Search PubMed⌕ Search

Biomedical subjects

G Elia

Publications and source records attributed to G Elia.

At least 55 records · Page 3Linked to original sources
PubMed1998

Activation of the heat shock factor 1 by serine protease inhibitors. An effect associated with nuclear factor-kappaB inhibition.

Heat shock proteins (HSPs) have a cytoprotective role in several human diseases, including ischemia and viral infection. Nuclear factor-kappaB (NF-kappaB) is a critical regulator of inflammation and virus replication. Here we report that a class of serine protease inhibitors with NF-kappaB-inhibitory activity are potent HSP inducers via activation of heat shock transcription factor 1 (HSF1) in human cells. 3,4-Dichloroisocoumarin, the most effective compound, rapidly induces HSF1 DNA binding activity and phosphorylation, leading to transcription and translation of heat shock genes for a period of several hours. HSF1 activation is independent of de novo protein synthesis and is correlated in a concentration- and time-dependent manner with NF-kappaB inhibition. Cysteine protease inhibitors E64 and calpain inhibitor II, which do not block NF-kappaB activation, do not induce HSF DNA binding activity. HSP induction by 3,4-dichloroisocoumarin is associated with antiviral activity during rhabdovirus infection. These results identify a new class of HSP inducers and indicate a link between the regulatory pathways of HSF and NF-kappaB, suggesting novel strategies to simultaneously switch on cytoprotective genes and down-regulate inflammatory and viral genes.

Coumarins↗
PubMed1997

Inhibition of nuclear factor kappa B by prostaglandin A1: an effect associated with heat shock transcription factor activation.

Prostaglandins (PGs) function as intracellular signal mediators in the regulation of a variety of physiological and pathological processes, including inflammation and immune responses. Cyclopentenone PGs are characterized by antiviral activity against several viruses, including human immunodeficiency virus type 1 (HIV-1), and by the ability to induce heat shock protein expression through activation of the heat shock transcription factor. Here we report that PGA1 is a potent inhibitor of nuclear factor-kappa B (NF-kappa B) activation in human cells and of NF-kappa B-dependent HIV-1 transcription in long terminal repeat-chloramphenicol acetyl-transferase transient transfection experiments. PGA1 acts by inhibiting phosphorylation and preventing degradation of the NF-kappa B inhibitor I kappa B-alpha. Inhibition does not require protein synthesis, is dependent on the presence of a reactive cyclopentenonic moiety, and is associated with heat shock transcription factor activation. Because NF-kappa B is critically involved in the activation of immunoregulatory and viral genes, inhibition of its activity could be a major component of the immunosuppressive and antiviral activity of PGs.

Cycloheximide↗
PubMed1997

Role of spasmolytic polypeptide in healing of stress-induced gastric lesions in rats.

Stress is known to induce gastric ulcerations but the mechanism of their healing has been little studied. This paper describes the studies on mucosal expression and the effect on ulcer healing of spasmolytic peptide (SP), one of the members of the trefoil peptide family. Gastric ulcerations were induced in rats by the exposition to 3.5 h of water immersion and restraint stress. It was found that the number of these lesions gradually declined at 4, 8 and 12 h after stress and this spontaneous healing was significantly accelerated by s.c. infusion of human recombinant SP in a constant dose of 50 micrograms kg-1 h-1. The healing of the stress-induced ulcerations was accompanied by a gradual restoration of gastric mucosal blood flow and the decrease in gastric acid and pepsin secretion towards the normal values. The expression of SP in rats (rSP) was detected by RT-PCR in the intact mucosa and during all tested time periods reaching a peak at 4 h after the stress. Immunostaining for rSP in the intact mucosa was confined to the mucous neck cells, but following the exposure to stress it was significantly enhanced and occurred also in the cells of the basal region of gastric glands, reaching a peak at 4 h after the stress. We conclude that SP plays an important role in healing of stress-induced gastric lesions possibly by the acceleration of the mucosal repair, the enhancement of mucosal blood flow and the inhibition of gastric secretion.

Animals↗
PubMed1997

Reference values of urinary chromium in Italy.

