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Biomedical subjects

M Trucco

Publications and source records attributed to M Trucco.

At least 91 records · Page 5Linked to original sources
PubMed1996

No linkage or association of telomeric and centromeric T-cell receptor beta-chain markers with susceptibility to type 1 insulin-dependent diabetes in HLA-DR4 multiplex families.

The T-cell receptor beta locus (TCRB) on chromosome 7q35 was studied as a candidate region for genetic susceptibility to type 1 insulin-dependent diabetes (IDDM). A highly polymorphic microsatellite marker mapping to the TCRBV6.7 gene and a TCRB C-region RFLP were used to genotype the members of a total of 21 multiplex IDDM families from two different geographical areas. There was no evidence to support linkage to either of these markers with IDDM, and conventional two-point analysis excluded linkage to the telomeric end of the TCRB complex, in the region of the highly informative TCRBV6.7 marker. There was significant linkage of IDDM to the class II HLA-D locus with significant lod scores > 3.0 obtained for the HLA-DRB1 and HLA-DQB1 genes. Affected sib-pair (ASP) and transmission disequilibrium (TDT) association tests confirmed these findings.

Adolescent↗
PubMed1996

The low prevalence of immunogenetic markers in Korean adult-onset IDDM patients.

OBJECTIVE: IDDM is an autoimmune disease that occurs among genetically susceptible individuals. In Asian populations, it is not uncommon for adult patients with NIDDM to eventually lose beta-cell function and develop IDDM. These individuals may be characterized by autoantibodies to GAD and high-risk HLA-DQ alleles, which are unlikely to be prevalent among patients with true NIDDM or in the general population. The objective of the present study was to evaluate and compare the prevalence of these immunogenetic markers in NIDDM patients and healthy nondiabetic individuals from Korea. RESEARCH DESIGN AND METHODS: The prevalences of anti-GAD antibodies and HLA-DQA1 and DQB1 alleles among 121 patients with newly diagnosed NIDDM identified from a population-based study in Yonchon, Korea, and 100 matched healthy control subjects were evaluated and compared. RESULTS: The overall prevalence of anti-GAD antibodies was 1.7% (2 of 121) in patients with previously undiagnosed NIDDM, whereas 1 of 100 control subjects had a positive test for antibodies. Among those who tested positive, titers of antibodies to GAD were not high. No statistically significant differences in the distributions of either mean levels of anti-GAD antibodies or DQA1 and DQB1 alleles were found comparing NIDDM patients with control subjects. Interestingly, the frequency of DQB1*non-Asp-57 and DQA1*Arg-52 alleles in the Korean adult control population was similar to that in the U.S. white population (DQB1*non-Asp-57: 0.431 vs. 0.475; DQA1*Arg-52: 0.492 vs. 0.463). CONCLUSIONS: The low prevalence of anti-GAD antibodies and HLA-DQA1 and DQB1 susceptibility alleles among recent-onset NIDDM patients, which was similar to observations in control subjects, suggests that diabetes in Korean adults is unlikely to have an autoimmune component to its pathogenesis.

Adult↗
PubMed1996

Analysis of the structure and expression of the augmenter of liver regeneration (ALR) gene.

BACKGROUND: The gene encoding the hepatotrophic factor Augmenter of Liver Regeneration (ALR) has recently been cloned in the rat. The availability of the mouse form of ALR would allow the analysis of the role of this factor in the physiology of liver and other organs, while the identification of the human homolog would allow the transfer of the great wealth of information that has been generated in animal models to clinically oriented pilot trials, and eventually the therapeutic application of this information. MATERIALS AND METHODS: Standard molecular biology approaches have been used to determine the genomic structure of the ALR gene in the mouse, and to characterize the ALR transcript and its protein product. The human ALR cDNA was also isolated and the amino acid sequence of the human gene product deduced. The mapping of mouse and human ALR genes on mouse and human chromosomes was then completed. RESULTS: The protein coding portion of the mouse ALR gene is comprised of three exons, the first containing the 5' untranslated sequence and the initial 18 bases after the ATG translation initiation codon, the second exon encompasses 198 bases, and the third exon contains the remaining portion of the protein coding sequence. Rat, mouse, and human ALR genes (and protein products) were found to be highly conserved and preferentially expressed in the testis and in the liver. The ALR gene maps to the mouse chromosome 17, in a region syntenic with human chromosome 16, where the T/t region has also been mapped. CONCLUSIONS: ALR appears to be a protein with important physiologic properties, not exclusively limited to liver regeneration, with roles that are involved in the synthesis or stability of the nuclear and mitochondrial transcripts that are present in actively regenerating cells, particularly the germ cells of the testes.

