Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The estrogenic effects of MER-25, an antiestrogen, on eating and body weight were studied in rats. As evidenced by its failure to cause an habitual aversion to saccharin and failure to alter spontaneous activity, MER-25 inhibited weight gain and eating. Estradiol benzoate (EB) and MER-25 both had similar effects in gonadectomized rats, and produced a transient decrease in food consumption and a permanent decrease in body weight. Progesterone ameliorated the effect of both agents on eating and body weight. MER-25 and EB were both more active in females than males. MER-25 did not markedly alter the effects of EB on body weight and eating, but did antagonize the effects of EB on the uterus, vagina, and sex behavior. The results indicate biochemical differences between the effects of estrogens on eating and body weight and other estrogen-dependent processes.
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PMID:Estrogenic effects of an antiestrogen, MER-25, on eating and body weight in rats. 94 84

Female ferrets that received injections of testosterone propionate (TP) early in postnatal life displayed significantly more masculine behavior than did control females when gonadectomized and administered either TP or estradiol benzoate in adulthood. This increased masculine response potential was not correlated with the effects of early TP treatment on phallic development. In contrast to results obtained in most other species, perinatal administration of TP to female ferrets failed to disrupt their ability to display the behavior that is characteristic of the sexually receptive animal in estrus. When estrogenic stimulation was provided in adulthood, the receptive behavior of three groups of perinatally androgenized females was indistinguishable from that of both male and female controls. However, after gonadectomy and administration of TP, control males and females that had received TP prenatally plus on Day 3 were significantly more receptive than were control females. The induction of receptivity by TP was significantly inhibited by simultaneous administration of the antiestrogen MER-25.
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PMID:Effects of testosterone propionate administered perinatally on sexual behavior of female ferrets. 94 19

58 female rats were divided into 6 groups -- controls; those injected with 30 mcg of testosterone propionate (TP) at 5 days of age; those bilaterally implanted with intrahypothalamic paraffin micropellets (sham) at .4 days of age, those similarly implanted but also injected with 30 mcg of TP, those implanted at 4 days with MER-25 impregnated pellets and injected with oil, and those implanted with MER-25 and injected with TP -- in order to determine the effect of intrahypothalamic implants of an estrogen antagonist to block neonatal androgen sterilization. The dose of TP was at threshold level for sterility. 9 of 12 animals (75%) receiving a sham operation and injection were sterile by 90 days of age. Of the 15 animals implanted with MER-25-paraffin plus injected with TP, 10 (67%) of the rats developed sterility. The block by MER-25 of androgen sterilization was insignificant. Previous interpretation of androgen sterilization as an exclusively estrogen function must be accepted with reservation.
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PMID:Failure of intrahypothalamic implants of an estrogen antagonist, ethamoxytriphetol (MER-25), to block neonatal androgen-sterilization. 94 89

Progesterone priming of the ovariectomized rat, followed by a single injection of estradiol-17beta (10 mug) is followed by an increased uterine synthesis of both PGF and PGE. The administration of an estrogen antagonist (MER-25; 10 mg) concomitantly with estradiol had no effect on uterine prostaglandin synthesis. Similarly, the administration of either Actinomycin D or cycloheximide, antibiotics demonstrated to inhibit mRNA and protein synthesis, respectively, is without effect on estrogen-stimulated uterine prostaglandin synthesis. These results are considered with regard to the classic receptor theory of estrogen action and are a preliminary indication that estrogen-stimulated uterine prostaglandin synthesis may not require those receptor mediated events.
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PMID:Considerations into the mechanism of estrogen-stimulated uterine prostaglandin synthesis. 95 89

