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Specific Antigen (specific + antigen)
Kinds of Specific Antigen Terms modified by Specific Antigen Selected AbstractsSerum Levels of Tissue Polypeptide Specific Antigen Are Correlated With Hepatocyte Cytokeratin Expression in Alcoholic Liver DiseaseALCOHOLISM, Issue 9 2004A Gonzalez-Quintela Background: Serum levels of the tumor marker tissue polypeptide specific antigen (TPS, cytokeratin 18 fragments) are increased in patients with alcoholic liver disease, particularly in cases of alcoholic hepatitis. Mallory bodies, characteristic of alcoholic hepatitis, are cytokeratin 8 and 18 aggregates. The study was aimed at investigating the possible relationship of serum TPS levels with hepatocyte cytokeratin expression in patients with alcoholic liver disease. Methods: Twenty-four patients with alcoholic liver disease were studied. Immunohistochemical staining for cytokeratins 8 and 18 was performed in liver specimens by means of CAM 5.2 monoclonal antibody. The number of hepatocytes containing CAM 5.2-reactive cytokeratin inclusions was compared with serum TPS levels. Main Results and Conclusions: The vast majority of alcoholics (95%) showed increased (>100 units/liter) serum TPS levels. Serum TPS levels were significantly correlated with the number of hepatocyte cytokeratin inclusions. Serum TPS levels can predict hepatocyte cytokeratin expression in patients with alcoholic liver disease. [source] Prostatic Specific Antigen in Patients with Hypogonadism: Effect of Testosterone ReplacementTHE JOURNAL OF SEXUAL MEDICINE, Issue 2 2005Ahmed I. El-Sakka MD ABSTRACT Introduction., The effect of parenteral testosterone replacement therapy on prostatic specific antigen (PSA) level or the development or growth of prostate cancer is unclear. Aim., To assess the effect of testosterone replacement on PSA level in patients with hypogonadism associated with erectile dysfunction (ED). Methods., A total of 187 male patients above the age of 45 with hypogonadism associated with ED were enrolled in this study. Patients were screened for ED by the erectile function domain of the International Index of Erectile Function (IIEF). Patients underwent routine laboratory investigations, plus total testosterone, and PSA assessment. Replacement treatment with parenteral testosterone every 2,4 weeks for 1 year was instituted. Total testosterone and PSA serum levels were assessed every 3 months during the treatment course. Results., Mean age ± SD was 62.8 ± 11.4. Of the patients 87.7% were sexually active. Of the patients 10.2% had mild, 40.6% had moderate and 49.2% had severe ED. Of the study population, 62.5% had ED complaints for less than 5 years and 84.5% had gradual onset of their complaint. The majority of the patients (91.4%) had either progressive or stationary course while the minority reported regressive course and improvement of the condition. There was a significant increase of the post-treatment testosterone level in comparison to pretreatment level (P < 0.05). No significant increase in the post-treatment PSA level in comparison to pretreatment (P > 0.05). No significant difference between pre- and post-treatment categories of PSA level (normal, borderline, high) in relation to the severity of ED (P > 0.05). There was no significant association between PSA level and the duration of testosterone replacement therapy in the study population (P > 0.05). Conclusion., The current study demonstrated that the level of PSA was not significantly changed after 1 year of testosterone replacement therapy in patients with hypogonadism associated with ED. [source] Amperometric Immunosensor for Prostate Specific Antigen Based on Co-adsorption of Labeled Antibody and Mediator in Nano-Au Modified Chitosan MembraneCHINESE JOURNAL OF CHEMISTRY, Issue 3 2008Jie-Hua LIN Abstract A quasi-reagentless amperometric immunosensor for prostate specific antigen (PSA) has been developed based on co-adsorption of horseradish peroxidase (HRP) labeled PSA antibody (anti-PSA) and tetramethyl benzidine (TMB) in nano-Au modified chitosan membrane (Au-chitosan). The immobilized TMB was used as an electron transfer mediator, which displayed a surface-controlled process at scan rates less than 45 mV/s, and a diffusion-controlled process at scan rates higher than 45 mV/s. The immunosensor with the co-immobilized anti-PSA and TMB was incubated with sample PSA antigen, and the formed immunoconjugate in the immunosensor was detected by a TMB-H2O2 -HRP electrochemical system. Under the optimal experimental conditions, PSA could be determined in the linear range from 5.0 to 30 ng·mL,1 with a detection limit of 1.0 ng·mL,1. The prepared PSA immunosensor is not only economic due to the low-cost ITO electrode obtained from industrial mass production, but also capable of batch fabrication with acceptable detection and storage stability. [source] Review article: drug-induced microscopic colitis , proposal for a scoring system and review of the literatureALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2005L. BEAUGERIE Summary The pathophysiology of microscopic colitis is unknown, although it is thought to be because of an abnormal immune reaction to luminal antigens in predisposed hosts. Specific antigens have not been proved, although various infectious triggers and drugs have been proposed. The responsibility of several drugs has been questioned, some with strong clinical and/or histological evidence suggesting causality. The issue of drug-induced microscopic colitis is important because of the burden of this disease. Thus, any case that can be cured by withdrawal of a drug must be identified. In this report, we propose a scoring system for drug-induced microscopic colitis, adapting existing criteria of drug causality, and review the literature using this framework. Based on this review, several drugs are identified with intermediate or high likelihood of inducing microscopic colitis. Finally, we suggest