OBJECTIVES: The paper describes the results of a polycentric study for the assessment of reference values of urinary chromium (U-Cr) in the Italian population. METHOD: A total of 890 subjects (58.3% males and 41.7% females) were selected on the basis of standardized criteria in eight different areas of Italy. Urinary chromium was determined on morning spot samples collected using standardized procedures. The U-Cr was determined independently by three laboratories using an Electrothermic atomization-Atomic Absorption Spectrometry (ETA-AAS) method with a detection limit of 0.05 microgram/l, adopting-for the statistical analysis-the median value of the results of the three laboratories. The between-laboratories within-subjects standard deviation was 0.049 microgram/l. Due to the high proportion (approx, 28%) of undetectable chromium levels, the geometric mean (GM) and geometric standard deviation (GSD) were estimated using a procedure of linear interpolation. The analysis of the effects of some variables (sex, age, center, residence, smoking and drinking habits) on the U-Cr values, was also performed, by multiple regression analysis after logarithmic transformation, using GM and SD. RESULTS: The reference value of U-Cr was of 0.08 microgram/l as an estimated GM, whereas the expected distribution ranged from not detectable (nd) (95% CI = nd-0.06) to 0.24 microgram/l (95th percentile; 95% CI = 0.20-0.31). Among the variables studied, only geographical area and sex significantly influenced the U-Cr levels. In subjects selected in the provinces of Bari and Venice values of U-Cr were significantly lower than those determined in subjects residing in other areas. CONCLUSIONS: From our investigation the reference values for U-Cr were lower than those obtained in previous investigations. In addition it confirms a further reduction in U-Cr levels following the previous decline reported in the 1970s and 1980s. In over 20 years U-Cr values in the general population dropped from values greater than 1 microgram/l to values between 0.5 and 0.2 microgram/l. The reasons of this progressive decline cannot be attributed in our opinion to a reduced intake of the metal, but mainly to the improvement in analytical instrumentation and methods. A further decrease may be ascribed to a more accurate definition of the reference groups and to a better control of pre-analytical factors. Considering that the reference values for U-Cr are much lower than those determined some decades ago, toxicological studies in order to verify the significance of biological limit values currently suggested for chromium seem to be necessary.

Adult↗
PubMed1996

2-Cyclopenten-1-one, a new inducer of heat shock protein 70 with antiviral activity.

The cytoprotective role of heat shock proteins (HSP) described in variety of human diseases, including ischemia, inflammation, and infection, suggests new therapeutic strategies relying upon the development of drugs that selectively turn on heat shock genes. Cyclopentenone prostaglandins, which contain an alpha, beta-unsaturated carbonyl group in the cyclopentane ring and possess antiviral activity against several RNA and DNA viruses, were shown to function as signal for HSP synthesis in a nonstressful situation in a variety of mammalian cells. We now report that 2-cyclopenten-1-one selectively induces the expression of the 70-kDa HSP (HSP70) in human cells, through cycloheximide-sensitive activation of heat shock transcription factor 1 (HSF1). The alpha, beta-unsaturated carbonyl group is the key structure triggering HSF1 activation. Induction is associated with antiviral activity during infection with vesicular stomatitis virus. These results identify the molecular structure of natural prostaglandins responsible for HSF1 activation and open new perspectives in the search for novel antiviral and cytoprotective drugs.

Blotting, Western↗
PubMed1996

Inhibition of HSP70 expression by calcium ionophore A23187 in human cells. An effect independent of the acquisition of DNA-binding activity by the heat shock transcription factor.

Heat shock proteins (HSPs) are induced in mammalian cells in a variety of pathophysiological states and have an important role in cytoprotection in vitro and in vivo. In this study, we report that the calcium ionophore A23187, a glucose-regulated protein (GRP) inducer, dramatically inhibits HSP70 synthesis and HSP70 mRNA transcription after induction by heat shock, sodium arsenite, or prostaglandin A1 treatment in human K562 cells. A23187 does not suppress, and it actually prolongs, the DNA-binding activity of the human heat shock transcription factor (HSF), while it alters HSF1 phosphorylation in heat shock-treated cells. To inhibit HSP70 expression, A23187 needs to be present during heat shock, while treatment before or after heat shock does not affect HSP70 mRNA transcription. The GRP inducer thapsigargin, which specifically inhibits the endoplasmic reticulum Ca2+-ATPase, has no effect on heat-induced HSP70 synthesis, indicating that A23187 inhibitory activity is not due to depletion of intracellular calcium stores and is independent of the concomitant induction of GRP genes. Inhibition of HSP70 expression is correlated with alterations in HSF1 phosphorylation in heat-shocked cells, but not in sodium arsenite-treated cells, indicating that different mechanisms may be involved in mediating A23187 inhibitory activity.

