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M Trucco

Publications and source records attributed to M Trucco.

At least 109 records · Page 6Linked to original sources
PubMed1994

Cloning and characterization of a glutamate transporter cDNA from human brain and pancreas.

L-Glutamate is the major excitatory neurotransmitter in the brain. Sufficient removal from the synaptic cleft after neurotransmission by the L-glutamate transport system is essential to prevent excitotoxicity and neurotoxicity. We isolated mRNA from human brain and pancreatic islet cells and screened for sequences of high homology to a previously characterized rat brain glutamate transporter. An isolated sequence (GLTR) shows a 87.5% and a 92.5% sequence similarity at the nucleotide and amino acid level, respectively, with a rat brain specific L-glutamate transporter but only a 65% homology to the recently cloned human glutamate/aspartate transporter. The human mRNA is differentially expressed in brain and to a lesser degree in pancreas and in fetal liver. The gene encoding for the newly identified cDNA is located on chromosome 5.

Amino Acid Sequence↗
PubMed1994

Evidence for superantigen involvement in insulin-dependent diabetes mellitus aetiology.

Insulin-dependent diabetes mellitus (IDDM) is a T-cell-mediated autoimmune disease whose onset is believed to be triggered by unknown environmental factors acting on a predisposing genetic background. Islet-infiltrating T (IIT) cells from two IDDM patients, who had died at the onset of the disease from brain swelling as a complication of ketoacidosis, were analysed. The results provided evidence for the involvement of a pancreatic islet cell membrane-bound superantigen as a diabetes aetiopathogenetic factor. There was a selective expansion of a T-cell receptor (TCR) variable segment of the beta-chain (V beta 7) in these IIT cells in association with unselected V alpha-chain segments; extensive junctional diversity of the TCR V beta 7 chains; and evidence of positive selection, after exposure to diabetic islet cell membrane preparations, of V beta 7+ T-cell clones among peripheral blood lymphocytes from non-diabetic individuals.

Amino Acid Sequence↗
PubMed1994

Bone marrow augmentation of donor-cell chimerism in kidney, liver, heart, and pancreas islet transplantation.

We have previously postulated that donor cell chimerism in organ transplantation is needed to attain a tolerant state. Here we show that donor cell chimerism can be augmented in organ recipients if they are infused perioperatively with 3 x 10(8) per kg of unmodified donor bone marrow cells and are kept on a conventional immunosuppressive regimen of tacrolimus (FK506) and prednisolone. 36 patients took part, of whom the first 18 patients have good transplanted kidney (n = 10), liver (n = 7), and heart (n = 7) function when followed up between 4 and 16 months. All patients are well. We found persistent multilineage leucocyte chimerism in blood of 17 recipients by flow cytometry and PCR techniques to detect donor alleles or Y chromosomes in female recipients of male organs. The use of the 5-antigben HLA matched same sex donor precluded detection of chimerism in one patient.

Adult↗
PubMed1994

Heteroduplexes for HLA DQB1 identity of family members and kidney donor-recipient pairs.

DNA heteroduplex (HD) electrophoretic patterns of DQB1 alleles from 124 individuals (38 members from 7 families and 43 kidney donor-recipient pairs) were analyzed in reference to each individual's DQB1 diallelic types determined by the polymerase chain reaction-RFLP method. The assignment of DQB1 homozygosity and heterozygosity, based solely on HD patterns, was accurate and correlated well with the typing results. DQB1 homozygotes invariably gave HD patterns of a single band while heterozygotes gave HD patterns of multiple bands. Distinct HD patterns of 2 heterozygotes predict the presence of at least 1 different DQB1 type between the pair. However, pairs with identical HD patterns may have different subtypes, because HDs with 1 or 2 nucleotide differences may sometimes give an identical HD pattern. Because of its simplicity and reproducibility, this HD analysis protocol serves as an excellent alternative to screen for DQB1 homozygotes and mismatched tissue donor-recipient pairs. This protocol is also useful for confirming the correctness of DQB1 allelic type assignments in a clinical setting.

Alleles↗
PubMed1994

Molecular diagnosis of 21-hydroxylase deficiency: detection of four mutations on a single gel.

Previous studies of the molecular basis of 21-hydroxylase deficiency have shown four common gene conversion mutations in exons 7 and 8. Current molecular diagnostic protocols use allele-specific oligonucleotide hybridization (ASOH) to individually detect each of these mutations and the corresponding normal alleles. This method is costly, labor intensive, and may not provide quantitative results. To expedite molecular diagnosis in families with 21-hydroxylase deficiency, we have designed and implemented single-strand conformational polymorphism (SSCP) analysis. We applied SSCP analysis to 12 families in whom mutations in exons 7 or 8 had been previously identified by ASOH. Using a single polymerase chain reaction (PCR) amplification, unique conformers can be assigned to three mutations: V281L, Q318X, and R356W. The fourth mutation, T insertion at nucleotide 1761, was detected by heteroduplex analysis of the same PCR product. Thus, we were able to identify all four mutations using a single PCR product on a single gel.

