Biomedical subjects

R R Tremblay

Publications and source records attributed to R R Tremblay.

At least 55 records · Page 3Linked to original sources

PubMed1990

Treatment of hirsutism with the pure antiandrogen flutamide.

The effectiveness of the antiandrogen flutamide in combination with an oral contraceptive was studied in 20 patients with moderate to severe hirsutism. Eight patients had no previous therapy, whereas 12 had failed to respond to oral contraceptives, spironolactone, or dexamethasone therapy. Treatment with the antiandrogen flutamide (250 mg twice daily) and an oral contraceptive (Ortho 1/35) resulted in a particularly rapid and marked decrease in the total hirsutism score, which reached the normal range at 7 months. Seborrhea, acne, and hair loss score were also rapidly corrected. Treatment was associated with a decrease in plasma luteinizing hormone, progesterone, and estradiol levels. Plasma sex hormone-binding globulin levels were initially low in 18 to 20 patients but increased significantly during therapy. No clinically significant side effects were observed.

Adult↗

PubMed1990

Intravenous fluid therapy in calves.

Intravenous fluid therapy is valuable as primary or ancillary therapy for many conditions in calves. The first step in developing an intravenous fluid plan is determination of the volume needed to replace the fluid deficit, estimated on the basis of clinical signs. The parenteral solution to be used is chosen to be similar in electrolyte composition to the fluid lost. Abnormalities of specific electrolytes, acid-base balance, and energy metabolism can be addressed during volume replacement; this requires an understanding of the pathophysiology of the primary clinical abnormality. The fluid delivery system is composed of an administration set and an intravenous catheter. The administration set allows sterile delivery and regulation of the rate of administration. An intravenous catheter is selected, inserted, and maintained to minimize the potential for catheter-related complications.

Animals↗

PubMed1990

Actin and creatine kinase mRNAs in rat levator ani and vastus muscles as a function of androgen status.

The plasticity of two selected mRNAs was studied in two typical fast-twitch muscles at different time intervals after orchiectomy (GDX). The levator ani muscle of the rat (LA) is exquisitely sensitive to androgens, whereas the superficial vastus lateralis (SVL) lacks such sensitivity. In vitro translation of RNA isolated from both tissues indicated that actin was among the most repressed proteins of the LA at day 10 postsurgery (GDX-10 days), whereas the template activity of the SVL mRNAs remains virtually unmodified. We used an available actin cDNA and demonstrated that the expression of the LA actin message is reduced by 85% in GDX-10 days and can be recovered after testosterone propionate (TP) injections (GDX + TP). In contrast, the actin expression in SVL remains constant up to day 20 postsurgery. In the LA, the expression of creatine kinase (CK) mRNA was increased 140% in GDX-5 days and decreased 34 and 17% in GDX-10 days and GDX-20 days, respectively, although the measured CK activity, as well as the in vitro translation of the message, remained elevated in those two latter groups. Control level of the CK mRNA expression was recovered in the GDX + TP group. Again, the expression of the message was unchanged in SVL, suggesting that the protein synthesis of this skeletal muscle is far less sensitive to androgen deprivation than that of the LA muscle.

Actins↗

PubMed1990

Alpha-1,4-glucosidase activity in ram seminal plasma is inversely related to serum testosterone.

The epididymis of adult rams is the primary source of alpha-glucosidase in seminal plasma. Two breeds of rams were selected to ascertain whether the enzyme was under androgenic control during adult life of rams. Opposite variations between serum testosterone and alpha-glucosidase were recorded over a period of 16 months in Suffolk and Finnish Landrace. In addition, the highest percentage of sperm motility was associated with a low alpha-glucosidase content of seminal plasma. Data from this study suggest that seasonal variations of testosterone in adult rams exert a negative control on the presence of alpha-glucosidase in semen.

Animals↗

PubMed1990

Fate of alpha-1,4-glucosidases and cathepsin D in the rat epididymis after vasectomy.

Short-term vasectomy was studied in adult male rats in order to ascertain whether cytosolic or lysosomal hydrolases were differently affected 100 days after vas ligation. The secretory form of alpha-1,4-glucosidase remained unchanged while the lysosomal form of the enzyme and also cathepsin D increased in the cytosol of both caput and cauda epididymis. This set of data demonstrates for the first time that a triggering mechanism which stimulates lysosomal activity is present all along the rat epididymis. Disposal of the continuous influx of spermatozoa from the testis could therefore require both an active and a passive process.

Animals↗

PubMed1990

Expression of Zn-alpha 2-glycoprotein and PSP-94 in prostatic adenocarcinoma. An immunohistochemical study of 88 cases.