how to treat individual patients suspected of having drug-induced colitis according to the level of evidence for that particular drug. [source] Fine-needle aspiration of metastatic prostatic neuroendocrine carcinomas: Cytomorphologic and immunophenotypic featuresDIAGNOSTIC CYTOPATHOLOGY, Issue 8 2008Guoping Cai M.D. Abstract Metastatic prostatic carcinoma may, in rare occasions, present as a neuroendocrine tumor. Its recognition is crucial to avert a wrongful exclusion of prostate as a primary site. We report five cases of metastatic prostatic neuroendocrine carcinoma diagnosed by image-guided fine-needle aspiration biopsy. The aspirate smears showed loosely cohesive or dyscohesive clusters of tumor cells with scanty (three cases) to moderate amount (two cases) of cytoplasm, speckled or coarse chromatin and inconspicuous nucleoli. Nuclear molding and necrosis were focally present in two cases. Immunohistochemically, the tumor cells were positive for synaptophysin or/and chromogranin, but negative for prostatic specific antigen and prostatic specific acid phosphatase. Review of prior prostate biopsies/resections revealed adenocarcinoma with focal neuroendocrine differentiation in all cases, with two cases being newly recognized on retrospective review. Confirming neuroendocrine differentiation in the prior biopsy/resection may help to establish a link between metastasis and prostate primary. Diagn. Cytopathol. 2008; 36: 545,549. © 2008 Wiley-Liss, Inc. [source] Monoclonal antibodies: a morphing landscape for therapeuticsDRUG DEVELOPMENT RESEARCH, Issue 10 2006Nicholas C. Nicolaides Abstract The concept of using antibodies as therapeutics to cure human diseases was postulated nearly 100 years ago by Paul Ehrlich and subsequently enabled by the discovery of hybridoma technology by Kohler and Milstein in 1975. While the use of monoclonal antibodies (mAbs) as drugs that can specifically target a disease-associated antigen is compelling, it has taken a quarter century for these molecules to be adopted as bona fide therapeutic agents. Despite their slow pursuit in drug development during the pioneering years, it is now estimated that there are nearly 500 mAb-based therapies in development. Major factors that have influenced the acceptance of monoclonal antibodies as therapeutics include their drug safety profiles, technological advancements for facilitating mAb discovery and development, and market success. Early on, it was demonstrated that antibodies could elicit clinical benefit by antagonizing a specific antigen without the common side effects that are prevalent with small chemical entities due to their nonspecific effects on homeostatic biochemical pathways. In addition, the significant technological advances that the biotechnology industry has established for developing and producing monoclonal antibodies at commercial scale in a more efficient and cost-effective manner has broadly enabled their use as therapeutics. However, despite the beneficial pharmacologic advantages and technological advances, it has been the sheer market success that monoclonal antibody products have achieved over the past few years that has propelled their vast pursuit by the biopharmaceutical industry in light of their value-creating potential. Here we provide an overview of the monoclonal antibody industry and discuss evolving technologies and strategies that are being pursued to overcome challenges in the changing marketplace. Drug Dev. Res. 67:781,789, 2006. © 2007 Wiley-Liss, Inc. [source] Mechanism of modulation of T cell responses by N-palmitoylated peptidesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2004Clara Bueno Abstract Small structural changes in the antigenic peptides recognized by TCR can alter the biological properties of those peptides and convert them into weak agonists, partial agonists, or antagonists of these receptors. These altered peptide ligands (APL) are usually generated by conservative amino acid substitutions at TCR contact residues. Here, we show that APL with therapeutic properties can also be generated by attachment of palmitic acid at the N terminus of the peptide without the need to modify the peptide's primary sequence. Using N-palmitoylated pigeon cytochrome-c peptide 81,104 (PALPCC81,104), we were able to induce T cell hyporesponsiveness to the wild-type peptide in vitro. More importantly, administration of the PALPCC81,104 to mice reduced the responsiveness to the native peptide when tested ex vivo. Biochemical and functional experiments indicated that the action of N-palmitoylated peptides was due to the conversion of the native peptide into a weak agonist that could then induce T cell anergy. Our results demonstrate that N-palmitoylation of antigenic peptides is a feasible strategy to generate APL, as it avoids the need to screen multiple amino acid variants of each specific antigen to identify those with therapeutic properties. [source] Comparison of a Stool Antigen Test and Serology for the Diagnosis of Helicobacter pylori Infection in Mass SurveyHELICOBACTER, Issue 2 2009Tadashi Shimoyama Abstract Background: Serum antibody to Helicobacter pylori is tested in mass screening for gastric cancer along with the level of serum pepsinogens (PG) I and II. Recently, stool antigen tests have been developed as a new non-invasive test. We examined H. pylori infection by both serology and stool antigen test in a mass survey and compared the results to estimate applicability of stool antigen test for mass survey. Methods: A total of 994 healthy adults who received mass survey in April 2005 were tested. There were 379 men and 615 women, and the mean age was 57.7 years old. Stool samples were used to measure a H. pylori- specific antigen by enzyme immunoassay. Serum samples were tested for the prevalence of IgG antibody to H. pylori, and the level of PGs I and II was also measured to determine the presence of atrophic gastritis. Results: Infection of H. pylori was defined as