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G Wick

Publications and source records attributed to G Wick.

At least 145 records · Page 8Linked to original sources

Association of serum antibodies to heat-shock protein 65 with carotid atherosclerosis.

Arteriosclerotic lesions can be induced in normocholesterolaemic rabbits by immunisation with heat-shock protein (hsp) 65, a stress protein expressed in high concentrations in human atherosclerotic lesions. If an immune reaction to hsp65 also plays a part in human atherogenesis, it should be possible to detect anti-hsp65 antibodies in patients with atherosclerotic lesions. To study the possible relation between immune reaction to hsp65 and atherosclerosis, 867 normal inhabitants of South Tyrol, aged 40-79 years, were selected randomly for determination of serum antibodies against hsp65, simultaneous sonographic assessment of carotid atherosclerotic lesions, and evaluation of established risk factors--ie, blood cholesterol, hypertension, smoking, diabetes mellitus, and obesity. Autoantibodies to nuclear antigens, thyroid antigens, and rheumatoid factors were also measured. Serum anti-hsp65 antibodies were significantly (p < 0.05) increased in subjects aged 60-79 years with carotid atherosclerosis compared with those without lesions, and increased antibody concentration was independent of age, sex, and other established risk factors. On the other hand, the incidence and titres of autoantibodies did not correlate with carotid atherosclerotic lesions. Our data provide the first evidence of a strong correlation between anti-hsp65 antibodies and carotid atherosclerosis, suggesting that hsp65 might be involved in the pathogenesis of atherosclerosis.

Adult↗

In situ analyses of in ovo graft-vs.-host reaction induced by thymic nurse cell lymphocytes.

In both mammalian and avian systems, thymic nurse cells (TNC) have been shown to harbor a heterogeneous population of T lymphocytes (TNC-L) some of which exhibit a postselectional phenotype. By transplanting micromanipulated single chicken TNC onto the chorionallantoic membrane (CAM) of major histocompatibility complex (MHC)-disparate embryos, an experimental system which allows for the detection of lymphocytes with graft-vs.-host (GVH) reactivity, we demonstrate here that TNC enclose lymphocytes that can develop into both CD4+ single-positive (sp) and CD8+ sp, T cell receptor (TcR) alpha beta+, or TcR gamma delta+ cells. This finding was additionally confirmed by serial transfer of primary expanded alloreactive T cells onto the CAM of secondary hosts. All donor TNC-L expressed MHC class II molecules and the interleukin-2 receptor alpha chain in primary and secondary GVH reactions. Furthermore, we observed selective accumulation of CD8+ and TcR gamma delta+ host lymphocytes in the CAM upon the induction of a local GVH reaction, most probably as a consequence of the pathological alteration of the epithelium.

Animals↗

Effects of cytokine application on glucocorticoid secretion in an animal model for systemic scleroderma.