The immunogenicity of leukemia L1210 in DBA/2 Ha and 6C3HED lymphosarcoma tumor cells in C3H/f mice was significantly increased after treatment with V. cholerae neuraminidase. DBA/2 Ha and C3H/f mice repeatedly immunized with neuraminidase-treated tumor cells rejected subsequent challenge of 10(7) or 10(6) untreated tumor cells, respectively. Based on the 51Cr microcytotoxicity assay, both strains of mice showed strong complement-dependent antibody titers and cell-mediated immunity. Sera and splenic lymphocytes from immunized C3H/f mice neutralized the tumorigenicity of 6C3HED lymphosarcoma and protected the recipient C3H/f mice against the disease. Immune lymphocytes pretreated with anti-theta sera lost their ability to neutralize the tumorigenicity of lymphosarcoma, and they failed to be stimulated by T-cell mitogens. We studied the effectiveness of chemoimmunotherapy in DBA/2 Ha mice with leukemia L1210. A single near optimal dose of BCNU 2 days after implantation of 10(6) tumor cells increased the survival time. A single immunization with 2 X 10(7) neuraminidase-treated L1210 tumor cells 4 days after cytoreductive therapy increased survival and resulted in cures for 50% of animals. Immunization of mice with neuraminidase-treated tumor cells and MER produced indefinite survival in a larger percentage of mice than did either treatment alone. AKR mice with spontaneous leukemia treated with combination chemotherapy sustained an 180% increase in life-span. Combination chemotherapy plus immunization with neuraminidase-treated syngeneic or allogeneic (Gross virus-induced) E2G leukemia cells were highly effective in prolonging the life-span of the immunized leukemic AKR mice. The experimental data led to clinical trials in acute myelocytic leukemia with neuraminidase-treated a-logeneic myeloblasts. Patients with acute myelocytic leukemia were randomized into two groups after remission induction. The median remission duration of patients on sustaining chemotherapy alone was 19 weeks (8 patients), whereas six of nine patients who received neuraminidase-treated allogeneic myeloblasts remain in remission 79-132 weeks. Statistical analysis of the remission duration and survival of patients who received chemoimmunotherapy versus the control group shows highly significant differences.
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PMID:Therapeutic effectiveness of neuraminidase-treated tumor cells as an immunogen in man and experimental animals with leukemia. 106 51

An immunosuppressed mouse model was devised to test the effects of immunopotentiators on the prevention of bacterial and fungal infections. The effects of BCG and Corynebacterium were tested against Staphylococcus aureus and Candida albicans infection. The effect of methanol-extraction residue (MER-BCG) was tested against S. aureus septicemia. CDF mice were given various doses of BCG, 1.0 mg of C. parvum, or 0.5 mg of MER intraperitoneally at varying intervals before injection of an intravenous bacterial challenge. Four days before challenge, 300 mg of cyclophosphamide per ml was given intraperitoneally. BCG (106 colony-forming units) reduced mortality due to S.aureus at pretreatment intervals of 3, 7, 14, and 28 days. Isonicotinic acid hydrazide treatment elimated the protective effect of the live BCG. C. parvum was as effective as BCG against S. aureus septicemia when given 3 days before infection, but lost most of its protective effect after that time. MER protected at doses as small as 0.25 mg when given 25 days prior to challenge. Both BCG and C. parvum exerted a protective effect against Candida albicans infection.
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PMID:Effects of BCG, Corynebacterium parvum, and methanol-extration residue in the reduction of mortality from Staphylococcus aureus and Candida albicans infections in immunosuppressed mice. 110 24

Gonadectomized male and female rats were treated with equimolar doses of estradiol benzoate (EB) or testosterone pripionate (TP) daily for one week and enzyme activities were measured in the basomedial hypothalamus, corticomedial amygdala, and pituitary. In females, the hypothalamus showed estrogen-dependent increases in glucose-6-phosphate dehydrogenase (G6PDH), isocitrate dehydrogenase (ICDH), and malate dehydrogenase (MDH). Activities of ICDH and MDH were elevated in the amygdala. In the pituitary, estrogen administration resulted in increased levels of G6PDH, 6-phosphogluconate dehydrogenase (6PGDH), and lactic dehydrogenase (LDH). The estrogen antagonist, MER-25, effectively blocked estrogen-dependent increases in pituitary G6PDH and 6PGDH. Administration of TP did not result in changed enzyme levels. In males, treatment with EB and TP resulted in significant elevations in some but not all enzymes that were increased by EB in the female. Estrogen-dependent increases of activity in males were noted in pituitary G6PDH, 6PGDH, and LDH, in hypothalamic MDH, and in amygdaloid ICDH. Administration of TP led to increased levels of pituitary G6PDH, 6PGDH, LDH, ICDH, and MDH, hypothalamic ICDH and G6PDH, and amygdaloid MDH. The pattern of enzyme changes found in male and female brain and pituitary is discussed in relation to behavioral responses to gonadal hormones, nuclear uptake of gonadal hormones, and metabolism of androgen.
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PMID:Effect of gonadal hormones on enzyme activities in brain and pituitary of male and female rats. 111 98