positive 61.4% and 56.4% by serology and stool antigen test, respectively. The concordance of both tests was not affected by gender and age of the subjects but difference was seen in subjects with atrophic gastritis. In particular, positivity of stool antigen test (81.8%) was significantly lower than that of serology (88.7%, p < .05) in 303 subjects with severe atrophic gastritis. Conclusions: Stool antigen test, which detects present but not previous infection of H. pylori, would be applicable to diagnose H. pylori infection in mass survey. Usefulness of stool antigen tests for the screening of gastric cancer should be examined. [source] Characterization and Application of a New Monoclonal Antibody with High Specificity for Helicobacter hepaticusHELICOBACTER, Issue 1 2009Yoshihiro Fukuda Abstract Background and Aims:, Infection with Helicobacter hepaticus is suggested to play a role in the pathogenesis of chronic liver disease in humans. However, reactive antigens among Helicobacter species make the development of an H. hepaticus ELISA test with high specificity difficult. A new monoclonal antibody from a hybridoma clone (HRII-51) showed high specificity to H. hepaticus without cross-reaction to other gastrointestinal bacteria. Methods:, The molecular weight of HRII-51 immunoreactive antigen was examined by Western blot of H. hepaticus probed with the monoclonal antibody HRII-51. A HRII-51-immunoreactive antigen capture ELISA was prepared in which the specific antigen was anchored by HRII-51-immobilized ELISA plate. Accuracy of HRII-51 antigen capture ELISA was examined using sera obtained from mice inoculated with Helicobacter species. Specificity of HRII-51 antigen capture ELISA was compared to that of H. hepaticus antigen-based ELISA using human sera with absorption by H. pylori cell lysate. Results:, HRII-51 immunoreactive antigen had a molecular weight of 15 kDa. Sensitivity and specificity of HRII-51 antigen capture ELISA were 87.0% and 97.6% in mice inoculated with Helicobacter species. In human sera, modification of the results by absorption with H. pylori lysate was smaller in HRII-51 antigen capture ELISA comparing with H. hepaticus -antigen-based ELISA. Conclusion:, Use of the HRII-51 antigen capture ELISA would be a useful approach for the serodiagnosis of H. hepaticus infection in both experimental animals and humans. [source] A UK-based investigation of inter- and intra-observer reproducibility of Gleason grading of prostatic biopsiesHISTOPATHOLOGY, Issue 6 2006J Melia Aims:, The frequency of prostatic core biopsies to detect cancer has been increasing with more widespread prostate specific antigen (PSA) testing. Gleason score has important implications for patient management but morphological reproducibility data for British practice are limited. Using literature-based criteria nine uropathologists took part in a reproducibility study. Methods:, Each of the nine participants submitted slides from consecutive cases of biopsy-diagnosed cancer assigned to the Gleason score groups 2,4, 5,6, 7 and 8,10 in the original report. A random selection of slides was taken within each group and examined by all pathologists, who were blind to the original score. Over six circulations, new slides were mixed with previously read slides, resulting in a total of 47 of 81 slides being read more than once. Results:, For the first readings of the 81 slides, the agreement with the consensus score was 78% and overall interobserver agreement was , 0.54 for Gleason score groups 2,4, 5,6, 7, 8,10. Kappa values for each category were 0.33, 0.56, 0.44 and 0.68, respectively. For the 47 slides read more than once, intra-observer agreement was 77%, , 0.66. The study identified problems in core biopsy interpretation of Gleason score at levels 2,4 and 7. Patterns illustrated by Gleason as 2 tended to be categorized as 3 because of the variable acinar size and unassessable lesional margin. In slides with consensus Gleason score 7, 13% of readings were scored 6 and in slides with consensus 6, 18% of readings were scored 7. Conclusions:, Recommendations include the need to increase objectivity of the Gleason criteria but limits of descriptive morphology may have to be accepted. [source] Mast cells and eicosanoid mediators: a system of reciprocal paracrine and autocrine regulationIMMUNOLOGICAL REVIEWS, Issue 1 2007Joshua A. Boyce Summary:, When activated by specific antigen, complement, or other transmembrane stimuli, mast cells (MCs) generate three eicosanoids: prostaglandin (PG)D2, leukotriene (LT)B4, and LTC4, the parent molecule of the cysteinyl leukotrienes (cysLTs). These diverse lipid mediators, which are generated from a single cell membrane-associated precursor, arachidonic acid, can initiate, amplify, or dampen inflammatory responses and influence the magnitude, duration, and nature of subsequent immune responses. PGD2 and cysLTs, which were originally recognized for their bronchoconstricting and vasoactive properties, also serve diverse and pivotal functions in effector cell trafficking, antigen presentation, leukocyte activation, matrix deposition, and fibrosis. LTB4 is a powerful chemoattractant for neutrophils and certain lymphocyte subsets. Thus, MCs can contribute to each of these processes through eicosanoid generation. Additionally, MCs express G-protein-coupled receptors specific for cysLTs, LTB4, and another eicosanoid, PGE2. Each of these receptors can regulate MC functions in vivo by autocrine and paracrine mechanisms. This review focuses on the biologic functions for MC-associated eicosanoids, the regulation of their production, and the mechanisms by which eicosanoids may regulate MC function in host defense and disease. [source] Increased expression of mRNA encoding interleukin (IL)-4 and its splice variant IL-4,2 in cells from contacts of Mycobacterium tuberculosis, in the absence of in vitro stimulationIMMUNOLOGY, Issue 4 2004Helen A. Fletcher Summary Expression of interleukin (IL)-4 is