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The in vitro effect of a calf thymus extract (thymostimulin) on the immunologic parameters of patients with untreated Hodgkin's disease.

The in vitro effect of a calf thymus extract, thymostimulin (TP--1), on the E-rosette-forming capacity and on the PHA blastogenic response of peripheral blood lymphocytes was evaluated in 20 patients with untreated Hodgkin's disease. The mean percentage of lymphocytes forming E rosettes increased in patients from 44.2% to 57.5% (P less than 0.005). The mean PHA stimulation index rose with all three concentrations tested, but returned to the normal range only with the highest PHA concentration (60 mu/ml). An increase in the immune parameters was greatest in those patients who presented with decreased E-rosetting cells of total lymphocyte counts or whose disease was Stage III or IV or of mixed cellular histology.

Adolescent↗

The in vitro effect of a calf thymus extract (thymostimulin) on T cell phenotypes in cord blood lymphocytes.

An investigation was carried out on the in vitro effect of a calf thymus extract, thymostimulin, on the distribution of T cell phenotypes as defined by OKT3, OKT4, and OKT8 murine monoclonal antibodies and on E-rosetting cells in human cord blood lymphocytes from healthy newborns. The percentages of E-rosette-forming lymphocytes and OKT3+ total T population were lower in newborns than in adults (E-rosettes: 43.8% +/- 13% vs 57.9% +/- 7.9%, p less than 0.01; OKT3+ cells: 53.3% +/- 15.5% vs 79.9% +/- 4.7%, p less than 0.01), while the OKT4+/OKT8+ (helper/suppressor) cell ratio was normal in both (newborns: 3.40; adults: 2.44-NS). Thymostimulin increased the number of E-rosette-forming cells from 43.8% +/- 13% to 49.9% +/- 12.7% (p less than 0.01), as well as the percentage of phenotypic T lymphocytes. The highest increases were observed in the OKT4+ cells (37.7% +/- 14% to 49.1% +/- 13.8%, p less than 0.001), while smaller changes were observed in the OKT3+ cells (53.3% +/- 15.5% to 58.1% +/- 13.3%, p less than 0.02) and OKT8+ cells (12.8% +/- 6.4% to 16.6% +/- 6.5%, p less than 0.02). The results of the present study suggest that thymostimulin mainly provokes an increase in the helper T cell phenotype in cord blood lymphocytes.

Antigens, Surface↗

[A thymus extract (thymomodulin) in the prevention of childhood asthma].

41 children aged 2-12 years affected with bronchial asthma, have been treated orally with a thymus extract for three months (sep.-oct.-nov. 1980); a further period of treatment has been repeated during the month of March 1981. The following immunologic tests have been performed before therapy, 2 months after therapy withdrawal and 12 months after the second therapeutical discontinuance: plasmatic immunoglobulins (P. Ig), C3-C4 complement's factors, E-rosette forming cells (both active and total), surface immunoglobulins (IgS), PHA lymphocyte stimulation. Periodic anamnestic and clinical controls of patients revealed a significant reduction of asthmatic attacks during the months of observation, in comparison with the crises remarked in the same period of the previous year (the mean number of crises per child being 6 and 0.7 respectively before and after treatment, P less than 0.001). The immunologic tests, despite the clinical results, did not show significant modifications at the 1st control. Nevertheless the control carried out 12 months after the second therapeutical withdrawal demonstrated: IgG and IgM plasmatic levels significantly increased (1097 +/- 63 vs 906 +/- 45 and 122 +/- 10 vs 104 +/- 10 respectively, P less than 0.02) while IgE, C3-C4 plasmatic levels significantly decreased (232 +/- 57 vs 396 +/- 71, 132 +/- 6 vs 162 +/- 7, 22 +/- 2 vs 30 +/- 2 respectively, P less than 0.005). No side effects have been seen in all the patients treated.

Asthma↗

Steroid economising effects of a calf thymus extract in three patients with juvenile chronic arthritis.

