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Analysis of insulin-like growth factor I gene expression in malignancy: evidence for a paracrine role in human breast cancer.

Insulin-like growth factor I (IGF-I) activity has been reported to be produced by several human cancers. Identification of RNAs transcribed from the IGF-I gene has been complicated by the detection of multiple hybridizing bands on Northern analysis. To determine if any of these RNAs are transcribed from the IGF-I gene, we have used a sensitive and specific ribonuclease (RNAse) protection assay for IGF-I. We have also studied the breast cancer tissue expression of IGF-I using in situ hybridization histochemistry. We have found no IGF-I mRNA in breast (zero of 11) or colon cancer (zero of 9) cel

Transforming growth factor alpha production and epidermal growth factor receptor expression in normal and oncogene transformed human mammary epithelial cells.

We have characterized the expression of transforming growth factor alpha (TGF alpha) and its receptor, the epidermal growth factor receptor (EGF-R), in normal and malignantly transformed human mammary epithelial cells. Human mammary epithelial cells were derived from a reduction mammoplasty (184), immortalized by benzo-a-pyrene (184A 1N4), and further transformed by the oncogenes simian virus 40 T (SV40 T), v-Ha-ras, and v-mos alone or in combination using retroviral vectors. 184 and 184A 1N4 cells require EGF for anchorage-dependent clonal growth. In mass culture, they secrete TGF alpha at hi

Human islet amyloid polypeptide gene: complete nucleotide sequence, chromosomal localization, and evolutionary history.

The gene-encoding human islet amyloid polypeptide (hIAPP), a recently discovered 37 amino acid hormone-like polypeptide which is expressed in the insulin-producing beta-cells of the endocrine pancreas, has been isolated and characterized. The coding region of the gene is interrupted in the 5'-untranslated region and NH2-terminal propeptide by introns of 330 and 4808 base pairs (bp), respectively. Exon 1 (104 bp) encodes most of the 5'-untranslated region of the mRNA; exon 2 (95 bp) encodes 15 nucleotides of 5'-untranslated region, the putative 22 amino acid signal peptide and five residues of

Multiple growth hormone-binding proteins are expressed on insulin-producing cells.

The insulin-producing rat islet tumor cell line, RIN-5AH, expresses somatogen binding sites and responds to GH by increased proliferation and insulin production. Affinity cross-linking shows that RIN-5AH cells contain two major GH-binding subunits of Mr 100-130K (110K), which appear to exist as disulfide-linked multimers of Mr 270-350K (300K). In addition, a minor Mr 180K GH-binding protein is identified which does not appear to be associated with other proteins by disulfide bridges. A plasma membrane-enriched fraction accounts for 86% of the RIN-cell GH-binding activity while cytosol and intr

Developmental and physiological regulation of aldose reductase mRNA expression in renal medulla.

Aldose reductase (AR), an enzyme that catalyzes the conversion of glucose to sorbitol, has been implicated in the pathogenesis of many of the complications of diabetes mellitus, but its normal physiological function in various tissues remains uncertain. It has been suggested that in the kidney, sorbitol production may be an important cellular protection against medullary intersitital hypertonicity. Using in situ and Northern hybridization analyses, we found that at the time of birth, AR mRNA expression in the kidney was very low and seen only in the papilla. By 12 days of age, at about the tim

Pituitary thyrotropin-releasing hormone receptors: local anesthetic effects on binding and responses.

Pharmacological agents are widely used to probe the mechanism of action of TRH. A number of these drugs behave as local anesthetics at high concentrations. The effect of local anesthetics on the binding of [3H]Me-TRH to specific receptors was studied using the GH4C1 line of rat pituitary tumor cells. [3H]Me-TRH binding was inhibited by classical local anesthetics with the order of potency (IC50 values): dibucaine (0.37 mM) greater than tetracaine (1.2 mM) greater than lidocaine (3.3 mM) greater than procaine and benzocaine (greater than 10 mM). IC50 values for other drugs with local anesthetic

A quantitative comparison of dual control of a hormone response element by progestins and glucocorticoids in the same cell line.

Progesterone receptor-containing T47D human breast cancer cells are responsive to progestins but fail to respond to other steroid hormones, in particular dexamethasone, because they have no measurable levels of receptors for estrogens, androgens, or glucocorticoids. To quantitatively study dual responsiveness of the mouse mammary tumor virus (MMTV) promoter to progestins and glucocorticoids, we have stably transfected T47D cells with a glucocorticoid receptor (GR) expression vector. A cloned derivative (A1-2) was isolated that expresses a normal, full length GR, as assessed by steroid binding

Tyrosine hydroxylase mRNA in the neurons of the tuberoinfundibular region and zona incerta examined after gonadal steroid hormone treatment.

