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Clinical impressions on the treatment of multiple sclerosis with thymus factor.

Nonspecific stimulation either with unfractionated thymus factor (TF) or fractions IV and VIII of TF was carried out in 13 patients with clinically definite multiple sclerosis (MS). Thymus hormones were given in a daily dose of 10 mg from 1 to 14 months. Three patients became non-tolerant to TF and were undergoing the treatment with TF IV or TF VIII. After immunostimulation 8 remained unchanged, 2 slowly improved (by one degree in Kurtzke's scale), 2 markedly worsened and 1 died. Five patients suffered 8 relapses, 3 showed slow progression and 2 developed either acute nephropyelitis or periodontitis. During this brief therapy, no convincing conclusion may be drawn regarding the effect upon the clinical course, although there is suggestion that thymus factor does not abolish the relapses in multiple sclerosis.

Adult↗

The reaction of human SLE antibodies with native, single stranded RNA: analysis of nucleotide sequence specificities and correlation with Sm and nRNP activities.

The antigenic specificities of RNA reactive IgG autoantibodies from three individual human SLE sera and pooled NZB/NZW mouse serum were studied by competition reactions with synthetic co-polymers and heteropolymers of varying nucleotide compositions. Although minor differences in the individual binding patterns were noted, the RNA reactive immunoglobulins showed a clear preference for G, C and G,C,U containing RNA sequences. All three SLE sera had Sm or RNP activities with rabbit thymus extractable nuclear antigen (ENA). Conversely, all SLE sera that were selected on the basis of their positive ENA reaction could also bind free, single stranded RNA. These results suggest that the autoimmune response to RNA in human and murine SLE is restricted to one or a very few antigenic determinants. They also raise the possibility that autoantibodies to native RNA in SLE sera are partly responsible for ENA reactivity.

Antigen-Antibody Complex↗

[Correction of the T immunological system deficit in experimental and clinical tuberculosis].

Thymus grafts, in semi-permeable chambers, from 7-10 day old white rats to guinea-pigs infected with M. tuberculosis, or to white rats that had underwent thymectomy and had been infected, is accompanied by a considerable decrease in the severity of the tuberculous process. A similar effect is obtained by the subcutaneous injection of a thymus preparation called Timalin. The addition to etiotropic therapy of the immunostimulant Levamisole in amounts of 2,5 mg/kg of body weight in white rats, and of 25 mg/kg of body weight in guinea-pigs, three times during a decade significantly enhanced the effect of the conventional therapy. Levamisole, when included in the complex therapy of tuberculosis patients (three times during a decade), accelerated the detoxification process, and the recovery of recent destructive lesions in the lung. In animals and in patients Levamisole increases the low activity of the T-lymphocytes immune system, as is indicated by data obtained with the leucocyte migration inhibition test, and with the rosette-formation test.

Animals↗

The lymphocyte activity of adenosine deaminase and enzymes of AMP metabolism in mammary carcinogenesis: the effect of thymostimulin.

Studies were undertaken on the activity of adenosine deaminase (ADA) and metabolic enzymes of AMP in the spleen and thymus cells of rats with DMBA-induced carcinogenesis of the mammary glands and on the effect of thymostimulin (TS) on this activity. In addition, we investigated the activity of ADA in the peripheral blood lymphocytes of the patients with premalignant diseases and cancer of the mammary glands (Stages I-IV) as well as the possibility of its enhancement by TS. The disturbances of these enzyme activities characterized by a decrease in ADA activity and an increase in activity of the AMP metabolism enzymes, predisposed for adenosine accumulation in lymphoid cells. Injection of TS normalized the ADA activity and decreased the activity of the AMP metabolic enzymes. Analogous results were obtained in the studies of ADA activity in the human materials. With the human tumor growth the in vitro effect of TS on the lymphocyte ADA activity decreased. We may suggest that measurement of the ADA activity in the lymphocytes may serve as a reliable tool to control the state of immune system and the effectiveness of immunotherapy with the thymic humoral factors.

5'-Nucleotidase↗

Antibodies against distinct nuclear matrix proteins are characteristic for mixed connective tissue disease.

