HLA-DR typing of organ donors and allograft recipients by SSO typing: correlation with serotyping in the North Italy Transplant Program.
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Biomedical subjects
Publications and source records attributed to F Poli.
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The finding that HLA-DR compatibility assessed by DNA typing correlates with short-term graft outcome better than serology prompted us to study the degree of genomic HLA-DR compatibility on 55 patients with a graft functioning for more than 10 years (group A), compared with 82 patients with more recent transplants regardless of survival (group B). Because adequate blood donor samples were not available for group A long-term survivors, we used donor renal cells obtained by fine needle aspiration biopsy as a source of DNA. We found that in long-term survivors, the distribution of HLA-DR mismatches was significantly different from that observed in group B patients. In particular, whereas a similar proportion of patients with 1 mismatch was seen in both groups, 27.3% of group A patients vs. 6.1% of group B patients had no mismatch, and 23.6% of group A vs. 41.5% of group B patients received transplants with no HLA-DR compatibility (P = 0.001). We also investigated a possible correlation between number of incompatibilities and graft function. Well-matched patients received less steroid pulses than less well-matched recipients, and steroid-resistant rejection episodes were more common among less well-matched recipients. These results suggest a prognostic role of genomic HLA-DR compatibility on long-term success of cadaver kidney transplantation.
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We investigated the iron status of 33 pyruvate kinase (PK) deficient patients, most of the cases reported in Italy. Serum ferritin (SF) was higher than the upper limit of the range of matched controls in 15/25 (60%) non-transfused patients (median 228 micrograms/l, range 58-3160 v 43, 22-310). Liver siderosis and fibrosis were found in 8/9, and cirrhosis in two who died at age 39 and 42 of complications of iron overload. SF was independent of age, sex, or severity of haemolysis. The prevalence of HLA-A3 antigen in PK deficient patients was not significantly different from that of our healthy population (29.6% v 23%). The HLA-A3 positive, non-transfused patients had significantly higher SF values than the HLA-A3 negative ones (median 675 micrograms/l, range 340-3160 v 145, 58-400). A pedigree study of six high SF-probands indicated that iron overload has a multifactorial pathogenesis. In particular, the association of PK deficiency-induced haemolysis, splenectomy and an additional factor (heterozygosity for idiopathic haemochromatosis, ineffective erythropoiesis) leads to severe iron accumulation. We suggest that monitoring iron status would be useful in PK deficient patients, particularly in splenectomized and HLA-A3 positive ones, to identify those at risk of iron overload and prevent the clinical consequences of iron accumulation.
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The effect of polyamines (PA) on the synthesis and deposition of wall constituents in Saccharomyces cerevisiae was investigated. Spermidine (Spd) in various doses was ineffective whereas spermine (Sp) in the same concentrations caused a marked inhibition (25-60%) of cell proliferation accompanied by evident morphogenetic malformations. Sp-treated cells were elongated, grouped in small clusters, and showed malformed septa and aberrant wall thickenings. The PATAg technique revealed that the aberrations consisted of an abnormal accumulation of both reactive materials, like 1,3-beta-glucans, and unstained chitin components. Since 1,3-beta-glucan synthases and chitin synthases are inserted in the plasma membrane, whose anionic sites interacted with the cation groups of Sp, it is assumed that the molecule determines a condition resulting in an unregulated activation of the two enzymes. The fact that Spd, which contains three cationic groups instead of the four contained in Sp, is without effect suggests that a compound must have at least four cation sites in order to affect the cell division and wall morphogenesis of S. cerevisiae.
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Genital Papillomavirus infection has now reached epidemic size. Several techniques may be used to treat genital condylomas, but none of them is 100 percent effective. At the first consultation for external genital condylomas, the choice of treatment is determined by the size, location, number and histology of the lesions. Typical condyloma acuminata that are present in small number and have a less than 5 mm base of implantation are treated by cryotherapy or trichloracetic acid. Podophyllin should be reserved for patients with diffuse lesions. When one or several lesions do not regress after 3 to 4 weeks of treatment, surgical procedures (electrocautery, CO2 laser) must preferably be used. Condylomas that have a base of implantation wider than 5 mm are directly destroyed by surgical excision, as are dysplastic lesions. Post-treatment cure of external genital lesions must be confirmed by a negative acetic acid test. Patients should be advised to utilize condoms throughout the duration of treatment.
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The specificity analysis of a CD3+, WT31+, CD8+ cytotoxic T lymphocyte (CTL) clone (CTL 49), isolated from peripheral blood lymphocytes of a melanoma patient (no. 665) after mixed lymphocyte culture with an HLA-A2+ allogeneic lymphoblastoid cell line (VSKB-LCL), revealed that CTL 49 could lyse, in addition to HLA-A2+ lines, autologous HLA-A2- melanoma (Me665/2) and K562 targets. Killing of VSKB-LCL, but not of Me665/2, could be inhibited by anti-CD3 and by anti-HLA-A2 antibodies or by modulation of the CD3 complex. Cold-target competition studies showed that K562, but not VSKB-LCL, could compete with Me665/2 for lysis by CTL 49. However, unlike K562, Me665/2 could be lysed by CTL 49 in a Ca2(+)-independent fashion in 4 h and 18 h assays. CTL 49 expressed mRNA specific for tumor necrosis factor (TNF alpha) and, to a lesser extent, for lymphotoxin (TNF beta). Exposure of the clone to anti-CD3 antibodies induced the expression of interferon(IFN)-gamma-specific mRNA. Antibodies to TNF alpha, TNF beta and IFN reduced the lysis of Me665/2, but not of K562, by CTL 49 in 18-h cytotoxic assays. Antibodies to TNF alpha and to IFN gamma almost completely inhibited the lysis seen on Me665/2 (but not on K562), in 96-h assays, by supernatants isolated from VSKB-LCL- or anti-CD3-stimulated CTL 49 cells. Taken together, these data indicate that major-histocompatibility-complex-independent lysis of autologous tumor cells and of natural killer reference targets by the same alloreactive T cell clone are activities related at the level of target recognition but distinct at the level of the lytic hit. Thus, efficient lysis of autologous tumor cells results from a complex mechanism based upon direct effector-target interaction as well as on cytokine-mediated cytolytic effects.
The use of loratadine was compared to dexchlorpheniramine in the treatment of children affected by perennial allergic rhinitis in order to assess its clinical efficacy and tolerability. Children were randomly assigned to two groups: 15 were treated with loratadine and 16 with dexchlorpheniramine. Loratadine was administered in a single daily dose of 5 mg (2.5 mg for children under 20 kg) and dexchlorpheniramine at a dose of 1 mg every 8 hours (0.5 mg for the youngest children). Clinical symptoms were recorded before and during the study using a score of 0.3 (from absent to severe). Symptoms were markedly reduced by both drugs. Eye burning was reduced more by loratadine (p less than 0.05) than the control drug. Rhinoscopic investigations revealed that both groups reacted favourably to the drugs used. Overall clinical assessment showed similar and revealed the good efficacy of both drugs. Tolerability was satisfactory and there were no signs of drowsiness. Hematological and hematochemical parameters showed no clinically significant changes and body weight remained constant. On the basis of these results, loratadine is preferable to dexchlorpheniramine thanks to its once-a-day dosing.