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Biomedical subjects

M Conti

Publications and source records attributed to M Conti.

At least 127 records · Page 7Linked to original sources
PubMed1996

Peak blood lactate and blood lactate vs. workload during acclimatization to 5,050 m and in deacclimatization.

Peak blood lactate ([Labl]peak) and blood lactate concentration ([Labl]) vs. workload (W) relationships during acclimatization to altitude and in the deacclimatization were evaluated in 10 Caucasian lowlanders at sea level (SL0); after approximately 1 wk (Alt1wk), 3 wk (Alt3wk), and 5 wk (Alt5wk) at 5,050 m; and weekly during the first 5 wk after return to sea level (SL1wk-SL5wk). Incremental bicycle ergometer exercises (30 W added every 4 min up to exhaustion) were performed. At Alt1wk and at Alt5wk, the experiments were repeated in hypobaric normoxia (Alt1wk-O2 and Alt5wk-O2). [Labl] was determined at rest and during the last approximately 30 s of each W. [Labl]peak was taken as the highest [Labl] during recovery. Acid-base status (pH and concentration of HCO-3 in arterialized capillary blood) was determined at rest. Mean [Labl]peak values were 11.5 (SL0), 8.0 (Alt1wk), 6.4 (Alt3wk), 6.3 (Alt5wk), 8.0 (SL1wk), 9.4 (SL2wk), 10.8 (SL3wk), 11.3 (SL4wk), and 11.6 (SL5wk) mM. At Alt1wk-O2 and Alt5wk-O2, peak W increased, compared with Alt1wk and Alt5wk, whereas no changes were observed for [Labl]peak. [Labl] vs. W was shifted to the left (i.e., higher [Labl] values were found for the same W) at Alt1wk compared with SL0 and partially shifted back to the right (i.e., lower [Labl] values were found for the same W) at Alt3wk and Alt5wk. At Alt1wk-O2 and Alt5wk-O2, [Labl] vs. W values were superimposed on that at SL0. At SL1wk-SL5wk, [Labl] vs. W values were shifted to the right compared with that at SL0. At Alt1wk, a condition of respiratory alkalosis was found, which was only partially compensated for during acclimatization. At SL1wk, the acid-base status was back to normal. We conclude that 1) the reduced [Labl]peak at altitude is still present for 2-3 wk after return from altitude; is not attributable to reduced peak W nor to hypoxia per se, nor to a reduced buffer capacity; alternatively, it could be related to some central determinants of fatigue. 2) The [Labl] vs. W leftward shift at altitude was due to hypoxia per se. 3) The factor(s) responsible for the [Labl] vs. W partial rightward shift during acclimatization could still be effective during the first weeks after return to sea level.

Acclimatization↗
PubMed1996

Asymptomatic cerebral infarctions in patients with ischemic stroke.

We studied 383 consecutive patients with stroke and ischemic lesions on CT scan for the presence of symptomatic cerebral infarction (SCI) and asymptomatic cerebral infarction (ACI). We evaluated risk factors as well as volume, site and number of the lesions. ACIs occurred in 34% of the cases (130/383); 88% of ACIs were lacunes and internal borderzone infarctions, with a volume of less than 2 ml. Larger infarctions were asymptomatic in 27 patients (20.8%); 114 (68.7%) out of 166 patients with two or more SCIs (68.7%) had one or more ACIs. Infarctions in the lateral middle cerebral artery (MCA) territory were SCIs, in the medial MCA territory ACIs. Independent risk factors for ACI were age above 70 years and smoking; cardioembolism prevailed in SCI, small vessel disease in ACI; high levels of disability prevailed in SCIs.

Aged↗
PubMed1996

Left-ventricular outflow tract obstruction by mitral valve ring calcification and proximal septal hypertrophy in elderly patients. Presentation of 2 clinical cases.