Specific nuclear proteins, separated according to their molecular weight (mol. wt) by polyacrylamide gel electrophoresis (PAGE) and subsequently transferred to nitrocellulose sheets, are able to bind antibodies in sera from patients suffering from different types of connective tissue diseases. Antibodies against a characteristic set of nuclear protein antigens are found in sera from patients with mixed connective tissue disease (MCTD). Screening of 21 MCTD sera revealed a typical immunoblot pattern with major protein antigens of mol. wt 70,000 (20/21) (not identical with the Scl-70 antigen characteristic for scleroderma), mol. wt 31,000 (17/21), two proteins around mol. wt 23,000 (15/21) and two around mol. wt 19,000 (10/21). The 70,000, 23,000 and 19,000 antigens appeared to be rather insoluble nuclear proteins (i.e. components of the nuclear matrix). On behalf of their structural character they were present in nuclei from several types of cells but only in low amounts detectable in salt extracts of thymus acetone powder. The presence of antibodies directed against the mol. wt 70,000 antigen correlated strongly with the diagnosis of MCTD. This 70,000 antigen is not identical with the RNP antigen, a soluble ribonuclease sensitive ribonucleoprotein, since antibodies against nuclear RNP can be separated from anti-nuclear matrix antibodies by affinity chromatography using immobilized thymus salt extract. The distinct character of soluble nuclear RNP and structural nuclear matrix antigens is further supported by the fact that from 14 other anti-RNP sera obtained from patients with systemic lupus erythematosus (SLE), only three contained antibodies against the mol. wt 70,000 protein. Since the immunoblot pattern obtained with MCTD sera mostly was clearly distinguishable from the patterns obtained with sera from patients with related connective tissue diseases our results suggest that the immunoblotting technique might be useful as a diagnostic tool and support the concept of MCTD as a distinct entity.

Antibodies, Antinuclear↗

[Thymic hormones. Neuroendocrine interactions and clinical use in congenital and acquired immune deficiencies].

The epithelial cells of the thymus synthesize at least 30 different polypeptides: the thymic hormones. The structure of 4 of them is well known. They are named thymosin alpha 1, thymopoietin, thymulin and thymic humoral factor. Biological functions and secretion regulation of thymic hormones are described as well as the interactions between brain, thymus and endocrine glands. Blood levels and clinical usefulness of thymic hormones are reviewed in different congenital or acquired immunodeficient states and in autoimmune diseases.

Acquired Immunodeficiency Syndrome↗

[Effect of T-activin on peripheral immunity organs in intact and thymectomized mice].

Morphometry of the spleen, axillary lymph nodes and cytological assay of the bone marrow and peripheral blood were performed in (CBA X C57BL)F1 mice 1, 5, 10 and 15 days after subcutaneous injection of 0.5 microgram T-activin to intact and thymectomized (when adult) mice 2 months after operation. It was demonstrated that in intact animals, injection of T-activin stimulated the whole system of immunogenesis. The time course of plasmatization and the response of the germinative centers differing from that seen during antigen administration suggests that T-activin is not immunogenous, acting as a stimulant of the previous immune responses. The permanent amount of the degenerating cells attests to the lack of the toxic drug effect.

Animals↗

[Effect of T-activin on thymus involution in mice].

The effect of T-activin on thymus involution in mice was studied. T-activin in a dose of 1.0 micrograms/mouse was injected into young male (CBA X C57BL)F1 mice weighing 24.0 +/- 2.0 g daily for 20 days. Morphometric analysis of the thymus was made 6 months after the treatment with T-activin was completed. It was found that T-activin induced the suppression of physiological involution of the thymus together with the enhancement of the processes of thymocyte transformation and proliferation.

Animals↗

[Effect of T-activin on thymocyte reproduction and migration].

Forty seven F1 (CBA X C57Bl) mice were used for quantitative morphologic examination of the thymus on 1, 5, 10 and 15 days after a single injection of 0.5 microgram T-activin, and injections of 0.1 microgram of T-activin once a day during 5 days. The number of transformed thymocytes and mitoses figures in cortex was found to be increased reaching a maximum at the 5th day as regards the magnitude and spreading. By the end of the research the number of transformed thymocytes and mitoses returned to initial values. There was a periodical (at the 5th and 10th days) 1 mm2 reduction in the number of thymocytes, an increase in the proportion of medullary thymocytes, reaching maximum at the 5th day, and a tendency towards the reduction of a relative area of the parenchyma. These indicators did not return to the initial values by the 15th days. However there was a tendency towards normalization. The conclusion is made about the stimulatory effect of T-activin on reproduction and migration of thymocytes.