increased in tuberculosis and thought to be detrimental. We show here that in healthy contacts there is increased expression of its naturally occurring antagonist, IL-4delta2 (IL-4,2). We identified contacts by showing that their peripheral blood mononuclear cells (PBMC) released interferon (IFN)-, in response to the Mycobacterium tuberculosis -specific antigen 6 kDa early secretory antigenic target (ESAT-6). Fresh unstimulated PBMC from these contacts contained higher levels of mRNA encoding IL-4,2 (P=0·002) than did cells from ESAT-6 negative donors (noncontacts). These data indicate that contact with M. tuberculosis induces unusual, previously unrecognized, immunological events. We tentatively hypothesize that progression to active disease might depend upon the underlying ratio of IL-4 to IL-4,2. [source] Soluble N-cadherin in human biological fluidsINTERNATIONAL JOURNAL OF CANCER, Issue 12 2006Lara Derycke Abstract Classical cadherins such as E-, P- and N-cadherin are transmembrane proteins that mediate cell,cell adhesion, and are important in embryogenesis, maintenance of tissue integrity and cancer. Proteolytic shedding of the extracellular domain results in the generation of soluble E-, P- or N-cadherin ectodomains. Circulating soluble E- and P-cadherin have been described in the serum, and elevated levels were detected in cancer patients when compared with healthy persons. Here we report the presence of soluble N-cadherin, a 90-kD protein fragment, in the serum of both healthy persons and cancer patients, using a direct ELISA and immunoprecipitation. A correlation was found between prostate specific antigen and soluble N-cadherin, and significantly elevated levels were detected in prostate cancer follow-up patients. The N-cadherin protein is neo-expressed by carcinomas of the prostate, and is responsible for epithelial to fibroblastic transition. This is reflected by the higher concentrations of soluble N-cadherin in prostate cancer patients than in healthy persons. © 2006 Wiley-Liss, Inc. [source] Prostate specific antigen (PSA)-based screeningINTERNATIONAL JOURNAL OF UROLOGY, Issue 9 2008Hiroyoshi Suzuki md Deputy Editor First page of article [source] Comparison of prostate and transition zone volume measured by the ellipsoid and planimetric methods with transrectal ultrasonography before seed implantation of prostate cancerINTERNATIONAL JOURNAL OF UROLOGY, Issue 2 2008Tetsuhiro Ikeda Abstract: A total of 122 men who were diagnosed with localized prostatic cancer underwent transrectal ultrasound and the volumes of their prostates and transitional zones were obtained using the planimetric method and the ellipsoid method. Mean age was 64.2 ±13.4 (48.2,85.8), and mean preimplant prostate specific antigen was 6.01 ± 2.35 mg/mL (0.92,15.5). The clinical stage was T1c in 70 patients, T2a in 46 and T2b in 6. Prostatic volumes and transitional zone volumes obtained by the planimetric method were 18 % and 39% greater than those obtained by the ellipsoid method, respectively. There were significant differences between the volumes obtained by the two different methods. However, there was a good correlation between the prostatic volume and the transitional zone volume obtained by both the ellipsoid method (r = 0.851) and the planimetric method (r = 0.908). The regression line of the prostate volume between these two methods was calculated as Value of power Doppler sonography with 3D reconstruction in preoperative diagnostics of extraprostatic tumor extension in clinically localized prostate cancerINTERNATIONAL JOURNAL OF UROLOGY, Issue 1 2008Miroslav Zalesky Aim: The aim of the study is to investigate the value of preoperative power Doppler sonography with 3D reconstruction (3D-PDS) for diagnostics of extraprostatic extension of prostate cancer. Patients and Methods: In the prospective study we examined 146 patients with clinically localized prostate cancer who underwent radical prostatectomy. Prior to surgery, each patient underwent 3D-PDS, transrectal ultrasound (TRUS), and digital rectal examination (DRE). Furthermore, we determined the prostate volume, prostate specific antigen (PSA) level, PSA density (PSAD), and Gleason score. The risk of locally advanced cancer was assessed using Partin tables. We determined the sensitivity, specificity, and predictive values of these diagnostic procedures. We plotted the receiver operating characteristic (ROC) curves and calculated the areas under the curves (AUC). Multivariate logistic regression was used to identify the significant predictors of extraprostatic tumor extension. Based on this we developed diagnostic nomograms maximizing the probability of accurate diagnosis. Results: The significant differences between patients with organ confined and locally advanced tumor (based on the postoperative assessment) were observed in the PSA levels (P < 0.014), PSAD (P < 0.004), DRE (P < 0.037), TRUS (P < 0.003), and 3D-PDS (P < 0.000). The highest AUC value of 0.776 (P < 0.000) was found for 3D-PDS. The observed AUC value for TRUS was 0.670 (P < 0.000) and for PSAD 0.639 (P < 0.004). In multivariate regression analysis, the PSAD, preoperative Gleason score, and 3D-PDS finding were identified as significant preoperative predictors of extraprostatic tumor extension. Conclusion: Our data suggest that the 3D-PDS is a valuable preoperative diagnostic examination to identify locally advanced prostate cancer. Therefore, it can be used to maximize the probability of the accurate diagnosis of extraprostatic tumor extension. [source] Effects of flutamide as a second-line agent for maximum androgen blockade of hormone refractory prostate cancerINTERNATIONAL JOURNAL OF UROLOGY, Issue 3 2007Kenji Nishimura Abstract: We analyzed clinical effects of flutamide as a second-line agent for maximum androgen blockade (MAB) in patients with relapsing prostate cancer who received bicalutamide as the first-line MAB agent. This study included 13 patients with progressive prostate cancer