Altered immunoendocrine dialogue in autoimmune disease.

Autoimmune diseases have a multifactorial pathogenesis including essential genetic and nonessential modulatory factors. Among the essential factors, not only should genes coding for an abnormal reactivity of the immune system be considered, but we have, in addition, provided experimental evidence for the existence of genes responsible for a susceptibility of the target organ/structure for the autoimmune attack. Only when both sets of essential genes are present does an autoimmune disease develop at all.

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).

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.

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.

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.

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.

[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.

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.

Investigation of ACTH responses of chickens with autoimmune disease.

An altered immunoendocrine feedback regulation within the hypothalamo-pituitary-adrenal axis may modulate the pathogenesis of an avian autoimmune disease. To date studies have been hampered by a lack of reliable, specific, and sensitive methods for determining adrenocorticotropic hormone (ACTH) in chickens. The present study describes the determination of ACTH in plasma of chickens with a commercial radioimmunoassay, the antibody of which binds to the midregion of human ACTH 1-39.

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.

Cultured fibroblasts in avian scleroderma, an autoimmune fibrotic disease, display an activated phenotype.

University of California, Davis, line 200 and 206 chickens spontaneously develop an autoimmune syndrome that has many features analogous to human scleroderma, including dermal fibrosis, antinuclear antibodies and antibodies to type II collagen. These birds also have thymic subcapsular epithelial defects and an abnormality in T cell calcium influx and proliferation in response to both T cell receptor-dependent and -independent activators. To determine whether fibroblast activation is a contributing factor to development of skin fibrosis in line 200/206 chickens, as it is in human scleroderma, we studied the collagen, non-collagenous protein and glycosaminoglycan (GAG) production of 34 separate fibroblast lines derived from the normal and fibrotic skin of line 200 and 206 chickens and from the skin of control chicken lines 058 and 254.

Lipid utilization by human lymphocytes is correlated with high-density-lipoprotein binding site activity.

The nature and physiological importance of high-density lipoprotein (HDL) binding sites on unstimulated (resting) and mitogen-activated (blast) human peripheral blood lymphocytes were investigated. Specific HDL binding on resting and blast T-lymphocytes was saturable at 50 micrograms of 125I-HDL/ml and of high affinity, with Kd values of 8.1 x 10(-8) M and 6.

Induction of arteriosclerosis in normocholesterolemic rabbits by immunization with heat shock protein 65.

Previous studies have established the presence of high numbers of activated T lymphocytes and "aberrant" expression of major histocompatibility complex class II antigens by endothelial and smooth muscle cells in human atherosclerotic lesions, implicating the involvement of a local cellular immune response. The identity of the antigen(s) eliciting this immune response, the extent of their effect, and the atherogenic stage at which they occur remain to be determined. In the present studies, 120 normocholesterolemic New Zealand White rabbits were immunized one or more times with various antigens, with or without adjuvants.

Avian scleroderma: evidence for qualitative and quantitative T cell defects.

T cell activation is dependent upon calcium influx and protein kinase C activation, with subsequent lymphocyte proliferation dependent upon IL-2. Abnormalities in T cell proliferation, including abnormal calcium influx and defective protein kinase C activation, have been identified in aged mice and humans and many autoimmune diseases including diabetes, lupus and scleroderma. Since UCD line 200 chickens, which spontaneously develop a scleroderma-like disease, have both thymic defects and a diminished peripheral blood lymphocyte response to IL-2, we have further investigated T cell function in these birds.

The role of the immunoendocrine interaction via the hypothalamo-pituitary-adrenal axis in autoimmune disease Emphasis on the obese strain chicken model.

The key to the molecular basis of the pathogenesis of autoimmune disease (AID) certainly lies in the identification of genes coding for the altered immune response and those responsible for the susceptibility of the target organ to the autoimmune attack. The elucidation of nonessential modulatory factors is, however, also of great importance, because it is via these routes that an effective AID therapy is practical at the present time. Hormones in general, and those affecting the hypothalamo-pituitary-adrenal (HPA) axis in particular, are among the best candidates for more rational new therapeutic approaches.

Free alpha-subunit, free beta-subunit of human chorionic gonadotropin (hCG), and intact hCG in sera of healthy individuals and testicular cancer patients.

To determine the serum concentrations of human chorionic gonadotropin (hCG), its free beta-subunit (hCG beta), and the free alpha-subunit (free alpha) common to all human glycoprotein hormones under physiological and pathological conditions, we developed monoclonal antibody-based immunoenzymometric assays. Free alpha-subunit was detected in the sera of all healthy individuals of both sexes; hCG was measurable in sera of 54% of the men, and 46% were positive for free hCG beta; in nonpregnant women, 69.5% were positive for hCG, 68.