Calcimycin↗
PubMed1996

Polyclonal origin of colonic adenomas in an XO/XY patient with FAP.

It is widely accepted that tumors are monoclonal in origin, arising from a mutation or series of mutations in a single cell and its descendants. The clonal origin of colonic adenomas and uninvolved intestinal mucosa from an XO/XY mosaic individual with familial adenomatous polyposis (FAP) was examined directly by in situ hybridization with Y chromosome probes. In this patient, the crypts of the small and large intestine were clonal, but at least 76 percent of the microadenomas were polyclonal in origin.

Adenomatous Polyposis Coli↗
PubMed1996

Modulation of prostaglandin A1-induced thermotolerance by quercetin in human leukemic cells: role of heat shock protein 70.

Prostaglandins of the A type (PGAs) function as signals for heat shock protein (hsp) synthesis in mammalian cells. In human K562 erythroleukemic cells, PGA1 induces the synthesis of a M(r) 70,000 hsp (hsp70) by cycloheximide-sensitive activation of heat shock transcription factor (HSF). Induction of hsp70 has been associated recently with the ability of PGA to protect K562 cells from thermal injury, establishing a thermotolerant state; however, the role of hsp70 in thermotolerance is still controversial. Because quercetin was shown to modulate hsp70 expression after heat shock in K562 cells, we have investigated the effect of this flavonoid on HSF activation, hsp70 synthesis, and thermotolerance in human K562 cells after induction with PGA1. Quercetin was found to inhibit hsp70 synthesis for a period of 3-6 h after PGA1 treatment. This transient block was exerted at the transcriptional level and was not due to the loss of HSF DNA-binding activity. After the initial delay, hsp70 synthesis reached the same rate as the PGA1-treated control, and it was actually prolonged in the presence of quercetin. In PGA1-treated cells, quercetin suppressed PGA1-induced thermotolerance completely if the heat shock was applied at a time (6 h) when hsp70 synthesis was inhibited, whereas it could not prevent the establishment of a thermotolerant state if the heat challenge was applied 24 h after treatment, when hsp70 synthesis was not affected. These results support strongly the hypothesis that hsp70 is involved in the establishment of thermotolerance in human cells.

Dose-Response Relationship, Drug↗
PubMed1996

Periurethral collagen implant: ultrasound assessment and prediction of outcome.

The objective of this study was to identify sonographic parameters that could predict successful outcome in women after periurethral collagen implant. Thirty-one women with a diagnosis of stress urinary incontinence with intrinsic sphincteric deficiency underwent one periurethral collagen implant between January and December 1994. Three months after the procedure ultrasound evaluation was performed using a 5 MHz probe placed at the vaginal introitus. Subjective assessment and cough stress test were used to measure outcomes. Twenty-five women were available for evaluation 1 year after the procedure. A successful outcome was found in 18 of the 25 women subjectively (72%) and in 16 objectively (64%). A distance of the collagen from the bladder neck of less than 7 mm was found to be associated with a positive outcome. This threshold was found to have a sensitivity of 83.3%, specificity of 85.7%, a positive predictive value of 93.7% and a negative predictive value of 66.6%.

Collagen↗
PubMed1996

Assessment of exposure to inorganic arsenic, a human carcinogen, due to the consumption of seafood.

To assess whether regular consumption of seafood, particularly fish and shellfish, by humans may lead to an overexposure to inorganic arsenic, a well-established human carcinogen, the urinary excretion of the relevant As metabolites (Asi, inorganic form; MMA, monomethylarsonic acid; DMA, dimethylarsinic acid) was compared in groups of subjects with different seafood consumption habits and in volunteers after ingestion of a known amount of seafood arsenicals. Studies of Italian cohorts, involving five groups of +/-30 subjects with different seafood consumption habits, and balance studies in Belgian volunteers failed to show a biologically significant absorption of inorganic arsenic either present as such in the food or formed from organoarsenicals during cooking or digestion. The results suggest that the digestion of some seafood, especially mussels, may increase the urinary excretion of the dimethylated arsenic metabolite. Therefore, the biological monitoring of exposure to inorganic arsenic in an industrial context should mainly rely upon specific measurement of the unmetabolized form when recent ingestion of seafood cannot be excluded.

Arsenic↗
PubMed1996

Characterization of monoclonal antibodies raised to C-terminal peptides of pS2: a major trefoil peptide and motility factor expressed in adenocarcinomas and regions of mucosal injury.

