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The release of luteinizing hormone from pituitaries perifused with thymic extracts.

Medium obtained by the perifusion of fragments of adult male CSE rat thymuses stimulates the release of luteinizing hormone (LH) from the anterior pituitary gland in vitro. The release of the stimulatory factor/s from the thymus appears to be stimulated by the depolarizing concentration of K+ and to be Ca++-dependent. Perifusates from heart, liver and spleen did not elicit the response suggesting that the effect is specific to the thymus gland. Neither LH nor its releasing hormone, LHRH, were detectable in the thymus perifusates by RIA. Levels of facteur thymique serique (FTS), as measured by bioassay are highest in K+ stimulated fractions that exhibit the greatest LH releasing activity. In separate experiments in vitro FTS, but not two other thymic peptides, thymopoietin and thymosin alpha 1, caused a dose-related release of LH from pituitary tissue. That ability of thymic perifusates to cause the release of LH was age-related because tissue from neonatal and ageing males failed to release compounds with any significant effect on the pituitary release of LH. However, when the thymus was enlarged in ageing rats as a result of orchidectomy 1 month before sacrifice LH release was similar to that observed in young male adults.

Aging↗

Botanical biocides. 4. Mosquitocidal activity of certain Thymus capitatus constituents.

Successive extraction of Thyme plant, Thymus capitatus (L.) Hoffm. and Link (Lamiaceae), by different solvents of increasing polarity, showed that potency was highly attributed to the non-polar fraction (e.g., petroleum ether) when tests were carried out against the larvae and adults of Culex pipiens (L). Of special concern to the mosquitocidal activity, the following fractions and isolates were recognized: the volatile oil, unsaponifiable portion, and certain compounds isolated from the unsaponifiable portion (e.g., Thymol, alpha-Amyrin, Carvacrol + beta-Caryophyllene). The volatile oil, Thymol, and the unsaponifiable portion proved high larvicidal potency against the tested insect (LC50 = 49.0, 58.0, and 100.0 ppm, respectively). Non-lethal concentrations of these substances synergized the toxicity of Malathion, while induced additive or antagonistic effects when mixed with Permethrin or Pirimiphos-methyl. The unsaponifiable portion and volatile oil showed the highest adulticidal potency (LC50 = 0.0070 and 0.0076 mg/cm2, respectively). The efficacy of the tested candidates as repellent agents was found in the following order: unsaponifiable portion > alpha-Amyrin > Thymol > volatile oil > Carvacrol + beta-Caryophyllene. Thymol as well as volatile oil affected egg hatchability, causing Sterility Indices accounting for 0.70 and 0.74, respectively, while the unsaponifiable portion showed lower degree of sterility (0.81). The results obtained in this study may shed light on the importance of T. capitatus as a probable source of some biologically active agents for mosquito control in the future.

Animals↗

Isolation of a thymocyte growth peptide from human thymus.

A thymocyte growth peptide (TGP), recruiting immature thymocytes into the S phase without affecting immunologically mature thymocytes or peripheral T cells, has previously been purified from bovine and rodent thymus. We now report the isolation of a corresponding human activity. Aqueous extracts of human thymus were found to stimulate the DNA synthesis of human thymocytes in vitro. Homogenates of suspended thymocytes displayed higher activity than extracts of intact thymus, whereas extracts of thymic stroma depleted of thymocytes contained much weaker activity. The results indicate the existence of a human TGP originating from the thymocytes and not from the stroma, implying an autocrine or paracrine growth regulation. Human TGP was purified from a formic acid extract of human thymus and found to have a molecular ratio between 1,000 and 2,000 and an isoelectric point of 4.5-4.9. The results demonstrate the existence of a human TGP similar but not identical to bovine TGP and it is proposed that this peptide acts as a progression factor for the intensely proliferating immature cortical thymocytes.

Chromatography, Gel↗

The role of Wobe-Mugos in reducing acute sequele of radiation in head and neck cancers--a clinical phase-III randomized trial.

