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Biomedical subjects

E Conti

Publications and source records attributed to E Conti.

At least 91 records · Page 5Linked to original sources
PubMed1995

Differences in vasodilatory response to dipyridamole between patients with angina and normal coronary arteries and patients with successful coronary angioplasty.

BACKGROUND: Previous studies reported a reduced coronary blood flow reserve, assessed by the intravenous administration of dipyridamole, in patients with angina and normal coronary arteries, and early after successful coronary angioplasty, which suggests the presence of small coronary vessel dysfunction. This study aimed to establish whether the mechanisms of small coronary vessel disease in these two groups of patients are similar. METHODS: The effects of the intracoronary infusion of adenosine and dipyridamole (maximum dose 2.7 and 7.5 mg/min, respectively) on coronary blood flow velocity were assessed in 11 patients with angina and normal coronary arteries (group A) and in 12 patients immediately after successful coronary angioplasty (group B) using a 0.018" Doppler wire. RESULTS: Baseline coronary blood flow velocity was significantly higher in group B than group A (34 +/- 14 versus 19 +/- 8 cm/s; P = 0.001). In group A, coronary blood flow velocity was higher during adenosine than dipyridamole infusion (74 +/- 17 versus 58 +/- 21 cm/s; P < 0.001), whereas in group B velocities were similar (85 +/- 30 versus 78 +/- 32 cm/s; NS). CONCLUSIONS: In patients with angina and normal coronary arteries, a maximal dose of adenosine causes a greater coronary dilation than that of dipyridamole. Given that dipyridamole operates mainly through an inhibition of adenosine re-uptake, it can only dilate the arteriolar segments exposed to endogenous adenosine. Therefore, the lower response to dipyridamole than to exogenous adenosine observed in patients with angina and normal coronary arteries suggests an impairment of the pre-arterioles that are not influenced by endogenous adenosine, resulting in a limited flow-mediated dilation in response to arteriolar dilation. Such an impairment is not apparent immediately after successful coronary angioplasty, where the most obvious abnormality is an increase of baseline coronary blood flow velocity.

Adenosine↗
PubMed1994

Overview of a quality assurance/quality control compliance program consistent with FDA regulations and policies for somatic cell and gene therapies: a four year experience.

Somatic cell and gene therapy involve the application of biological technologies to an individual patient through the use of living cells which provide a therapeutic benefit (Aliski, 1991). Various forms of cellular and gene therapies are being developed and evaluated in an increasing number of clinical trials for congenital and acquired disorders. The potential and progress of these therapeutic applications have resulted in an increasing effort by the Food and Drug Administration (FDA) to develop the regulatory framework under which these therapeutic approaches would insure safety and efficacy, the primary mandate of the FDA. Over five years ago Cellcor began to define the parameters, specifications, and conditions relevant to a Quality Assurance/Quality Control (QA/QC) program that has evolved to insure safety and maximize the efficacy of applications of the company's ex vivo technology, autolymphocyte therapy. Autolymphocyte therapy is an outpatient form of somatic cell immunotherapy based upon the infusion of T cells that have been activated ex vivo using a combination of previously generated autologous cytokines and an anti-CD3 monoclonal antibody. We have been able to demonstrate the feasibility for the safe, controlled, and consistent preparation and delivery of a cellular therapy by application of relevant GMP regulations. This presentation reviews aspects of this program and chronicles our experience which at present amounts to over 4400 in fusions for over 700 patients. This program provides a high degree of assurance that a cellular therapy program can be carried out in a multisite mode involving hundreds of patients through the strict adherence to cGMP as set forth in existing regulations.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Transplantation↗
PubMed1994

Kaposi's sarcoma in Italy before and after the AIDS epidemic.

