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Biomedical subjects

P B Hudson

Publications and source records attributed to P B Hudson.

At least 19 recordsLinked to original sources
PubMed2000

Serum prostate specific antigen is a strong predictor of future prostate growth in men with benign prostatic hyperplasia. PROSCAR long-term efficacy and safety study.

PURPOSE: We analyze patterns of prostate growth in men diagnosed with benign prostatic hyperplasia (BPH) and treated with placebo during 4 years, and determine which baseline parameters were the strongest predictors of growth. MATERIALS AND METHODS: A total of 3,040 men were enrolled in the 4-year randomized, placebo controlled Proscar Long-Term Efficacy and Safety study. Of these men a subgroup of 10% underwent pelvic magnetic resonance imaging prostate volume measurement at baseline and yearly thereafter. Absolute and percent volume changes during 4 years were calculated in the 164 placebo treated men in the subgroup. The ability of age, baseline prostate volume and prostate specific antigen (PSA) to predict prostate growth in placebo treated patients was assessed by multiple linear regression analyses, receiver operator characteristics curves, and evaluations of growth stratified by tertiles of baseline serum PSA and decades of life. RESULTS: In placebo treated patients a steady increase in mean plus or minus standard deviation prostate volume from year to year was noted (2.5+/-6.1, 4.9+/-6.8, 6.4+/-8.5 and 7.2+/-8.8 ml. at years 1, 2, 3 and 4, respectively). Mean volume changes at 4 years ranged from -9 to +30 ml. Mean percent change from baseline ranged from 12.5% to 16.6% for men 50 to 59 years old to those 70 to 79 years old. Baseline serum PSA was a strong predictor of growth with 7.4% to 22.0% change at 4 years from the lowest to highest PSA tertiles. Annualized growth rates from baseline were 0.7 ml. per year for PSA 0.2 to 1.3, 2.1 for PSA 1.4 to 3.2 and 3.3 for PSA 3.3 to 9.9 ng./ml. Multiple linear regression analysis showed that serum PSA was a stronger predictor of prostate growth than age or baseline prostate volume. All but 1 man with baseline serum PSA greater than 2.0 ng./ml. had prostate growth during 4 years, and 32.6% of men with serum PSA less than 2.0 exhibited a decrease in volume. CONCLUSIONS: Serum PSA is a stronger predictor of growth of the prostate in placebo treated patients than age or baseline prostate volume. Since prostate volume is a risk factor for acute urinary retention and the need for BPH related surgery, the ability of PSA to predict prostate growth may be an important factor when considering individual treatment options for BPH. Such use of PSA represents a shift in paradigm away from focusing solely on symptoms of BPH toward a more comprehensive approach with consideration of predicting and preventing risk factors of BPH related outcomes.

Aged↗
PubMed1999

Efficacy of finasteride is maintained in patients with benign prostatic hyperplasia treated for 5 years. The North American Finasteride Study Group.

OBJECTIVES: The purpose of this open-label study extension was to assess the long-term safety and efficacy of finasteride in the treatment of men with benign prostatic hyperplasia (BPH). METHODS: A Phase III North American BPH trial originally enrolled 895 men, 297 of whom were randomized to receive finasteride 5 mg. An enlarged prostate gland by digital rectal examination, symptoms of urinary obstruction, and a maximal urinary flow rate of less than 15 mL/s were required for entry. Patients who completed the initial 12-month, double-blind, placebo-controlled study were invited to participate in an open-label extension for 4 additional years. RESULTS: Of the 297 patients initially randomized to receive finasteride 5 mg, 259 completed 12 months in the double-blind period and 186 completed 48 months of open-label therapy. Prostate volume reached a nadir of -24.6% at month 24, and the effect was maintained through month 60. Compared with baseline values, month 60 prostate volume was decreased by 22.7% (P<0.001), the quasi-American Urological Association symptom score was decreased by 4.3 points, and maximal urinary flow was increased by 2.3 mL/s (P<0.001) on average. Finasteride was well tolerated, with no significant increase in the prevalence of sexual adverse events over time. CONCLUSIONS: Patients treated with finasteride 5 mg maintained an initial decrease in prostate volume and improvement in symptom score and maximal urinary flow rate over 5 years.

Double-Blind Method↗
PubMed1998

Expression of macrophage migration inhibitory factor in the human prostate.