Oral enzymes act as a potent antiinflammatory, antiedematous agents thereby decreasing acute toxigenic effect of radiation and increasing compliance, quality of life of our patients. Fifty patients were randomized 25 allocated in enzyme and radiotherapy arm, 25 in radiotherapy alone. Pre RT and post RT biopsies were taken from both arms. In our study it was found that there was clinical, histopathological as well as statistical significant difference in both arms. The enzyme arm patients had mucostis of grade I in 76%, grade II in 12%, grade III in 8% while as 8% had grade I, 68% grade II, 24% had grade III in RT arm alone. In enzyme patients skin reactions of grade I in 72%, 20% had grade II, 8% had grade III. In control arm 12% had grade I, 76% had grade II, 8% had grade III skin reaction.

Acute Disease↗

[The favorable effect of hydrolytic enzymes in the treatment of immunocytomas and plasmacytomas].

At present attention is focused on research of biomodulating influences on tumorous processes, in particular inhibition of metastatic spread of tumors. In the aetiopathogenesis an important part is played by immune complexes, interaction of cytokines. The authors tested the supporting effect of hydrolytic enzymes in plasmocytoma and immunocytoma. The enzymes were administered along with cytostatic preparations according to the MOCCA pattern. They recorded a more rapid onset and longer persistence of remissions, a marked decline of total proteins, paraproteins, beta-2-microglobulin. Complications associated with paraprotein (hyperviscosity syndrome, nephrotic syndrome, peripheral angiopathy) improved. A combination of chemotherapy and enzymatic treatment proved effective and suitable, in particular for patients with interferon intolerance.

Chymotrypsin↗

Some endocrine aspects of the thymus gland.

In studies of the mouse thymus, lymphocyte mitoses are seen to be most frequent in the thymus cortex. There is evidence from thymic grafts that a hypothetical factor, thymopoietin, may stimulate mitosis of thymic lymphocytes. It is a factor which is postulated to act in conjunction with the PAS-positive mesenchymal reticular cells and epithelial reticular cells of the cortex. The thymus medulla is necessary for the integrity of thymic grafts, and may also elaborate a secretion for maintaining the cellular functions of the gland. Thymectomy has been used as a gauge for judging normal thymic function and results, in the mouse, in lymphopenia, degeneration of spleen and lymph nodes, delayed rejection of skin allografts, reduced ability of spleen cells to mount the graft versus host reaction, and reduced primary immune response to certain antigens. Correction of these deficiencies offers a means of evaluating various thymic extracts and grafts. Lymphocytosis-stimulating hormone (LSH) is known to maintain the peripheral lymphoid organs and cause lymphocytosis in the thymectomized animal. Diffusion chamber studies of thymic grafts also show restored lymphoid tissue by a cell-free factor (CIF). These two factors may be the same and probably represent the basis of the highly purified lymphocyte-stimulating proteins, LSHr and LSHh, which restore the L/P ratio in thymectomized animals and may stimulate lymphopoiesis in spleen and lymph nodes. LSHr, unlike LSHh, increases the total lymphocyte count. LSHr has been found to increase the humoral antibody response in neonatal mice both by the PFC technique and by direct hemolysis of sheep erythrocytes. Homeostatic thymic hormone (HTH) is a thymic extract of small molecular weight and contains nucleic acid. In the thymectomized guinea pig it has been found to maintain normal levels of lymphocytes in the blood, spleen and lymph nodes, to restore antibody titers to typhoid H antigen and to restore the toxic allergic reaction. Thymic humoral factor (THF) is of smaller molecular weight (less than 1,000) and probably is not a protein. It also enhances lymphoid proliferation in neonatally thymectomized mice. There is evidence that THF participates in humoral antibody formation because it stimulates PFC formation from neonatally thymectomized mice after inoculation with sheep erythrocytes. Its effects on cell-mediated immunity are seen from findings that injection of THF restores the ability of thymectomized mice to reject skin allografts. THF enables spleen cells from thymectomized or neonatal animals to mount the graft versus host reaction, and causes maturation of bone marrow cells and spleen or lymph node cells so that they can participate in the graft versus host reaction. It has been reported to stimulate lymphocytes to kill isogeneic tumor cells in vitro. Thymosin is protein extracted from the thymus. It has been found to alleviate leukopenia slightly and provide some improvement in lymphoid histology in thymectomized mice...