The dopamine-producing neurons of the tuberoinfundibular region are known targets of estrogen and progesterone, and are of considerable neuroendocrine importance. To determine the anatomical distribution, and number of cells that contain tyrosine hydroxylase (TH) mRNA in the tuberoinfundibular region and other regions of the brain we carried out in situ hybridization on sections prepared from ovariectomized female rats given either oil vehicle, or estrogen, or estrogen plus progesterone. The intensity of label per cell was assessed to compare the relative amount of mRNA found per cell among TH

Characterization of the domain structure of chick c-erbA by deletion mutation: in vitro translation and cell transfection studies.

Chicken c-erbA (Ck-c-erbA) cDNA (1250 base pairs), a cellular homologue of the avian erythroblastosis virus v-erbA gene, encodes a 408 amino acid protein which binds L-T3 and its analogs with affinities similar to that of endogenous thyroid hormone nuclear receptors. By analogy with steroid receptors, Ck-c-erbA(Met1-Val408) contains an A and B domain (amino acids 1-50); a putative DNA binding C domain (amino acids 51-118); a hydrophilic D domain (amino acids 119-189); and a putative ligand binding E domain (amino acids 187-408). To further characterize the ligand binding region of Ck-c-erbA, t

Glucocorticoid and cyclic nucleotide regulation of plasminogen activator and plasminogen activator-inhibitor gene expression in primary cultures of rat hepatocytes.

Primary cultures of rat hepatocytes produce tissue-type plasminogen activator (tPA) and plasminogen activator-inhibitor type 1 (PAI-1). Incubation of hepatocytes with 50 microM 8-(4-chlorophenylthio)cAMP (CPT-cAMP) results in a 4-fold increase in tPA activity, whereas the synthetic glucocorticoid dexamethasone (1 microM) causes a more than 90% decrease. In combination, dexamethasone completely overcomes the CPT-cAMP effect and markedly decreases PA activity. PAI-1 is induced by both CPT-cAMP and dexamethasone, and the effects of these agents are additive. Accumulation of tPA mRNA is increased

Full expression of uncoupling protein gene requires the concurrence of norepinephrine and triiodothyronine.

We have examined the uncoupling (UCP) protein gene expression in euthyroid and hypothyroid rats. UCP mRNA levels were estimated by northern blot analysis of total RNA from brown adipose tissue (BAT). Stimuli were endogenous (cold) and exogenous norepinephrine (NE), isoproterenol, T3, and T4. While the euthyroid rats UCP mRNA levels increase 2- to 3-fold by 2 h after NE or overnight cold exposure, these stimuli and isoproterenol are ineffective in hypothyroid rats. One single dose of T4, equal to the daily production rate, brings about a normal response in hypothyroid rats exposed to cold overn

Evidence that receptor aggregation may play a role in transmembrane signaling through the insulin-like growth factor-I receptor.

alpha IR-3 is a mouse monoclonal antibody that binds to an epitope on the human insulin-like growth factor I (IGF-I) receptor and inhibits [125I]IGF-I binding to this receptor on human skin fibroblasts (HSF) and Hep G2 human hepatoblastoma cells. Unlike the natural ligand (IGF-I), neither intact alpha IR-3 nor its monovalent Fab fragment stimulate aminoisobutyric acid (AIB) uptake in HSF, and both competitively antagonize IGF-I's ability to produce this effect. However, when HSF are incubated with alpha IR-3 or its Fab' fragment, subsequent exposure to anti-mouse immunoglobulin G (IgG) produce

Chromogranin A biosynthetic cell populations in bovine endocrine and neuronal tissues: detection by in situ hybridization histochemistry.

Chromogranin A is a highly acidic protein that is found in the secretory granules of many endocrine and neuronal cells. To localize bovine cell populations involved in chromogranin A biosynthesis, the distribution of the mRNA encoding this protein was determined with in situ hybridization histochemistry. In the adrenal gland, the mRNA was found in the chromaffin cells of the medulla but was absent from the cortex. The distribution of the mRNA in the medulla was uneven; cells located at the periphery were more heavily labeled than those in the center of the gland. Because the adrenal medulla is

Distribution and regulation of rat insulin-like growth factor I messenger ribonucleic acids encoding alternative carboxyterminal E-peptides: evidence for differential processing and regulation in liver.

Alternative splicing of insulin-like growth factor I (IGF-I)/somatomedin C mRNAs generates two IGF-I mRNAs coding for IGF-I peptides with different sequences in the E domain of the IGF-I prohormone. These two mRNAs encode alternative E peptides due to the presence (IGF-Ib) or absence (IGF-Ia) of a 52-base insert in the region coding for the E domain. We have used a solution hybridization/RNase protection assay to determine the tissue distribution and regulation by GH of the expression of these alternative IGF-I mRNAs. IGF-Ib mRNAs are present in low abundance (representing approximately 2.5% o

Proopiomelanocortin gene is expressed in many normal human tissues and in tumors not associated with ectopic adrenocorticotropin syndrome.