The expression of macrophage migration inhibitory factor (MIF) in prostate tissue was investigated by immunohistochemistry (IHC), enzyme-linked immunosorbent assay (ELISA), and Northern blot analysis using a prostate tissue bank. MIF expression was examined in each of the following established prostate tissue categories: prepubertal, pubertal, adult normal, benign hyperplastic (BPH), focal carcinoma within the prostate, and metastatic prostate cancer. IHC showed that all samples tested were positive for MIF protein, which localized to the glandular epithelial cells with no apparent staining of stroma. The most intense staining was observed in the metastatic prostatic adenocarcinoma and the human prostatic adenocarcinoma cell line LNCaP. Using quantitative ELISA, MIF expression was found to be at least three times higher in metastatic adenocarcinoma than in normal, BPH, or focal carcinoma in the adult prostate. This study is the first to report that prostate glandular epithelial cells express MIF. The exact role of MIF in prostate development and disease progression requires further study.

Adolescent↗
PubMed1997

Preliminary evaluation of 5 alpha-reductase type 2 in urine as a potential marker for prostate disease.

The objective of this study was to find a biomarker, easily detectable and measurable, that could be useful to the physician for the diagnosis and management of prostate cancer. An immunoaffinity-purified polyclonal antibody to the 5 alpha-reductase type 2 isozyme was prepared following standard procedures in New Zealand White rabbits. One hundred and seven urine samples were examined for the presence of this isozyme by Western blot, dot blot, and enzyme-linked immunosorbent assay assays. In a control group of 91 subjects (46 females and 45 males) with no history of prostate disease, only 1 female tested positive. In a test group of 16 males, 4 males with adenocarcinoma of the prostate under treatment with lupron/flutamide tested negative. Four males with untreated adenocarcinoma of the prostate tested positive. Two males with transitional cell carcinoma invading the prostatic ducts and two males with basal cell hyperplasia of the prostate with intraductal dysplasia tested positive. These results support the need for an extended study to explore the use of the Western blot or the simple dot blot and enzyme-linked immunosorbent assays for the detection of 5 alpha-reductase type 2 in urine as a potential marker for prostate disease.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1996

Preliminary studies on the isolation and characterization of predominant prostatic proteins.

BACKGROUND: The increasing incidence of prostate cancer demands that we give our full attention not only to the etiology and prevention of this common type of cancer, but also to the diagnosis and prognostic course of this disease. In an effort to develop new prostatic tumor markers that could be useful to the physician at the current state of our knowledge in the diagnosis and prognosis of this disease, our laboratories have undertaken an effort to isolate and characterize the nature of the major proteins in the normal prostate and in prostatic neoplasia. METHODS: In this preliminary study, tissue was obtained from open prostatic surgery in patients with a pre- and postoperative diagnosis of benign prostatic hyperplasia. The initial fractionation and separation of the proteins was achieved through the use of ultrafiltration of homogenates followed by SDS-PAGE. Initial analysis of four prominent protein bands was accomplished by amino acid sequencing, and identified by a search in GeneBank data base. RESULTS: Two proteins previously identified in prostatic tissue were prostate specific antigen (M(r) 26,496) with 240 amino acid residues and beta-inhibin (M(r) 10,704) with 94-amino acid residues. A third protein was identified as human cysteine rich protein (hCRP). This protein functions as a DNA binding protein and has previously been postulated to contain four putative zinc fingers and to play a fundamental role in cellular function. Ubiquitin, the fourth major protein identified was a 76-amino acid polypeptide whose function is to target other proteins for destruction. CONCLUSIONS: hCRP and ubiquitin are reported as being found in high levels in prostatic tissue for the first time.

Amino Acid Sequence↗
PubMed1996

Immunochemical detection of 5 alpha-reductase in human serum.

This study represents a continuing effort to find a new biomarker for the diagnosis and management of prostatic cancer. Polyclonal antibodies were prepared to a peptide (CAKP) representing amino acids 28 to 43 of the 5 alpha-reductase type 2 isozyme. Using immunoaffinity-purified antibodies, the sera of 62 patients were examined by Western blot following polyacrylamide gel electrophoresis. A positive band was detected in the sera of several patients at 42 kDa compatible with the purified native glycosylated 5 alpha-reductase type 2. These bands were nullified on coincubation of the antibody with the CAKP peptide. Analysis by high-performance liquid chromatography and amino acid sequencing by N-terminal Edman degradation of the immunoaffinity-purified antigen to the antipeptide antibodies of a patient with adenocarcinoma of the prostate suggests that the 5 alpha-reductase type 2 isozyme may be linked to an immunoglobulin. An identical immunoaffinity-purified antigen to the CAKP peptide was isolated from a section of prostatic tissue from a different patient showing benign prostatic hypertrophy with severe dysplasia. It is suggested that an immunological response to the 5 alpha-reductase type 2 isozyme was elicited in both instances.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1996

Enhanced expression of macrophage migration inhibitory factor in prostatic adenocarcinoma metastases.

