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Biomedical subjects

C Labrie

Publications and source records attributed to C Labrie.

At least 55 records · Page 3Linked to original sources
PubMed1997

Long-term inhibitory effects of a novel anti-estrogen on the growth of ZR-75-1 and MCF-7 human breast cancer tumors in nude mice.

The effects of the novel anti-estrogen EM-343 on the growth of 2 hormone-responsive human breast cancer tumors have been examined in athymic nude mice. At the low daily dose of 5 microg, EM-343 administered subcutaneously for 6 months completely blocked the stimulatory effect of endogenous estrogens on the growth of ZR-75-1 and MCF-7 tumors implanted in nude mice. In addition, uterine weight decreased by 60% while ovarian weight increased by 37%. Estrogen receptor (ER) levels measured by [3H]-labeled estrogen binding were markedly reduced (by 96%, 96% and 92%) in ZR-75-1 and MCF-7 tumors, and in the mouse uterus, respectively. Accompanying the decrease in ER, progesterone receptor levels were reduced by 79%, 87% and 76%, respectively, in the above-mentioned tissues following EM-343 treatment. Our data show the pure anti-estrogenic properties of EM-343 and its high potency as an inhibitor of growth of human ZR-75-1 and MCF-7 breast tumors in nude mice.

Animals↗
PubMed1997

Inhibitory effect of the novel anti-estrogen EM-800 and medroxyprogesterone acetate on estrone-stimulated growth of dimethylbenz[a]anthracene-induced mammary carcinoma in rats.

The novel anti-estrogen EM-800 and medroxyprogesterone acetate (MPA) inhibit estrone (E1)-stimulated growth of dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in a rat model. After 65 days, ovariectomy (OVX) decreased total tumor area to 9.6 +/- 3.9% of initial size, while E1 (1.0 microg, s.c., twice daily) stimulated tumor growth to 225 +/- 40.9% of initial size. Daily oral administration of 2.5 mg/kg body weight of EM-800 completely abolished E1-stimulated tumor growth. A low daily dose of EM-800 (0.25 mg/kg body weight) or MPA (1 mg, s.c., twice daily) used alone partially reversed the stimulatory effect of E1 on the growth of DMBA-induced tumors. The combination of both compounds, however, caused a more potent inhibitory effect than each compound used alone. A high dose of EM-800 completely or almost completely inhibited the E1-stimulated vaginal and uterine weights, respectively. The same dose of EM-800 completely reversed the inhibitory effect of E1 on serum luteinizing hormone levels. Uterine, vaginal and tumoral estrogen and progesterone receptor levels were reduced markedly following treatment with EM-800. Our data show that the combination of the pure anti-estrogen EM-800 with the androgenic compound MPA achieves greater inhibition of the growth of DMBA-induced mammary carcinoma than that achieved by each compound used alone.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Comparative effects of 28-day treatment with the new anti-estrogen EM-800 and tamoxifen on estrogen-sensitive parameters in intact mice.

Following 28 days of oral administration, in intact mice, the novel non-steroidal anti-estrogen EM-800 was at least 30-fold more potent than tamoxifen in inhibiting uterine weight. Moreover, the maximal inhibitory effect achieved with tamoxifen on uterine weight was only 40% that with EM-800. The pure anti-estrogenic activity of EM-800 on the hypothalamo-pituitary-gonadal axis is illustrated by the increase in ovarian weight, while tamoxifen, due to its estrogenic activity, decreased ovarian weight. EM-800 is 10- to 30-fold more potent than tamoxifen in inhibiting uterine and vaginal estrogen receptors. Since 17beta-hydroxysteroid dehydrogenase (17beta-HSD) is the key enzyme in estradiol formation, the potent inhibitory effect of EM-800 on uterine 17beta-HSD could play an additional role by decreasing the availability of estradiol in the uterine tissue, while tamoxifen, on the contrary, stimulates activity of the enzyme. The atrophic changes in both the endometrial and myometrial layers achieved with EM-800 almost reached those observed 28 days after ovariectomy. EM-800 also resulted in a marked decrease in the number of ovarian developing follicles and corpora lutea, while the number of atretic follicles was increased. Tamoxifen treatment, on the other hand, produced an increase in both the number and crowding of the endometrial glands and a mild atrophy of the myometrial layer. Tamoxifen caused atrophic changes of the vaginal epithelium, especially at the highest doses, though the atrophy was much less pronounced than that following EM-800 treatment or ovariectomy. In addition to being at least 30-fold more potent than tamoxifen in inhibiting uterine weight, the novel anti-estrogen causes atrophy of the endometrium, stimulates the hypothalamo-pituitary-gonadal axis and inhibits uterine 17beta-HSD activity, while tamoxifen exerts opposite and estrogen-like effects on these parameters.

