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Biomedical subjects

A Albertini

Publications and source records attributed to A Albertini.

At least 235 records · Page 13Linked to original sources

Origin of the sarcosine molecules of actinomycins.

1. Streptomyces V-187 produces on minimal medium a mixture composed mainly of actinomycin C(1) (actinomycin D) and actinomycin A(1) (actinomycin I). If sarcosine is added to the medium, the micro-organism produces, in addition to actinomycins C(1) and A(1), actinomycin F(8) (actinomycin II) and actinomycin F(9) (actinomycin (III), characterized by the substitution by sarcosine of one or both the proline molecules present in actinomycin C(1). 2. Exogenous sarcosine seems to be incorporated as such by Streptomyces V-187 only in the sarcosine molecule(s) that replace proline in the actinomycins of the F group, whereas, for the synthesis of the other sarcosine molecules, the amino acid is first demethylated to glycine. 3. The incorporation of sarcosine and glycine into actinomycin by Streptomyces antibioticus appears to follow a similar pattern, except that a portion of the methyl group produced in the degradation of sarcosine is utilized as a source of the methyl groups of the antibiotic. This explains the previously reported lack of cross-dilution between glycine and sarcosine observed in the incorporation of these amino acids into actinomycin.

Chromatography, Thin Layer↗

Assessment of T-cell receptor beta-chain diversity by heteroduplex analysis.

The aim of this work was to search for a simple and alternative approach to the currently used methodologies for the analysis of T-cell receptor repertoire diversity. To this end we studied whether the heteroduplex analysis could be adapted to study the clonality of the T-cell receptor beta chain (TCRBV). We therefore analyzed, by sequencing, the molecular characteristics of the V-D-J junctions of numerous TCRBV chains from a variety of patients and from normal individuals, and compared the results with those obtained with the heteroduplex analysis. The latter procedure involves the amplification of the target TCRBV chains and the denaturation and renaturation of the amplified product to permit the random association of the distinct DNA strands encoding the different junctional regions. Whereas amplified material from polyclonal lymphoid cells migrates on a polyacrylamide gel as a "smear" of bands composed of different-sized polyclonal PCR fragments, the mismatched chains derived from oligoclonal populations migrate as discrete "heteroduplexes" and can be separated from the matched "homoduplex" obtained from homogeneous clonal cells. Our results provide evidence demonstrating that heteroduplex analysis can successfully be applied to the analysis of T-cell clonality in a variety of samples and can be complementary or substitute for the standard approach of TCR cloning and multiple sequencing of junctional regions. Thus, the procedure should facilitate the implementation of the analysis of TCR in diagnostic routine and should find applications in numerous physiologic and pathologic conditions.

Amino Acid Sequence↗

Positive and negative immunoregulation through CD4 depends on the concentration of the specific ligand and on the state of activation of the responding cells.

In order to better define the functional role of the interaction of CD4 polypeptide with the T-cell receptor (TCR) complex, we analysed the effect of an anti-CD4 monoclonal antibody (mAb) on T-cell activation and on the modulation of expression of CD3, CD4 and TCR variable (V) regions. The results presented here demonstrate that both positive and negative modulation of CD3 and TCR V regions can be obtained with different concentrations of the same anti-CD4 mAb and that these effects are functionally directly related to differences in IL2-receptor expression. Moreover, our data show that the dose of anti-CD4 mAb required for modulating CD3- and CD4-molecule expression on activated E+ peripheral blood mononuclear cells is at least 30 times higher than that required to obtain the same effect on resting cells. Thus, our results demonstrate that the interaction of CD4 molecule with its ligand can result in both up and downregulation of TCR and IL2-receptor expression, and that this differential modulation is strictly dependent on the concentration of available ligand as well as on the activation state of the responding cells.

Adult↗

Superoxide dismutase: possible therapeutic use in cardiovascular disease.

Superoxide dismutase (SOD) for parenteral administration is in clinical use in several European countries, where it is prescribed principally for treatment of musculoskeletal inflammation, especially osteoarthritis. However, new possibilities for its usefulness are arising from recent progresses of the pathophysiology of several diseases. From the beginning of this decade there has been a virtual explosion of the available informations about the mechanisms and control of free radical-mediated tissue injury. This progress has led us to the threshold of what will probably be broad clinical applications in the next future. Taking into account the mortality and morbidity caused by cardiovascular injury, the most promising application of SOD in human therapy seems to relay in the protection against ischaemia and post-ischaemic reperfusion damage of various organs and tissues but, particularly, of the myocardium. A large body of evidence suggests that myocardial damage following both global or regional ischaemia can be ameliorated by the blockade of free radical mediated injury. SOD has been proposed as a protective agent in various experimental models. The premises of this action, and the available results will be reviewed.

Animals↗

Alpha-fetoprotein monoclonal assay: preliminary clinical findings in a high risk population.

A two-site solid phase immunoradiometric assay was developed for measurement of human alpha-fetoprotein, utilizing two high-affinity monoclonal antibodies directed against distinct and separate epitopes on the proteic structure. The analytical sensitivity of the assay is 0.5 ng/ml. The clinical sensitivity was evaluated by comparison of patients with cirrhosis and patients with hepatocellular carcinoma with cirrhosis. This assay gave good diagnostic discrimination. In a preliminary clinical trial, the specificity of the assay was 92.3%, the clinical sensitivity 88.2%, and predictive values were 78.9% in the clinically positive stage and 96.0% in the negative stage. The diagnostic efficacy of the assay was 91.3%.

Animals↗

Evaluation of a radioreceptor assay to assess exogenous estrogen activity in serum of patients with breast cancer.

