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T Thomas

Publications and source records attributed to T Thomas.

At least 307 records · Page 17Linked to original sources
PubMed1988

Modulation of the binding of progesterone receptor to DNA by polyamines.

Putrescine, spermidine, and spermine are a group of small organic cations, collectively known as polyamines. They are present in all living cells, and their levels are generally increased in tumor cells. Progesterone receptor is a gene-regulatory protein that plays a major role in gestation and in hormonal responsiveness of breast cancer. We studied the effects of putrescine, spermidine, 2 lower homologues of spermidine, N1- and N8-acetyl spermidines, spermine, and N1-acetyl spermine on the sedimentation profile and DNA binding of progesterone receptor from rabbit uterus. Progesterone receptor, prepared in hypotonic buffer, sedimented at the 7S region of sucrose gradients. In the presence of 1 mM putrescine, a part of the receptor was converted to a 5S form. In the presence of 1 mM spermidine or 0.25 mM spermine, the receptor was completely transformed to the 5S form. The DNA binding of the 7S form of progesterone receptor was 7 +/- 3%. After incubating this receptor with 1 mM putrescine, 1 mM spermidine, or 0.25 mM spermine, its DNA binding increased to 16 +/- 4, 37 +/- 3, and 44 +/- 5%, respectively. The structural specificity of polyamines in facilitating the DNA binding of progesterone receptor was examined by using two spermidine homologues. The first homologue with one methylene group less than that of spermidine was as effective as spermidine in transforming progesterone receptor. Removal of two methylene groups, however, had a dramatic effect in reducing the efficacy of the resulting molecule to the level of putrescine. Taken together, our results show that natural polyamines are capable of modulating the binding of progesterone receptor to DNA. Since progesterone receptor is associated with the hormonal responsiveness of human breast cancer, polyamine levels in tumor cells might play an important role in the gene-regulatory function of progesterone receptor.

Acetylation↗
PubMed1988

The development of rat alpha 2-macroglobulin. Studies in vivo and in cultured fetal rat hepatocytes.

During inflammation and tissue injury, there is an increase in the plasma concentration of several proteins, the acute-phase proteins. The levels of some acute-phase proteins have been reported to increase in pregnant and tumour-bearing animals. Rat alpha 2-macroglobulin is classified as an acute-phase protein. In this study we report the expression of alpha 2-macroglobulin in various tissues during development of the rat embryo by analysis of mRNA. The tissues studied are liver, visceral yolk sac, placental labyrinth, decidua and trophoblast. In addition, the sites of alpha 2-macroglobulin expression are localized by in situ hybridization of cDNA for alpha 2-macroglobulin to mid-sagittal cryosections of rat embryos. The level of mRNA coding for alpha 2-macroglobulin is determined in the liver of rats aged between 12 days gestation and 2 days postnatal. alpha 2-Macroglobulin mRNA is first observed in fetal liver from 12 days of gestation and increases after day 17, reaching a maximum on day 20. At this time the level is greater than that found in the liver of an adult rat suffering from acute inflammation. alpha 2-Macroglobulin mRNA is detectable in the yolk sac, placental labyrinth, trophoblast tissue and decidua. In the decidua the alpha 2-macroglobulin message is first detected at 8 days of gestation, with high levels observed from 10 to 21 days of gestation. These observations are supported by in situ hybridization studies. Experiments using cultured hepatocytes show that cells derived from rats at 15 days and 19 days of gestation are capable of synthesizing and secreting alpha 2-macroglobulin. Both synthesis and secretion can be induced by the addition of dexamethasone to the culture medium.

Animals↗
PubMed1988

Structure and expression of the rat transthyretin (prealbumin) gene.

The rat transthyretin gene, 7.3 kilobase pairs (kb) long, with 14.5 kb of 5' flanking and 12.2 kb of 3' flanking region was cloned and characterized. The gene contained four exons. A "TATA box" sequence (5'-TATATAA-3') and a "CAAT box" sequence (5'-GTCAAT-3') were located 23 and 95 nucleotides upstream, respectively, from the major transcription start site. Nucleotides -51 to -189 were highly conserved (93% homology between rats and humans, 97% homology between rats and mice). Tandem repeats of sequences of 5'-AC-3' and 5'-ACACATGC-3' in the 5' flanking region, of 5'-GAAA-3' in the first intron, and of 5'-GT-3' in the third intron of the gene were observed. Using specific cDNA probes, tissue specificity and regulation of transthyretin mRNA biosynthesis during embryogenesis were analyzed. Transthyretin expression occurred first in the yolk sac, then decreased when expression increased in fetal liver. Presumptive choroid plexus cells in the inner lining of the neural tube expressed transthyretin early in gestation (11 days before birth) with a maximum immediately preceding the spurt of brain growth around birth. Partial hepatectomy of adult rats induced both an acute phase response and regenerative growth in liver. The decrease in transcription of the transthyretin gene in liver, which is characteristic for the acute phase response, was overridden by stimulation of gene expression after partial hepatectomy. This stimulation also affected transthyretin expression in choroid plexus.

