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Biomedical subjects

M Conti

Publications and source records attributed to M Conti.

At least 55 records · Page 3Linked to original sources

Specific expression of soluble adenylyl cyclase in male germ cells.

The cAMP signaling pathway is an important mediator of extracellular signals in organisms from prokaryotes to higher eukaryotes. In mammals two types of adenylyl cyclase synthesize cAMP; a ubiquitous family of transmembrane isoforms regulated by G proteins in response to extracellular signals, and a recently isolated soluble enzyme insensitive to heterotrimeric G protein modulation. Using the very sensitive reverse transcription-polymerase chain reaction (RT-PCR), soluble adenylyl cyclase (sAC) expression is detectable in almost all tissues examined; however, Northern analysis and in situ hybridization indicate that high levels of sAC message are unique to male germ cells. Elevated levels of sAC mRNA are first observed in pachytene spermatocytes and expression increases through spermiogenesis. The accumulation of high levels of message in round spermatids suggests sAC protein plays an important role in the generation of cAMP in spermatozoa, implying possible roles in sperm maturation through the epididymis, capacitation, hypermotility, and/or the acrosome reaction.

Adenylyl Cyclases↗

Training neural networks to be insensitive to weight random variations.

Neural network weights are subject to errors caused by technological tolerances when implemented in digital or analog hardware. Since these random variations are unavoidable and unpredictable, they can seriously affect the expected performances. This work proposes a learning algorithm that takes weight tolerances into account and guarantees a low sensitivity to them. Some experimental results show the validity of the suggested approach.

Algorithms↗

Superior vena cava syndrome of malignant origin. Which surgical procedure for which diagnosis?

OBJECTIVE: Since some malignancies causing superior vena cava syndrome (SVCS) are only sensitive to a specific treatment regimen, it is crucial to diagnose the underlying pathology in such cases. The aim of the present study was to review the surgical procedures used to establish the aetiology of SVCS of a malignant origin. METHODS: This retrospective study was based on a series of 88 patients referred to surgeons for SVCS, for whom biological and/or endoscopic procedures had failed to establish the diagnosis. On the basis of the results of clinical examination, biological tests and CT-scan presentation, we performed 99 sampling procedures to obtain a diagnosis for all 88 patients. These procedures were the following: biopsy of peripheral adenopathy (n=11), CT-guided biopsy (CTGB; n=23), axial mediastinoscopy (MDS; n=23), anterior mediastinotomy (n=26), anterior mediastinoscopy (n=6), biopsy of the suprascapular mass (n=3), pericardioscopy (n=3), thoracoscopy (n=1), thoracotomy (n=2) and sternotomy (n=1). RESULTS: Per-operative morbidity consisted of one case of massive venous bleeding during MDS requiring a salvage sternotomy to achieve hemostasis. The diagnoses finally established for the 88 patients were non-Hodgkin's lymphoma (NHL) for 36, small cell lung cancer for 25, non-small cell lung cancer for 17, Hodgkin's disease for five, thymoma for three, germ cell tumour for one and sarcoma for one. For the diagnosis of lung cancer, the sensitivities of CTGB and MDS were 85 and 100%, respectively. For the diagnosis of NHL, the sensitivity of anterior mediastinotomy was 95%. CONCLUSION: The surgical diagnostic procedure, chosen on the basis of the clinical presentation and CT-scan, can be performed safely in the case of SVCS, with the same accuracy as in the absence of this syndrome. Among the patients referred to surgeons, NHL is the most frequent aetiology of SVCS, together with small cell lung cancer.

Adenocarcinoma↗

Surgical treatment of primary sarcoma of the lung.

OBJECTIVE: To study the results of surgical treatment of primary lung sarcoma. METHODS: Between 1982 and 1998, we performed 18 macroscopically complete resections for primary sarcomas of the lung. The records of all patients were reviewed, as were pathological slides. Presence of symptoms, tumour size (more or less than 5 cm), complete resection, TNM stage and histology grade were analyzed for predictors of survival. RESULTS: Patients comprised 11 women and seven men whose age ranged from 19 to 73 years (mean 50 years). Mean tumour diameter was 8.05 cm (range 2.5-15 cm) There were one grade 1, eight grade 2 and nine grade 3 tumours. Tumours in two patients were unresectable at first presentation, and another was of doubtful resectability according to computed tomography scan. These three patients received pre-operative chemotherapy, with a partial response in the two unresectable patients allowing macroscopically complete resection in both cases. We performed 12 lobectomies (extended to the chest wall in two cases and to the diaphragm in two cases) and six pneumonectomies (extended to the chest wall in one case and the superior vena cava in one case). Operative and 30 days post-operative mortality were nil. Resection margins were invaded in two cases. Six patients received post-operative chemo- or radiotherapy and three others underwent repeat resections for pulmonary sarcoma recurrence. No patients were lost to follow-up. Pulmonary sarcomas recurred in eight patients (44%) leading to death in five cases after a mean period of 17 months. Overall median survival was 48 months, and actuarial 5-year survival 43%. Only TNM stage correlated with significantly increased survival. CONCLUSION: As complete resection is the best therapeutic option for obtaining an acceptable survival rate in primary pulmonary sarcoma, pre-operative chemotherapy can be a useful adjunct in increasing the resectability of these tumours.

