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 objective of this study was to determine whether anti-oestrogens (nafoxidine, MER-25) would block the suppressive effects of ACTH on gonadotrophin secretion in immature rats. Female rats were castrated at 25-26 days of age, and an Alzet osmotic minipump containing ACTH (1-24) or saline was implanted in each animal. ACTH was administered at a rate of 1 IU/day by constant infusion. Beginning on the day of surgery, animals were injected daily for 5 days with 0.25, 5 or 25 micrograms/100 g body weight of nafoxidine or 5 mg MER-25 and sacrificed on the sixth day following castration. ACTH lowered serum LH concentrations and increased pituitary LH levels. Serum androstenedione concentrations were more than two times greater in ACTH-infused than in control rats, but serum oestrone levels were not affected. Serum testosterone and oestradiol concentrations in ACTH-infused rats remained below levels of detection. Administration of 0.25 micrograms of nafoxidine prevented the suppressive effects of ACTH on serum LH. Serum levels of LH in these animals were comparable to saline-treated controls (418 +/- 94 vs 443 +/- 73 ng/ml). The two higher doses of nafoxidine and MER-25 were ineffective in suppressing the actions of ACTH on serum LH. MER-25 reduced serum LH values in both controls and ACTH-infused rats. Serum FSH concentrations were not altered by ACTH or nafoxidine treatment. MER-25 elevated pituitary FSH concentrations in both control and ACTH-infused rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of anti-oestrogens on gonadotrophin secretion in control and ACTH-infused immature rats. 632 94

Women with breast carcinoma and four or more involved ipsilateral axillary lymph nodes were randomly assigned to receive an induction course and 2 yr of maintenance chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF, 150 patients), CMF plus vincristine and prednisone (CMFVP, 166 patients), or chemoimmunotherapy with CMF plus the methanol extraction residue of BCG (CMF-MER, 85 patients). After 5 yr of accrual and a median follow-up of 34 mo, CMFVP is superior to CMF (p less than 0.01) with disease-free survival estimates at 4 yr of 60% for CMFVP compared to 45% for CMF. The disease-free survival advantage of CMFVP over CMF was greater in postmenopausal (p = 0.02) than in premenopausal patients (p = 0.09). CMF-MER was similar to CMF alone. CMF related side effects were similar in each regimen (see text), except for a greater incidence of leukopenia during induction with CMF than with CMFVP (p less than 0.01).
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PMID:A randomized trial of five and three drug chemotherapy and chemoimmunotherapy in women with operable node positive breast cancer. 636 33

The aim of the present study was to investigate specific structural alterations in the cochlea of ears with sensory neural hearing loss and to determine the relation between structural damage and loss of auditory function. The results show that with the methods used in this study it is possible to obtain well preserved structures with consistent morphological characteristics. Examination and identification of small pathological alterations were thus possible. The stereocilia of the IHCs were found by scanning electron microscopy to be the structure most susceptible to damage by noise in the rabbit. The extent of IHC damage corresponded rather well with the frequency range for loss of auditory function, particularly threshold shift of the MER. The damage of the IHCs consisted of fusion, fracture and inclination of the stereocilia towards the OHCs. The OHC were frequently left unaltered even when the stereocilia of most IHCs exhibited pronounced alterations. In animals with a severe hearing loss and a postexposure time of more than two months, long "giant" cilia and often also a small thin kinocilium were found on the IHCs. IHC ciliary damage was found also in other species including man, but to a smaller extent than in the rabbit. The stereocilia of IHCs were also damaged by noise in ears of rabbits where the OHCs had been experimentally removed prior to the noise exposure. It was concluded that stereocilia damage is an important morphological alteration in ears with sensory neural hearing loss particularly with NIHL, and that cilia damage contributes to the observed loss of auditory function.
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PMID:Stereocilia of sensory cells in normal and hearing impaired ears. A morphological, physiological and behavioural study. 642 Aug 77

The authors present data from a group of 55 patients suffering from chronic renal diseases. Twenty-two were treated by haemodialysis; the rest had serum creatinine levels ranging from normal to 950 mumol/l. The molar esterification rats [MER] and total cholesterol [TCH] values decreased parallel to the gradual extinction of renal function. A reduced fractional esterification rate [FER] was found in about two thirds of the dialysed patients and in about half of those whose kidney function was still relatively well preserved. It can thus be concluded that reduction of FER values indicative of a disturbance of cholesterol metabolism can already be detected in the early stages of chronic nephropathies.
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PMID:Lecithin cholesterol acyltransferase activity in chronic nephropathies. 647 41

