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PubMed1990

Atrial natriuretic peptide in lymphoid organs of various species.

1. Evidence for the occurrence of atrial natriuretic peptide (ANP) in various lymphoid organs of different species (rat, mouse, pig, chicken) is provided. 2. ANP precursor material (1-126) as well the physiologically active ANP (99-126), were identified by chromatographic analysis and RIA in extracts of thymus, spleen and lymph nodes of rat, mouse and pig. 3. mRNA coding for ANP was demonstrated both in the thymus and in isolated thymocytes of these species. Furthermore, mRNA for ANP was detected in spleen and lymph nodes (rat and pig). 4. The bursa of Fabricius, thymus glands and spleen of chickens were also shown to express mRNA coding for ANP. 5. These findings provide a firm basis for a link of ANP to the immune system, a novel aspect of possible biological functions of this peptide.

Animals↗
PubMed1992

Use of a molecularly cloned human SS.B antigen to detect anti-SS.B antibodies.

The aim of this study was to examine the utility of diagnostic assays based on recombinant SS.B/La (rSS.B). Using this antigen, we have developed an ELISA and an immunoblot and compared these recombinant antigen-based assays with traditional thymus extract-based counterimmunoelectrophoresis (CIEP). Using the recombinant ELISA, the incidence of anti-SS.B in 184 normal blood donors was 2.2% (four sera). These four sera were all low titre, i.e., 3-5 SD above the mean. Of 38 sera positive for anti-SS.B by CIEP, 37 were positive in both recombinant assays (97.4% concordance). Anti-SS.B titre in CIEP correlated strongly with results of the rSS.B-based ELISA, but the ELISA was 3,000-fold more sensitive. In an analysis of 152 autoimmune sera containing anti-DNA, anti-RNP, anti-centromere, anti-SS.A/Ro or anti-cardiolipin, all of which were negative for anti-SS.B/La by CIEP, the recombinant assays detected 17 new anti-SS.B positives. These positive results were found only in sera which had previously been characterised by CIEP as anti-SS.A/Ro positive. Anti-SS.B/La antibodies detected by recombinant SS.B assays were found to be highly predictive of primary Sjögren's syndrome. Our results show that rSS.B can have an important role in the design of sensitive and specific assays for anti-SS.B. The diagnostic significance of anti-SS.B/La as a guide to primary Sjögren's syndrome is not diminished by the increased sensitivity of recombinant SS.B assays.

Antibodies, Antinuclear↗
PubMed1996

A randomised study comparing granulocyte-colony stimulating factor (G-CSF) with G-CSF plus thymostimulin in the treatment of haematological toxicity in patients with advanced breast cancer after high dose mitoxantrone therapy.

54 patients with advanced breast cancer were randomised into a prospective, non-blinded, controlled trial to receive: mitoxantrone 28 mg/m2 intravenous day 1 and granulocyte-colony stimulating factor (G-CSF) 5 micrograms/kg/day subcutaneously days 2 to 16 (n = 27) or the same regimen plus thymostimulin (TS) 50 mg/day intramuscular at days 2 to 16 (n = 27). The median time to reach a neutrophil count greater than 0.5 x 10(9)/l was lower in the G-CSF+TS treated group (9.13 versus 3.24 days; P < 0.0005). More patients experienced neutropenic fever in the G-CSF group than in the G-CSF+TS group (59.3% versus 22.2%, P = 0.0119). The incidence, duration and severity of clinically or bacteriologically documented infection were lower in patients who received TS. 16 patients (59.3%) in the G-CSF group contracted infection, and 4 patients (14.8%) receiving G-CSF+TS (P = 0.0016). These data indicate that the combination of G-CSF and TS is well-tolerated and may enhance haematological recovery following myelosuppressive chemotherapy in patients with advanced breast cancer.

Adult↗
PubMed2004

A nonradiometric, high-throughput assay for poly(ADP-ribose) glycohydrolase (PARG): application to inhibitor identification and evaluation.

The enzyme poly(ADP-ribose) glycohydrolase (PARG) catalyzes the hydrolysis of glycosidic bonds of ADP-ribose polymers, producing monomeric ADP-ribose units. Thus, in conjunction with poly(ADP-ribose) polymerase (PARP), PARG activity regulates the extent of in vivo poly(ADP-ribosyl)ation. Small molecule inhibitors of PARP and PARG have shown considerable promise in cellular models of ischemia-reperfusion injury and oxidative neuronal cell death. However, currently available PARG inhibitors are not ideal due to cell permeability, size, and/or toxicity concerns; therefore, new small molecule inhibitors of this important enzyme are sorely needed. Existing methodologies for in vitro assessment of PARG enzymatic activity do not lend themselves to high-throughput screening applications, as they typically use a radiolabeled substrate and determine product quantities through TLC analysis. This article describes a method whereby the ADP-ribose product of the PARG-catalyzed reaction is converted into a fluorescent dye. This highly sensitive and reproducible method is demonstrated by identifying two known PARG inhibitors in a 384-well plate assay and by subsequently determining IC(50) values for these compounds. Thus, this high-throughput, nonradioactive PARG assay should find widespread use in experiments directed toward identification of novel PARG inhibitors.

