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Biomedical subjects

R Bianchi

Publications and source records attributed to R Bianchi.

At least 145 records · Page 8Linked to original sources
PubMed1994

Calpactin I binds to the glial fibrillary acidic protein (GFAP) and cosediments with glial filaments in a Ca(2+)-dependent manner: implications for concerted regulatory effects of calpactin I and S100 protein on glial filaments.

Calpactin I, a heterotetrameric, cytoskeletal protein complex composed of two copies of annexin II cross-linked by two copies of p11, an S100-like protein, binds to the glial fibrillary acidic protein (GFAP) and cosediments with glial filaments (GF) in a Ca(2+)-dependent manner, apparently without affecting GFAP polymerization under the present experimental conditions. Cosedimentation of calpactin I with GF, which occurs at micromolar free Ca2+ concentrations, is proportional to the concentrations of both calpactin I and GFAP and does not occur under conditions where GFAP assembly is maximally inhibited by, e.g., S100 protein. Annexin II also cosediments with GF and binds to GFAP, although to much smaller extents. Other annexins, such as annexins I, V, and VI, or p11 do not bind to either GF or GFAP. Calpactin I and S100 protein bind to different sites on GFAP, as investigated by fluorescence spectroscopy using acrylodan-labeled GFAP. Calpactin I and S100 protein might act, in the presence of Ca2+, in a concerted manner to determine the number and topography of GF in differentiating and/or mature glial cells.

2-Naphthylamine↗
PubMed1994

Defective activity of Na+,K(+)-ATPase in peripheral nerve of diabetic rats is independent of the axonal transport of the enzyme.

This study addressed the question as to whether the reduced activity of Na+,K(+)-ATPase reported to occur in diabetic nerves and to play a crucial role in the pathogenesis of diabetic neuropathy could be due to derangements in the axonal transport of the enzyme. A micromethod was developed to evaluate the ATPase accumulation in individual segments of ligated sciatic nerves from streptozotocin-induced diabetic rats. The results confirmed a approximately 40% decrease in the background activity, but showed that the enzyme was transported at similar rates in both anterograde and retrograde directions, suggesting that the decrease in its activity does not depend on an altered delivery along the axons.

Analysis of Variance↗
PubMed1994

Use of a skin test assay to determine tumor-specific CD8+ T cell reactivity.

We have observed delayed-type hypersensitivity (DTH) reactions in immunized mice challenged subcutaneously with class I-binding peptides related to rejection antigens recognized by cytotoxic T lymphocytes on mutagenized (tum-) variants of mastocytoma P815. As observed by skin test in virally infected mice challenged with viral peptides, the intrafootpad injection of tum- peptides resulted in a dose-dependent DTH that peaked at approximately 24 h. The response was mediated by CD8+ cells and could be induced by previous vaccination of mice with live tumor cells, intrasplenic deposition of the eliciting peptide, or adoptive transfer with peptide-pulsed syngeneic dendritic cells. These sensitization procedures resulted in an immunologically specific footpad reaction detectable for up to 2-6 months after priming. The evaluation by DTH in cancer patients of long-lived CD8+ anti-tumor T cell responses following local challenge with tumor-specific peptides may be of great interest in human immunotherapy trials involving immunization against identified tumor antigens.

Animals↗
PubMed1994

Elevated serum levels of neopterin and soluble interleukin-2 receptor in patients with ovarian cancer.