17-Hydroxysteroid Dehydrogenases↗
PubMed1997

Characterization of the effects of the novel non-steroidal antiestrogen EM-800 on basal and estrogen-induced proliferation of T-47D, ZR-75-1 and MCF-7 human breast cancer cells in vitro.

Since estrogens play a predominant role in the development and growth of human breast cancer, antiestrogens represent a logical approach to the treatment of this disease. The present study compares the effects of the novel nonsteroidal anti-estrogen EM-800 and related compounds with those of a series of anti-estrogens on basal and 17 beta-estradiol (E2)-induced cell proliferation in human breast cancer cell lines. In the absence of added E2, EM-800 and related compounds failed to change basal cell proliferation, thus showing the absence of intrinsic estrogenic activity in the ER-positive T-47D, ZR-75-1 and MCF-7 cell lines. The stimulation of T-47D cell proliferation induced by 0.1 nM E2 was competitively blocked by a simultaneous incubation with EM-652, EM-800, OH-tamoxifen, OH-toremifene, ICI 182780, ICI 164384, droloxifene, tamoxifen and toremifene at apparent Ki values of 0.015, 0.011-0.017, 0.040-0.054, 0.043, 0.044, 0.243 and 0.735 nM, approx. 10 nM and > 10 nM, respectively. Similar data were obtained in ZR-75-1 and/or MCF-7 cells. Moreover, EM-652 was 6-fold more potent than OH-Tamoxifen in inhibiting the proportion of cycling MCF-7 cells. Our data show that EM-800 and EM-652 are the most potent known antiestrogens in human breast cancer cells in vitro and that they are devoid of the estrogenic activity of OH-tamoxifen and droloxifene suggested by stimulation of cell growth in the absence of estrogens in ZR-75-1 and MCF-7 cells.

Benzopyrans↗
PubMed1997

Blockade of the stimulatory effect of estrogens, OH-tamoxifen, OH-toremifene, droloxifene, and raloxifene on alkaline phosphatase activity by the antiestrogen EM-800 in human endometrial adenocarcinoma Ishikawa cells.