Animals↗

[Effect of long-term administration of T-activin on the structure of the thymus].

Morphometry was used to study the effect of T-activin on the morphology of the thymus of (CBA X C57BL) F1 mice given 10, 15 and 20 injections of T-activin (1.0 micrograms i.p.). T-activin did not cause any pathological alterations in the thymus. Ten injections of T-activin activated the proliferation and migration of thymocytes from the thymus. Fifteen injections of T-activin eventuated in an increased surge of thymocyte migration from the thymus, whereas 20 injections gave rise to a new surge of proliferation and preparation or beginning of thymocyte migration from the thymus. It is concluded that prolonged injection of T-activin does not disturb the fluctuation pattern of thymus functioning but activates the transformation and migration of thymocytes.

Animals↗

[Pyoderma vegetans of facial orifices in T-cell immunodeficiency].

This is a report of a 24-year follow-up of a man now 33 years of age, who suffers almost continuously from severe inflammatory lesions of the lips, nose and eyelids, with increased susceptibility to respiratory infections since early childhood. The condition, previously described as "pyo-rhino-blepharo-stomatitis vegetans (McCarthy)", was treated with systemic corticosteroids and antimicrobial agents for years, but failed to improve until the immune status of the patient was checked after withdrawal of the steroids. T lymphocytes were found to be abnormal as to count in peripheral blood and various functional qualities determined in vivo and in vitro. For treatment, levamisole and thymopoietin pentapeptide (TP-5) were given. Subsequently each drug induced rapid and complete clearing of all lesions, but was followed by the recurrence of facial periorificial lesions after drug withdrawal. Change of the regimen by administering either inosiplex orally or commercial calf thymus extract parenterally, remained ineffective. During therapy with levamisole as well as TP-5, the number of T lymphocytes in peripheral blood normalized, yet impaired functions failed to improve. There was an elevated ratio of T-suppressor/T-inducer cells in blood using OKT antibodies. In vitro testing of different functions of polymorphonuclear leucocytes revealed normal results except for a slight decrease of chemotactic activity during levamisole. In view of the long clinical course, the mass of clinical and immunological data collected over decades, and the therapeutic results as a whole, the disease can be characterized as a peculiar type of pluriorificial pyoderma vegetans, caused by a distinct immunodeficiency of T lymphocytes.

Adult↗

Serial estimation of anti-RNP antibody titers in systemic lupus erythematosus, mixed connective tissue disease and rheumatoid arthritis.

Anti-nuclear ribonucleoprotein (RNP) antibody titers were estimated serially in 19 anti-RNP antibody-positive patients, which included 10 patients with systemic lupus erythematosus (SLE), 6 patients with mixed connective tissue disease (MCTD) and 3 patients with rheumatoid arthritis (RA). Counterimmunoelectrophoresis was used for antibody detection and a calf thymus extract was utilized as an antigen. Anti-RNP antibody titers in most patients with MCTD and RA did not fluctuate significantly, whereas those in patients with SLE fluctuated by more than a four-fold serum dilution. The anti-RNP antibody titers in SLE seemed to correlate with disease activity. Previous reports have stated that anti-RNP antibody titers do not fluctuate easily throughout the disease course. The present report shows that they do fluctuate in patients with SLE. The use of high dose of steroids in SLE might be responsible for the fall in antibody titer.

Antibodies, Antinuclear↗

[Physiological dependency between the hypothalamus and the thymus in Wistar rats. III. Hypothalamic cells cultured in vitro in the presence of Thymus Factor X (TFX) and fresh thymus filtered homogenate].

The studies were carried out on the hypothalamic cells cultured in vitro in the presence of low-molecular proteins (constituting the control): the thymic hormone, known as Thymus Factor X [TFX]; or fresh thymus filtered homogenate prepared from the glands collected from 1 h or 7 d old rats. All the cultures were supplemented with 3H-thymidine. The experiments demonstrated that TFX in when added to the culture caused a decrease 3H-thymidine synthesis in comparison to the control. In other cultures, which were enriched with the fresh thymus filtrated homogenate, especially from 7 d old rats, a high level of thymidine synthesis in the cellular nuclei was observed.

Animals↗