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Biomedical subjects

A Riccio

Publications and source records attributed to A Riccio.

At least 109 records · Page 6Linked to original sources
PubMed1988

The regulatory region of the human plasminogen activator inhibitor type-1 (PAI-1) gene.

The human gene for plasminogen activator inhibitor type-1 (PAI-1) has been isolated and its promoter region characterized. PAI-1 regulation by glucocorticoids, transforming growth factor-beta (TGF-beta) and the phorbol ester PMA is shown to be exerted at the promoter level. A fragment spanning 805 nucleotides of the 5' flanking and 72 of the 5' untranslated region contain information enough to promote transcription and to respond to glucocorticoids when fused to a reporter gene and transfected into human fibrosarcoma cells. A moderately repetitive DNA sequence, containing a TATA box, a GRE consensus, a Z-DNA forming sequence and two imperfect direct repeats at the extremities, is present a few nucleotides 5' of the human PAI-1 gene transcription start site, raising the possibility that this gene could have been activated by DNA insertion during evolution.

Base Sequence↗
PubMed1988

Analgesic action of methylphenidate on parkinsonian sensory symptoms. Mechanisms and pathophysiological implications.

Intravenous administration of methylphenidate hydrochloride, a central stimulant, was unexpectedly found to exert a potent analgesic effect on primary sensory symptoms in a group of patients with Parkinson's disease. This effect, which has now been studied in a short-term, double-blind, placebo-controlled experiment, subsequently disappeared if patients were pretreated with a beta-blocker or with a serotonin antagonist. Cerebrospinal fluid monoamine metabolites were determined in some of these patients, and the 5-hydroxyindoleacetic acid level was found to be significantly lower than in parkinsonian patients without pain and in normal volunteers. Given the mechanism of action of methylphenidate on the central nervous system, the adrenergic and serotoninergic mediation of its analgesic effect, and the demonstration of impaired central serotonin metabolism in the patient group, it is concluded that not only central dopaminergic deficiency but also altered noradrenergic and serotoninergic transmission in the spinal cord are quite likely to play a role in the pathophysiology of pain in Parkinson's disease.

Aged↗
PubMed1988

Establishment, characterization and chemosensitivity of two human glioma derived cell lines.

Two continuous human glioma derived cell lines, LI and DF, were established in our laboratory. Both cell lines showed cytological features and in vitro behavior similar to those of the respective original neoplasms. These two lines were characterized for their main biological properties including in vitro and in vivo growth rate, clonogenic ability and tumorigenicity in nude mice. The plating efficiencies were generally high both during exponential and stationary growth phases and a high tumorigenicity was observed. All injected nude mice developed tumors. The two lines were tested for chemosensitivity to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and cis-Diamminedichloroplatinum II (DDP). Heterogeneity in biological features and in drug sensitivity was observed. Exposure of the two lines to BCNU and DDP showed that the glioblastoma (LI) was less sensitive than the anaplastic astrocytoma (DF). For both lines BCNU was more effective on cells in plateau than in exponential phase, while the killing effect of DDP was not phase-dependent.

Animals↗
PubMed1988

Peripheral pharmacokinetic parameters of levodopa/carbidopa and the on-off phenomenon in parkinsonian patients.

The principal peripheral pharmacokinetic parameters of the levodopa/carbidopa association were investigated in 11 healthy volunteers and in 16 patients at various stages of Parkinson disease, with and without the on-off phenomenon. After oral administration of a standard dose of drug (levodopa 250 mg + carbidopa 25 mg) the peak plasma concentrations, peak onset time and area under the curve/time proved to be similar across the groups. There was no difference in peripheral pharmacokinetics of the association between parkinsonian patients with swings in response and those without.

Age Factors↗
PubMed1988

Metabolic control during total parenteral nutrition: use of an artificial endocrine pancreas.