Two novel monoclonal antibodies, GE1 and GE2 raised against the C-terminal 31 and 28 amino acids of the estrogen-inducible trefoil peptide pS2, are described. Both antibodies are able to detect pS2 in formalin-fixed, paraffin-embedded tissues. Conditions are presented under which pS2 can be shown in cell lines by immunohistochemistry that has previously been problematic. The antibodies can specifically show the presence of pS2 in cell lysates by Western blotting and immunoprecipitation. In the form of an affinity column, the GE1 monoclonal antibody can be used to purify pS2 from MCF-7 supernatants. The eluted peptide from the GE1 affinity column shows a single band at 6,600 Da (predicted size for pS2) on Western blotting. These antibodies are valuable reagents in the analysis of the role of trefoil peptides in the maintenance of mucosal integrity, and may have applications in the assessment of pS2 expression in chronic gastrointestinal ulceration and adenocarcinomas that secrete pS2, where it may serve as a prognostic marker.

Adenocarcinoma↗
PubMed1996

Distribution and expression of pancreatic secretory trypsin inhibitor and its possible role in epithelial restitution.

Pancreatic secretory trypsin inhibitor (PSTI) is a potent serine protease inhibitor that prevents excessive digestion of the gastrointestinal mucus but may also directly affect epithelial function. We therefore examined the distribution of PSTI in the human adult and fetus using immunohistochemistry and in situ hybridization and examined its effects on cell proliferation and migration in vitro. PSTI peptide and mRNA were found in the exocrine pancreas, mucus-producing cells of the normal gastrointestinal tract, acinar component of the normal breast, and surface epithelial cells at the edge of benign gastric ulcers. Peptide, but not message, was identified in the renal proximal tubule, probably reflecting reabsorption of filtered peptide. Purified human PSTI did not affect proliferation of the human colonic cell line HT-29 but caused a threefold increase in the rate of migration in an in vitro wounding model of restitution. This effect was inhibited by co-administering a PSTI-neutralizing antibody, a transforming growth factor-beta-neutralizing antibody, or an epidermal growth factor receptor-blocking antibody. As PSTI is widely distributed in several human organ systems and stimulates cell migration in vitro, we conclude that PSTI is likely to have additional roles to that of preserving the gastrointestinal mucous layer from excessive digestion.

Adult↗
PubMed1996

[The innervation of the digestive tract: its morphofunctional and neurochemical aspects].

The innervation of the alimentary tract (or enteric nervous system, ENS) represents the third division of the autonomic nervous system and it appears to be unique for its intrinsic ability to mediate reflex activity even when disconnected from the central nervous system. Enteric nerve cells can be classified in subclasses according to combined classic morphological criteria (Dogiel type I, II and III) and electrophysiological properties (type S and AH). A further major feature of the ENS lies in the variety of chemical messengers expressed in its neuronal elements. These substances can act either as neurotransmitters or neuromodulators. A common finding of enteric neurons is to synthetize and store several chemical messengers, a phenomenon known as neurochemical coding. As a consequence, neurotransmission involves the release and action of more than one messenger, an event referred to as plurichemical transmission. Recently, the use of combination of methods (such as immunohistochemical, pharmacological and electrophysiological techniques) has led to the identification of specific functionally distinct categories of enteric neurons. Thus, inhibitory and excitatory motor neurons, interneurons, vasomotor and sensory neurons are now recognized to constitute the complex network of the ENS. These neuronal elements are synaptically connected to form microcircuits which play a pivotal role to control digestive functions, including motility, blood flow, secretion and absorbtion.

Animals↗
PubMed1995

Abnormalities of the RB1 and DCC tumor suppressor genes: uncommon in human pancreatic adenocarcinoma.

Evidence of RB1 allele loss was found in only 6% of pancreatic cancers, and we found no significant sequence abnormalities nor loss of RB protein expression in a panel of tumors and cell lines. Using reverse transcription-polymerase chain reaction and Southern blot analysis, we found no evidence for loss of DCC expression in pancreatic cancer cell lines, and allele loss only rarely in tumor biopsies. These findings suggest that abnormalities of RB1 and DCC are unlikely to play a major role in pancreatic carcinogenesis.

Adenocarcinoma↗
PubMed1995

A prospective randomized comparison of an attached silver-impregnated cuff to prevent central venous catheter-associated infection.