Zn-Alpha 2-Glycoprotein (Zn-Alpha 2-GP) and prostatic secretory protein of 94 amino-acids (PSP-94) were recently isolated from the human prostate. Their expression in benign and malignant well-differentiated and poorly differentiated components of 88 prostates with prostatic adenocarcinomas, and in 25 metastases, was evaluated using polyclonal antibodies developed against these antigens. Zn-Alpha 2-GP was present in benign hyperplastic glands in 91.1% of cases, but in only 40.7% (poorly differentiated component) to 48.5% (well-differentiated component) of prostatic adenocarcinomas, and in 8% of metastases. The expression of PSP-94 was present in 89.3% of benign hyperplastic glands, but in only 50% (well-differentiated adenocarcinoma component) to 57.3% (poorly differentiated component) of prostatic adenocarcinomas and 28% of metastases. The expression of these proteins by the tumor was unrelated to the initial stage and the tumor grade. Because of their low frequency in prostatic adenocarcinomas, especially in metastases, Zn-Alpha 2-GP and PSP-94 appear to have a limited diagnostic usefulness. Further studies are needed, however, to explore other clinical applications of these two new prostatic secretory proteins.

Adenocarcinoma↗

PubMed1989

Effect of denervation on the androgen-induced expression of actin and CPK mRNAs in the levator ani muscle of the rat.

In the adult male rat, the castration-induced atrophy of the levator ani (LA) muscle was found to be associated with a decrease in the relative levels of both actin and creatine phosphokinase (CPK) mRNAs. The typical recovery of these two sequences following 5 days of testosterone propionate (TP) replacement therapy was not impaired by the bilateral denervation of the LA. This indicated that TP was the sole trophic factor regulating the plasticity of these two mRNAs and challenged the hypothesis that androgen action might be neuronally mediated. The observation that denervation led to a severe repression of both actin and CPK messages only in the absence of TP replacement therapy suggested that the nerve impulse could play an accessory role in the control of their expression.

Abdomen↗

PubMed1989

Synthesis of alpha 1-acid glycoprotein by the human prostate.

In order better to define the extent of protein synthesis capacity of the human prostate, we have studied the translation of selected serum proteins using isolated poly(A)+ RNA preparations and the rabbit reticulocyte lysate system. The translation of alpha 1-acid glycoprotein could be conclusively demonstrated but there was no apparent translation of albumin and plasmatic transferrin. Labeled alpha 1-acid glycoprotein was identified by specific immunoprecipitation with a commercial anti alpha 1-acid glycoprotein antiserum and correct processing by canine pancreatic microsomal membranes. Furthermore, we have shown by the immunoperoxidase technique that alpha 1-acid glycoprotein was indeed localized mainly in prostatic epithelial cells in 2 out of 2 patients with benign prostatic hypertrophy and in 3 out of 11 patients with prostatic adenocarcinoma. The significance of the synthesis and secretion of alpha 1-acid glycoprotein by prostatic cell themselves is presently unknown. However, we think that it could represent an interesting subject to explore further in relation with prostatic inflammation.

Cell-Free System↗

PubMed1989

Looking for human glandular kallikrein-1 in the prostate.

Based on recent studies indicating that human glandular kallikrein-1 (hGK-1) mRNA was present in the prostate, we have undertaken to determine whether the prostate contained trypsin-like proteases with properties compatible with those deduced from hGK-1 gene nucleotide sequence. The first series of experiments showed that only minimal levels of trypsin-like enzymatic activity, determined with synthetic substrates, were present in chromatographic fractions of prostatic glycoproteins having a molecular weight in the range expected for hGK-1, i.e., 25,000-35,000. Because of this, we used [3H]diisopropylfluorophosphate (DFP) labeling alone or in the presence of various serine-protease inhibitors to identify trypsin-like proteases in the prostate. Two-dimensional gel electrophoresis of prostatic glycoproteins showed the presence of minor spots of 18-32 kDa. These spots were slightly more acidic than were those of prostate specific antigen (PSA) and were completely inhibited by preincubation with tosyl lysine chloromethyl ketone and p-nitrophenyl-p-guanidobenzoate in contrast to PSA spots that were not affected by these treatments. When a similar procedure was applied to total cytosolic proteins instead of glycoproteins, an additional 30 kDa DFP binding protein was observed. This relatively abundant protein was much more acidic than was PSA and was not inhibited by any of the protease inhibitors tested. In conclusion, this study has permitted us to demonstrate the presence of two sets of proteins that have physicochemical properties compatible with those that can be deduced from the information contained in the hGK-1 gene.

Amino Acid Sequence↗

PubMed1989

Acetazolamide-sensitive and resistant carbonic anhydrase activity in rat and rabbit skeletal muscles of different fiber type composition.