The present study determined the source and regulation of 17 alpha-hydroxyprogesterone (17-OHP4) during mid-late baboon pregnancy. Serum 17-OHP4 (ng/ml) in 5 untreated baboons increased from low values at mid-late gestation to a mean (+/- SEM) of 0.49 +/- 0.02 during the final 20 days of gestation. Fetectomy of 5 baboons resulted in serum 17-OHP4 concentrations which declined to and remained at baseline. Serum 17-OHP4 concentrations were 5- to 10-fold greater (P less than 0.001) in the uterine, utero-ovarian, and umbilical veins than peripherally. Apparently the fetal adrenal provides precursors for placental 17-OHP4 formation because the fetal adrenal gland develops delta 5-3 beta-hydroxysteroid dehydrogenase only late in gestation, and because the fetal adrenal and not the placenta has the capacity for 17-hydroxylation. Thus, at mid-late gestation the placenta appears to supply a major, and at term the corpus luteum a minor portion of the total 17-OHP4. Administration of the estrogen antagonist ethamoxytriphetol (MER-25, 15 mg/kg BW) to 4 baboons did not affect 17-OHP4 during mid-late gestation, when the placenta was the only source of 17-OHP4. However, MER-25 resulted in serum 17-OHP4 concentrations (ng/ml) at term which were greater (1.08 +/- 0.10, P less than 0.001) than in untreated baboons (0.49 +/- 0.02). Prior removal of the corpus luteum of pregnancy in 4 animals subsequently given MER-25 prevented this rise in 17-OHP4. This suggests that the marked elevation in 17-OHP4 observed near term after MER-25 administration was of luteal origin and that antiestrogen enhanced 17-OHP4 secretion by the corpus luteum.
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PMID:Source and regulation of 17 alpha-hydroxyprogesterone during baboon pregnancy. 648 91

The present study determined whether the reduction in serum progesterone (P4) concentrations which follows the administration of the antiestrogen ethamoxytriphetol [1-(rho-2-diethylaminoethoxyphenyl)1-phenyl-2-rho-methoxyphenyl ethanol (MER-25)] to pregnant baboons reflects a decline in placental and/or luteal function. Maternal saphenous venous blood was collected at 1- to 4-day intervals between day 70 of gestation and term in pregnant baboons. Four females received no other treatment, and eight females received MER-25 (15 mg/kg BW, orally) daily between day 130 of gestation and term. Four of the MER-25-treated baboons received no other treatment, and four had the corpus luteum of pregnancy surgically excised between days 104 and 118 of gestation. Serum P4 concentrations in the untreated baboons fluctuated, but no significant progressive rise or fall in P4 occurred. Administration of antiestrogen to intact pregnant baboons resulted in a 50% decline (P less than 0.001) in serum P4 concentrations from mean pretreatment values of 7.0-25.1 to 4.2-10.8 ng/ml thereafter. Although removal of the corpus luteum alone had no effect on serum P4, administration of MER-25 to luteectomized females resulted in an 80% decrease (P less than 0.001) in serum P4 concentrations from pretreatment means of 10.6-16.6 to 2.5-3.2 ng/ml thereafter. The results indicate that most or all of the P4 that remained in the peripheral circulation after MER-25 administration to intact pregnant baboons originated from the ovary, primarily the corpus luteum. Thus, the major site of action of antiestrogen in reducing P4 production during baboon pregnancy is on the placenta.
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PMID:Effect of the antiestrogen ethamoxytriphetol (MER-25) and luteectomy on serum progesterone concentrations in pregnant baboons. 648 60

In three experiments, 6- to 7-week-old chickens were exposed to one or two standard heating episodes and were injected immediately afterward with different concentrations of heat-killed Salmonella pullorum antigen (Ag) or phosphate-buffered saline. The standard heat episode consisted of three .5-hr exposures of 44 to 46 C with .5-hr periods of 22 C between exposures. Nonheated chickens were maintained at 22 C. When two heating episodes were used, there was a 12-hr interval between episodes. Sera from blood collected at 0 through 15 days postimmunization (PI) were titrated for total agglutinins and assayed for corticosteroids in all three experiments. Additionally, in Experiment 3, sera were titrated for 2-mercaptoethanol-resistant (2-MER) antibody. Total agglutinins were suppressed from 5 through 13 days PI by one heating episode in birds receiving lower doses of Ag but not in those receiving higher doses. When birds were exposed to two heat episodes, 12 hr apart, total agglutinin titers were suppressed in birds receiving the low Ag dose during the induction phase (4 to 5 days PI) only. During the declining phase (7 to 14 days PI), the effect was reversed, and titers were significantly lower in heated birds receiving the higher dosage. These results are similar to those previously obtained with ACTH (adrenocorticotropin). Determination of 2-MER antibody indicated that IgM was probably suppressed during the induction of the immune response but that IgG was suppressed during the declining phase of the response. Serum corticosteroid concentrations were significantly increased immediately after exposure to high temperature.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interaction of high temperature and Salmonella pullorum antigen concentration on serum agglutinin and corticosteroid responses in white rock chickens. 653 35