who had relapsed after first-line MAB, with bicalutamide at 80 mg/day. After checking for antiandrogen withdrawal syndrome, they were given flutamide at 375 mg/day as second-line MAB. The effectiveness of that therapy was evaluated by changes in prostatic specific antigen (PSA) levels, with response defined as a decrease of greater than 50% from the start of therapy. We also compared several factors between responders and non-responders. Nine (69.2%) of the 13 patients showed a decrease in PSA levels, of whom five (38.5%) had a greater than 50% decrease and were defined as responders. The median duration of PSA response was 11.0 months (range 5,20 months). Patients who had a longer duration of response to first-line MAB had a significantly greater response to second-line MAB. For advanced prostate cancer patients who progressed on first-line MAB with bicalutamide, flutamide administration as a second-line antiandrogen was found to be relatively effective, especially for those who showed a longer duration of response to the first-line MAB. Our results confirm previous findings that MAB using flutamide is an effective second-line hormonal therapy. [source] Lower urinary tract symptoms and risk of prostate cancer in Japanese menINTERNATIONAL JOURNAL OF UROLOGY, Issue 8 2006AKIO MATSUBARA Aim: Our aim was to investigate whether or not men with lower urinary tract symptoms are at increased risk of prostate cancer. Methods: A total of 3511 men aged 50,79 years who underwent mass screening for prostate cancer between 2002 and 2004 for the first time, and completed the International Prostate Symptom Score (IPSS) questionnaire at the time of the prostate specific antigen (PSA) test, were enrolled in the present study. All men with PSA values greater than 4.0 ng/mL were advised and encouraged to undergo transrectal systematic sextant biopsy. The number of cancers subsequently detected was compared between men with IPSS scores of 0,7 and 8,35. Results: Of the 3511 men, 219 (6.2%) had PSA values greater than 4 ng/mL, 178 (5.1%) underwent biopsy, and 51 (1.5%) were found to have prostate cancer. Although the PSA positivity rate for men with IPSS scores of 8,35 was significantly higher than that in the 0,7 group, there were no significant intergroup differences in the cancer detection rates for biopsied men and for total screened subjects. Multivariate logistic regression analysis revealed that prostate volume was the dominant predictor for the detection of prostate cancer, followed by PSA level, but the IPSS made no significant contribution. No significant difference was noted in the IPSS scores between men with cancer and the others of the same age group. Conclusions: Symptomatic Japanese men are not at higher risk of prostate cancer despite their higher PSA values compared with asymptomatic men of the same age group. [source] Value of prostate specific antigen ,1 -antichymotrypsin complex for the detection of prostate cancer in patients with a PSA level of 4.1,10.0ng/mL: Comparison with PSA-related parametersINTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2001Hideaki Miyake Abstract Background: The aim of the present study was to evaluate the usefulness of prostate specific antigen ,1 -antichymotrypsin complex (PSA-ACT) in the differential diagnosis of prostate cancer in patients with a PSA level of 4.1,10.0 ng/mL compared to several PSA- and PSA-ACT-related parameters. Methods: Serum samples were obtained from 103 patients with no evidence of malignancy on biopsy and 29 with histologically confirmed prostate cancer. All patients had pretreatment serum PSA levels between 4.0 and 10.0 ng/mL. The different forms of serum PSA, including total PSA (tPSA), free PSA (fPSA) and PSA-ACT were measured using immunofluorometric techniques with different monoclonal antibodies against PSA and ACT. Furthermore, tPSA and PSA-ACT densities of the whole prostate (PSAD and ACTD, respectively) and the f-to-tPSA and the f-to-PSA-ACT ratios (F/T ratio and F/ACT ratio, respectively) were calculated. Results: The differences between patients with prostate cancer and benign prostatic disease were significant with respect to all six parameters examined in this study. Analysis of receiver operating characteristics revealed that the areas under the curve for PSA-ACT, ACTD and the F/ACT ratio were larger than those for tPSA, PSAD and the F/T ratio, respectively. However, there were no significant differences in discrimination between benign and malignant diseases among these six parameters. Conclusions: In patients who have an intermediate serum PSA level, PSA-ACT and its associated parameters may not be significantly superior in the differential diagnosis between prostate cancer and benign prostatic diseases compared to tPSA and its traditional relatives. [source] Testosterone Supplementation Therapy for Older Men: Potential Benefits and RisksJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 1 2003David A. Gruenewald MD Serum testosterone levels decline gradually and progressively with aging in men. Many manifestations associated with aging in men, including muscle atrophy and weakness, osteoporosis, reduced sexual functioning, and increased fat mass, are similar to changes associated with testosterone deficiency in young men. These similarities suggest that testosterone supplementation may prevent or reverse the effects of aging. A MEDLINE search was performed to identify studies of testosterone supplementation therapy in older men. A structured, qualitative review was performed of placebo-controlled trials that included men aged 60 and older and evaluated one or more physical, cognitive, affective, functional, or quality-of-life outcomes. Studies focusing on patients with severe systemic diseases and hormone deficiencies related to specific diseases were excluded. In healthy older men with low-normal to mildly decreased testosterone levels, testosterone supplementation increased lean body mass and decreased fat