Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD01092 (DMAP)
 1,129 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to assess the multiple steroid receptor mediated activities of a series of synthetic 'progestins' on breast cancer cell growth, using the human ZR-75-1 cell line which possesses functional estrogen (ER), androgen (AR), and glucocorticoid (GR) receptors as well as progesterone (PgR) receptors. Four 17-hydroxyprogesterone derivatives (chlormadinone acetate, CMA; cyproterone acetate, CPA; medroxyprogesterone acetate, MPA; and megestrol acetate, MGA) and two 19-nortestosterone derivatives (norethindrone, NRE, and norgestrel, NRG) were thus investigated. Based on the requirement of estrogens for PgR-mediated antiproliferative effects and the reversal of PgR-mediated action by insulin, it was found that although all 'progestins' could inhibit ZR-75-1 cell growth through the PgR at low concentrations, the relative contribution of this receptor in cell growth control is highly variable between compounds. The quantitative importance of PgR-mediated inhibition of cell proliferation was inversely related to the amplitude of the androgenic effects induced by the compounds, the AR-mediated effects increasing in the order CPA less than MGA less than CMA less than NRE less than NRG less than MPA. The specificity of these androgenic effects is further supported by their reversal upon addition of the antiandrogen hydroxyflutamide. In addition, the 17-hydroxyprogesterone derivatives, but not the 19-nortestosterone derivatives, had glucocorticoid activities at high (micromolar) concentrations, as shown by reversal of growth inhibition by the antagonist RU486 in the presence of saturating concentrations of 5 alpha-dihydro-testosterone. All 'progestins' tested, except MPA and NRE, also had some antiglucocorticoid activity, NRG being the most potent in this respect. Finally, NRE and NRG exerted a marked mitogenic effect in estrogen-free medium which was clearly mediated through the ER as shown by the competitive reversal of their action by the steroidal antiestrogen EM-139. The present results show that growth measurements of the human breast cancer cells ZR-75-1 permit, with the appropriate steroid additions, the assay of progestin, androgen, estrogen, and glucocorticoid agonistic as well as antagonistic activities of test compounds. The present study shows, somewhat surprisingly, that while the AR is almost completely responsible for the action of MPA at low concentrations, the majority of the action of NRE, NRG, and MGA is also exerted through AR, while the androgenic action of CPA plays a lower role in the growth inhibition induced by this compound.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Multiple actions of synthetic 'progestins' on the growth of ZR-75-1 human breast cancer cells: an in vitro model for the simultaneous assay of androgen, progestin, estrogen, and glucocorticoid agonistic and antagonistic activities of steroids. 164 5

A single-room dedicated mass spectrometer can be used to measure carbon dioxide, halogenated anesthetic agents, nitrous oxide, nitrogen, and oxygen. This device challenges the multiplexed mass spectrometer, a current standard in measurement. This study compared the single-room dedicated mass spectrometer with a conventional mass spectrometer that is normally used in a multiplexed setting. In this study, a single-room dedicated Ohmeda 6000 Mini-Mass Spectrometer and the Perkin-Elmer MGA-1100 mass spectrometer were calibrated with the same reference gases and both devices sampled various concentrations of dry gases. Regression lines and intercepts were plotted and showed excellent correlation between the two devices. The intraclass correlation test of Lee, Koh, and Ong, showed the devices to be equivalent with regard to the ability to determine various gas concentrations. Various advantages of a single-room dedicated mass spectrometer are discussed.
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PMID:Evaluation of a single-room, dedicated mass spectrometer. 177 80

