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Biomedical subjects

G Bianchi

Publications and source records attributed to G Bianchi.

At least 127 records · Page 7Linked to original sources

[Renal oncocytoma: its differential diagnosis and the indications for surgical treatment].

The authors report an uncommon renal oncocytoma rate stressing difficulties that modern diagnostic modalities meet in a correct preoperative differential diagnosis with nephrocarcinoma. Oncocytoma is a low multifocal involvement. Surgical treatment is the primary choice, nephrectomy about localized monofocal lesions in advisable, with short and long term positive outcomes. In ambilateral involvement case without malignancy evident signs (scarce likelihood to infiltrate nephritic capsule, without lymphoadenopathy) conservative operations with partial resections are suggested with a five years survival from 84 to 96%.

Adenoma, Oxyphilic↗

[Current therapeutic orientation toward testicular germ cell tumors].

Personal experience in a case of primary germinal tumor of the testis in advanced state is described. The initial treatment was chemioterapy: the patient received four complete cycles of cisplatin-based chemoterapy (PEB scheme). A surgical treatment consisted of a radical inguinal orchiectomy with high ligation of the spermatic cord at the deep inguinal ring associated with interaortocaval lymphonodes dissection. Actually, after two years from the beginning of treatment, the patient is well, without signs of neoplasm disease.

Adult↗

Study of calcium metabolism in idiopathic hypercalciuria by strontium oral load test.

Calcium excretion and absorption were evaluated in hypercalciuric calcium stone formers by the study of Sr2+ excretion and absorption after an oral load. Ca2+ stone formers (n = 140) were studied, and the results were compared in the 83 of them who had idiopathic hypercalciuria and in the 57 who had Ca2+ excretion within reference values. Hypercalciuric patients showed increased renal Sr2+ clearance (CRE; 5.26 +/- 0.358 vs 3.29 +/- 0.277 mL/min; P <0.001), whereas Sr2+ absorption [assessed as the area under the serum concentration-time curve (AUC)] was increased at 30 and 60 min (1.53 +/- 0.087 vs 1.21 +/- 0.071 mmol. L-1. min; P <0.05), but not at 240 min after the load. In hypercalciuric patients, the AUCs were positively correlated with urinary Sr2+ fractional excretion (P <0. 001). Conversely, in normocalciuric patients plasma parathyroid hormone (PTH) was negatively correlated with the AUCs (P <0.01) and CRE (P <0.05), whereas 1,25-dihydroxyvitamin D plasma concentrations normalized to PTH were positively correlated with the AUCs (P <0.05). The results of Sr2+ load tests suggest that in the hypercalciuric population, Ca2+ absorption is altered predominantly in the duodenum and that the normal regulation exerted by calciotropic hormones on tubular and enteral Ca2+ handling is lost.

Administration, Oral↗

The viral chemokine macrophage inflammatory protein-II is a selective Th2 chemoattractant.

Kaposi's sarcoma (KS) lesions are characterized by a prominent leukocyte infiltrate composed of mononuclear phagocytes and T cells. KS-associated CD4(+) and CD8(+) cells showed predominantly a type II cytokine profile. The CC chemokine viral macrophage inflammatory protein-II (vMIP-II) encoded by the KS-associated herpes virus 8 was a selective chemoattractant for T helper 2 (Th2 cells) and for monocytes, whereas it was inactive on other leukocytes, including Th1 cells, dendritic cells, and natural killer (NK) cells. vMIP-II was an agonist for CCR8, a chemokine receptor selectively expressed on CD4(+) and CD8(+) cells with a type II cytokine profile. Hence, vMIP-II has agonist activity for a chemokine receptor (CCR8), which is preferentially expressed on polarized Th2 cells. The capacity of vMIP-II to attract type II T cells selectively is likely to be a component of the virus strategy to subvert the host immune response.

Cell Movement↗

Differential regulation of chemokine receptors during dendritic cell maturation: a model for their trafficking properties.