Intradermal, interlesional and intravenous MER/BCG have been reported to possess immunostimulatory properties and combined with chemo-radiotherapy an anti-neoplastic effect. Due to local and systemic side effects of the methanol extraction residue of BCG therapy a new approach to oral administration was investigated. Seventeen patients with inoperable non-oat cell lung cancer were given oral MER for 30 days. Skin tests to 5 recall antigens and various concentrations of MER, lymphocyte stimulation by PHA were done before and repeated during therapy. The initial group of patients received a dose of 1.25 mg per day and when no side effects were detected the dose was gradually escalated in subsequent groups of patients up to 5 mg. Oral MER was well tolerated even at the higher dose with no clinical or laboratory side effects. No regression in tumor size was seen. In 6 of 17 patients the disease remained stationary for a mean of 6 months (Range 6-14 months). In the remainder, disease progressed after a mean of 15 weeks. Two patients had cutaneous PPD reactivity converted from negative to positive, in one it became negative, while the remaining patients maintained their original responsiveness. No major changes could be observed in the in vivo immune tests performed following the course of treatment. In view of the reported relative efficacy of oral BCG administration, and considering the very low toxicity with oral MER, further studies employing considerably higher doses of this nonviable vaccine are now justified.
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PMID:Oral administration of the methanol extraction residue of BCG (MER/BCG): a phase I study in non-oat cell lung cancer patients. 662 93

Rat skeletal muscle cytosol proteins bound 3H-diethylstilbestrol (3H-DES). More than 90% of this binding was high capacity and low affinity. Serum albumin accounted for roughly 50-60% of the binding, as evidenced by its precipitation with anti-rat albumin IgG. About half of the binding was distinguishable from albumin and other serum proteins by its precipitation in 40% saturated ammonium sulfate. This material sedimented at 4-5S in high-salt sucrose gradients, and resolved into two components (8S and 4-5S) in low-salt. Following incubation at 23-27 degree C for one hour, 2% of the bound 3H-DES in whole cytosol (approximately 2 fmole/Mg cytosol protein) was retained by DNA cellulose, and was eluted with 0.6 M KCl. This small fraction of the total binding was inhibited by estrogens and DES analogues: estradiol-17 beta, DES, dienestrol, and hexestrol were strong inhibitors; isodienestrol, dimethylstilbestrol, estradiol-17 alpha, estrone, tamoxifen, MER-25, CI-628, and nafoxidine were weak inhibitors; dihydrotestosterone, testosterone, and prednisone did not compete. These observations indicate that specific estrogen-binding sites exist in rat skeletal muscle.
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PMID:Specific cytosol binding of diethylstilbestrol in rat skeletal muscle. 675 12

The present study determined whether estrogen is important in the production of progesterone (P) during primate pregnancy. Serum P production rates (metabolic clearance rate [MCR] x peripheral serum concentration) were determined in baboons prior to and following maternal administration of the antiestrogen ethamoxytriphetol (MER-25) at 30, 15, 6, or 3 mg/kg of body weight by mouth daily for 10 or 20 day periods during or throughout the last one third of gestation. Maternal peripheral serum P concentrations decreased (p less than 0.05 to P less than 0.001, t test) 37 to 60% in 7 of 9 baboons following daily administration of MER-25. Since mean MCR-P prior to (1,567 1/day) and following (1,361 1/day) MER-25 were similar, the decline in serum P concentration reflected decreased P production. Serum P concentrations in five untreated baboons during the last one third of gestation fluctuated in level, but no significant sequential rise or fall occurred. The decrease in P production in baboons following antiestrogen administration suggests that the action of estrogen is required for sustaining the elevated P production typical of baboon pregnancy.
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PMID:A role for estrogen in progesterone production during baboon pregnancy. 676 69


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