A radioreceptor assay (RRA) for the determination of total estrogen activity, was set up and used to assess the possible presence of exogenous molecules with estrogen activity in serum; a comparison was made with the specific radioimmunoassay (RIA) for the endogenous estrogen 17-B estradiol (17-B-E2). The assay was first performed on sera from healthy people taking estrogens in the form of oral contraceptives or lotions for local application whose total estrogenic activity in the blood was assumed to be abnormal. The assay was then performed on serum from 98 patients with early breast cancer and 20 patients with metastasis, not undergoing hormone therapy. A higher estrogen activity was found in 2.5% of sera compared to the activity found using the RIA method which is specific for endogenous estrogen 17-B-E2, the RRA/17-B-E2 ratio being higher than 3. Increased estrogen activity was found in 10% serum samples from digoxin treated cardiopathic patients, with an RRA/17-B-E2 ratio ranging from 4.4 to 20. The RRA assay could prove useful for showing up exogenous estrogen activity from various sources (drugs, food) in sera of people in whom estrogen stimulation could be potentially dangerous (i.e. in patients with hormone-sensitive tumors). This exogenous activity could support a certain degree of neoplastic stimulation and, therefore, unfavourably condition the patients' therapeutic response.

Biomarkers, Tumor↗

Progesterone agonists and antagonists induce down- and up-regulation of estrogen receptors and estrogen inducible genes in human breast cancer cell lines.

The effects of the synthetic progestin R5020 and the antiprogestin RU486 on the cellular content of estrogen receptors (ER) and on cell responsiveness to estrogens, have been investigated in the sex hormone-sensitive human breast cancer cell lines MCF-7 and T47D. When T47D cells were treated with R5020 (Promegestone) (10(-8) M), ER was down-regulated to about 50% of the control level in a time-dependent manner. Maximum down-regulation was observed after 24 hours and remained at this level for the next 24 hours. Dihydrotestosterone (DHT) or dexamethasone (DEX) had no effect on ER sites. R5020 also down-regulated, although to a lesser extent, ER in the MCF-7 cells which contain fewer progesterone receptor (PR) sites. When MCF-7 cells were transfected with a progesterone receptor expression vector (tMCF-7) to increase the number of PR sites, R5020 down-regulated the ER to a level similar to that reached in T47D cells. In both cell lines ER down-regulation was completely inhibited by a 10-fold molar excess of the antiprogestin RU486 (Mifepristone) (10(-7) M). Surprisingly, when incubated with RU486 alone, T47D cells responded by up-regulating ER 2-4 fold. The functional relevance of inhibition and up-regulation of ER for the estrogen responsiveness of hormone-sensitive human breast cancer cells was tested by assaying the synthesis of an estrogen-regulated product, the PS2 protein. Estrogen induction of this protein was inhibited by at least 70% in T47D cells exposed to R5020 for 24 hours before estrogen administration and by about 25% in MCF-7 cells under the same conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗

[Gastrin and colorectal cancer].

The aim of present study was to assess preoperative/postoperative serum gastrin level variations and their prognostic value in patients with colo-rectal cancer. Levels have been evaluated in 66 subjects undergoing colo-rectal cancer surgery, with curative intent, from may 1990 to february 1994. Preoperative gastrin analysis was performed on peripheral blood samples in starred patient just prior surgery. Postoperative gastrin assessment was performed 7 day after surgery in starred patients as well. Follow-up ranged from 5 to 8 years. No association between preoperative gastrin levels and tumor site, stage or grading was observed. No significant variation of preoperative gastrin levels (p > 0.05) was ascertained postoperatively neither in the whole patient series nor after correction for tumor stage. Postoperative levels were therefore not affected by surgical removal of cancer. Neither preoperative nor postoperative serum gastrin levels influenced significantly the 5-year survival. In our experience, with the limitation of a small series assessment, serum gastrin level do not seem to have any prognostic value in colo-rectal cancer.

Aged↗

Functional depletion of T cells by vincristine and methylprednisolone as an in vitro model for the prevention of graft versus host disease.

BACKGROUND AND METHODS. The outcome of mismatched bone marrow transplantation is still severely hampered by graft versus host disease (GVHD) and graft rejection. Procedures for the recognition and selective elimination of T cells are still unsatisfactory due to the increased incidence of graft failure and late rejection. Lymphocyte proliferation and generation of cytotoxic T cells (CTL) in response to allogeneic cells are considered good in vitro correlates of GVHD and have been used in the present study to asses the capacity of two drugs (vincristine, VCR, and methylprednisolone, MP) to affect the T cells involved in these reactions. RESULTS AND CONCLUSION. Treatment in vitro with VCR and MP has been shown to inhibit the functional capacity of peripheral blood lymphocytes to proliferate (mean reduction 95.8%) and to generate CTL in response to haploidentical stimulator cells. Responsiveness to antigens and mitogens was affected to a minor extent (mean reduction 40% and 65.5%, respectively), and the method allowed recovery of hemopoietic precursors. The results suggest that treatment of donor bone marrow with VCR and MP is worth studying as a new approach to the prevention of GVHD in haploidentical bone marrow transplantation.

Bone Marrow Cells↗

[Hypoparathyroidism following total thyroidectomy: prognostic value of intraoperative parathyroid hormone assay].

Transient and definitive hypoparathyroidism represent a frequent complication after thyroid surgery. Recently some authors proposed the use of intraoperative parathyroid hormone assay for the rapid detection of this complication. In this paper the authors describe the data obtained from 42 total thyroidectomies with intraoperative measurements of parathyroid hormone. When parathormone decrement was over 75% during thyroidectomy, the hypocalcemic symptomatology was found in all cases during postoperative observation. The authors emphasize intraoperative PTH dosage for immediate identification of patients at risk for postoperative hypoparathyroidism. In this cases parathyroid autotransplantation is suggested to prevent postoperative hypoparathyroidism.

Adult↗