Although temporary benefits of tamoxifen therapy are observed in up to 40% of women with breast cancer, this compound, which is known to possess mixed estrogenic and antiestrogenic activities, has been associated with increased risk of endometrial carcinoma. This study compares the effects of the novel nonsteroidal pure antiestrogen EM-800 and related compounds with those of a series of antiestrogens on the estrogen-sensitive alkaline phosphatase (AP) activity in human endometrial adenocarcinoma Ishikawa cells. Exposure to increasing concentrations of up to 1000 nM EM-800 or its active metabolite EM-652 alone failed to affect basal AP activity. In contrast, incubation with 10 nM (Z)-4-OH-tamoxifen, (Z)-4-OH-toremifene, droloxifene, or raloxifene increased the value of this estrogen-sensitive parameter by 3.3-, 3.5-, 2.2-, and 1.6-fold, respectively, a stimulatory effect that was completely reversed by simultaneous exposure to 30 nM EM-800. Moreover, the stimulation of AP activity induced by 1 nM 17beta-estradiol was completely reversed by EM-800, EM-652, or ICI-182780, at the IC50 value of 1.98 +/- 0.23, 1.01 +/- 0.16, and 5.64 +/- 0.59 nM, respectively, whereas the partial blockade exerted by (Z)-4-OH-tamoxifen, (Z)-4-OH-toremifene, or raloxifene was observed at IC50 values of 13.5 +/- 3.80, 41.0 +/- 7.2, and 3.74 +/- 0.43 nM, respectively. Thus, as assessed by their activity in the human Ishikawa endometrial carcinoma cells, EM-800 and EM-652 are the most potent known antiestrogens in Ishikawa cells, and, most importantly, they are devoid of the estrogenic activity observed in these human endometrial cancer cells with (Z)-4-OH-tamoxifen, (Z)-4-OH-toremifene, droloxifene, and raloxifene.

Adenocarcinoma↗
PubMed1997

The key role of 17 beta-hydroxysteroid dehydrogenases in sex steroid biology.

17 beta-Hydroxysteroid dehydrogenase (17 beta-HSD) controls the last step in the formation of all androgens and all estrogens. This crucial role of 17 beta-HSD is performed by at least five 17 beta-HSD isoenzymes having individual cell-specific expression, substrate specificity, regulation mechanisms, and reductive or oxidative catalytic activity. Both estrogenic and androgenic 17 beta-HSD activities were found in all 25 rhesus monkey and 15 human peripheral intracrine tissues examined. Type 1 17 beta-HSD is a protein of 327 amino acids catalyzing the formation of 17 beta-estradiol from estrone. Its x-ray structure was the first to be determined among mammalian steroidogenic enzymes. Initially crystallized with NAD, the crystal structure of type 1 17 beta-HSD has just been determined as a complex with 17 beta-estradiol, thereby illustrating the conformation of the substrate-binding site. Type 2 17 beta-HSD degrades 17 beta-estradiol into estrone and testosterone into androstenedione, and type 4 17 beta-HSD mainly degrades 17 beta-estradiol into estrone and androst-5-ene-3 beta, 17 beta-diol into dehydroepiandrosterone. Types 3 and 5 17 beta-HSD, on the other hand, catalyze the formation of testosterone from androstenedione in the testis and peripheral tissues, respectively. The various types of human 17 beta-HSD, because of their tissue-specific expression and substrate specificity, provide each peripheral cell with the necessary mechanisms to control the level of intracellular androgens and/or estrogens, a new area of hormonal control that we call intracrinology.

17-Hydroxysteroid Dehydrogenases↗
PubMed1997

Daily dosing with flutamide or Casodex exerts maximal antiandrogenic activity.

OBJECTIVES: Because the large increase in luteinizing hormone secretion induced by flutamide in the intact rat is not found in men, we have used castrated rats and mice supplemented with androstenedione (4-dione) instead of intact animals to measure the activity of the pure antiandrogens flutamide and Casodex. METHODS: We first compared the effect of different schedules of administration of various doses of the two antiandrogens on prostate and seminal vesicle weights in the castrated rat and mice models. RESULTS: For both flutamide and Casodex, no consistent difference was found between the effects of once daily and thrice daily oral dosing in the rat. It was observed, however, that flutamide, especially at the high and therapeutically more effective doses, is about three times more potent than Casodex under both schedules of dosing. When flutamide was administered subcutaneously three times a day, twice a day, once a day, or once every second day in rats and mice, no difference was observed in the degree of inhibition achieved on prostate and seminal vesicle weights. CONCLUSIONS: The present data show that Casodex is about three times less potent than flutamide on the well-recognized parameters of androgen responsiveness in the rat, namely prostate and seminal vesicle weights. Another finding is that once daily dosing with flutamide exhibits an effectiveness comparable to thrice daily dosing; such data may have potential significance in facilitating compliance by administration of flutamide once daily instead of the current thrice daily schedule in men. Moreover, these data, if obtained in a reliable in vivo model, should be helpful in determining the choice of an appropriate dose of Casodex for the treatment of prostate cancer.

