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Richard B Alexander

Publications and source records attributed to Richard B Alexander.

18 recordsLinked to original sources
PubMed2006

Activation of innate immunity by prostate specific antigen (PSA).

BACKGROUND: Prostate specific antigen (PSA) is a serine protease secreted by the prostatic epithelium. The only known function of the protein is to cleave seminogelin. We wished to determine if PSA activated peripheral blood mononuclear cells (PBMC). METHODS: PBMC and selected sub-populations were cultured with purified PSA. Secretion of IFNgamma was measured by cytokine capture flow cytometry and enzyme-linked immunosorbent assay. RESULTS: We observed secretion of IFNgamma and a proliferative response in PBMC cultured with PSA. We found that NK cells were the source of the IFNgamma but NK cells were not directly stimulated by PSA. Rather, a soluble factor secreted primarily by CD14 monocytes in response to PSA stimulated NK cells to secrete IFNgamma. DISCUSSION: PSA induces a pro-inflammatory response that results in the secretion of INFgamma by NK cells. The presence of large amounts of PSA could contribute to the common finding of inflammatory infiltrates in the prostate.

Cell Proliferation↗
PubMed2006

Prostate-specific antigen test in diagnostic evaluation of chronic prostatitis/chronic pelvic pain syndrome.

OBJECTIVES: To determine whether prostate-specific antigen (PSA), the percent free PSA, or free PSA isoforms may be used as diagnostic markers for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS; National Institutes of Health category IIIa and IIIb). METHODS: We evaluated 421 patients enrolled in the Chronic Prostatitis Cohort Study and 112 age-matched controls. Subjects were stratified by the number of white blood cells (WBCs) in their expressed prostatic secretions and pain as determined by the National Institutes of Health Chronic Prostatitis Symptom Index. RESULTS: Total PSA, free PSA, and [-2]proPSA ([-2]pPSA) were significantly elevated in those with CP/CPPS compared with controls (mean PSA 1.97 ng/mL versus 1.72 ng/mL, P = 0.03; mean free PSA 0.76 ng/mL versus 0.70 ng/mL, P = 0.01; and [-2]pPSA 2.38 ng/mL versus 1.80 ng/mL, P = 0.04). The percent free PSA was not significantly different between the patients and controls. For those with CP/CPPS, the percent free PSA was significantly lower as the WBC count rose in the expressed prostatic secretions (0 WBCs = 43.29 versus more than 25 WBCs = 26.52; P < .0001). A PSA level of 4.0 ng/mL or greater was found in 10% of patients and 7% of controls (P = 0.03). CONCLUSIONS: Men with elevated PSA values and CP/CPPS should be treated as one would any other patient screened for prostate cancer with an elevated PSA level. Although PSA, free PSA, and [-2]pPSA were slightly elevated in men with CP/CPPS, the low sensitivity and specificity do not warrant using them as biomarkers for CP/CPPS.

Biomarkers↗
PubMed2006

Catastrophizing and pain-contingent rest predict patient adjustment in men with chronic prostatitis/chronic pelvic pain syndrome.

UNLABELLED: Cognitive/behavioral and environmental variables are significant predictors of patient adjustment in chronic pain. Using a biopsychosocial template and selecting several pain-relevant constructs from physical, cognitive/behavioral, and environmental predictors, outcomes of pain and disability in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) were explored. Men (n = 253) from a North American multi-institutional NIH-funded Chronic Prostatitis Cohort Study in 6 US and 1 Canadian centers participated in a survey examining pain and disability. Measures included demographics, urinary symptoms, depression, pain, disability, catastrophizing, control over pain, pain-contingent rest, social support, and solicitous responses from a significant other. Regressions showed that urinary symptoms (beta = .20), depression (beta = .24), and helplessness catastrophizing (beta = .29) predicted overall pain. Further, affective pain was predicted by depression (beta = .39) and helplessness catastrophizing (beta = .44), whereas sensory pain was predicted by urinary symptoms (beta = .25) and helplessness catastrophizing (beta = .37). With regard to disability, urinary symptoms (beta = .17), pain (beta = .21), and pain-contingent rest (beta = .33) were the predictors. These results suggest cognitive/behavioral variables (ie, catastrophizing, pain-contingent rest) may have significant impact on patient adjustment in CP/CPPS. Findings support the need for greater research of such pain-related variables in CP/CPPS. PERSPECTIVE: This article explores predictors of patient adjustment in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Cognitive/behavioral variables of catastrophizing and pain-contingent rest respectively predicted greater pain and disability. Catastrophic helplessness was a prominent pain predictor. These findings inform clinicians and researchers on several new variables in CP/CPPS outcomes and suggest future research.