Recent therapeutic trials in rheumatology using different immunomodulating agents have given encouraging results. In this study an aqueous calf thymus extract (CTE) was administered to three patients, two with systemic juvenile chronic arthritis (JCA), Still's disease, who could not be weaned from steroids during 2 years of conventional therapy, and one girl with a chronic juvenile monarthritis who had responded unsatisfactorily to nonsteroidal antirheumatics for 19 months. A striking clinical improvement was observed in all three patients. Prednisone (PRED) was discontinued in one case with systemic (JCA) and 0.25 mg/kg body weight/day is presently being given to the other patient. The girl is doing well on 4 mg chloroquin kg body weight/day; indomethacin (IND) was discontinued. Laboratory data including cellular immunoreactivity normalized in all three patients.

Animals↗

The effect of calf thymus extract (TFX) on human and mouse hemopoiesis.

The in vitro and in vivo effects of calf thymus extract (TFX) on mouse and human hemopoiesis were studied. TFX enhanced the growth of mouse T- and B-lymphocyte colonies when given in vitro and in vivo; in humans it increased the low colony formation typical for some blood donors failing to act on lymphocytes of high responders. TFX markedly stimulated colony-stimulating factor (CSF) production by human leukocytes presumably influencing the interactions between monocytes and lymphocytes. Although TFX did not affect the proliferation and differentiation of myeloid progenitors of bone marrow and peripheral blood, it strongly stimulated myelopoiesis in mouse and human spleen.

Animals↗

[Effect of calf thymus extracts on the surface structure and the lysosomal apparatus of lymphocytes in patients with chronic lymphatic leukemia].

In 6 patients with chronic lymphatic leukaemia receiving subcutaneously purified calf thymus extract a greater frequency of the following processes was observed: 1) increase in the number of smooth-surface lymphocytes (T cells) in scanning electron microscopy, 2) increased number of lymphocytes forming rosettes with uncoated sheep erythrocytes, 3) increased number of lymphocytes showing high activity of acid phosphatase in cytochemical investigations.

Acid Phosphatase↗

The in vitro effect of a calf thymus extract on the peripheral blood lymphocytes of patients with warts.

T and B lymphocyte populations were evaluated in forty-one patients with multiple recurring warts. Active rosettes (T-Ea) and total T lymphocytes (T-Et) were significantly decreased. The in vitro effect of a calf thymus extract (TP-I) on peripheral blood lymphocytes was evaluated in thirty-three patients. A statistically significant increase in E-rosette forming cells was observed in twenty-three patients (69%). Serum blocking factors were not found in the patients with a positive response to TP-I, which suggests the possibility of a thymic hormone deficiency. In the case of non-responders to TP-I, on the other hand, an anti-lymphocyte antibody capable of directly blocking the hormone receptors on the undifferentiated lymphocytes may be postulated.

Adolescent↗

A pilot study of thymus extract in chronic non-A, non-B hepatitis.

In previous studies it has been suggested that activation of cellular immunity may have a role in controlling the activity of chronic non-A, non-B liver disease. We conducted a pilot study of therapy with a bovine thymus extract for 6 weeks in 15 consecutive patients with chronic non-A, non-B hepatitis, most of them sporadic cases. Treatment induced immunomodulation, and in five patients a significant but transient diminution in aminotransferase levels was observed associated with increments in several parameters of cellular immunity. This suggests that a longer administration of this or other related compounds, or treatment with a more potent immunomodulating agent, might be effective in these patients.

Animals↗

Effect of DTC on humoral response of SRBC-immunized mice exposed to restraint stress. Comparison with calf thymus extract.