Preoperative serum neopterin, soluble interleukin-2 receptor (sIL-2R), and CA125 levels were assayed in 47 patients with ovarian cancer and 113 patients with benign ovarian disease undergoing laparotomy. The cutoff limits of the antigens for the preoperative evaluation of ovarian cancer were fixed according to the Youden plot, using the patients with benign ovarian disease as controls. These limits were 7.9 nmole/liter for neopterin, 71 U/ml for sIL-2R, and 83 U/ml for CA125. The preoperative mean values of serum neopterin and sIL-2R were significantly higher in patients with ovarian cancer than in those with benign ovarian disease. Therefore these tests would seem to be useful in distinguishing benign from malignant ovarian masses. Serum levels of neopterin, sIL-2R, and CA125 above the cutoff limits were detected in 66.0, 78.7, and 76.6% of patients with ovarian cancer. Patients with advanced-stage disease (FIGO > or = III) were significantly more likely to have a higher percentage of elevated values of sIL-2R and CA125, but not neopterin, compared to patients with early-stage disease. However, neopterin was the antigen most often raised in early disease. As for advanced ovarian cancer, preoperative serum sIL-2R levels were higher in patients who developed progressive disease than in those who were progression-free (P = 0.02) after a median follow-up time of 18 months. Furthermore, a trend to higher preoperative serum neopterin values was found in the former patients (P = 0.08). Tumor progression occurred in 3 of 8 (37.5%) patients with low serum preoperative neopterin (< 7.9 nmole/liter) and in 16 of 19 (84.2%) patients with elevated serum neopterin, respectively (P = 0.027). Multivariate analysis on a larger number of patients followed for a longer time is warranted to elucidate the prognostic relevance of these immunologic markers in ovarian cancer. Changes in serum neopterin, sIL-2R, and CA125 levels correlated with the disease course in 50.0, 54.8, and 92.9% of 42 instances, respectively. Moreover, serum CA125 was more sensitive than the other two antigens in the early detection of tumor progression. Therefore serial neopterin and sIL-2R measurements seem to be of limited value in monitoring the disease course in patients with ovarian cancer.

Adult↗
PubMed1994

The beta-carboline derivative DMCM decreases gamma-aminobutyric acid responses and Ca(2+)-mediated K(+)-conductance in rat neocortical neurons in vitro.

Electrophysiological recordings from neurons of rat frontal neocortical slices have been used to investigate the action of the beta-carboline methyl-6,7-dimethoxy-4-ethyl-beta- carboline-3-carboxylate (DMCM), on responses to gamma-aminobutyric acid (GABA) and on the excitability of the neurons. Iontophoretic application of GABA close to the intracellularly recorded cells (resting membrane potential -74 +/- 0.9 mV) elicited a depolarization associated with a decrease of input resistance, mediated by GABAA receptors. Bath application of DMCM (0.1-1 microM) reduced these GABA responses decreasing the affinity of the receptors for GABA. This effect was blocked by the benzodiazepine receptor (BZR) antagonist ZK 93426 (1 microM). DMCM (0.1 microM) also decreased the hyperpolarization that followed a train of action potentials (AHP), mediated by Ca(2+)-dependent K+ conductance, and increased the duration of Ca(2+)-dependent action potentials recorded after blockade of Na+ and K+ conductances. Neither effect was blocked by BZR antagonists. These results indicate that DMCM increases the excitability of neurons not only by reducing the gain of the GABAA/BZR complex, but also by modulating intrinsic membrane mechanisms.

Action Potentials↗
PubMed1994

Kinetic study of atrial natriuretic peptide in patients with idiopathic dilated cardiomyopathy: evidence for resistance to biologic effects of the hormone even in patients with mild myocardial involvement.