Adaptation, Psychological↗
PubMed2006

How does the pre-massage and post-massage 2-glass test compare to the Meares-Stamey 4-glass test in men with chronic prostatitis/chronic pelvic pain syndrome?

PURPOSE: The Meares-Stamey 4-glass test is the standard method of assessing inflammation and the presence of bacteria in the lower urinary tract in men presenting with the chronic prostatitis syndrome. However, most urologists do not use it in daily practice because of the time and difficulty in performing it, as well as the additional expense. We evaluated a simpler test, the 2-glass pre-massage and post-massage test, and compared it with the Meares-Stamey 4-glass test to detect inflammation and bacteria in men with chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS: The study population included 353 men enrolled in the National Institutes of Health Chronic Prostatitis Cohort study with baseline leukocyte counts and 2-day bacterial cultures on specimens obtained from a standard 4-glass test (VB1, VB2, expressed prostatic secretions, VB3). The chi-square test was performed to assess associations of white blood cell counts in expressed prostatic secretions and VB3. A receiver operating characteristic curve was constructed to determine the optimal cut point of white blood cells in VB3 in predicting white blood cells in expressed prostatic secretions. Sensitivity and specificity of VB3 cultures predicting expressed prostatic secretions and positive Meares-Stamey results were calculated from 2 x 2 contingency tables. RESULTS: Analysis of binary leukocyte outcomes (no white blood cells vs any white blood cells) suggests that white blood cells tend to be present in expressed prostatic secretions when there are any white blood cells in VB3, p <0.0001, the optimal cut point being white blood cell counts of 3 in VB3 (best predictive ability with area under ROC 0.771) to predict 5+ in expressed prostatic secretions with a sensitivity of 76% and specificity of 70%. The optimal cut point of white blood cells in VB3 to predict 10 white blood cells in expressed prostatic secretions was 4 (62% sensitivity and 75% specificity). Uropathogens localizing to expressed prostatic secretions or VB3 confirms a positive 4-glass Meares-Stamey localization test. The sensitivity and specificity of a VB3 localizing culture only in predicting a positive Meares-Stamey 4-glass test result for any uropathogen were 44% to 54% (depending on definition) and 100%, respectively. The pre-massage and post-massage test predicted a correct diagnosis in more than 96% of subjects. CONCLUSIONS: The value of localizing leukocytes and uropathogens to prostate specific specimens remains controversial in chronic heavily pretreated patients, but these data may help direct therapy (anti-inflammatory or antimicrobial) when obtained at first presentation. The pre-massage and post-massage test has strong concordance with the 4-glass test and is a reasonable alternative when expressed prostatic secretions are not obtained.

Bacteria↗
PubMed2006

Modeling denitrification in terrestrial and aquatic ecosystems at regional scales.

