[Rationale for metabolic treatment of left ventricular dysfunction].
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Adenosine Triphosphate↗
Biomedical subjects
G Bianchi
Publications and source records attributed to G Bianchi.
Interleukin-12 is chemotactic for natural killer cells and stimulates their interaction with vascular endothelium.
We investigated the chemotactic activity of interleukin (IL)-12 on human natural killer (NK) cells and other leukocyte subsets. It was found that IL-12 induced directional migration of highly enriched preparations of NK cells (> 80% CD16+ and CD56+) and CD3-activated T cells (both of CD4 and CD8 subset), but not resting T cells and monocytes. On the contrary, purified polymorphonuclear cells (PMN) showed significant and reproducible chemotactic response to IL-12. The effects of IL-12 on leukocyte migration were observed in a narrow concentration range with a peak at approximately 7.5 ng/mL, and were abrogated by monoclonal antibody (MoAb) anti-IL-12 or after cytokine boiling. We also investigated the interaction of NK cells with vascular endothelium in vitro. Overnight treatment of NK cells with IL-12 augmented their binding to cultured endothelial cells (EC) obtained from umbilical veins. IL-12-increased binding was better observed when resting rather than IL-1-activated EC were used as substratum of adhesion. IL-12-augmented binding of NK cells to resting or IL-1-activated EC involved the LFA-1/ICAM-1 and VLA-4/VCAM-1 pathways. Thus, by inducing migration and interaction with EC, IL-12 regulates crucial determinants of NK-cell recruitment in tissues.
CD3 Complex↗
Erythrocyte membrane calcium transport in patients with primary hyperparathyroidism.
The chronic effect of PTH on erythrocyte membrane Ca transport was examined. (Ca+Mg)ATPase activity and passive Sr influx were measured to assess the rate of passive Ca influx (total and inhibited by dihydropyridines [DHPs]), in erythrocytes from patients with primary hyperparathyroidism and normal controls. Erythrocyte Sr influx was lower in patients, due to a decreased DHP-sensitive Sr influx. Conversely, efflux activity of (Ca+Mg)ATPase was not different in patients and controls. We hypothesize that in primary hyperparathyroidism chronic PTH stimulation may induce a downregulation of the erythrocyte Ca influx mediated by DHP-sensitive Ca carrier.
Biological Transport↗
Two point mutations within the adducin genes are involved in blood pressure variation.
The Milan hypertensive strain of rats (MHS) develops a genetic form of renal hypertension that, when compared to its normotensive control (MNS), shows renal dysfunction similar to that of a subset of human patients with primary hypertension. MHS and MNS were shown to be homozygous by multilocus minisatellite analysis and monolocus microsatellite markers. We show here that one point mutation in each of two genes coding for the membrane skeleton protein adducin is associated with blood pressure in the Milan strain of rats. Adducin is a heterodimer formed by alpha and beta subunits that promotes the assembly of actin with spectrin. MHS and MNS differ, respectively, by the amino acids Y and F at position 316 of the alpha subunit. In the beta-adducin locus, MHS is always homozygous for R at position 529 while in MNS either R or Q occurs in that position. The R/Q heterozygotes showed lower blood pressure than any of the homozygotes. In vitro phosphorylation studies suggest that both of these amino acid substitutions occur within protein kinase recognition sites. Analysis of an F2 generation demonstrated that Y alleles segregated with a significant increment in blood pressure. This effect is modulated by the presence of the R allele of the beta subunit. Taken together, these findings strongly support a role for adducin polymorphisms in causing variation of blood pressure in the Milan strain of rats.
Amino Acid Sequence↗
Induction of natural killer cell migration by monocyte chemotactic protein-1, -2 and -3.
