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Biomedical subjects

M Elhilali

Publications and source records attributed to M Elhilali.

At least 55 records · Page 3Linked to original sources

Response of urethral smooth muscles to pharmacological agents. II. Noncholinergic, nonadrenergic agonists and antagonists.

We studied the effects of a variety of noncholinergic, nonadrenergic agents on the smooth muscles of the cat urethra. Prostaglandin F2 alpha contracted both urethral muscle layers to a similar extent. Prostaglandin E2 contracted the longitudinal and relaxed the circular muscle layers. The effects of the prostaglandins seem to be directly myogenic since cholinergic and adrenergic blockers and tetrodotoxin did not affect them. Bradykinin and substance P contracted both urethral muscle layers. Other tested agonists (neurotensin, vasoactive intestinal peptide, cyclic 3,5 adenosine monophosphate, adenosine diphosphate sodium, cyclic 3,5 guanosine monophosphate sodium, bombesin) had no effect on the cat urethral smooth muscles.

Animals↗

Nuclear androgen receptors of human prostatic tissue--a quantitative histological study.

The objective of this study was to determine the nuclear dihydrotestosterone (DHT) nuclear receptors content in tissues of normal prostate, benign prostatic hypertrophy (BPH), and prostatic cancer. We also attempted to correlate this with the histological pattern of these tissues. Specimens were obtained from five normal subjects, 24 BPH, and 19 prostatic cancer patients. Nuclear receptors content was determined. All histological sections were reviewed by three independent pathologists. The criteria for the quantitative analysis were the degree of cellularity and the stromal content. The mean receptor content was not significantly different between neoplastic tissue (52.6 fmol/mg protein) and hyperplastic tissue (38.9 fmol/mg protein). The number of binding sites in normal prostatic tissue was 8.5 fmol/mg protein. The correlation between the degree of cellularity and DHT receptors showed no significant difference for both BPH, as well as prostatic cancer. Similar results were obtained when stromal content was compared.

Adenocarcinoma↗

Orthotopic implantation of primary N-[4-(5-Nitro-2-furyl)-2-thiazolyl]formamide-induced bladder cancer in bladder submucosa: an animal model for bladder cancer study.

Primary bladder tumors induced in Fischer 344 inbred rats by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide were transplanted in syngeneic rats by the intravesical, s.c., i.v., and orthotopic routes. Attempts were made to establish bladder cancer cell lines in vitro. No success was achieved in transplantation by either the s.c., i.v., or intravesical routes when primary tumor cells were transplanted as cell suspensions. Cell suspensions of primary tumors also failed to grow in culture. However, orthotopic implantation into the bladder submucosa gave 45% success. Tumor fragments obtained from either the primary tumor or its lung metastases resulted in 10.6 and 36% tumor takes, respectively, when implanted s.c. However, after one orthotopic passage in the bladder submucosa, the tumor cells injected as cell suspension grew s.c. in 14% and orthotopically in 79% of the animals. Tumor fragments obtained from orthotopic tumors and implanted s.c. resulted in 15% tumor takes. After the second orthotopic passage, tumor cells could be grown in cultures and orthotopically in 100% of animals. The technique of orthotopic implantation as well as the usefulness of this tumor model for bladder cancer studies are described.

Animals↗

Urorectodynamic evaluation of healthy volunteers.

Twelve female and 8 male healthy volunteers underwent urorectodynamic evaluation. Mean bladder capacity was 594 ml. and mean maximal vesical pressure 12.5 cm. water (H2O). Maximal bladder pressure correlated significantly with maximal mural tension (r = 0.96) but did not correlate well with bladder capacity (r = 0.20). Mean bladder volume at first desire to void was 32 per cent of mean bladder capacity. The bladder volume at the first desire did not correlate significantly with the capacity. Mean bladder pressure at 100 ml. volume was 2.9 +/- 0.4 cm. H2O (X +/- SEM). After bethanechol injection, the bladder pressure at 100 ml. volume increased by 8.8 +/- 1.2 cm. H2O (X +/- SEM) at twenty minutes. In only 1 subject did bladder pressure rise higher than 15 cm. H2O (5 per cent). Rectal pressure increased from 1.4 +/- 0.3 to 14.1 +/- 2 cm. H2O (X +/- SEM) at sixteen minutes. Electromyogram (EMG) of the external and sphincter did not follow regular pattern with vesical filling or attempt of voiding. The data obtained in these normal subjects may serve as a basis for comparison in the interpretation of data obtained in patients.