Aging↗

Intracellular events involved in the induction of immune competence in lymphoid cells by a thymus humoral factor.

A humoral factor extracted from calf thymus (THF) restores the immunocompetence of spleen cells from neonatally thymectomized (NTx) mice to induce an in vitro graft-vs-host (GVH) response. This acquistion of immunocompetence consists of a series of biochemical events, the first of which involves an obligatory rapid increase in adenyl cyclase acitivity and in intracellular levels of cyclic AMP. Protein synthesis occurs as a further step in the events leading to induction of immunocompetence by THF and could be blocked by cycloheximide with the consequent abolishment of the immunocompetence of the lymphoid cells tested. The induction of competence by THF is accompanied by a simultaneous reduction in DNA synthesis resulting from the increase in intracellular cyclic AMP levels. These steps have been studied in the absence of antigenic stimulation which is not required for the induction of competence by THF. Spleen extracts prepared by a similar procedure as THF were found to be devoid of the properties described above.

Adenosine Triphosphate↗

[Palatine tonsils and immunity. VI. Effect of thymosin and palatine tonsil extract on the immunologic reactivity of neonatally thymectomized and intact mice].

Experiments were conducted on Wistar rats, intact and neonatally thymectomized CBA mice; a study was made of the immunological activity of the extracts of the thymus and the palatine tonsils of calves obtained by the method of Goldstein et al (1966). The extract of the palatine tonsils obtained proved to contain a small amount of thymosin at whose expense an insignificant restoration of immunological reactivity occurs in its administration neonatally to thymectomized mice.

Animals↗

[Specific substances of the thymus reacting with thymus-dependant antigens].

A fraction was isolated from the sulphate extract of rats and calfs thymus. This fraction reacts with sheep erythrocytes and rabbits IgG in the agglutination test. An identical fraction from the rats spleen and liver is not active in the same concentration. Active substance was purified by affinity chromatography on IgG cellulose column. The absorption spectrum of the purified substance in 220-300 nm region was studied at pH 7. This substance has not the absorption maxima in 280 nm. The sedimentation constant of the crude preparation is approximately 1.7 s. It supposed, that this substance is a specifical receptor of thymic cells.

Animals↗

Immunosuppressive factor(s) specific for L-glutamic acid50-L-tyrosine50 (GT) II. Presence of I-J determinants on the GT-suppressive factor.

The responses to the synthetic antigens, L-glutamic acid(60)-L- alanine(30)-L-tyrosine(10) (GAT) and L-glutamic acid(50)-L-tyrosine(50) (GT) are controlled by genes in the I region of the mouse H-2 complex (1-3). Preimmunization of the mice bearing the H-2(p,q,s) nonresponder haplotypes with GAT stimulates the development of suppressor T cells that inhibit in vivo or in vitro antibody responses to GAT complexed to the immunogenic carrier, methylated bovine serum albumin (GAT-MBSA) (4). The copolymer GT is not immunogenic in any inbred mouse strain tested, and has a suppressive effect on the antibody responses to GT-MBSA in mouse strains bearing the H-2(d,f,k,s) haplotypes; suppressor T cells have been demonstrated to be responsible for specific GT suppression (3). We have obtained specific suppressive extracts from thymus and spleen cells of GAT-or GT-primed suppressor strains (5,6). The specific suppressive T-cell factors in the active extracts have been characterized (6,7) and appear similar to the carrier-specific suppressor factor described by Tada and Taniguchi (8). These products belong to a family of newly identified molecules coded for by the I region of the H-2 complex with affinity for antigen and helper (9,10) or suppressive (5-8) regulatory activity on the immune response. Recently, Tada et al. have reported that the keyhole limpet hemocyanin (KLH)-specific suppressor factor is coded for by the I-J subregion of the H-2 complex (11). We now demonstrate also that a GT-specific suppressor factor extracted from the spleens and thymuses of B10.BR (H-2(k)) mice bears determinants controlled by the I-J subregion of the H-2 complex.