Quantifying where, when, and how much denitrification occurs on the basis of measurements alone remains particularly vexing at virtually all spatial scales. As a result, models have become essential tools for integrating current understanding of the processes that control denitrification with measurements of rate-controlling properties so that the permanent losses of N within landscapes can be quantified at watershed and regional scales. In this paper, we describe commonly used approaches for modeling denitrification and N cycling processes in terrestrial and aquatic ecosystems based on selected examples from the literature. We highlight future needs for developing complementary measurements and models of denitrification. Most of the approaches described here do not explicitly simulate microbial dynamics, but make predictions by representing the environmental conditions where denitrification is expected to occur, based on conceptualizations of the N cycle and empirical data from field and laboratory investigations of the dominant process controls. Models of denitrification in terrestrial ecosystems include generally similar rate-controlling variables, but vary in their complexity of the descriptions of natural and human-related properties of the landscape, reflecting a range of scientific and management perspectives. Models of denitrification in aquatic ecosystems range in complexity from highly detailed mechanistic simulations of the N cycle to simpler source-transport models of aggregate N removal processes estimated with empirical functions, though all estimate aquatic N removal using first-order reaction rate or mass-transfer rate expressions. Both the terrestrial and aquatic modeling approaches considered here generally indicate that denitrification is an important and highly substantial component of the N cycle over large spatial scales. However, the uncertainties of model predictions are large. Future progress will be linked to advances in field measurements, spatial databases, and model structures.

Agriculture↗
PubMed2005

Identification of HLA-DRB1*1501-restricted T-cell epitopes from prostate-specific antigen.

The development of immunotherapy for prostate cancer based on the induction of autoimmunity to prostate tissue is very attractive because prostate is not a vital organ beyond the reproductive years. CD4 T cells play an important role in the development of antitumor immune responses, yet the identification of naturally processed MHC Class II-restricted epitopes derived from prostate differentiation antigens has not been described. To facilitate the search for prostate-specific antigen (PSA)-derived MHC class II-restricted peptides, we immunized mice transgenic for HLA-DRB1*1501 with human PSA and showed a robust dose-dependent immune response to the antigen. Screening a library of overlapping 20-mer peptides that span the entire PSA sequence identified two 20-mer peptides, PSA(171-190) and PSA(221-240), which were responsible for this reactivity. Immunization of DR2b transgenic mice with these peptides induced specific responses to the peptide and whole PSA. Identified peptides were used to stimulate CD4 T cells from HLA-DRB1*1501+ patients with a rare condition, granulomatous prostatitis, and who seem to have a preexisting immune response directed against the prostate gland. We previously showed a linkage of granulomatous prostatitis to HLA-DRB1*1501, suggesting that this disease may have an autoimmune etiology. Peptide-specific CD4 T-cell lines were generated from the peripheral blood of these patients as well as one patient with prostate cancer. These lines also recognized whole, processed PSA in the context of HLA-DRB1*1501. This study will be instrumental in understanding the interaction between circulating self-reactive T cells, organ-specific autoimmunity, and antitumor immune response. The use of these peptides for the immunotherapy of prostate cancer is under investigation.

Amino Acid Sequence↗
PubMed2004

Ciprofloxacin or tamsulosin in men with chronic prostatitis/chronic pelvic pain syndrome: a randomized, double-blind trial.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in men is principally defined by pain in the pelvic region lasting more than 3 months. No cause of the disease has been established, and therapies are empirical and mostly untested. Antimicrobial agents and alpha-adrenergic receptor blockers are frequently used. OBJECTIVE: To determine whether 6-week therapy with ciprofloxacin or tamsulosin is more effective than placebo at improving symptoms in men with refractory, long-standing CP/CPPS. DESIGN: Randomized, double-blind trial with a 2 x 2 factorial design comparing 6 weeks of therapy with ciprofloxacin, tamsulosin, both drugs, or placebo. SETTING: Urology outpatient clinics at 10 tertiary care medical centers in North America. PATIENTS: Patients were identified from referral-based practices of urologists. One hundred ninety-six men with a National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score of at least 15 and a mean of 6.2 years of symptoms were enrolled. Patients had received substantial previous treatment. MEASUREMENTS: The authors evaluated NIH-CPSI total score and subscores, patient-reported global response assessment, a generic measure of quality of life, and adverse events. INTERVENTIONS: Ciprofloxacin, 500 mg twice daily; tamsulosin, 0.4 mg once daily; a combination of the 2 drugs; or placebo. RESULTS: The NIH-CPSI total score decreased modestly in all treatment groups. No statistically significant difference in the primary outcome was seen for ciprofloxacin versus no ciprofloxacin (P = 0.15) or tamsulosin versus no tamsulosin (P > 0.2). Treatments also did not differ significantly for any of the secondary outcomes. LIMITATIONS: Treatment lasting longer than 6 weeks was not tested. Patients who had received less pretreatment may have responded differently. CONCLUSION: Ciprofloxacin and tamsulosin did not substantially reduce symptoms in men with long-standing CP/CPPS who had at least moderate symptoms.

