Papers by Javier Hernandez
Not all T cells specific for autoantigens are eliminated in the thymus, and therefore alternate m... more Not all T cells specific for autoantigens are eliminated in the thymus, and therefore alternate mechanisms are required to prevent potentially autoreactive T cells from developing into effectors. Adoptive transfer of CD8 ϩ T cells from influenza hemagglutinin-specific Clone 4 TCR transgenic mice into mice that express hemagluttinin in the pancreatic islets results in tolerance. This is preceded by activation of Clone 4 T cells that encounter antigen cross-presented in the draining lymph nodes of the pancreas. In this report we compare the phenotype, function, and costimulatory requirements of Clone 4 T cells activated by endogenous self-antigen, with Clone 4 T cells stimulated by influenza virus. The cells undergoing tolerance upregulate both CD69 and CD44, yet only partially downregulate CD62L, and do not express CD49d or CD25. Most importantly, they lack the ability to produce interferon-␥ in response to antigen and show no cytolytic activity. Clone 4 T cells disappear after several cycles of division, apparently without leaving the site of initial activation. Surprisingly, despite the fact that such stimulation occurs through recognition of antigen that is cross-presented by a professional antigenpresenting cell, we find this activation is not dependent on costimulation through CD28. These data demonstrate that the recognition by naive CD8 ϩ T cells of cross-presented selfantigen results in localized proliferation and deletion, without the production of effector cells.
Urology, 2006
Objectives. To evaluate the recently developed Prostate Cancer Prevention Trial (PCPT) prostate c... more Objectives. To evaluate the recently developed Prostate Cancer Prevention Trial (PCPT) prostate cancer risk calculator in the San Antonio Center of Biomarkers of Risk for Prostate Cancer (SABOR) cohort of the Early Detection Research Network, a younger and more ethnically diverse population than that in the PCPT. Methods. From 3488 SABOR participants, we identified 446 who had undergone prostate biopsy and had undergone prostate-specific antigen measurement and digital rectal examination before biopsy. Most biopsies were performed for abnormal digital rectal examination findings, a prostate-specific antigen level of more than 2.5 ng/mL, or elevated risk because of a first-degree relative with prostate cancer. We evaluated the operating characteristics of the PCPT calculator for detecting prostate cancer in this cohort of SABOR participants. Of the 446 men in this cohort, 24% were younger than 55 years of age. Results. Of the 446 men who had undergone biopsy, 148 (33.2%) had prostate cancer. The observed SABOR prostate cancer rates increased with increasing PCPT risk: 15.7%, 39.0%, 48.8%, and 100.0% for a PCPT risk calculator value of less than 25%, 25% to 50%, 50% to 75%, and greater than 75%, respectively. The PCPT risk calculator had an area under the receiver operating characteristic curve of 65.5% (95% confidence interval 60.2% to 70.8%, P Ͻ0.0001), was greater in African-American men (area under curve of 80.0%, 95% confidence interval 67.8% to 92.2%) than in other races (P ϭ 0.02), and was not different in Hispanic men (P Ͼ0.05). Conclusions. The results of our study have shown that the PCPT risk calculator, available from the Internet and incorporating the current best panel of risk factors, is valid in other, more diverse, populations. UROLOGY 68: [1152][1153][1154][1155] 2006. Published by Elsevier Inc.
Research in Microbiology, 1995
The polymerase chain reaction (PCR) technique was used to obtain randomly amplified polymorphic D... more The polymerase chain reaction (PCR) technique was used to obtain randomly amplified polymorphic DNA (RAPID) profiles from 64 type and serotype reference strains and 114 isolates of Campylobacterjejuniand C. colifrom food, seawater and human faeces, Genetic diversity was detected among the strains as a total of 118 different RAPID profiles were obtained, each one containing from 4 to 11 bands between 0.30 and 1.50 ld). The discriminatory power of a random 10-mer primer (sequence 5'-CAATCGCCGT~3") was assessed. In general, no profiles were common to strains of the same Penner serogroup, but occasional strains from different Penner serotypes shared identical band profiles, RAPID analysis also differentiated between the species, and after numerical analysis, five main clusters were defined at the 40 % similarity level, corresponding to C. jejuni, C. co/i and C./at/with some exceptions. RAPD profiling of Campy/obeyer is highly discriminatory and is a valuable new alternative to traditional typing in epidem-iok~ stud, s.
