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Biomedical subjects

F Poli

Publications and source records attributed to F Poli.

At least 91 records · Page 5Linked to original sources

Detection of maternal DNA in human cord blood stored for allotransplantation by a highly sensitive chemiluminescent method.

Human cord blood (CB), a rich source of hematopoietic stem and progenitor cells, is currently used for bone marrow reconstitution. However, the level of contamination of CB with maternal cells that could provoke graft-versus-host disease (GvHD) is a matter of concern. In the present study, 60 consecutive CB samples collected and stored in the Milan CB Bank, for which no maternal DNA was detected through genomic HLA typing, were examined to ascertain maternal cell contamination using polymerase chain reaction amplification of two minisatellites, apolipoprotein B gene (ApoB) and D1S80, followed by chemiluminescent detection. The sensitivity of the method employed in this study was 0.04%, comparable to that of radioactive methods. A maternal specific allele was found in 11 of the 60 CB units, at a level ranging from 1:100 to 1:2500. We could also detect the child paternal allele in 3 of the 30 mothers whose newborn was heterozygous at the loci examined. Our study indicates that maternal cells are present in 18.3% of the 60 samples examined. The clinical relevance of such a presence remains to be established. In our opinion, information on maternal cell contamination should be included within the quality control tests performed before delivering a unit.

Blood Banks↗

Unrelated mismatched cord blood transplantation in an adult with secondary AML.

Umbilical cord blood (CB) has been widely used for related and unrelated transplants in pediatric patients. We present the case of an adult with secondary AML who received an unrelated, one-antigen mismatched CB transplant due to the lack of a matched donor. The patient was a 26-year-old female (35 kg/bw) who had received an autologous bone marrow transplant for Hodgkin's disease in April 1994 and, 6 months later, developed secondary MDS (RAEB, 46, XX, -7, +mar), which slowly evolved into acute myelogenous leukemia. In May 1995, she was transplanted with a 165 ml CB unit containing a total of 1.6 x 10(9) nucleated cells, 11 x 10(6) CD34+ cells and 7.2 x 10(5) CFU-GM. GVHD prophylaxis consisted of standard CsA and methotrexate. Myeloid engraftment occurred on day +28 (PMN > 500) and full donor chimerism was confirmed twice (on days +33 and +56) by means of cytogenetics and DNA microsatellite analysis. Erythroid and megakaryocytic engraftment was documented by immunohistochemical analysis of a bone marrow biopsy on day +40, showing the presence of erythroblastic islands and isolated CD61+ immature cells. The patient did not develop GVHD but died on day +56 from idiopathic interstitial pneumonia and multiorgan failure. To our knowledge, this is one of the first case reports of unrelated mismatched CB transplantation in an adult.

Adult↗

Anticentromere antibody--clinical associations. A study of 44 patients.

The objective of this study was to determine the clinical features of 44 patients with anticentromere antibody (ACA) positivity. We undertook a retrospective review of 44 ACA-positive patients (1 male and 43 females with a mean +/- SD age of 53.6 +/- 12.2 years). There were 25 patients with limited systemic sclerosis, 12 with Raynaud's disease, 2 with Sjögren's syndrome, 2 with systemic lupus erythematosus and 3 with polyarthritis. ACA was more frequently found in patients affected by limited systemic sclerosis with mild visceral involvement and in patients with Raynaud's disease. Moreover, ACA was detected in other connective tissue diseases that were characterized by an atypical autoantibody profile.

Adult↗

HLA-DRB1 compatibility in cadaver kidney transplantation: correlation with graft survival and function.

The introduction of genomic HLA-DR typing has stimulated a re-evaluation of the role of HLA-DR compatibility on cadaver kidney transplantation. We retrospectively studied the influence of HLA-DRB1 matching on the survival of 416 patients using univariate and Cox regression analysis as well as its influence on the occurrence of rejection episodes and on creatinine level at the 3rd month in the 198 recipients for whom these data were available. The following parameters were also considered: HLA-A,B compatibility, donor and recipient age, graft number, pre-transplant blood transfusions and panel reactive antibodies (PRA). Twenty-four month graft survival was 100% for transplants with zero mismatches (n = 47), 87.9% for those with one mismatch (n = 191) and 81.3% for those with two mismatches (n = 178). In the Cox model, HLA-DRB1 matching was the most significant variable influencing graft survival (47% of chi 2 P = 0.001), followed by HLA-A,B matching (23%, P = 0.02) and donor age (19%, P = 0.04). Ninety-two percent of the patients with zero mismatches experienced no rejection episodes in the first 3 posttransplant months compared with 62% and 41% of patients with one and two mismatches, respectively. Mean creatinine level (mg/dl) was 1.2, 1.4, and 1.5 in patients with zero, one, and two mismatches, respectively. Should these results be confirmed by prospective studies, HLA-DRB1 compatibility will have to be considered as an organ allocation criterion.