Androgen Antagonists↗
PubMed1997

Combined effects of dehydroepiandrosterone and EM-800 on bone mass, serum lipids, and the development of dimethylbenz(A)anthracene-induced mammary carcinoma in the rat.

Although treatment with dehydroepiandrosterone (DHEA) and the antiestrogen EM-800 alone decreased dimethylbenz(A)anthracene (DMBA)-induced mammary tumor incidence from 95% to 57% and 38%, respectively, approximately 9 months after DMBA administration, only two tumors developed in the group of animals that received the combination of DHEA and EM-800, and these two tumors disappeared before the end of the experiment (P < 0.01 vs. DHEA or EM-800 alone). Average tumor number per tumor-bearing animal as well as average tumor area per tumor-bearing animal were further decreased in animals that received the combination therapy compared with the effect of each treatment alone (P < 0.01). DHEA induced 6.9% (P < 0.01), 10.6% (P < 0.05), and 8.2% (P < 0.01) increases in bone mineral density of total skeleton, lumbar spine, and femur, respectively. The addition of EM-800 to DHEA did not affect the enhancing effect of DHEA on bone mass. The combination of the two drugs had important inhibitory effects on the urinary excretion of calcium and phosphorus as well as on the urinary hydroxyproline/creatinine ratio. Serum total alkaline phosphatase was stimulated by DHEA. Treatment with EM-800 decreased both serum triglyceride and cholesterol levels, whereas DHEA had an inhibitory effect on serum triglycerides. Although treatment with EM-800 caused a marked atrophy of the mammary gland, DHEA alone reduced lobular hyperplasia seen in aged intact rats while causing an androgen-specific stimulation of the same structures in animals already receiving the antiestrogen EM-800. The combination of DHEA and EM-800 lowered ovarian weight by 24% (P < 0.01) and decreased serum estradiol concentrations to intact control levels, whereas each compound alone had no effect on ovarian weight and stimulated serum estradiol levels by 45% (P < 0.05) and 46% (P < 0.05), respectively. Treatment with EM-800 caused a marked inhibition of uterine and vaginal weight. The present data show the additive inhibitory effects of DHEA and EM-800 on the development of DMBA-induced mammary carcinoma in the rat, thus suggesting the potential benefits of such a combination for the prevention of breast cancer in women while preserving or even increasing bone mass and maintaining a favorable lipid profile.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Morphological changes induced by 6-month treatment of intact and ovariectomized mice with tamoxifen and the pure antiestrogen EM-800.

The present study compares the effects of tamoxifen and EM-800, both administered at the oral daily dose of 100 microg for 6 months, on the uterus, vagina, and mammary gland in the mouse at histopathological examination. Treatment of intact animals with EM-800 resulted in uterine and vaginal atrophy even greater than that achieved after ovariectomy, while the developmental growth of the mammary gland was completely blocked and serum LH was increased. In ovariectomized animals, treatment with EM-800 decreased uterine and vaginal wt below the values observed in control ovariectomized mice while no significant change was observed on serum LH, thus indicating the lack of estrogenic activity of EM-800. Tamoxifen, on the other hand, showed a stimulatory estrogenic-like action on the mouse uterus in both intact and ovariectomized animals, thus resulting in moderate to severe endometrial hyperplasia. These morphological changes were accompanied by a marked stimulation of both the estrogenic and androgenic 17beta-hydroxysteroid dehydrogenase as well as 5alpha-reductase uterine activities. The histological atrophic changes observed in the vagina after tamoxifen treatment were less pronounced than those seen after treatment with EM-800. The agonistic estrogen-like action of tamoxifen was also illustrated by the suppression of serum LH levels in ovariectomized animals. A marked stimulation of the ovarian stroma, accompanied by a significant reduction in folliculogenic activity, was observed after EM-800 or tamoxifen administration, although the interstitial ovarian hyperplasia was more pronounced after EM-800 treatment. While both antiestrogens blocked the developmental growth of the mammary gland, EM-800 showed more potent antiestrogenic activity than tamoxifen. The highly potent and specific antiestrogenic activity of EM-800 suggests that this compound could improve the therapy of breast cancer while avoiding the undesirable stimulation of the endometrium.

