Search PubMed⌕ Search

Biomedical subjects

C Bagnis

Publications and source records attributed to C Bagnis.

At least 55 records · Page 3Linked to original sources
PubMed1994

Prevention of acute cyclosporin nephrotoxicity by verapamil and atrial natriuretic factor in the rat.

Nephrotoxicity is the most common and important side-effect of cyclosporin (CsA) therapy. CsA alters renal haemodynamics with a reduction in renal blood flow (RBF) and glomerular filtration rate (GFR) and a significant increase in renal vascular resistances (RVR). The present experimental study investigates whether verapamil or atrial natriuretic factor (ANF) are able to prevent the nephrotoxicity of CsA. All studies were conducted in an in-situ autoperfused rat kidney model which allows continuous measurement of renal blood flow without dissection of the renal artery. CsA as a 40 mg/kg bolus dose significantly decreased RBF (from 2.15 +/- 0.1 and 2.19 +/- 0.1 before CsA, to 1.29 +/- 0.16 ml/min/100 g BW, 60 min after CsA administration) (P < 0.05), and GFR (from 0.14 +/- 0.1 and 0.13 +/- 0.01 before CsA, to 0.08 +/- 0.01 ml/min/100 g BW, 60 min after CsA administration) (P < 0.05). CsA significantly increased RVR (from 9.5 +/- 0.73 and 9.8 +/- 0.78 before CsA, to 16.7 +/- 2.9 mmHg x min/ml 60 min after CsA administration) (P < 0.05). Verapamil pretreatment (as continuous intrarenal infusion at the rate of 1.25 micrograms/kg/min) attenuated the fall in GFR (from 0.16 +/- 0.01 and 0.19 +/- 0.03 ml/min/100 g before CsA to 0.20 +/- 0.05 ml/min/100 g BW, 60 min after CsA administration) (NS) and in RBF (from 2.42 +/- 0.2 and 2.6 +/- 0.22 ml/min/100 g before CsA to 1.79 +/- 0.17 ml/min/100 g BW, 60 min after CsA administration (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Highly efficient retroviral gene transfer into human primary T lymphocytes derived from peripheral blood.

T lymphocytes are a promising cell vehicle for gene therapy purposes. By cocultivating retroviral vector producing cells and target cells, highly efficient gene transfer was achieved with activated human T lymphocytes derived from peripheral blood with vectors carrying different forms of the bacterial beta-galactosidase gene including the regular LacZ gene, the Sh-ble::LacZ gene and the nlsLacZ gene. Infection kinetics of T cells activated by a combination of monoclonal antibodies directed against CD2 and CD28 indicated that the highest efficiencies of transduction were obtained when the cocultivation began 4 days after stimulation. In fact, with the FLac vector, a new retroviral vector which expresses the Sh-ble::LacZ gene, we observed up to 78% transduction efficiency assessed by X-gal staining performed 2 days after the end of the cocultivation. Expression of the transduced genes was observed throughout the period of culture. Neither the cocultivation step nor the expression of the transduced Sh-ble::LacZ gene altered cell culture proliferation or the expression of selected cell surface antigens. In addition, we showed that CD4+ and CD8+ T cells were equally transduced.

Antibodies, Monoclonal↗
PubMed1994

[Prevalence of severe arterial hypertension in patients with renal grafts and surgical indications. Experience of the La Pitié Hospital].

Five hundred eighty five renal transplantations were performed in our group from January 1982 to December 1992. The observed incidence of hypertension in this group is 45%. Invasive treatment was indicated in 20 hypertensive patients (3.4%): 4 patients had bilateral-nephrectomy and 16 patients were treated for renal artery stenosis. This last group consisted of 12 men and 4 women (mean age of 36 years), who received a cadaveric transplant. 7 patients were hypertensive prior to transplantation. Only 25% of the patients received cyclosporine. Initial nephropathy was a glomerular in 9 cases. Before surgical treatment, an average of 3.2 anti-hypertensive drugs were necessary to control arterial pressure. Percutaneous transluminal angioplasty was indicated in 11 patients, whereas surgical correction of arterial stenosis was realized in 6 cases. Angioplasty was associated with poor results (persistent HTA and renal failure in 7 out of 11 patients). After surgery of renal artery, all patients had normal blood pressure. Renal artery stenosis would require surgical treatment, when possible. If not, percutaneous transluminal angioplasty will be proposed. The most efficient surgical procedure seems to be resection of the structure and termino-terminal anastomosis. When usable, internal iliac artery can be sutured beyond the stenosis.