Adolescent↗

HLA DQA1-DQB1-TAP2 haplotypes in IDDM families: no evidence for an additional contribution to disease risk by the TAP2 locus.

The TAP2 gene, located in the HLA class II region, encodes a subunit of a transporter involved in the endogenous antigen-processing pathway, and has been suggested to contribute to the genetic risk for insulin-dependent diabetes (IDDM). In order to determine whether the TAP2 locus modulates the risk conferred by HLA DQ loci, HLA DQA1-DQB1-TAP2 haplotypes were analysed in 48 IDDM probands, their first degree relatives, and in 62 normal control subjects. A decreased frequency of the TAP2B allele was confirmed in this IDDM cohort (12 vs 28% in control subjects, pc < 0.05). Analysis of 73 informative meiotic events in IDDM and control families demonstrated a recombination fraction between HLA DQB1 and TAP2 loci of 0.041 (Log of the odds score = 16.5; p < 10(-8)) indicating strong linkage between these loci. Family haplotype analysis demonstrated linkage disequilibrium between TAP2 and HLA DQA1-DQB1, and showed that the reduced frequency of TAP2B was associated with its absence on the IDDM susceptible DQA1*0301-DQB1*0302 haplotype, its low frequency on DQA1*0501-DQB1*0201, and the association of TAP2B with DQA1*0101-DQB1*0501 haplotypes which were less frequent in IDDM patients. Comparison of transmitted with non-transmitted haplotypes in IDDM families showed a slight but not significant decrease in TAP2B allele frequency on transmitted (3 of 37) vs non-transmitted (2 of 9) HLA DQA1*0501-DQB1*0201 haplotypes. No other differences were observed. Twenty-four unrelated DQA1*0501-DQB1*0201 haplotypes from non-diabetic families had a TAP2B allele frequency (4%) similar to that in IDDM haplotypes.(ABSTRACT TRUNCATED AT 250 WORDS)

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Morphogenetic effects induced by spermine and ruthenium red in yeasts.

Spermine (Sp) produces growth inhibition and wall malformation in Saccharomyces cerevisiae in response to oversynthesis of beta-glucans and chitin. The effect is related to the polycation nature of the molecule. In the present work, to verify this hypothesis, the yeast was treated with the abiogenic polycation ruthenium red (RR). The strict analogy observed between the RR- and Sp-induced alterations reinforced our earlier assumption that Sp interacted with the anionic sites of the plasmalemma determining a spurious activation of the two inserted enzymes beta-glucan and chitin synthases. This view was further confirmed by the aberrant accumulation of beta-glucans in Schizosaccharomyces pombe and of chitin in Rhodotorula glutinis treated with Sp and RR. In these micro-organisms spermidine, which bears three amino groups instead of the four encountered in Sp, was ineffective. It is inferred that at least four cation sites must be present in a compound in order to affect wall morphogenesis in yeasts.

Cations↗

Crossover study of thalidomide vs placebo in Jessner's lymphocytic infiltration of the skin.

BACKGROUND AND DESIGN: An effective therapy is still unavailable for Jessner-Kanof lymphocytic infiltration of the skin. Thalidomide's efficacy was suggested in an open study. Twenty-eight patients were randomly assigned to receive thalidomide (100 mg/d) or placebo over a period of 2 months and were then switched to the other treatment. RESULTS: After the first period, 11 of 13 patients treated with thalidomide were in complete remission (CR), and there were two failures. There was no CR in the patients who received placebo (chi y2 = 17.5; P < .0001). After the second period, nine of 14 patients who had received thalidomide were in CR. Eleven of the 13 patients who had received thalidomide during the first period were given placebo (two were unavailable for follow-up). Ten of them were in CR: four were still free of lesions at the end of the second period, and six experienced a relapse of their lesions after a mean duration of 26 +/- 10 (SD) days. A total of 25 patients participated in the two study periods; CR was observed in 19 (76%) after thalidomide therapy and in four (16%) after treatment with placebo (chi y2 = 11.1; P < .001). Of 27 patients who received thalidomide, 16 (59%) were in CR after 1 month and 20 (74%) were in CR after 2 months. Two patients treated with thalidomide experienced neurologic changes that were not consistent with typical thalidomide-induced neuropathy. CONCLUSIONS: A therapeutic regimen of thalidomide administered at a dosage of 100 mg/d for 2 months is able to suppress the clinical symptoms of Jessner-Kanof lymphocytic infiltration of the skin. The long-term risk-benefit has still to be evaluated.