17-Hydroxysteroid Dehydrogenases↗
PubMed1997

Effect of dehydroepiandrosterone on bone mass, serum lipids, and dimethylbenz(a)anthracene-induced mammary carcinoma in the rat.

The present study investigated the effect of dehydroepiandrosterone (DHEA) on bone mass and serum lipids in the rat with dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma. The animals received DHEA once daily, percutaneously, at the dose of 5, 10, or 20 mg for 9 months following a single dose of 20 mg DMBA at 50-52 days of age. Bone mineral content (BMC) and bone mineral density (BMD) of total skeleton, lumbar spine, and femur were measured by dual energy x-ray absorptiometry. A 9-month treatment with DHEA increased BMC and BMD of total skeleton by 14.2% to 14.5% (all P < 0.01) and 6.7% to 8.3% (all P < 0.01), respectively. Similarly, femoral BMC and BMD were stimulated by 13.6% to 14.7% (all P < 0.05) and by 8.1% to 9.5% (all P < 0.01), respectively. In addition, BMD of lumbar spine was increased by 10.4% to 10.8% (all P < 0.05), whereas the 9.4% to 11.1% increment in BMC of lumbar spine was not statistically significant. Treatment with DHEA led to 26% (NS), 60% (P < 0.01), and 62% (P < 0.01) decreases in serum triglyceride levels at the same doses. On the other hand, no significant change in serum cholesterol concentrations was observed. Two hundred and seventy-nine days after DMBA administration, the incidence of mammary carcinoma had decreased from 95% in control animals to 73% (P < 0.05), 57% (P < 0.01), and 38% (P < 0.01) at the daily percutaneous doses of 5, 10, and 20 mg of DHEA, respectively. Moreover, the mean tumor number per tumor-bearing animal and the mean tumor area per tumor-bearing animal were also reduced by the same treatments. DHEA increased serum total alkaline phosphatase activity and decreased urinary calcium excretion, but had no effect on the urinary ratio of hydroxyproline to creatinine and urinary phosphorus excretion. These data show that DHEA exerts a stimulatory effect on bone mass and an inhibitory effect on serum triglycerides, as well as a preventive effect on the development of mammary carcinoma induced by DMBA in the rat. Such data suggest that while decreasing the risk of breast cancer, DHEA replacement therapy could also exert beneficial effects on the bone and lipid metabolism in women receiving DHEA replacement therapy.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1996

A p18 mutant defective in CDK6 binding in human breast cancer cells.

Progression from G1 to the S-phase of the cell cycle is controlled by a family of low molecular weight cyclin-dependent kinase (CDK) inhibitors. The importance of these proteins in cell growth control is underscored by the observation that some members of this family are deleted or mutated in human cancers. For example, the gene encoding the CDK inhibitor p18 is located on a segment of chromosome 1 that is often abnormal in human breast tumors. We have identified an alanine to proline substitution at codon 72 of the p18 gene in BT-20 human breast cancer cells. This mutation abrogates the ability of p18 to interact with CDK6 and renders p18 deficient in suppressing cell growth in a colony formation assay. Our results suggest that p18 inactivation by point mutations may contribute to deregulated growth control in certain cell lines and/or tumors.