We previously reported on an altered immune-endocrine feedback loop via the hypothalamo-pituitary-adrenal (HPA) axis in Obese strain (OS) chickens afflicted with spontaneous autoimmune thyroiditis. These animals are deficient in plasma corticosterone increase after antigenic challenge or application of cytokine-containing conditioned medium of mitogen-stimulated spleen cells (CM). To investigate whether the impaired ability to respond to cytokines with glucocorticoid-increasing factor (GIF) activity, e.g. interleukin 1 (IL 1), is restricted to OS chickens as a model for an organ-specific autoimmune disease, we extended our experiments to another autoimmune-prone animal strain, the chickens of the University of California at Davis line 200 (UCD-200). These animals develop an inherited inflammatory fibrotic disease that closely resembles human progressive systemic sclerosis (scleroderma). Application of GIF-containing CM to UCD-200 chickens leads to a transient increase in glucocorticoid serum levels within 1-2 hours comparable to that of controls. But, while corticosterone levels in the latter returned to normal baseline levels after 4 hours, they were still elevated in autoimmune chickens. Although the peak of the glucocorticoid hormone serum concentrations was equal to that of controls, UCD-200 had to secrete twice as much adrenocorticotropic hormone to achieve this corticosterone serum level due to an apparent hyporesponsiveness of the adrenal gland to this secretagogue. The altered cytokine-induced glucocorticoid secretion is found in early as well as in chronic, sclerotic stages of the disease. Cellular alterations in the peripheral blood of UCD-200 chickens during the prolonged elevated corticosterone section, i.e. between 2-4 hours after CM application, are characterized by a significant decrease in the percentage of CD4+ and CD8+ cells. Furthermore, a significant increase in B cells up to 24 hours with a maximum after 1 hour was found. The proliferative response to the mitogen concanavalin A of peripheral mononuclear cells was inversely correlated to the serum corticosterone level, showing a permanent decrease of 80-90% after 1-4 hours in autoimmune animals. This functional alteration in UCD-200 was accompanied by an 80% decrease in serum interleukin 2 (sIL 2) activity 4 hours after CM application. Twenty-four hours later an eight-fold increase in sIL 2 rebound activity was found, indicating that the inhibitory effect of corticosterone in UCD-200 chickens is not long-lasting.

Adrenocorticotropic Hormone↗

Estimation of reference intervals from a SENIEUR protocol compatible aged population for immunogerontological studies.

Because many laboratory values change with age, the study of healthy aging as well as diagnosis of disease in geriatric patients requires specific age-corrected reference intervals. We have established such reference intervals for a healthy population aged 65-74 years by selection of a sample group applying the clinical criteria of the SENIEUR protocol and we have compared them with those of a young control group (20-33 years) fulfilling the same criteria. Significant or minor elevations were seen, e.g. for plasma concentrations of fasting glucose, urea, total and LDL-cholesterol, triglycerides, gamma-glutamyl-transferase, alkaline phosphatase, erythrocyte sedimentation rate and serum neopterin levels. These reference intervals can be used for selecting a SENIEUR compatible population aged between 65 and 74 years. Additionally, plasma lipid parameters (cholesterol, triglycerides) are proposed to be included in the SENIEUR protocol.

Adult↗

Oral administration of a bacterial immunomodulator enhances murine intestinal lamina propria and Peyer's patch lymphocyte traffic to the lung: possible implications for infectious disease prophylaxis and therapy.

LW50020, a bacterial immunomodulator, is a preparation consisting of seven bacteria, commonly causing respiratory disease. When given orally, LW50020 has been shown to enhance the host defense of the respiratory tract. Intestinal lamina propria lymphocytes (LPL), Peyer's patch lymphocytes (PPL), and splenocytes from BALB/c mice gavaged either with LW50020 or carrier alone were isolated, labeled with either H33342, a supravital nuclear fluorochrome, or 51Cr, and injected i.v. into untreated, age-matched BALB/c mice. Two hours later, spleen, liver, lung, kidneys, Peyer's patch, and mesenteric lymph nodes of the recipients were harvested and screened for the presence of labeled cells. LPL from mice gavaged with carrier only (controls) migrated preferentially to the lung, PPL equally well to the lung, and the spleen and splenocytes were found mostly in the spleen. LPL and PPL from LW50020-treated mice were found in significantly larger numbers in the lungs of recipients than LPL and PPL from control animals. Both labeling techniques gave roughly the same results. Sixty-five per cent of LPL in the lung were Thy-1.2+ and 20% B cells. These findings should contribute to the understanding of parameters necessary for the assessment of the mode of action and efficacy of immunomodulation and vaccination via the mucosa-associated lymphoid tissue.

Adjuvants, Immunologic↗

Functional and immunological relevance of the COOH-terminal extension of human chorionic gonadotropin beta: implications for the WHO birth control vaccine.