Atrial natriuretic peptide (ANP) kinetics was studied in 12 patients with idiopathic dilated cardiomyopathy at different sodium excretion (30-175 mmol/day) and variable degrees of hemodynamic dysfunction [New York Heart Association (NYHA) class range I-III] to investigate whether differences in renewal and distribution of this hormone (as compared with those of a control group) play a role in pathogenesis and evolution of heart failure. [125I]Labeled ANP was injected as a bolus, and a high-performance liquid chromatography (HPLC) procedure was used to purify the labeled hormone in venous plasma samples collected for < or = 50 min after injection; the main ANP kinetic parameters were then derived from the disappearance curve of the labeled hormone. As in controls, a positive linear regression between ANP metabolic clearance rate (MCR, ml/min/m2) values and daily urinary excretion of sodium (NaUE, mmol/day) was noted in patients. The different linear regression coefficients between normal subjects (MCR = 365 +/- 8.08 NaUE, r = 0.986, p < 0.0001) and patients (MCR = 497 + 18.5 NaUE, r = 0.867, p = 0.001) indicate that in patients a higher peptide clearance rate is needed to obtain the same biologic effect (sodium excretion) and suggest that resistance to biologic effects of the hormone exists in patients at an early stage of disease (NYHA class I). When the efficiency of the ANP system in excreting sodium was expressed as the ratio of NaUE to ANP production rate (PR = MCR x ANP plasma concentration, microgram/day/m2) patients showed significantly lower values (p = 0.0126) than normal volunteers, thus confirming resistance to the hormone effects. Significantly lower values for ANP total distribution volume (16.5 +/- 8.4 L/m2), mean residence time in the sampling space (4.04 +/- 1.14 min), mean residence time in the body (7.25 +/- 2.13 min), and fewer recycles through the initial (sampling) space (0.27 +/- 0.16) were noted in patients, indicating an altered mechanism regulating distribution of the hormone. The positive correlations between ANP MCR (L/min/m2) values and cardiac index (CI, L/min/m2) (MCR = -1.24 + 1.17 CI, r = 0.689, p = 0.0092) and between initial distribution volume (IDV, L/m2) and CI (IDV = -11.2 + 6.85 CI, r = 0.730, p = 0.0046) in all patients indicate that hemodynamic factors contribute to the progressive reduction in MCR and IDV values throughout the progression of myocardial involvement.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

Carbachol-induced synchronized rhythmic bursts in CA3 neurons of guinea pig hippocampus in vitro.

1. Carbachol effects on CA3 hippocampal cells were studied in the absence of ionotropic glutamatergic and GABAergic transmission with intracellular and extracellular recordings from guinea pig septohippocampal slices. 2. In all experiments the perfusing solution contained ionotropic glutamate and gamma-aminobutyric acid (GABA) receptor blockers [6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10-20 microM), 3-((+/-)-2-carboxypiperazin-4-il)propyl-1-phosphonic acid (CPP, 10-20 microM), and picrotoxin (50 microM), respectively]. Under these conditions, the excitatory and early inhibitory postsynaptic potentials, evoked in CA3 pyramidal cells by mossy fiber stimulation before the addition of the blockers, were completely suppressed. 3. Carbachol (50 microM) introduced via bath perfusion or pulse application elicited a series of rhythmic bursts with overriding action potentials. Each rhythmic burst lasted up to 30 s and repeated at intervals of 0.7-6 min. Rhythmic bursts were blocked by atropine (1 microM). 4. At membrane potentials more depolarized than -70 mV, carbachol also elicited a sustained depolarization associated with an increase in membrane input resistance and action-potential firing. This response was blocked by atropine (1 microM). 5. Carbachol can induce both rhythmic bursts and sustained depolarizations in the same cell. Rhythmic bursts were elicited when the membrane potential of the cell was more hyperpolarized than -70 mV; sustained depolarizing responses were activated by carbachol when the cell membrane potential was more depolarized than -70 mV. 6. Extracellular field potential responses in the CA3 region occurred simultaneously with rhythmic bursts, indicating the synchronization of the event in the CA3 field. Dual intracellular recordings confirmed that rhythmic bursts occurred simultaneously in CA3 hippocampal pyramidal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Amyloid deposits inside myocardial fibers in transthyretin-Met30 familial amyloidotic polyneuropathy. A histological and biochemical study.