The incidence of Kaposi's sarcoma (KS) in 1976-90 was assessed in Italy, taking advantage of a network of nine population-based cancer registries covering, at its maximum, approximately 5.6 million subjects. The first examined period (1976-84) substantially reflects the epidemiology of KS prior to the AIDS epidemic in the registration areas. Elevated incidence rates, standardised to the Italian population of 1981, of 1.05/100,000 men and 0.27/100,000 women emerged in 1976-84 (i.e. from two- to threefold higher than in the USA and Sweden, more than tenfold higher than in England and Wales). These high rates, especially remarkable in the Registry from the south of Italy (i.e. Ragusa, 3.01/100,000 men and 0.54/100,000 women) suggest that the prevalence of the still unknown causative agent for KS was high, at least in some parts of Italy, prior to the AIDS epidemic. In the most recent period (1985-90), an approximately twofold increase in KS incidence rates in Italian men below age 50 was observed (from 0.15 in 1976-84 to 0.47 in 1985-90). Conversely, declines in KS incidence were recorded in older men.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Fertility drugs and risk of epithelial ovarian cancer in Italy.

The report of an increase of ovarian cancer risk among women who had used fertility drugs prompted us to analyse the relationship between fertility drugs and ovarian cancer in a case-control study which has been ongoing in four areas of Italy since 1992. The present analysis is based on 195 epithelial ovarian cancer cases and 1339 controls admitted to hospital for diseases other than gynaecological or malignant conditions. Fewer ovarian cancer cases than controls reported use of fertility drugs (odds ratio, after allowance for potential confounding factors: 0.7, 95% confidence interval: 0.2-3.3). Among nulligravid women, 5/177 control women compared with 0/36 cancer cases reported having ever used fertility drugs. Although only based on small numbers of women who were suffering from ovarian cancer and who had also used fertility drugs, the present study indicated that a role of ovarian stimulation in the aetiology of epithelial ovarian cancer is not established, although it is worth investigating.

Adolescent↗
PubMed1994

[Wall stress in the assessment of left ventricular function in surgery of abdominal aortic aneurysm. Validity and importance of transesophageal echocardiography (TEE) in intraoperative monitoring].

OBJECTIVE: To verify the applicability and the clinical significance of left ventricular wall stress determinations by intraoperative transesophageal echocardiography (TEE) during resections of abdominal aortic aneurysms. DESIGNS: Prospective comparison of changes in left ventricular wall stress between two groups of patients with and without coronary artery disease. SETTING: Operatory room of Universitary Institute. PATIENTS: Twenty-three patients with abdominal aortic aneurysms; 8 had clinically evident coronary artery disease (CAD+); 15 patients did not have clinical or electrocardiographic evidence of coronary artery disease (CAD-). INTERVENTIONS: Resection of the aortic aneurysm and insertion of a synthetic prosthesis. MEASUREMENTS AND MAIN RESULTS: During operation transesophageal monitoring of left ventricular volumes and wall stress was performed during induction of anesthesia (T1), for two minutes after aortic clamping (T2), at the end of the proximal anastomosis (T3), for two minutes after aortic declamping (T4) and at the end of the procedure (T5). Circumpherential stress at end systole (sES) and end diastole (sED) was more sensitive than hemodynamic and volumetric parameters in detecting changes i function of the ischemic myocardium. In detail we observed: a significant increase of sES in CAD+versus CAD- at T2: 98 (sd 18) vs 83 (sd 14) 10(3) dyne/cm2. a significant increase of sED in CAD + versus CAD- at T2: 28.5 (sd 6) vs 22 (sd 4.5) 10(3) dyne/cm3. a similar trend of sES and sED at T4: 73 (sd 20.5) vs 46 (sd 15) 10(3) dyne/cm2 and 31 (sd 12) vs 16 (sd 7.7) 10(3) dyne/cm2 respectively. a significant increase of sED in CAD + at T5 (about 20' after T4): 26.5 (sd 9.5) vs 16 (sd 5.2) 10(3) dyne/cm2 which is expression of a persistent reduction of ventricular compliance in the ischemic patients. CONCLUSIONS: Wall stress modifies MVO2 and subsequently is sensitive in detecting changes in myocardial performance. TEE could valuably integrate routine hemodynamic monitoring of patients with coronary heart disease who undergo surgical resection of abdominal aortic aneurysms.