Adult↗

Vesicourethral electromyography: facts or artefacts.

A vesicourethral electromyographic study was carried out on 21 cats of both sexes with extracellular electrodes along with monitoring of contraction and relaxation of various parts of the bladder and urethra. No consistent electromyographic pattern of slow and fast waves was observed in the bladder and urethra either in any empty bladder or during filling and voiding phases. Most of the recorded waves were traced to a defined source of artefact. Twenty-two experiments were done with glass microelectrodes recording intracellularly in bladder strips of various animals bathed in normal and modified Krebs solutions. No spike activity was recorded during periods of contractions, whether spontaneous or electrically stimulated. Both in vivo and in vitro experiments suggest that the mechanism of excitation-contraction coupling of the bladder remains unidentified. The clinical application of bladder electromyography (EMG) has to be interpreted cautiously.

Action Potentials↗

Bromocriptine therapy in oligozoospermic infertile men.

A prospective, randomized double-blind study with crossover using bromocriptine and placebo was performed on a group of 17 infertile males with idiopathic oligozoospermia. Twelve patients completed the duration of this study of eight months by receiving 5 mg of bromocriptine per day for four months followed by four months of placebo or vice versa. Prior to treatment, the sperm count was 8.76 +/- 1.32 (10(6)/ml). The hormonal profile was performed prior to treatment and included estimation of prolactin, T3, T4, thyroid stimulating hormone (TSH), testosterone, follicle stimulating hormone (FSH), and plasma LH. Stimulation studies using LHRH and TRH were also performed. All hormonal estimations were within normal limits. Compared to placebo, bromocriptine had no significant effect on sperm analysis, or basic hormonal profile. The stimulation test with luteinizing hormone releasing hormone (LHRH) was unchanged except for the basic plasma testosterone, which increased. The prolactin decreased following the thyrotropin releasing hormone (TRH) stimulation. Two pregnancies were noted four to six weeks following the end of treatment. Bromocriptine did not seem to be more effective than placebo in the treatment of idiopathic oligozoospermia.

Adult↗

Primary infertility: correlation between sperm migration test and humoral immunity.

Eleven couples with unexplained primary infertility were studied. The only abnormality appeared to be a poor sperm migration test (P.S.M.T.). The importance of circulating immune factors in these couples was assessed using a modified Kibrick test. Control sera included four provided by the WHO, four of our known positive samples, 49 sera obtained prevasectomy, and 17 sera collected from infertile couples with organic female pathology. A positive titer was found in one out of 49 control sera before vasectomy and in four out of 17 control coupled with organic female factors. In the 11 couples with poor sperm migration test, the titer was positive in two female and three male subjects. The wives of two of these male subjects with a positive titer became pregnant without any therapy. These results cast some doubts about the predictive value of such a test.

Agglutination Tests↗

The contractile effect of bombesin on the rat isolated urinary bladder.

We have investigated and compared the myotropic effects of bombesin (BB) and carbachol (C) in the rat isolated urinary bladder. BB (0.5 x 10(-9) to 0.5 x 10(-5) M) and C (2.7 x 10(-8) to 5.4 x 10(-5) M) were found to produce dose-dependent increases of the basal tone of the rat detrusor muscle. The maximal contraction produced by C was about 4 times greater than that elicited by BB or substance P (SP). However, the threshold concentrations of BB and SP required to stimulate the detrusor muscle were much lower than those of C. The pD2 (-log ED50) values of BB, SP and C were respectively 7.63, 7.05 and 5.8. The tissues exposed to BB relaxed more slowly after washout than those challenged with C or SP. The contractile effects of medium range concentrations of BB were not affected by pretreating the tissues with tetrodotoxin, atropine, antihistaminics, indomethacin, alpha- and beta-adrenergic blockers, methysergide or 8-leucine-angiotensin II. Tissues desensitized with high concentrations of bradykinin maintained their sensitivity to BB. The result suggest that the contractile effect of BB on the rat isolated urinary bladder is likely to be the result of a direct effect on the smooth muscle cells.

