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Biomedical subjects

E Gatti

Publications and source records attributed to E Gatti.

At least 37 records · Page 2Linked to original sources
PubMed1995

Blood cell redistribution in the lung after administration of recombinant human granulocyte-macrophage colony-stimulating factor.

Granulocyte-macrophage colony-stimulating factor (GM-CSF), in addition to being a haematopoietic growth factor, has been shown to stimulate in vitro the production of interleukins 1, 6 and 8 (IL-1, IL-6 and IL-8), tumour necrosis factor-alpha (TNF-alpha) and GM-CSF by polymorphonuclear cells (PMNs), alveolar macrophages (AMs), fibroblasts and endothelial cells of the lung, and the growth and differentiation of resident alveolar macrophages. The aim of this study was to establish whether recombinant GM-CSF (rhGM-CSF), administered subcutaneously at a dose of 5 micrograms.kg-1 for 3 days in five patients with unresectable non-small cell lung cancer before starting chemotherapy, induces an increase in the alveolar cell count, and whether these cellular lung variations may be related to increases in the above-mentioned cytokines. In the bronchoalveolar lavage fluid (BALF) total cell count, polymorphonuclear cells, neutrophils, and alveolar macrophages increased significantly in comparison with the baseline, and the extent of variation of the BAL cell count was considerably greater than that of the circulating leucocytes. The mean levels of all the cytokines increased, but a significant difference with respect to the basal condition was observed only for IL-6 and IL-8. After rhGM-CSF treatment, significant correlations were found between neutrophil counts and the levels of IL-6 and IL-8. In conclusion, rhGM-CSF administration induces a cellular expansion in the lung, and the neutrophil increase appears to be related to increased levels of IL-8.

Aged↗
PubMed1994

Specific interactions of Mss4 with members of the Rab GTPase subfamily.

Mss4 is a mammalian protein that was identified as a suppressor of a yeast secretory mutant harboring a mutation in the GTPase Sec4 and was found to stimulate GDP release from this protein. We have now performed a biochemical characterization of the Mss4 protein and examined the specificity of its association with mammalian GTPases. Mss4 is primarily a soluble protein with a widespread tissue distribution. Recombinant Mss4 binds GTPases present in tissue extracts, and by a gel overlay assay binds specifically Rab Rab10proteins. We further define the Mss4-GTPase interaction to a subset of Rabs belonging to the same subfamily branch which include Rab1, Rab3, Rab8, Rab10, Sec4 and Ypt1 but not Rab2, Rab4, Rab5, Rab6, Rab9 and Rab11. Accordingly, Mss4 co-precipitates from a brain extract with Rab3a but not Rab5. Mss4 only stimulates GDP release from, and the association of GTP gamma S with, this Rab subset. Recombinant Mss4 and Rab3a form a stable complex in solution that is dissociated with either GDP or GTP gamma S. Injection of Mss4 into the squid giant nerve terminal enhances neurotransmitter release. These results suggest that Mss4 behaves as a guanylnucleotide exchange factor (GEF) for a subset of Rabs to influence distinct vesicular transport steps along the secretory pathway.

Animals↗
PubMed1994

O-linked oligosaccharides in yeast glycosyl phosphatidylinositol-anchored protein gp115 are clustered in a serine-rich region not essential for its function.

The protein gp115 is an exocellular yeast glycoprotein modified by O- and N-glycosylation and attached to the plasma membrane through a glycosylphosphatidylinositol. The more remarkable structural feature in gp115 is the presence of a 36-amino acid serine-rich region. Similar sequences have been found in mammalian glycoproteins, such as the low density lipoprotein receptor, the decay-accelerating factor, and the mucins, where they are targets of multiple sites of O-glycosylation. The modification of these regions greatly influences their conformation and gives rise to "rodlike" structures. In this work, we have deleted or duplicated the Ser-rich region of gp115. The analysis of the size and glycosylation state of both mutant proteins indicates that about 52% of the total contribution of the O-glycosylation to the mass of the protein is concentrated in this region. The phenotype of ggp1 null mutant expressing the mutant proteins was also analyzed to understand if this region is important for gp115 function. The defects of slow growth rate and resistance to zymolyase of the ggp1 cells are completely complemented by both mutant proteins, suggesting that this region could be dispensable for gp115 function. A tentative model of gp115 structure is presented on the basis of the obtained data.