Adult↗
PubMed1993

Determinants of oxalate balance in patients on chronic peritoneal dialysis.

We assessed plasma levels and removal rates of oxalate in 24 patients on chronic peritoneal dialysis (CPD) for oxalosis-unrelated renal failure. The ion-chromatographic (IC) measurements of oxalate in plasma, dialysate, and urine (in seven patients with residual renal function) were used to calculate peritoneal and renal clearances of oxalate. The serum state of saturation with calcium oxalate was calculated by means of a computer-based model system. Patient data were compared with those from 19 healthy individuals. Peritoneal clearance of oxalate was 6.3 +/- 4.7 mL/min, ie, 8% of the normal renal clearance. As a result, both plasma oxalate and calcium oxalate saturation were higher than in controls and did not overlap. Plasma was supersaturated with calcium oxalate in only two of 24 patients (8%). Removal of oxalate by dialysis was related to the amount of fluid infused. Overall removal of oxalate (dialysate plus urine) was similar to 24-hour excretion of normal subjects and was taken as a measure of its generation. Oxalate generation rate was dependent on protein (whole and animal) intake, but not on caloric intake or pyridoxine status. Pyridoxine supplementation, 75 and 300 mg daily for 1 months, was not effective in reducing plasma levels or generation rates of oxalate. Residual renal function had a minor influence on oxalate patterns. We conclude that current programs are adequate to maintain oxalate balance in patients on CPD under basic conditions.

Adult↗
PubMed1993

Leukemogenicity of v-myb-transformed monoblasts cells can be modulated by normal bone marrow environment.

The avian myeloblastosis virus (AMV) causes monoblastic leukemia in the chick. Two non-producer clones of AMV-transformed monoblasts, BM2/C3A and BM2L/A2B5, have been described (see Bottazzi et al., this issue). They differ in their growth requirements and in their ability to induce leukemia when injected into the chick embryo. We first genetically tagged these clones by retroviral infection with a vector expressing the bacterial lacZ gene. Then, we injected the lacZ-positive cells via the chorioallantoic vein into chick embryos. With BM2L/A2B5 cells, the bone marrow of the injected birds was rapidly invaded by lacZ-positive cells. In addition, these cells rapidly overgrew cultures of bone marrow cells derived from injected animals. Conversely, the growth of BM2/C3A was inhibited in the injected animals and only a few blue cells, with the morphology of macrophages, were detected in cultures of bone marrow cells. We developed an in vitro assay to mimic in vitro the differential growth of BM2/C3A and BM2L/A2B5 observed in vivo. These data strongly suggest that BM2/C3A cells retain their ability to differentiate into macrophages in the normal bone marrow environment and that BM2L/A2B5 cells differ from BMC/C3A in the loss of this capacity.

Animals↗
PubMed1992

[Primary bladder lymphoma in kidney transplant recipients: report of a case].

The authors report the case of a type B EBC (+) primary lymphoma of the bladder occurring in a renal transplant patient 14 months after the graft. The postoperative course had been marked by three episodes of early rejection, the last of which required the use of anti-CD3 antibody, then the later addition of cyclosporin. After immune labelling showing oligoclonal proliferation, the lesion was treated with CD24 and CD21 monoclonal antibodies. Ten months after treatment, the patient is in remission with renal function at 200 mumol plasma creatinine. Azathioprine and cyclosporin have been stopped. This apparently unique case provides the authors with an opportunity to review the usual characteristics of lymphocyte tumours in transplant patients and to stress the rarity of primary lesions of the urinary tract. They conclude that the new therapeutic approach based upon monoclonal antibodies is of value in comparison with the attempts at surgery, radiotherapy and/or chemotherapy used in the past.

Adult↗
PubMed1989

CAPD with an amino acid dialysis solution: a long-term, cross-over study.

This prospective cross-over study was undertaken to evaluate the safety and efficacy of a 1% amino acid dialysis solution on the nutritional and metabolic changes, plasma amino acid profiles and peritoneal membrane function of patients on CAPD. Six CAPD patients had one exchange a day with two liters of this solution over a six month period. Every month there was a medical examination, anthropometric measurements and dietary inquiry were made, blood biochemistry tests were done. Every three months renal function, peritoneal function, aminograms of plasma and dialysate and nitrogen balance were determined. Data were compared with those obtained one month prior to and three months after withdrawal of amino acid administration. Nitrogen balance, which was negative (-1.3 g/day) became positive (+3.1 g/day). Patients who were already overweight increased in weight, both in fat and lean mass. Plasma cholesterol and triglycerides significantly decreased and the amino acid profile moved towards normal; plasma urea levels increased and pH and bicarbonate decreased slightly but significantly (P less than 0.05). Plasma protein concentrations did not change. All the above parameters turned towards basal values when amino acids were discontinued. We conclude that amino acids can be used as osmotic agents for CAPD since they do not cause toxic effects or impair peritoneal membrane function. Moreover, they can help the nutritional status, provided that an increase in weight is prevented and the slight worsening of systemic acidosis is corrected.

