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PubMed1985

Thymopentin structure and relation to thymic factors.

High-performance liquid chromatography (HPLC) was used to evaluate the purity and batch-to-batch consistency of four commercially available thymic extracts and thymopentin, the synthetic pentapeptide corresponding to the biologically active region of the thymic hormone thymopoietin. The thymus extracts were all extremely heterogeneous, differing one from the other. Additionally, they showed high batch-to-batch variation. In contrast, thymopentin was homogeneous and this homogeneity was consistent in different batches.

Animals↗
PubMed1986

Human chorionic gonadotropin binding to rat testis receptors is inhibited by a thymus factor.

An interrelationship between immune and reproductive systems has been postulated, and involves, among others, bidirectional effects between gonads and thymus. To this effect a rat thymus fraction of about 28000 mol wt has been reported to inhibit the effect of hCG on in vitro suspension of Leydig cells. We have investigated the antigonadotropin activity of thymus extracts on rat testis receptors. Acetonic powder obtained from thymus of 14 day-old rats was separated by molecular sieve chromatography. The effect of the collected fractions on the 125I-hCG binding to receptor sites in rat testes was evaluated. A fraction corresponding to 27000-28000 mol wt named thymus factor (TF), was found to inhibit the binding activity of 125I-hCG to its testicular receptor. The inhibitory effect of TF on hCG binding is dose related. By Scatchard analysis a competitive interaction at the receptor level between TF and hCG was demonstrated. The Ka values of hCG binding were diminished in the presence of TF while no significative changes were detected in the number of receptor sites. Present results strongly suggest a modulation function of TF at the testis receptor level.

Animals↗
PubMedDate not supplied

Immunological and patho-clinical observations of a patient with rectal carcinoma after long term administration of thymic extract (TFX).

TFX (Thymus Factor X) extract from calf thymuses, was given for the first time in Poland to the patient suffering from advanced rectal cancer with perforation to the peritoneal cavity, diffuse fecal peritonitis and multiple metastases to the liver. The immunological, clinical and histopathological observations of the patient for the period of 12 months of treatment are presented. The patient was given the biologically active thymus extract in the total amount of 14.2 mg in 34 subcutaneous injections initially in single dose of 0.1 mg and later on in amount of 0.5 mg. The remarkable restoration of the immunological reactivity of the patient from a total energy to the state of hyperreactivity has to be emphasized. It has been confirmed by the delayed hypersensitivity skin tests (Rt-23, PHA), the increase of the number of RFC (TEa and TEt rosette test with the SRBC), the diminishing of the autolymphocytotoxicity of the peripheral lymphocytes (evaluated by DTL) and also by the high level of the absolute number of circulating lymphocytes in the peripheral blood. The improvement of the clinical condition of the patient consisted in total regression of the inflammatory and functional changes in the respiratory and cardiovascular systems and also in the renal function. The regular rectal endoscopic examinations of the patient revealed the diminished size of the tumor and its unusual appearance described as an induration and sharp delimitation from the surrounding tissues. The histological examinations performed 5 times during the observation period of 11 months revaled the essential changes in the structure of the growth: the marked increase of the stroma with the signs of active proliferation, foci calcification and ossification. These changes were interpreted as extremely rare in the rectal cancer stroma and are considered to represent dystrophic calcification at the neoplastic foci followed by ossification. It should be also pointed out that twelve months survival of the patient with advanced rectal cancer and multiple metastases to the liver represents an unusually long rate in comparison to that generally accepted in the literature for this grade of rectal cancer advancement.

Adenocarcinoma↗
PubMed1975

Further purification of the lymphocyte inhibiting extract from the thymus.

A crude thymic extract, demonstrated to possess both immunosuppressive activity on T lymphocytes in vivo, and inhibitory action on DNA synthesis in T lymphocytes in vitro, has been purified by ultra-filtration and ion exchange chromatography procedures. The immunosuppressive activity was found to be associated with a high molecular weight fraction (greater than 50,000 daltons), devoid of immunosuppressive properties, a basic peptide has been isolated which retains the in vitro inhibitory activity on DNA synthesis.

Animals↗
PubMed1987

Description and partial characterization of a nucleolar RNA-associated autoantigen defined by a human monoclonal antibody.