The pathophysiology, clinical presentation and prognosis of left-ventricular obstruction still represent an important cardiological problem. Various anatomical and/or functional mechanisms can cause this phenomenon. This report concerns 2 patients over 75 years old in whom the simultaneous presence of localized proximal septal hypertrophy and massive calcification in the anterior portion of the mitral valve ring provoked significant systolic intraventricular gradients. Cardiac rhythm disturbances and consequent variability of R-R intervals, found in both subjects, appear fundamental in determining the value of such gradients. Occasionally an anterior mitral ring calcification may bring about left-ventricular outflow tract obstruction in aged hearts where localized hypertrophy of the proximal portion of the intraventricular septum is present.

Aged↗
PubMed1996

Developmental regulation of unique adenosine 3',5'-monophosphate-specific phosphodiesterase variants during rat spermatogenesis.

Previous studies from our laboratory have shown that messenger RNAs (mRNAs) coding for a cAMP-specific phosphodiesterase (PDE4A) are present in mature rat and mouse germ cells. However, no information is available about the properties of the expressed proteins. To determine their structure and regulation, the PDE4A isoforms expressed in the rat testis were identified and compared to the variants expressed in the brain. Western blot analysis using an antiserum specific for PDE4A demonstrated the presence in testis extracts of two distinct proteins with apparent masses of 98.8 and 86 kDa. The electrophoretic mobilities of these proteins differ from those of proteins detected in the brain extracts (113 and 76 kDa). Reverse transcriptase-PCR of the different splicing mRNA variants expressed in testis confirmed the presence of at least one novel PDE4A mRNA that is distinct from the PDE4A splicing variants identified in the brain and other tissues. Expression of the complementary DNA encoding this variant in a heterologous system resulted in an increase in PDE activity and the appearance of an immunoreactive protein with a mass of 98.8 kDa. No 86-kDa protein could be generated with this transfection. Upon fractionation of testis extracts by HPLC diethylaminoethyl-chromatography, a peak of cAMP-PDE activity coeluted with the two immunoreactive species. During testicular development, the 98.8-kDa protein is present in trace amounts at 10 days, and its level increases with the age of the animals, reaching a plateau at 40 days. The 86-kDa protein appears at 20 days of age and reaches its maximum at 40 days. Studies on the cellular site of expression demonstrated that the two polypeptides are most abundant in round spermatids and are expressed in trace amounts in pachytene spermatocytes, whereas they could not be detected in Sertoli or interstitial cells. The 98.8-kDa, but not the 86-kDa, protein was also expressed in epididymal spermatozoa. These data demonstrate the expression of novel cAMP-specific PDEs coded by the PDE4A gene. The expression of these isoforms is maximal in round spermatids and is maintained in mature spermatozoa. The genesis of the lower mol wt species remains to be determined.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

The C-terminal third of the human luteinizing hormone (LH) receptor is important for inositol phosphate release: analysis using chimeric human LH/follicle-stimulating hormone receptors.