Aged↗
PubMed1993

X-ray crystal structure of ferric Aplysia limacina myoglobin in different liganded states.

The X-ray crystal structure of the ligand-free ferric form of Aplysia limacina myoglobin (pH 6.0) has been refined at 1.7 A resolution (R = 15.1%), and its cyanide, thiocyanate and imidazole derivatives studied by difference Fourier techniques at atomic resolution. The crystallographic R-factors of the three different derivatives reported are 16.1%, 16.1% and 15.6% at 1.8 A, 2.0 A and 2.0 A resolution, respectively. The present results have been analyzed in parallel with previous crystallographic studies on the molecular structures of the fluoride and azide derivatives of ferric Aplysia limacina myoglobin. Ligand binding to the distal site of the heme pocket results in different networks of hydrogen bonds involving to various degrees the bound ligand, residue Arg(66)E10, the heme propionate III, ordered water molecules and/or protein backbone atoms from the CD region. In particular, Arg(66)E10 stabilizes the bound ligand and compensates for the absence of the hydrogen bond donor residue HisE7, commonly present in oxygen-carrying globins.

Animals↗
PubMed1993

Activated estrogen receptor mediates growth arrest and differentiation of a neuroblastoma cell line.

Several reports demonstrate estrogen receptor involvement in specific brain functions. In addition, estrogen receptors are expressed at early stages of brain development, suggesting that estrogens or related molecules may play an instructive role in the differentiation of specific brain areas. The lack of model systems in which these phenomena could be studied prompted us to develop a neuroblastoma cell line expressing the estrogen receptor. The cell line expresses the hormone receptor at levels compatible with a physiological activity. The activated estrogen receptor is capable of blocking proliferation of the cells without exerting toxic effects. Following growth arrest, the cells display a neuron-like morphology and express tau and synaptophysin, two proteins synthesized in differentiating neurons. The cell line generated will provide a valuable model system for molecular and biochemical studies of the activity of estrogens in neural-derived cells.

Cell Differentiation↗
PubMed1993

Cocaine effects on brain noradrenergic neurons of anesthetized and unanesthetized rats.

The present study characterized and quantified the effects of systemically administered cocaine on spontaneous, sensory-evoked and stress-elicited activity of noradrenergic locus coeruleus (LC) neurons of anesthetized and unanesthetized rats. Cocaine (0.1-3.0 mg/kg, i.v.) decreased LC spontaneous discharge rate and discharge evoked by repeated sciatic nerve stimulation in halothane-anesthetized rats. In unanesthetized rats cocaine (0.3-10.0 mg/kg, i.v.) also decreased LC spontaneous discharge rate and LC discharge evoked by repeated auditory stimulation. However, analysis of variance revealed a statistically significant shift to the right in the cocaine dose-response curves for effects on tonic and evoked LC discharge in unanesthetized compared to anesthetized rats. Thus, cocaine was somewhat less potent in inhibiting tonic and evoked discharge of unanesthetized rats compared to anesthetized rats. In anesthetized rats cocaine (1.0 mg/kg) did not affect LC activation by intracerebroventricularly (i.c.v.) administered corticotropin-releasing factor (3.0 micrograms in 3.0 microliters) or by hemodynamic stress elicited by i.v. nitroprusside infusion. The present findings demonstrate that cocaine has similar effects on LC neurons of anesthetized and unanesthetized rats but that it is less potent in unanesthetized rats. These effects of cocaine at noradrenergic cell bodies acting in concert with its effects at noradrenergic terminals in LC target regions may be important in the overall action of cocaine on arousal and cortical information processing.

Anesthesia↗
PubMed1993

Long term prognosis of asymptomatic carotid artery occlusion.