Adult↗

Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus.

Limbic status epilepticus was induced in rats by unilateral 60-min electrical stimulation of the CA3 region of the ventral hippocampus. As assessed by RT-PCR followed by Southern blot analysis, transcripts of interleukin-1beta, interleukin-6, interleukin-1 receptor antagonist and inducible nitric oxide synthase were significantly increased 2 h after status epilepticus in the stimulated hippocampus. Induction was maximal at 6 h for interleukin-1beta (445%), interleukin-6 (405%) and tumour necrosis factor-alpha (264%) and at 24 h for interleukin-1 receptor antagonist (494%) and inducible nitric oxide synthase (432%). In rats with spontaneous seizures (60 days after status epilepticus), interleukin-1beta mRNA was still higher than controls (241%). Immunocytochemical staining of interleukin-1beta, interleukin-6 and tumour necrosis factor-alpha was enhanced in glia with a time-course similar to that of the respective transcripts. Sixty days after status epilepticus, interleukin-1beta immunoreactivity was increased exclusively in neurons in one third of the animals. Multiple intracerebroventricular injections of interleukin-1 receptor antagonist (0.5 microg/3 microL) significantly decreased the severity of behavioural convulsions during electrical stimulation and selectively reduced tumour necrosis factor-alpha content in the hippocampus measured 18 h after status epilepticus. Thus, the induction of spontaneously recurring seizures in rats involves the activation of inflammatory cytokines and related pro- and anti-inflammatory genes in the hippocampus. These changes may play an active role in hyperexcitability of the epileptic tissue.

Animals↗

Relationship between endothelin-1 concentration and metabolic alterations typical of the insulin resistance syndrome.

The purpose of the study was to examine the relationship between the endothelin-1 (ET-1) concentration and the metabolic variables characteristic of the insulin resistance syndrome ([IRS] hyperinsulinemia, insulin resistance, hypertriglyceridemia, low high-density lipoprotein [HDL] cholesterol, visceral obesity, and glycemic abnormalities). The measurement of circulating ET-1 is a well-recognized marker of endothelial atherosclerotic and cardiovascular disease. Two hundred subjects were divided into 3 groups. Group 1 included 50 subjects with impaired glucose tolerance (IGT) or non-insulin-dependent diabetes mellitus (NIDDM) with IRS. Group 2 included 50 subjects with IGT or NIDDM without IRS. Group 3 included 100 normal subjects as controls. ET-1 levels were higher in group 1 versus groups 2 and 3 in women (11.2 +/- 0.7 v 7.9 +/- 0.5 and 6.6 +/- 0.4 pg/mL, P < .01) and men (10.1 +/- 0.6 v 6.5 +/- 0.8 and 7.2 +/- 0.3 pg/mL, P < .01). No differences were found between groups 2 and 3. With simple regression analysis, ET-1 levels significantly correlated with insulin, glycosylated hemoglobin, body weight, waist to hip ratio, and triglyceride values. However, with multiple regression analysis, only triglycerides (P < .009) and glycosylated hemoglobin (P < .001) remained independently correlated with ET-1. In conclusion, this cross-sectional study indicates that glycosylated hemoglobin and triglycerides are independently correlated with ET-1 levels in patients with IRS.

Blood Glucose↗

Modulatory role of neuropeptides in seizures induced in rats by stimulation of glutamate receptors.

