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Biomedical subjects

W Porter

Publications and source records attributed to W Porter.

15 recordsLinked to original sources
PubMed1996

Effect of transient expression of the oestrogen receptor on constitutive and inducible CYP1A1 in Hs578T human breast cancer cells.

Hs578T human breast cancer cells are an oestrogen receptor (ER)-negative cell line. Treatment of these cells with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) resulted in formation of a 6.9 S nuclear aryl hydrocarbon (Ah) receptor complex, which bound to a [32P]dioxin-responsive element in a gel electrophoretic mobility shift assay. However, TCDD does not induce CYP1A1 gene expression or chloramphenicol acetyl transferase (CAT) activity in cells transiently transfected with pRNH11c or pMCAT5.12, which are Ah-responsive plasmids derived from the 5'-flanking region of the human and murine CYP1A1 genes respectively. Restoration of Ah responsiveness was investigated by co-transfecting Hs578T cells with pRNH11c or pMCAT5.12 and plasmids that express the ER (hER), Ah receptor (AhR) and AhR nuclear translocator (Arnt) proteins. ER expression resulted in significantly increased basal CAT activity; however, TCDD did not induce CAT activity in the transiently transfected cells. Expression of the AhR or Arnt proteins did not alter basal or inducible CAT activity. Expression of N- or C-terminal truncated ER in Hs578T resulted in differential regulation of Ah responsiveness. In Hs578T cells transiently expressing the ER, which contains C-terminal deletions (amino acids 282-595), basal CAT activity was also increased; however, Ah responsiveness was not restored. In contrast, transient expression of N-terminal-deleted (amino acids 1-178) ER resulted in a marked decrease in basal CAT activity but a restoration of Ah responsiveness. These results suggest that basal and inducible CAT activity in Hs578T cells transiently transfected with pRNH11c is modulated differentially by ER domains that are present in the N- and C-terminal regions of the ER.

Base Sequence↗
PubMed1995

Molecular mechanism of inhibition of estrogen-induced cathepsin D gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in MCF-7 cells.

17 beta-Estradiol (E2) induces cathepsin D mRNA levels and intracellular levels of immunoreactive protein in MCF-7 human breast cancer cells. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alone does not affect cathepsin D gene expression in this cell line; however, in cells cotreated with TCDD and E2, TCDD inhibited E2-induced cathepsin D mRNA levels, the rate of gene transcription, and levels of immunoreactive protein. The inhibitory responses were observed within 30 to 120 min after the cells were treated with TCDD. TCDD also inhibited E2-induced secreted alkaline phosphatase activity in aryl hydrocarbon (Ah)-responsive MCF-7 and wild-type mouse Hepa 1c1c7 cells cotransfected with the human estrogen receptor (hER) and the pBC12/S1/pac plasmid, which contains the 5' promoter region (-296/+57) of the cathepsin D gene and an alkaline phosphatase reporter gene. The E2-responsive ER/Sp1 sequence (-199 to -165) in the cathepsin D 5' region contains an imperfect GTGCGTG (-175/-181) xenobiotic responsive element (XRE); the role of this sequence in Ah responsiveness was investigated in gel electrophoretic mobility shift assays and with plasmid constructs containing a wild-type ER/Sp1 oligonucleotide or a mutant ER/Sp1-"XRE" oligonucleotide containing two C-->A mutations in the XRE sequence (antisense strand). In plasmid constructs which contained a chloramphenicol acetyltransferase reporter gene and the wild-type ER/Sp1 promoter sequence, E2-induced chloramphenicol acetyltransferase activity and mRNA levels were inhibited by TCDD whereas no inhibition was observed with the mutant ER/Sp1-"XRE" plasmids. Electrophoretic mobility shift assays showed that the nuclear or transformed cytosolic Ah receptor complex blocked formation of the ER-Sp1 complex with the wild-type but not the ER/Sp1 mutant oligonucleotide. Moreover, incubation of the wild-type bromodeoxyuridine-substituted ER/Sp1 oligonucleotide with the nuclear Ah receptor complex gave a specifically bound cross-linked 200-kDa band. These data demonstrate that Ah receptor-mediated inhibition of E2-induced cathepsin D gene expression is due to disruption of the ER-Sp1 complex by targeted interaction with an overlapping XRE.