Gonadotropin and TSH receptors represent a subgroup of seven transmembrane-spanning, G protein-coupled receptors with a large extracellular ligand-binding region. After ligand binding to their receptors, the majority of actions of gonadotropins and TSH are believed to be mediated by the cAMP-protein kinase A pathway. Although formation of inositol phosphates (IP) has been reported after stimulation of rodent gonadotropin receptors, activation of phospholipase C after ligand binding of human LH or FSH receptors has not been investigated. Human gonadotropin receptors were transiently expressed in 293 cells, and the agonist-induced stimulation of IP formation was measured. The LH receptor responded to a saturating dose of human CG (hCG) with a 5.2-fold increase of IPs whereas the FSH receptor responded to a saturating dose of FSH with only a 50% increase. On the basis of these differences and in view of the homologous nature of the two gonadotropin receptors, chimeric receptors were constructed using domain transfer to identify the regions in the human LH receptor important for phosphatidylinositol hydrolysis. Chimeric receptors containing the entire extracellular region of the FSH receptor and the seven transmembrane region plus the cytoplasmic tail of the LH receptor responded to FSH treatment with a 4.7-fold increase in IP accumulation. In contrast, the chimeric receptor with the extracellular region of the LH receptor and the TM region plus the cytoplasmic tail of the FSH receptor responded minimally (50%) to hCG treatment. When the C-terminal third (from TM V to the cytoplasmic tail) of the FSH receptor was replaced with the LH receptor sequence, the chimeric receptor still responded to FSH treatment with a large (6.2-fold) increase in IP release, similar to that of the wild type LH receptor (to hCG), suggesting that C-terminal third of the human LH receptor confers IP signaling ability. This functional domain was further divided into two areas, namely TM V to TM VI and TM VII to the cytoplasmic tail. The chimeric receptors F(I-IV)L(V-VI)F(VII-C)R and F(I-VI)L-VII-C)R, in which these two regions of the FSH receptor were replaced by the corresponding sequences of the LH receptor, responded to FSH treatment with partial increases in phosphatidylinositol hydrolysis (2.0- and 3.7-fold, respectively). Furthermore, when TM VII and the cytoplasmic tail of the LH receptor were replaced with the corresponding sequence of the FSH receptor, this chimeric receptor showed a diminished (2.0-fold) response to hCG in IP release. For all the chimeric receptor constructs analyzed, overall expression, equilibrium binding constants, and adenyl cyclase activation were not altered. Thus, unlike studies using chimeric muscarinic and dopaminergic receptors in which the second and third intracellular loops were found to be important for IP signaling, the entire C-terminal third of the human LH receptor is important for IP release. Future analysis using the chimeric receptor approach should provide new information on the structure-function relationship of gonadotropin, TSH, and other seven transmembrane-spanning receptors.

Amino Acid Sequence↗
PubMed1996

Hypertriglyceridemia and hyperinsulinemia are potent inducers of endothelin-1 release in humans.

The purpose of the study was to evaluate fasting endothelin-1 levels in subjects with syndrome X, in subjects with insulinoma, and in normal subjects. The single and synergistic contributions of insulin and triglyceride levels to endothelin-1 release were studied in normal subjects. This was achieved by the evaluation of endothelin-1 levels in response to an insulin bolus combined with a euglycemic clamp (protocol A) and during intralipid (test 1) or saline (test 2) infusions lasting 360 min (protocol B). In protocol B, a euglycemic two-step hyperinsulinemic (25 and 125 mU x kg-1 x h-1) clamp was started at 120 min. Subjects with syndrome X showed significantly higher endothelin-1 levels than normal subjects and subjects with insulinoma (7.22 +/- 0.89 vs. 2.61 +/- 0.38 and 2.49 +/- 0.24 pg/ml, P < 0.01). After an insulin bolus, endothelin-1 levels peaked at 10 min (3.71 +/- 0.96 pg/ml). The incremental area of endothelin-1 was significantly higher after insulin than after a saline bolus. In test 1, an acute increase in triglyceride levels significantly enhanced endothelin-1 levels, with were further increased by the synergistic contribution of high insulin and triglyceride levels. In test 2, endothelin-1 release was achieved at high insulin levels but remained significantly lower than in test 1. In conclusion, subjects with syndrome X showed higher endothelin-1 levels than normal subjects and subjects with insulinoma. These levels were reproduced in normal subjects by a simultaneous increase in insulin and triglyceride levels.

Adult↗
PubMed1996

Sinus skeletonization: a treatment for dural arteriovenous malformations of the tentorial apex. Report of two cases.

Two cases of dural arteriovenous malformation of the tentorial apex are presented. Both were treated surgically by means of a sinus skeletonization technique. The operative technique included a combined bioccipital and median suboccipital craniotomy in which the posterior third of the superior sagittal and the straight and bilateral transverse sinuses were skeletonized by incising the falx and the tentorium along the sinuses. Endovascular embolization was used prior to the surgical approach in one case. Clinical and angiographic cure was achieved in both patients, with a follow up of 4 years in the first case and 1 year in the second one. The surgical technique is described in detail.