1. Acetazolamide (ACET)-resistant and -sensitive carbonic anhydrase (CA) activity was measured in post-mitochondrial supernatants from the soleus (SOL), deep vastus lateralis (DVL) and superficial vastus lateralis (SVL) muscles of rats and rabbits. 2. The relative total CA activity in the three muscles of both species can be summarized as SOL greater than DVL greater than SVL. 3. ACET-resistant CA activity was found in the SOL and DVL muscles of both species whereas a low level of ACET-sensitive CA activity was detected in the SVL muscle. 4. ACET-sensitive CA activity was also found in sarcoplasmic reticulum preparations from rat and rabbit SOL muscles.

Acetazolamide↗

PubMed1989

Depressed translational activity in the androgen sensitive levator ani muscle of the rat.

The androgen-dependent levator ani (LA) muscle of the rat provides a suitable model to explore the molecular mechanism of steroid hormone action in target tissues. The objective of the present series of experiments was to study the effect of gonadectomy (GDX) and androgen replacement therapy on the in vitro protein synthetic capacity of the LA muscle. The incorporation of labeled methionine into the contractile protein fraction of the LA muscle maintained in organ culture decreases in a time-dependent manner following GDX. Translation of total polyadenylated mRNA in the rabbit reticulocyte translation system revealed that the decrease in protein synthetic capacity was not associated with differences in the template activity of the mRNA derived from GDX tissue. However, when polyribosomes were used to direct the same in vitro synthesis system, a significant time-dependent loss of translational activity was observed following GDX. The polyribosomes of the LA muscle of control and GDX rats were shown to contain equivalent amount of rRNA and mRNA of comparable translation efficiency. Collectively the results of these experiments indicate that the decrease in protein synthetic capacity of the LA muscle in androgen deficient rats is due, in part, to a repression of the translation process associated to the functional integrity of polyribosomes.

Animals↗

PubMed1989

Effect of the androgenic status on the phenotype of the plantaris muscle of the rat.

1. The early demonstration of specific androgen binding sites in skeletal muscle suggested that androgen might be involved in the homeostasis of the tissue in adult mammals. 2. Following five weeks of androgen withdrawal, a noticeable increase in the plantaris (PLT) myosin heavy chain cleavage occurs. No other alteration of the contractile proteins pattern was detected. 3. No effect on the template activity of major mRNAs associated with the polysomal fraction was observed in GDX or GDX + TP group compared to control rats. 4. As opposed to the PLT muscle, the template activity of polyribosomes isolated from the androgen sensitive levator ani muscle displays a severe alteration following GDX. 5. Force-frequency analysis of PLT indicated however that the MHC modification was of no functional significance.

Androgens↗

PubMed1989

Zinc binding to major human seminal coagulum proteins.

In vitro binding of zinc to proteins of the human ejaculate and of the various male accessory gland secretions was evaluated. The proteins were separated by sodium dodecyl sulfate gel electrophoresis and transferred to nitrocellulose filters that were subsequently incubated with 65ZnCl2. High levels of zinc binding were observed to approximately 20 protein bands (14 to 70 kDa) of the coagulated seminal plasma. There was only low binding to proteins of the spermatozoa and virtually no binding to any protein of the epididymal and prostatic fluids. When sperm liquefaction was allowed to occur, 65ZnCl2 binding to high-molecular weight proteins decreased rapidly, and after 15 min only the binding to proteins of molecular weights less than 25 kDa remained. In addition, zinc concentration was determined both in the centrifugate and in the supernatant after centrifugation of the coagulum. Zinc concentrations in the centrifugate and the supernatant were, respectively, 147 +/- 72 micrograms/g and 31 +/- 22 micrograms/g. The whole supernatant contained only 12% +/- 4% of total sperm zinc. Finally, in highly viscous sperm samples the concentration of zinc was not significantly different from that in normally liquefying sperm (167 +/- 87 micrograms/ml compared to 188 +/- 107 micrograms/ml). The main extracellular targets of prostatic zinc in humans are the secreted seminal vesicle proteins. The role of this binding remains unknown, however, because no direct relationship could be established between the concentrations of this metal and the phenomena of coagulation and liquefaction.

Humans↗

PubMed1989

Failure of aspirin to impair bovine platelet function.