Thymic nurse cell lymphocytes react against self major histocompatibility complex.

It has been postulated that thymic nurse cells (TNC), lymphoid-epithelial complexes composed of thymocytes enclosed within major histocompatibility complex (MHC) class I+ and class II+ cortical epithelial cells, may provide an optimal microenvironment for the process of T cell selection. By transplanting single TNC in the avian chorionallantoic membrane assay we demonstrate that a significant portion of intra-TNC lymphocytes (TNC-L) possess reactivity against self-MHC molecules. The frequency of these autoreactive cells among TNC-L exceeds by far that of thymocytes or peripheral blood lymphocytes of the same donor.

Complete clarification of a case of farmer's lung.

The diagnostic curriculum to clarify a case of farmer's lung in a fibrotic stage is presented, including clinical functional tests, X-ray, analysis of cellular elements recovered from bronchioalveolar lavage, determination of precipitating antibodies in the circulation, histological and immunohistological studies of transbronchial lung biopsies. The patient had precipitating antibodies against several species of hay molds, especially Micropolyspora faeni, and immune complex deposition in the lung. Elution experiments on frozen sections of the lung biopsies and subsequent administration of patient's serum- or mold antigen-specific antibodies combined with appropriate serum absorption experiments allowed the identification of the relevant antigen, i.

Effects of sex steroid analogs on spontaneous autoimmune thyroiditis in obese strain chickens.

Treatment of obese strain chickens, either in ovo or after hatching, with testosterone or various testosterone-derived steroid analogs having no or only weak endocrine activities causes significant protection from spontaneous autoimmune thyroiditis occurring in these birds. This effect is not correlated with the endocrinological properties of these steroids. This observation and similar results in other models for autoimmunity may present a basis for a more selective therapy in human autoimmune diseases in that hormonal side effects no longer preclude this approach.

Target organ susceptibility and autoantibody production in an animal model of spontaneous autoimmune thyroiditis.

F1-hybrids of Obese strain (OS) chickens, afflicted with spontaneous autoimmune thyroiditis (SAT), and normal, inbred CB chickens, do not develop severe thyroiditis. About 50% of these crosses show circulating autoantibodies to thyroglobulin (TgAAb), but the thyroid glands are only slightly infiltrated, suggesting that the target organ is not susceptible to autoimmune attack. In the present study we show that despite this mild infiltration TgAAb are only synthesized by lymphoid cells within the thyroid gland.

Human foamy virus antigens in thyroid tissue of Graves' disease patients.

Human foamy virus (HFV) is a recently characterized member of the retrovirus subfamily Spumaretrovirinae. HFV has a complex structure: it encodes the classical three retroviral structural genes gag, pol and env, but also possesses additional regulatory, so-called bel sequences. Foamy viruses have been discussed occasionally as being possibly involved in the pathogenesis of autoimmune thyroiditis.

Electron microscopy analysis of mineral fibers in human lung tissue.

In the present study, lung samples from 126 autopsied cases were examined to determine the content of mineral fibers using analytical transmission electron microscopy (ATEM). The cases were divided into four groups (22 lungs of persons exposed to ambient environmental pollution, 32 cases of mesothelioma, 38 cases of primary lung cancer, and 34 asbestosis cases, 13 of these with additional pleural plaques). Fibers were counted, measured, and mineralogically identified using a combination of X-ray microanalysis and electron diffraction of the non-oriented fiber.

[Asbestos content in bronchoalveolar lavage fluid].

The concentration and size distribution of bronchoalveolar lavage (BAL) asbestos fibers (AF) longer than 2 microns was determined by analytical transmission electron microscopy (TEM). The concentration of asbestos bodies (AB) was measured by TEM and light microscopy (LM). The study group consisted of 110 patients.

Correlation of lymphocyte lipid composition membrane microviscosity and mitogen response in the aged.

Healthy aged and young blood donors were investigated for the role of membrane lipid composition in the age-related increase in membrane microviscosity and decline of mitogen responsiveness. Membrane microviscosity was shown to correlate positively with membrane cholesterol/phospholipid molar ratios, which were significantly elevated in the elderly. A positive correlation also was confirmed between lymphocyte membrane microviscosity, which was measured using the probe 1,6-diphenyl 1,3,5-hexatriene, and phytohemagglutinin responsiveness of cells from the same donor.