In 1989, staff at WHO headquarters in Geneva, Switzerland developed teaching software that can be used on IBM-PC and IBM-compatible computers to train public health workers in schistosomiasis. They tested in several schools of public health. They then improve it by incorporating a schistosomiasis information file (stack) in ASCII file format and a routine to organize and present data. The program allows the addition of other stacks without abandoning the user interface and the instructor can change data in the stacks as needed. In fact, any text editor such as Word-Perfect can create a stack. This software teaching program (ZOOM) organizes and presents the information (Dr. Schisto). Dr. Schisto is divided into 8 chapters: introduction, epidemiology, parasitology, diagnostics, treatment, data analysis, primary health care, and global database. Users can command ZOOM to communicate in either English, French, Spanish, or Portuguese. Basic hardware requirements include MS-DOS, 8086 microprocessor, 512 Kbytes RAM, CGA or MGA screen, and 2 floppy disc drives. ZOOM can also configured itself to adapt to the hardware available. ZOOM and Dr. Schisto are public domain software and thus be copied and distributed to others. Each information stack has chapters each of which contains slides, subslides, text, graphics, and dBASE, Lotus or EpiInfo files. ZOOM has key words and an index file to access more information. It also can do user defined searches using Boolean logic. Since ZOOM can be used with any properly formatted data, it has the potential to become the standard for global information exchange and for computer assisted teaching purposes.
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PMID:ZOOM: a generic personal computer-based teaching program for public health and its application in schistosomiasis control. 178 18

A potent tumor-regressing activity was found in the serum of mice with S180 tumor undergoing rapid regression caused by antitumor polysaccharides. Beta (1-3) glucan including CM-TAK and lentinan and mannoglucan MGA induced such activity. It causes a rapid decrease in the number of tumor cells accompanied with a marked increase in neutrophiles in solid tumors. The entity of the activity was named as tumor-regressing factor (TRF) and was partially purified revealing a proteinaceous nature with an approximate molecular weight of 250,000. The factor was induced in a serum of tumor-bearing mice in various host-tumor combinations after the tumor growth had been established but only weakly in normal mice. The sensitivity of tumors to the factor was also dependent on the stage of tumor growth. The serum of normal mice or tumor-bearing mice without polysaccharide treatment exhibited similar activity as TRF after definite chromatographic step. The chromatographic behavior of the revealed activity was closely similar to that of the induced factor. It was postulated that a TRF-like activity exists in normal serum in a inactivated form being bound by antagonist(s) and the appropriate chromatography might remove the antagonist resulting in the active form of the factor. The concept was confirmed by reconstituting the chromatographic fractions, the revealed activity was again obscured after mixing with a certain fraction.
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PMID:[Tumor-regressing factor induced by antitumor polysaccharide in the serum of tumor-bearing mice]. 208 76

Two trials were conducted to examine reproductive function and feedlot performance by heifers after active immunization against GnRH. In trial 1, heifers were not immunized or were immunized with one of three doses of a GnRH-KLH (keyhole limpet hemocyanin) conjugate in Freund's complete adjuvant. Antibodies against GnRH were not detectable in non-immunized heifers (n = 9). However, antibodies against GnRH were noted in all immunized animals (n = 30) within 8 wk of primary immunization; anti-GnRH antibody concentrations were at a maximum 16 to 20 wk after immunization. This increased anti-GnRH titer was associated with a decreased serum concentration of progesterone. Ovarian and uterine weight and tissue concentrations of LH and GnRH receptor were reduced (P less than .05) by immunoneutralization of GnRH. Similarly, immunization against GnRH reduced (P less than .05) weight gain during feedlot confinement. In trial 2, feedlot performance after insertion of anabolic steroid implants (Synovex H) was evaluated in non-immunized heifers (n = 15), heifers actively immunized against GnRH-KLH (n = 15) or KLH alone (n = 15), or non-immunized heifers treated with melengestrol acetate (MGA; n = 15). Serum concentrations of progesterone were depressed in anti-GnRH and MGA-fed groups, but ovarian and uterine weights were depressed (P less than .05) only in heifers immunized against GnRH. Total weight gain and gain during the final 4 wk of confinement did not differ (P greater than .05) among groups with steroid implants. The GnRH-KLH conjugate is an effective immunogen in heifers, leading to suppression of reproductive activity. The depression of weight gain that attends development of anti-GnRH titers may be reversed by use of implants that contain anabolic steroids.
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PMID:Reproductive function and feedlot performance of beef heifers actively immunized against GnRH1. 221 9