Alanine↗

Proteinases reduce metastatic dissemination and increase survival time in C57Bl6 mice with the Lewis lung carcinoma.

The effect of combined proteolytic enzymes, administered by the rectal route, on the metastatic process and the time of survival in C57Bl6 mice with the Lewis lung carcinoma inoculated subcutaneously was investigated. In the control group, which received no enzyme treatment, 90% of animals died of the metastatic spread of cancer by day 18 after primary tumor extirpation. In Group A, which received the multi-enzyme solution from the time of primary tumor extirpation, 30% of mice died of disseminated cancer by day 25. In Group B, which was treated with the enzymes from 6 days before primary tumor extirpation, only 10% of animals showed the metastatic process by day 15. In Group C, which received the enzymes from 24 hours after intracutaneous tumor inoculation, no metastatic dissemination was discernible. In these three groups, the enzyme treatment was carried out throughout the study. None of the control animals survived for 100 days when the study was ended. The treated groups A, B and C showed survival rate 60%, 90% and 100% of animals, respectively, by 100 days.

Administration, Rectal↗

[The effect of the preparation Wobe-Mugos E on the functional and biochemical status of the kidneys in the polyuric stage of sublimate-induced nephropathy].

The protective effect of Wobe-Mugos appliance on the kidney function and biochemical state in polyuric stage of sublimate nephropathia at the moment of tubulointerstitial component formation was revealed in experiments on 40 white male rats. It appeared in the increase of hydrogenous ion excretion, titred acids, renal tissue fibrinolytic and proteolytic activity. The succinatdehydrogenase activation in renal cortex matter pointed out on the improvement of energy balance.

Animals↗

[Modification of liver parameters by adjuvant administration of proteolytic enzymes following chemotherapy in patients with ovarian carcinoma].

In a single-blind placebo controlled trial with 3 parallel groups the effects of concomitant administration of proteolytic enzymes (either tablets or dragees) on the influence of the liver parameters to a carboplatinum chemotherapy were investigated. 59 female patients were enrolled into this study after ovarial cancer surgery. Out of these 59 patients 23 were allocated to the placebo group, 24 to the tablet form and 12 to the dragees preparation. The study medication was administered from day 2 to 7 after each of the 6 chemotherapy cycles in monthly intervals in a dosage of 2 tablets t.i.d. placebo, 2 tablets t.i.d. Wobe-Mugos and 10 dragees t.i.d. The main efficacy criteria for the adjuvant study treatments were SGOT, SGPT, Gamma-GT, alkaline phosphatase and lactate dehydrogenase. The data of these parameters indicate an overall beneficial effect in patients in both of the verum groups compared to placebo and provide--in combination with other safety data documented in this study--evidence, that the concomitant administration of Wobe-Mugos does not negatively affect the overall tolerability.

Adolescent↗

Detection of human-specific anti-la(SSB) antibodies in patients with rheumatoid arthritis.

Sera from anti-Ro(SSA) positive and negative patients with rheumatoid arthritis (RA) were compared with those from patients with primary Sjogren's syndrome (pSS) and systemic lupus erythematosus (SLE) with regard to anti-La(SSB) antibodies. Several assays for anti-La(SSB) (RNA precipitation, counterimmunoelectrophoresis, and immunoblotting) demonstrated the presence of such antibodies in selected anti-Ro(SSA) positive (10/19 in RA and 18/37 in pSS and SLE) but not in anti-Ro(SSA) negative sera. In agreement with previous reports, anti-La(SSB) antibodies from pSS and SLE patients uniformly reacted with various cellular extracts used as sources of La(SSB) antigen, including extracts from human cultured cells (HeLa), calf thymus and rabbit thymus. In contrast, while all 10 anti-La(SSB) sera from RA patients reacted with the human HeLa cell extracts, only three of them also reacted with calf and rabbit thymus extracts. These results were further supported by the analysis of a cohort of 70 consecutively selected sera (displaying monospecific anti-Ro(SSA) reactivity against calf thymus extract) from patients with various rheumatic disorders, where human-specific anti-La(SSB) were detected in two out of the five of RA patients studied.

Animals↗