B lymphocytes from a patient with systemic lupus erythematosus (SLE) and several circulating autoantibodies (including antinucleolar antibodies) were immortalized by fusion with a hypoxanthine/guanine phosphoribosyl transferase (HGPRT)-deficient human B cell line. Multiple human monoclonal antibodies (mAb) were obtained which, in solid-phase enzyme immunoassay, were reactive with DNA. One mAb was of special interest because it reacted strongly with both single-stranded DNA and an extractable nuclear antigen found in rabbit thymus extract (RTE). In an immunofluorescent assay using fixed human cells, the latter mAb also bound predominantly to cell nucleoli. A combination of enzyme digestion and metabolic inhibitor studies of the target cells in this immunofluorescent assay suggested that the antigen(s) bound by the mAb was an RNA-associated protein or a ribonucleoprotein that is distinct from intact RNA polymerase I and not associated with the transcriptional units of the nucleolus. In other experiments, using fractions of RTE isolated by ion-exchange chromatography, the antigens bound by the mAb were shown to be highly negatively charged molecules. Immunoprecipitation and SDS-PAGE analyses of labeled cell extracts bound by the mAb revealed a doublet of 17 and 18 kD. Since the original patient's serum autoantibodies also bound to both an RNase-sensitive, acidic, extractable nuclear antigen and to nucleoli, and immunoprecipitated proteins of similar molecular masses in SDS-PAGE, it appears that the described mAb is a product of an immortalized autoantibody-producing B cell clone from the SLE patient's peripheral blood. This mAb probably defines a novel RNA-associated autoantigen residing predominantly in the nucleolus or, less likely, a variant of either RNA polymerase I or the ribosomal autoantigens (P proteins).

Adolescent↗
PubMed1989

C-reactive protein reacts with the U1 small nuclear ribonucleoprotein.

C-reactive protein (CRP) was found to produce a small, discrete, speckled fluorescence pattern in the nucleus of HEp-2 cells. Double staining with anti-RNP serum and CRP produced very similar staining patterns. By counterimmunoelectrophoresis CRP was bound to extractable nuclear antigens found in rabbit thymus extract. The reactive components of the extract were only partially sensitive to treatment with RNase. CRP immunoprecipitated the U1 RNA species from [32P]labeled HeLa cells and the protein bands of the Sm/RNP complex from [35S]-methionine-labeled HeLa cells. By blotting, CRP bound to several discrete bands in a calcium-dependent, PC-inhibitable manner. Two of the bands comigrated with the 70K protein band associated with the U1 snRNP, and its major breakdown product. Binding to these bands was inhibited by both EDTA and PC indicating that CRP binds these proteins through the PC-binding site. Binding to the 70K protein of the U1 snRNP was confirmed by reactivity with the recombinant 70K protein in a dot blot. These findings indicate the CRP binds to the U1-RNP snRNP particle. Considering the ability of CRP to inhibit antibody responses to its ligands and its ability to activate C and promote phagocytosis it is suggested that CRP may play a role in the regulation of autoantibody responses to nuclear Ag.

Antigen-Antibody Reactions↗
PubMed1999

[Immunomodulating therapy of psoriasis vulgaris].

BACKGROUND: Newest studies have shown that psoriasis is not primarily a skin disorder but an immunological disturbance under the skin. The skin manifestations are a result of overstimulation of superficial skin cells (Langerhans cells) due to increased production of interleukin 2, 6 and 8 as well as transforming growth-factor-alpha. Interleucin-10 production is diminished. In a recent study (11 German University Skin Clinics) fumaric acid was shown to improve the skin leasons in 80% of treated patients. OWN EXPERIENCES: Our own studies on 54 patients which where treated in addition with intravenous thymus extract (Thymoject) and selenium (Selenase) showed a faster healing rate with fumaric acid alone. From these results one can postulate that the above treatments (fumaric acid, thymus and selenium) have a synergystic effect. CONCLUSIONS: Internal immunmodulating treatments should therefore have preference over external symptomatic treatments like UV-light, ointments, salt water bath, etc.

Administration, Oral↗
PubMed1975

The isolation of thymopoietin (thymin).

The isolation from bovine thymus of two closely related polypeptides, thymopoietin I and II, is described. These are considered to be thymic hormones, which physiologically induce the differentation of prothymocytes to thymocytes within the thymus. Ths isolation of the thymopoietins was monitored not by their differentiative effects, but by a presumably secondary effect on neuromuscular transmission. This was discerned in experimental studies related to the human disease myasthenia gravis in which it was suggested that autoimmune thymitis was regularly present. In an animal model, experimental autoimmune thymitis, the thymic disease was shown to result in the release of a substance that depressed neuromuscular transmission and this substance was shown to be also secreted in small amounts by the normal thymus. A bioassay was developed, this being the delayed appearance of neuromuscular impairment after in vivo injection of the active material, and this bioassay was used to monitor the fractionation of thymus extracts and isolate thymopoietin. Pure thymopoietin was active at subnanogram concentrations, both in producing its effect on neuromuscualr transmission and in inducing the differentiation of prothymocytes to thymocytes. This potency of activity of the purified polypeptide, as well as its specificity in inducing the differentiation of T-cells and not B-cells, support the consideration that thympoietin is a physiological inducing hormone produced by the thymus. This is further supported by the evidence that thymopoietin is only produced in the thymus: neuromuscular blocking effects are not present in extracts of other tissues and immunofluorescent localization of thymopoietin shows it to be present only in thymic epithelial cells.