Upon exposure to immune or inflammatory stimuli, dendritic cells (DC) migrate from peripheral tissues to lymphoid organs, where they present Ag. CC chemokines induce chemotactic and transendothelial migration of immature DC, in vitro. Maturation of DC by CD40L, or by LPS, IL-1, and TNF, induces down-regulation of the two main CC chemokine receptors expressed by these cells, CCR1 and CCRS, and abrogates chemotaxis to their ligands. Inhibition was rapid (<1 h) and included the unrelated agent FMLP. Concomitantly, the expression of CCR7 and the migration to its ligand EBI1 ligand chemokine (ELC)/macrophage inflammatory protein (MIP)-3beta, a chemokine expressed in lymphoid organs, were strongly up-regulated, though with slower kinetics (24-48 h). Rapid inhibition of responsiveness to chemoattractants present at sites of inflammation and immune reaction may be permissive for leaving peripheral tissues. Conversely, the slower acquisition of responsiveness to ELC/MIP-3beta may guide subsequent localization of DC in lymphoid organs.

CD40 Antigens↗

Adhesion, transendothelial migration, and reverse transmigration of in vitro cultured dendritic cells.

Dendritic cells (DC) are migratory cells which exhibit complex trafficking properties in vivo, involving interaction with vascular and lymphatic endothelium and extracellular matrix (ECM). The underlying mechanisms involved in these processes are still ill defined. In the present study we have investigated the ability of DC to interact in vitro with human vascular endothelial cells (EC) and ECM. DC were differentiated from monocytes by in vitro exposure to granulocyte-macrophage colony-stimulating factor and interleukin-13 for 7 days. In adhesion assays a considerable proportion of DC bound to resting EC monolayers: (17% +/- 4%, mean +/- SE of eight experiments). Adhesion to tumor necrosis factor (TNF)-activated EC was increased to 29% +/- 5% (n = 8). Binding to resting EC was strongly inhibited by anti-CD11a and CD11b, but not by CD11c monoclonal antibodies (MoAbs); on TNF-activated EC, anti-VLA-4 in concert with anti-CD18 inhibited adhesion by more than 70%. Binding to a natural ECM, derived from cultured EC, or to purified fibronectin was high: 52% +/- 6% (n = 8) involved VLA-4 and VLA-5 integrins. In a transmigration assay, 10% +/- 2% (n = 6) of input cells were able to cross the EC monolayer. Unlike adhesion, transendothelial migration was significantly reduced by anti-CD31 MoAb. The amount of DC transmigrated through a monolayer of EC was increased twofold to threefold by a defined set of C-C chemokines including RANTES, MIP1alpha, MIP5, and, to a lesser extent, by MIP1beta and MCP-3. Most importantly, in view of the trafficking pattern of these cells, a significant proportion of DC (13% +/- 4% of input cells seeded) was able to migrate across the endothelial basement membrane and, subsequently, across the endothelial barrier (reverse transmigration). The adhesion molecules and chemoattractants characterized herein are likely to underlie the complex trafficking of DC in vivo.

CD11 Antigens↗

Adducin in essential hypertension.

In Milan hypertensive rats (MHS) the sequence of events going from renal function to cell membrane ion transport abnormalities and finally to the molecular defect responsible of hypertension has been established. A polymorphism of the cytoskeletal protein adducin has been identified as a likely culprit for hypertension in these rats. Two point mutations in MHS alpha- (F316Y) and beta- (Q529R) adducin genes have been shown to be associated with hypertension in genetic crosses of MHS and MNS rats. Also in humans, a polymorphism of alpha-adducin gene (Gly460Trp) has been found to be significantly associated both to hypertension and salt sensitivity. Studies aimed at clarifying the functional role of alpha-adducin variants have shown that adducin from the MHS rats is able to stimulate Na-KATPase activity both after transfection in renal tubular cells and after incubation with the enzyme in a cell-free system. Also the human hypertensive alpha-adducin variant displays the same activity of MHS adducin in a cell-free system. Therefore, both in humans and in rats, adducin polymorphisms may affect blood pressure and kidney function by modulating the overall capacity of tubular epithelial cells to transport ions, through variations of the Na-KATPase activity. However adducin polymorphisms account for only a portion of hypertension both in humans and rats. Therefore additive or epistatic interactions with other genes involved in renal sodium handling need to be studied.

Animals↗

Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s.