The World Health Organisation (WHO) Task Force on Birth Control Vaccines has selected the pregnancy hormone human chorionic gonadotropin (hCG) as a target molecule for a contraceptive vaccine. A synthetic peptide antigen corresponding to the amino acid sequence 109-145 of the carboxyl-terminal portion of the hCG beta-subunit (hCG beta CTP), which is supposed to elicit hCG-immunoneutralizing antibodies, has been submitted to clinical trials. Recent findings suggest that hCG beta CTP does not play a role in the biological activity of hCG. This raises the question concerning the assumed mechanism of action of the hCG beta CTP-based birth control vaccine. We therefore investigated the immunoneutralizing capacity of antibodies directed against hCG beta CTP. Although it is possible to generate specific monoclonal and polyclonal antibodies for hCG by using hCG beta CTP as an immunogen, it appeared that the biological response to hCG was not affected by such antibodies. The reason for this is that the hCG-antibody-complex is still able to bind to target cell receptors and therefore the intended contraceptive effect should not occur. In addition there is a risk of hazardous possible side effects such as an autoimmune reaction against the ovary because we found that at least one epitope is still accessible for antibody binding on receptor-bound hCG. We conclude from our results that both the efficacy and safety of the WHO vaccine are not yet ensured.

Animals↗

Possible role of human foamy virus in Graves' disease.

Human foamy virus (HFV) is a member of the retroviral family of Spumaretrovirinae. In addition to the three retroviral structural genes, gag, pol and env, HFV also contains regulatory sequences, called bel. Foamy viruses have been previously associated with human thyroid disease, notably DeQuervain's thyroiditis. In indirect immunofluorescence tests we have demonstrated the reactivity of the thyroid glands of 7/7 patients with Graves' disease and antibodies to HFV gag proteins. No reactivity was observed with antibodies to pol, env and bel proteins. Nine thyroids of patients with struma parenchymatosa, 4 with follicular carcinoma and 2 normal thyroids were negative throughout. From the thyroids of 5 patients with Hashimoto's disease, 4 were negative and 1 showed a single small focus of anti-gag antibody reactivity. The uniform immunofluorescent staining was restricted to the basal and lateral intercellular areas between the thyroid epithelial cells. Extension of these studies to the retrobulbar tissue of 1 Graves' disease patient with malignant exophthalmus revealed positive staining with anti-gag antibodies of fibroblasts and fat cells but not eye muscles. Furthermore, we were successful in establishing several T-cell lines derived from the retrobulbar tissue of this patient. They were CD8+ and proliferated, in contrast to peripheral blood cells, upon cocultivation with autologous retroorbital fibroblasts. It remains to be determined whether these observations are of relevance in the pathogenesis of Graves' disease.

Graves Disease↗

Antinuclear antibody profile in UCD line 200 chickens: a model for progressive systemic sclerosis.

The fully blown disease of human progressive systemic sclerosis (PSS, scleroderma) is serologically associated with the emergence of several types of autoantibodies, some of them regarded as more specific for scleroderma (e.g. Scl-70, anti-centromere) and some common also to other connective tissue diseases (e.g. anti-ssDNA). Since most patients suffering from PSS are not under medical control until clinical manifestations are fully established, only scarce data are available on the dynamics and clinical significance of autoantibodies in the very early stages of this systemic fibrotic disease. The University of California at Davis line 200 (UCD 200) of chickens spontaneously develop a PSS-like disorder with an acute inflammatory stage around 60 days after hatching, leading to fibrosis with fast progression. In order to address a possible correlation between the occurrence and titer of autoantibodies and the initial disease activity, we have chronologically investigated the presence and titer of autoantibodies directed against several human nuclear antigens in this animal strain. In UCD-200 chickens, we found a progressive increase in autoantibodies to histones, to ssDNA and--to a lesser degree--dsDNA with peaks at the age of 60 and 120 days, to poly(I) and poly(G) with a peak at 120 days and an elevation in anti-cardiolipin antibodies. Total immunoglobulin concentrations, anti-Ro, anti-La and anti-Sm showed no significant differences as compared to negative results in healthy normal controls. Our data reveal parallels in the antinuclear antibody (ANA) spectrum between UCD-200 chickens and human autoimmune collagen diseases, but do not reflect the typical ANA spectrum found in the foudroyant form of diffuse scleroderma.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Disturbed immuno-endocrine communication via the hypothalamo-pituitary-adrenal axis in autoimmune disease.