Adolescent↗
PubMed1994

Release hallucinations and tiapride.

The authors describe seven patients in whom the administration of tiapride led to the disappearance of visual hallucinatory manifestations with the characteristics of "release hallucinations", the results being maintained throughout the period of treatment. The authors also discuss the mechanism and presumed site of action of the drug.

AIDS-Related Opportunistic Infections↗
PubMed1994

Self-peptides bound to the type I diabetes associated class II MHC molecules HLA-DQ1 and HLA-DQ8.

Genetic susceptibility to several autoimmune disorders is associated with the expression of certain MHC class II alleles. Insight into the etiology of such diseases awaits the identification of the class II restriction elements and the possible pathogenic peptides. Towards these aims, self-peptides bound to HLA-DQ1 and HLA-DQ8, allotypes considered to be neutral and permissive respectively towards the development of insulin-dependent diabetes mellitus, are reported. These naturally processed peptides were isolated from immunoaffinity purified HLA-DQ molecules expressed in cultured B lymphocytes. The chromatographic profiles of the peptide repertoires are unique, whereas the size distributions exhibit general similarity to those reported for naturally processed self-peptides bound to HLA-DR. Twenty-eight individual peptides representing 10 nested sets were identified by combined Edman microsequencing and mass spectrometry. Peptide length varied from 13 to 74 amino acids. Source proteins included MHC molecules and other integral membrane proteins, as well as secretory, cytosolic and mitochondrial proteins. Promiscuous invariant chain peptides were identified among the self-peptides bound to HLA-DQ8. No dominant amino acid markers suggestive of particular enzymatic processing events were detected. Some structural features of DQ1 and DQ8 that may relate to the bound peptides are discussed. Peptide specificity was confirmed in binding assays with purified HLA-DQ and HLA-DR protein.

Amino Acid Sequence↗
PubMed1994

Renal transplantation at the University of Pittsburgh: the impact of FK506.

1. In an unselected adult renal transplant population, FK506 as the primary immunosuppressive agent yielded one- and 2-year actuarial patient survival rates of 95% and 93% and one- and 2-year actuarial graft survival rates of 89% and 83%, respectively. Forty-nine percent of successfully transplanted patients were weaned off steroids. 2. In pediatric renal transplant patients, FK506 has been associated with 100% one- and 3-year actuarial patient survival rates and 98% and 85% one- and 3-year actuarial graft survival rates, respectively. Sixty-two percent of successfully transplanted patients were taken off prednisone, with dramatic improvements in height. 3. FK506 has been used successfully in rescuing 70-74% of adult or pediatric renal transplant patients with an acute rejection that failed conventional therapy. 4. Kidney/bone marrow transplantation under FK506 therapy has been successfully performed without graft-versus-host disease and with routine augmentation of chimerism. 5. The side effects of FK506 included nephrotoxicity, neurotoxicity, and diabetogenicity; they were comparable to those seen with CsA. 6. FK506 is an important new addition to the immunosuppressive armamentarium in renal transplant patients.

Actuarial Analysis↗
PubMed1994

Migratory nonparenchymal cells after organ allotransplantation: with particular reference to chimerism and the liver.

Evidence has been summarized that the migration from organ allografts of donor leukocytes of bone marrow origin and their ubiquitous persistence in recipient tissues is the previous unrecognized seminal explanation for allograft acceptance, and the first stage in the development of donor-specific nonreactivity (tolerance). The unusual immunologic privilege of the liver (called hepatic tolerogenicity) has been explained by its heavy content of leukocytes and its diverse lineage profile that includes precursor dendritic cells. In a direct extension of this new and generically applicable paradigm of transplantation immunology, unconditioned patients have been infused with donor bone marrow cells on the day of cadaveric liver, renal, and heart transplantation and treated otherwise with standard FK506-prednisone immunosuppression. All of the first 16 patients on this protocol have good whole organ function 2.5 to 13 months later. Using flow cytometry and qualitative or quantitative PCR techniques to detect donor HLA alleles, and with study of Y chromosomes in female recipients of male organs, persistent multilineage leukocyte chimerism was regularly found in the blood of these recipients. Rejection was diagnosed and successfully treated in 9 (56%) of these first 16 patients and transient GVHD in 2 (12.5%). Sustained donor-specific hyporeactivity as early as 40 days postoperatively was demonstrable with in vitro tests in the majority of these recipients.

Animals↗