Amino Acid Sequence↗
PubMed1996

High bioavailability of dehydroepiandrosterone administered percutaneously in the rat.

Dehydroepiandrosterone (DHEA) administered percutaneously by twice daily application for 7 days to the dorsal skin of the rat stimulates an increase in ventral prostate weight with approximately one third the potency of the compound given by subcutaneous injection. The doses required to achieve a 50% reversal of the inhibitory effect of orchiectomy are approximately 3 and 1 mg respectively. By the oral route, on the other hand. DHEA has only 10-15% of the activity of the compound given percutaneously. Taking the bioavailability obtained by the subcutaneous route as 100%, it is estimated that the potencies of DHEA by the percutaneous and oral routes are approximately 33 and 3% respectively. Similar ratios of activity were obtained when dorsal prostate and seminal vesicle weight were used as parameters of androgenic activity. When examined on an estrogen-sensitive parameter, namely uterine weight in ovariectomized rats, the stimulatory effect of DHEA was much less potent than its androgenic activity measured in the male animal, a 50% reversal of the inhibitory effect of ovariectomy on uterine weight being observed at the 3 and 30 mg doses of DHEA administered by the subcutaneous and percutaneous routes respectively. When measured on uterine weight, percutaneous DHEA thus shows a 10% potency compared with the subcutaneous route. The sulfate of DHEA (DHEA-S), on the other hand, was approximately 50% as potent as DHEA at increasing ventral prostate weight after subcutaneous or percutaneous administration. When the effect was measured on dorsal prostate and seminal vesicle weight, percutaneous DHEA-S had 10-25% of the activity of DHEA. DHEA decreased serum LH levels in ovariectomized animals, an effect which was completely reversed by treatment with the antiandrogen flutamide. On the other hand, flutamide had no significant effect on the increase in uterine weight caused by DHEA, thus suggesting a predominant estrogenic effect of DHEA at the level of the uterus and an estrogenic effect on the feedback control of LH secretion. The present data show a relatively high bioavailability of percutaneous DHEA as measured by its androgenic and/or estrogenic biological activity in well-characterized peripheral target intracrime tissues in the rat.

Administration, Cutaneous↗
PubMed1995

Transcription factors RFX1/EF-C and ATF-1 associate with the adenovirus E1A-responsive element of the human proliferating cell nuclear antigen promoter.

The proliferating cell nuclear antigen (PCNA) is an adenovirus E1A-inducible factor that is intimately linked to the processes of DNA replication and cell cycle regulation. Previously, we defined a novel cis-acting element, the PCNA E1A-responsive element (PERE), that confers induction by the E1A 243R oncoprotein upon the human PCNA promoter. To better understand the regulation of PCNA expression by E1A 243R, we have identified cellular transcription factors that associate with the PERE. In electrophoretic mobility shift assays, the PERE formed three major complexes (P1, P2 and P3) with proteins in nuclear extracts from HeLa or 293 cells. Formation of complexes P2 and P3, which correlates with PCNA promoter activity in vivo, requires the activating transcription factor (ATF) binding site found within the PERE [Labrie et al. (1993) Mol. Cell. Biol., 13, 1697-1707]. Antibody interference experiments and mobility shift assays performed with in vitro-synthesized protein indicated that the transcription factor ATF-1 is a major component of these complexes. Similar assays demonstrated that the hepatitis B virus enhancer-associated protein RFX1 constitutes a major component of the P1 complex. In addition, we examined the binding of proteins to the minimal E1A-responsive promoter to identify other factors important for transcription from the PCNA promoter. Mobility shift assays revealed that a fragment encompassing the region from -87 to +62 relative to the transcription initiation site forms at least five complexes, EH1-EH5, with HeLa cell nuclear extracts. The transcription factor YY1 associates with the initiator element of the PCNA promoter. The identification of these transcription factors will allow their roles in the activation of PCNA by E1A to be evaluated.