mass. Upper and lower body strength, functional performance, sexual functioning, and mood were improved or unchanged with testosterone replacement. Variable effects on cognitive function were reported, with improvements in some cognitive domains (e.g., spatial, working, and verbal memory). Testosterone supplementation improved exercise-induced coronary ischemia in men with coronary heart disease, whereas angina pectoris was improved or unchanged. In a few studies, men with low testosterone levels were more likely to experience improvements in lumbar bone mineral density, self-perceived functional status, libido, erectile function, and exercise-induced coronary ischemia with testosterone replacement than men with less marked testosterone deficiency. No major unfavorable effects on lipids were reported, but hematocrit and prostate specific antigen levels often increased. Based on these results, testosterone supplementation cannot be recommended at this time for older men with normal or low-normal testosterone levels and no clinical manifestations of hypogonadism. However, testosterone replacement may be warranted in older men with markedly decreased testosterone levels, regardless of symptoms, and in men with mildly decreased testosterone levels and symptoms or signs suggesting hypogonadism. The long-term safety and efficacy of testosterone supplementation remain uncertain. Establishment of evidence-based indications will depend on further demonstrations of favorable clinical outcomes and symptomatic, functional, and quality-of-life benefits in carefully performed, long-term, randomized, placebo-controlled clinical trials. J Am Geriatr Soc 51:101,115, 2003. [source] Biomarkers for prostate cancerJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2009Eddy S. Leman Abstract The detection of prostate cancer using a blood test has by many standards changed the face of the disease. Despite this tremendous success, there are limitations attributed to the use of prostate specific antigen (PSA) as a means to screen and detect prostate cancer. PSA, as its name implies, is not specific for prostate cancer and as such is often found elevated in other prostatic diseases/symptoms associated with the aging male. Clearly, more specific marker(s) that could identify which individuals actually have prostate cancer and differentiate them from those without the disease would be of tremendous value. The search for more accurate and clinically useful biomarkers of prostate cancer has been extensive. This has focused on individual markers, as well as groups of markers. Included among these are PSA isoforms, pathological indicators and stains, nucleic acids and others. This article highlights the discovery of PSA as a first blood-based biomarker for prostate cancer detection, as well as other molecular biomarkers and their potential application in detection of the disease. J. Cell. Biochem. 108: 3,9, 2009. © 2009 Wiley-Liss, Inc. [source] Amino-terminus domain of the androgen receptor as a molecular target to prevent the hormonal progression of prostate cancerJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2006Gang Wang Abstract Prostate cancer has a propensity to metastasize to the bone. Currently the only effective systemic treatment for these patients is androgen ablation therapy. However, the tumor will invariably progress to an androgen-independent stage and the patient will succumb to his disease within approximately 2 years. The earliest indication of hormonal progression is the rising titer of serum prostate specific antigen. Current evidence implicates the androgen receptor (AR) as a key factor in maintaining the growth of prostate cancer cells in an androgen-depleted state. Under normal conditions, binding of ligand activates the receptor, allowing it to effectively bind to its respective DNA element. However, AR is also transformed in the absence of androgen (ligand-independent activation) in prostate cells via multiple protein kinase pathways and the interleukin-6 (IL-6) pathway that converge upon the N-terminal domain of the AR. This domain is the main region for phosphorylation and is also critical for normal coregulator recruitment. Here we discuss evidence supporting the role of the AR, IL-6 and other protein kinase pathways in the hormonal progression of prostate cancer to androgen independence and the mechanisms involved in activation of the AR by these pathways. Receptor-targeted therapy, especially potential drugs targeting the N-terminal domain, may effectively prevent or delay the hormonal progression of AR-dependent prostate cancer. J. Cell. Biochem. 98: 36,53, 2006. © 2006 Wiley-Liss, Inc. [source] Detection of carcinomas in an asymptomatic Chinese population: advantage of screening with multiple tumor markersJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 2 2006Kuo-Chien Tsao Abstract A total of 73,443 asymptomatic individuals were screened on a voluntary basis for cancer at Chang Gung Memorial Hospital in Taiwan using a panel of tumor markers, including alpha fetoprotein (AFP), CA 125, CA 15-3, CA 19-9, carcinoembryonic antigen (CEA), prostate specific antigen (PSA), chromogranin A (CgA), and squamous cell specific antigen (SCC). The results are derived from data collected from January 1998 to October 2003. A total of 210 cancers (approximately 0.3%) were detected, including cancers of the liver, lung, colon, prostate, stomach, pancreas, breast, cervix, ovary, and bladder. Of the tumor markers monitored, elevated CA 19-9, CEA, and CA 125 were the most frequently detected in a variety of cancers. It was surprising to find that many cancers were not detected by their dominant markers but by the elevation of tumor markers not recommended for monitoring their tumor activity. Screening with multiple circulating tumor markers provides improved sensitivity for cancer detection in asymptomatic individuals before they reach the fatal advanced stage. Screening with multiple tumor markers