Combined Modality Therapy↗
PubMed1996

[Lobular carcinoma in situ: the mammographic aspects and the therapeutic problems].

Lobular carcinoma in situ is an uncommon noninvasive breast neoplasm; it accounts for about 0.8-3.8% of breast cancers and presents 3 peculiar characteristics: multicentricity (60-90%), bilaterality (35-59%), and the risk of invasive cancer (17-37%). The latter feature led some authors to consider this lesion as a marker of the development of an invasive cancer rather than a real malignant neoplasm. The main problem after histologic diagnosis is the choice of treatment: follow-up or surgery? Some authors reported, in the patients with lobular carcinoma in situ, the same incidence of ipsilateral invasive carcinoma as that in the normal population, which suggests a "wait and see" policy. This study, carried out on 27 patients (mean age: 49 years) with histologic diagnosis of lobular carcinoma in situ yielded the following aspecific mammographic findings: clustered microcalcifications; stellate masses and irregular nodular lesions with or without calcifications; architectural distortion with calcifications. In 10 surgical patients, 2 ductal carcinomas were demonstrated near the lobular carcinoma in situ. In the 17 patients submitted to follow-up, lobular carcinoma in situ recurrences were found in 4 patients at biopsy; a comedocarcinoma associated with a metastatic axillary node was found in one patient. Thus, we conclude that, in the patients with lobular carcinoma in situ, a "wait and see" policy of close observation should be adopted.

Adult↗
PubMed1996

[Development of a device allowing for the perfusion and preservation of rat kidneys at -4 degrees C].

OBJECTIVES: In order to prolong the cold ischaemia time and to improve the quality of donor kidneys, we have designed and developed a renal perfusion machine allowing the control of perfusion parameters (temperature, pressure, flow rate, resistance) during the various phases of a kidney perfusion and storage protocol at -4 degrees C. ANIMALS, MATERIALS AND METHODS: Twenty four rat kidneys were removed and the effects of perfusion and storage at -4 degrees C were studied using a perfusion/storage machine allowing the controlled addition of 2,3 butanediol in University of Wisconsin (UW solution). The kidneys were stored for 96 hours at -4 degrees C and were studied in terms of perfusion parameters (pressure, resistance) and according to their histological appearance. RESULTS: The machine allows controlled perfusion of a cryoprotective agent and preservation of kidneys at -4 degrees C for 96 hours. CONCLUSION: In animals, it is possible to store kidneys at a temperature of -4 degrees C for 96 hours by using a vecor solution (UW solution) and a cryoprotective agent (2,3 butanediol). The perfusion and storage of organs under these conditions must be performed by a computer-assisted machine, allowing monitoring and control of the various steps of perfusion/storage.

Animals↗
PubMed1995

Characterization of a hormone-inducible, high affinity adenosine 3'-5'-cyclic monophosphate phosphodiesterase from the rat Sertoli cell.

