Grand unification and the supersymmetric threshold.
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Biomedical subjects
Publications and source records attributed to R Barbieri.
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OBJECTIVES: We attempted to determine the clinical usefulness of a preoperative platelet count for predicting malignancy in patients presenting with a pelvic mass. Additionally, in patients in whom a preoperative serum CA 125 level was also determined, the clinical usefulness was compared. STUDY DESIGN: A retrospective review of charts of 241 patients presenting with a pelvic mass was carried out. The patients were then divided by pathologic diagnosis into group 1, benign disease (n = 102), and group 2, invasive (n = 121) or borderline (n = 18) malignancies. Thrombocytosis (platelet count greater than 400,000/microliters) was present in 16% (n = 16) of patients in group 1 and in 56% (n = 78) of patients in group 2 (p less than 0.0001). Of the 241 patients, 130 also had preoperative serum CA 125 levels measured. Elevated values of serum CA 125 (greater than 35 U/ml) occurred in 14% (n = 8) of group 1 and in 81% (n = 60) of group 2 (p less than 0.0001). The chi 2 test was used to analyze results of data. RESULTS: Statistically significant differences in preoperative platelet count and serum CA 125 values were found between group 1 and group 2 patients. The specificity and positive predictive value for thrombocytosis (84% and 83%) compared well with those for serum CA 125 (86% and 88%). The combined use of the tests resulted in specificity of 96% and positive predictive value of 95%. CONCLUSIONS: Preoperative platelet count is a test that is rapidly available and easily obtained. The test results may be of value in planning the original management of women presenting with a pelvic mass.
The extent of 2-hydroxylation of estradiol (E2), which yields a non-estrogenic metabolite (2-OHE1), increased significantly with decreasing subcutaneous fat (ScF)/total volume percent (TV%) and total fat (TF)/TV% evaluated by magnetic resonance imaging (MRI) for five athletes during low- and high-intensity training, and four controls. The increase in 2-hydroxylation with decreasing adiposity was associated with anovulation and amenorrhea among the athletes.
The timing of fetal lung maturation is regulated, at least in part, by the fetal endocrine milieu, which in turn may be influenced by environmental factors. Infants of smoking mothers are at decreased risk of neonatal respiratory distress syndrome (RDS), a disease of lung immaturity. Therefore, we measured fetal lung maturity and cigarette smoke exposure to determine whether the lungs of smoke-exposed fetuses mature more quickly and whether changes in maturation are associated with alterations in amniotic fluid (AF) cortisol levels. Amniotic fluid lecithin-sphingomyelin ratio (L/S) and saturated phosphatidylcholine levels were used as measures of lung maturity, while smoke exposure was assessed by measuring AF cotinine, a stable nicotine metabolite. Lung maturity was more advanced in smoke-exposed fetuses as measured by saturated phosphatidylcholine (P = .02) and L/S ratio (P = .04). Smoke-exposed fetuses attained sufficient lung maturity to minimize the risk of RDS approximately 1 week earlier than in unexposed fetuses. The AF of smoke-exposed fetuses also had higher levels of free, conjugated, and total cortisol. Acceleration of lung maturation in smoke-exposed fetuses is consistent with the decreased risk of RDS in infants of smoking mothers. Maternal smoking could influence lung maturation by directly or indirectly enhancing the production and/or secretion of cortisol. Despite the decreased risk of RDS, the developmental process by which smoke-exposed fetuses attain early pulmonary maturity is abnormal and may contribute to the decreased lung function and increased respiratory illness noted in infants of smoking mothers.
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We have developed a simple and rapid method for recovering DNAs of a wide range of molecular weights from agarose gels. A DNA-containing gel slice is placed on a Parafilm sheet in the center of a circular (positive) electrode and covered with a drop of buffer, while a linear (negative) electrode is placed on the top of the gel and driven about 1 mm into the gel itself. When a continuous current is applied, the DNA migrates into the buffer toward the circular electrode. We have obtained almost total recovery of DNAs up to 10 kb in size. Our method may also be used, under appropriate conditions, for higher molecular weight DNAs. The yield and all the biological assays performed on the DNAs obtained by our method recommend it for routine laboratory use.
The methylation pattern of the human HLA-DR alpha gene has been studied in different tissues of transgenic mice. Offspring from two transgenic lines was selected for this analysis, carrying the integrated HLA-DR alpha gene in either single or multiple (8-10) copies per diploid genome. In transgenic animals two distinct methylation patterns of the HLA-DR alpha gene are generated, due to a complete methylation of all the GCGC and CCGG sites the former, and to unmethylation restricted to one or both the GCGC sites located in the 5' portion of the HLA-DR alpha gene, the latter. Unmethylation restricted to the 5' portion of the HLA-DR alpha gene is a highly conserved feature in human tissues and in vitro cultured cell lines; therefore, it is concluded that the methylation pattern of the human HLA-DR alpha transgene may be faithfully reconstituted in transgenic animals. Northern blotting analysis of the RNA isolated from tissues of the transgenic mouse carrying single-copy HLA-DR alpha transgene demonstrates its tissue specific expression, suggesting that transgenic mice may represent an "in vivo" experimental system to study the relationship between methylation state and transcriptional activation.
In this study we analyse the effects of the anti-tumor compound distamycin on the binding of nuclear factor(s) to a synthetic oligonucleotide (GTATA/IFN-gamma) mimicking a putative regulatory region of the human HLA-DR alpha gene. This region contains the sequence (GTATA), that is required for nuclear protein binding and is likely to interact with distamycin. The present results, by showing that distamycin inhibits the interaction between nuclear factors and the GTATA/IFN-gamma oligonucleotide, suggest that distamycin might alter the binding of transacting factors to cis-elements containing AT/TA sequences. Alterations of nuclear protein binding to specific target sequences could be one of the molecular mechanism(s) by which distamycin exerts its antiproliferative activity on living cells.