Alkaline Phosphatase↗
PubMed1993

Mechanism of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated decrease of the nuclear estrogen receptor in MCF-7 human breast cancer cells.

Treatment of MCF-7 cells with 1 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 1 nM [3H]17 beta-estradiol resulted in decreased radiolabeled nuclear estrogen receptor (ER) levels as determined by velocity sedimentation analysis. In parallel studies, nuclear extracts from TCDD-treated cells also exhibited decreased binding to a consensus 32P-genomic estrogen responsive element (ERE) as determined in a gel mobility shift assay. Time-course studies showed that the decreases in nuclear ER and ER-ERE binding in TCDD-treated cells were observed within 1 to 3 h after treatment, respectively, and persisted for up to 24 h. Cycloheximide (10 microM) did not affect the TCDD-mediated response, whereas 1 microM alpha-naphthoflavone, an aryl hydrocarbon (Ah) receptor antagonist, partially blocked downregulation of nuclear ER binding by TCDD. TCDD did not significantly affect steady state ER mRNA levels as determined by Northern analysis or the rate of ER gene transcription in a nuclear run-on assay. These results suggest that the TCDD-mediated decrease in nuclear ER levels is an Ah receptor-mediated response which occurs at the translational or post-translational level.

Analysis of Variance↗
PubMed1988

Thermodynamics in the prediction of the solubilities of binary mixtures of the diastereoisomers and enantiomers of ephedrine.

Equations derived from the Clausius-Clapeyron and Prigogine-Defay equations were used to determine the free energy of mixing for diastereoisomers and enantiomers from heats of fusion and transition temperature data. These equations are applied to the thermodynamics of mixing of the six binary equimolar combinations of (1R,2S)-ephedrine, (1S,2R)-ephedrine; and (1R,2R)- and (1S,2S)-pseudoephedrine isomers. The relative equilibrium solubility of the binary mixtures in water is consistent with thermodynamic calculations.

Chemical Phenomena↗
PubMed1987

Postpartum haemorrhage--a continuing problem.

The factors responsible for postpartum haemorrhage (PPH) in singleton vaginal deliveries, not complicated by a retained placenta, were identified by comparing labour characteristics in 86 women who had a PPH (blood loss greater than 500 ml) with 351 women whose blood loss at delivery was less than 350 ml. Primiparity, induction of labour by amniotomy/oxytocin, forceps delivery, long first and second stages, oxytocin compared with syntometrine (oxytocin plus ergometrine maleate), as a prophylactic oxytocic, were identified as significant risk factors. Epidural analgesia contributed indirectly to an increase in the risk of postpartum haemorrhage. The changes in labour ward practice over the last 20 years have resulted in the re-emergence of PPH as a significant problem.

Amnion↗
PubMed1986

Surfboard-related ocular injuries.

Three cases of ocular trauma caused by surfboards are reported. The severe nature of the injuries is discussed and the prevalence of this type of injury is reviewed.

Adult↗
PubMed1986

Comparison of psychomotor skills and amnesia after induction of anesthesia with midazolam or thiopental.

In two groups of 31 healthy patients undergoing minor elective surgery, anesthesia was induced intravenously with either midazolam maleate, 0.2 mg/kg, or thiopental, 3.5 mg/kg. All subjects received 2 micrograms/kg fentanyl 5 min before the induction agents. Induction time with midazolam was significantly longer than with thiopental (97.1 +/- 10.9 sec vs 59.4 +/- 5.0 sec) and time to orientation postoperatively was significantly longer after midazolam (31.7 +/- 4.2 min vs 11.0 +/- 1.1 min). Continued recovery after orientation, measured by a series of psychomotor tests, was also significantly longer with midazolam than with thiopental. Anterograde amnesia was evident in 84.8% of the midazolam treated patients and in only 31.4% of the thiopental group. This degree of absence of recall was acknowledged positively by the affected patients. The protracted recovery period may limit the use of midazolam in short surgical procedures.