Previous studies in our laboratory demonstrated an altered immuno-endocrine feedback communication via the hypothalamo-pituitary-adrenal (HPA) axis, which may be an important modulatory factor in the development of spontaneous autoimmune thyroiditis in Obese strain (OS) chickens. These birds show a significantly lower, or even absent, increase in serum glucocorticoid levels in response to an intravenous injection of antigen or conditioned medium (CM) from mitogen-stimulated spleen cells known to contain glucocorticoid-increasing factors (GIFs), notably interleukin-1 (IL-1). The present study was aimed at investigating this feedback regulation in animal models with spontaneous systemic autoimmune diseases, such as the UCD-200 chicken, which serves as a model for human scleroderma, and various murine lupus models. In contrast to OS chickens, UCD-200 chickens displayed a nearly normal plasma corticosterone surge in response to CM, and IL-1 was again identified as the primary GIF in CM. Recombinant IL-1 also induced a drastic increase in plasma corticosterone levels in various strains of normal mice. A similar increase was observed in the bacterial lipopolysaccharide-resistant C3H/HeJ strain, thus excluding the possibility of bacterial endotoxin contamination. However, in young lupus-prone (NZB/W)F1 and MRL/MP-lpr mice, a significantly lower increase in plasma corticosterone levels was observed after injection of recombinant IL-1, suggesting a deficient immuno-endocrine communication via the HPA loop in this instance as well. Detailed studies to identify further cytokines with GIF activity in the avian and murine systems showed that both IL-6 and tumor necrosis factor-alpha could induce increased plasma corticosterone levels in mice, but not in chickens. IL-3, IL-8, transforming growth factor-beta, interferon-gamma and granulocyte-macrophage colony-stimulating factor were devoid of GIF activity in both chickens and mice.

Animals↗

Staining of endothelial cells and macrophages in atherosclerotic lesions with human heat-shock protein-reactive antisera.

Our previous epidemiological studies have shown that levels of serum antibodies against mycobacterial heat-shock protein (hsp) 65 correlate positively with carotid atherosclerosis in subjects aged 40 to 79 years. To determine whether these high-titer sera also react with homologous human hsp60 and/or cell components of atherosclerotic lesions, we selected 15 human sera samples, each with high or low titers to recombinant mycobacterial hsp65, and investigated their reactivity with human arterial lesion components by immunoblotting and immunofluorescence techniques. All five higher-titer sera against hsp65 reacted with a 60-kDa band of atherosclerotic lesion proteins and human recombinant hsp60 on Western blots. Pooled sera with low antibody titers to hsp65 diluted similarly as high-titer sera did not show reactivity with atherosclerotic lesion and media proteins. By immunohistochemistry and immunofluorescence with human immunoglobulin G isolated from different sera, labeled with biotin, and visualized with a streptavidin conjugate, positive staining was observed in sections of fatty streaks and atherosclerotic plaques of carotid arteries, and weak staining was observed in the normal intima. Double immunofluorescence identified the majority of positively stained cells as macrophages, endothelial cells, and a few smooth muscle cells. In summary, serum antibodies against hsp65 cross-react with the human 60-kDa homologue present in high levels in atherosclerotic lesions and are mainly reacting with macrophages and endothelial cells, supporting our concept of a possible involvement of humoral-mediated immune reaction against hsp60 in atherogenesis.

Aged↗

Increased expression of heat shock protein 65 coincides with a population of infiltrating T lymphocytes in atherosclerotic lesions of rabbits specifically responding to heat shock protein 65.