T helper cells type 1 (Th1s) that produce interferon-gamma predominantly mediate cellular immune responses and are involved in the development of chronic inflammatory conditions, whereas Th2s which produce large amounts of IL-4 and IL-5 upregulate IgE production and are prominent in the pathogenesis of allergic diseases. The precise factors determining whether Th1- or Th2-mediated immune responses preferentially occur at a peripheral site of antigen exposure are largely unknown. Chemokines, a superfamily of polypeptide mediators, are a key component of the leukocyte recruitment process. Here we report that among four CXC (CXCR1-4) and five CC (CCR1-5) chemokine receptors analyzed, CXCR3 and CCR5 are preferentially expressed in human Th1s. In contrast, Th2s preferentially express CCR4 and, to a lesser extent, CCR3. In agreement with the differential chemokine receptor expression, Th1s and Th2s selectively migrate in response to the corresponding chemokines. The differential expression of chemokine receptors may dictate, to a large extent, the migration and tissue homing of Th1s and Th2s. It may also determine different susceptibility of Th1s and Th2s to human immunodeficiency virus strains using different fusion coreceptors.

Cell Movement↗

Effects of systemic prostaglandin E1 on hepatic amino acid-nitrogen metabolism in patients with cirrhosis.

Prostaglandins of the E (PGE) series have long been considered "catabolic" hormones, but recent data suggest that they may be secreted in critically ill patients to counteract stress hormones, stimulating protein synthesis. Their use is under scrutiny to improve hepatic microcirculation and as cytoprotective agents. We tested the effects of PGE1 on hepatic and whole-body nitrogen metabolism in eight patients with cirrhosis. Urea-nitrogen synthesis rate, alpha-amino-nitrogen levels, and nitrogen exchange were measured in the basal, postabsorptive state and in response to continuous alanine infusion, in paired experiments, during superinfusion of PGE1 or saline. Splanchnic and systemic hemodynamics were assessed by echo-Doppler at the beginning and at the end of each experiment. PGE1 produced a rapid fall in plasma amino acids and in urea-nitrogen synthesis rate, as well as a positive nitrogen exchange. The slope of the regression of alpha-amino-nitrogen levels on urea-nitrogen synthesis rate, a measure of liver cell metabolic activity, was not affected, but the regression line was shifted rightward, suggesting a nitrogen-sparing effect of PGE1. Mesenteric artery and portal flow were unchanged, whereas femoral artery flow increased by 30%. Insulin and glucagon levels were not systematically different. We conclude that PGE1 reduces hepatic urea synthesis rate, independent of hormones and/or hepatic flow, possibly acting at the peripheral level on amino acid transport, thus reducing amino acid supply to the liver. The resulting net nitrogen sparing might be the basis for the beneficial effect of PGE1 in clinical hepatology.

Aged↗

Effects of systemic prostaglandin E1 on splanchnic and peripheral haemodynamics in control subjects and in patients with cirrhosis.

Prostaglandins of the E series showed metabolic and clinical effects in patients with liver disease; changes in splanchnic haemodynamics might be involved. Blood flow in femoral and mesenteric artery and in the portal vein was measured by echo-Doppler in 10 controls and 14 cirrhotic patients, in response to the systemic infusion of a PGE1 analogue (30 micrograms/h for 2-6 h) or saline, performed in random order. Intraparenchymal resistive and pulsatility indices in the liver, spleen and kidney were also measured. In both groups PGE1 increased femoral artery flow by 40%, irrespective of infusion time. Heart rate increased slightly, whereas mean arterial pressure decreased. There were no changes in mesenteric artery and portal vein flow, as well as in resistance indices. Saline infusion increased femoral artery flow by 4%. PGE1 infusion does not produces significant effects on Doppler-assessed splanchnic hemodynamics in controls and in cirrhotic patients, in spite of significant effects on peripheral circulation.

Aged↗

Alpha-adducin polymorphisms and renal sodium handling in essential hypertensive patients.