Amino Acid Sequence↗
PubMed1994

A rat brain Sec1 homologue related to Rop and UNC18 interacts with syntaxin.

Sec1 is a hydrophilic protein that plays an essential role in exocytosis from the yeast Saccharomyces cerevisiae. Two high copy suppressors of mutations in the Sec1 gene, SSO1 and SSO2, were recently identified that encode proteins of the syntaxin family. Syntaxin (a T-SNARE), together with SNAP-25 and synaptobrevin/VAMP (a T- and a V-SNARE, respectively), is thought to form the core of the docking-fusion complex in synaptic vesicle exocytosis. Proteins that exhibit similarity to Sec1 were identified in the nervous system of Drosophila melanogaster (Rop) and Caenorhabditis elegans (UNC18). Based on the amino acid sequence alignment of Sec1, Rop, and UNC18, we have used a PCR-based approach to isolate a rat brain cDNA encoding a Sec1 homologue. The cDNA hybridizes to a 3.5-kb brain-specific mRNA by Northern blot analysis and encodes a protein of 593 amino acids (rbSec1). Antibodies raised against a central portion of rbSec1 recognize a 67.5-kDa protein in total homogenates of rat brain but not of nonneuronal tissues. When incubated with a Triton X-100 brain extract, rbSec1-glutathione S-transferase (GST) fusion protein, but not GST protein alone, specifically interacts with syntaxin but not with SNAP-25 or synaptobrevin/VAMP. We conclude that the function of proteins of the Sec1 family in membrane fusion involves an interaction with a T-SNARE.

Amino Acid Sequence↗
PubMed1994

Plasma amino acids changes in obese patients on very low-calorie diets.

The reduced feeling of hunger alleged by obese patients on very low-calorie diets (VLCD) could be supposed due to restoration to a normal level of plasma TRP:LNAA ratio, previously found lowered in these subjects. We tested this hypothesis measuring weekly the changes of plasma amino acid concentration in obese individuals who followed a 5 week slimming regimen consisting in a powdered formula diet (500 kcal/d). A decrease in plasma TRP:LNAA ratio was seen, since tryptophan decreased, whereas valine and isoleucine increased over time. An increase in plasma lysine, threonine, glycine and aminobutyrate was also observed. The early decrease shown by alanine and glutamate was followed by an increase in the last weeks of the study. Our hypothesis was not confirmed, since VLCD failed to carry back the plasma TRP:LNAA ratio to a normal level.

Adult↗
PubMed1993

Evolutionary conservation of genomic sequences related to the GGP1 gene encoding a yeast GPI-anchored glycoprotein.

The GGP1 gene encodes the only GPI-anchored glycoprotein (gp115) that has been purified to-date in the budding yeast Saccharomyces cerevisiae. It is a single-copy gene whose deduced amino-acid sequence shares no significant homology to any other known protein. In this paper we report a Southern hybridization analysis of genomic DNA from different eukaryotic organisms to identify homologues of the GGP1 gene. We have analyzed DNA prepared from a unicellular green alga (Chlamydomonas eugametos), from two distantly related yeast species (Candida cylindracea and Schizosaccharomyces pombe), and from the common bean Phasoleus vulgaris. The moderate stringency of the experimental conditions and the high specificity of the probes used indicate that a single-copy of GGP1-related sequences exists in all these eukaryotic organisms. The chromosomal localization of the GGP1 gene in S. cerevisiae has also been determined.

Animals↗
PubMed1993

Physiological analysis of mutants indicates involvement of the Saccharomyces cerevisiae GPI-anchored protein gp115 in morphogenesis and cell separation.