Animals↗

Condyloma acuminatum of bladder.

A patient with a condyloma acuminatum of the bladder is presented. This is a rare manifestation of the lesion. The salient features which characterize the lesion are described, and the differential diagnosis is discussed.

Aged↗

Clinical and urodynamic evaluation of urethrocystopexy for stress urinary incontinence: preliminary report.

Thirteen patients presenting with stress urinary incontinence associated with a notion of urgency were evaluated. Each patient underwent a full clinical and paraclinical preoperative evaluation. The urodynamic evaluation included flowmetry, urethral profile, cystometry lying down and standing, and intrarectal pressure measurement. All these patients were operated on (urethrocystopexy), and the evaluation was repeated between one and eight months. The frequency, both diurnal and nocturnal, was reduced in the postoperative period. The urgency decreased from 46 per cent prior to surgery to 7.6 per cent postoperatively. Thirty-eight per cent of patients had urgency incontinence prior to surgery, and none of these patients was incontinent postoperatively. Stress incontinence was corrected in all patients during the period of follow-up. The urodynamic parameters were practically unchanged by the surgery. These parameters included the urethral length, maximum urethral pressure, vesical capacity, and maximum vesical pressure both while lying down and standing. In 4 patients with urgency incontinence preoperatively, the bladder capacity lying down was significantly higher than the bladder capacity standing up whereas the difference was not significant in the patients without urgency incontinence. This difference disappeared postoperatively. No evidence of true uninhibited bladder contractions were noted in any of these patients while lying down or standing.

Adult↗

Urorectodynamics in patients with colonic inertia.

Sixteen female patients with colonic inertia and 12 control women underwent manometric evaluation of their bladder and rectal cavities. After subcutaneous injection of 0.035 mg./Kg. bethanechol, bladder intraluminal pressure increased by over 15 cm. water in 5 patients (31 per cent) and in none of the control group; maximal pressure after injection was 11.5 +/- 1.6 cm. H2O (mean +/- SE) in patients and 8.5 +/- 1 in controls (p less than 0.025). The intraluminal rectal pressure reached 23 +/- 4 cm. H2O in patients and only 11.9 +/- 1.4 in controls (p less than 0.0025). Time taken to reach a peak pressure was faster in patients both in bladder (17.4 +/- 0.7 vs. 19.8 +/- 1.2 minutes; p less than 0.01) and in the rectum 914.6 +/- 0.8 vs. 16.3 +/- 1.2; p less than 0.025). These findings and the clinical presentation suggest an autonomic neuropathic lesion in this group of patients.

Adult↗

The antitumour activity of maltose tetrapalmitate compared with other immunoadjuvants, and its effectiveness after tumour surgery.

The effectivenss of maltose tetrapalmitate (MTP) as an antitumour immune adjuvant was verified by its comparison with other known immunopotentiators, namely BCG, Corynebacterium parvum, levamisole and pyran copolymer. Copenhagen x Fisher 344/CRBL F1 hybrid male rats inoculated s.c. with the Dunning R3327A prostatic adenocarcinoma were used as the test system. All animals treated with immunoadjuvants showed a delay in tumour appearance and inhibition of early tumour growth. MTP was found to be the most effective, followed by levamisole, BCG, pyran copolymer and C. parvum in order of decreasing efficacy. Intratumoral treatment of small or large s.c. tumours with BCG, MTP and C. parvum was ineffective in our cases. However, this treatment was effective with MTP and BCG if they were used against a differentiated form of R3327 tumour. MTP and levamisole were found to be equally effective when given orally in drinking water. Experiments involving surgical excision of tumours followed by MTP therapy in two s.c. implanted animal tumour models (viz. a poorly immunogenic ascites mammary carcinoma 13762 in Fisher 344/CRBL rats, and an SV40 virus-induced sarcoma of low immunogenicity in Syrian hamster) showed beneficial effects of MTP on local tumour recurrence and tumour growth. Pre- and postoperative MTP treatment was at least as effective as postoperative MTP treatment alone.

