that the chronic ingestion of alcohol incorporated into a total liquid diet during a 24-week period inhibits the development of fatty streak lesions in hyperlipidemic C57Bl/6 mice.

Regression of poloxamer 407-induced atherosclerotic lesions in C57BL/6 mice using atorvastatin.

HMG-CoA reductase inhibitor drugs or 'statins' have been shown to effectively reduce plasma total cholesterol (CHOL), CHOL associated with low-density-lipoprotein (LDL), and triglycerides (TG). In addition, slight elevations in HDL-CHOL are also typically observed. Poloxamer 407 (P-407), a nonionic surfactant, effectively elevates both plasma CHOL and especially TG in a dose-controlled fashion and results in formation of atherosclerotic lesions in the aortas of C57BL/6 mice without the requirement of dietary cholic acid [1,2].

Potential downregulation of HMG-CoA reductase after prolonged administration of P-407 in C57BL/6 mice.

This study investigated the potential alteration in the amount of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase messenger RNA (mRNA) and lipoprotein lipase (LPL) mRNA in the livers of C57BL/6 mice after long-term (200 days) treatment with the nonionic surfactant called poloxamer 407 (P-407). Previously, P-407 has been used to produce a dose-controlled hyperlipidemic state in C57BL/6 mice with subsequent formation of atherosclerotic lesions. Five groups of mice were studied; controls (C); mice fed a standard chow diet enriched with only cholic acid (CH); mice fed the high-cholesterol, high-fat Paigen diet (HF); mice treated with 0.

Poloxamer 407-induced atherogenesis in the C57BL/6 mouse.

Poloxamer 407 (P-407) induces hyperlipidemia in the rat. It was the purpose of this investigation to determine if chronic P-407 administration would produce atherogenic arterial lesions in the C57BL/6 mouse, a strain reported to be susceptible to hyperlipidemia-induced atherosclerotic plaque formation. One injection (i.

The poloxamer 407-induced hyperlipidemic atherogenic animal model.

We are attempting to develop a chemically-induced murine model for the study of atherosclerosis. Injection of poloxamer-407 (P-407) into rats and mice causes significant dose-dependent hypercholesterolemia and hypertriglyglyceridemia. The elevated triglycerides (TG) seem to result primarily from the compound's inhibition of lipoprotein lipase.

Inhibition of atherosclerosis in CD4 T-cell-ablated and nude (nu/nu) C57BL/6 hyperlipidemic mice.

T lymphocytes and monocyte/macrophages are prominent components of atherosclerotic lesions, and many of these cells are activated and secreting cytokines. To determine the role of these cells in the pathogenesis of atherosclerosis, we studied its development in T-cell-deficient mice fed a high fat atherogenic diet. Depleting euthymic mice of their CD4+ lymphocytes by 20 weekly injections of CD4 monoclonal antibodies reduced the mean area of their aortic lesions by approximately 70%.

Chronic alcohol feeding inhibits atherogenesis in C57BL/6 hyperlipidemic mice.

Although there is abundant clinical evidence that the consumption of alcohol (ethanol) in moderate amounts has a protective effect on coronary artery disease, the mechanism of this effect is not understood. The prevailing theory supported by a limited number of clinical and experimental animal studies indicates that the ability of alcohol to elevate serum high-density lipoprotein cholesterol levels is an important mechanism. Although there have been a large number of studies on the effects of alcohol on serum lipoprotein and apolipoproteins on coronary artery disease, there have been very few that have, at the same time, looked directly and systematically at its effects on the histopathological development of atherosclerotic lesions.

Accelerated atherosclerosis in hyperlipidemic C57BL/6 mice treated with cyclosporin A.

We and others have demonstrated that T lymphocytes are prominent components of atherosclerotic lesions. We hypothesized that if T cells were necessary for the development of atherosclerosis it would be possible to demonstrate its prevention or retardation in T-cell-suppressed mice. To test this hypothesis, CyA, a potent suppressor of T-cell activation, was used to treat C57BL/6 mice undergoing lipid hyperalimentation.

T lymphocytes in aortic and coronary intimas. Their potential role in atherogenesis.

In order to investigate the role of mononuclear cells in infiltrates during the initial stages of atherogenesis, the authors have studied by immunohistochemical methods the aortas and coronary vessels of children and young adults (ages 15-34) dying of acute trauma. Eccentric intimal thickening often accompanied by intimal mononuclear cell infiltration was commonly observed in sections of the lower thoracic aorta. These changes were usually related to intercostal branching sites and thus greater in the dorsal (posterior) than on the ventral aspect of the aorta in 64 of 75 cases examined.

Human immunodeficiency virus (HIV) antigenemia (p24) in the acquired immunodeficiency syndrome (AIDS) and the effect of treatment with zidovudine (AZT).

Infection with human immunodeficiency virus (HIV) may cause viral antigenemia, detected primarily as p24 viral core protein. Among 16 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex studied serially, 12 had or developed antigenemia ranging from 16 to 3006 pg/mL in plasma. The level could be categorized as high (greater than 100 pg/mL) or low (15 to 65 pg/mL).

Cyclosporine-induced tolerance in experimental organ transplantation. Evidence of diminished donor-specific cytotoxicity relative to donor-specific proliferative response.

Alloreactivity of intragraft and peripheral blood lymphocytes from tolerant canine lung allograft recipients was examined. Tolerance was induced by variable periods of treatment with cyclosporine. Analysis of effector cells from lung allografts (obtained by bronchoalveolar lavage) revealed the absence of specific cytolytic T lymphocyte (CTL) activity and the presence of a low level of cytolytic activity detected in a lectin-dependent cell-mediated cytotoxicity assay.