OBJECTIVES: Determining the genetic changes associated with the development of metastatic prostate cancer is of utmost importance in patient prognosis and therapy. Our goal is to identify genes whose enhanced expression is associated with metastatic prostate cancer. METHODS: Total ribonucleic acid was isolated from prostatic tissue exhibiting no histologic evidence of carcinoma and from a prostatic adenocarcinoma lymph node metastasis. The differential display polymerase chain reaction (DD-PCR) technique was used to isolate genes that exhibited increased expression in the metastatic tissue sample. Isolated PCR products were cloned, sequenced, and identified by screening complementary deoxyribonucleic acid (cDNA) databases. RESULTS: Using DD-PCR, we identified three cDNA clones that exhibit enhanced expression in metastatic prostatic tissue. Two of these cDNA clones have not been identified because they show no homology to known database sequences. The third cDNA is 166 base pairs in length and exhibits 93% homology to nucleotides 662 to 828 of human macrophage migration inhibitory factor (MIF). Slot blot analysis using RNA from various prostate-derived sources suggests that increased expression of MIF is associated with metastatic prostate cancer. CONCLUSIONS: These results show that the DD-PCR technique is applicable for the identification and cloning of human genes that exhibit enhanced expression in prostate cancer metastases. These results indicate the possibility that MIF production by prostate cancer cells plays a role in the development of metastases. The enhanced expression of MIF by prostate cancer cells may be a potential prognostic marker for metastatic prostate cancer.

Adenocarcinoma↗
PubMed1994

Testicular androgens in prostate cancer patients treated with a luteinizing hormone releasing hormone agonist.

Luteinizing hormone releasing hormone agonists have been shown to reduce the levels of androgens in the peripheral circulation and to reduce prostate volume. The objective of this study was to quantify testicular function in patients with metastatic carcinoma of the prostate treated with a luteinizing hormone releasing hormone agonist, leuprolide, by analysis of spermatic vein blood for testosterone and androstenedione, and by determination of the maximum velocity of the 17 beta-hydroxysteroid oxidoreductase enzyme in testicular tissue in vitro. A chemical analysis of the spermatic vein blood of 19 patients with a median age of 78 years revealed the presence of significantly high levels of testosterone and androstenedione, 20.7 +/- 1.9 micrograms % and 6.7 +/- 0.7 micrograms %, respectively. These androgens could not be detected in patients treated with leuprolide before orchiectomy. Patients treated with leuprolide for several months followed by a period of no treatment before orchiectomy secreted testosterone and androstenedione levels comparable to the control group. The maximum velocity of the 17 beta-hydroxysteroid oxidoreductase enzyme in vitro in the testes of the leuprolide treated patients was significantly inhibited. Enzyme activity returned to normal levels when leuprolide treatment was followed by a recovery period of no treatment before orchiectomy.

17-Hydroxysteroid Dehydrogenases↗
PubMed1993

A study of androgen biosynthesis by the human testis in vitro.

The biosynthetic pathways in human testicular tissue have been studied extensively in our laboratory without the use of radioisotopes. Experiments were conducted with normal testicular tissue from patients undergoing orchiectomy for prostatic cancer. These studies have shown that the preferred pathway of testosterone biosynthesis is influenced by the nature and concentration of cofactor added to the incubation medium. Four enzymes are involved in the transformation of pregnenolone to testosterone, that is, 3 beta-hydroxysteroid dehydrogenase, 17 alpha-hydroxylase, C17-C20 lyase and 17 beta-hydroxysteroid oxidoreductase. Our studies show that the 4-ene pathway predominates in the biosynthesis of testosterone from pregnenolone. Analysis of several samples of human testicular vein blood supports the contention that 4-androsten-3,17-dione is the immediate precursor of testosterone.

Aged↗
PubMed1993

In vitro studies on the inhibition of testosterone synthesis in the human testis by atamestane.