also allows cancers to be detected in the absence of their dominant markers. If we had not measured the multiple tumor markers, these cancers would have gone undetected. J. Clin. Lab. Anal. 20:42,46, 2006. © 2006 Wiley-Liss, Inc. [source] Diffusion-weighted MRI for monitoring tumor response to photodynamic therapyJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 2 2010Hesheng Wang MS Abstract Purpose: To examine diffusion-weighted MRI (DW-MRI) for assessing the early tumor response to photodynamic therapy (PDT). Materials and Methods: Subcutaneous tumor xenografts of human prostate cancer cells (CWR22) were initiated in athymic nude mice. A second-generation photosensitizer, Pc 4, was delivered to each animal by a tail vein injection 48 h before laser illumination. A dedicated high-field (9.4 Tesla) small animal MR scanner was used to acquire diffusion-weighted MR images pre-PDT and 24 h after the treatment. DW-MRI and apparent diffusion coefficients (ADC) were analyzed for 24 treated and 5 control mice with photosensitizer only or laser light only. Tumor size, prostate specific antigen (PSA) level, and tumor histology were obtained at different time points to examine the treatment effect. Results: Treated mice showed significant tumor size shrinkage and decrease of PSA level within 7 days after the treatment. The average ADC of the 24 treated tumors increased 24 h after PDT (P < 0.001) comparing with pre-PDT. The average ADC was 0.511 ± 0.119 × 10,3 mm2/s pre-PDT and 0.754 ± 0.181 × 10,3 mm2/s 24 h after the PDT. There is no significant difference in ADC values pre-PDT and 24 h after PDT in the control tumors (P = 0.20). Conclusion: The change of tumor ADC values measured by DW-MRI may provide a noninvasive imaging marker for monitoring tumor response to Pc 4-PDT as early as 24 h. J. Magn. Reson. Imaging 2010;32:409,417. © 2010 Wiley-Liss, Inc. [source] Serum Levels of Tissue Polypeptide Specific Antigen Are Correlated With Hepatocyte Cytokeratin Expression in Alcoholic Liver DiseaseALCOHOLISM, Issue 9 2004A Gonzalez-Quintela Background: Serum levels of the tumor marker tissue polypeptide specific antigen (TPS, cytokeratin 18 fragments) are increased in patients with alcoholic liver disease, particularly in cases of alcoholic hepatitis. Mallory bodies, characteristic of alcoholic hepatitis, are cytokeratin 8 and 18 aggregates. The study was aimed at investigating the possible relationship of serum TPS levels with hepatocyte cytokeratin expression in patients with alcoholic liver disease. Methods: Twenty-four patients with alcoholic liver disease were studied. Immunohistochemical staining for cytokeratins 8 and 18 was performed in liver specimens by means of CAM 5.2 monoclonal antibody. The number of hepatocytes containing CAM 5.2-reactive cytokeratin inclusions was compared with serum TPS levels. Main Results and Conclusions: The vast majority of alcoholics (95%) showed increased (>100 units/liter) serum TPS levels. Serum TPS levels were significantly correlated with the number of hepatocyte cytokeratin inclusions. Serum TPS levels can predict hepatocyte cytokeratin expression in patients with alcoholic liver disease. [source] Heparin-binding proteins of human seminal plasma: purification and characterizationMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 12 2008Vijay Kumar Abstract Human seminal plasma (HuSP) contains several proteins that bind heparin and related glycosaminoglycans. Heparin binding proteins (HBPs) from seminal plasma have been shown to participate in modulation of capacitation or acrosome reaction and thus have been correlated with fertility in some species. However, these have not been studied in detail in human. The objective of this study was to purify major HBPs from HuSP in order to characterize these proteins. HBPs were isolated by affinity,chromatography on Heparin,Sepharose column, purified by reverse-phase high-performance liquid chromatography (RP-HPLC) and Size-exclusion chromatography and checked for purity on sodium-dodecyl PAGE (SDS,PAGE). Identification of HBPs was done by matrix-assisted laser desorption-ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS). Here we report the purification and identification of seven HBPs in seminal fluid. The major HBPs are lactoferrin and its fragments, semenogelin I fragments, semenogelin II, prostate specific antigen, homolog of bovine seminal plasma-proteins (BSP), zinc finger protein (Znf 169) and fibronectin fragments. In this study we are reporting for the first time the purification and identification of BSP-homolog and Znf 169 from HuSP and classified them as HBPs. Here we report the purification of seven clinically important proteins from human seminal fluid through heparin affinity chromatography and RP-HPLC, in limited steps with higher yield. Mol. Reprod. Dev. 75: 1767,1774, 2008. © 2008 Wiley-Liss, Inc. [source] Role of Chlamydia pneumoniae -infected macrophages in atherosclerosis developments of the carotid arteryNEUROPATHOLOGY, Issue 1 2003Satoshi Kuroda Chlamydia pneumoniae (C. pneumoniae) infection has been recently accepted as an important cause of atherosclerosis. However, the precise mechanisms remain unclear. The present study was aimed to clarify the distribution link among C. pneumoniae, chlamydial HSP 60, and activated macrophages. Atheromatous carotid plaques were obtained from 40 consecutive carotid endarterectomies (CEA). The specimens were prepared for HE and elastica,van Gieson staining. Parallel sections were stained immunocytochemically with monoclonal antibodies for a C. pneumoniae -specific antigen, chlamydial HSP 60, activated macrophages, and smooth muscle cells. Immunoreactivity for the C. pneumoniae -specific antigen was observed within the endothelial cells, activated macrophages, and smooth muscle cells in 36 of 40 specimens (90%). Chlamydial HSP 60 was found in all specimens positive for the C. pneumoniae -specific antigen, and mainly co-localized with the C. pneumoniae -specific antigen within the activated macrophages. The present results suggest that C. pneumoniae is a key microbial organ that causes atheroma developments in the carotid artery. Chlamydia pneumoniae -infected macrophages may come into the arterial intima and mediate inflammatory and autoimmune processes through the production of chlamydial HSP 60, leading to atherosclerosis. [source] Transrectal ultrasound-guided biopsy of prostate voxels identified as suspicious of malignancy on three-dimensional 1H MR spectroscopic imaging in patients with abnormal digital rectal examination or raised prostate specific antigen level of 4,10 ng/mlNMR IN BIOMEDICINE, Issue 1 2007Virendra Kumar Abstract Results of the evaluation of transrectal ultrasound (TRUS) guided needle biopsy of voxels identified as suspicious of malignancy on magnetic resonance spectroscopic imaging (MRSI) in a large cohort of men (n,=,83) with abnormal digital rectal examination (DRE) [prostate specific antigen (PSA) 0,4,ng/ml] or PSA less than 10,ng/ml, are reported. Three-dimensional 1H MRSI was carried out at 1.5 T using a pelvic-phased array coil in combination with an endorectal surface coil. Voxels were classified as suspicious of malignancy based on Cit/(Cho,+,Cr) metabolite ratio. TRUS-guided biopsy of suspicious voxels was performed using the z - and x -coordinates obtained from MR images and two to three cores were taken from the suspected site. A systematic sextant biopsy was also carried out. MRSI showed voxels suspicious of malignancy in 44 patients while biopsy revealed cancer in 11 patients (25%). Patients who were negative for malignancy on MRSI were also negative on biopsy. An overall sensitivity of 100%, specificity of 54%, negative predictive value of 100% and accuracy of 60% were obtained. The site of biopsy was confirmed (n,=,20) as a hypo-intense area on repeat MRI while repeat MRSI revealed high choline and low citrate. The overall success rate of MRI-directed TRUS-guided biopsy of 25% was higher compared with a 9% success rate achieved without MR guidance in another group of 120 patients. Our results indicate that TRUS-guided biopsy of suspicious area identified as malignant from MRSI can be performed using the coordinates of the voxel derived from MR images. This increases the detection rate of prostate cancer in men with PSA level <10,ng/ml or abnormal DRE and also demonstrates the potential of MR in routine clinical practice. Copyright © 2006 John Wiley & Sons, Ltd. [source] Apoptosis: a mechanism of immunoregulation during human schistosomiasis mansoniPARASITE IMMUNOLOGY, Issue 6 2000Patricia Carneiro-Santos People infected with schistosomes may present with a variety of clinical manifestations ranging from the relatively asymptomatic intestinal (INT) form to the hepatointestinal (HI) or hepatosplenic (HS) forms characterized by hepatomegaly and hepatosplenomegaly with severe portal hypertension, respectively. Flow cytometry analyses were used to evaluate the contribution of apoptosis in specific cell populations from schistosomiasis patients to the development of the different clinical forms of the disease. The results showed that cell death induced by combinations of specific antigen and cytokines corresponds with specific clinical presentations. It was shown that soluble egg antigen (SEA) increased the level of apoptosis only in T cells from INT patients. Stimulation with soluble lung worm antigen preparation (SLAP) did not induce significant differences in the levels of apoptosis in T cells from the patients with the different clinical forms of schistosomiasis. These results suggest for the first time that apoptosis plays an important role in the modulation of the anti-SEA response in INT patients. [source] Prostatic Specific Antigen in Patients with Hypogonadism: Effect of Testosterone ReplacementTHE JOURNAL OF SEXUAL MEDICINE, Issue 2 2005Ahmed I. El-Sakka MD ABSTRACT Introduction., The effect of parenteral testosterone replacement therapy on prostatic specific antigen (PSA) level or the development or growth of prostate cancer is unclear. Aim., To assess the effect of testosterone replacement on PSA level in patients with hypogonadism associated with erectile dysfunction (ED). Methods., A total of 187 male patients above the age of 45 with hypogonadism associated with ED were enrolled in this study. Patients were screened for ED by the erectile function domain of the International Index of Erectile Function (IIEF). Patients underwent routine laboratory investigations, plus total testosterone, and PSA assessment. Replacement treatment with parenteral testosterone every 2,4 weeks for 1 year was instituted. Total testosterone and PSA serum levels were assessed every 3 months during the treatment course. Results., Mean age ± SD was 62.8 ± 11.4. Of the patients 87.7% were sexually active. Of the patients 10.2% had mild, 40.6% had moderate and 49.2% had severe ED. Of the study population, 62.5% had ED complaints for less than 5 years and 84.5% had gradual onset of their complaint. The majority of the patients (91.4%) had either progressive or stationary course while the minority reported regressive course and improvement of the condition. There was a significant increase of the post-treatment testosterone level in comparison to pretreatment level (P < 0.05). No significant increase in the post-treatment PSA level in comparison to pretreatment (P > 0.05). No significant difference between pre- and post-treatment categories of PSA level (normal, borderline, high) in relation to the severity of ED (P > 0.05). There was no significant association between PSA level and the duration of testosterone replacement therapy in the study population (P > 0.05). Conclusion., The current study demonstrated that the level of PSA was not significantly changed after 1 year of testosterone replacement therapy in patients with hypogonadism associated with ED. [source]
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