The effect of aspirin on bovine platelet function and thromboxane A2 (TXA2) production in stimulated platelets was evaluated. A single dose of aspirin (100 mg/kg of body weight) was administered orally to Holstein cows, and blood samples were obtained before and at regular intervals for 7 days after treatment. The production of TXA2 was assessed by measuring the stable metabolite thromboxane B2, using a specific radioimmunoassay. Within 4 hours of aspirin administration, the production of TXA2 was significantly (P less than 0.05) decreased, irrespective of whether collagen, adenosine diphosphate, or platelet activating factor was used to initiate platelet aggregation. Despite the inhibition of TXA2 release from the stimulated platelets, platelet function, assessed by initial rate of aggregate formation and extent of aggregation, was unaffected by aspirin administration. The extent of aggregate formation in response to collagen, adenosine diphosphate, or platelet activating factor was independent of the amount of TXA2 released from platelets before and after aspirin treatment. The results suggested that TXA2 formation is not the primary biochemical pathway involved in the aggregation of stimulated bovine platelets.

Animals↗

PubMed1988

High level of expression in the prostate of a human glandular kallikrein mRNA related to prostate-specific antigen.

Using a synthetic oligonucleotide primer complementary to human prostate-specific antigen mRNA, we found that an additional sequence possibly similar to human glandular kallikrein-1 could be read by a primer-extension sequencing technique. We were able to confirm the identity of that additional sequence with another oligonucleotide primer complementary to a specific region of the human glandular kallikrein-1 mRNA sequence. Northern blot analysis with 2 oligonucleotide probes respectively specific for prostate-specific antigen and human glandular kallikrein-1 mRNAs showed that the length of both mRNAs was similar at 1.5 kb. The level of human glandular kallikrein-1 mRNA relative to that of prostate-specific antigen could be estimated as approx. 10-20%. This study constitutes the first evidence that the human glandular kallikrein-1 gene is expressed at a high level in a human tissue.

Antigens, Neoplasm↗

PubMed1988

Nucleotide sequence of the androgen-dependent arginine esterase mRNA of canine prostate.

The nucleotide sequence of canine prostate arginine esterase mRNA was determined using a 400 bp cDNA clone and primer-extended cDNA transcripts for the 5'-coding and noncoding regions. The mRNA contains 864 nucleotides encoding a protein of 236 amino acids preceded by 24 amino acids which constitutes both the signal and the zymogen peptides. The sequence indicates the presence of one potential glycosylation site. A high degree of homology was found between the canine enzyme and other members of the kallikrein family including human prostate specific antigen. The protein appears to be specified by a single gene.

Amino Acid Sequence↗

PubMed1987

Radioimmunoassay in blood plasma of arginine esterase: the major secretory product of dog prostate.

We have developed a radioimmunoassay to determine serum levels of arginine esterase, the major secretory product of the canine prostate. Although the antibodies recognized other related proteins in immunoblotting conditions, particularly in the pancreas, the radioimmunoassay appeared specific for arginine esterase of prostatic origin and reacted only slightly or not at all with cytosolic proteins from salivary glands, liver, skeletal muscles, and kidney. In serum samples, the sensitivity limit of the assay was about 2.5 ng per ml. The interassay and intraassay variations for serum samples that contained concentrations of arginine esterase ranging from 6 to 21 ng per ml were, respectively, 14% and 24%. Sera from 30 adult males and 14 adult females contained, respectively, 71 +/- 9 and 5.3 +/- 0.4 ng per ml. In a group of 12 dogs treated daily for 36-39 days with 50 micrograms of D-Trp6-luteinizing hormone-releasing hormone ethylamide, the concentrations of arginine esterase in the serum decreased progressively and became identical with those observed in the females. These results constitute the first evidence for the presence of a serum marker of the normal prostate in an experimental model. It should be particularly useful to test the effects of various agents on the prostate.

Animals↗

PubMed1987

Excretion of three major prostatic secretory proteins in the urine of normal men and patients with benign prostatic hypertrophy or prostate cancer.

We have studied the mode of excretion of three prostatic secretory proteins, namely acid phosphatase (PAP), prostate-specific antigen (PSA) and beta-inhibin, in the urine of normal adult men, and we have determined the urinary levels of these proteins in men with benign prostatic hypertrophy (BPH) or adenocarcinoma. The output of the three proteins was highly variable during the day. In order to minimize these variations, 24-hour urine samples were collected thereafter. Our study showed that PAP concentrations in 50% of men with or without symptomatic BPH were similar to those of normal young men. In the remaining 50%, PAP was undetectable. In contrast, average PSA and beta-inhibin concentrations were higher in patients with BPH than in young men (p less than 0.05). The three markers were decreased or nondetectable in about half of the patients with untreated prostatic cancer. This phenomenon was even more pronounced in patients receiving hormonal treatment (castration or diethylstilbestrol). However, some of these patients still excreted normal amounts of PAP, PSA, and beta-inhibin. Urinary and serum PAP levels showed no correlation. These results indicate that urinary prostatic markers provide an easy means to study the behavior of the primary prostatic tumor. This information may be of potential value since it is not obtained with serum markers which originate mostly from metastatic cells.

Acid Phosphatase↗