Amino Acid Sequence↗
PubMed1988

The expression of transthyretin mRNA in the developing rat brain.

Specific cDNA and oligonucleotide probes were used to study the appearance of transthyretin mRNA in developing rat brain using Northern gel analysis, cytoplasmic dot hybridization, and in situ hybridization. Transthyretin mRNA in embryonic rat brain was found to be confined to the epithelial layer of the choroid plexus primordia appearing first in the fourth ventricle, followed by appearance in the lateral ventricles, and subsequently in the third ventricle. Transthyretin mRNA was localized in these cells from early stages of neuroepithelium differentiation, showing that it is a sensitive marker for the differentiation of the choroid plexus within the fetal brain.

Animals↗
PubMed1988

Separation and characterization of the subunits of the laminin of EHS sarcoma.

A rapid and sensitive method was developed for the preparative separation of laminin subunits. Laminin was extracted and purified from mouse EHS sarcoma. On SDS-PAGE, the reduced and carboxymethylated molecule separated into two components corresponding to molecular weights of about 400 KDa (subunit A) and 200 KDa (subunit B). These two subunits were preparatively separated using heparin-agarose affinity chromatography. The larger subunit quantitatively adhered to the affinity column while the smaller one did not adhere. Amino acid analyses of the separated subunits showed distinct differences. Subunit B was further resolved into two distinct polypeptides of 200 KDa, B1 and B2, by means of reverse-phase HPLC. Although the amino acid compositions of B1 and B2 were very similar, the peptide maps generated by digestion of the B1 and B2 chains with Staphylococcus aureus V8 protease or by cyanogen bromide showed B1 and B2 to differ from each other. Thus, at least three different polypeptide subunits are present in this laminin and probably arise from separate gene origins. These studies provide a basis for the subsequent localization and analysis of the specialized structural and functional domains of laminin.

Animals↗
PubMed1987

Additive growth-inhibitory effects of DL-alpha-difluoromethylornithine and antiestrogens on MCF-7 breast cancer cell line.

We studied the growth inhibitory effects of DL-alpha-difluoromethylornithine, and antiestrogens (tamoxifen, 4-hydroxytamoxifen, trioxifene, keoxifene, and LY117018) as single agents and in combinations on the proliferation of a breast cancer cell line, MCF-7. At 0.1 mM difluoromethylornithine, the proliferation of MCF-7 cells was inhibited to 75 +/- 6% of the controls. Treatment of the cells with 0.1 microM 4-hydroxytamoxifen reduced cell growth to 72 +/- 4%. Combination of 0.1 mM difluoromethylornithine and 0.1 microM 4-hydroxytamoxifen reduced cell growth to 38 +/- 5%, indicating additive growth inhibitory effects. Similar additive effects were observed with all 5 antiestrogens in combination with difluoromethylornithine.

Breast Neoplasms↗
PubMed1987

Structural alterations and stabilization of rabbit uterine estrogen receptors by natural polyamines.

Estrogenic regulation of gene expression involves interaction of the hormone with its receptors, which undergo structural and conformational changes to interact with specific DNA sequences. Putrescine, spermidine, and spermine, are ubiquitous cellular components. We studied the effects of these polyamines on rabbit uterine estrogen receptors by sucrose gradient centrifugation and ligand dissociation kinetics. The native 7S receptor converted to a 9S-10S form in the presence of 100 microM spermidine or spermine. Higher concentrations caused precipitation of the receptor. This precipitation was reduced by RNase treatment of the receptor. RNase-treated receptors sedimented at 4S and 7S regions of sucrose gradient. The dissociation rate constant (k) of the 4S receptor is 2.8 X 10(-3) min-1 in the presence of 1 mM spermidine, compared to a control value of 7.7 X 10(-3) min-1. Similar effects were observed with putrescine and spermine. The dissociation of the RNase-treated 7S receptor was biphasic, with about 50% of the receptors dissociating at a faster rate (k1 = 40 X 10(-3) min-1) than the other half (k2 = 7.4 X 10(-3) min-1). Spermidine (1 mM) caused a 2-fold reduction in k2, whereas k1 was not affected. This study shows that polyamines affect the structural organization and ligand dissociation kinetics of estrogen-receptor complexes.

Animals↗
PubMed1987

Fibromatosis of the breast: a case report and literature review.

Fibromatosis is an uncommon, relatively benign though locally infiltrating neoplasm consisting of well-differentiated fibroblasts surrounded by collagen bundles. The majority of the literature suggests that prevention of local recurrence mandates wide (en bloc) excision. Few more than a dozen cases of primary breast fibromatosis have been reported. Herein the clinical characteristics, diagnostic evaluation, and therapeutic options are presented. Management should be based upon principles utilized for extra-mammary primary disease-en bloc resection. This may require total mastectomy and removal of pectoralis major muscle. Breast reconstruction should be deferred for a minimum of 3 years, during which time the majority of recurrences will have become manifest.