Using the PHA method, streptococcal type-specific antibody was studied in sera from 230 patients with various types of nephritis diagnosed by renal biopsy in order to clarify the relationship between streptococcal infection and the histological types of glomerulonephritis. Two or more serologic types of streptococcal type-specific antibodies with high titers (1:384 or more) were significantly increased in patients with MGA, FGS, PGN, endocapillary proliferative GN, MPGN and IgA GN as compared with those in healthy subjects. Two or more serologic types having high titers (1:384 or more) were significantly increased in MGA, PGN, MPGN and IgA GN as compared with MN. The highest titers (1:768 or more) of streptococcal type-specific antibodies were significantly more frequent in endocapillary proliferative GN as compared with healthy subjects, and such titers were significantly increased in endocapillary proliferative GN and MPGN as compared with MN. The frequency of detection of streptococcal serologic types having high titers (1:384 or more) as found in patients with various nephritis, was in the order of Types 18, 3, 30, 1, 12, 10, 6 and 37, and more than half of the nephritogenic types were included in these serologic types. The above data, which suggest a higher probability of contact with nephritogenic strains during alternative establishment of streptococci by different serologic types, may indicate a close relationship of streptococcal infections with MGA, PGN, MPGN, IgA GN, FGS and endocapillary proliferative GN.
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PMID:Streptococcal type-specific antibody in patients with glomerulonephritis (2): Correlation to their histological types. 225 Apr 2

The long sampling tubes required for remote mass spectrometry alter the sampling system's performance characterized by sample flow, residence time, and 10 to 90% response time. We searched for an easy-to-handle tube with (1) a length of 30 m, (2) sample flow less than 50 ml.min-1, and (3) residence and response times approaching those predicted by our mathematical model. We tested tubes of various geometries and various commercially available materials by using them as inlet catheters for a quadrupole mass spectrometer (Centronic 200 MGA, Centronic Ltd, Craydon, UK). We measured their responses at 0 to 10% (on transients) and 10 to 0% (off transients) step changes in gas concentration for nitrogen, argon, nitrous oxide, oxygen, and carbon dioxide and 0 to 3% and 3 to 0% for halothane, enflurane, and isoflurane. With 5 polyethylene tubes, halothane response times were up to 38 times longer than predicted. One 30-m polyethylene tube combined a 158-ms response time for nitrogen and argon with a 2,205-ms response time for halothane. Teflon, polyvinyl chloride, and stainless steel also proved to be unsuitable because of unacceptable signal distortion: the carbon dioxide response time for a 30-m Teflon tube was 2,600 ms. A glass tube showed the least signal distortion but was hard to handle. Our requirements were fulfilled by a 29.77-m tube made from nylon with a 1.00-mm inside diameter to which a 0.23-m length of nylon with a 0.25-mm inside diameter was added at the patient end. It offers (1) sample flow equals 46 ml.min-1, (2) residence time equals 11.1 seconds, and (3) response times approaching our theoretical predictions, that is, 159, 164, 180, 159, 188, 302, 298, and 300 ms (means of on and off transients) for nitrogen, argon, nitrous oxide, oxygen, carbon dioxide, halothane, enflurane, and isoflurane, respectively. This tube allows the accurate monitoring of breathing frequencies up to 25 and 50 breaths/min for volatile agents and gases, respectively.
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PMID:Evaluation of long sampling tubes for remote monitoring by mass spectrometry. 229 95

