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Biomedical subjects

M Schena

Publications and source records attributed to M Schena.

At least 19 recordsLinked to original sources
PubMed2004

Weekly cisplatin paclitaxel and continuous infusion fluorouracil in patients with recurrent and/or metastatic head and neck squamous cell carcinoma: a phase II study.

BACKGROUND: Cisplatin, paclitaxel and 5-fluorouracil (5-FU) have demonstrated significant activity in patients with advanced squamous head and neck cancer (HNSCC) despite relevant toxicity. A weekly administration of cisplatin and paclitaxel with continuous infusion of 5-FU could offer a better toxicity profile without affecting dose intensity or treatment outcome. We evaluated the toxicity and the activity of weekly cisplatin/paclitaxel with continuous infusion 5-FU in patients with recurrent and/or metastatic HNSCC. METHODS: A total of 44 patients were studied. Treatment consisted of two 6-week cycles with weekly cisplatin 20 mg/m2 and paclitaxel 60 mg/m2 and daily continuous infusion 5-FU 200 mg/m2 from day 1 to 42. Patients were evaluated for toxicity and response. RESULTS: 40 out of 44 patients were evaluable for response. After two cycles we observed seven complete responses (16%) and 12 partial responses (27%), with a 43% (95% CI 28-58%) overall response rate. Stable disease was seen in 13 patients (29%) and progressive disease in 12 patients (27%). Toxicity was mild in treated patients: we observed less than 10% of grade 3/4 hematological and gastroenteric toxicity. CONCLUSIONS: A weekly schedule of cisplatin and paclitaxel associated with continuous infusion 5-FU showed low toxicity in the treatment of advanced HNSCC while significant activity was conserved.

Adult↗
PubMed2000

Identification of the SAAT gene involved in strawberry flavor biogenesis by use of DNA microarrays.

Fruit flavor is a result of a complex mixture of numerous compounds. The formation of these compounds is closely correlated with the metabolic changes occurring during fruit maturation. Here, we describe the use of DNA microarrays and appropriate statistical analyses to dissect a complex developmental process. In doing so, we have identified a novel strawberry alcohol acyltransferase (SAAT) gene that plays a crucial role in flavor biogenesis in ripening fruit. Volatile esters are quantitatively and qualitatively the most important compounds providing fruity odors. Biochemical evidence for involvement of the SAAT gene in formation of fruity esters is provided by characterizing the recombinant protein expressed in Escherichia coli. The SAAT enzyme showed maximum activity with aliphatic medium-chain alcohols, whose corresponding esters are major components of strawberry volatiles. The enzyme was capable of utilizing short- and medium-chain, branched, and aromatic acyl-CoA molecules as cosubstrates. The results suggest that the formation of volatile esters in fruit is subject to the availability of acyl-CoA molecules and alcohol substrates and is dictated by the temporal expression pattern of the SAAT gene(s) and substrate specificity of the SAAT enzyme(s).

Acyltransferases↗
PubMed1999

Cardiopulmonary bypass and oxygen consumption: oxygen delivery and hemodynamics.

BACKGROUND: This study was undertaken to investigate the relations between whole body oxygen consumption (VO2), oxygen delivery (DO2), and hemodynamic variables during cardiopulmonary bypass. METHODS: One hundred one patients were studied during cooling, hypothermia, and rewarming. Oxygen consumption, DO2, hemodynamics, and DO2crit were measured at these times. RESULTS: There was a direct linear relation between DO2 and VO2 during all three times. No relation between VO2 and hemodynamics was detected during cooling; during hypothermia, an inverse linear relation with peripheral arterial resistance was found. Finally, during rewarming, there was a direct relation with pump flow rate, and an inverse relation with arterial pressure and arterial resistance. The same relations among the variables were found at delivery levels above or below DO2crit. CONCLUSIONS: During cardiopulmonary bypass there is a direct linear relation between DO2 and VO2; the relations with hemodynamic variables depend on the phases of cardiopulmonary bypass. This suggests that increasing delivery levels may recruit and perfuse more vascular beds, and higher delivery levels are advisable during perfusion. During rewarming and hypothermia, lower arterial resistances are also desirable to optimize VO2.

Aged↗
PubMed1999

Ca2+ channels of the L-type in peripheral blood lymphocytes of essential hypertensives.