Amino Acid Sequence↗
PubMed1995

The changing immunology of organ transplantation.

The engrafted organ becomes a chimera as the recipient's leukocytes station themselves in the transplant. Remarkably, the recipient becomes chimeric as well, in a reverse migration involving immune cells from the graft. Interactions between donor and recipient cells are tolerogenic--a process with implications for the goal of graft acceptance with minimal immunosuppression.

Cell Movement↗
PubMed1995

Growth of donor-derived dendritic cells from the bone marrow of murine liver allograft recipients in response to granulocyte/macrophage colony-stimulating factor.

Allografts of the liver, which has a comparatively heavy leukocyte content compared with other vascularized organs, are accepted permanently across major histocompatibility complex barriers in many murine strain combinations without immunosuppressive therapy. It has been postulated that this inherent tolerogenicity of the liver may be a consequence of the migration and perpetuation within host lymphoid tissues of potentially tolerogenic donor-derived ("chimeric") leukocytes, in particular, the precursors of chimeric dendritic cells (DC). In this study, we have used granulocyte/macrophage colony-stimulating factor to induce the propagation of progenitors that give rise to DC (CD45+, CD11c+, 33D1+, nonlymphoid dendritic cell 145+, major histocompatibility complex class II+, B7-1+) in liquid cultures of murine bone marrow cells. Using this technique, together with immunocytochemical and molecular methods, we show that, in addition to cells expressing female host (C3H) phenotype (H-2Kk+; I-E+; Y chromosome-), a minor population of male donor (B10)-derived cells (H-2Kb+; I-A+; Y chromosome+) can also be grown in 10-d DC cultures from the bone marrow of liver allograft recipients 14 d after transplant. Highly purified nonlymphoid dendritic cell 145+ DC sorted from these bone marrow-derived cell cultures were shown to comprise approximately 1-10% cells of donor origin (Y chromosome+) by polymerase chain reaction analysis. In addition, sorted DC stimulated naive, recipient strain T lymphocytes in primary mixed leukocyte cultures. Evidence was also obtained for the growth of donor-derived cells from the spleen but not the thymus. In contrast, donor cells could not be propagated from the bone marrow or other lymphoid tissues of nonimmunosuppressed C3H mice rejecting cardiac allografts from the same donor strain (B10). These findings provide a basis for the establishment and perpetuation of cell chimerism after organ transplantation.

Animals↗
PubMed1995

Microchimerism linked to cytotoxic T lymphocyte functional unresponsiveness (clonal anergy) in a tolerant renal transplant recipient.

A patient was found to be functionally tolerant of a maternal kidney allograft as evidenced by good graft function 5 years after cessation of all immunosuppressive drug therapy. Despite normal in vitro proliferative and IL-2 responses, patient anti-donor 1 degree MLR cultures yielded little donor-specific CTL activity in either bulk or limiting dilution analysis (LDA) cultures. Using polymerase chain reaction, the patient's PBL and skin were found to contain donor-derived Bw6+ cells. Removal of Bw6+ donor cells from the patient PBL with mAb and immunomagnetic beads before stimulation with donor PBL on day 0 failed to restore donor-specific CTL in either bulk 1 degree MLR or LDA cultures. Restimulation of 1 degree cultures with donor stimulator cells plus exogenous IL-2, however, completely restored anti-donor HLA class I-specific CTL, indicating class I-specific CTL precursors were not clonally deleted. Fresh patient PBL, as well as donor cell-enriched fractions, when added at the initiation of 3 degrees MLR cultures, inhibited the generation of anti-donor CTL, whereas donor cell-depleted fractions did not. The inhibition was cell dose-dependent, was specific for the anti-donor response, and was radioresistant (1200 rad). Thus, the clinical tolerance observed in patients with microchimerism may be due to the presence of veto cells within the circulating donor cell pool.

Base Sequence↗
PubMed1995

Detection of Y chromosome sequences in a 45,X/46,XXq--patient by Southern blot analysis of PCR-amplified DNA and fluorescent in situ hybridization (FISH).