A case of severe cardiac involvement is reported in a patient affected with familial amyloidotic polyneuropathy due to the Portuguese type I variant (Val-->Met30) of the transthyretin (prealbumin) molecule. Echocardiographic and hemodynamic studies suggested the presence of a progressive infiltrative cardiomyopathy that was later confirmed by endomyocardial biopsy. Amyloid deposits were found in both intra- and extra-myofiber location and thought to be related to primary involvement of the heart. Norepinephrine content of myocardial bioptic specimens was about threefold lower than normal, indicating that autonomic denervation may contribute to the maintenance and progression of cardiomyopathy. A sample obtained from the sural nerve showed a loss of myelinated fibers along with accumulation of amyloid masses in the endoneurial space. This histopathologic pattern correlated with a sharp decrease in the activity of the enzyme subserving electrochemical conduction through the axonal membrane, Na+, K(+)-ATPase.

Amyloid↗
PubMed1994

[Liver cirrhosis and pregnancy].

A clinical case of a woman 25 year old with Laennec's cirrhosis at 18th, week of gestation was admitted in our hospital. In the 30th week a cesarean section was performed, resulting a healthy infant. The infrequency relationship between pregnancy and cirrhosis is discussed an a review of the literature is presented.

Adult↗
PubMed1994

A cluster analysis of the neurons of the rat interpeduncular nucleus.

The morphometric characteristics of the neurons of the interpeduncular nucleus (IPN) in the rat were investigated by cluster analysis in order to identify neuronal groups which are morphometrically homogeneous, and to define their position and density in the IPN subnuclei. Two clusters of cells were detected. Cluster 1 neurons had a larger perikaryal size with a mean cross-sectional area of 170 microns2 and a high nuclear/cytoplasmic ratio. They were located mainly in the pars dorsalis (37%) and pars medialis (34%) rather than in the pars lateralis (29%). Cluster 1 neurons were also more frequent at the rostral (31%) and caudal (57%) poles than in the central part of the IPN. Cluster 2 cells showed a smaller mean perikaryal area (110 microns2), a small nucleus and abundant cytoplasm. They were equally distributed throughout the whole IPN. These findings suggest the existence of a magnocellular region at the rostral pole of the IPN which has not been described previously. The presence of IPN regions endowed with specific cytoarchitectural characteristics is discussed with respect to the complex neurochemical organisation of the nucleus.

Animals↗
PubMed1994

[Gastric carcinoma. Our experience].

This study analysed 66 cases of gastric cancer from 1985 to 1992. Twenty-seven patients (41%) has been treated with anti-H2 drug, either medical care or Jerkily "a la demande": 12 patients have been treated several years. Of the 66 patients: 52 (89%) were operated on while the other 16 received medical treatment because of the extension disease and their precarious condition. Long-term 35 (67%) patients (of the 52 operated) died four years later, independently of the stage and PKT of the first and the second level. The 27 patients treated with anti-H2 drug showed the most undifferentiated grading and 88% belong to the third and the fourth stage; moreover 81% underwent first diagnostic endoscopy notwithstanding a clinical and surgical history of gastric ulcer. Is it possible, therefore, that anti-H2 drug delay the diagnosis.

Adult↗
PubMed1993

Decrease of nerve Na+,K(+)-ATPase activity in the pathogenesis of human diabetic neuropathy.

A decrease in Na+,K(+)-ATPase activity is claimed to play a central role in the pathogenesis of electrophysiological and morphological abnormalities that characterize the neuropathic complications in different animal models of diabetes mellitus. The peripheral nerves from 17 patients with either type I or type II diabetes mellitus were studied to assess the importance of changes in Na+,K(+)-ATPase activity in chronic human diabetic neuropathy. Sixteen nerves from age- and sex-matched normal individuals, and 12 nerves from non-diabetic neuropathic subjects undergoing vascular or orthopedic surgery served as negative and positive controls, respectively. All specimens were processed blind. Ouabain-sensitive ATPase activity was measured by a modified spectrophotometric coupled-enzyme assay. Standard histology, fiber teasing and electron microscopy were used to establish the normal or neuropathological patterns of surgical material. Morphometric analysis permitted calculation of fiber density in each nerve specimen and correlation of this figure with the relevant enzymatic activity. Na+,K(+)-ATPase activity was approximately 59% lower in nerves from diabetic patients than in normal controls (P < 0.01) and approximately 38% lower in nerves from non-diabetic patients with neuropathy (P < 0.01). Although nerves from both neuropathic conditions had significantly fewer fibers than those from normal individuals (diabetic -33%, and non-diabetic -22%), the decreases in Na+,K(+)-ATPase activity and fiber density were not correlated only in specimens from diabetic patients (r2 = 0.096; P = 0.22). Taken together with data from experimental animal models, these results suggest that the reduction in Na+,K(+)-ATPase activity in diabetic nerves is not an epiphenomenon secondary to fiber loss; rather, it may be an important factor in the pathogenesis and self-maintenance of human diabetic neuropathy.