Adenocarcinoma↗

Dihydrotestosterone receptors in the human prostate. I. Nuclear concentration in normal, benign, and malignant tissues.

A technique was standardized to measure nuclear dihydrotestosterone receptors in human prostate. Normal, hyperplastic (BPH), and cancer tissues were homogenized and the homogenate centrifuged at 600 g X 10 min; the pellet was purified on sucrose density gradient. Purified nuclei were extracted with 0.4 M KC1. The nuclear extract was then incubated in the presence of [3H]dihydrostestosterone (DHT) at 4 degrees C for 20 hr. Competition studies with different steroids indicated a high specificity of the receptor towards DHT and no affinity towards progesterone and 17 beta-estradiol. Isolation and purification of [3H]DHT after its incubation in the presence of the KC1 nuclear extract indicated that no significant degradation of the hormone occurred during incubation. The number of binding sites measured was 8.5 +/- 0.77 fmol/mg protein (mean +/- SEM) for normal, 38.6 +/- 5.9 for BPH, and 79.9 +/- 21.9 for cancer. The possible clinical application of these results will require a long-term follow-up of the hormonal responsiveness of the prostatic-cancer patients investigated.

Binding, Competitive↗

Characterization and partial purification of the 8-9S androgen receptor from benign prostatic hyperplasia tissues.

The present study reports a 3,800-fold purification of the 8-9S androgen-receptor complex from benign prostate hyperplasia (BPH) tissues using differential chromatography. In addition, the BPH androgen receptor complexes have been characterized using sucrose density gradient (SDG) ultracentrifugation, gel permeation, and anion exchange high performance liquid chromatography (HPLC). Results indicate that a) under nontransforming conditions, BPH cytosols contained both 8-9S (40-78%) and 4S (22-60%) androgen-receptor forms, b) apparent molecular weights of these androgen-receptor apparent molecular weights of these androgen-receptor complexes, as analyzed by gel permeation HPLC, were estimated to correspond at 270 kDa, and 90 kDa respectively, c) 8-9S androgen-receptor complexes were retained on an anion exchange HPLC column and could be eluted at 0.22 M KCl at a linear gradient, whereas 4S complexes were not retained on anion exchange columns under identical experimental conditions, d) 10X dilution of BPH cytosols containing only the 4S (0.6 M KCl) form and subsequent chromatography on anion exchange HPLC system was indicative of fragmentation (these fragments were retained on anion exchange columns and could be eluted by 0.33 M KCl on a linear gradient HPLC), and e) increased temperature (22 C) was permissive of proteolytic fragmentation (fragments were estimated to correspond at 30, 15, and 5 kDa). The results are discussed in relationship with the composition of the nontransformed androgen-receptor molecules.

Aged↗

Sucrose density gradient and exchange high performance liquid chromatography characteristics of rat prostate androgen receptor forms.

In this study, we characterized rat prostate androgen receptor using sucrose density gradient ultracentrifugation, gel permeation and anion exchange high performance liquid chromatography (HPLC). Our results indicated that 1) androgen receptor complexes in rat prostate cytosols containing no KCl were of 8-9S form corresponding to 270kDa, and in cytosols containing 0.6M KCl were of 5-6S form corresponding to 90kDa; 2) 8-9S androgen receptor complexes were retained and could be eluted by 0.22M KCl in a linear gradient anion exchange HPLC; 3) Dilution (10X) of the 8-9S and of the 5-6S receptor complexes and subsequent chromatography on anion exchange columns was indicative of fragmentation. Fragments were of 3-4S form and were eluted by 0.33M KCl on anion exchange HPLC. Temperature (22 degrees C) was permissive of proteolysis generating a 30kDa androgen receptor fragment. These results are discussed in the context of the composition of non-transformed rat prostate androgen receptor.

Animals↗