In view of the well established clinical results of the deprivation of androgens through orchiectomy in prostatic cancer and the structural similarities of 4-androsten-3,17-dione and atamestane (1-methyl-ADD), we studied the influence of 1-methyl-ADD on the conversion of 4-androsten-3,17-dione to testosterone by the 17 beta-hydroxysteroid reductase enzyme in human testicular tissue. Our studies, presented in this manuscript, demonstrate that 1-methyl-ADD is a competitive inhibitor of 4-androsten-3,17-dione in its reduction to testosterone by the 17 beta-hydroxysteroid reductase enzyme in the human testis.

17-Hydroxysteroid Dehydrogenases↗
PubMed1992

In vitro studies on the effect of cofactors on the 5 alpha-reductase and 3 alpha- and 3 beta-hydroxysteroid reductase activities in the hyperplastic human prostate.

Many studies have intimated that the accumulation and hence elevation of dihydrotestosterone (DHT) in the human prostate may be the primary factor in the development of benign prostatic hyperplasia (BPH). This accumulation has been explained in terms of an increase in the 5 alpha-reductase enzymatic activity which converts testosterone to DHT and a decrease in the relative activities of the 3 alpha-HSORred and 3 beta-HSORred enzymes. To investigate this hypothesis further, the activities of these two enzymes were studied in the presence and absence of NADPH in benign hyperplastic tissue and in normal peripheral (NPR) and benign hyperplastic periurethral (BPH) tissue taken from the same prostate. The results of these studies demonstrate a several fold increase in the activities of 3 alpha-HSORred and 3 beta-HSORred in the presence of NADPH in the hyperplastic human prostate. This increase in the activities of these two enzymes is found to the same degree in normal peripheral and benign hyperplastic periurethral tissue taken from the same prostate. There was no difference in percent increase in 3 alpha- and 3 beta-diol formation from DHT with NADPH in normal peripheral versus benign hyperplastic periurethral prostatic tissue. In subsequent experiments, Vmax/Km, as an index of the enzymatic capacity of the 3 alpha-HSORred and 3 beta-HSORred enzymes, was determined in both NPR and BPH tissue in media fortified with one mM NADPH. This quotient was found to be essentially the same in NPR and BPH tissue for both the 3 alpha-HSORred and the 3 beta-HSORred. Subsequently, the Vmax/Km value for the 5 alpha-reductase in BPH tissue was found to be equal to the combined Vmax/Km values of the 3 alpha-HSORred and 3 beta-HSORred. The reverse reaction or the conversion of 5 alpha-androstane-3 alpha,17 beta-diol and 5 alpha-androstane-3 beta,17 beta-diol is completely blocked in a medium containing one mM NADPH. These studies suggest that the concentration of DHT in prostatic tissue is dependent on the level of NADPH necessary for the 3 alpha-HSORred and 3 beta-HSORred enzymes to convert DHT to its respective diols.

Androstanes↗
PubMed1983

A strategy of malaria control.

A field investigation was designed to determine the feasibility of a single annual application of DDT which could fulfil the objectives of malaria control. The concept of a single spraying cycle would eliminate the risks and disadvantages associated with the standard methodology of two spraying cycles, and would result in logistic and economic gains to the country. The timing of the spraying cycle in this modified control methodology is based on the determination of the malaria season solely from entomological data. Details of the field investigation for the years 1974 and 1975, the parameters for calculation of vectorial capacity, estimates of the relative malaria receptivity within the study area, and determination of the malaria season of six months' duration have already been published. The present paper applies the concept of a single spraying cycle to the findings of the investigation and discusses the implementation of the strategy.

Anopheles↗
PubMed1980

Biting prevalence and malaria transmission patterns in the Anopheles punctulatus complex (Diptera: Culicidae) in Papua New Guinea.

Seasonal prevalence and malaria transmission patterns of Anopheles farauti, An. punctulatus and An. koliensis were studied in two coastal and two inland villages in the Madang district of northern Papua New Guinea. The monthly manbiting rates (average biting density of vector mosquitoes per man per night) were observed over a two-year period to establish typical seasonal prevalence patterns. Observations on the frequency of feeding and the human blood index were combined to derive the manbiting habit. A daily survival rate was determined from the dissection of mosquito ovaries by Polovodova's age-grading method. The extrinsic cycle in the mosquito was not observed, and the value for this parameter was extracted from the literature. All parameters were combined to estimate the monthly variations in vectorial capacity of each of the vector species, and the vectorial capacities of the individual species were added together to give a total monthly vectorial capacity of the punctulatus complex in each locality. The results showed that malaria transmission can be perennial, with a period of more intense transmission between August and January in the southern area, and between September and February in the northern. A period of very low transmission can be expected between February/March and July/August.

Animals↗