Glutathione S-transferase isoenzymes in human lung tumors

In the present studies we have compared the levels of glutathione(GSH) and GSH-related enzymes in lung tumors and correspondingnormal tissues obtained from the same individuals. We have alsoimmunologically quantitated the relative amounts of glutathioneS-transferase (or GST-P) type antigen in tumors and adjacentnormal tissues from five patients. GST activities towards 1-chloro-2,4-dinitrobenzene (CDNB) and ethacrynic acid were found to beelevated in tumors from two out of five patients (patients #1and 4), whereas the activity towards these substrates was markedlysuppressed in the tumor tissue from one of the patients (#5).Immunotitration and Western blot studies using antibodies raisedagainst -type GST isoenzymes of human lung and placenta indicatedinduction of GST -type isoenzyme in tumors from patients #1and 4 and suppression of this isoenzyme in tumor from patient#5. The tumors from patients #2 and 3 did not show any increasein GST activity or GST -type antigen. Except for the tumor frompatient #5, the GSH content was higher in the tumors from otherpatients. GSH reductase activity was found to be elevated intumors of all the patients examined in this study. These resultsindicate that GSH and GSH related enzymes are differentiallyaltered in lung tumors and GSH levels and GST - or GST-P-typeisoenzyme(s) are not uniformly elevated in all tumors.     

Recombinant human interferonsα,β andγ reduce the antiproliferative action of cytarabine in K562 human myeloid leukaemia clonogenic cells

Summary The effects of recombinant human interferons , and (IFN) on the antiproliferative activity of cytarabine in K562 human myeloid leukaemia clonogenic cells were studied in an agar capillary microassay. The addition of IFN- did not affect the antiproliferative activity of cytarabine in K562 cultures treated with low concentrations of cytarabine (10–50 nM), whereas in those treated with high concentrations (100–150 nM) IFN increased the IC₅₀ of cytarabine on day 5 from 102 nM to 214 nM, i.e., cytarabine combined with IFN was about two-fold less potent than cytarabine alone. Similarly, low concentrations of IFN and IFN did not affect the antiproliferative activity of cytarabine on K562 colonies, but high concentrations of these two interferons: 4×10³ U/ml and 10⁴ U/ml respectively, increased the IC₅₀ of cytarabine on day 5 to 304 nM and to 316 nM respectively, i.e. cytarabine combined with IFN or IFN was about threefold less potent than cytarabine alone. The evaluation of the present negative interactions of interferons with cytarabine is warranted in fresh cells from myeloid leukaemia patients in primary culture.Abbreviation IFN interferon     

Some nucleophilic substitutions in 2,4-and 2,4,8-trichloro-pyrido [3,2-d] pyrimidines

Reaction of 6-(acetoxymethyl)-2,4-dichloropyrido[3,2-d]pyrimidine (I) with some nucleophiles was investigated. When I reacted with sodium azide afforded 2,4-diazido derivative (II). Treatment of II with sodium hydroxide underwent cyclization of the 2-azido group to tetrazolo, replacement of 4-azido group by hydroxide ion, and hydrolysis of 6-acetoxy moiety to hydroxy methyl derivative (III). While, reaction of I with hydrazine hydrate resulted in the formation of 2,4-dihydrozino-6-hydroxymethyl derivative (IV).     

Macrophage activation and Fcgamma receptor-mediated signaling do not require expression of the SLP-76 and SLP-65 adaptors

The Src-homology 2 domain-containing, leukocyte-specific phosphoprotein of 76 kDa (SLP-76) is a hematopoietic adaptor that plays a central role during immunoreceptor-mediated activation of T lymphocytes and mast cells and collagen receptor-induced activation of platelets. Despite similar levels of expression in macrophages, SLP-76 is not required for Fc receptor for immunoglobulin G (IgG; FcgammaR)-mediated activation. We hypothesized that the related adaptor SLP-65, which is also expressed in macrophages, may compensate for the loss of SLP-76 during FcgammaR-mediated signaling and functional events. To address this hypothesis, we examined bone marrow-derived macrophages (BMM) from wild-type (WT) mice or mice lacking both of these adaptors. Contrary to our expectations, SLP-76(-/-) SLP-65(-/-) BMM demonstrated normal FcgammaR-mediated activation, including internalization of Ig-coated sheep red blood cells and production of reactive oxygen intermediates. FcgammaR-induced biochemical events were normal in SLP-76(-/-) SLP-65(-/-) BMM, including phosphorylation of phospholipase C and the extracellular signaling-regulated kinases 1 and 2. To determine whether macrophages functioned normally in vivo, we infected WT and SLP-76(-/-) SLP-65(-/-) mice with sublethal doses of Listeria monocytogenes (LM), a bacterium against which the initial host defense is provided by activated macrophages. WT and SLP-76(-/-) SLP-65(-/-) mice survived acute, low-dose infection and showed no difference in the number of liver or spleen LM colony-forming units, a measure of the total body burden of this organism. Taken together, these data suggest that neither SLP-76 nor SLP-65 is required during FcgammaR-dependent signaling and functional events in macrophages.     