Under certain physiological and pathological conditions, natural killer (NK) cells rapidly accumulate in tissues. Chemokines are an essential component of the current paradigm of leukocyte recruitment. The present study was designed to investigate the responsiveness of NK cells to the prototypic C-C chemokine, monocyte chemotactic protein-1 (MCP-1). MCP-1 induced migration across filters of interleukin (IL)-2-activated NK cells, whereas it was a weak attractant for unstimulated cells. Maximal induction of migration required a positive concentration gradient between the lower and the upper compartment of the chemotaxis chamber. Preliminary characterization of the MCP-1 receptor on NK cells indicated that the chemotactic response to MCP-1 was blocked by pre-treatment of cells with Bordetella pertussis toxin, and MCP-1 but not IL-8 displaced 125I-labeled MCP-1 from IL-2-activated NK cells. The related chemokines MCP-2 and MCP-3 were also active--though less potent--attractants for activated NK cells. Thus the spectrum of action of MCP-1, -2 and -3 encompasses NK cells and chemokines are likely to play a role in regulating extravasation of these cells.
Binding, Competitive↗
Role of leukocyte function-associated antigen-1 and very late antigen-4 in the adhesion and transmigration of c-myc-transfected B-lymphoblastoid cell lines across vascular endothelium.
The present study was designed to characterize the adhesive interaction of c-myc-transfected B-lymphoblastoid cell lines with resting and interleukin-1-activated endothelial cells. The transfected cell lines expressed lower levels of leukocyte function-associated antigen-1 compared with control non-transfected lines, while no reduction of expression of other surface structures, including the beta 1 integrin very late antigen-4, was observed. The transfected cell lines adhered to resting or activated endothelial cells less than control cells. Anti-CD18 monoclonal antibody inhibited binding of control cell lines but had a modest or no effect on adhesion of transfected cell lines. Anti-very late antigen-4 monoclonal antibody effectively inhibited binding of both transfected and control cell lines; this was more pronounced in the presence of anti-CD18, suggesting a cooperative interaction between these adhesion pathways. Transfected cell lines also had an impaired ability to penetrate endothelial cell monolayers in a transmigration assay. Our results indicate that activation of the c-myc oncogene in B-cells causes alterations in the adhesive interaction with endothelial cells. This may be relevant in the localization and malignant behavior of B-cell lymphomas carrying an activated c-myc oncogene.
B-Lymphocytes↗
Prognostic significance of diabetes in patients with cirrhosis.
Alterations in carbohydrate metabolism are frequently observed in cirrhosis, and approximately 15% to 30% of patients have overt diabetes. In a retrospective and prospective study in cirrhosis, we analyzed the prognostic significance of diabetes, which was defined as the presence of hyperglycemia and overt glycosuria that in most cases required dietary restrictions or active treatment. The clinical records of all patients with cirrhosis admitted to our department for the period 1980 to 1985 were reviewed in 1985 and 1986, and surviving patients were prospectively followed up until December 1991. Final status could be obtained in 354 (98 with diabetes) of 382 eligible patients; 110 were alive at the end of follow-up. Prognostic factors were identified by Kaplan-Meier analysis, followed by Cox's stepwise regression. The model identified, in sequence, albumin, ascites, age, encephalopathy, bilirubin, diabetes, and platelets as prognostic factors. The larger mortality rate in patients with diabetes was not due to complications of diabetes but to an increased risk of hepatocellular failure. Diabetes was no longer a risk factor as a covariate in a subgroup of 271 patients when varices were added but was again significant when patients who died of gastrointestinal bleeding were excluded. The presence of diabetes, clinically detectable and often requiring adequate treatment, is a risk factor for long-term survival in cirrhosis.
Adolescent↗
Solid state and microscopy NMR study of the chemical constituents of Afzelia cuanzensis seeds.
Multi-echo, chemical shift selective, and 3D NMR imaging at microscopy resolution, and CP/MAS 13C NMR spectroscopy have been applied to the chemistry study of oil in oil-rich seeds of Afzelia cuanzensis, a tropical plant belonging to the Leguminosae taxum Caesalpinoideae or Caesalpinaceae.
Image Processing, Computer-Assisted↗
Increased risk of hepatocellular carcinoma development in patients with cirrhosis and with high hepatocellular proliferation.