This paper reports a phenotypic characterization of ggp1 mutants. The cloned GGP1 (GAS1) gene, which encodes a major GPI-anchored glycoprotein (gp115) of Saccharomyces cerevisiae of unknown function, was used to direct the inactivation of the chromosomal gene in haploid and diploid strains by gene replacement. The analysis of the null mutants reveals a reduction in the growth rate of 15 to 40%. Cells are round, with more than one bud, and extensively vacuolized. In the stationary phase, mutant cells are very large, arrest with a high percentage of budded cells (about 54 and 70% for haploid and diploid null mutants, respectively, in comparison with about 10 to 13% for control cells), and have reduced viability. The observed phenotype suggests defects in cell separation. Flow cytometric analysis of DNA reveals an increase in the fraction of cells in the G2+M+G1* compartment during exponential growth. Conjugation and sporulation are not affected. The exocellular location of gp115 led us to examine cell wall properties. Cell wall and septum ultrastructure of abnormally budded cells was analyzed by electron microscopy analysis, and no appreciable differences from wild-type cells were found. Microscopic analysis revealed an increase in chitin content and delocalization. In comparison with control cells, ggp1 null mutants are shown to be resistant to Zymolyase during the exponential growth phase. A fivefold overexpression of gp115 does not bring about any effects on cell growth parameters and cell wall properties.

Cell Division↗
PubMed1992

Olive oil, corn oil, and n-3 fatty acids differently affect lipids, lipoproteins, platelets, and superoxide formation in type II hypercholesterolemia.

To evaluate which dietary fat may provide the best response in terms of plasma lipids and lipoproteins and also of platelet aggregability and superoxide formation by white blood cells, 12 type II patients were randomly allocated to three different diets, which provided polyunsaturated fatty acids (corn oil), monounsaturated fatty acids (olive oil), and a supplementation of ethyl esters of n-3 fatty acids to a prudent diet. Olive oil and, more significantly, n-3 ethyl esters lowered total cholesterol best (-2.2% and -5.8%, respectively); the latter diet, as expected, also significantly lowered triglyceridemia (-21.4%). The corn-oil diet exerted a small, statistically significant reduction of high-density-lipoprotein cholesterol (HDL) (-4.3%), and it also lowered plasma total apo B concentrations (-3.8%). n-3 ethyl esters significantly raised both total (+3.1%) and particularly HDL2 cholesterol (+24%). Platelet reactivity was insignificantly reduced by the three regimens, but all three significantly reduced thrombin-stimulated formation of thromboxane B2. Finally, only the n-3 fatty acid supplementation significantly reduced O2- generation by adherent monocytes. Dietary unsaturated fatty acids are generally effective on the plasma lipid and lipoproteins in type II patients, but significant differences may be found between the three tested regimens.

Apolipoproteins↗
PubMed1992

Differential effect of unsaturated oils and butter on blood glucose and insulin response to carbohydrate in normal volunteers.

Plasma glucose and insulin responses were monitored in normal volunteers after a standard carbohydrate meal with unsaturated oils (olive and corn oil, in identical volumes) or butter. Both unsaturated oils almost totally blunted the glycaemic response; butter, instead, only delayed the plasma glucose rise, without significantly changing the area under the curve. The insulin rise was essentially unaffected by the three experimental meals, only a slight delay in the peak being observed with no differences between unsaturated oils and butter. These findings support previous data indicating reduced glucose levels after prolonged administration of olive oil, and reduced glycaemic response, in the absence of clear-cut insulin changes, differentiates unsaturated oils from indigestible fibres; it may be linked to an altered polysaccharide handling at the intestinal level.

Adult↗
PubMed1991

Isolation and deduced amino acid sequence of the gene encoding gp115, a yeast glycophospholipid-anchored protein containing a serine-rich region.

gp115 is a N- and O-glycosylated protein of Saccharomyces cerevisiae. It is also modified by addition of glycosylphosphatidylinositol, which anchors the protein to the plasma membrane. The gene encoding gp115 (GGP1) has been cloned by a two-step procedure. By an immunoscreening of a yeast genomic DNA library in the expression vector lambda gt11, a 3'-terminal 0.9-kilobase portion of the gene has been isolated and then used as a molecular probe to screen a yeast genomic DNA library in YEp24. In this way, the whole GGP1 gene has been cloned. Its identity with the gp115 gene has been confirmed by gene disruption, which has also indicated that the function of gp115 is not essential for cell viability. The features of the sequence are also entirely consistent with it corresponding to the gp115 gene. The nucleotide sequence of GGP1 predicts a 60-kDa polypeptide, in agreement with the molecular mass of the gp115 precursor detected in sec53 mutant cells at restrictive temperature. Two hydrophobic sequences, one NH2- and the other COOH-terminal were found. The former has the features of the cleavable signal sequence, which allows the entry of proteins in the secretory pathway. The latter could be the signal sequence that has to be removed during the addition of glycosylphosphatidylinositol. The predicted amino acid sequence of gp115 shows 10 sequons for N-glycosylation and a high proportion of serine-threonine residues (22%) that could provide several sites for O-glycosylation. The unusual concentration of 27 serines in the COOH-terminal portion of the protein shares homology with a similar polyserine repeat of the serine repeat antigen (SERA protein) of Plasmodium falciparum. A two-dimensional analysis of the "in vitro" translational product of the GGP1 mRNA has been carried out, allowing the identification of the "in vivo" gp115 precursor in a two-dimensional gel.

