Papers by J. González-Larriba
35 A sequence-dependent paclitaxel-etoposide phase II trial in patients with non-small cell lung cancer (NSCLC)
Lung Cancer, 1997
ABSTRACT
CHIMERISM IN PEDIATRIC PATIENTS WITH ALLOGENEIC TRANSPLANT OF HEMATOPIETIC PRECURSORS
Transplantation, 2008
Medicina, 1999
Pemphigus vulgaris (PV) is an autoimmune blistering disease affecting the skin and mucous membran... more Pemphigus vulgaris (PV) is an autoimmune blistering disease affecting the skin and mucous membranes. It is characterized by the presence of an autoantibody directed against desmoglein 3, which causes acantholysis and blister formation. In this study, we examined the HLA antigens of 30 caucasian argentinian patients compared with 199 controls. We used the PCR-SSO method (Polymerase Chain Reaction-Sequence Specific Oligonucleotide). We found that PV patients had significantly increased frequencies of HLA DR4 (RR = 3.80, P = 0.001) and HLA DR 14 (RR = 5.97, P = 0.0001). As in other populations, two associated alleles were found: the first was DR beta 1*0402 (RR = 44.70, P = 10.7) and DQ beta 1*0302 (RR = 71.82, P = 10(-7)) and the second was DR beta 1*1401 (RR = 117.94, P = 10(-7)) y DQ beta 1*0503 (RR = 86.95, P = 10(-7)).
Lecture Notes in Computer Science, 2003
The efficient parallelization of an algorithm is a hard task that requires a good command of soft... more The efficient parallelization of an algorithm is a hard task that requires a good command of software techniques and a considerable knowledge of the target computer. In such a task, either the programmer or the compiler have to tune different parameters to adapt the algorithm to the computer network topology and the communication libraries, or to expose the data locality of the algorithm on the memory hierarchy at hand.
Pharmacogenetics of Immunosuppressant Polymorphism of CYP3A5 in Renal Transplant Recipients
Transplantation Proceedings, 2010
The tacrolimus is metabolized primarily by CYP3A5, a member of the single nucleotide polymorphism... more The tacrolimus is metabolized primarily by CYP3A5, a member of the single nucleotide polymorphism family. It shows cytochrome P450 (SNP) in intron 3, which consists of a change of base, G for A, producing a stop codon. The result is a nonfunctional protein (allele *3). Allele *1 is the wild type. The patients that show the allelic variant *3 in homozygosis (G/G) are slow metabolizers of the immunosuppressant, increasing its concentration in blood. In contrast, heterozygote A/G alleles *1/*3 are intermediate metabolizers, whereas those of allele *1 in homozygosis (A/A) are normal metabolizers. The aim of this study was to determine CYP 3A5 polymorphism among adult renal transplant recipients and the general Argentinean population. We analyzed 21 recipients and 36 healthy controls. All subjects gave written informed consent approved by the local committee. To determine the polymorphism, we extracted DNA from peripheral blood and used polymerase chain reaction (PCR) to amplify intron 3 of the CYP 3A5. The presence of variant was confirmed by direct sequencing. Among the controls the CYP3A5 genotype *3/*3 (G/G) was detected in 32 individuals, 4 showed *1/*3 (A/G), and none had *1/*1 (A/A); among the recipients, the results were as follows: 18, 2, and 1, respectively. The frequencies of polymorphism in both groups were similar, although they differed from those published for other populations. These results are the basis for the development of a pharmacogenomic program applied to organ transplantation. The genetic polymorphisms can determine responses to drugs. The molecular diagnosis must be transferred to clinical practice so as to guide selection of medicine and drug doses to be optimal for each individual.
Tissue Antigens, 2013
Studies of the effect of minor H antigen mismatching on the outcome of renal transplantation are ... more Studies of the effect of minor H antigen mismatching on the outcome of renal transplantation are scarce and concern mainly single center studies. The International Histocompatibility and Immunogenetics Workshops (IHIW) provide a collaborative platform to execute crucial large studies. In collaboration with 16 laboratories of the IHIW, the role of 15 autosomal, 10 Y-chromosome encoded minor H antigens and 3 CD31 polymorphisms, was investigated in relation to the incidence of renal graft rejection and graft loss in 444 human leukocyte antigens (HLA)-identical sibling renal transplantations. Recipient and donor DNA samples were genotyped for the minor H antigens HA-1, HA-2, HA-3, HA-8, HB-1, ACC-1, ACC-2, SP110, PANE1, UGT2B17, C19Orf48, LB-ECGF-1, CTSH, LRH-1, LB-ADIR and HY. The correlation between minor H antigen mismatch and the primary outcome graft rejection or graft loss was statistically analyzed. The incidence of rejection was very low and no correlation was observed between one or more minor H antigen mismatch(es) and a rejection episode (n = 36), of which only eight resulted in graft loss. In summary, in our study cohort of 444 renal transplants, mismatching for neither autosomal nor HY minor H antigens correlate with rejection episodes or with graft loss.