The immunohistochemical determination of the accessory protein of DNA-polymerase delta (PCNA), a marker of an early S-phase of the cell cycle, was used to evaluate cell proliferation retrospectively in formalin-fixed, paraffin-embedded liver biopsy sections in a group of patients with cirrhosis of similar age and duration of follow up, and with no evidence of hepatocellular carcinoma (41), including 17 patients with and 24 without hepatocellular carcinoma appearance during follow up. Proliferation was expressed as total (PCNA-TOT) and strongly (PCNA-STRO) positive nuclei per 1000 hepatocytes. The presence of dysplasia was also recorded. Histological findings and biochemical data, at the time of liver biopsy, were compared in the two groups. While total PCNA positivities were not significantly different in the two groups, strong reactivity was significantly higher in patients who eventually developed hepato-cellular carcinoma (median 0.7 vs 2.6). Univariate analysis of histological and biochemical data at the time of biopsy, followed by a stepwise regression study, showed that the significant parameters for a time-dependent disease-free state were, in decreasing order: cholesterol, PCNA-STRO, PCNA-TOT and alpha foeto-protein. Other clinical, biochemical and histological parameters, including dysplasia, provided no further information. From these data, hepatocellular proliferation can be evaluated in patients with cirrhosis with a currently available technique. Patients with high cell proliferation are at increased risk of developing hepatocellular carcinoma and may require differentiated follow up.
Adult↗
Hepatocellular expression of HLA-A, B, C molecules predicts primary response to interferon in patients with chronic hepatitis C.
Primary response rate to alpha-interferon (IFN) is about 50% in patients with chronic hepatitis C. Criteria for predicting a positive primary response are lacking. HLA-A,B,C molecule expression is known to be stimulated by viral infections. In 36 consecutive interferon-treated anti-HCV positive patients with an available frozen liver biopsy sample, the predictive value of liver HLA-A,B,C expression, and of histologic, clinical, and biochemical parameters was evaluated. Response to treatment was defined by normalization of transaminases, and disappearance of serum HCV-RNA within 3 months. According to these criteria, 17 patients were classified as nonresponders and 19 were classified as responders. The pattern of HLA-A,B,C hepatocellular positivity varied from normal (negative or occasional faint staining of hepatocellular membranes) to diffuse, strong "honeycomb" positivity. The highest scores of positivity were found in nonresponder patients. The discriminant capacity of HLA-A,B,C scores of positivity was compared with clinical, biochemical and histologic parameters by discriminant analysis. HLA-A,B,C expression was found to be the main discriminant parameter, in addition to alkaline phosphate (ALP) and gamma-glutamyl-transpeptidase (GGT) which added little additional information. The higher hepatocellular expression of class I MHC molecules in nonresponder cases may reflect a different viral effect on hepatocytes, which is induced by different HCV genotypes or levels of viremia. From a clinical point of view, the pretreatment HLA-A,B,C pattern of positivity represents a powerful tool in the selection of patients for interferon treatment.
Adult↗
Kinetics of hepatic amino-nitrogen conversion in ageing man.
Previous studies have shown that hepatic function, quantitatively measured by dynamic liver function tests, progressively declines with ageing. Urea synthesis is a specific process taking place in the liver; a reduced urea synthesis in response to a protein-rich metal has previously been demonstrated in the elderly, but the process has never been standardized in relation to amino acid supply. We measured the hepatic conversion of alpha-amino nitrogen into urea nitrogen in response to alanine infusion in 32 subjects, with normal routine liver and renal function tests and without evidence of previous hepatic disorders, belonging to three different age-groups (< or = 55 years, 56-70, > or = 71). The functional hepatic nitrogen clearance was reduced on average by 20% in subjects aged 56-70 years, and by 30% in subjects over 70 years old in comparison to the age-group under 55 years (ANOVA: P = 0.0001), and significantly correlated with age (r = -0.684). No sex differences were observed on the effects of age on hepatic clearance. Also, liver volume, measured by ultrasonography, was reduced with advancing age, but the age-related decrease in hepatic nitrogen conversion was not primarily dependent on decreased liver volume. The measurement of functional hepatic nitrogen clearance has already been validated as a quantitative liver function test in clinical hepatology. In keeping with previous studies, the age-related decline in hepatic nitrogen conversion points to a decreased functional capacity of the ageing hepatic parenchyma.
Aged↗
Propionyl-L-carnitine prevents myocardial mechanical alterations due to pressure overload in rats.