Amino Acids↗
PubMed1989

Generation of a helper cell line for packaging avian leukosis virus-based vectors.

We constructed an avian leukosis virus-based packaging cell line, pHF-g, containing Rous-associated virus DNA with several alterations to abolish RNA packaging. One of them is a 52-base-pair deletion encompassing the putative encapsidation signal in the leader region. The 3' long terminal repeat was also removed and replaced by the polyadenylation sequence from the herpes simplex virus thymidine kinase gene. When pHF-g cells were transfected by an avian leukosis virus-based vector, they produced replication-defective virus at high titer but they did not release any replication-competent particles. Proviral DNA was shown to be correctly integrated as well as correctly expressed. Viral RNAs were shown to be correctly translated into gag-related polypeptides.

Animals↗
PubMedDate not supplied

Peripheral stem cells in bone marrow transplantation. Peripheral blood stem cell and gene therapy.

Mobilized peripheral blood stem cells characterized by sustained re-populating ability could be optimal target cells for ex-vivo gene transfer. In spite of very attractive preliminary results obtained in the murine studies, therapeutically efficient gene transfer and expression in human targeted cells must be proven. In recent years, effort has been spent on the identification of factors limiting gene transfer efficiency of haematopoietic stem cells. Increasing knowledge concerning haematopoiesis and gene transfer has helped in identifying a number of limiting factors. These factors as well as the strategies that showed increased retroviral infection of haematopoietic stem cells will be discussed. Finally, the results of the clinical trials will be reported.

Animals↗
PubMedDate not supplied

[Renal tolerance of cidofovir].

Renal failure, proteinuria and proximal tubular acidosis are the features of cidofovir renal toxicity, its main side-effect. Proteinuria occurs in more than 40 per cent of patients and correlates with early renal dysfunction. A fall in serum potassium, bicarbonate, uric acid, calcium and phosphorus levels associated with glucosuria is the hallmark of proximal tubular acidosis. Most of the patients exhibit only glucosuria. Renal failure, diagnosed in 12 per cent of treated patients, is a late feature, usually discovered after the onset of proteinuria and glucosuria. Prevention of cidofovir-induced renal toxicity involves a search for other risk factors, probenecid treatment, and requires an optimal hydration status.

Acidosis, Renal Tubular↗
PubMedDate not supplied

Renal stones: from metabolic to physicochemical abnormalities. How useful are inhibitors?

Despite intensive studies in the last decades many aspects of nephrolithiasis still remain to be elucidated. Supersaturation with respect to lithogenic substances explains stones composed of cystine, uric acid, struvite, and calcium stones secondary to systemic diseases. In this subset there is a clear separation between patients and controls, and stone activity is well related to alterations in the physicochemistry of the urine environment. The understanding of the mechanisms of idiopathic calcium nephrolithiasis, on the other hand, is controversial, because we are still unable to establish clear-cut cause-effect relations between metabolic and physicochemical abnormalities and stone formation. Recent studies have been centered on the kidney, not only as the end organ of biochemical derangements due to systemic or environmental factors, but also as a complex laboratory where some events conduct to and others defend from lithogenesis. Many of these phenomena occur in the proximal tubule. Molecular biology has explained some types of hypercalciuria, which are due to genetic mutations altering tubular function, and similar results are expected for hypocitraturia and hyperoxaluria. The latter is conducive to stone formation through several mechanisms including supersaturation, oxidative stress on tubular cells, and interference with some natural inhibitors. The long list of inhibitors includes ionic and macromolecular moieties, some being produced within the nephron in response to lithogenic insults, and some affecting not only crystallization but also crystal cell adherence. Crystal trapping is believed to anticipate a renal stone. However, much has still to be clarified on their actual role in calcium nephrolithiasis, by what mechanisms they act, if patients and controls differ in the excretion and structure of some inhibitors, and whether differences are genetically determined.

Chemical Phenomena↗
PubMedDate not supplied

[Intact whole bioactive parathormone: problems arising from comparing different methods].