Animals↗
PubMed2005

Avian thymic hormone treatment of peripheral blood mononuclear cells from young chicks stimulates acute graft-versus-host reaction in chicken embryos.

Avian thymic hormone (ATH) is a parvalbumin produced by epithelial cells in the thymic cortex of chickens and circulates in the blood on a 5-day cycle. It stimulates precocious development of cell-mediated immunity. The effect of partially purified extracts of thymus (TE) and purified ATH were tested for their effect on the acute graft-versus-host reaction (GVHR). Treatment of chicks for their first 3-days of life did not enhance the acute GVHR produced by their PBMC in 14-day-old embryos. PBMC from 3-day-old chicks were treated in vitro with TE, ATH, thymosin fraction 5 or thymosin alpha1 for 2 h and injected into 14-day-old embryos. Bone marrow cells and thymic lymphocytes were treated with TE. Only PBMC treated with TE or ATH produced an enhanced acute GVHR. Because ATH targets gammadelta T cells, the data implicate participation of donor gammadelta T cells in the acute GVHR.

Animals↗
PubMed2004

Elevated caspase-3 and Fas mRNA expression in jejunum of adult rats during subclinical zinc deficiency.

The programmed cell death-so-called apoptosis-is a physiological process occurring in all multicellular organisms to control cell-number homeostasis. Nevertheless, increase of apoptotic cell death in different organs can lead to pathological alterations. As zinc is a potent inhibitor of apoptosis, we investigated the influence of zinc deficiency on mRNA expression levels of caspase-3 and Fas in adult rats. For this purpose, 24 adult rats fed a Zn-deficient diet for up to 29 days were compared to seven animals in the control group. After 1, 2, 4, 7, 11, 16, 22 and 29 days of treatment three animals were sacrificed (n = 24). Total RNA extraction from thymus, liver, jejunum and colon was carried out. Samples were reverse transcribed and subjected to real-time PCR. Relative quantification of caspase-3 and Fas mRNA expression was achieved on the basis of normalisation by glycerolaldehyd-3-phosphate-dehydrogenase mRNA expression levels in all samples. In jejunum, up to day 11 the relative mRNA expression of the respective genes decreased. A significant increase in caspase-3 and Fas expression was found from day 11 of zinc deficiency onward. In contrast, mRNA expression in liver and colon remained unaffected, whereas thymus showed a slight but not significant increase in the expression of these genes. This study provides the first evidence that even moderate zinc deficiency in an adult, non-growing rat model is able to elevate mRNA expression levels of factors involved in early stages of apoptosis.

Animals↗
PubMed2005

The effects of thyme volatiles on the induction of DNA damage by the heterocyclic amine IQ and mitomycin C.

The leafy parts of thyme and its essential oil have been used in foods for its flavour, aroma and preservation for many years. In the present study the genotoxic potential of major compounds of thyme oil, i.e. thymol, carvacrol, and gamma-terpinene and of the methanolic extracts of thyme, were investigated in human lymphocytes by single-cell gel electrophoresis. Also, the effects of these substances on the induction of DNA damage by 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ) and mitomycin C (MMC) were evaluated. No increase in DNA strand breakage was observed at thymol and gamma-terpinene concentrations below 0.1 mM, but at the higher concentration of 0.2 mM significant increases in DNA damage were seen. Thymol and gamma-terpinene significantly reduced the DNA strand breakage induced by IQ and MMC at the lower concentrations studied. Carvacrol, which is an isomer of thymol, seemed to protect lymphocytes from the genotoxic effects of IQ and MMC at non-toxic concentrations below 0.05 mM, but at the higher concentration of 0.1 mM carvacrol itself induced DNA damage. Also the constituents of the n-hexane and ethyl acetate fractions prepared from the concentrated aqueous methanolic extracts of Thymus spicata protected lymphocytes against IQ- and MMC-induced DNA damage in a concentration-dependent manner.

Alkylating Agents↗
PubMed2004

Experimental malignancy in the rat induces early hypersensitivity indicative of neuritis.