The metabolic impact of total parenteral nutrition (TPN) was evaluated in nine subjects who underwent esophagogastroplasty for esophageal carcinoma. On the second day after operation all subjects were connected to an artificial endocrine pancreas. In four patients only glucose was infused (5.5 mg/kg X min). The remaining five subjects received glucose (4.0 mg/kg X min), amino acid (0.5 mg/kg X min), and lipid emulsion (0.6 mg/kg X min). Plasma glucose concentration was kept constant over 24 hours. However, both insulin requirement (111 +/- 15 v 70 +/- 2 mU/kg X h) and plasma insulin level (99 +/- 15 v 30 +/- 7 microU/mL; P less than .01) were higher during combined TPN. Blood lactate concentration was higher during glucose infusion (P less than .05). No difference was found in blood concentrations of pyruvate, alanine, and ketone bodies. Both glycerol and FFA were higher during combined TPN. The ratio between glucose infusion rate and the average plasma insulin level was calculated as an index of insulin-mediated glucose metabolism; G/I X 100 was markedly reduced during combined TPN (4.5 +/- 0.8 v 20.7 +/- 3.7; P less than .05). Plasma FFA levels were positively correlated with plasma insulin concentration (r = .76) and inversely correlated to G/I X 100 (r = -.73; both P less than .05). In conclusion, during combined TPN a state of insulin resistance is induced and more insulin is required to achieve a normal glucose utilization.

Blood Glucose↗
PubMed1987

Late multifocal gliomas in adolescents previously treated for acute lymphoblastic leukemia.

Three of 37 adolescents in long-term remission from childhood acute lymphoblastic leukemia (ALL) developed malignant multifocal gliomas several years after completing treatment that included central nervous system (CNS) prophylaxis with radiation (RT) and intrathecal methotrexate (IT-MTX). No recurrence of the leukemia was evident when the CNS tumors were discovered. Seventeen other similar cases have been recorded. The occurrence of second malignancies is reviewed in the context of this development and of the oncogenic effects of radiation. It is probable that prolonged exposure to IT-MTX may have had a synergistic effect with radiation in contributing to the unusual incidence of glial tumors in these patients.

Adolescent↗
PubMed1987

Tight linkage of glnA and a putative regulatory gene in Rhizobium leguminosarum.

Rhizobium leguminosarum, biovar viceae, strain RCC1001 contains two glutamine synthetase activities, GSI and GSII. We report here the identification of glnA, the structural gene for GSI. A 2 kb fragment of DNA was shown to complement the Gln- phenotype of Klebsiella pneumoniae glnA mutant strains. DNA sequence analysis revealed an open reading frame (ORF) of 469 codons specifying a polypeptide of 52,040 daltons. Its deduced amino acid sequence was found to be highly homologous to other glutamine synthetase sequences. This ORF was expressed in Escherichia coli minicells and the corresponding polypeptide reacted with an antiserum raised against GSI. Upstream of glnA we found an ORF of 111 codons (ORF111) preceded by the consensus sequence for an ntrA-dependent promoter. Minicells experiments showed a protein band, with a molecular weight in good agreement with that (10,469) deduced from the nucleotide sequence. On the basis of homology studies we discuss the possibility that the product of ORF111 is equivalent to the PII protein of E. coli and plays a similar role in regulation of nitrogen metabolism.

DNA Restriction Enzymes↗
PubMed1987

Transforming growth factor-beta is a strong and fast acting positive regulator of the level of type-1 plasminogen activator inhibitor mRNA in WI-38 human lung fibroblasts.

We have studied the mechanism of a transforming growth factor-beta (TGF-beta)-stimulated production of type-1 plasminogen activator inhibitor (PAI-1) in WI-38 human lung fibroblasts. TGF-beta causes an early increase in the PAI-1 mRNA level which reaches a maximal 50-fold enhancement after 8 h. Blocking of protein synthesis with cycloheximide causes an equally strong increase in the level of PAI-1 mRNA. Quantitative studies of the effect of TGF-beta on PAI-1 protein levels in cell extracts and culture media by using monoclonal antibodies are consistent with the effect on PAI-1 mRNA. The results suggest a primary effect of TGF-beta on PAI-1 gene transcription, and also suggest the possibility that the transcription of this gene in non-induced cells may be suppressed by a short-lived negatively regulating protein. Urokinase-type (u-PA) and tissue-type (t-PA) plasminogen activators are decreased in the culture media of TGF-beta-treated cells concomitantly with the increase in PAI-1 accumulation. These findings show that a primary and important biological effect of TGF-beta may be an overall decreased extracellular proteolytic activity, and give an insight into the molecular mechanisms underlying TGF-beta action at the genetic level.

Cell Line↗
PubMed1987

Plasminogen activator inhibitor type 1 gene is located at region q21.3-q22 of chromosome 7 and genetically linked with cystic fibrosis.