Adult↗
PubMed1987

Aldosterone and the mobilization of energy.

Aldosterone diminishes the ability to endure starvation. Its exogenous administration to adrenalectomized rats advances the onset of hypothermia and death. The impairment seems to lie in an inability to mobilize energy stores fully: animals given the steroid are unable to lose weight at a normal rate. The findings help to establish the significance of mineralocorticoids in the regulation of energy exchange and solve some theoretical questions as to their general mode of action.

Adrenalectomy↗
PubMed1986

Levels of messenger ribonucleic acids for plasma proteins in rat liver during acute experimental inflammation.

The levels of mRNA for plasma proteins and for metallothionein in rat liver during the acute-phase response were studied by hybridization to specific cDNA probes. The mRNA for alpha 2-macroglobulin, the beta-chain of fibrinogen, alpha 1-acid glycoprotein (so-called acute-phase reactants) reached a maximum level between 18 and 36 h after inducing an acute inflammation. The level of mRNA for metallothionein-I peaked earlier, after 12 h. The mRNA for transferrin showed a delayed increase with a broad maximum for its relative level after 36-60 h. The mRNA levels for albumin and alpha 2u-globulin (so-called negative acute-phase reactants) decreased, reaching a minimum of 25% of the normal level after 36 h (albumin) and after 72 h (alpha 2u-globulin). The ratios of the rates of incorporation of leucine into the proteins over the levels of their mRNA in liver changed only a little, indicating that the rates of synthesis of plasma proteins in the liver are regulated at the mRNA level during the acute-phase response to inflammation.

Animals↗
PubMed1986

Ribonuclease-induced transformation of progesterone receptor from rabbit uterus.

The effect of RNase on the transformation of progesterone receptor from rabbit uterus was studied by density-gradient centrifugation and DNA-cellulose binding assay. The 7S form of the receptor in crude cytosol was RNase sensitive, and converted to the 4S form after RNase treatment. This reaction was prevented by an RNase inhibitor and reversed by the addition of ribosomal RNA. RNase treatment also caused a two-fold increase in the DNA binding of cytosolic receptor, and reduced the time required for heat-induced transformation. However, sucrose-gradient-purified progesterone receptor (7S) did not undergo transformation by warming unless exogenous RNase was added, thereby suggesting that a cytosolic factor, which might be endogenous RNase, is necessary for the heat-induced transformation of progesterone receptor. Furthermore, degradation of the receptors which occurred after prolonged warming at 25 degrees C in the presence of RNase could be prevented by the addition of DNA-cellulose to the reaction mixture. These results indicate that RNA is associated with the 7S form of progesterone receptor, and that its hydrolysis by RNase might be involved in the transformation of this receptor.

Animals↗
PubMed1986

The selective role of endoscopic sclerotherapy in the management of bleeding esophageal varices.

Twenty-one patients (62% Child's C) underwent endoscopic sclerotherapy (ES) to control hemorrhage from esophageal varices. Four patients exsanguinated; bleeding was controlled in the remaining 17 patients (81%). Of this latter group, 14 patients were discharged from the hospital and three patients died from causes other than hemorrhage. A protocol of continued ES was offered to those patients with estimated poor hepatic reserve and to those with excellent reserve who refused portasystemic shunt procedures. During a mean 13 month follow-up of the six patients in this group, rebleeding occurred in two patients (one of whom died). All three patients with excellent hepatic reserve who underwent elective portacaval shunt have suffered neither morbidity nor further hemorrhagic episodes. No significant morbidity related to ES was encountered. ES is recommended in the acute phase of managing all patients with unremittent variceal hemorrhage, and on a continued basis for those with poor hepatic reserve. Patients with excellent reserve should be offered elective portasystemic shunt, accepting the risk of surgical intervention as fair trade-off for its superiority over ES in controlling hemorrhage.

Esophageal and Gastric Varices↗
PubMed1985

Acute-phase response of plasma protein synthesis during experimental inflammation in neonatal rats.

The pattern of plasma protein concentrations in neonatal rats differs characteristically from that in adult animals. Immediately after birth, the concentration of alpha 2-macroglobulin is about 200 times higher, that of major acute-phase alpha 1-protein the same, and that of alpha 1-acid glycoprotein, another acute phase protein, is considerably lower, compared with the values observed in healthy adults. The concentration of prealbumin, a negative acute-phase protein, remains low in the immediate postnatal period, but increases at a time when concentrations of both thyroxine and corticosterone increase. At this time, there is also a distinct increase in the concentration of alpha 1-acid glycoprotein. Despite the differences in concentration of plasma proteins in the adult rat and the neonate, the neonatal liver has the capability to respond to an acute inflammation with a coordinated change in the synthesis rates of plasma proteins similar to that observed in adult animals.

Aging↗