Adult↗
PubMed1993

Immunogenic properties of retroviral protein P15E from drug-treated murine mastocytoma P815.

A triazene-xenogenized tumor sub-line was derived from the mouse mastocytoma cell line P815 following several transplant generations in vivo on DTIC. The highly immunogenic P815/DTIC variant line expressed new CTL-defined antigens. Novel antigens were also detected by antibodies in immunoprecipitation and by Western blot analysis. Upon immunoprecipitation of metabolically labeled cells, one such variant-specific 20-kDa antigen was shown to be related to retroviral envelope protein p15E. When injected intrasplenically into recipient mice, the electroblotted nitrocellulose-bound 20-kDa antigen resulted in increased frequency in CTL precursors to P815/DTIC cells. In addition to previous data in the L5178Y/DTIC tumor-model system, these data suggest that expression of aberrant, retrovirus-related proteins may be a common finding in different parental tumors xenogenized by triazene treatment.

Animals↗
PubMed1993

Effect of gangliosides on diacylglycerol content and molecular species in nerve from diabetic rats.

The effects of ganglioside treatment on 1,2-diacylglycerol content and on molecular species in 1,2-diacylglycerol, phosphatidic acid and total diacylglycerolipids, as well as Na+,K(+)-ATPase activity, were examined in sciatic nerves from streptozotocin-induced diabetic rats. Beginning 2 weeks after induction of diabetes, animals were administered mixed bovine brain gangliosides, AGF1, an inner ester derivative of this mixture, or saline for 5 weeks. The levels of 1,2-diacylglycerol and arachidonoyl-containing molecular species in age-matched non-diabetic animals were not affected by ganglioside treatment. In nerves from saline-treated diabetic animals, 1,2-diacylglycerol levels were not reduced, but both Na+,K(+)-ATPase activity and all arachidonyl-containing species except for 18:0/20:4 1,2-diacylglycerol were significantly decreased. The content of 1,2-diacylglycerol was lowered by 23 and 16% in bovine brain ganglioside and AGF1-treated diabetic animals, respectively, and the quantity of 18:0/20:4 1,2-diacylglycerol was also selectively reduced. Ganglioside administration did not affect the diminished levels of arachidonoyl-containing molecular species in 1,2-diacylglycerol, phosphatidic acid or diacylglycerolipids in nerve from diabetic rats. In the same nerves, bovine brain gangliosides partially and AGF1 completely restored Na+,K(+)-ATPase activity. The results suggest that gangliosides depress the content of total 1,2-diacylglycerol and the quantity of 18:0/20:4 1,2-diacylglycerol, specifically, in diabetic nerve. The possible relationship between the corrective action of gangliosides on Na+,K(+)-ATPase activity and the effect of these substances on 1,2-diacylglycerol molecular species composition and metabolism is discussed.

Animals↗
PubMed1993

S-100 protein, but not calmodulin, binds to the glial fibrillary acidic protein and inhibits its polymerization in a Ca(2+)-dependent manner.