Stimulation of glutamate receptors has been reported to modulate the expression of neuropeptides and their receptors in neurons. On the other hand, neuropeptides are known to regulate the presynaptic glutamate release and neuronal responses to excitatory neurotransmission. This evidence indicates a functional interaction between glutamatergic and neuropeptidergic transmission in the central nervous system (CNS). In this report, we provide pharmacologic evidence in experimental models of seizures, suggesting that somatostatin (SRIF) and neuropeptide Y (NPY) are endogenous modulators of glutamate-mediated hyperexcitability in the CNS. Electroencephalographic (EEG) and behavioral seizures were induced in rats by intrahippocampal or systemic injection of kainic acid, a glutamate analog. The number of EEG seizures and their total duration were inhibited significantly by intracerebral application of a SRIF(1) receptor agonist. Similarly, kainate seizures were reduced by N[-2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl-D-arginamide++ +] (BIBP 3226), a NPY Y(1) receptor antagonist. Enhanced seizure susceptibility to pentylentetrazol, ensuing in rats after a systemic administration of kainic acid, was reduced significantly by intracerebral application of RC 160, a SRIF(1) receptor agonist, or NPY 13-36, a Y(2)/Y(5) receptor agonist. This evidence suggests that neuropeptide analogs may be of value for controlling seizures and possibly in other pathologic conditions associated with excessive glutamate function.

Animals↗

Oxidative stress occurs in absence of hyperglycaemia and inflammation in the onset of kidney lesions in normotensive obese rats.

BACKGROUND: Several factors favour the development of kidney lesions. We examined the role of oxidative stress in the onset of renal alterations that occur in Zucker obese (ZO) fa/fa rats. METHODS: Kidney structure, biological data, glycation parameters, advanced glycation end products (AGE), thiobarbituric acid-reactive substances (TBARS), circulating antibodies anti-malondialdehyde (MDA)-modified low-density lipoprotein (LDL), antioxidant defenses (Cu/Zn and Mn superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) activities, glutathione level), were determined in plasma and/or kidney of young and old ZO rats and lean (ZL) Fa/fa littermates. RESULTS: Renal lesions and functional decline appeared at 3 months in hyperlipidaemic, hyperinsulinaemic, normotensive ZO rats, independently of any macrophage-ED(1)(+)-cell infiltration. At 6 months and thereafter, kidney lesions and functional impairment worsened while numerous ED(1)(+)-cells invaded the interstitium. At 3 and 9 months, TBARS level in the LDL/very low-density lipoprotein fraction and in the kidney was higher in ZO than in ZL rats. Anti-MDA-LDL antibodies were increased in ZO rats. At 3 months, renal activity of Cu/Zn SOD was higher, and activities of catalase and GPx lower in ZO than in ZL rats, leading to an accumulation of hydrogen peroxide (H(2)O(2)). At 9 months, a decrease in Cu/Zn SOD activity and an increase in glutathione level were observed. Blood glucose and glycated proteins, as well as AGE in kidney, remained similar in both ZL and ZO rats, whatever their age. CONCLUSION: These data suggest that oxidative stress triggers, at an early age, the onset of kidney lesions and functional impairment in ZO rats, in absence of hyperglycaemia, hypertension and inflammation.

Animals↗

Biomarkers of oxidative stress: an analytical approach.

Oxidative stress is implicated in many pathological processes and results from a disruption of the prooxidant/antioxidant balance. This review will focus on noninvasive biomarkers of radical-induced damage in biological fluids and particularly in blood. Special attention will be addressed to new analytical methods for the measurement of radical-mediated alterations in the integrity of lipids, proteins and DNA.

Animals↗

Thermal and chemical diffusion in the rapid solidification of binary alloys

Solidification of binary alloys is characterized by the necessity to reject away from the advancing front two conserved quantities: the latent heat released at the solid-liquid interface and the solute atoms that cannot be accommodated in the solid phase. As thermal diffusion is much faster than chemical diffusion, the latter is generally assumed to be the rate limiting mechanism for the process, and the problem is addressed through the isothermal approximation. In the present paper we use the phase-field model to study the planar growth of a solid germ, nucleated in its undercooled melt. We focus on the effects of a noninstantaneous thermal relaxation. The steady growth predicted at large supersaturation in the isothermal limit is prevented. Depending on the value of the Lewis number the growth rate is limited by either mass or heat diffusion; in the latter case we observe a sharp transition between two different regimes, in which originates a nonmonotonic time dependence of the interface temperature. The effects of this transition reflect in the composition of the solidified alloy.

Journal Article↗

Alterations in nitric oxide/cyclic-GMP pathway in nondiabetic siblings of patients with type 2 diabetes.