Adrenergic alpha-Antagonists↗
PubMed2004

Granulomatous prostatitis linked to HLA-DRB1*1501.

PURPOSE: Granulomatous prostatitis is characterized by a pattern of granulomatous inflammation in the prostate. In most cases the etiology is unknown. Based on the hypothesis that granulomatous prostatitis may be an autoimmune disease we performed intermediate and selective high resolution typing of HLA-DR in a group of patients with the disease and compared the frequency of class II HLA phenotypes to that in a control group of volunteer marrow donors in the military. MATERIALS AND METHODS: Histological records from 1 institution from 1990 to 2000 revealed 12 patients with diffuse granulomatous prostatitis. Three patients were dead and 1 refused blood drawing. Peripheral blood from the remaining 8 patients was typed along with blood from an additional 3 identified at the practice of one of us from 1999 through 2002. All slides were reviewed by 1 pathologist. Intermediate resolution typing of HLA-A, B and DR was performed by polymerase chain reaction-sequence specific oligonucleotide probe. High resolution, allele specific identification of HLA DR15 was performed if patients were DR15 positive by intermediate resolution typing. RESULTS: There were 3 black and 8 white individuals identified with diffuse nonspecific granulomatous prostatitis. Six of 8 white patients (75%) were HLA-DR15 by intermediate resolution typing. One of the 3 black American patients (33%) was HLA-DR15. In the control group 127 of 451 white (28.2%) and 23 of 89 black (25.8%) volunteer marrow donors were HLA-DR15. The case-control comparison of white patients was significantly different (Fisher's exact test p = 0.0086). There were no statistically significant differences between case-control comparisons for any other HLA-DR phenotype. High resolution DR15 typing showed that the white patients were HLA-DRB1*1501 and the black patient was HLA-DRB1*1503. CONCLUSIONS: The data suggest an association between HLA-DRB1*1501 and granulomatous prostatitis. HLA-DR15 is strongly associated with other autoimmune diseases, notably multiple sclerosis. The data are consistent with an autoimmune etiology for nonspecific granulomatous prostatitis.

Aged↗
PubMed2003

Natural background concentrations of nutrients in streams and rivers of the conterminous United States.

Determining natural background concentrations of nutrients in watersheds in the developed world has been hampered by a lack of pristine sampling sites covering a range of climatic conditions and basin sizes. Using data from 63 minimally impacted U.S. Geological Survey reference basins, we developed empirical models of the background yield of total nitrogen (TN) and total phosphorus (TP) from small watersheds as functions of annual runoff, basin size, atmospheric nitrogen deposition rate, and region-specific factors. We applied previously estimated in-stream loss rates to yields from the small watershed models to obtain estimates of background TN and TP yield and concentration throughout the stream/river network in 14 ecoregions of the conterminous United States. Background TN concentration varies from less than 0.02 mg L(-1) in the xeric west to more than 0.5 mg L(-1) along the southeastern coastal plain. Background TP concentration varies from less than 0.006 mg L-(1) in the xeric west to more than 0.08 mg L(-1) in the great plains. TN concentrations in U.S. streams and rivers currently exceed natural background levels by a much larger factor (6.4) than do TP concentrations (2.0). Because of local variation in runoff and other factors, the range of background nutrient concentrations is very large within some nutrient ecoregions. It is likely that background concentrations in some streams in these regions exceed proposed nutrient criteria.