Cancer pain mechanisms involve multiple factors including the accompanying inflammatory process neural effects. Inflammation along a nerve trunk (neuritis) has been shown to induce hypersensitivity at the innervated target organ. In this experiment the neural effects of MAT B mammary adenocarcinoma cells implanted adjacent to sciatic nerve (MAT group) were compared to those induced by thymus cell extract (THY), saline (SAL) and the potent proinflammatory agent Complete Freund's adjuvant (CFA). Significant pain behavior was detected only in the ipsilateral hindpaw of MAT and CFA rats lasting seven days post-operatively (dpo). On the ninth dpo MAT rats developed significant hyposensitivity to mechanical and electrical stimuli. Interleukin (IL)-6 levels (ELISA) from MAT and CFA exposed nerves were significantly elevated at dpo 2 and remained so in MAT at dpo 8. Indomethacin (1 mg/kg i.p.) abolished the observed pain responses in MAT and CFA rats exposed nerves. Light microscopy of the MAT nerves at the second dpo revealed neural infiltration of immune and malignant cells with mild edema. By the seventh dpo there was nerve damage and at dpo 14 nerve tissue was largely replaced by malignant and immune cells. Electrophysiology of saphenous nerves exposed to MAT, CFA or SAL revealed significantly increased spontaneous activity in MAT and CFA groups. Spike response to hindpaw mechanical stimulation was significantly reduced only in the MAT group (dpo 6-9) suggestive of nerve damage. Inflammatory neuritis is an early expression of malignancy and may play a role in chronic cancer-related pain initiation and additionally may offer diagnostic opportunities.

Action Potentials↗
PubMedDate not supplied

Immunochemotherapy (thymostimulin/cyclophosphamide) in dogs.

This article demonstrates the positive effect of thymostimulin (TP-1) on leucolymphopoiesis in dogs, based on its apparent ability to counteract the immunodepression induced by cyclophosphamide chemotherapy. Thymostimulin administered to healthy cyclophosphamide-treated dogs prevented the initial drop in the values of leucocytes and lymphocytes due to the chemotherapy and restored these values to the higher levels existing before the treatment. In a control group given a placebo instead of TP-1, the immune depression provoked by cyclophosphamide was maintained during all the therapeutic cycles.

Animals↗
PubMed1989

Liquid chromatographic analysis of amino and imino acids in protein hydrolysates by post-column derivatization with o-phthalaldehyde and 3-mercaptopropionic acid.

A method for the simultaneous determination of imino and amino acids is reported. The method, based on the derivatization of amino acids, separated by ion-exchange chromatography, by reaction with alkaline hypochlorite and o-phthalaldehyde-3-mercaptopropionic acid, increases the sensitivity towards imino acids to the picomole level. The use of 3-mercaptopropionic acid gives intensely fluorescent derivatives and improves the stability of primary and secondary amino acid fluorophores towards oxidation. The accuracy and reproducibility of the method are increased by using three internal standards. The determination of all amino and imino acids present in protein hydrolysates, including tryptophan, in a single run is demonstrated.

3-Mercaptopropionic Acid↗
PubMed1988

Thymostimulin treatment in AIDS-related complex.

Thirty-four patients with AIDS-related complex (ARC) were treated for 6 months with thymostimulin, a thymic hormone. Clinical and immunological findings after a 1-year follow-up were compared with those in 24 age- and sex-matched controls receiving no immunotherapy. Statistical evaluation after 6 and 12 months showed significant differences in the two groups. The thymostimulin-treated group had higher leukocyte and lymphocyte counts, more positivity in intradermal tests with multiple recall antigens, and less lymphadenopathy and weight loss. The number of OKT3+ and OKT4+ lymphocytes decreased significantly in the control group, but did not change in the thymostimulin-treated patients. Finally, after 18 months of follow-up, no progression to AIDS was seen among the treated subjects, whereas 3 of the controls developed the disease. We conclude that thymostimulin, alone or in combination with antiviral drugs, may be helpful in the management of ARC patients.

AIDS-Related Complex↗
PubMed1975

Thymosin-induced reduction of "null cells" in peripheral-blood lymphocytes of patients with systemic lupus erythematosus.

Although thymosin, a thymic hormone, has been shown to restore cellular immunity in NZB/NZW mice, its effect in human systemic lupus erythematosus (S.L.E.) and other auto-immune disorders has not been tested. The present study shows for the first time that the proportion of "null cells" in peripheral-blood lymphocytes of patients with active S.L.E. is significantly decreased after in-vitro thymosin treatment. Thymosin has no effect on the percentages of T cells, B cells, and "null" cells in peripheral-blood lymphocytes from normal controls and patients with inactive S.L.E. and active rheumatoid arthritis. These findings suggest that thymosin may play an important part in the pathogenesis and treatment of this condition.

Adolescent↗
PubMed2002

The influence of nonspecific immunostimulation of pregnant sows on the immunological value of colostrum.

The purpose of this experiment was to estimate the influence of nonspecific immunostimulation of pregnant sows on the immunological value of colostrum. The studies were done in the fall-winter season on 20 pregnant sows (Polish Landrace) divided into four groups, five animals each. The sows were clinically healthy and unvaccinated. Group I received isoprinosine, group II (TFX), group III (HMB), and group IV served a control. The immunostimulants were applicated 4-6 weeks before the expected date of delivery. The following parameters were determined in colostrum taken from sows after completed delivery: specific gravidity; total proteins, lysozyme activity, IgG level. It was found that the nonspecific immunostimulation of pregnant sows increased in colostrum the level of IgG, total protein content and lysozyme activity.

Adjuvants, Immunologic↗