The VitaCuff catheter, a specialized central venous catheter (CVC) with an attached silver-impregnated cuff, is designed to permit percutaneous placement and prolonged venous access. A prospective randomized study was undertaken comparing the VitaCuff with standard triple lumen catheters to determine if the VitaCuff reduces infection during extended use. All consenting patients underwent percutaneous placement of subclavian lines. By study design, control and VitaCuff catheters could remain in site for up to 7 and 14 days, respectively. Cultures were obtained from the preinsertion skin site, and upon removal, from the skin, hubs, infusates, CVC tip, and cuff. Statistical methods included chi 2, the Student t test, and the log-rank test on Kaplan-Meier estimates. Of 133 patients completing this study, 64 patients (48.1%) underwent VitaCuff placement and 69 patients (51.8%) served as controls. In 124 patients (93.2%), the indication for catheter placement was for perioperative care. Overall, 67 patients (50.4%) required central venous access > 7 days, necessitating > or = 1 additional line in 29 patients (21.8%). The incidence of pneumothorax per patient from the initial central line insertion was 4/104 (3.85%), significantly lower than the 4/29 (13.8%) incidence during secondary catheter placement (P = 0.046). Culture results upon catheter removal demonstrated a reduction in colonization of skin sites and hubs for the VitaCuff patients, but not for catheter tips or infusates. Regardless of the type of catheter used, colonization was dependent upon duration of insertion. The incidence of catheter-related sepsis was 6.8%, and did not differ significantly between the study groups. Multiple CVC insertions increase the incidence of pneumothorax. Because VitaCuff catheters permit extended access up to 14 days without increasing the incidence of sepsis, we recommend their use in patients who require prolonged CVC access.

Catheterization, Central Venous↗
PubMed1995

Three surgical procedures for genuine stress incontinence: five-year follow-up of a prospective randomized study.

OBJECTIVE: Our purpose was to evaluate and compare the long-term results of the Kelly plication, modified Pereyra needle suspension, and Burch urethropexy for the treatment of stress urinary incontinence in women. STUDY DESIGN: One hundred twenty-seven consecutive women underwent surgery at the gynecologic urology division at Women's Hospital, Los Angeles County-University of Southern California Medical Center between January 1986 and June 1987. The only indication for surgery was stress urinary incontinence. Women with previously failed antiincontinence procedures were excluded. Fifty-three patients were premenopausal and 74 postmenopausal. History, physical examination, urethocystoscopy, cotton swab test, filling cystometry, urethral pressure profile at rest and on cough, and uroflowmetry were performed preoperatively, 3 months, 1 year, and 5 years postoperatively. The subjects and surgeons were randomly allocated to one of three surgical procedures: group 1 had anterior colporrhaphy with Kelly plication, group 2 had modified Pereyra needle urethropexy, and group 3 had Burch urethropexy. One hundred seven women were available after 1 year, and 93 were the subjects of the 5-year evaluation. Fisher exact text, chi 2, t test, and paired t test were used for statistical analysis. RESULTS: The results of the 1-year postoperative evaluation has been previously published. The objective success rate for groups 1, 2, and 3 after 5 years was 37%, 43%, and 82%, respectively, and the difference was statistically significant. The drop in the success rate in 4 years was 26%, 22%, and 7% for groups 1, 2, and 3, respectively. Urodynamically all three procedures significantly increased the abdominal pressure transmission to the urethra, when successful. Ninety-one percent of women after the Burch procedure had a negative cotton swab test after 5 years compared with 46% for the Pereyra and 30% for the Kelly procedures. CONCLUSIONS: In our hands the Burch urethropexy has a higher cure rate that holds over time when compared with the modified Pereyra needle suspension and the Kelly plication. The lower incidence of the positive cotton swab test in women after Burch urethropexy may be proof of a better anatomic suspension of the bladder neck.

Adult↗
PubMed1995

Supernumerary ovary with an endometrioma and osseous metaplasia: a case report.

A 32-year-old-woman with a history of endometriosis and chronic pelvic pain had left-sided pain and ultrasonographic documentation of a left pelvic complex cyst approximately 5 cm in diameter. Laparotomy revealed a left retroperitoneal cystic mass adjacent to the iliopsoas muscle and overlying the major pelvic vessels. The mass was dissected and excised. Histopathologic study revealed endometrioma and osseous metaplasia in a supernumerary ovary.

Adult↗