Epidemiology and Infection, 1993
Ribosomal RNA gene patterns, randomly amplified polymorphic genomic DNA (RAPD) profiles and plasm... more Ribosomal RNA gene patterns, randomly amplified polymorphic genomic DNA (RAPD) profiles and plasmid profiles were used to discriminate between 28 strains of Campylobacterjejuni serogroups 01 and 02 (Penner). Most isolates were biotype I (Lior). The strains were representative isolates from a UK school outbreak of enteritis (7 cases) and from 21 sporadic human cases of enteritis in 4 countries. The molecular techniques discriminated to various degrees between strains in each of the serogroups. The outbreak strains were homogeneous in most molecular features but a variety of types was detected amongst the isolates from the sporadic cases. Five groups of two or more strains with identical ribopatterns were identified and within each, strains from different patients were homogenous with respect to serogroup. RAPD profile typing based on numerical analysis generally matched ribotyping. Plasmid profiling overall gave least discrimination but was useful in separating some strains similar in other features. We concluded that optimal discrimination of C. jejuni could best be achieved using a combination of phenotypic and genotypic properties. Hae III ribotyping was the single most discriminatory and reproducible technique investigated. Several strains of C. jejuni from sporadic infections had similar molecular profiles which have potential for general typing purposes.
Epidemiology and Infection, 1990
DNA restriction endonuclease (Hae III and Hind III) total digest and 16S and 23S ribosomal (r)RNA... more DNA restriction endonuclease (Hae III and Hind III) total digest and 16S and 23S ribosomal (r)RNA gene patterns (ribopatterns) were determined for 18 isolates of Campylobacter jejuni from three separate outbreaks of diarrhoea in the north of England. Strains were also characterized by biotyping, serotyping and phage typing. Comparisons of the DNA patterns by visual and numerical methods revealed five distinct strain groupings with clear differences between isolates from different outbreaks as well as some heterogeneity between strains within the community outbreak and one of the school outbreaks. An excellent correlation was observed between the genomic DNA fingerprints data and the Preston bacteriophage group, both of which gave better discrimination than biotyping and serotyping alone or in combination. Only one phage group (PG 37) was not confirmed by the DNA data. DNA fingerprints therefore provide additional information of value in studying the epidemiology of outbreaks of C. jejuni.
Journal of Urology, 2004
Hormonal therapy (HT) is the current mainstay of systemic treatment for prostate specific antigen... more Hormonal therapy (HT) is the current mainstay of systemic treatment for prostate specific antigen (PSA) only recurrence (PSAR), however, there is virtually no published literature comparing HT to observation in the clinical setting. The goal of this study was to examine the Department of Defense Center for Prostate Disease Research observational database to compare clinical outcomes in men who experienced PSAR after radical prostatectomy by early versus delayed use of HT and by a risk stratified approach. Of 5,382 men in the database who underwent primary radical prostatectomy (RP), 4,967 patients were treated in the PSA-era between 1988 and December 2002. Of those patients 1,352 men who had PSAR (PSA after surgery greater than 0.2 ng/ml) and had postoperative followup greater than 6 months were used as the study cohort. These patients were further divided into an early HT group in which patients (355) received HT after PSA only recurrence but before clinical metastasis and a late HT group for patients (997) who received no HT before clinical metastasis or by current followup. The primary end point was the development of clinical metastases. Of the 1,352 patients with PSAR clinical metastases developed in 103 (7.6%). Patients were also stratified by surgical Gleason sum, PSA doubling time and timing of recurrence. Univariate and multivariate Cox proportional hazard models were used to evaluate the effect of early and late HT on clinical outcome. Early HT was associated with delayed clinical metastasis in patients with a pathological Gleason sum greater than 7 or PSA doubling time of 12 months or less (Hazards ratio = 2.12, p = 0.01). However, in the overall cohort early HT did not impact clinical metastases. Race, age at RP and PSA at diagnosis had no effect on metastasis-free survival (p >0.05). The retrospective observational multicenter database analysis demonstrated that early HT administered for PSAR after prior RP was an independent predictor of delayed clinical metastases only for high-risk cases at the current followup. Further study with longer followup and randomized trials are needed to address this important issue.
Journal of Urology, 2007
were done to derive outcome reporting (efficacy or side effects) for the treatment of clinical st... more were done to derive outcome reporting (efficacy or side effects) for the treatment of clinical stage T1 or T2 N0M0 prostate cancer. A database was constructed containing descriptions relating to erectile function as well as numerical frequency rates of complete erectile dysfunction, and partial and intact erectile function for various treatments. A literature review was also done, consisting of a PubMed Services search of current measures and protocols used for assessing erectile function outcomes and a survey of consensus opinion sources on the management of male sexual dysfunctions. Results: Based on inclusion criteria 436 articles were selected. Of these articles database extraction from 100 pertaining to radical prostatectomy garnered various characterizations of erectile function, including qualitative descriptions, generic terminology and rating systems. Database extraction from 31 articles, in which results for at least 50 patients were reported, yielded ranges of rates for complete erectile dysfunction, partial erectile function and intact erectile function that were 26% to 100%, 16% to 48% and 9% to 86% for radical prostatectomy, 8% to 85%, 21% to 47% and 36% to 63% for external beam radiation, and 14% to 61%, 21% and 18% for interstitial radiation, respectively. The literature review showed an evolution in standards for studying and reporting erectile function outcomes. Conclusions: Clinical studies reporting erectile function outcomes after localized prostate cancer treatment often demonstrate poorly interpretable and inconsistent manners of assessment as well as widely disparate rates of erectile dysfunction and erectile function. Future studies must apply scientifically rigorous methodology and standard outcomes measures to advance this field of study.