Activating Transcription Factor 1↗
PubMed1995

Effect of gamma-hydroxybutyrate and its antagonist NCS-382 on spontaneous cell firing in the prefrontal cortex of the rat.

Gamma-hydroxybutyrate (GHB) at low doses (5-10 mg/kg i.p.) increased and at high doses (160-320 mg/kg i.p.) decreased the spontaneous firing rate of prefrontal cortex (PFC) neurons recorded in urethane-anesthetized rats. Only excitations were blocked by NCS-382, a specific GHB receptor antagonist; this suggests that the excitatory effect of low doses of GHB is mediated by a GHB receptor whereas the inhibitory effect of high doses of GHB involves a more complex mechanism.

Animals↗
PubMed1995

Inhibitory effect of a steroidal antiestrogen (EM-170) on estrone-stimulated growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in the rat.

Recently, compounds having pure antiestrogenic activity have become available. In this study, we examined the activity of the new steroidal antiestrogen EM-170 (N-n-butyl, N-methyl-11-(16' alpha-chloro-3',17' alpha-dihydroxy-estra-1',3',5'-(10')-trien-7' alpha-yl) undecanamide) on the growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma stimulated by treatment with estrone (E1), a steroid known to play an important role as precursor of 17 beta-estradiol (E2), especially in postmenopausal women. Twenty-five days after ovariectomy (OVX), tumor volume in control OVX animals decreased to 51.4 +/- 11% of the initial volume; treatment with E1, administered by Silastic implants, stimulated tumor growth to 179 +/- 21%. Treatment with the antiestrogen EM-170 at a dose of 200 micrograms (twice daily) not only completely reversed the stimulatory effect of E1, but also inhibited tumor growth to 30.5 +/- 9.6%, an effect that is 41% (P < 0.01 vs OVX control) greater than that of ovariectomy alone. At a relatively low dose of 40 micrograms (twice daily), 20 days of treatment with EM-170 reversed by 55% the stimulatory effect of E1 (1.0 micrograms, subcutaneously, twice daily) on tumor growth in OVX animals. On the other hand, the antiestrogen also induced a significant inhibitory effect on 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity in the DMBA-induced mammary tumors, an effect that is in agreement with the marked reduction caused by the same treatment on tumor estradiol (E2) levels in E1-treated OVX animals.(ABSTRACT TRUNCATED AT 250 WORDS)

17-Hydroxysteroid Dehydrogenases↗
PubMed1995

Myoclonic-like finger microdisplacements in patients with cerebellar deficits.

BACKGROUND: Here we assess the ability of patients with cerebellar disease to execute a simple visually-guided movement task involving tracking of a target with the index finger. METHODS: Spontaneous microdisplacements in index finger position are compared in patients with cerebellar deficits (ischemia [n = 3], multiple sclerosis [n = 3], degenerative cerebellar disease [n = 3]) and age-matched healthy subjects. Subjects were required to maintain a constant finger position relative to a stationary baseline displayed on an oscilloscope. RESULTS: Unusual transient abrupt movements (saccadic or myoclonic-like) directed with or against gravity were seen in patients whose neurological deficits were the most severe (7/9 patients). These abrupt myoclonic-like movements occurred independently of visual input, were not associated with clinically observable myoclonus, and were not detected previously in patients with Parkinson's disease. These abrupt myoclonic-like movements were not associated with abnormalities in either physiological tremor, or oscillations in finger microdisplacements induced by insertion of a delay (300-1400 ms) into the visual feedback of this finger "holding" experiment. An unexpected finding is that the results obtained for patients with cerebellar deficits by insertion of an experimental delay are not significantly different from those obtained with their age-matched controls. CONCLUSIONS: These observations suggest that abrupt myoclonic-like movements are a characteristic abnormality of patients with a variety of cerebellar deficits and emphasize the value of this simple motor tracking task for characterizing movement disorders.

Adolescent↗