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C Navarrete

Publications and source records attributed to C Navarrete.

At least 55 records · Page 3Linked to original sources
PubMed1996

Oligoclonality of V beta 3 TCR chains in the CD8+ T cell population of rheumatoid arthritis patients.

It has been established that oligoclonal expansion is a common feature of the CD8+ T cell population, particularly within the CD8+ CD57+ lymphocyte subset. In addition, clonal malignancies involving CD8+ CD57+ T cells (large granulocytic lymphocytic leukemias) are often accompanied by rheumatoid arthritis, Felty's syndrome, or both. Therefore, to identify disease-related alterations in the CD8+ T cell repertoire, we have compared the patterns of oligoclonality in the CD8+ T cells of rheumatoid arthritis patients (n = 32) with those of age-matched controls (n = 25). By using a multiplex PCR assay for the CDR3 length of TCR beta-chains, we have found a striking increase in the frequency of CD8+ oligoclonality involving V beta 3 TCR: 50% of the rheumatoid arthritis patients had evidence of oligoclonality in this TCR family compared with 4% of controls (p < 0.0002). In addition, two unrelated RA patients had clonally dominant CD8+ T cell beta receptors that were identical in amino acid sequence, suggesting selection by a common Ag. An analysis of a subset of RA patients with mAbs specific for V beta 3 TCR revealed the presence of clonal expansion in a minority of patients usually, but not exclusively, involving the CD57+ subset. These data define a phenotype of the T cell repertoire that is strongly associated with rheumatoid arthritis; the mechanisms and genetic and environmental factors that explain this phenomenon remain to be defined.

Adult↗
PubMed1996

The HLA system: an update and relevance to patient-donor matching strategies in clinical transplantation.

In recent years the development of recombinant DNA and sequencing techniques has led to a greatly increased understanding of the genetic complexity, structure and function of the human major histocompatibility complex. This system may be subdivided into the "classical' HLA (human leukocyte antigen) class I and II transplantation antigens and novel HLA and non-HLA genes, involved in antigen processing and presentation to T cells. Parallel technological developments in HLA DNA typing in the clinical laboratory have resulted in a more precise awareness of the role of HLA matching for the classical HLA antigens in bone marrow and solid organ transplantation, while alternative strategies and techniques for donor selection are currently under evaluation. This review offers a current perspective on the genetics, structure and function of the HLA system, its relevance to clinical transplantation and future prospects for improvements in donor selection.

Bone Marrow Transplantation↗
PubMed1996

Effects of SCA40 on human isolated bronchus and human polymorphonuclear leukocytes: comparison with rolipram, SKF94120 and levcromakalim.

1. SCA40 (0.1 nM-0.1 mM) produced concentration-dependent suppression of the spontaneous tone of human isolated bronchus (-log EC50 = 6.85 +/- 0.09; n = 10) and reached a maximal relaxation similar to that of theophylline (3 mM). The potency (-log EC50 values) of SCA40 compared to other relaxants was rolipram (7.44 +/- 0.12; n = 9) > SCA40 > or = levcromakalim (6.49 +/- 0.04; n = 6) > SKF94120 (5.87 +/- 0.10; n = 9). 2. When tested against the activity of the isoenzymes of cyclic nucleotide phosphodiesterase (PDE) isolated from human bronchus, SCA40 proved highly potent against PDE III (-log IC50 = 6.47 +/- 0.16; n = 4). It was markedly less potent against PDE IV (4.82 +/- 0.18; n = 4) and PDE V (4.32 +/- 0.11; n = 4). 3. Human polymorphonuclear leukocytes (PMNs) stimulated with N-formylmethionyl-leucyl-phenylalanine (FMLP) produced a concentration-dependent superoxide anion generation and elastase release. SCA40 (1 nM-10 microM) produced a concentration-related inhibition of FMLP (30 nM approximately EC50)-induced superoxide production (-log IC50 = 5.48 +/- 0.10; n = 6) and elastase release (-log IC50 = 5.50 +/- 0.26; n = 6). Rolipram was an effective inhibitor of superoxide generation and elastase release (-log IC50 values approximately 8) while SKF94120 and levcromakalim were scarcely effective. 4. FMLP (30 nM) and thimerosal (20 microM) induced leukotriene B4 production and elevation of intracellular calcium concentration in human PMNs. The production of leukotriene B4 was inhibited by SCA40 in a concentration-related manner (-log IC50 = 5.94 +/- 0.22; n = 6) but SCA40 was less effective against the elevation of intracellular calcium. Rolipram was an effective inhibitor of leukotriene B4 synthesis (-log IC50 approximately 7) and intracellular calcium elevation (-log IC50 approximately 6) while SKF94120 and levcromakalim were scarcely effective. 5. It is concluded that SCA40 is an effective inhibitor of the inherent tone of human isolated bronchus. The bronchodilatation produced by SCA40 appears mainly related to PDE inhibition since the potency of SCA40 as a relaxant of human isolated bronchus was found to be close to its potency as inhibitor of PDE III activity isolated from human bronchus. In addition, SCA40 exhibited inhibitory effects on human PMN function stimulated by FMLP. These effects may be related to the ability of SCA40 to inhibit PDE IV from human PMNs while the contribution of PDE V inhibition is uncertain. We found no evidence of a role for levcromakalim-sensitive plasmalemmal K+-channels in human PMNs.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Inhibition of phosphodiesterase IV and intracellular calcium levels in human polymorphonuclear leukocytes.