We have shown previously that atherosclerotic lesions can be induced in normocholesterolemic rabbits by immunization with mycobacterial heat shock protein 65 (hsp65), which has a high degree of sequence homology with mammalian hsp60. To investigate a possible relationship between hsp60 expression and the antigenic specificities of infiltrating T cells in the lesion, 38 New Zealand White rabbits were treated either by immunization with recombinant mycobacterial hsp65 or by administration of a 0.2% cholesterol diet. Atherosclerotic lesions were observed after 16 wk, particularly in the aortic arch and arterial bifurcations of rabbits immunized with hsp65 or fed with a cholesterol-rich diet. Hsp65 staining of aortas showed a heterogeneous distribution, and significantly increased staining intensity in atherosclerotic lesions compared to aortic media or adventitia. This abundantly expressed hsp65 was observed in atherosclerotic lesions induced by hsp65 immunization as well as those induced by cholesterol-rich diet alone. Interestingly, a population of the T lymphocytes isolated from all forms of atherosclerotic lesions specifically responded to hsp65 in vitro. IL-2-expanded T cell lines derived from atherosclerotic lesions showed a significantly higher hsp65 reactivity than those developed from peripheral blood of the same donor. Furthermore, levels of circulating antibodies and numbers of spleen cells specifically reacting against hsp65 were elevated in all experimental animals. Flow cytometric analysis of spleen cells showed elevated immune response-associated antigen expression in treated animals. In conclusion, increased hsp65 expression in intimal cells and the presence of hsp65-specific T cells in blood and in atherosclerotic lesions may be important in initiating the development of atherosclerosis and perpetuating the lesions.

Animals↗

Variants of human chorionic gonadotropin from pregnant women and tumor patients recognized by monoclonal antibodies.

In biological fluids, hCG and its free alpha- (hCG alpha) and beta-subunits (hCG beta), occur in multiple forms. These various forms differ at the molecular level primarily in glycosylation, but also differ in protein backbone modifications corresponding to the urinary low molecular weight fragment of the hCG beta-subunit (beta-core fragment). This microheterogeneous nature can be demonstrated by isoelectric focusing in which variants are separated into bands with different isoelectric points (pI). To determine whether such isoelectric variants differ in antigenicity and consequently might escape immunoassay detection due to overspecificity of monoclonal antibodies (MCA), urinary pregnancy hCG (NIH, CR123) and tumor hCG preparations, such as a tumor-specific acidic variant of hCG (hCGav) and the hCG beta-core fragment, were separated by isoelectric focusing in the absence or presence of 8 M urea, or by sodium docedyl sulfate-polyacrylamide gel electrophoresis and enzymatically immunostained using an MCA panel directed against 17 different hCG epitopes. MCA against 14 different epitopes accessible on holo-hCG recognized all pI variants of pregnancy holo-hCG or tumor-derived hCGav, as was true for the three MCA recognizing epitopes hidden on holo-hCG but accessible on the free subunits after hCG dissociation by urea. We conclude that each individual pI-isoform of holo-hCG and its free subunits expresses the entire set of epitopes recognized by our MCA panel. The carbohydrate moieties that form a biochemical basis for hCG heterogeneity seem to be neither of major antigenic relevance, nor are they structurally related to any particular epitope. Thus, various glycosylation forms of hCG, hCG alpha, hCG beta, and hCG beta-core in normal as well as in pathological samples should safely be detectable and measureable by immunoassays employing MCA with appropriate subunit specificity.

Antibodies, Monoclonal↗

[Antigenic determinants of human chorionic gonadotropin (hCG): identification of epitopes and determination of their biological functions, for use in immunometric test systems and development of a fertility regulating vaccine].