Climate↗
PubMed2003

Leukocytes and bacteria in men with chronic prostatitis/chronic pelvic pain syndrome compared to asymptomatic controls.

PURPOSE: Chronic prostatitis has been traditionally characterized by inflammation and/or infection of the prostate gland, objectively categorized by white blood cells and cultured bacteria in prostate specific specimens. We compared leukocyte counts and localization rates for bacterial cultures of segmented urine samples (VB1, VB2, VB3), expressed prostatic secretion (EPS) and semen in men diagnosed with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) to men without pelvic pain (controls). MATERIALS AND METHODS: A total of 463 men enrolled in the National Institutes of Health Chronic Prostatitis Cohort study and 121 age matched men without urinary symptoms had leukocyte counts performed and 5-day bacterial cultures on specimens obtained from a standard 4-glass test (VB1, VB2, EPS, VB3) and semen. All risk factor comparisons between case and control analyses were tested using generalized Mantel-Haenszel methods, and multivariable models were developed using logistic regression methods, adjusting for clustering by clinical center within both methods. RESULTS: Men with CP/CPPS had statistically higher leukocyte counts in all segmented urine samples and EPS, but not in semen compared to asymptomatic control men. However, the control population also had a high prevalence of leukocytes. Of the men with CP/CPPS 50% and 32% had 5 or more, or 10 or more white blood cells (WBCs) per high power field, respectively, in EPS compared to 40% and 20% of the control population. Similarly, 32% and 14% of the patients with CP/CPPS had 5 or more, or 10 or more WBCs per high power field in VB3 compared to 19% and 11% in the control population. Localization of uropathogenic bacteria in EPS, VB3 and/or semen was similar in men with CP/CPPS (8.0%) and asymptomatic men (8.3%). CONCLUSIONS: Men with CP/CPPS have significantly higher leukocyte counts in all segmented urine samples and EPS but not in semen as compared to controls. There is no difference in rates of localization of bacterial cultures for men with CP/CPPS compared to control men. The high prevalence of WBCs and positive bacterial cultures in the asymptomatic control population raises questions about the clinical usefulness of the standard 4-glass test as a diagnostic tool in men with CP/CPPS.

Adult↗
PubMed2002

Magnetic resonance spectroscopic imaging-guided brachytherapy for localized prostate cancer.

PURPOSE: Prostate brachytherapy (PB) entails the placement of radioactive sources throughout the entire prostate gland to treat localized cancer. Typically, the target volume in PB encompasses the entire prostate gland because of the inability to localize the cancer and the multifocal nature of this malignancy. However, because of the unique biochemical nature of the prostate gland, recent advances in magnetic resonance spectroscopic imaging (MRSI) of the prostate have allowed precise delineation of the cancer location within the prostate gland. This report reveals our initial experience of MRSI-guided PB. METHODS: A MRSI study was obtained in 15 localized prostate cancer patients before their scheduled PB. The results of this study were used to internally map 7 x 7 x 9-mm volumes of prostate tissue to assign cancerous areas a higher dose of radiation. Such tumor-bearing areas had a low citrate/(choline+creatine) ratio consistent with cancer. On the basis of the anatomic MRI and MRSI correlation, three-dimensional coordinates were assigned to the locations of MRSI-defined cancer. The entire target volume was treated to a standard prescription dose using I-125 or Pd-103. Abnormal citrate regions, termed the biologic tumor volume, were prescribed a dose of 130% of the target volume dose to dose escalate in the abnormal citrate regions while respecting the normal radiation tolerances of the surrounding areas. Three-dimensional treatment planning was used to perform the implant. RESULTS: Of the 15 prostate cancer patients evaluated, all had successful three-dimensional MRSI acquisition before their scheduled PB procedure. In 14 of the 15 patients planned with MRSI, the data were successfully incorporated into their treatment planning and were used to increase the radiation dose prescription to 130% in the MRSI-defined volumes. In 1 patient, MRSI revealed significant background artifact that made a focal boost impractical. Postimplant dosimetry confirmed a median V100 of 95% (range 72%-100%) in the 15 evaluated patients for the prescription dose. Furthermore, the median BTV100 for the abnormal citrate region was 90% (range 80-100%) as determined by postimplant dosimetry. Urethral and rectal dose-volume histograms were within normal limits. Morbidity was comparable with that for conventionally treated patients. CONCLUSION: MRSI offers a promising new approach for the delivery of ionizing radiation in PB. Although this series was small and with a short follow-up, MRSI-guided implants are feasible and warrant further investigation as a means of improving the therapeutic ratio in PB [corrected].

