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Biomedical subjects

M Muro

Publications and source records attributed to M Muro.

At least 19 recordsLinked to original sources
PubMed2006

Study of Fas (CD95) and FasL (CD178) polymorphisms in liver transplant recipients.

The Fas receptor is capable of transducing apoptotic cell death upon interaction with their ligand (FasL). Recent studies suggest that the Fas/FasL system is involved both in graft rejection and in transplantation tolerance. In this study, we analyzed the effect of Fas and FasL polymorphisms in liver allograft outcome. Fas and FasL polymorphisms were analyzed in 151 primary liver graft recipients. The Fas (-670 A/G) and the FasL (IVS2nt -124 A/G and IVS3nt 169 T/delT) polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. Fas -1377 G/A polymorphism was determined by allele-specific amplification. Fas and FasL polymorphisms were not associated with acute and chronic rejection in liver transplant. In contrast, those recipients bearing the AA -670 Fas genotype showed significantly lower graft survival rate (S = 40%) than those bearing the GA genotype (S = 63.1%). These differences were detected from the first year post-transplant. Multivariate analysis confirmed that the AA genotype increased the risk of liver graft loss. This work suggests for the first time a possible harmful effect of Fas -670 AA genotype on liver graft survival, whereas the Fas and FasL polymorphisms are not associated with acute or chronic rejection in liver graft recipients.

Adult↗
PubMed2005

Evaluation of CD86 gene polymorphism at +1057 position in liver transplant recipients.

BACKGROUND: Efficient T cell-APC interaction requires the participation of primary and co-stimulatory signals. The main co-stimulatory pathway involves the interaction of CD80 and CD86, expressed on the APCs, with their T cell counter-receptor, CD28 and CTLA-4. Recently, a G to A transition has been described at position +1057 of the CD86 gene, located in their cytoplasmic tail. METHODS: CD86 polymorphism was analyzed by sequence based typing in DNA samples obtained from 205 liver transplant recipients. Acute rejection and chronic rejection were diagnosed based upon conventional clinical, biochemical and histological criteria. RESULTS: The study of CD86 +1057 (G/A) polymorphism revealed that recipients bearing the A allele or the AA genotype have a reduced risk of acute rejection. In fact, the AA genotype was absent in the group of patients showing acute rejection episodes, whereas its frequency in those patients without acute rejection episodes was 8.8% (P=0.009, OR=0.07). This polymorphism did not reveal any association with the incidence of chronic rejection, but patients bearing the AA genotype showed a higher graft survival rate (83.3%) than those bearing the GA genotype (49.3%) or GG genotype (56.5%). CONCLUSIONS: The results of the present report suggest that the CD86 AA genotype at +1057 position could be involved in liver transplant acceptance, given that its presence is related to a decrease of acute rejection frequency and to a graft survival increase.

Acute Disease↗
PubMed2003

Impact of HLA-C on acute rejection in liver transplantation.

Although liver transplants show a special tolerogenic behaviour, rejection remains an important problem that involves several immunological mechanisms, some of which are unknown. Our study sought to analyze the influence of HLA-C polymorphism on short-term liver graft acceptance by HLA-C genotyping of 100 orthotopic liver transplant recipient-donor pairs. Recipients were statified according to the occurrence of acute rejection. HLA-Cw*06 allele appeared to be underrepresented among recipients without versus those with acute rejection or those in control groups. With regard to HLA-C allelic compatibility, the frequency of acute rejection or those in episodes decreased with fewer HLA-C mismatches. These findings suggest the participation of HLA-C molecules in liver graft alloresponses, involving HLA-C genotyping, as well as compatibility.

Alleles↗
PubMed2003

Relationship between CDC cross-match in liver recipients and antibody screening by flow cytometry.

Several authors have shown that anti-donor antibodies before liver transplantation are associated with decreased graft survival. The aim of this study was to investigate the relationship between anti-donor antibodies detected by the CDC technique or by FlowPRA, and acute or chronic rejection as well as graft survival. Furthermore, we sought to determine whether anti-donor antibodies, detected by the CDC technique, correlated with those discovered by cytometric screening. The acute rejection incidence among patients with complement-dependent cytotoxicity positive CDC cross-match was similar to that for patients with a negative cross-match. None of the patients with a positive cross-match developed chronic rejection. Allograft survival was significantly lower among recipients with a positive T-lymphocyte cross-match. Indeed, the majority of recipients with positive CDC cross-matches displayed graft failures before first posttransplant year. The results of a positive FlowPRA determination were concordant with a positive CDC cross-match in 85.71% of cases. Our data demonstrate that pretransplant FlowPRA correlates with the final CDC cross-match results. This finding suggests that in the future prospective pretransplant antibody screening with FlowPRA or CDC techniques may be useful to identify high-risk recipients.