In this study, we have compared resistance to insulin-mediated glucose disposal and plasma concentrations of nitric oxide (NO) and cyclic-GMP in healthy volunteers with (n = 35) or without (n = 27) at least one sibling and one parent with type 2 diabetes. The 62 volunteers were further divided into groups of those with normal glucose tolerance or impaired glucose tolerance. Insulin-mediated glucose disposal was quantified by determining the insulin sensitivity index (ISI) in response to a low-dose, constant infusion of insulin (25 mU/kg x h) and glucose (4 mg/kg x min) for 150 min. The mean (+/-SEM) ISI [(mL kg(-1) min(-1)/pmol/L) x 10(3)] was significantly greater in those without a family history (30.3 +/- 2.3) as compared with nondiabetic volunteers with a family history of type 2 diabetes, whether they had normal glucose tolerance (17.0 +/- 7.2) or impaired glucose tolerance (9.5 +/- 1.4). In addition, basal NO levels, evaluated by the measurement of its stable end products [i.e. nitrite and nitrate levels (NO2-/ NO3-)], were significantly higher, and cyclic-GMP levels, its effector messenger, were significantly lower in those with a family history, irrespective of their degree of glucose tolerance, when compared with healthy volunteers without a family history of type 2 diabetes. Furthermore, when the 62 volunteers were analyzed as one group, there was a negative correlation between ISI and NO2-/NO3- levels (r = -0.35; P < 0.005) and a positive correlation between ISI and cyclic-GMP levels (r = 0.30; P < 0.02). These results have shown that alterations of the NO/cyclic-GMP pathway seem to be an early event in nondiabetic individuals with a family history of type 2 diabetes and these changes are correlated with the degree of insulin resistance.

Blood Glucose↗

Induction of specific phosphodiesterase isoforms by constitutive activation of the cAMP pathway in autonomous thyroid adenomas.

Thyrocytes largely depend on cAMP signaling for replication and differentiation. This pathway may be constitutively activated by mutations of the TSH receptor (TSHR) and Gsalpha in autonomous thyroid adenomas (ATAs). Because steady state cAMP results from production by adenylyl cyclase and degradation by phosphodiesterases (PDEs), we evaluated PDE activity and expression in ATAs with wild-type and mutant TSHR and Gsalpha. Activating mutations of TSHR and Gsalpha were identified in 7 and 1 of 18 ATAs, respectively. No difference was observed in the cAMP content in ATAs with or without activating mutants. In the surrounding normal thyroid tissue (NTs), PDE activity was 80% isobutylmethylxanthine sensitive, with the major contribution by PDE1 and a minor contribution by PDE4. No differences were observed in PDE activities between NTs and ATAs with wild-type TSHR and Gsalpha. In contrast, in the presence of mutant TSHRs or Gsalpha, total PDE activity was higher. This increase was primarily due to PDE4 induction (917 +/- 116% over NTs), associated with a minor PDE1 increase only in ATAs with mutant TSHR. By RT-PCR, increments of PDE4D and 4C messenger ribonucleic acids were found in the ATAs with mutant TSHR or Gsalpha, whereas messenger ribonucleic acids encoding other cAMP-specific PDEs were not significantly increased. This study provides a characterization of the PDEs expressed in human thyroid and demonstrates a dramatic PDE4 induction in the ATAs bearing mutant TSHR or Gsalpha genes. The increase in cAMP-degrading activity may represent a marker of constitutive adenylyl cyclase activation and constitutes an intracellular feedback mechanism with significant impact on the phenotypic expression of the activating mutations.

Adenoma↗

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Cost Savings↗

[Gallbladder carcinoma and laparoscopic cholecystectomy. An emergent problem].

BACKGROUND: Gallbladder cancer (GC) is reported in 1.5-3% of cholecystectomies. Since the introduction of laparoscopic surgery, cholecystectomies have increased and occult GC may therefore be more frequent. METHODS: Here we conduct a retrospective study on a series of 1200 LC performed between January 1991 and December 1998 at our Institution, to determine whether there was an increase in GC. We also evaluated the risk factors for this outcome and the possibilities of treatment, in case of unsuspected GC discovered after LC at histological examination. Seven cases of GC undiagnosed before surgery (0.6% of the study population) were submitted to LC (against 0.3% GC discovered after open surgery). The clinical course depended on the histopathologic stage of the cancer. RESULTS: After a median follow-up of 18 months (range 12-48), 2 pT1 patients were alive and well, 2 pT2 patients were alive and disease free (in 1 case after a surgical removal of a trocar site metastasis appeared 6 months after LC). The other 3 patients died, 2 (1 pT2 and 1 pT3) after an additional resection of the liver bed with lymph node dissection, due to peritoneal dissemination of the disease. In 2 cases we found a gallbladder polyp pre and intraoperatively, which proved to be a carcinoma. CONCLUSIONS: Undiagnosed GC is on the increase with the introduction of LC. Polypoid lesions of the gallbladder, age > 70 years: a long history of stones and a thickened gallbladder wall all represent significant risk factors. If one or more is present, examination of the gallbladder and a frozen section are recommended.

Adenocarcinoma↗