Adult↗

Cadaver kidney transplantation in the north Italy transplant program in the nineties.

The most relevant changes which have taken place in the NITp in the nineties include the introduction of HLA-DRB1 matching, the extension of both recipient and donor selection criteria, and an increase in donor procurement and consequently, in transplantation activity. Some of the changes in policy resulted from extensive analysis of our previous experience. For the future years, the NITp has set the following priorities: Consolidate the increase of donor procurement activity registered in the past 15 months by educational campaigns for health workers and the public, and organizational measures aimed at strengthening ICUs, nominating transplant coordinators and introducing a system of reimbursement for organs procured. Improve the quality of results in terms of patient rehabilitation and cost-benefit through: continued evaluation of protocols for patient admission on the waiting lists and careful selection of donors; and prospective use of genomic HLA Class II matching and also consider genomic typing for HLA Class I which is almost a reality. Establish a single pool of patients on the waiting list evaluated according to common protocols with the possibility of performing the transplant in each of the authorized centers in turn, respecting the best HLA match and the local use of organs. Finally, standards for donor treatment, organ procurement, histocompatibility testing and transplantation must be established. For this purpose, accreditation programs which have begun to be applied in Europe seem to be the adequate tool.

Adolescent↗

Studies of skin-window exudate human neutrophils: complex patterns of adherence to serum-coated surfaces in dependence on FMLP doses.

Human neutrophils were isolated both from peripheral blood (PB) and from aseptic inflammatory exudates obtained by the Senn's skin-window (SW) technique. The respiratory burst (O2- release) and the adherence to serum-coated wells of culture microplates was investigated using a simultaneous assay. Unstimulated PB resting neutrophils did not produce a significant amount of O2- and were incapable of adhering to serum-coated plastic surfaces, while unstimulated SW neutrophils showed augmented adhesion to serum-coated culture wells. SW neutrophils were primed to enhanced FMLP-dependent O2- release in response to n-formyl-methionyl-leucylphenylalanine (FMLP). Adhesion of SW neutrophils was significantly decreased by addition of low doses (10(-10)-10(-8) M) of FMLP (from 17.1% to 8.4%, P < 0.01, N = 12), while fully activating doses (> 5 x 10(-8) M) of FMLP induced a marked increase of the cell adhesion, more pronounced in SW (39.2%) than in PB cells (27.2%). Low (5 x 10(-9) M) and high (5 x 10(-7) M) FMLP doses induced morphological changes (polarization) and actin polymerization in the neutrophils from both sources. Biphasic dose-response curves of SW neutrophil adherence were observed using FMLP, but not using concanavalin A or phorbol myristate acetate as stimulatory agents. Therefore, the adherence of SW cells appears to be regulated in a complex fashion, nonlinearly dependent on the chemotactic peptide doses and specifically regulated according to the receptors involved.

Cell Adhesion↗

Stimulation of the autophagic activity in blastospores of Candida albicans exposed in vitro to fluconazole.

Blastospores of Candida albicans were exposed in vitro to fluconazole, a bis-triazole which inhibits ergosterol biosynthesis in fungi by interfering with the cytochrome P-450 dependent 14 alpha-demethylase. Electron microscope examination revealed that a low dose (3 micrograms/ml), short treatment (1-3 h) with this compound greatly stimulated autophagic activity not accompanied by alterations of the cell organelles. Only rarely, wall thickenings and some damage to the membrane system, except for the plasma membrane, was noted. This unusual phenomenon suggests that in the presence of fluconazole, due to the depletion of ergosterol and the consequent accumulation of 14 alpha-methylsterols, changes are induced in the properties of the tonoplast. It seems that in the presence of the molecule the membrane is not able to distinguish what is to be degraded from what is still useful for intracellular metabolism with the consequent disintegration of cell compartmentation. Fluconazole may be useful for indicating the mechanism for controlling lytic activity and the homeostatic role of the vacuole in yeasts.

Autophagy↗