Amino Acid Sequence↗
PubMed1989

Combined measurements of neuron specific enolase and bombesin/gastrin releasing peptide in lung cancer.

Pretreatment serum neuron specific enolase (NSE) and plasma bombesin/gastrin releasing peptide (BN/GRP) were measured in 92 lung cancer patients and 17 controls. The mean level of NSE (p less than 0.001) and BN/GRP (p less than 0.05) was significantly raised in patients with small cell lung cancer (SCLC, n = 62) compared to non-SCLC (n = 30) and controls. The mean concentration of NSE in extensive SCLC was significantly greater (p less than 0.005) than in limited stage but with a substantial overlap of values. Forty-seven out of 62 SCLC patients had at least one of the two markers raised (sensitivity 76%, specificity 83%), 44 had raised NSE (sensitivity 71%, specificity 89%) but only 24 had BN/GRP raised (sensitivity 42%, specificity 91%). At restaging, 16 of 19 patients with SCLC responsive to chemotherapy showed a significant fall of NSE; on the other hand, BN/GRP fell significantly in only 3 patients, remaining unchanged in the majority of responding patients. In conclusion, the combined determination of NSE and BN/GRP in SCLC, at diagnosis and during the follow-up, was not found to be superior to NSE determination alone.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Alterations in high-density lipoprotein subfractions during postprandial lipidaemia induced by fat with and without ethanol.

1. Serum lipid and apolipoprotein levels, distribution and composition of high-density lipoprotein (HDL) subfractions and lecithin:cholesterol acryltransferase activity were analysed in nine normolipidaemic subjects, in whom a hypertriglyceridaemic state was induced by the acute administration of ethanol (40 g) plus fat (70 g) or of fat only. 2. Triglyceride (TG) levels increased by 180% 4-6 h after fat plus ethanol intake, the hypertriglyceridaemic response being inversely correlated with the basal HDL2 mass (r = -0.82). Serum apolipoprotein (apo) B levels rose by 8%, HDL-cholesterol decreased by 10% and HDL-TG increased by 57% at 6-8 h. 3. When ethanol was omitted, serum cholesterol and TG rose by 6% and 70%, respectively; both apo AI and apo B levels went up by 8%, whereas HDL-cholesterol rose progressively (15%) at 12 h. 4. The flotation rates of both HDL2 and HDL3 increased, reaching a maximum 6-8 h after ethanol plus fat intake. These changes were due to an increase in TG and phospholipid contents, whereas cholesteryl esters and proteins decreased. 5. The alterations in HDL are attributable to the increase in TG-rich lipoproteins, to the stimulated cholesterol esterification (+15%) and to an enhanced transfer of newly formed cholesteryl esters to apo-B-containing lipoproteins in exchange for TG. 6. Changes in HDL properties were evident only when ethanol was given concomitantly with fat. 7. These findings suggest that in the postprandial phase lipoprotein changes may occur, which facilitate an improved removal of cholesterol from tissues.

Adolescent↗
PubMed1987

Hypercholesterolaemia treated by soybean protein diet.

After a period of stabilisation on a controlled low lipid low cholesterol diet with animal proteins a group of 16 children with familial hypercholesterolaemia were given a textured soybean protein based diet, with a similar fat composition. All the children had a highly significant reduction in total cholesterol, averaging -21.8% against the baseline after eight weeks. Compliance became less strict afterwards, but more than half of the patients have regularly continued the diet and results have been maintained for one year. Minimal changes were noted in triglyceridaemia and in high density lipoprotein cholesterol concentrations, which showed a slight rise only at the end of treatment. The children's growth during the trial was normal. In view of the psychological difficulties of prescribing treatment with drugs to children with severe hypercholesterolaemia before puberty and of the relative ineffectiveness of standard low lipid diets in this condition the soybean protein diet may offer a satisfactory alternative.