The relationship between blood pressure and sodium (Na) excretion is less steep in hypertension caused by increased renal tubular reabsorption. We recently demonstrated that one mutation in rat alpha-adducin gene: (1) is responsible for approximately 50% of the hypertension of MHS rats, and (2) stimulates tubular Na-K pump activity when transfected in renal epithelial cell, suggesting that its pressor effect may occur because an increased tubular reabsorption. Linkage and association studies demonstrated that the alpha-adducin locus is relevant for human hypertension. A point mutation (G460W) was found in human alpha-adducin gene, the 460W variant (G/W) is more frequent in hypertensives than in normotensives. The aim of this study was to test whether acute changes in body Na may differently affect blood pressure in humans as a function of alpha-adducin genotype. The pressure-natriuresis relationship was analyzed in 108 hypertensive using two different acute maneuvers: Na removal (furosemide 25 mg p.o.) and, two days later, Na load (310 mmoles i.v. in 2 hr). We found that 80 patients were wild-type homozygous (G/G), 26 were G/W heterozygous, and 2 were W/W homozygous with similar blood pressure, age body mass index, gender, plasma and urinary sodium and potassium. In basal condition G/W-W/W patients showed a lower plasma renin activity and fractional excretion of Na. In either case the pressure-natriuresis relationship was less sleep in G/W-W/W than in G/G patients, obviously negative for Na depletion with furosemide (-0.011 +/- 0.004 vs. -0.002 +/- 0.002 mm Hg/mumol/min, P < 0.03), and positive for Na load (0.086 +/- 0.02 vs. 0.027 +/- 0.007 mm Hg/mumol/min, P < 0.001). The finding of reduced slope after Na depletion or Na load supports the hypothesis that, as MHS rats, humans bearing one W alpha-adducin variant display an increased of renal tubular sodium reabsorption.

Adult↗

Unilateral laparoscopic retroperitoneal lymphadenectomy for clinical stage I nonseminomatous testicular cancer.

Since June 1993, unilateral laparoscopic retroperitoneal lymph-node dissection (LRPLND) has been performed in six patients with clinical Stage I nonseminomatous germ-cell tumors (NSGCT). All of the patients had undergone prior radical orchiectomy. The testicular cancer was left-sided in three cases and right-sided in three cases. Preoperative staging by means of tumor marker assessment, CT scan of the chest and abdomen, and chest radiography was unremarkable for metastatic disease. All procedures were accomplished without any complications in a mean time of 325 minutes (275-420 minutes). The estimated perioperative and postoperative blood loss was minimal, and none of the patients required blood transfusion. In the case of the first patient, the hospital stay was 18 days because of a widespread subcutaneous emphysema. In the remaining five cases, the average hospitalization was 4.8 days (range 4-6 days). The patients resumed normal activities within 12 to 27 days (mean 16.16 days) postoperatively. The mean number of lymph nodes removed was 6.8 (range 5-9). Histologic examination of these nodes revealed microscopic metastases from embryonal carcinoma in two patients, both of whom were subjected to adjuvant chemotherapy. The mean follow-up period is 27.1 months (range 12-42 months). To date, no relapses have been observed. In accordance with other reports, we believe that LRPLND is both feasible and effective. However, larger and more comprehensive studies with long-term follow-up are required to determine whether this approach is reliable and definitely superior to standard open surgery in the management of clinical Stage I NSGCT.

Adult↗

Genetic analysis of the SA and Na+/K+-ATPase alpha1 genes in the Milan hypertensive rat.