The regional chromosomal location of the human gene for plasminogen activator inhibitor type 1 (PAI1) was determined by three independent methods of gene mapping. PAI1 was localized first to 7cen-q32 and then to 7q21.3-q22 by Southern blot hybridization analysis of a panel of human and mouse somatic cell hybrids with a PAI1 cDNA probe and in situ hybridization, respectively. We identified a frequent HindIII restriction fragment length polymorphism (RFLP) of the PAI1 gene with an information content of 0.369. In family studies using this polymorphism, genetic linkage was found between PAI1 and the loci for erythropoietin (EPO), paraoxonase (PON), the met protooncogene (MET), and cystic fibrosis (CF), all previously assigned to the middle part of the long arm of chromosome 7. The linkage with EPO was closest with an estimated genetic distance of 3 centimorgans, whereas that to CF was 20 centimorgans. A three-point genetic linkage analysis and data from previous studies showed that the most likely order of these loci is EPO, PAI1, PON, (MET, CF), with PAI1 being located centromeric to CF. The PAI1 RFLP may prove to be valuable in ordering genetic markers in the CF-linkage group and may also be valuable in genetic analysis of plasminogen activation-related diseases, such as certain thromboembolic disorders and cancer.

Chromosomes, Human, Pair 7↗
PubMed1987

Plasminogen activator inhibitor type 1 biosynthesis and mRNA level are increased by dexamethasone in human fibrosarcoma cells.

Dexamethasone increases type 1 plasminogen activator inhibitor (PAI-1) activity released from the human fibrosarcoma cell line HT-1080. We demonstrated that dexamethasone caused about 10-fold increases in the intracellular and extracellular levels of PAI-1 protein, as measured by an enzyme-linked immunosorbent assay, in the rate of PAI-1 biosynthesis, and in the PAI-1 mRNA level. The effects on PAI-1 biosynthesis and mRNA level were detectable within 4 h and were maximal 16 to 24 h after the addition of dexamethasone. Cycloheximide did not inhibit the dexamethasone-induced increases in the capacity of the cells to synthesize PAI-1 and in the PAI-1 mRNA level.

Cell Line↗
PubMed1987

Responses to nifedipine by patients with Raynaud's disease and Raynaud's phenomenon secondary to another disease.

Thirteen patients with Raynaud's phenomenon were studied; six patients had the primary disorder and in the other seven progressive systemic sclerosis was diagnosed. Each patient received 10 mg of nifedipine; telethermographic evaluation of the hands was performed in basal conditions and 30 minutes after the administration of the drug. A more marked increase of hand tissue temperature was observed in the patients with progressive systemic sclerosis than in those with the primary disorder.

Adult↗
PubMed1987

Alcohol impairs insulin sensitivity in normal subjects.

The effects of alcohol on insulin action are not yet clearly established. To assess the effects of intravenously administered ethanol on insulin mediated glucose disposal, euglycaemic clamps at 3 different plasma insulin levels and insulin receptor binding studies on circulating monocytes after alcohol infusion were performed. Ethanol infusion leads to a significant reduction of insulin mediated glucose disposal (7.08 +/- 0.4 vs 8.6 +/- 0.6 mg/Kg/min; 9.8 +/- 0.7 vs 13.4 +/- 0.7; 14.7 +/- 0.7 vs 18.1 +/- 0.7 at 33, 73 and 760 mU/m2/min insulin infusion rate respectively). Monocyte insulin-receptor binding was decreased in all the subjects from 30 to 60% after ethanol infusion. These results demonstrate that alcohol can adversely influence the insulin mediated glucose disposal.

Blood Glucose↗
PubMed1986

Plasminogen activator inhibitor type-1: reactive center and amino-terminal heterogeneity determined by protein and cDNA sequencing.

Both the urokinase-type and tissue-type plasminogen activator can convert their approximately 54 kDa type-1 inhibitor (PAI-1) to an inactive form with a lower apparent molecular mass. We have determined the amino-terminal amino acid sequences of human native and converted PAI-1, and isolated PAI-1 cDNA and determined the nucleotide sequence in regions corresponding to the amino-terminus and the cleavage site. The data show that the conversion of the inhibitor consists of cleavage of an Arg-Met bond 33 residues from the carboxy-terminus, thus localizing the reactive center of the inhibitor to that position. In addition, a heterogeneity was found at the amino-terminus, with a Ser-Ala-Val-His-His form and a two-residue shorter form (Val-His-His-) occurring in approximately equal quantities.

Amino Acid Sequence↗