Ca2+ channels of the L-type were assayed in human peripheral blood lymphocytes of normotensive control subjects and of essential hypertensives using radioligand binding assay techniques. The dihydropyridine Ca2+ channel blocker [3H](+)-PN 200-110 [isopropyll-4-(2,1,3-benzoxadiazol-4-yl)1,4-dihydro-5-methox ycarbonyl-2,6-dimethyl-3-pyridine carboxylate] was used as a ligand. [3H](+)-PN 200 110 was bound specifically to human peripheral blood lymphocytes in a manner consistent with the labeling of Ca2+ channels of the L-type. No significant differences in the dissociation constant (Kd), in the maximum density of binding sites (Bmax) or in the pharmacological profile of [3H](+)-PN 200 110 binding were found between normotensive subjects and different degree essential hypertensives. Analysis of the intralymphocytic free Ca2+ concentration did not reveal differences between normotensive subjects and essential hypertensives. Although hypertension is associated with altered membrane handling of Ca2+, no changes in the expression of peripheral blood lymphocyte Ca2+ channels of the L-type or in intralymphocytic Ca2+ concentrations were found in essential hypertensives. Human peripheral blood lymphocytes therefore cannot represent a peripheral marker of altered Ca2+ handling in hypertension.

Adult↗
PubMed1999

alpha1-adrenergic receptor subtypes in human peripheral blood lymphocytes.

We investigated the expression of alpha1-adrenergic receptor subtypes in intact human peripheral blood lymphocytes using reverse transcription-polymerase chain reaction (RT-PCR) and radioligand binding assay techniques combined with antibodies against the three subtypes of alpha1-adrenergic receptors (alpha1A, alpha1B, and alpha1D). RT-PCR amplified in peripheral blood lymphocytes a 348-bp alpha1A-adrenergic receptor fragment, a 689-bp alpha1B-adrenergic receptor fragment, and a 540-bp alpha1D-adrenergic receptor fragment. Radioligand binding assay with [3H]prazosin as radioligand revealed a high-affinity binding with a dissociation constant value of 0. 65+/-0.05 nmol/L and a maximum density of binding sites of 175. 3+/-20.5 fmol/10(6) cells. The pharmacological profile of [3H]prazosin binding to human peripheral blood lymphocytes was consistent with the labeling of alpha1-adrenergic receptors. Antibodies against alpha1A-, alpha1B-, and alpha1D-receptor subtypes decreased [3H]prazosin binding to a different extent. This indicates that human peripheral blood lymphocytes express the three alpha1-adrenergic receptor subtypes. Of the three different alpha1-adrenergic receptor subtypes, the alpha1B is the most represented and the alpha1D, the least. Future studies should clarify the functional relevance of alpha1-adrenergic receptors expressed by peripheral blood lymphocytes. The identification of these sites may represent a step for evaluating whether they represent a marker of alpha1-adrenergic receptors in cardiovascular disorders or for assessing responses to drug treatment on these receptors.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1999

Vasoactive hormones induce nitric oxide synthase mRNA expression and nitric oxide production in human endothelial cells and monocytes.

Isoform-2 nitric oxide synthase (NOS-2) mRNA expression and nitric oxide (NO) production are induced in endothelial cells and monocytes by cytokines such as gammaIFN and LPS. We evaluated NOS-2 and isoform-3 NOS (NOS-3) mRNA expression and NO production in human monocytes and human umbilical vein endothelial cells (HUVEC), under basal conditions and after incubation with physiologic concentrations of vasoactive hormones. NOS mRNA expression was detected by reverse transcription polymerase chain reaction (RT-PCR) and NO production by electronic paramagnetic resonance spectroscopy (EPR). We showed that NOS-2 mRNA expression and NO production were induced by stimulation with epinephrine, dopamine, endothelin-1, and angiotensin II, both in monocytes and HUVEC. NOS-3 mRNA expression and NO production were detected under basal conditions in monocytes and HUVEC and were not modified by the presence of vasoactive hormones. Human endothelial cells and monocytes express the NOS-2 and NOS-3 mRNA and the inducible NOS-2 mRNA expression increases after vasoactive hormone stimulation.

Adult↗
PubMed1998

Microarrays: biotechnology's discovery platform for functional genomics.

Advances in microarray technology enable massive parallel mining of biological data, with biological chips providing hybridization-based expression monitoring, polymorphism detection and genotyping on a genomic scale. Microarrays containing sequences representative of all human genes may soon permit the expression analysis of the entire human genome in a single reaction. These 'genome chips' will provide unprecedented access to key areas of human health, including disease prognosis and diagnosis, drug discovery, toxicology, aging, and mental illness. Microarray technology is rapidly becoming a central platform for functional genomics.

Biotechnology↗
PubMed1998

[Oxygen consumption during cardiovascular surgery conducted under extra-corporeal circulation].