Immunoreactive (IR) POMC peptides have been detected in several human nonpituitary tissues and most pheochromocytomas and lung cancers, including those not associated with ectopic ACTH syndrome. We found IR-ACTH, IR-gamma MSH, IR-beta-endorphin (beta END), and IR-lipotropin in extracts from the following 10 normal human tissues, listed in order of decreasing POMC peptide concentrations: adrenal, testis, spleen, kidney, ovary, lung, thyroid, liver, colon, and duodenum. IR-ACTH, IR-gamma MSH, and IR-beta END were detected in all six pheochromocytomas and all 12 lung tumors (six squamous cell car

Progesterone induction of metallothionein-IIA gene expression.

Expression of the metallothionein gene is known to be induced by glucocorticoids in a variety of cells. Here we show that in human cell lines containing functional progesterone receptors, the endogenous metallothionein-IIA (hMTIIA) gene is inducible by the synthetic progestins R5020 and medroxy-progesterone acetate. That this effect reflects a direct interaction with the metallothionein gene is supported by our finding that the partially purified progesterone receptor binds to the promoter region of the gene in vitro. The limits of the DNase I footprint and the guanine residues protected in me

The polypeptide P16 is a carboxy-terminal cleavage product of rat growth hormone in anterior pituitary and GH3 pituitary tumor cells.

P16 is a small polypeptide originally found in GH3 rat pituitary tumor cells whose expression is tightly linked to the expression of rat GH (rGH) at a genetic level. It is estimated to be 3-5 kilodaltons smaller than rGH and exhibits the same complex response to T3, dexamethasone, and insulin in GH3 cells as does rGH. P16 was also found in high but variable abundance in anterior but not posterior pituitary. To approach the question of whether it arises from a unique gene or derives instead from the rGH gene by a posttranscriptional mechanism, we have measured its structural relatedness to rGH

Hormonal regulation of a chicken oviduct messenger ribonucleic acid that shares a common domain with gizzard myosin light chain kinase.

Changes in myosin light chain kinase (MLCK) and calmodulin (CaM) mRNAs have been evaluated during estrogen-mediated differentiation of the chicken oviduct. Also examined were acute changes that occur in oviduct RNA from animals stimulated with estrogen, withdrawn from hormone and then injected for 1, 2, and 4 days with synthetic estrogen [diethylstilbestrol (DES)], progesterone (P), or testosterone (T). Small changes were noted in both CaM and MLCK RNAs during primary stimulation when oviduct cells are actively dividing. On the other hand no significant changes were observed during secondary s

Осуществление инициативы по осуществлению программы обеспечения безопасности для мониторинга вливания заболеваний, изменяющего методы лечения множественных склерозов.

ЦЕЛЬ: Определение эффективности программы обеспечения безопасности, предназначенной для контроля за лечением впрыскивания (ДМТ), предписанной в отношении множественных склерозов (МС). СПРАВОЧНАЯ ИНФОРМАЦИЯ: Высокоэффективные ДМТ, основанные на вливании, представляют собой значительный прогресс в лечении НР. Однако безопасное управление требует тщательного контроля. Несоблюдение требований в отношении контроля за безопасностью может привести к осложнениям, связанным с ДМТ. МЕТОДЫ: Навигатор по технике безопасности изучил карты для вливания пациентов ДМТ в период с ноября 2020 года по декабрь 20

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… , Baltimore, MD, USA. … Dhanajay Vaidya, Department of Internal Medicine, Johns Hopkins University, Baltimore, MD, USA. Scott D Newsome, Department of Neurology, Johns Hopkins University, Baltimore, MD, USA. References …

Anaesthesia as an influence in tumour progression.

PURPOSE: Tumour growth and the formation of metastases are essential elements in the progression of cancer. The centre of treatment is the surgical resection of primary solid tumours. But even if the tumour can be removed without microscopic residual cells, local recurrences and distant metastases occur and determine the patient's fate. During the operation, tumour cells are shed from the primary tumour and released into the circulation. These circulating tumour cells might play an important role in the formation of new tumour sites. Therefore, a functional innate and adaptive immune system is

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… Sen Y Xiyang H Yu H Effect of thoracic paraspinal block-propofol intravenous general anesthesia on VEGF and TGF-β in patients receiving radical resection of lung cancer Medicine (Baltimore) 2019 98 47 e18088 10.1097/md.0000000000018088 31764844 PMC6882595 17. … Wang K Qu X Wang Y Shen H Liu Q Du J Effect of mu agonists on long-term survival and recurrence in non-small cell lung cancer patients Medicine (Baltimore) 2015 94 33 e1333 10.1097/md.0000000000001333 26287418 PMC4616430 44. …