Serologic, immunologic, and clinical features of parenteral drug users from contrasting populations.

We screened inpatient and outpatient parenteral drug users with no clinical evidence of AIDS for immunodeficiency and antibodies to HTLV-III by ELISA. Among 20 outpatient drug users, 5 (25%) were seropositive. Three of these (and 2 who were seronegative) had low T-cell ratios.

Concanavalin A-dependent cell-mediated cytotoxicity in bronchoalveolar lavage fluid. Correlation with lung allograft rejection in mongrel dogs during cyclosporine dose tapering.

Although cyclosporine (CsA) is widely used as the primary agent for inhibiting the rejection of organ allografts in man, the ideal immunosuppressive regimen for utilizing this drug is still uncertain. To investigate this question, a concanavalin A (con A)-dependent cell-mediated cytotoxicity (CDCMC) assay was used to examine the development of intragraft and peripheral blood cytolytic T lymphocyte activity during CsA dose tapering. These studies were conducted in a canine single-lung transplantation model that facilitates serial examination of intragraft effector cells by bronchoalveolar lavage (BAL).

Ocular sarcoidosis and Graves' ophthalmopathy.

Sarcoidosis, a granulomatous disease first recognized as a dermatologic disorder, is now known to involve multiple organs, including the eye. Indeed, ocular involvement may be the only clinical manifestation of this protean disease; it may involve any part of the visual apparatus and its adnexal structures. In this paper we report on the concurrence of sarcoidosis of the lid with Graves' ophthalmopathy in the same patient.

Bronchial anastomotic healing in canine lung allotransplants treated with cyclosporine.

Bronchial anastomotic healing was evaluated in 22 long-term-surviving canine lung allotransplant recipients treated with cyclosporine as the major immunosuppressive agent. Mean survival in these dogs was over 155 days, and 4 animals survived 1-3 years. Bronchial anastomotic complications were limited to 5 cases of minimal (less than 15%) bronchostenosis.

Influence of bronchial circulation and corticosteroid therapy on bronchial anastomotic healing.

In order to assess the effect of revascularization on the healing of bronchial anastomoses in a canine model, we developed a microsurgical technique that permits the immediate reperfusion of the distal bronchial segment by a direct anastomosis of the bronchial artery to an intercostal artery. This technique was applied to dogs that underwent hilar stripping and bronchial transection and reanastomosis, and it prevented the development of ischemic bronchial damage. In addition, several groups of dogs that had undergone bronchial transection and reanastomosis and, in some cases, reestablishment of bronchial arterial circulation, were treated with 40 mg of prednisone daily for periods of 7 and 21 days.

Ferritin-bearing lymphocytes in patients with cancer.

Ferritins, a group of isomeric proteins that have important functions in iron metabolism and storage, have been demonstrated to be carcinoembryonic antigens. It has been recently shown that a subpopulation of lymphocytes from the peripheral blood of patients with Hodgkin's disease or breast cancer bear ferritin on their surface membranes. In view of the potential diagnostic and prognostic value of ascertaining the number of ferritin-bearing lymphocytes, the authors developed a simple indirect immunofluorescent technique for identifying them and used this technique to examine the peripheral blood lymphocytes of 44 patients with carcinomas of the head and neck (26), colon (14), and lung (4).

Single lung transplantation with cyclosporin immunosuppression. Evaluation of canine and human recipients.

Cyclosporin, a potent new immunosuppressive agent, was used (alone or in combination with other drugs) in 28 canine single lung allograft recipients. Mean recipient survival with good allograft function was 155 days with cyclosporin and far exceeded that obtained in previous single lung allograft recipients treated with standard immunosuppression (15 to 22 days). The results of these experiments were as follows: (1) 20% of the recipient animals exhibited no evidence of rejection whatsoever; (2) four of 28 animals survived more than 350 days with good allograft function; (3) 79% of the animals exhibited some evidence of rejection that was easily reversed in 74% of instances with corticosteroids; (4) 10 of 28 animals exhibited good lung allograft function 5 months or more after operation; (5) in cyclosporin-treated lung allograft recipients, rejection was diagnosed by the presence of infiltrate on chest roentgenogram, analysis of the cellular content of bronchoalveolar lavage samples, and decreased perfusion on 99mtechnetium lung scan; (6) complete healing without stenosis of the bronchial anastomosis occurred in 82% of the animals studied.

Immunodeficiency in female sexual partners of men with the acquired immunodeficiency syndrome.

Because the current outbreak of acquired immunodeficiency syndrome (AIDS) among previously healthy adults may be caused by a transmissible biologic agent, and because it may be preceded by immunologic abnormalities with or without a prodromal illness, we studied seven female sexual partners of male patients with the syndrome. The male patients were all drug abusers. One of the seven women was found to have the full-blown syndrome, a second had an illness consistent with the prodrome of AIDS (generalized lymphadenopathy, lymphopenia, and a decreased ratio of helper to suppressor T cells), and four others had generalized lymphadenopathy or lymphopenia, with or without a decreased ratio of helper to suppressor T cells.

Community-acquired opportunistic infections and defective cellular immunity in heterosexual drug abusers and homosexual men.

Fourteen previously healthy young patients with unusual community-acquired opportunistic infections were seen over a period of three years. They differ from patients previously described in that 11 were heterosexual drug abusers (including two women) and only three were homosexual men. There were eight Puerto Ricans, five blacks, and one white.