PubMed Health⌕ Search

Biomedical subjects

M Pupillo

Publications and source records attributed to M Pupillo.

At least 19 recordsLinked to original sources
PubMed1995

Impaired left ventricular diastolic function and vascular postischemic vasodilation associated with microalbuminuria in IDDM patients.

OBJECTIVE: Microalbuminuria is considered an important predictor of cardiovascular events in diabetic patients. In this study, a possible association of microalbuminuria with significant changes in left ventricular (LV) morphology and function and generalized vascular dysfunction was analyzed in insulin-dependent diabetes mellitus (IDDM) patients without hypertension, coronary artery disease, or autonomic dysfunction. RESEARCH DESIGN AND METHODS: Thirty-four young long-term IDDM patients, 16 with and 18 without microalbuminuria, and 20 control subjects were studied. LV systolic function and wall thickness were evaluated by M-mode echocardiography. LV diastolic function was studied using a combined echo-Doppler and phonocardiographic technique. The hyperemic response to forearm ischemia was measured by strain-gauge plethysmography. All patients underwent 24-h ambulatory blood pressure monitoring. RESULTS: LV mass index and wall thickness:radius ratio were significantly higher in microalbuminuric patients. LV relaxation was significantly impaired in both diabetic groups compared with control subjects; moreover, this impairment was significantly greater in microalbuminuric than in normoalbuminuric patients. In microalbuminuric patients, forearm postischemic vasodilation was also significantly lower and mean awake diastolic blood pressure (dBP) was significantly higher than in the other two groups. CONCLUSIONS: Our data suggest that microalbuminuria is associated with significant changes in LV morphology, a more severe impairment of cardiac diastolic function, altered vascular dilatory capacity, and higher daytime dBP. Therefore, microalbuminuric patients should be considered to have a higher risk of cardiovascular complications and be kept under closer surveillance.

Adult↗
PubMed1992

Multiple cyclic AMP receptors are linked to adenylyl cyclase in Dictyostelium.

cAMP receptor 1 and G-protein alpha-subunit 2 null cell lines (car1- and g alpha 2-) were examined to assess the roles that these two proteins play in cAMP stimulated adenylyl cyclase activation in Dictyostelium. In intact wild-type cells, cAMP stimulation elicited a rapid activation of adenylyl cyclase that peaked in 1-2 min and subsided within 5 min; in g alpha 2- cells, this activation did not occur; in car1- cells an activation occurred but it rose and subsided more slowly. cAMP also induced a persistent activation of adenylyl cyclase in growth stage cells that contain only low levels of cAMP receptor 1 (cAR1). In lysates of untreated wild-type, car1-, or g alpha 2- cells, guanosine 5'-O-'(3-thiotriphosphate) (GTP gamma S) produced a similar 20-fold increase in adenylyl cyclase activity. Brief treatment of intact cells with cAMP reduced this activity by 75% in control and g alpha 2- cells but by only 8% in the car1- cells. These observations suggest several conclusions regarding the cAMP signal transduction system. 1) cAR1 and another cAMP receptor are linked to activation of adenylyl cyclase in intact cells. Both excitation signals require G alpha 2. 2) cAR1 is required for normal adaptation of adenylyl cyclase. The adaptation reaction caused by cAR1 is not mediated via G alpha 2. 3) Neither cAR1 nor G alpha 2 is required for GTP gamma S-stimulation of adenylyl cyclase in cell lysates. The adenylyl cyclase is directly coupled to an as yet unidentified G-protein.

Adenylyl Cyclases↗
PubMed1991

Molecular genetic analysis of two G alpha protein subunits in Dictyostelium.

In Dictyostelium, chemotaxis to folate during growth and cAMP during aggregation is controlled via cell surface receptors. To study the role of two G alpha proteins (G alpha 1 and G alpha 2) in these responses, we examined the physiological and biochemical effects of null mutations caused by antisense mutagenesis and gene disruptions. Disruption of G alpha 2 results in an aggregation-deficient phenotype and a loss of cAMP receptor-mediated functions, including activation of adenylate cyclase, guanylate cyclase, and gene expression and in a loss of GTP-mediated decrease in receptor affinity for cAMP, but it has no effect on chemotaxis to folate or folate activation of guanylate cyclase. These phenotypes can be rescued by a vector expressing G alpha 2, suggesting G alpha 2 is coupled to a cAMP receptor but not to folate receptors. Loss of G alpha 1 expression resulted in no visible growth or developmental phenotype, including cAMP- and folate-stimulated responses, suggesting G alpha 1 function is either not essential under standard laboratory conditions or is encoded by multiple genes. Availability of null mutations provides suitable genetic backgrounds for expressing mutant G alpha protein subunits which can then be used to examine the physiological roles of G alpha 1 and G alpha 2. Construction of these gene disruptions was facilitated by using the auxotrophic marker THY1, which allowed for selection of single-copy insertions into the genome.