Aged↗
PubMed2002

Leukocyte and bacterial counts do not correlate with severity of symptoms in men with chronic prostatitis: the National Institutes of Health Chronic Prostatitis Cohort Study.

PURPOSE: We examine whether leukocytes and bacteria correlate with symptom severity in men with chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS: All 488 men screened into the National Institutes of Health Chronic Prostatitis Cohort Study before close of recruitment on August 22, 2001 were selected for analysis. The National Institutes of Health Chronic Prostatitis Symptom Index, including subscores, were used to measure symptoms. Urethral inflammation was defined as white blood cell (WBC) counts of 1 or more (1+) in the first voided urine. Participants were classified as category IIIa based on WBC counts of 5 or more, or 10 or more (5+, 10+) in the expressed prostatic secretion, or 1+ or 5+ either in the post-expressed prostatic secretion urine (voided urine 3) or semen. Uropathogens were classified as localizing if the designated bacterial species were absent in voided urine 1 and voided urine 2 but present in expressed prostatic secretion, voided urine 3 or semen, or present in expressed prostatic secretion, voided urine 3 or semen at 2 log concentrations higher than at voided urine 1 or 2. Associations between symptoms, and inflammation and infection were investigated using generalized Mantel-Haenszel methods. RESULTS: Of all participants 50% had urethral leukocytes and of 397 with expressed prostatic secretion samples 194 (49%) and 122 (31%) had 5+ or 10+ WBCs in expressed prostatic secretion, respectively. The prevalence of category IIIa ranged from 90% to 54%, depending on the composite set of cut points. None of the index measures were statistically different (p >0.10) for selected leukocytosis subgroups. Based on prostate and semen cultures, 37 of 488 men (8%) had at least 1 localizing uropathogen. None of the index measures were statistically different (p >0.10) for selected bacterial culture subgroups. CONCLUSIONS: Although men with chronic prostatitis routinely receive anti-inflammatory and antimicrobial therapy, we found that leukocytes and bacterial counts as we defined them do not correlate with severity of symptoms. These findings suggest that factors other than leukocytes and bacteria also contribute to symptoms associated with chronic pelvic pain syndrome.

Chronic Disease↗
PubMed2002

Design of a multicenter randomized clinical trial for chronic prostatitis/chronic pelvic pain syndrome.

OBJECTIVES: To describe the study design and rationale for the first placebo-controlled, randomized clinical trial to be conducted by the Chronic Prostatitis Collaborative Research Network sponsored by the National Institutes of Health. METHODS: The clinical trial will use a 2 by 2 factorial design to evaluate four treatments: placebo, tamsulosin hydrochloride alone, ciprofloxacin alone, and tamsulosin hydrochloride and ciprofloxacin combined. The primary objectives are to compare the efficacy and safety endpoints in patients with chronic prostatitis/chronic pelvic pain syndrome. The study population consists of men with symptoms of discomfort or pain in the pelvic region for at least a 3-month period. One hundred eighty-four participants will be treated for 6 weeks and followed up for an additional 6 weeks. The primary endpoint is the change in the overall National Institutes of Health Chronic Prostatitis Symptom Index from baseline to 6 weeks. Secondary endpoints include a patient-reported global assessment of response and white blood cell counts and cultures in urine, expressed prostatic secretions, and semen. The evaluation of changes from 6 to 12 weeks will be used to assess the durability of the response. RESULTS: This trial was opened to enrollment in July 2001. The study is expected to require 14 months of accrual and follow-up. CONCLUSIONS: The issues considered in the design of this clinical trial may provide guidelines for future clinical trials in chronic prostatitis/chronic pelvic pain syndrome.