Twenty six asymptomatic patients with internal carotid artery occlusion had ultrasound follow-up for a mean period of 34.3 months. During follow-up 3 patients (11.5%) reported transitory ischemic attacks (TIAs), one of these (3.8%) occurred in the vascular territory ipsilateral to the occlusion. There were not strokes. Annual TIA rate was 4% for all vascular territories, and 1.3% for the territory ipsilateral to the occlusion. Annual mortality was 9.4%. Our data on stroke risk in patients with asymptomatic carotid artery occlusion show a good prognosis in the long-term.

Adult↗
PubMed1992

Structural study and preliminary crystallographic data for the hemoglobin from reindeer (Rangifer tarandus tarandus)

The ferric form of reindeer hemoglobin (Rangifer tarandus tarandus) has been crystallized in an orthorhombic crystalline form from polyethylene glycol solutions, at pH 8.2. The crystals belong to the orthorhombic space group P2(1)2(1)2(1), with unit cell edges a = 84.2 A, b = 59.9 A, c = 119.5 A; one hemoglobin tetramer is contained in the asymmetric unit. The crystals diffract X-rays to a limit spacing of 3.0 A. Inspection of amino acid sequences in the N-terminal region of beta-chains, and analysis of hemoglobin three-dimensional models, allows one to rationalize, on a molecular basis, the reduced O2 affinity and the decreased effect of organic phosphates observed in ruminant hemoglobins. By analogy, the analysis is extended to birds and reptiles, whose hemoglobin beta-chains display, as in ruminants, the deletion of the N-terminal residue and a methionine at the NA2 position.

2,3-Diphosphoglycerate↗
PubMed1992

Mechanism of loss of thermodynamic control in mitochondria due to hyperthyroidism and temperature.

Incubation of normal mitochondria at 45 degrees C results in increases of respiration and of total apparent proton conductance (TAPC, respiration/proton motive force) and in an upward shift of the flow-force relationships. Similar effects are observed during operation of the redox proton pumps at different sites of the respiratory chain. These effects are accompanied by an almost equivalent increase of the passive proton conductance (PPC, proton leakage/proton motive force). In mitochondria from 3,3,5-triiodo-L-thyronine (T3)-treated rats there are also increases of respiration and of TAPC and an upward shift of flow-force relationships, more pronounced at the level of the cytochrome oxidase proton pump. However, at variance from the incubation at 45 degrees C, in mitochondria from T3-treated rats there is only a slight increase of PPC. Addition of bovine serum albumin to normal mitochondria incubated at 45 degrees C results in a marked depression of TAPC in the nonlinear range of the flow-force relationships. An equivalent effect is not observed in mitochondria from T3-treated rats. The experimental results have been compared with computer simulations obtained on the basis of a chemiosmotic model of energy transduction. The increase of TAPC following incubation at high temperature is apparently due to changes of the proton conductance mainly at the level of PPC, while the increase of TAPC following T3 administration is rather due to changes presumably at the level of the redox or ATPase proton pumps.

Adenosine Triphosphate↗
PubMed1992

Quantitation of red cell-bound IgG by an enzyme-linked antiglobulin test in human immunodeficiency virus-infected persons.

Anemia, thrombocytopenia, and neutropenia have been observed in patients with acquired immune deficiency syndrome (AIDS) and AIDS-related complex. To investigate whether red cells (RBCs) of patients with human immunodeficiency virus infection were coated with IgG and/or complement (C3), blood samples of 239 patients were tested. The prevalence of a positive direct antiglobulin test on RBCs was 16.7 percent. By use of an enzyme-linked antiglobulin test (ELAT) to measure more accurately the number of IgG molecules per RBC in a group of 67 patients, 30 of the 67 individuals were observed to have increased numbers (mean, 155) compared to normal controls and to patients with hypergammaglobulinemia due to multiple myeloma or chronic liver disease. Hemoglobin level was correlated with the number of IgG molecules per RBC (p = 0.008), but no correlation could be demonstrated between those numbers and serum immunoglobulin (p = 0.10) or circulating immune complexes (p = 0.38). Our results with ELAT suggest that some AIDS patients may have specific binding of IgG on the surface of their RBCs, rather than nonspecific uptake; further clinical correlations are necessary to confirm these findings.