In previous reports we have shown that FSH and beta-adrenergic agonists regulate the levels of mRNA and increase the activity of a high affinity cAMP phosphodiesterase (cAMP-PDE) in the immature rat Sertoli cell in culture. To identify and characterize the hormone-inducible form(s), the cAMP-PDE activity of the Sertoli cell was partially purified and its properties were determined using biochemical and immunological tools. The cAMP-PDE activity present in the 100,000g supernatant of Sertoli cell extracts was purified more than 2000-fold by four HPLC chromatographic steps. The major purified form of cAMP-PDE had a specific activity of 1-2 mumol/(min.mg of protein). Polyacrylamide gel electrophoresis and silver staining analysis showed that a 67-68 kDa polypeptide comigrated with the major peak of cAMP hydrolytic activity. The molecular weight of the crude or purified enzyme determined by gel filtration and sucrose density gradients was 150,000, suggesting that the native enzyme is an oligomeric structure. This PDE hydrolyzed cAMP with a Km of 1.97 +/- 0.26 microM. The hydrolysis of cAMP was neither inhibited nor stimulated by cGMP concentrations lower than 50 microM. Cyclic nucleotide catalysis required Mg2+, but was insensitive to Ca2+. The activity of this form was competitively inhibited by several inhibitors with the following potency: rolipram > RO 20-1724 > methylisobutylxanthine > cilostamide = milrinone. Because mRNAs derived from two distinct PDE4B and PDE4D genes are present in the Sertoli cell, selective and nonselective PDE antibodies were used to determine the origin of the inducible PDE protein.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1995

Screening of umbilical cord blood hemoglobins by isoelectric focusing in capillaries.

Separation and quantitation of the three main hemoglobin components of umbilical cord blood (fetal, acetylated fetal and adult hemoglobins; Hb F, Fac, A) by capillary isoelectric focusing (IEF) in a pH 6-8 gradient is reported. Even in coated capillaries (with covalently bound chains of linear acrylamido derivatives, notably N-acryloylaminoethoxyethanol), no base line separation is obtained between Hb F and A, although this is routinely achieved in gel slab IEF. However, when the carrier ampholyte buffers were added to 3% short-chain liquid linear polyacrylamide, base line resolution and stabilization of peak transit times were obtained. This suggests that even in the best coating procedures, patches of the inner capillary surface could still be naked, so that the static coating is complemented by a dynamic coating on the unoccupied sites. An additional improvement in separation occurs if the above mixture, comprising 5% carrier ampholytes in the pH 6-8 range and 3% soluble polyacrylamide, is made to contain 50 mM beta-alanine, a "separator" known to flatten the pH gradient around pH 7. In the normal newborns analyzed (n = 30), the following average values were obtained: Hb F, 70.1% (range 65-75%); Hb A, 20.2% (range 15-25%); and HbFac, 9.5% (range 7-11%).

Acetylation↗
PubMed1995

Effect of aging on left ventricular filling in untreated hypertensive patients.

The aim of this study was to evaluate the influence of age and other clinical and echocardiographic parameters on left ventricular filling in a group of 174 untreated patients with mild to moderate hypertension (aged 20-82 years; mean 51.2 years) and in 189 age-matched normotensive subjects. All subjects underwent an echocardiographic study with pulsed Doppler evaluation of left ventricular filling. Left ventricular dimensions and indexes of systolic function were similar and within normal limits in both groups. Left ventricular filling was altered in hypertensive subjects < 65 years with a decrease of peak early velocity (peak E), an increase of peak atrial velocity (peak A) and a reduced E/A ratio. However in subjects > or = 65 years, we did not observe any differences in transmitral flow velocity pattern between hypertensive and normotensive subjects. The stepwise regression analysis showed that age alone explains up to 8% of peak E variance, 14% of peak A and 26% of E/A ratio in hypertensives, while in normotensives it explains up to 18% of peak E variance, 50% of peak A and 61% of E/A ratio. The other variables entered into the regression slightly improved the predictive power. In conclusion, age is the major independent factor affecting left ventricular filling in both groups, even if its predictive power was smaller in the hypertensive group. The similarity of diastolic filling pattern in elderly hypertensive and normotensive subjects suggests that the 'aging factor' plays an important role in influencing left ventricular filling pattern so as to mask the effect of hypertension in the elderly patients.

Adult↗
PubMed1995

Plasma from patients exposed to ischemia reperfusion contains clastogenic factors and stimulates the chemiluminescence response of normal leukocytes.