Adrenergic alpha-Antagonists↗
PubMed2002

Demographic and clinical characteristics of men with chronic prostatitis: the national institutes of health chronic prostatitis cohort study.

PURPOSE: We describe the study design of the National Institutes of Health Chronic Prostatitis Cohort (CPC) study characterizing men with chronic prostatitis/the chronic pelvic pain syndrome. MATERIALS AND METHODS: All 488 men screened into the CPC study before close of recruitment on August 22, 2001 were selected for analysis. The National Institutes of Health Chronic Prostatitis Symptom Index, including subscores, was used to measure symptoms. A comprehensive history, physical examination and demographic profile were obtained from each participant. Generalized Mantel-Haenszel procedures were used to investigate baseline associations between selected factors and symptoms. RESULTS: Chronic prostatitis/chronic pelvic pain syndrome is a chronic syndrome affecting men over a wide age range. The majority of CPC study participants are white, well educated and affluent. However, lower education, lower income and unemployment were associated with more severe symptoms. Patients most frequently reported pain in the perineum and tenderness in the prostate. The highest self-reported diseases were genitourinary (55%), allergies (53%), neurological (40%) and hematopoietic, lymphatic or infectious (40%). This disease has a significant negative impact on mental and physical domains of quality of life. Almost all patients (95%) reported antimicrobial drug use. Of these 488 participants 280 (57%) reported the previous or current use of 5 or more categories of prostatitis related treatments. CONCLUSIONS: Chronic prostatitis/chronic pelvic pain syndrome is a multifactorial problem affecting men of all ages and demographics. Patients with the chronic pelvic pain syndrome have dismal quality of life and many have benefited only minimally from empirical, goal directed therapy. Long-term followup of this cohort may answer important questions on the natural treated history of this syndrome.

Adult↗
PubMedDate not supplied

CD4 and CD8 T-lymphocyte recognition of prostate specific antigen in granulomatous prostatitis.

In order to develop immunotherapies for prostate cancer, many groups are exploring vaccination strategies to induce an immune response against prostate specific antigen (PSA). To determine if T-cell recognition of PSA might be a feature of a naturally occurring human disease, we have studied patients with prostatitis, a poorly understood clinical syndrome of men in which there is evidence that an immune response directed against the prostate may be occurring. We wished to determine if a T-cell response to PSA might be occurring in these patients. We generated long-term T-cell lines from peripheral blood mononuclear cells (PBMC) of one patient with granulomatous prostatitis using purified PSA as an antigen. Several CD4+ and CD8+ TcR alpha/beta+ T-cell lines were selected for PSA reactivity as measured by at least a threefold increase in IFN-gamma secretion in response to PSA presented by irradiated autologous PBMC. CD4 and CD8 T-cell lines recognized PSA in the context of HLA-DRbeta1*1501 and HLA-B*0702, respectively. The specificity and HLA restriction of the lines was confirmed using EBV-B cell lines infected with a recombinant PSA-expressing vaccinia virus and also engineered to express PSA by retroviral transfection. HLA-matched targets infected by control vector as well as HLA-mismatched PSA-expressing targets did not induce the response. The data demonstrate that PSA-specific T cells are present in the PBMC of this patient with granulomatous prostatitis, who may be manifesting naturally the type of immune response directed at the prostate that is the goal of prostate cancer immunotherapy. However, the Class I-restricted epitope has not yet been demonstrated to be expressed on the surface of prostate cancer cells. To our knowledge, this is the first demonstration of HLA-DRB1*1501- or HLA-B*0702-restricted responses to PSA and extends the number of HLA molecules accommodating the use of PSA antigen as a candidate vaccine for prostate cancer immunotherapy.

Amino Acid Sequence↗