BACKGROUND: Parathyroid hormone (PTH) has important applications in the nephrological clinical practice. Because assays of Intact PTH (I-PTH) are liable to interferences by N-truncated fragments, a novel method for whole-(1-84) PTH has been proposed. This study is aimed at comparing the latter with some of the previous I-PTH assays. For each method the results are referred to pertinent markers of mineral metabolism. METHODS: We enrolled 171 subjects, including 56 healthy controls (C), 65 calcium stone- formers (CaSF), 40 haemodialysis patients (HD), 10 with primary hyperparathyroidism (PHP). On blood samples we measured: I-PTH by four methods (N-Tact, Advantage, Elecsys, Scantibodies), whole-(1-84) PTH, defined as CAP (Cyclase Activating PTH), total and ionised calcium, phosphate, vitamin D, osteocalcin and Crosslaps. The difference between I-PTH and CAP Scantibodies is defined as CIP (Cyclase Inhibiting PTH). RESULTS: Despite relating to each other (r>0.97) PTH values varied remarkably among methods. For all methods, the reference intervals differed from those provided by the producer. Assuming these new ranges, 10 CaSF had over-range values not always associated with abnormalities of mineral metabolism. One of the PHP patients was normal for I-PTH with 2/4 methods. In HD the differences among methods were even greater, there were inverse (p<0.05) and direct (p<0.001) relationships with ionised calcium and osteocalcin-crosslaps, respectively. The CAP/CIP ratio was lower in low bone turnover patients, but the two subgroups widely overlapped. CONCLUSIONS: This study indicates that the reliability of I-PTH assays is still unsatisfactory, and none of the four methods emerged as the best. Assay for CAP only improves diagnostic efficiency, whereas the CAP/CIP ratio does not exhibit powerful discriminating capacity. Our suggestion is that each Centre should establish its own reference ranges. PTH assay should always be coupled with measurements of other markers of mineral metabolism as well as renal function.

Adult↗
PubMedDate not supplied

beta-galactosidase transduced T lymphocytes: a comparison between stimulation by either PHA and IL-2 or a mixed lymphocyte reaction.

BACKGROUND: Retroviral-mediated gene transfer stably introduces exogenous genes into normal and neoplastic cells of the hematopoietic system. METHODS: We used two retroviral vectors [the first, FLac, expresses a chimeric protein (Sh-ble::LacZ) between the product of the phleomycin resistance gene (Sh-ble) and the bacterial beta-galactosidase encoded by the LacZ gene; the second, NuNL vector, contains a fusion sequence (LacZ::Neo) that expresses the LacZ and the neomycin resistance genes] to transduce T lymphocytes derived from the peripheral blood of healthy human donors. Two lymphocyte activation procedures were employed: a) phytohemagglutinin/interleukin-2 (PHA/IL-2) polyclonal stimulation; b) allogeneic stimulation in a mixed irradiated or non irradiated lymphocyte reaction, both supplemented with IL-2 (MLR/IL-2). Infection was achieved by co-cultivating activated T cells with the producing amphotropic cell line pretreated with mitomycin C for 96 hours. Infection and transduction efficiency were assayed by LacZ gene expression, which is detected as indigo blue staining with the chromogenic substrate 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X..Gal). RESULTS: The highest percentage of transduced T cells was reached on the 3rd PHA/IL-2 and on 9th MLR/IL-2 activation days. In these conditions with FLac vector we obtained up to 80% X-Gal+ cells after PHA/IL-2 activation and 66% and 44%, respectively, with non irradiated and irradiated MLR/IL-2, respectively. Up to 40% X-Gal+ cells were obtained with NuNL vector after PHA/IL-2 stimulation, 40% with irradiated and 48% with non irradiated MLR/IL-2 activated cells. In term of transduction efficiency, large variability was observed among patients. There were no immunophenotypical differences between FLac or NuNL vector-transduced cells activated by either of the two techniques and the control cells. CONCLUSIONS: Our results indicate that: a) the use of FLac or NuNL vector retroviral-mediated gene transfer into T-lymphocytes derived from peripheral blood and stimulated by either PHA/IL-2 or a MLR produces a high percentage of transduced T cells; b) MLR is a good system for generating a transduced alloreactive lymphocyte population. The combination of high transduction efficiency and the capacity to obtain alloreactive transduced lymphocytes should open up the possibility of generating new in vitro and in vivo studies with selectable genes for in vivo therapeutic use.

Drug Resistance, Microbial↗