Analysing immunologically relevant structures of human chorionic gonadotropin (hCG), a glycoprotein hormone, has bearing on a variety of clinical features. These structures are of importance for the establishment of immunometric assays for the diagnosis and monitoring of pregnancy and hCG producing tumours. Moreover, the development of fertility regulating vaccines by the use of one of the subunits of hCG (hCG beta) or a synthetic peptide corresponding to the carboxyl-terminal peptide thereof (hCG beta CTP, beta 109-145) requires detailed knowledge of the antigenic properties of hCG. It appeared that 16 different antigenic epitopes are localized on the protein backbone of hCG and that the carbohydrate moieties do not contribute significantly to the immunological properties of this hormone. Reduced and carboxylmethylated subunits of hCG, i.e., hCG alpha and hCG beta, express only 1 alpha- and 2 beta-epitopes, the majority of antigenic determinants being destroyed by this chemical procedure. Epitopes of hCG are thus predominantly dependent on the intact tertiary or quaternary structure of the protein. The urinary low molecular weight fragment of hCG beta (hcG beta cf), a predominant molecular fraction in the urine of pregnant women or patients with various tumours expresses 7 out of 9 epitopes of hCG beta (beta 1- beta 7), whereas two antigenic determinants, beta 8 and beta 9, are localized on the hCG beta CTP.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

Immunology of atherosclerosis. Demonstration of heat shock protein 60 expression and T lymphocytes bearing alpha/beta or gamma/delta receptor in human atherosclerotic lesions.

Our previous work revealed the presence of a great number of activated T lymphocytes in early human atherosclerotic lesions, and we were able to induce atherosclerosis in normocholesterolemic rabbits by immunization with Mycobacterium tuberculosis heat-shock protein (HSP) 65. We hypothesized this latter phenomenon to arise from cross-reactivity of mycobacterial HSP 65 with the endogenously expressed homologous 60-kd form of this stress protein. To study HSP 60 expression and the phenotype of intima infiltrating T lymphocytes relative to the T cell receptor (TCR) in human atherosclerotic lesions, specimens of aorta, carotid arteries, and internal mammary arteries and veins, as well as saphenous veins and vena cava from 27 subjects, aged 23 to 80 years, were examined using immunohistochemical and immunofluorescence techniques on serial frozen tissue sections. HSP 60 was detected on endothelium, smooth muscle cells, and/or mononuclear cells of all carotid and aortic specimens, whereas vessels of smaller diameter, serving as reference specimens for normal intima without atherosclerotic lesions and mononuclear infiltration, showed no detectable expression of this stress protein. Furthermore, although the majority of CD3+ cells within the mononuclear cell infiltrates of atherosclerotic lesions bear the alpha/beta TCR, a considerable portion also consisted of gamma/delta TCR+ cells. Thus, 9.7% of T cells in the transition zone between normal intima and fatty streaks carry the gamma/delta TCR, a proportion that decreases to 6.6% and 4.3% in fatty streaks and atherosclerotic plaques, respectively. We conclude that the intensity of HSP 60 expression correlates positively with the atherosclerotic severity and that most lymphocytes participating in atherogenesis bear the alpha/beta TCR, although gamma/delta TCR+ cells are also enriched in atherosclerotic lesions. Expression of HSP 60 by intimal cells, caused, eg, by hemodynamic shear forces, may be responsible for recruitment of HSP-sensitized T cells, thus leading to the induction of an initiating inflammatory process in atherosclerosis. Other risk factors, such as high serum cholesterol levels, contribute to the final outcome of the disease.

Adult↗

Time-resolved immunofluorometry and other frequently used immunoassay types for follicle-stimulating hormone compared by using identical monoclonal antibodies.

The influence of assay design and quantification system on assay performance was investigated by developing, optimizing, and comparing a time-resolved immunofluorometric assay (IFMA), an immunoenzymometric assay (IEMA), an immunoradiometric assay (IRMA), and a competitive radioimmunoassay (RIA), all performed with the same monoclonal antibodies (MCA) directed against human follicle-stimulating hormone (hFSH). The lowest detection limit (2 ng/L for hFSH-I-3, corresponding to 2.5 mIU of 1st International Reference Preparation of hFSH 78/549 per liter), the widest measuring range (2-160,000 ng/L), and the greatest signal-to-noise ratio (13,000:1 at 160,000 ng/L) were obtained in the IFMA. For analysis of serum samples from 101 male (ages 2-91 years) and 99 female (ages 2-90 years) individuals at a single dilution, 100% of samples were within the measuring range of the IFMA, whereas only 87%, 55%, 32%, and 8% of the sera were for the IRMA, the IEMA evaluated with double-wavelength measurement, the conventional IEMA, and the competitive MCA-based RIA, respectively. These studies demonstrate clear advantages of the IFMA in sensitivity and assay range, which allows reliable and cost- and time-effective determination of hFSH in individuals from infancy to senescence.