Brazil↗
PubMed1992

Effects of subinhibitory concentrations of ciclopirox on the adherence of Candida albicans to human buccal and vaginal epithelial cells.

At present, only a limited number of studies of the effects of sub-inhibitory antifungal agents on the adherence of Candida to epithelial (buccal and vaginal) host cells are available. The adherence of Candida albicans to the epithelial cell surface is accepted as an important first step in persistent colonization and in the following symptomatic or asymptomatic infection of mucosal surface. Ciclopirox (ciclopiroxolamine, CAS 29342-05-0) is a substituted pyridone antimycotic drug, unrelated to the imidazole derivatives and its topical application ensures maximum local bioavailability. The present study was done to investigate the effects of sub-inhibitory concentrations of ciclopirox on the adherence of Candida albicans to human buccal and vaginal epithelial cells. The findings on the adherence of different strains of Candida indicate that the drug caused a significant reduction in the mean number of Candida adhering to both buccal and vaginal cells. This reduction was maximal at concentration of 1/2 MIC and still significant at 1/4, 1/8, 1/16 MIC, but with progressive return to mean control values at 1/32 MIC. Ciclopirox acts on fungi by inhibiting the intracellular uptake of essential substrates and ions and this probably acts on the Candida ability to express its adherence mechanisms.

Antifungal Agents↗
PubMed1991

Activation of respiration and loss of thermodynamic control in hyperthyroidism. Is it due to increased slipping in mitochondrial proton pumps?

T3 administration increases the extent of non-linearity in the flow-force relationship between pump proton conductance and protonmotive force. The effect is present also at the ATPase proton pump. These effects are not accompanied by changes in passive proton conductance. Incubation of mitochondria at 45 degrees C also causes an increased non-linearity, accompanied by a partial increase of proton conductance. It appears that the increase of respiratory activity following T3 administration is due to loss of thermodynamic control within or at the proton pumps, an effect which might be attributed to increased slipping.

Adenosine Triphosphatases↗
PubMed1991

Flux ratios and pump stoichiometries at sites II and III in liver mitochondria. Effect of slips and leaks.

Addition of bovine serum albumin to state 4 mitochondria results in a depression of the proton leak and of the resting respiration of 70 and 25%, respectively. The conductance membrane potential diagram, both in the ohmic and in the non-ohmic region, shows that in the presence of bovine serum albumin the level of ohmic conductance is lowered while that of non-ohmic conductance is increased toward higher delta psi values. The same effect is observed during operation of the different proton pumps. Addition of chloroform affects the conductance membrane potential diagram in the following manner: there is no effect in the ohmic region with all pumps, while there is an effect in the non-ohmic region either at site III or at sites II plus III but not at site II. This suggests a possible effect of chloroform at the level of the cytochrome oxidase proton pump. During titration with oligomycin of the ATPase proton pump the conductance potential diagram shows a region of non-ohmicity only in the presence but not in the absence of an ATP-regenerating system. Protonophoric uncouplers such as carbonyl cyanide p(trifluoromethoxy)phenylhydrazone and intrinsic uncouplers such as chloroform have different effects on the relationship between rates of charge translocation and of oxygen consumption, and thus on the pump stoichiometries, in that the slope of the diagram is modified by the latter but not by the former. The differential effects of protonophores and of intrinsic uncouplers on the stoichiometries have been analyzed by computer simulations and represent an additional criterion to distinguish between extrinsic and intrinsic mechanisms of uncoupling.

Adenosine Triphosphatases↗