Journal of Urology, 2007
The American Urological Association Prostate Guideline Update Panel was charged with updating the... more The American Urological Association Prostate Guideline Update Panel was charged with updating the Guidelines for Clinically Localized Prostate Cancer. In assessing outcomes with treatment, it became apparent that a highly variable number of definitions exist with respect to biochemical recurrence. Herein, we review the variability in published definitions of biochemical recurrence and make recommendations directed toward improving this terminology by recommending a standard definition in patients treated with radical prostatectomy.Four PubMed® literature searches were performed between May 2001 and April, 2004 and covered articles published from 1991 through early 2004. The search terms included the MeSH® major headings of prostate cancer and prostatic neoplasm. All potentially relevant articles were retrieved and a more detailed screen for relevance was performed. An article was considered relevant if it reported treatment outcomes of patients with clinical T1 or T2N0M0 prostate cancer. Data extractors recorded the definition of biochemical recurrence and definitions were then collapsed into categories representing the same criteria. The results of biochemical failure were subcategorized by initial treatment.Of 13,800 citations, a total of 436 articles were selected. Among these, a total of 145 articles contained 53 different definitions of biochemical recurrence for those treated with radical prostatectomy. Of these, the most common definition (35) was a prostate specific antigen of >0.2 ng/mL or a slight variation thereof. In addition, a total of 208 articles reported 99 different definitions of biochemical failure among those treated with radiation therapy. Of these, the American Society for Therapeutic Radiology and Oncology definition (70) and/or a variation thereof was the most commonly reported. In total, 166 different definitions of biochemical failure were identified. Following radical prostatectomy, the Panel recommends defining biochemical recurrence as an initial serum prostate specific antigen of ≥0.2 ng/mL, with a second confirmatory level of prostate specific antigen of >0.2 ng/mL. The Panel recommends the use of the American Society for Therapeutic Radiology and Oncology criteria for patients treated with radiation therapy and acknowledges that these criteria will soon be updated although not yet published.A high degree of variability in the definition of biochemical recurrence exists following treatment for localized prostate cancer. Strict definitions for biochemical recurrence are necessary to identify men at risk for disease progression and to allow meaningful comparisons among patients treated similarly. The Panel acknowledges the American Society for Therapeutic Radiology and Oncology criteria and future modifications thereof for those receiving radiation therapy and recommends the newly developed American Urological Association criteria for those treated with radical prostatectomy. The purpose for the establishment of this standard is for data reporting purposes and for comparison of similarly treated patients. It is not intended to represent a threshold value for which to initiate treatment. The Panel acknowledges that the clinical decision to initiate treatment will be dependent on multiple factors including patient and physician interaction rather than a specific prostate specific antigen threshold value.
Cancer, 2005
BACKGROUNDRecent studies of men with prostate carcinoma suggest that obesity may be associated wi... more BACKGROUNDRecent studies of men with prostate carcinoma suggest that obesity may be associated with more advanced-stage disease and lower overall survival rates. One possible link between body mass index (BMI) and prostate carcinoma prognosis may be disease ascertainment. Prostate-specific antigen (PSA) is widely used to screen for prostate carcinoma.Recent studies of men with prostate carcinoma suggest that obesity may be associated with more advanced-stage disease and lower overall survival rates. One possible link between body mass index (BMI) and prostate carcinoma prognosis may be disease ascertainment. Prostate-specific antigen (PSA) is widely used to screen for prostate carcinoma.METHODSThe authors examined the association between BMI and PSA in a population-based study of 2779 men without prostate carcinoma. Between 2001 and 2004, these men were enrolled in a study sponsored by the San Antonio Center of Biomarkers of Risk, a clinical and epidemiologic center of the Early Detection Research Network of the National Cancer Institute.The authors examined the association between BMI and PSA in a population-based study of 2779 men without prostate carcinoma. Between 2001 and 2004, these men were enrolled in a study sponsored by the San Antonio Center of Biomarkers of Risk, a clinical and epidemiologic center of the Early Detection Research Network of the National Cancer Institute.RESULTSThe mean PSA value decreased in a linear fashion with an increase in BMI category, from 1.01 ng/mL in normal weight men to 0.69 ng/mL in obese (Class III) men, after adjusting for race/ethnicity and age.The mean PSA value decreased in a linear fashion with an increase in BMI category, from 1.01 ng/mL in normal weight men to 0.69 ng/mL in obese (Class III) men, after adjusting for race/ethnicity and age.CONCLUSIONSLower levels of PSA in obese and overweight men could mask biologically consequential prostate carcinoma. Cancer 2005. Published 2005 by the American Cancer Society.Lower levels of PSA in obese and overweight men could mask biologically consequential prostate carcinoma. Cancer 2005. Published 2005 by the American Cancer Society.
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Papers by Javier Hernandez