Whole-body oxygen consumption (VO2) is universally considered both a measure of the metabolic activity of the body and an indicator of the adequacy of tissue perfusion during cardiopulmonary bypass as well. There is little agreement in the literature about the main determinants of oxygen consumption during CPB, except for the role of temperature in reducing the metabolic activity of the body. Many studies, which have been performed both on animals and in humans, have reached some contradictory conclusions about the role of delivery and perfusion flow rates, of haemodynamic variables, of the acid-base status, and of drugs influencing the variations of oxygen consumption during CPB. Aim of this paper is to review the evidences in literature about the determinants of whole-body oxygen consumption during cardiopulmonary bypass in man.

Cardiopulmonary Bypass↗
PubMed1997

Discovery and analysis of inflammatory disease-related genes using cDNA microarrays.

cDNA microarray technology is used to profile complex diseases and discover novel disease-related genes. In inflammatory disease such as rheumatoid arthritis, expression patterns of diverse cell types contribute to the pathology. We have monitored gene expression in this disease state with a microarray of selected human genes of probable significance in inflammation as well as with genes expressed in peripheral human blood cells. Messenger RNA from cultured macrophages, chondrocyte cell lines, primary chondrocytes, and synoviocytes provided expression profiles for the selected cytokines, chemokines, DNA binding proteins, and matrix-degrading metalloproteinases. Comparisons between tissue samples of rheumatoid arthritis and inflammatory bowel disease verified the involvement of many genes and revealed novel participation of the cytokine interleukin 3, chemokine Gro alpha and the metalloproteinase matrix metallo-elastase in both diseases. From the peripheral blood library, tissue inhibitor of metalloproteinase 1, ferritin light chain, and manganese superoxide dismutase genes were identified as expressed differentially in rheumatoid arthritis compared with inflammatory bowel disease. These results successfully demonstrate the use of the cDNA microarray system as a general approach for dissecting human diseases.

Arthritis, Rheumatoid↗
PubMed1997

Non-invasive haemodynamic effects of two nasal positive pressure ventilation modalities in stable chronic obstructive lung disease patients.

The aim of this study was to compare the haemodynamic effects of a 45-min session of two modalities of non-invasive positive pressure ventilation (nPPV), by means of cardiac echo-Doppler and right heart catheterization, in chronic obstructive lung disease (COPD) patients with chronic respiratory insufficiency. Fourteen patients with stable COPD (11 males, mean age 62.9 +/- 9.8 years) underwent right heart catheterization using a floating Grandjean catheter and simultaneous echo-Doppler measurements before and during two randomly applied 45-min ventilatory sessions, consisting of nasal intermittent positive pressure ventilation in assist/control mode (nIPPV) and nasal pressure support ventilation (nPSV). Blood gases improved significantly during both modalities of ventilation. A significant increase during ventilatory sessions was found in invasive pulmonary right atrial pressure and cardiac output. A statistically significant decrease was found in the flow velocity peak of the superior vena cava and hepatic vein, and in systodiastolic flow velocity integral of the superior vena cava and hepatic vein. The inferior vena cava collapsibility index also decreased significantly during both ventilations. Right atrium diameter and area significantly decreased while right ventricular diameter significantly increased. The echo-Doppler cardiac output decreased significantly while systolic pulmonary artery pressure increased. A short session of both nIPPV and nPSV even without PEEP can induce significant haemodynamic changes in patients with stable COPD. Two-dimensional Doppler echocardiography is a non-invasive device with sufficient reliability to monitor the haemodynamic effects of nPPV. Further studies are needed to assess the effects of nPPV on vascular peripheral flows.

Adult↗
PubMed1997

Dopamine D3 receptor in peripheral mononuclear cells of essential hypertensives.

Dopamine D3 receptor was studied in peripheral mononuclear cells of high-normal, stage 1, stage 2, and stage 3 essential hypertensives using a radioligand binding assay technique with [3H]-7-hydroxy-N,N-di-n-propyl-2-aminotetraline (7-OH-DPAT) as a radioligand. A group of de novo Parkinsonian patients was also examined as a reference group of impaired dopaminergic function. [3H]-7-OH-DPAT was bound specifically to human peripheral mononuclear cells in a manner consistent with the labeling of a dopamine D3 receptor. No changes in free dopamine, norepinephrine, epinephrine and aldosterone levels, renin activity, dissociation constant of [3H]-7-OH-DPAT binding, or the pharmacological profile of [3H]-7-OH-DPAT binding were found between normotensive control subjects and essential hypertensives or Parkinsonians. The density of peripheral mononuclear cell [3H]-7-OH-DPAT binding sites increased in essential hypertensives parallel to blood pressure value augmentation. A higher density of [3H]-7-OH-DPAT binding sites was found in Parkinsonians. In these patients, the density of [3H]-7-OH-DPAT binding sites was similar to that observed in high-normal subjects and in stage 1 essential hypertensives. The increased density of peripheral mononuclear cell dopamine D3 receptor in hypertension as well as in Parkinson's disease may represent an upregulation mechanism consequent to impaired dopaminergic function. In view of the difficulty in identifying markers of peripheral dopamine function, analysis of dopamine D3 receptor in peripheral mononuclear cells may help evaluate whether the dopaminergic system is involved in hypertension.