Animals↗
PubMed1979

Immunologic and clinical investigation on a bovine thymic extract. Therapeutic applications in primary immunoedificiencies.

Thirteen patients with primary immunodeficiencies (eight with T-cell deficiency, one with Wiskott-Aldrich (W-A) syndrome, two with common variable agammaglobulinemia (CVA), and two with severe combined immunodeficiency (SCID) were treated with a calf thymus extract, called thymostimulin (TS). It has been shown that this extract causes in vitro differentiation of T-cell precursors in patients with T-cell defect. Five of eight patients with pure T-cell defect showed immunologic recovery and clinical remission lasting for several months after interruption of the therapy; one had only transient reconstitution, one had slight increase in T-cells (clinical conditions not yet estimated), and two patients soon died from severe infections after showing a slight increase of T-cells. Immune recovery was assess by an increase of the absolute number of E-rosettes forming cells, of human T-lymphocyte antigen positive cells and of PHA responsiveness in the peripheral blood, and by a positive delayed hypersensitivity reaction to antigens. In five patients, there was also B-cell increase after TS treatment. Clinical remission consisted of disappearance of infections, weight gain, and in improvement in general conditions. No effect was observed in one patient with W-A syndrome, in two with CVA, and in two with SCID. Several hypotheses on the mechanisms involved in immune reconstitution are discussed. It seems likely that TS acts on prethymic cells or on the epithelial cells of hypoplastic thymuses. TS was not effective, either in vitro or in vivo, in patients with SCID probably because of a defect in stem cells.

Agammaglobulinemia↗
PubMed1973

Immunotherapy of the Dunning leukaemia with thymic extracts.

Injections of thymic extract (TE), TE primed lymphocytes or normal lymph node cells were effective in bringing about total remission of the Dunning leukaemia in inbred Fisher CD rats. Survival greater than 365 days occurred in 10-80% of the various treated groups whereas untreated leukaemic rats, or leukaemic rats treated with spleen "mock thymus extract" or bovine serum albumin, died within an average of 10-17 days. Administration of antilymphocyte serum into leukaemic rats enhanced their death rate. Stimulation of cell mediated immunity via the production of functional thymus stimulated lymphocytes is postulated as the mechanism by which tumour rejection occurred.

Animals↗
PubMed1995

Antibodies to the extractable nuclear antigens (ENA) in Pakistani patients with systemic rheumatic disease.

Autoantibodies to the saline extracts of cells are being used as diagnostic and prognostic markers in the investigation of patients with suspected systemic rheumatic disease. These are also called antibodies to the extractable nuclear antigens or anti ENA antibodies. We used saline extracts of human spleen cells and rabbit thymus extract to detect six subtypes of anti ENA antibodies, namely anti SSA (anti Sjogren's syndrome A), anti SSB (anti Sjogren's syndrome B), anti RNP (anti Ribonucleoprotein), anti Sm (anti Smith), anti Jo-1 (anti Jo-1) and anti Scl 70 (anti Systemic sclerosis 70) antibodies. Two hundred and thirty-seven patients' sera were screened in the department of Immunology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, over a period of 16 months. Fifty-seven were positive for auto antibodies, of which 26 had anti SSA antibodies, 12 anti SSA+ anti RNP+ anti Sm antibodies, 7 anti RNP+ anti Sm antibodies, 6 anti SSA+ anti SSB antibodies, 5 anti SSA+ anti RNP antibodies while one patient showed only anti RNP antibody. The detection of the anti ENA antibodies was specially helpful in diagnosing patients with systemic lupus erythematosis presenting with atypical features and with mixed connective tissue disease.

Adolescent↗
PubMed1984

Precipitating antibodies to nuclear antigens in systemic vasculitis.

We have examined sera from 61 patients with systemic vasculitis for precipitating antibodies to components of saline tissue extracts. Precipitins were rare in patients with polyarteritis nodosa (PAN) and their absence helped to distinguish PAN from vasculitis associated with other connective tissue diseases. Precipitins were detected in some patients with other vasculitides. Previously described precipitating antibodies (anti-Ro [SSA] and anti-La [SSB]) were restricted to a few patients with features of systemic lupus erythematosus (SLE). A different, as yet unidentified, precipitin which reacted with a component of rabbit thymus extract but not calf thymus or human spleen extracts was detected in many patients with rheumatoid disease. This precipitin was present in all patients with active rheumatoid vasculitis (RV) as well as 52% of patients with uncomplicated but active rheumatoid synovitis. Higher titres of precipitating antibody were present in patients with active RV than those with inactive RV or uncomplicated rheumatoid synovitis, and serial studies showed a good correlation between a fall in antibody titre and healing of vasculitis with treatment. These studies suggest that this unidentified precipitin may be an important marker of RV.

Antigens↗