Nucleolar Organizer Regions (NORs) code for ribosomal RNA and are thought to be an accurate representation of the percentage of cells in S-phase. NORs are associated with nonhistone nucleoproteins, which can be stained with silver (AgNORs). An increased number of AgNORs has been observed in many malignancies. AgNORs were counted in three groups of patients with endometriosis (Group I), atypical endometriosis (Group II), and clear cell or endometrioid carcinomas (Group III) to assess the malignant potential of atypical endometriosis. Each group consisted of 10 patients. Mean AgNOR counts were 5.83 (Group I), 7.68 (Group II), and 15.42 (Group III). The results were analyzed and were significantly different for all groups (P less than 0.05 for Groups I and II, P less than 0.02 for Groups II and III, and P less than 0.01 for Groups I and III). A critical AgNOR count of 8.20 was calculated utilizing AgNOR counts from Group I. Three of the four patients with AgNORs greater than 8.20 and atypical endometriosis developed a malignancy. AgNOR counts provide useful information, represent an inexpensive test which can be obtained from fixed tissue, and may aid in clinical management of patients with atypical endometriosis.
Bis(adeninato-N9)diphenyltin(IV) has been selected as a tumor panel compound by the U.S. National Cancer Institute and tested against a number of tumors according to standard protocols. The activity criteria were not passed. The solid state structure of the environment of tin in the complex has been definitely established to be of the tetrahedral type by means of 119Sn Mössbauer-Zeeman spectroscopy; this configuration has been assumed to be maintained also in aqueous suspensions of the drug, in conditions corresponding to the administration to mice. The occurrence of strong Sn-N bonds, consistently resistant to hydrolytic processes, has been assumed, and correlated to the observed low toxicity of the drug. The extent of the antitumor action corresponds to the standard response to Ph2SnIV moieties.
The reaction of aqueous native DNA (calf thymus) with the solvated organotin(IV) species [(CH3)2SnCl2(C2H5OH)n], as well as with [(CH3)2Sn(OH)(H2O)n]+ and (CH3)2Sn(OH)2 (i.e., the hydrolysis products of aqueous (CH3)2SnCl2 at pH approximately 5 and pH approximately 7.4 respectively), was investigated by 119Sn Mössbauer spectroscopy. The addition of [(CH3)2SnCl2(C2H5OH)n] to DNA yielded a solid product, possibly (CH3)2Sn(DNA phosphodiester)2, where the environment of the tin atom is trans-octahedral with linear CSnC skeleton, and the equatorial atoms may consist of oxygen or nitrogen from water as well as from the nucleic acid constituents. No interaction with DNA apparently takes place due to hydrolyzed dimethyltin(IV) species, which occur in aqueous phases at approximate physiological pH values. The reaction pathway is then assumed to require weakly solvated, easily dissociable species such as [(CH3)2SnCl2(C2H5OH)n], which would imply in vivo reactivity of cellular DNA with organotins from hydrophobic sites.
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Synthetic oligonucleotides containing putative regulatory sequences are currently employed to identify and isolate genes coding for nuclear binding factors. Upstream DNA sequences of eukaryotic genes required for transcriptional activity and tissue specificity can be identified by means of biochemical techniques as well as computer analysis using homology searching. An alternative approach has been recently proposed by our research group. Scanning DNA sequences 1.8 megabases in length from a Genetic Sequence Data Bank, we have identified rare oligonucleotides 5 base pairs (bp) long, which are localized within or close to regulatory segments in mammalian promoters. In this paper we demonstrate that the rare GTATA sequence identifies an upstream region of the HLA-DR alpha gene which operates in conjunction with the sequence AGAAGTCAG, homologous to a box found in many interferon-inducible genes, in binding nuclear proteins.
In the present paper we have investigated the effects of aromatic tetra-amidines on attachment, oriented migration and in vitro invasiveness of the Chinese Hamster FH06T1-1 fibroblast lung cell line, transformed with the activated human T24-Ha-ras-1 oncogene. The FH06T1-1 cell line is tumorigenic in nude mice and displays growth properties and biological features clearly distinct from those of the FH06N1-1 cell line, obtained after transfection of the same fibroblast cells with the normal Ha-ras-1 proto-oncogene. Attachment, oriented migration and invasiveness were analysed by culturing the cells on a reconstituted extracellular matrix, composed of collagen IV, laminin, entactin and heparan sulphate proteoglycans. The results obtained demonstrate that oriented migration is performed only by FH06T1-1 cells and that tetra-benzamidines are effective inhibitors of oriented migration and "in vitro" invasiveness of these tumorigenic cells. These findings should encourage further studies on the possible antimetastatic effects of these antiproteinase tetra-benzamidines on experimental animals.
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The methylation pattern of the human HLA-DR alpha gene was analyzed in primary tumors and lymph node metastases isolated from patients with a variety of tumors, including thyroid, pancreas, breast and gastric carcinomas and melanomas. In normal tissues (including breast, muscle, brain, sperm, T-and B-lymphocytes) the HLA-DR alpha gene is hypermethylated at CCGG and GCGC sites. In all tissues studied, the only constantly unmethylated region was located in the 5' portion of the gene. Our results indicate that the HLA-DR alpha gene is hypomethylated in metastatic lymph nodes, as well as in the carcinomas and melanomas studied. These findings lend support to the hypothesis that DNA hypomethylation of the human HLA-DR alpha gene may represent a molecular marker of malignant tumors.
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