Levothyroxine treatment in thyroid peroxidase antibody-positive women undergoing assisted reproduction technologies: a prospective study

BACKGROUND: Infertile women positive for thyroid antibodies suffer from a poor pregnancy/delivery outcome, although conflicting data have been published. Our objective was to investigate if levothyroxine (LT4) exerts any effect on pregnancy and/or delivery rates in thyroid peroxidase antibody (TPOAb)-positive (+) women undergoing assisted reproductive technologies. METHODS: Patients undergoing treatment were screened for TPOAb, thyroid-stimulating hormone (TSH) and free thyroxine (FT4). A total of 72 (15%) out of the 484 euthyroid women selected were TPOAb (+). These 72 patients were randomly divided into two groups: group A (n = 36) underwent LT4 treatment, group B (n = 36) placebo. Group C consisted of 412 women (85%) who were TPOAb negative (-). All patients received controlled ovarian stimulation. The endpoints of treatment were pregnancy rate, miscarriage rate and delivery rate. RESULTS: No differences in pregnancy rate were observed between the three groups. Miscarriage rate was higher in TPOAb (+) in comparison to TPOAb (-) [relative risk: 2.01 (95% CI = 1.13-3.56), P = 0.028]. CONCLUSIONS: The pregnancy rate is not affected either by presence of TPOAb or treatment with LT4. However, TPOAb (+) women show a poorer delivery rate compared to TPOAb (-). LT4 treatment in TPOAb (+) does not affect the delivery rate.     

Anatomical parameters of cardiopulmonary system in three different lines of chickens: further evidence for involvement in ascites syndrome.

The present study was designed to compare the anatomical parameters of the cardiopulmonary system in three different lines of chickens with different susceptibility to ascites syndrome. Eggs from three different genetic lines-commercial broiler and layer lines and one native to Iran--were incubated and hatched, and 1-day-old chicks used. The relative heart and lung weights, the volumes of the heart, lung and thorax cavity, the incidence of ascites, and the related physiological parameters in these chickens were followed. Lung weight as a percentage of body weight, the relative lung and heart volume, and the volumes of the thorax cavity, before and after removing heart and lung tissues, were lower in fast-growing broiler chickens compared with the layer and native chickens. Additionally, most of these parameters (e.g. relative lung weight, lung volume and thorax cavity) were significantly decreased with age in broiler chickens but were increased in layer and native chickens, which was concomitant with the incidence of ascites in broiler chickens. Our data indicate that all cardiopulmonary parameters investigated are extremely unfavourable to broiler chickens and suggest a reduction in gas exchange area in broilers, and therefore higher susceptibility to pulmonary hypertension and ascites.     

Induction of apoptosis of human primary osteoclasts treated with extracts from the medicinal plant <Emphasis Type="Italic">Emblica officinalis</Emphasis>

Background  

Osteoclasts (OCs) are involved in rheumatoid arthritis and in several pathologies associated with bone loss. Recent results support the concept that some medicinal plants and derived natural products are of great interest for developing therapeutic strategies against bone disorders, including rheumatoid arthritis and osteoporosis. In this study we determined whether extracts of Emblica officinalis fruits display activity of possible interest for the treatment of rheumatoid arthritis and osteoporosis by activating programmed cell death of human primary osteoclasts.     

The immunological consequences of gold therapy: a prospective study in patients with rheumatoid arthritis.

Gold sodium thiomalate (GST) is known to modify the disease process in patients with active rheumatoid arthritis (RA). To help understand the mechanism of action of GST, several immunological parameters were prospectively evaluated in 10 patients with active RA following the introduction of gold therapy. Before therapy, absolute numbers of peripheral blood T suppressor/cytotoxic lymphocytes were significantly depressed (P less than 0.01) and a raised T helper/T suppressor cell ratio was found. After 1 g of GST, an absolute reduction in total lymphocyte numbers including HLA/DR positive mononuclear cells, was evident (P less than 0.01). This lymphopenic effect was not selective for a single population since the proportions of T cells, T cell subsets and B cells remained unchanged. Lymphocyte function was also examined. Raised in vitro production of IgG (P less than 0.01) and IgA (P less than 0.05) was found before therapy. After GST, in vitro immunoglobulin synthesis was reduced and this was significant with respect to the IgM (P less than 0.001) and IgA (P less than 0.01) isotypes. Similarly, a parallel reduction in serum immunoglobulin levels developed. GST therapy was also associated with a reduced proliferative response to phytohaemagglutinin, concanavalin A and pokeweed mitogen in the initial phase of gold administration. The significant finding in this study suggest that the in vivo immunosuppressive effect of GST is explained not only by impaired mononuclear cell function but also by a significant reduction in T and B lymphocyte numbers.     

Epidemiologic and diagnostic evaluation of a recent mumps outbreak using oral fluid samples.

OBJECTIVE: To determine the optimal strategy to investigate mumps virus infection in a partially vaccinated cohort. STUDY DESIGN: 122 oral fluid and serum samples were collected in a recent outbreak in Ireland. The largest age cohort, students aged 18-21 years old attending third level institutions, were investigated using virus isolation, detection of mumps specific IgM, IgG, RT-PCR and molecular genotyping. RESULTS: 97% of patients had both detectable serum IgM and IgG. Mumps virus RNA was detected in 17 oral fluid samples and 14 of these originated from a single geographic location. Only 6 of the IgM positive samples had detectable mumps virus RNA whereas this could be detected in 11 IgM negative samples. Genotyping studies revealed that genotypes G and J were co-circulating during this outbreak. CONCLUSIONS: The use of an oral fluid sample to detect mumps virus RNA and IgM offers a major improvement over serological diagnosis in acute infection in both non-vaccinated or partially vaccinated individuals, and has the advantage that specimens are collected non-invasively.