Acute Disease↗
PubMed2002

Report of recombinations between HLA loci within two families: utility of high resolution typing.

We have analysed two Caucasian families in which recombinant individuals have been identified. In both families, initial low resolution typing of class I and II antigens of possible patients referred for bone marrow transplantation and their respective potential donors (based on inherited haplotypes analysis) revealed them to be HLA identical and supposedly inheriting-non-recombinant haplotypes. The mothers were found to be DRB1*04 generic allele homozygous, but possessing two DRB1*04 specific alleles, DRB1*0403 and DRB1*0404 (family A) and DRB1*0401 and DRB1*0402 (family B). In both cases the patients inherited a maternal haplotype that is the result of a recombination event between the mother's HLA-DRB1 and -B genes on their chromosomes. Based on linkage disequilibrium it is likely that the recombinant haplotypes are present in the patients rather than their brothers. In both families, the results of the MLC in terms of relative response was positive. Thus, these cases illustrate the importance of high resolution DNA class II typing when assignment of MHC antigens is of extreme importance (i.e. bone marrow transplantation).

Adult↗
PubMed2002

Interleukin-10, interleukin-6 and interferon-gamma gene polymorphisms in melanoma patients.

The immune response against melanoma can be influenced by cytokines with potentially opposite effects on tumour cell growth, such as interleukin-10 (IL10), interleukin-6 (IL6) and interferon-gamma (IFNgamma). Our objective in this study was to investigate whether polymorphisms in the regulatory regions of IL10, IL6 and IFNgamma genes are associated with the development of primary cutaneous melanoma and/or the prognosis of this tumour. We studied genotypic variations at positions -1082, -819 and -592 in the IL10 promoter, -174 in the IL6 promoter and +874 in the IFNgamma intron 1 in 42 melanoma patients and 48 healthy controls. These two populations showed very similar genotypic frequencies for IL10, IL6 and IFNgamma gene polymorphisms. There was a significant increase in the prevalence of IL10 low expression genotypes, specially the ACC/ATA genotype, among patients with a poorer prognosis. In contrast, IL6 promoter and IFNgamma intron 1 gene polymorphisms did not correlate with melanoma prognosis. These data indicate that investigation of polymorphisms in the regulatory regions of IL10, IL6 and INFgamma genes does not seem to be useful for predicting the risk of development of primary cutaneous melanoma. However, IL10 low expression genotypes may be associated with a poorer outcome in melanoma patients.

Adult↗
PubMed2001

HLA polymorphism in the Murcia population (Spain): in the cradle of the archaeologic Iberians.

Human leukocyte antigen (HLA) study in Murcian individuals was performed in order to provide information of their historical origins and relationships with other Iberian and Mediterranean populations. HLA class I and class II alleles were determined in 173 unrelated Caucasoid donors from Murcia Region in the Southeast of Spain by serologic and DNA based polymerase chain reaction (PCR) typing. Class I antigen and class II allele frequencies of our series were not very different to those found in Spaniards. The analysis of extended haplotypes showed that the three haplotypes most frequent in our population were respectively, A29-B44-Cwb-DRB1*0701-DRB4*0101-DQA1*0201-DQB1*0202, A1-B8-Cw7-DRB1*0301-DRB3*0101-DQA1*0501-DQB1*0201 and A30-B18-Cw5-DRB1*0301-DRB3*0101-DQA1*0501-DQB1*0201. They were followed by A26-B38-Cwb-DRB1*1301-DRB3*0202-DQA1*0103-DQB1*0603, which could point to an ancestral relationship between Murcian and Portuguese Iberian populations, and by A2-B7-Cw7-DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602 also present in all Iberian Peninsula populations. Allelic frequencies, populations distance dendrogram and correspondence analysis were used to study the relationships between Murcian and other populations. The closest relation was observed with Spaniards and Portuguese, followed in decreasing order by French, Italians, Algerians, Germans, Catalans, Basques, Cretans, Sardinians, and Greeks. Thus, Murcian population seems to belong to the European genetic pool, revealing a lesser genetic distance with the North Africans and the rest of populations from the Iberian Peninsula.

Africa↗
PubMed2001

Involvement of caspases in apoptotic cell death of murine macrophages infected with Actinobacillus actinomycetemcomitans.