OBJECTIVE: To study whether the SA gene locus (on rat chromosome 1) and the sodium potassium ATPase alpha1 gene locus (on rat chromosome 2) contribute to the elevated blood pressure in the Milan hypertensive rat. DESIGN: Co-segregation analysis using polymorphisms in the SA and Na+/K+-ATPase alpha1 genes in F2 rats from a cross of Milan hypertensive and Milan normotensive rats. Analysis of SA and N+/K+-ATPase alpha1 gene expression in kidneys of 6 and 25 weeks old Milan hypertensive and normotensive rats. METHODS: Genotyping of F2 rat DNA by restriction digestion and Southern blotting and comparison of messenger RNA levels by northern blot analysis. RESULTS: Renal expression of SA was considerably higher in normotensive than it was in hypertensive rats aged 6 and 25 weeks. Despite this difference the SA genotype did not co-segregate with blood pressure, although the Milan hypertensive rat allele did co-segregate with greater body weight (P = 0.0014) for male F2 rats. Expression of Na+/K+-ATPase alpha1 was higher in the kidneys of young hypertensive rats than it was in those of normotensive rats and did not decline with age as occurred in the normotensive rats. However, again the Na+/K+-ATPase alpha1 genotype did not co-segregate with blood pressure. CONCLUSIONS: Despite differences in the patterns of expression of SA and Na+/K+-ATPase alpha1 genes in the kidneys of Milan hypertensive and normotensive rats, we found no evidence of co-segregation of either gene with blood pressure. Our results suggest that either SA is simply acting as marker for a linked gene in other crosses for which co-segregation with blood pressure has been observed, or at least, the level of its renal expression is not the sole determinant of its effect on blood pressure. The failure of the Na+/K+-ATPase alpha1 gene to co-segregate with blood pressure suggests that its greater expression in the kidney of the Milan hypertensive rat is either reactive or controlled by other genetic loci.

Animals↗

Unilateral laparoscopic retroperitoneal lymph node dissection for clinical stage I nonseminomatous germ cell testicular neoplasm.

OBJECTIVE: The aim of this study is to evaluate the reliability of laparoscopic retroperitoneal lymph node dissection (LRPLND) in the management of clinical stage I nonseminomatous germ cell tumors (NSGCT). METHODS: Since June 1993, unilateral LRPLND was performed in 6 patients diagnosed with clinical stage I NSGCT. All patients had undergone prior radical orchiectomy. The testicular cancer was left-sided in 3 cases and right-sided in the other 3 cases. Preoperative staging by means of tumor marker assessment, computerized tomography scan of the chest and abdomen and chest X-ray was unremarkable for metastatic disease. RESULTS: All procedures were accomplished without any complications in a mean time of 325 min (275-420 min). The estimated perioperative blood loss was minimal (< 50 ml), and none of the patients required blood transfusion. In the case of the first patient, the hospital stay was 18 days due to a widespread subcutaneous emphysema. In the remaining 5 cases, the average hospitalization was 4.8 days, ranging from 4 to 6 days. The patients resumed normal activities within 12-27 days (mean 16.16 days) postoperatively. The mean number of lymph nodes removed was 6.8, ranging from 5 to 9. Histologic examination of the dissected lymph nodes revealed microscopic metastases from embryonal carcinoma in 2 patients. Both of these patients received adjuvant chemotherapy. The mean follow-up period is 21.3 months, ranging from 6 to 36 months. To date, no relapses have been observed. CONCLUSION: In accordance with other reports, we believe that LRPLND is both feasible and effective. However, the definitive assessment of the efficacy and morbidity of this diagnostic procedure requires a larger and more comprehensive series as well as longer follow-up.

Adult↗

Glucocorticoid receptor polymorphism in genetic hypertension.

The Milan hypertensive strain of rat (MHS) displays abnormalities in both renal function and adrenocortical activity. While the pressor role of the former has been studied in detail, the role of the latter has not yet been clearly evaluated. In the present study, glucocorticoid receptor (GR) binding characteristics in liver cytosol from adult MHS and Milan normotensive controls (MNS) have been investigated. Dexamethasone, aldosterone and corticosterone were bound with lower affinity to cytosol of MHS rats compared with that of MNS rats. This pattern of binding could explain the raised plasma corticosterone concentrations and adrenocortical hypertrophy previously noted in MHS. The coding sequence of MHS and MNS GR genes have been determined. The MHS gene differed in four respects from that of MNS: three silent point mutations and a polymorphic microsatellite region in exon 2. The latter polymorphism has been used in cosegregation studies of F2 hybrids of MHS x MNS. The MHS GR genotype was associated with hypercalciuria and lower blood pressure in female rats and lower body weight in male rats. Although the effect on blood pressure is small, it is consistent with the affinity data. MHS GR genotype cosegregated with lower blood pressure in F2 rats and displayed a lower affinity in binding studies. In conclusion, GR polymorphism may be responsible for differences of adrenocortical function between MHS and MNS. This may lead to a reduction in the blood pressure difference between the two strains.

Animals↗