Adolescent↗

Does tumor-derived human chorionic gonadotropin act as a thyroid stimulator in vivo?

To evaluate in vivo the proposed intrinsic thyroid-stimulating hormone (TSH) activity (TSA) of human chorionic gonadotropin (hCG), we monitored over 0.5-1 years the thyroid status of eight patients with hCG-producing non-seminomatous testicular cancer. The patients' sera were analyzed for concentrations of hCG, free thyroxine (fT4), hTSH, and thyroxine-binding globulin (TBG). All patients had excessively high concentrations of hCG (1 x 10(5)-5 x 10(8) ng/L, mean: 1 x 10(7) ng/L) before polychemotherapy, which decreased under successful therapy to physiological values (< 240 ng/L). Although the serum concentrations of hCG varied by more than six orders of magnitude, we saw no changes and no correlation (P > 0.05) between the concentrations of hCG and the concentrations of fT4 and hTSH. Not even when hCG concentrations were greatest (> 5 x 10(7) ng/L) were any signs of hyperthyroidism observed: fT4 (3.5-13 ng/L) and hTSH (9-700 ng/L) were in the physiological range in all patients and remained so during chemotherapy. The results of this longitudinal study were confirmed in analyzing the data for all eight patients (total: 82 samples) cross-sectionally. Again, we found no correlation (P > 0.05) between the concentrations of hCG and fT4 or hCG and hTSH. We conclude that even excessive amounts of testicular tumor-derived hCG do not display any TSH-like activity in vivo.

Chorionic Gonadotropin↗

A high-density-lipoprotein receptor appears to mediate the transfer of essential fatty acids from high-density lipoprotein to lymphocytes.

It has been shown previously that a specific high-density lipoprotein (HDL) receptor exists on human lymphocytes that recognizes apoprotein (apo) A1 as its ligand, and may be responsible for utilization of HDL lipids to respond optimally to mitogenic stimulation when cultured in serum-free medium supplemented with HDL. To clarify further the relationship between various HDL lipids used by lymphocytes and HDL receptor activity, the lipid composition of the cells and the regulation of HDL and low-density lipoprotein (LDL) receptors on freshly isolated lymphocytes and mitogen-activated T-blasts after treatment with lipoproteins, liposomes or fatty acids were investigated. Our data show that the linear increase in cell proliferation correlates with the presence of HDL in fatty-acid-free culture medium in the concentration range of HDL receptor saturation. Decreased binding/uptake of dioctadecylindocarbocyanine (DiI)-fluorescence-labelled HDL by freshly isolated lymphocytes was observed in the presence of unlabelled HDL in 4-day culture, whereas T-blast binding/uptake was down-regulated by preincubation not only with HDL but also with LDL. T-blasts pretreated with HDL showed increased cellular contents of phosphatidylcholine, oleic acid (C18:1,n-9) and linoleic acid (C18:2,n-6), which are essential for optimal proliferation of mitogen-stimulated lymphocytes. Furthermore, DiI-HDL binding on lymphocytes was down-regulated by up to 20% (resting T cells) and 50% (T-blasts) when cultured in the presence of apoA1-phosphatidylcholine liposomes (T-blasts only), oleic acid or linoleic acid, but not by stearic acid (C18:0). The results indicate that HDL provide lymphocytes with essential fatty acids, which in turn regulate HDL receptor activity.

Adult↗