This study investigated if propionyl-L-carnitine (PLC) treatment can directly affect cardiac mechanics, secondary to increase in myocardial carnitine content, in rats with aortic constriction and sham-operated controls. After weaning, rats were fed one of the following diets for 8 wk: 1) a low-carnitine diet (containing 2 nmol/g carnitine); 2) the same diet supplemented with PLC (710 mumol/kg body wt); 3) L-carnitine (LC; 118 mumol/kg body wt, given in tap water; or 4) a standard diet (containing 56 nmol/g carnitine). A 4-wk constriction of the abdominal aorta caused left ventricular hypertrophy associated with significantly prolonged timing parameters and reduced rate of tension decay in papillary muscles. In group 2, however, PLC treatment prevented hypertrophy-induced changes in these parameters and the reduction in unloaded shortening velocity in skinned trabeculae. Finally, PLC treatment maintained the relative proportion of myosin heavy chain isoforms in left ventricular wall of animals subjected to aortic constriction. Both PLC and LC completely prevented carnitine depletion due to hypertrophy and to dietary restriction. Because LC did not modify papillary muscle contractile function, these results demonstrate that PLC affects hypertrophy-induced changes in muscle mechanics and ventricular wall composition independently of tissue carnitine levels.
Animals↗
Vesicovaginal fistulas: our experience and review of literature.
Vesicovaginal fistulas (VVF) still represent a sad complication of surgery of the female genital system. In this article an extensive review of the literature was conducted, analyzing the etiological, pathological and clinical aspects, as well as the therapeutical problems. For this purpose, we have compared the many surgical techniques proposed for treatment of VVF and have also evaluated their results. Furthermore, we report on our series of 35 patients who had undergone treatment for VVF.
Adult↗
[Transduodenal drainage in pancreatic pseudocysts. Role of computerized tomography and treatment planning].
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Drainage↗
[Hemangiopericytoma of the duodenum. Report of a case].
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Adult↗
[Surgical repair of congenital penile curvature].
Congenital penile curvature is not such a rare pathology and it is responsible for important aesthetic and functional problems. This malformation, can render intercourse difficult and painful, but it can be cured with a simple surgical procedure that almost always guarantees excellent results. In this work we report on the treatment of 48 patients (aged 16-34) with congenital penile curvature with a follow-up of 6 months to 10 years. The aetiology is also briefly analysed. A discussion follows on the diagnostic criteria for better interpretation of the main characteristics of this problem in relation to its functional appearance. A comparison of different surgical techniques is also shown, focusing over the procedure we perform: plissettage of the tunica albuginea. This technique is performed through a penile skin incision opposite to the maximal curvature of the organ, exposure of the tunica albuginea and the positioning of one or more series of stitches. The overall results show that 44 out of 48 patients were fully satisfied both from the aesthetic and functional points of view, while 4 were partly satisfied from the aesthetic point of view alone.
Adolescent↗
Migration of natural killer cells across endothelial cell monolayers.
Under certain conditions, NK cells accumulate rapidly at extrahematic sites. In an effort to define the mechanisms underlying recruitment of NK cells in tissues, we investigated their ability to migrate across endothelial cell (EC) monolayers. A considerable proportion of NK cells adhered to EC and about 30 to 40% of the adherent NK cells migrated across EC. NK cells were two to three times more efficient than resting unseparated T cells but were considerably less efficient than monocytes. Exposure of NK cells to IL-2 or of EC to IL-1, TNF, or IFN-gamma augmented transendothelial migration. mAb directed against CD18 and CD11a inhibited binding and migration of NK cells across resting or IL-1-activated EC, whereas anti-CD11b and c mAb did not. Thus, the LFA-1 pathway is a crucial determinant of the adhesive and migratory interactions of NK cells with vascular endothelium. Using IL-1-activated EC, We found that anti-VLA-4 and anti-VCAM-1 mAb, utilized in concert with anti-CD18, significantly reduced adhesion and transmigration. The CS-1 peptide of fibronectin had no effect on binding and migration but, when used in concert with anti-CD18 and anti-VCAM-1 (but not anti-VLA-4), caused a small, but significant, increase in inhibition. The capacity to bind and migrate across endothelial monolayers underlies the recruitment of NK cells in tissues under certain physiologic and pathologic conditions.
Amino Acid Sequence↗