Blotting, Southern↗
PubMed1989

Regulation and function of G alpha protein subunits in Dictyostelium.

We have examined the developmental regulation and function of two G alpha protein subunits, G alpha 1 and G alpha 2, from Dictyostelium. G alpha 1 is expressed in vegetative cells through aggregate stages while G alpha 2 is inducible by cAMP pulses and preferentially expressed in aggregation. Our results suggest that G alpha 2 encodes the G alpha protein subunit associated with the cAMP receptor and mediates all known receptor-activated intracellular signal transduction processes, including chemotaxis and gene regulation. G alpha 1 appears to function in both the cell cycle and development. Overexpression of G alpha 1 results in large, multinucleated cells that develop abnormally. The central role that these G alpha proteins play in signal transduction processes and in controlling Dictyostelium development is discussed.

Chromosome Deletion↗
PubMed1989

Multiple alpha subunits of guanine nucleotide-binding proteins in Dictyostelium.

Previous results have shown that chemotaxis and the expression of several classes of genes in Dictyostelium discoideum are regulated through a cell surface cAMP receptor interacting with guanine nucleotide-binding proteins (G proteins). We now describe cloning and sequencing of cDNAs encoding two G alpha protein subunits from Dictyostelium. The derived amino acid sequences show that they are 45% identical to each other and to G alpha protein subunits from mammals and yeast. Both cDNAs are complementary to multiple mRNAs that are differentially expressed during development. This evidence and analysis of mutants presented elsewhere suggest that they have distinct physiological functions.

Amino Acid Sequence↗
PubMed1989

G-protein-linked signal transduction systems control development in Dictyostelium.

G-protein-linked cAMP receptors play an essential role in Dictyostelium development. The cAMP receptors are proposed to have seven transmembrane domains and a cytoplasmic C-terminal region. Overexpression of the receptor in cells, when the endogenous receptor is not present, results in a 10- to 50-fold increase in cAMP-binding sites. Antisense cell lines, which lack cAMP receptors, do not enter the developmental program. Ligand-induced phosphorylation is proposed to occur on serine and threonine residues in the receptor C-terminus. The kinetics of receptor phosphorylation and dephosphorylation correlate closely with the shift of receptor mobility and the adaptation of several cAMP-induced responses. Two alpha-subunits, G-alpha-1 and G-alpha-2, have been cloned and specific antisera developed against each. Both subunits are expressed as multiple RNAs with different developmental time courses. The mutant Frigid A has a functional defect in G-alpha-2 which prevents it from entering development. We propose that G-protein-linked receptor systems will be a major component in the development of many organisms.

Amino Acid Sequence↗
PubMed1988

Immunological detection of G-protein alpha-subunits in Dictyostelium discoideum.

Putative G-protein alpha-subunits in Dictyostelium discoideum were detected on western blots using the antiserum A-569, raised against a peptide whose sequence is found in alpha-subunits of all known GTP-binding signal transducing proteins. Two bands with a MW of 40 kDa and 52 kDa were specifically recognized by the common peptide antiserum; the staining of both bands was strongly reduced when the antiserum was preincubated with the peptide that was used for antibody production. D.discoideum mutant HC213 (fgd A) lacks staining of the 40 kDa band, while the 52 kDa band is still present. This mutant is severely defective in cAMP receptor-G-protein interaction. We concluded that the primitive eukaryote D.discoideum contains proteins which show functional and physical similarity with the alpha-subunits of vertebrate G-proteins.

Blotting, Western↗
PubMed1985

[Monoclonal gammopathies in the aged].

60 cases of monoclonal (benign and malignant) are presented. All the patients are divided into two sub-groups according to the age (until and after 65th years old). They were recovered in the Medical and Geriatric divisions of "Renzetti" civic Hospital in Lanciano. The differences between the two groups with respect to different types of gammapathy, median survival rates, response to therapy, are discussed.

Aged↗
PubMed1984

[Neonatal gastric obstruction].

Gastric outlet obstruction in newborn may be due to segmental atresia or mucosal diaphragm. The authors report two cases of pyloric obstruction and they consider the etiopathogenetic and diagnostic aspects.

Duodenum↗
PubMed1983

[Sick sinus syndrome probably caused by cardiac metastases].

A case of Sick Sinus Syndrome probably secondary to cardiac metastasis in a patient affected by metastatic breast cancer is described. The diagnostic and etiopathogenetic aspects in the case under examination are also discussed.

Bone Neoplasms↗