Gonadectomized male and female rats were treated with equimolar doses of estradiol benzoate (EB) and testosterone propionate (TP) daily for periods of 3 days to 1 week and activities of monoamine oxidase (MAO) and choline acetyltransferase (ChAc) were measured in the cortex, hippocampus, basomedial hypothalamus, corticomedial amygdala and medial preoptic areas. After hormone treatment, changes in enzyme activities were found in those brain regions where gonadal hormones are known to affect sexual behavior and/or gonadotropin release and which contain putative hormone receptor sites. More specifically, EB administration to females resulted in decreased activity of MAO in the corticomedial amygdala and basomedial hypothalamus and an elevation of ChAc activity in the medial preoptic area and corticomedial amygdala while TP administration did not alter enzyme levels in any brain region. In contrast, EB administration to castrated males was without significant effect on enzyme activities while TP administration resulted in increased activity of MAO and ChAc in the medial-preoptic area. The estrogen antagonist, MER-25, given concomitantly with EB, effectively blocked EB-dependent changes in both enzymes in ovariectomized female rats. EB treatment to hypophysectomized females led to similar enzymatic changes as in ovariectomized females in all areas except the basomedial hypothalamus. Estradiol added directly to the enzyme incubation medium did not result in altered enzyme activities. Results obtained are discussed in relation to sexual differentiation of the brain, metabolism of gonadal hormones, and possible mechanism of gonadal hormone regulation of enzyme activities.
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PMID:Effect of gonadal steroids on activities of monoamine oxidase and choline acetylase in rat brain. 111 99

The experimental treatment of a rat sarcoma (McFiFi 2) by intratumoral injection of BCG2 is described. Tumors which have a mean diameter of less than 10 mm at the beginning of treatment are fully susceptible to BCG, although spontaneous regression is not observed at this stage. The effective dose of living BCG ranges from two injections of 0.1 mg to two injections of 1 mg, given IT at an interval of 7 days. The permanent cure of a proporation of the tumors may also be induced by IT injection of a similar dose of heat-killed BCG or of MER, or of 10(9) heat-killed C. parvum, according to the same schedule. Preimmunization of the rats with living BCG does not improve the efficiency of heat-killed BCG. Direct contact between the therapeutic material and the tumor cells is critical. If rats are grafted with two pieces of the same tumor in widely separated sites, the intratumoral treatment of only one of these tumors with living BCG is sufficient to induce regression of both tumors in 50% of the animals. The effect of BCG is counteracted by injection of silica or by ingestion of polaramine. The same intratumoral treatment with living BCG was applied to different rat and mouse tumors. Only McFiFi 2 tumors were cured by intralesional BCG. C3H mouse plasmocytoma 5563 was not cured by intratumoral BCG but its growth could be prevented by mixing BCG and tumor cells at the time of grafting; this tumor was considered to be of medium susceptibility. However, until there is definite proof that the two mechanisms are identical, one should consider the regression and cure of a growing tumor, and the prevention of tumor growth, as two different phenomena. The clinical treatment of human tumors resembles the first experimental procedure more closely than the second.
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PMID:Therapeutic effect of intratumoral injection of bcg and other substances in rats and mice. 117 5

In the first experiment castrated male rats were injected daily with either vehicle or 800 mug testosterone together with either 6 hr pretreatment or concurrent treatment with the anti-estrogens CI-628 (4 mg) or MER-25 (20 mg). The only treatment found to significantly reduce male copulatory behavior was concurrent treatment with CI-628. Anti-estrogen treatment was also found to slightly reduce body weights, increase seminal vesicle weights in response to testosterone and to have no significant effects on androgen stimulated increases in penis weight and length. In the second experiment castrated male rats were injected daily with either vehicle or 500 mug testosterone together with 2.5 mg injections of CI-628 given 6 hr before and concurrent with the androgen injections. The anti-estrogen treatment was found to markedly inhibit the desplay of male sexual behavior, to reduce body weights, and to stimulate seminal vesicle weights. Penile weights and lengths were again not effected by the anti-estrogen therapy. These results were interpreted as supporting the theory that testosterone stimulated male sexual behavior in the rat following its aromatization to estradiol in the brain.
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PMID:Effects of anti-estrogens on testosterone stimulated male sexual behavior and peripheral target tissues in the castrate male rat. 118 41


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