Beef (n = 783) and dairy (n = 209) heifers at 14 locations were used to evaluate the efficacy of feeding melengestrol acetate (MGA; .5 mg/d) for 7 d followed by an i.m. injection of 25 mg prostaglandin F2 alpha (PGF) on the last day of MGA feeding (MGA + PGF) to synchronize estrus. Untreated heifers (C) and heifers injected once i.m. with PGF served as contemporary controls. Heifers were observed for estrual behavior for a minimum of 38 d starting on the 2nd d of MGA feeding. Heifers in estrus from d 1 through d 60 after PGF injection were artificially inseminated (AI) or bred to bulls (d 30 to 60 post PGF only). During the 7-d MGA feeding period fewer (P less than .01) MGA + PGF (1.5%) than C (20.6%) or PGF (18.1%) heifers were observed in estrus. Percent of heifers in estrus d 1 to 6 post PGF was different among groups (P less than .05; 30.5, 52.8, 72.3 for C, PGF and MGA + PGF, respectively). More (P less than .01) MGA-fed (92%) than non-MGA-fed (C and PGF combined) heifers (85.4%) were observed in estrus during d 1 to 24. Conception rate (CR) during d 1 to d 6 was not different (P = .19) between C (58.9%) and MGA + PGF (51.2%) heifers; CR was lower (P = .01) for MGA + PGF than for PGF (68.3%) heifers.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Synchronization of estrus with melengestrol acetate and prostaglandin F2 alpha in beef and dairy heifers. 231 21

A method of identifying thymidylate synthase (TS) at the cellular level was developed using anti-TS monoclonal antibody (M-TS-4), a monoclonal antibody created against purified TS from a HeLa cell line. In HeLa cells and four human glioma cell lines (U-251, U-87, 343-MGA, and SF-188), TS was identified primarily in the cytoplasm. Autoradiographic and flow cytometric studies showed that TS appeared mainly in the G1 phase and subsided early in the S phase; thus, the G1 phase can be divided into TS-positive and -negative fractions. Nuclear TS was not demonstrated unequivocally with M-TS-4, and the relationship between nuclear TS and DNA synthesis could not be determined. Although the percentage of TS-positive cells was larger than the S-phase fraction measured by autoradiography after a pulse of tritiated thymidine or by the immunoperoxidase method using BUdR, the ratios were within a similar range (1.2-1.4) in all cell lines studied. Therefore, the S-phase fraction can be estimated indirectly from the percentage of TS-positive cells measured by M-TS-4. Because the emergence of TS detected by our method is cell cycle dependent, M-TS-4 may be useful for biochemical studies of TS and for cytokinetic analysis.
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PMID:Cell cycle phase dependent emergence of thymidylate synthase studied by monoclonal antibody (M-TS-4). 247 89

The amount and distribution of glial fibrillary acidic protein (GFAP) were determined by flow cytometry (FCM) and an enzyme-linked immunosorbent assay (ELISA) in five human glioma cell lines stained by the indirect immunofluorescence method using anti-GFAP monoclonal antibody. Standard reference beads containing a known amount of fluorescein were used to calibrate the flow cytometer; however, the intensity of fluorescence from these beads was too weak to allow direct comparison with the fluorescence from the stained cells. Therefore, the flow cytometer was recalibrated using reference beads with a fluorescence intensity similar to that of the glioma cells. By comparing the fluorescence intensities of the two types of reference beads, it was possible to determine the fluorescein content of the stained cells directly from the relative fluorescence intensity (channel number). Glioma cell lines 343 MGA, SF 126, SF 188, U 251, and U 87 had fluorescein concentrations of 72.0 +/- 6.8, 8.1 +/- 0.3, 52.6 +/- 3.1, 86.4 +/- 4.0, and 56.2 +/- 2.9 x 10(5) (mean +/- standard error) Eq Sol Mol (equivalent solution of mole), respectively. The GFAP content of these cell lines, determined by ELISA, was 15.7 +/- 5.2, 0.5 +/- 0.1, 11.1 +/- 2.0, 20.8 +/- 4.6, and 9.5 +/- 2.7 pg GFAP/cell, respectively, and correlated closely with the results of FCM (R = 0.983, p less than 0.0028). A linear regression analysis yielded the following equation: pg GFAP/cell = -2.3376 + 0.2518 x FCM integrated mean channel number (fluorescein concentration: 10(5) Eq Sol Mol).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Quantitation and distribution analysis of glial fibrillary acidic protein in human glioma cells in culture. 276 8


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