Infection of murine macrophages in vitro with periodontopathic bacterium Actinobacillus actinomycetemcomitans induces apoptotic cell death. In this study, we investigated the involvement of caspases in apoptotic cell death of A. actinomycetemcomitans-infected macrophages. Two peptide inhibitors of caspases, benzyloxycarbonyl-Val-Ala-Asp (OMe)-fluoromethyl ketone (Z-VAD-FMK) and benzyloxycarbonyl-Asp-Glu-Val-Asp (OMe)-fluoromethyl ketone (Z-DEVD-FMK), inhibited apoptotic cell death of murine macrophage cell line J774.1 infected with A. actinomycetemcomitans. During the process of apoptosis, interleukin-1beta (IL-1beta) was detected in the culture supernatants of J774.1 cells. IL-1beta secretion was blocked by the caspase-1 inhibitor, Z-VAD-FMK, indicating that caspase-1 is involved in not only the induction of apoptosis but also the IL-1beta secretion from A. actinomycetemcomitans-infected J774.1 cells. Immunoblot analysis revealed that the infection of A. actinomycetemcomitans to J774.1 cells induced the cleavage of retinoblastoma protein (Rb), suggesting that caspase-3 was activated by A. actinomycetemcomitans infection. The cytosol from A. actinomycetemcomitans-infected J774.1 cells induced Rb proteolysis in vitro, which was inhibited by the caspase-3 inhibitor, Z-DEVD-FMK. Furthermore, caspase-3-like activity was markedly increased in J774.1 cells infected with A.actinomycetemcomitans between 12 h and 24 h, which was subsequently inhibited by the addition of caspase-3 inhibitor, Z-DEVD-FMK. These findings indicate that caspase-3 induces apoptosis in J774.1 cells infected with A. actinomycetemcomitans. Taken together, these results suggest that caspase-1 and caspase-3 are involved in the induction of apoptosis in A. actinomycetemcomitans-infected macrophages.

Aggregatibacter actinomycetemcomitans↗
PubMed2001

A new method to analyze basic rest-activity cycle.

A new method was proposed to analyze a basic rest-activity cycle (BRAC), termed BRAC-A. This method calculates a significant cycle length by chi-squared method and the starting points of a resting phase and an active one by analysis of the array consisting of the segmented time series in the same length. Using 20 3-day computer-simulated time series of standard deviation in fetal heart rate fluctuation with known periodicity of the BRAC, we demonstrated that the BRAC-A was a useful tool to reveal the characteristics of the BRAC.

Activity Cycles↗
PubMed2001

A longitudinal study of diurnal variation in baseline fetal heart rate in one dichorionic-diamniotic twin pregnancy.

A longitudinal study to analyse the diurnal variations in baseline fetal heart rate (FHR) and sustained fetal tachycardia (SFT) in twin pregnancy was performed on one dichorionic twin. Twenty-four hour FHR recordings on twins were made at 32, 34 and 36 weeks of gestation simultaneously. Significant diurnal variations were found in both twins in all gestational weeks. The diurnal variations in baseline FHR of twins were highly correlated with no phase-lag. No coincidence was recognized in the appearance of SFT between twins. These results suggest the maternal influence equally affects FHR in each fetus of dichorionic twin since 32 weeks of gestation, while the appearance of SFT might be independent from maternal influence.

Adult↗
PubMed2001

Polymorphism in the upstream regulatory region of the HLA-DQB1 gene in liver graft recipients.

HLA-DQB1*0302 allele frequency is increased in liver graft recipients with acute rejection. We investigated polymorphism in the upstream regulatory regions (URRs) of the DQB1 gene to determine whether polymorphism in the DQB1 promoter region influences liver graft acceptance. A combination of typing protocols based on the polymerase chain reaction were used in 103 first-time liver transplants and 108 healthy Spanish controls. The QBP3.21 allele frequency and QBP3.21-DQB1*0302 haplotype were significantly different in recipients with acute rejection compared to those with good graft acceptance and to controls. Of major interest for acute rejection development are the promoter "splits" of DQB1*0302 (QBP3.21, QBP3.22, and QBP3.3 alleles), which are in linkage disequilibrium with DQB1*0302. The promoter splits were equally distributed in all groups. Thus, although there are significant differences in the frequencies of the QBP alleles and QBP-DQB1 haplotypes between recipients with and without acute rejection and controls, the composition of these haplotypes is essentially the same in all groups. In conclusion, our data show that the polymorphism in the DQB1 promoter region does not clearly influence liver graft acceptance, and, as occurs in other populations, QBP alleles exhibit strong linkage disequilibrium with the DQB1 locus.

Alleles↗