Clastogenic factors (CFs) are released by cells exposed to superoxide radicals and are found in various situations of oxidative stress. Certain of their components stimulate further superoxide production by competent cells, as shown with cytochrome c assay in previous work. In the present study, we report CF formation after ischemia reperfusion in patients undergoing coronary bypass surgery. Plasma ultrafiltrates, collected 20 min after reperfusion, had clastogenic properties in contrast to those collected before ischemia. We also show that the luminol-enhanced chemiluminescence response of neutrophils from healthy persons is increased when these cells are exposed to CF-containing postreperfusion samples from patients. Light emission was reduced to control values in the presence of superoxide dismutase. The burst of oxyradicals upon reperfusion is probably the initiating event of CF formation, which in turn leads to further oxyradical generation. This amplification process may explain why detectable levels of CF need a delay of at least 10 min. The activated state of neutrophils in ischemia reperfusion is at once a consequence and a source of CFs. Individual variation in the persistence of this clastogenic and leukocyte-activating material was observed. Therefore, antioxidants for prevention of ischemia reperfusion injury should be continued during the postoperative course.

Antioxidants↗
PubMed1995

Chromosomal localization of the human and rat genes (PDE4D and PDE4B) encoding the cAMP-specific phosphodiesterases 3 and 4.

Through the use of somatic cell hybrids segregating either human or rat chromosomes, we determined the chromosome localizations of two genes encoding cAMP-specific phosphodiesterases (cAMP-PDEs). PDE4D, the gene encoding the cAMP-PDE isoform 3 (IVd), was assigned to human chromosome 5 and rat chromosome 2, and PDE4B, the gene encoding the cAMP-PDE isoform 4 (IVb), was assigned to human chromosome 1 and rat chromosome 5. These localizations extend the homology between rat chromosome 2 and human chromosome 5, on the one hand, and between rat chromosome 5 and human chromosome 1, on the other hand.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1995

Stage and cell-specific expression of the adenosine 3',5' monophosphate-phosphodiesterase genes in the rat seminiferous epithelium.

Four genes (ratPDE1/IVc, ratPDE2/IVa, ratPDE3/IVd, and ratPDE4/IVb) encoding different isoforms of phosphodiesterase that specifically hydrolyze the second messenger cAMP (cAMP-PDEs) are present in the rat. Previous data from our laboratory indicated that these genes are differentially expressed in the somatic and germ cells of the seminiferous epithelium of the testis. To further characterize their spatial and temporal expression in the seminiferous tubules, in situ hybridization was used to monitor the expression of the four cAMP-PDE messenger RNAs (mRNAs). The signals corresponding to ratPDE1/IVc and ratPDE2IVa mRNAs were localized in two restricted layers of the seminiferous epithelium. The ratPDE1/IVc mRNA was present in a region of the epithelium corresponding to the location of middle-late pachytene spermatocytes. Conversely, the ratPDE2/IVa signal was confined to a more adluminal area corresponding to the location of maturing round spermatids. The ratPDE3/IVd and ratPDE4/IVb mRNAs were distributed throughout the span of the seminiferous epithelium, indicating a localization in the Sertoli cell cytoplasm. Although the intensity of the signal corresponding to ratPDE4/IVb was similar in all seminiferous tubule stages, the ratPDE3/IVd signal varied in intensity in tubules at different stages of the seminiferous cycle. Maximal expression was present in tubules at stages I-V and XI-XIII of the cycle and minimal at stages VIII-IX of the cycle. The expression of the ratPDE3/IVd mRNA positively correlated with the ability of specific inhibitors of the cAMP-PDEs to potentiate the FSH-dependent cAMP accumulation in tubules at different stages of the seminiferous cycle, with maximal potentiation observed at stages II-VI of the cycle. These data demonstrate that different cAMP-PDE genes are active in different cells of the seminiferous tubules and that the ratPDE3/IVd gene is expressed in the Sertoli cell in a cyclical fashion during the seminiferous cycle.

3',5'-Cyclic-AMP Phosphodiesterases↗