Phosphodiesterase (PDE) isoenzyme type IV is the predominant cyclic AMP hydrolytic activity in polymorphonuclear leukocytes (PMNs). PDE IV inhibitors depress functional responses of PMNs but their influence on intracellular calcium concentration ([Ca2+]i) has not been extensively studied. The present study examined the effects of rolipram (a selective PDE IV inhibitor) on the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (fMLP)-induced changes of [Ca2+]i in fura-2 loaded human PMNs. Rolipram (1 nM-10 microM) did not alter basal [Ca2+]i values. fMLP (10 nM approximately EC50) produced a transient calcium response, i.e., a peak followed by decay to a residual value above baseline. Peak [Ca2+]i values after fMLP were not altered but a faster decay and a lower residual [Ca2+]i were observed in rolipram (0.1-10 microM)-treated cells. fMLP added after thimerosal (20 microM) produced a peak followed by a sustained oscillatory response. Rolipram (up to 10 microM) did not alter the peak but inhibited the sustained response (-log IC50 = 6.39 +/- 0.12). The inhibitory effects of rolipram may be due to alterations in the mobilization of Ca2+ produced by the increase in the cellular content of cyclic AMP. SKF94120 (a selective PDE III inhibitor) produced minor effects on the fMLP-induced calcium response. SCA40 (a mixed PDE III/IV/V inhibitor) produced similar effects but was less potent than rolipram. Reduction of the calcium response probably underlies the inhibition of PMN functions produced by PDE IV inhibitors.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1994

Tuberculin reactivity after newborn BCG immunization in mono- and dizygotic twins.

SETTING: Studies showing significantly higher concordance of tuberculosis among monozygotic twins than dizygotic twins have provided support for genetically determined susceptibility to tuberculosis. OBJECTIVE: We wished to explore whether the development of delayed type hypersensitivity to tuberculin after newborn BCG immunization of twins suggested genetic regulation of the response to BCG in humans. DESIGN: Our study population consisted of 17 monozygotic twin pairs, 18 dizygotic twin pairs, and 64 single infants 3-34 months of age from Santiago, Chile. All had a BCG scar and were tuberculin tested by one trained nurse. RESULTS: The mean birth weight of both groups of twins was significantly lower than that of singletons and the percentage of individuals who failed to respond to tuberculin was approximately twice as high in twins as in singletons. After adjustment for birth weight and age by regression analysis, it was found that the distribution of tuberculin reactivity in both monozygotic and dizygotic twins was not significantly different from that of singletons. Both twin pair correlations is adjusted tuberculin reactivity were significantly greater than zero (P < 0.01) and led to a heritability estimate of 0.28. However, the monozygotic twin correlation was not significantly larger than the dizygotic twin correlation so that heritability is poorly estimated. CONCLUSION: These results are consistent with a genetic regulation of the response to newborn BCG immunization in humans by a mechanism capable of producing similar responses in identical and nonidentical twins alike.

BCG Vaccine↗
PubMed1994

Recurrent erythema multiforme: tissue typing in a large series of patients.

Previous reports have shown an increased frequency of certain HLA antigens in association with erythema multiforme, including HLA-B15(B62), HLA-B35, HLA-A33, HLA-DR53 and, more recently, HLA-DQB1*0301. A strong association with HLA-DQ3 has been documented in patients with recurrent erythema multiforme. We have performed HLA typing in 39 patients with recurrent erythema multiforme, of whom 33 were associated with herpes simplex virus infection. The results were compared with 309 controls. In the recurrent erythema multiforme patients there was a statistically significant increase in HLA-B62 and HLA-B35. An increase in HLA-DR53 was also found, although this did not reach statistical significance. There was no increase in HLA-A33. The presence of HLA-DQ3 in the study population approached that in the controls. Finally, the study population demonstrated a trend towards a reduction in the HLA antigens A1, B8 and DR3. The study confirms the previously reported associations with HLA-B62 (B15), HLA-B35 and HLA-DR53. We have been unable to confirm an association of HLA-A33 or HLA-DQ3 with erythema multiforme. The HLA antigens A1, B8, and DR3 are associated with autoimmune disease, reflecting an increased host response to tissue self antigens. Their absence in patients with recurrent erythema multiforme (REM) may be an indicator of a poor host response to an antigen, which in the case of REM is the herpes simplex virus.

Adult↗
PubMed1993

HLA antigen frequencies in renal transplant recipients and non-immunosuppressed patients with non-melanoma skin cancer.