The studies were conducted on Balb/c mice exposed to restraint stress twice for 12 h at 24 h intervals. Some of the experimental mice were immunized i.p. with sheep red blood cells (SRBC). The antigen was injected before the first exposure of the mice to restraint stress, or immediately after the second loading was ended. Sodium diethyldithiocarbamate (DTC) at a dose of 20 mg/kg or calf thymus extract (TFX) at a dose of 10 mg/kg were injected i.p. four times at 24 h intervals, before or after the exposure to restraint stress. In our experiment restraint stress drastically reduced the number of thymocytes and splenocytes as well as the weight ratio of the thymus and spleen and the changes sustained for 10 days of the observation. Besides, humoral response of the restrained mice to SRBC was deteriorated, as the number of plaque forming cells (PFC) and anti-SRBC antibody titers (total and 2-mercaptoethanol resistant) decreased. The suppressive action of the stress on humoral response was weaker when the antigen injection preceded the first exposure of mice to restraint stress as compared with that observed when antigen stimulation took place immediately after the exposure of mice to stress. It has been found that DTC and TFX administered to mice either before or after the exposure to restraint stress effectively inhibit stress-induced immunosupression. The protective or immunomodulating action of the two drugs is expressed in accelerated and enhanced recovery of the spleen and thymus and in total or partial restoration of the humoral response to thymus-dependent antigen. TFX, administered after the exposure of mice to restraint stress, proves to have a stronger protective and reconstructive impact on thymus, while DTC has a stronger restoring effect on the humoral response dependent on effector T lymphocytes. DTC administered immediately after the exposure of mice to restraint stress results in total restoration of humoral response to SRBC.

Adjuvants, Immunologic↗

Restoration of cyclophosphamide-suppressed primary immune response in mice by Tołpa Peat Preparation (TPP)--comparison with calf thymus extract.

In order to induce pharmacological immunosuppression in Balb/c mice, the animals were given cyclophosphamide intraperitoneally, 200 mg/kg 144 hours or 24 hours prior to SRBC immunization. Tołpa Peat Preparation (TPP) was administered in doses of 10 and 50 mg/kg on the day of immunization and then every 24 hours for 3 consecutive days. It was given both to mice cyclophosphamide-treated and non-treated. Calf thymus extract (TFX) was administered (1 and 5 mg/kg) parallelly, for comparison with TPP. The following immunologic indices were determined: percent of splenocytes forming E- and EAC-rosettes, number of plaque-forming cells (PFC) and the levels of 19S+7S and 7S anti-SRBC haemagglutinins. The immunosuppressing action of a single cyclophosphamide dose decreased the percentage of EAC rosettes, number of PFC and serum anti-SRBC haemagglutinin titre. TPP is able to restore the percent of EAC rosettes, the number of PFC and anti-SRBC haemagglutinin titre, either partially or totally, after cyclophosphamide-induced immunosuppression. The effectiveness of TPP depends mainly on the dose and timing of cyclophosphamide administration prior to SRBC immunization. The most pronounced restoration of the cells in mice was observed with the TPP dose of 50 mg/kg after cyclophosphamide suppression 144 h before immunization. TFX (1 mg/kg) only partially restored the number of PFC and 7S anti-SRBC haemagglutinin titre, which had been depressed due to cyclophosphamide treatment 144 h prior to immunization. However, it did not change the depressing effect of cyclophosphamide on the percent of EAC rosette-forming splenocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Precipitating antibodies to rabbit thymus extractable antigens in chronic liver disease: relationship with anti-actin antibodies.

Using counterimmunoelectrophoresis (CIE), serum antibodies to rabbit thymus extractable antigens were detected in 15% (38/259) of patients with chronic liver disease (CLD) of various aetiologies and 33% (41/124) of patients with miscellaneous connective tissue diseases (CTD). A remarkable diversity of precipitating systems was apparent among cases with the two classes of disorders. All the five systems found in CLD (XR, XR2, SS-B, XR3, XR4) were associated mostly with immunological hepatic disorders. In the 52 autoimmune hepatitis cases, XR was mainly detected (29%), whereas in the 82 primary biliary cirrhosis patients the whole spectrum of reactivities was represented (XR: 11%, XR2: 10%, SS-B and XR3: 2% each, XR4: 1%). XR proved to be closely associated with smooth muscle antibodies (SMA, detected by indirect immunofluorescence on rat kidney sections) both qualitatively and quantitatively. Since all SMA positive sera with anti-actin specificity (SMAT, SMAG) were XR positive and purified actin could absorb out XR CIE reactivity, the hypothesis is made that a cross-reaction occurs between XR antigen and actin epitope(s).

Actins↗