In some cases of gonadal dysgenesis, cytogenetic analysis seems to be discordant with the phenotype of the patients. We have applied techniques such as Southern blot analysis and fluorescent in situ hybridization (FISH) to resolve the phenotype/genotype discrepancy in a patient with ambiguous genitalia in whom the peripheral blood karyotype was 45,X. Gonadectomy at age 7 months showed the gonadal tissue to be prepubertal testis on the left side and a streak gonad on the right. The karyotype obtained from the left gonad was 45,X/46,XXq- and that from the right gonad was 45,X. Three different techniques, PCR amplification, FISH, and chromosome painting for X and Y chromosomes, confirmed the presence of Y chromosome sequences. Five different tissues were evaluated. The highest percentage of Y chromosome positive cells were detected in the left gonad, followed by the peripheral blood lymphocytes, skin fibroblasts, and buccal mucosa. No Y chromosomal material could be identified in the right gonad. Since the Xq- chromosome is present in the left gonad (testis), it is likely that the Xq- contains Y chromosomal material. Sophisticated analysis in this patient showed that she has at least 2 cell lines, one of which contains Y chromosomal material. These techniques elucidated the molecular basis of the genital ambiguity for this patient. When Y chromosome sequences are present in patients with Ullrich-Turner syndrome or gonadal dysgenesis, the risk for gonadal malignancy is significantly increased. Hence, molecular diagnostic methods to ascertain for the presence of Y chromosome sequences may expedite the evaluation of patients with ambiguous genitalia.

Adolescent↗
PubMed1995

Genetic background and environment contribute synergistically to the onset of autoimmune diseases.

Autoimmune diseases result from the breakdown of "self" tolerance. Environmental factors appear to be responsible for triggering this errant immune response, directed against self-tissue determinants, only when a susceptible genetic background is present in an individual. Autoimmune diseases, normally characterized by their association with certain HLA alleles, also share other features: the presence of autoantibodies, autoreactive T lymphocytes, and an intermittent clinical course of exacerbations and remissions. In cases of organ-specific diseases, as well as in cases of multi-system autoimmune diseases, viruses are increasingly implicated as such environmental triggers. Current molecular biology techniques have permitted a fine dissection of the genetic background of susceptible individuals and have enabled a more complete characterization of the immunocompetent cells involved in this autoaggression. Molecular approaches will soon allow us to pinpoint the characteristics of the environmental stimuli, so that protective strategies could be formulated to spare susceptible individuals from their ill effects.

Autoimmune Diseases↗
PubMed1995

HLA-DQ screening for risk assessment of insulin dependent diabetes in northern Italy.

Genetic markers may be used to improve the prediction of insulin-dependent diabetes mellitus (type 1) in individuals with islet autoantibodies. In order to develop a risk assessment strategy for the Lombardy region of northern Italy based on genetic and immunological markers, we analyzed HLA DQA1 and DQB1 alleles in 60 type 1 probands and their first-degree relatives and 65 unrelated control subjects from the same area using polymerase chain reaction (PCR) and oligonucleotide probes. The major risk haplotypes were DQA1 *0501-DQB1*0201 (39.1% of diabetic vs. 8.9% of non-diabetic haplotypes) and DQA1 *0301-DQB1*0302(20% of diabetic vs 7.1% of non-diabetic haplotypes). Stratified analysis showed DQA1*0102-DQB1*0502 also to be associated with type 1 susceptibility when found together with DQA1*0501-DQB1*0201 or DQA1*0301-DQB1*0302. One type 1 patient had the type 1-protective DQA1*0102-DQB1*0602 haplotype. Overall, 88% of patients and 20% of unrelated control subjects had either DQA1*0501-DQB1*0201 or DQA1*0301-DQB1*0302 in the absence of DQA1*0102-DQB1*0602. These data suggest that typing for markers identifying these three haplotypes in the Lombardy population will achieve a sensitivity of almost 90% and exclude 80% of children from subsequent islet autoantibody testing.

Adolescent↗
PubMed1995

Further evidence for an association between schizophrenia and the HLA DQB1 gene locus.

A case-control study was conducted in Singapore, in order to examine a proposed association between schizophrenia and the HLA DQB1 gene locus. The probands were male inpatients of Chinese ethnicity with schizophrenia (ICD-10 criteria, n = 102) and the controls were adults matched for gender and ethnicity (n = 111). Polymorphisms of the HLA DQB1 gene were examined using molecular typing by reverse dot-blotting (MTRB), a novel PCR based method. Among the patients, a positive association with HLA DQB1*0303 (odds ratio 4.46, C.I. 1.63, 12.17), as well as a negative association with HLA DQB1*0602 (odds ratio 0.22, C.I. 0.18, 0.83) was detected.

Adult↗