An increased frequency of human leukocyte antigen (HLA)-DR1 was found in 49 non-immunosuppressed patients with non-melanoma skin cancer (NMSC), being highest in patients under the age of 60 with multiple squamous cell carcinomas (SCC). Of 266 patients receiving long-term immunosuppression following renal transplantation 46 (17%) were found to have NMSC. No increase in HLA-DR1 was found in renal transplant recipients (RTR) with non-melanoma skin cancer (RTR+C) when compared with matched renal transplant recipients without skin cancer (matched RTR-C), or when compared with healthy controls. There was an increased frequency of DQw2 in RTR+C, most pronounced in RTR with SCC (61.9% compared with 18.75% in matched RTR-C), giving a relative risk of 13.98. We found statistically significant differences in the frequency of a number of HLA antigens on comparing RTR+C with healthy controls, but none of these differences were found when we compared RTR+C against matched RTR-C.

Antigens, Neoplasm↗
PubMed1992

Nicotine stimulates adrenergic terminals and inhibits contractions of mouse uterine horns.

1. Nicotine (1-100 microM) stimulated both basal and electrically evoked release of 3H-norepinephrine and also caused a transient inhibition of contractions in an in vitro preparation of mouse uterine horns. 2. The inhibitory effect of nicotine on electrically evoked contractions was potentiated by aminophylline (89 micrograms/ml), and overcome by both propranolol (1 microM) and by omitting magnesium from the physiological solution. Acetylcholine (10 microM), in the presence of atropine (10 microM) was able to reproduce the inhibitory effect of nicotine. 3. These pharmacological findings suggest that the inhibitory action of nicotine on electrically evoked contractions in mouse uterus could be indirect, i.e. mediated through the action of this compound on presynaptic nicotine receptors located on adrenergic terminals.

Acetylcholine↗
PubMed1990

Further DNA sequence microheterogeneity of the HLA-DR4/Dw13 haplotype group: importance of amino acid position 86 of the DR beta 1 chain for T-cell recognition.

Using the polymerase chain reaction we have isolated and sequenced cDNA clones corresponding to the polymorphic first domain of the DR beta 1 chain from the DR4, "Dw13" cell line, JHa. We have found that the JHa DR beta 1 allele differs from previously reported Dw13 alleles by a single amino acid substitution at position 86. The functional relevance of this polymorphism is supported by the reactivity pattern of a T-cell clone, E38. E38 is an alloreactive T-cell clone which reacts with all Dw14 stimulator cells and all Dw13-positive cells tested except the "Dw13"-positive homozygous typing cell line JHa. Inhibition studies with monoclonal antibodies revealed the stimulating determinant to be on DR and not on DQ or DP molecules. These data indicate that position 86 of the DR beta 1 chain can play an important role in the formation of determinants recognized by T cells.

Amino Acid Sequence↗
PubMed1989

DNA sequence analysis of the HLA-DRw12 allele.

The complete DNA sequence of a DR beta chain cDNA encoding the DRw12 allele has been determined. The sequence of this DRB1 allele reveals a structural relationship to the group of other DRB1 genes found on DRw52 haplotypes, such as DR3, -w11, -w13, -w14, and -w8. The structural similarities among this group of alleles are particularly evident in the first hypervariable as well as in the 3' untranslated region. The second hypervariable region contains a unique sequence not identified in any other DRB1 allele. The third hypervariable region appears to have arisen by gene conversion events involving two DRB1 chain genes, DR7 and DR1 or DR2/Dw21.

Alleles↗
PubMed1989

HLA-D region heterogeneity in a Nigerian population.

HLA class II antigens were studied in a panel of 130 Nigerians. Complex patterns of associations were seen between HLA-Dw, -DR and -DQ specificities, differing widely from those reported for other populations. A number of Dw types were associated with the same DR antigen: Dw'1N' and Dw'BERN' with DR1, Dw2 and Dw'2N' with DR2, Dw5 and Dw'5N' (Dw5 + Dw'F5') with DRw11. It was also observed that a Dw type associated with more than one DR antigen: HLA-Dw3 was assigned to individuals who were DR3 negative and similarly Dw10, Dw13 and Dw14 to individuals negative for DR4. HLA-DRw8 and Dw8 were completely dissociated in Nigerians, and Dw8 did not show a preferential DR association. These results demonstrate that DR and DQ identity between HTC stimulator and responder cell is not necessarily a prerequisite for Dw to be assigned. Preliminary studies show that subtypes of HLA-Dw1 and Dw8 detected by HTC typing correlate with restriction fragment length polymorphisms (RFLPs) detected with a combination of Bgl II enzyme and DRA/DRB cDNA probes. HLA-DP antigen frequencies differed between Nigerians and British Caucasoids. The most common DP antigen in Nigerians was DPw1, compared with DPw4 in Caucasoids. HLA-DPw6 appeared to be absent or rare in both Nigerians and British Caucasoids. Only five out of 68 Nigerians tested were assigned two DP specificities. The association between HLA-DR3 and DPw1 reported in Caucasoid panels was absent in Nigerians.

Black People↗