S-100 protein, a Ca(2+)-binding protein of the EF-hand type, interacts with the glial fibrillary acidic protein (GFAP) in a Ca(2+)-dependent manner. The binding of S-100 protein to GFAP was investigated by fluorescence spectroscopy using acrylodan-S-100 protein and cross-linking experiments using the bifunctional cross-linker, disuccinimidyl suberate. The binding affinity was observed to be in the nanomolar range with a stoichiometry of 2 mol of GFAP/mol of S-100 protein (dimer). S-100 protein was found to inhibit the polymerization of GFAP in a dose- and Ca(2+)-dependent manner, with a half-maximal effect at an S-100 protein/GFAP molar ratio of 0.2 and maximal effect at a molar ratio of 0.5. Identical results were obtained irrespective of whether the unfractionated bovine brain S-100 protein mixture (S-100a plus S-100b), S-100ao, S-100a, or S-100b was used. S-100 protein was observed to be maximally effective as an inhibitor of GFAP polymerization at approximately 3 microM free Ca2+. Calmodulin neither bound to GFAP nor inhibited its polymerization. Altogether, the present results suggest that S-100 protein might be involved in the regulation of the state of assembly of glial filaments by binding to and sequestering unpolymerized GFAP.

2-Naphthylamine↗
PubMed1993

Analysis of the cost-effectiveness ratio of the health campaign for the early diagnosis of cutaneous melanoma in Trentino, Italy.

BACKGROUND: The cost-effectiveness ratio of a health campaign for the early diagnosis of cutaneous melanoma (CM), currently the only means to reduce mortality from this melanoma, was calculated for the Trentino region in Italy. METHODS: Health campaigns in Trentino were carried out, and comparisons were made with neighboring regions where there had been no campaigns. To do this, the trend of the mortality rates calculated according to sex and age using the direct standardized method and data provided by ISTAT (the Central Italian Institute of Statistics) was considered. RESULTS: It was determined that 22.3 lives were saved by early diagnosis during the period 1977-1985, resulting in a savings of $494,636 to the Italian National Health Service in avoided treatments. The total cost to the Health Service of the campaign was $70,800. The cost per year of lives saved was calculated to be $400. CONCLUSIONS: The outcome of this campaign was a recommendation for the use of such programs in other countries and regions.

Aged↗
PubMed1993

Benfluorex decreases insulin resistance and improves lipid profiles in obese type 2 diabetic patients.

Benfluorex hydrochloride has known lipid- and glucose-lowering effects. We evaluated the change in lipids, fasting glucose, and insulin sensitivity in ten obese type 2 diabetic patients after treatment with benfluorex or a placebo for 2 weeks using a double-blind, cross-over design. Insulin sensitivity was measured using the euglycaemic-hyperinsulinaemic glucose clamp technique at two insulin infusion rates for 2 h each: 0.05 U/kg per h (clamp 1) and 0.10 U/kg per h (clamp 2). Mean fasting glucose decreased from 13.1 +/- 1.1 to 10.2 +/- 0.9 mmol/l after benfluorex (p < 0.001) and rose from 11.9 +/- 0.9 to 13.3 +/- 1.0 mmol/l after the placebo (p = 0.028). Insulin did not change significantly. Glucose uptake (GU) as a parameter for insulin sensitivity was compared for treatment with benfluorex versus the placebo. Total GU during clamp 1 was 643.4 +/- 323.8 mmol after benfluorex and 250.1 +/- 193.3 mmol after the placebo (p = 0.035), and during clamp 2, 2490.7 +/- 490.5 mmol after benfluorex and 1544.3 +/- 693.9 mmol after the placebo (p = 0.018). The dynamic analysis on the last 30 min of clamp 2 showed a significant difference in glucose infusion rate (GIR) profile, with mean levels yielding 5.36 mmol/kg per min after benfluorex and 3.87 mmol/kg per min after the placebo (p = 0.018); there were no differences in plasma insulin concentrations or plasma glucose levels. It is concluded that in this short-term study benfluorex increases insulin sensitivity in obese type 2 diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