Child↗
PubMed1987

Plasma glucose and insulin responses to carbohydrate food (rice) with different thermal processing.

The effects of thermal processing on plasma glucose and insulin responses in healthy subjects were examined. Fourteen volunteers, after being tested with a glucose load, were randomly administered a test meal, consisting of an amount of rice, calculated to yield the same quantity of glucose, used for the glucose tolerance test (70 g). Rice (90 g, raw) was cooked in two different manners: (a) boiled in salted water and (b) baked for 10 min at 160 degrees C after boiling as in the first test. A clear difference in viscosity and in in vitro hydrolytic rates between the two rice items could be established, whereas the plasma glucose and insulin responses in the volunteers differed to a smaller extent. In particular the 60-min incremental area for glucose was significantly lower in the case of baked rice, compared to boiled rice. These findings suggest that thermal processing of complex carbohydrates may differently affect glycemic responses in man.

Adult↗
PubMed1986

Controlled evaluation of fat intake in the Mediterranean diet: comparative activities of olive oil and corn oil on plasma lipids and platelets in high-risk patients.

Activities of low-fat diets with olive oil or corn oil on lipids and platelets were studied in 23 middle-aged patients with high atherosclerosis risk for 8 wk. The olive oil diet had a polyunsaturated-saturated ratio of 0.33 vs 1.28 for the corn oil diet. Plasma total cholesterol was reduced with corn oil, but high-density lipoprotein cholesterol levels were lower with corn oil and unchanged or raised by olive. Plasma apolipoprotein B levels were equally reduced by both diets; apolipoprotein AI and the apo AI:B ratio rose only with olive oil. Plasma-glucose levels were lowered significantly with olive oil. Changes in platelet function were characterized by a reduced sensitivity to arachidonic acid (particularly with corn oil) and to collagen (particularly with olive). An olive oil diet with a moderate fat intake (about 30% of total calories) leads to favorable plasma lipoprotein and platelet changes.

Adult↗
PubMed1985

Cholesterol-lowering and HDL-raising properties of lecithinated soy proteins in type II hyperlipidemic patients.

Plasma lipoprotein changes were evaluated in 65 type II patients undergoing sequential 4-week dietary treatments with: (I) standard low-lipid diet; (II) low-lipid diet with total replacement of animal proteins with textured soy proteins containing 6% of lecithin (L-TVP); (III) standard low-lipid diet; (IV) low-lipid diet with a 50% substitution of animal proteins with L-TVP. Total cholesterolemia was significantly reduced in both periods of L-TVP administration: -18.6% during phase II (total replacement) and -13.2% during phase IV (partial replacement). High-density lipoprotein (HDL) cholesterol levels tended to increase during L-TVP administration. However, only patients in the mid- and low tertiles for HDL cholesterolemia showed a significant increase of HDL levels during L-TVP. This 'normalizing' activity of L-TVP on plasma lipoproteins, even when administered as a partial dietary substituent, may be of clinical interest for subgroups of patients at high vascular risk.

Adult↗
PubMed1985

Unresectable non-small cell lung cancer chemotherapy with high-dose cisplatin and etoposide.

69 patients with unresectable non-small cell lung cancer, previously untreated, received cisplatin 100 mg/m2 on day 1 and etoposide 120 mg/m2 on days 4, 6, 8 at 4-week intervals. 66 patients were evaluable for tumor response and toxicity. Overall objective response was 25.7% (3 complete responses and 14 partial responses). Response rate in limited disease was 41% and in patients with performance score 0 it was 40%. Squamous cell carcinoma and adenocarcinoma responded in 31 and 24% of evaluable patients. Complete response was associated with a long duration of remission. Median survival time of responding patients was significantly superior to the median of nonresponding patients (p less than 0.001) but compared to stable disease no statistical significance was demonstrable (p greater than 0.05). Hematological and renal toxicity of proposed regimen was generally mild. Nausea and vomiting were the most noxious side effects.

Aged↗