Hepatology, 1999
The aim of this study was to compare major histocompatibility complex (MHC) class II susceptibili... more The aim of this study was to compare major histocompatibility complex (MHC) class II susceptibility to type 1 autoimmune hepatitis (AH) between children and adults of the same ethnic group. HLA-DRB1, HLA-DRB3, HLA-DQA1, and HLA-DQB1 gene subtypes were examined by high resolution oligonucleotide typing in 122 pediatric (PAH) and 84 adult (AAH) patients and in 208 controls. In children, HLA-DRB1*1301 was the primary susceptibility allele (66.4% patients vs. 10.6% controls, relative risk [RR] ؍ 16.3, Pc F 10 ؊24 ) whereas HLA-DRB1*1302, which differs from HLA-DRB1*1301 by only 1 amino acid, appeared to be protective. The exclusion of individuals with HLA-DRB1*1301 from control and pediatric patients allowed us to find a secondary association of PAH with HLA-DRB1*0301. Possession of HLA-DRB1*1301, however, was associated with a lower therapeutic response rate. Analysis of peptide binding pocket residues indicated that Tyr 10, Ser 11, Ser 13, and Val 86 in the class II  chain were present in 85% of patients compared with 37% of controls, suggesting that a high proportion of AH susceptibility is attributable to these residues (etiologic fraction [EF] ؍ 76%). In contrast to the class II associations in children, AAH was associated with HLA-DRB1*0405 (RR ؍ 10.4, Pc F .005) but not with HLA-DRB1*1301 or HLA-DRB1*0301. In addition, HLA-DR4 with the class I gene, HLA-A11, appeared synergistic in predisposing AAH patients to develop extra-hepatic autoimmune (AI) manifestations (odds ratio [OR] ؍ 104.9, Pc F 10 ؊4 ). Concomitant differences in autoantibody profiles were also observed in PAH versus AAH: smooth muscle antibodies (SMA) were most prevalent in PAH but antinuclear antibodies were most prevalent in AAH (P ؍ .003). This study therefore reveals that different HLA-DRB1 allotypes confer susceptibility to AH in children and adults and raises the possibility that PAH and AAH may be triggered by different factors. (HEPATOLOGY 1999;30:1374-1380
European Journal of Neurology, 2009
Background: The association of multiple sclerosis (MS) with HLA DR subtypes, and particularly hum... more Background: The association of multiple sclerosis (MS) with HLA DR subtypes, and particularly human leukocyte antigen (HLA)-DRB1*15 has been a consistent finding across nearly all Caucasian MS populations. In South America, scarce data exist about this issue. As the complete characterization of the HLA association range around the world is important to understand the role of this locus in MS susceptibility, we analyzed the frequency of HLA-DRB1* allelic groups in an MS population in Argentina. Methods: HLA-DRB1 locus was genotyped using PCR and sequence-specific primer amplification in 61 MS patients born in Buenos Aires, Argentina and 1216 healthy controls. Allele frequencies were compared between groups. Results: The HLA-DRB1*15 allele frequency significantly differed between controls and patients (13.5% and 33.9% respectively, P < 0.001, OR 2.51, 95% CI: 1.7-3.0). The other allele frequencies did not show significant differences between patients and controls. Conclusions: The present HLA class II population study is in accordance with other Caucasian MS surveys which have found that HLA-DRB1*15 allele is strongly associated with MS disease. In Argentina, this is the first study performed to analyze the association of HLA-DRB1*15 and MS susceptibility in a Caucasian population and therefore contributes with new data to the immunogenomic global MS map.
American Journal of Reproductive Immunology, 2004
Is the Paternal Mononuclear Cells' Immunization a Successful Treatment for Recurrent Spontaneous Abortion?
American Journal of Reproductive Immunology, 2000
Alloimmunization as a treatment for recurrent spontaneous abortion (RSA) is still controversial d... more Alloimmunization as a treatment for recurrent spontaneous abortion (RSA) is still controversial due to the lack of enough controls to evaluate its effectiveness. The present study was conducted to compare the live birth rate in the presence or absence of immunotherapy. Ninety-two women with RSA (79 primary [PA] and 13 secondary aborters[SA]) received immunotherapy. Thirty-seven RSA couples not receiving paternal alloimmunization, constituted the &quot;control&quot; group. The pregnancy rate in alloimmunized was 58 vs 46% in the control group. The live birth increased from 71% in the controls to 88% after immunotherapy. The alloimmunization induced mixed lymphocyte reaction blocking factors (MLR BFs) in 79% of women. However, they were also present in 83% of immunized women experiencing a new abortion. These results indicate that alloimmunization may be useful in the treatment of RSA.
BMC Urology, 2015
We produced a novel model of bladder outlet obstruction (BOO) by periurethral injection of hyalur... more We produced a novel model of bladder outlet obstruction (BOO) by periurethral injection of hyaluronic acid and compared the cystometric features, postoperative complications, and histopathological changes of that model with that of traditional open surgery. Methods: Forty female Sprague-Dawley rats were divided into three groups. Fifteen rats were subcutaneously injected with 0.2 ml hyaluronic acid at 5, 7, and 12 o'clock around the urethral orifice. Another fifteen rats underwent traditional open partial proximal urethral obstruction surgery, and 10 normal rats used as controls. After 4 weeks, filling cystometry, postoperative complications, and histopathological features were evaluated in each group. Three rats were also observed for 12 weeks after hyaluronic acid injection to evaluate the long-term effect. Results: Hyaluronic acid periurethral injection caused increased maximum cystometric capacity, maximum bladder pressure, micturition interval, and post-void residual urine volume compared with control (p < 0.01). The injection group had significantly shorter operative time, less incidence of incision infection and bladder stone formation compared with the surgery group (p < 0.01). Hematoxylin and eosin (HE) staining showed suburothelial and interstitial hyperemia edema and smooth muscle hypertrophy in both injection and surgery bladders; these were not observed in the control group. Bladder weight and thickness of smooth muscle in the injection and surgery groups were significantly greater than those in the control group (p < 0.01). Urethral epithelial hyperplasia and lamina propria inflammation were observed in the surgery group but not in the injection or control groups. Rats periurethrally injected hyaluronic acid were stable the compound was not fully absorbed in any rat after 12 weeks. Conclusions: Hyaluronic acid periurethral injection generates a simple, effective, and persistent animal model of BOO with lower complications, compared with traditional surgery.
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Papers by J. González-Larriba