Adult↗
PubMed1996

Parallel human genome analysis: microarray-based expression monitoring of 1000 genes.

Microarrays containing 1046 human cDNAs of unknown sequence were printed on glass with high-speed robotics. These 1.0-cm2 DNA "chips" were used to quantitatively monitor differential expression of the cognate human genes using a highly sensitive two-color hybridization assay. Array elements that displayed differential expression patterns under given experimental conditions were characterized by sequencing. The identification of known and novel heat shock and phorbol ester-regulated genes in human T cells demonstrates the sensitivity of the assay. Parallel gene analysis with microarrays provides a rapid and efficient method for large-scale human gene discovery.

Cells, Cultured↗
PubMed1996

Genome analysis with gene expression microarrays.

Advances in biochemistry, chemistry and engineering have enabled the development of a new gene expression assay. This 'chip-based' approach utilizes microscopic arrays of cDNAs printed on glass as high-density hybridization targets. Fluorescent probe mixtures derived from total cellular messenger RNA (mRNA) hybridize to cognate elements on the array, allowing accurate measurement of the expression of the corresponding genes. Array densities of > 1,000 cDNAs per cm2 enable quantitative expression monitoring of a large number of genes in a single hybridization. A two-color fluorescence detection scheme allows rapid and simultaneous differential expression analysis of independent biological samples. Mass-produced microarrays provide a new tool for genome expression analysis that may revolutionize genetic dissection, drug discovery and human disease diagnostics.

Animals↗
PubMed1996

Echo-Doppler evaluation of left ventricular impairment in chronic cor pulmonale.

The effects of acute right ventricular (RV) pressure and volume overloads on left ventricular (LV) filling are well known, while the significance of chronic RV pressure overload on LV function has been less studied. To evaluate the LV impairment, 30 patients with chronic cor pulmonale and pulmonary arterial hypertension secondary to chronic obstructive lung diseases (COLDs) were studied. All patients underwent respiratory tests and arterial blood gas assessment. An echo-Doppler examination was made to measure LV ejection fraction (EF), RV and LV end-diastolic and end-systolic diameters and areas, RV/LV area indexes, LV diastolic and systolic eccentricity indexes, mitral and tricuspid flow patterns, and mitral flow velocity in late and early diastole (A/E) indexes. A right heart catheterization was carried out to determine the resting mean pulmonary arterial pressure (mPAP). The data showed a marked enlargement of RV, compressing the left through a leftward shift of interventricular septum. A linear regression analysis detected a significant correlation between mPAP and the following parameters: RV/LV diastolic and systolic area indexes (r=0.75, p<0.0001; r=0.84, p<0.000, respectively), mitral A/E index (r=0.61, p<0.0005), and LV diastolic and systolic eccentricity indexes (r=0.93, p<0.0001; and r=0.83, p<0.0001). No correlations were found between echo-Doppler data and functional respiratory parameters. From these results, we conclude that chronic RV pressure overload induces LV filling impairment despite a normal systolic phase, due to septal leftward shift. In fact, chronic RV pressure overload distorts early diastolic LV geometry delaying LV filling phase, and the functional diastolic impairment of the LV is closely correlated to pulmonary hypertension levels.

Aged↗
PubMed1995

Quantitative monitoring of gene expression patterns with a complementary DNA microarray.

A high-capacity system was developed to monitor the expression of many genes in parallel. Microarrays prepared by high-speed robotic printing of complementary DNAs on glass were used for quantitative expression measurements of the corresponding genes. Because of the small format and high density of the arrays, hybridization volumes of 2 microliters could be used that enabled detection of rare transcripts in probe mixtures derived from 2 micrograms of total cellular messenger RNA. Differential expression measurements of 45 Arabidopsis genes were made by means of simultaneous, two-color fluorescence hybridization.

Arabidopsis↗