Adult↗
PubMed1985

Hemodialysis clearance of pentobarbital during continuous infusion.

The hemodialysis clearance of pentobarbital during continuous infusion was determined in a 34-year-old man in acute renal failure. Pentobarbital specimens were obtained simultaneously from arterial blood entering and leaving the dialysis machine at five 1-h intervals. The mean hemodialysis clearance of pentobarbital was 22.3 ml/min. Pentobarbital concentration was relatively unaffected throughout the dialysis period, because of the high dose and continuous infusion of a drug with low hepatic intrinsic clearance and a short dialysis period. A large contribution to total body clearance was not evident, and dosage adjustment would have been unwarranted.

Acute Kidney Injury↗
PubMed1981

Hazardous materials management and control program at Oak Ridge National Laboratory--health protection.

Maintaining reasonable control of all hazardous materials used in a large research laboratory can be a formidable task. At Oak Ridge National Laboratory, a Hazardous Material Coordinator for Health Protection (HMC-Hlth) and a Hazardous Material Coordinator for Environmental Protection (HMC-Env) control hazardous materials from acquisition to disposal. The HMC-Hlth, a member of the Industrial Hygiene Department, is responsible for control of the purchase and use of hazardous materials. If the material has not had a hazard evaluation, the user is required to contact the HMC-Hlth to find out if the material is hazardous before ordering it. If the material is hazardous, the user must get permission from his divisional representative to purchase it. The user is required to fill out Part 2 of a Hazardous Material Control Card (HMCC), describing the proposed use and location of the material and to return HMCC to the HMC-Hlth. This allows the Industrial Hygiene Department to evaluate the use of the materials and to take air samples as needed. Part 1 of the HMCC also contains computer printed information on the hazards.

Chemical Industry↗
PubMed1980

Comparison of dye dilution method to radionuclide techniques for cardiac output determination in dogs.

A study was undertaken to identify the most accurate 99mTc-labeled radiopharmaceutical and to determine the accuracy of a noninvasive radionuclide technique (antecubital injection and precordial detection) for cardiac output determinations. Phase I employed sodium pertechnetate, stannous pyrophosphate with sodium pertechnetate, technetium-99m red blood cells, and technetium-99m human serum albumin as radionuclide tracers. Cardiac output was determined by the dye dilution method and then by the invasive radionuclide technique. The radiopharmaceutical was injected into the same intracardiac catheter used in the dye dilution method. Seven to 10 mongrel dogs were used to test the accuracy of each radiopharmaceutical. A paired t test and regression analysis indicated that technetium-99m human serum albumin was the most accurate radiopharmaceutical for cardiac output determinations, and the results compared favorably to those obtained by the dye dilution method. In Phase II, technetium-99m human serum albumin was used as the radionuclide tracer for cardiac output determinations with the noninvasive technique. The results compared favorably to those obtained by the dye dilution method. Regression analysis indicated a correlation coefficient of 0.91. A paired t test demonstrated that the difference between the two methods was not statistically significant (p greater than 0.05). The data suggest that a noninvasive radionuclide technique using cardiac output determinations in humans.

Animals↗
PubMed1980

The toxic materials control program at ORNL revisited.

For large industrial and research operations, maintaining reasonable control of all toxic materials used in their operations can be a formidable task. A system utilizing cards has been developed which serves a dual purpose, informing the user regarding hazards of a particular material and also facilitating appropriate workplace surveillance during its use. Selected hazard data and spill notification message, if applicable, are printed on the card. The card contains a label which the user detaches and affixes to the container. This label classifies the material according to toxicity, flammability, reactivity, special properties on a 0 through 4 hazard rating, and spill message if needed to comply with environmental requirements.

Accident Prevention↗
PubMed1977

Effect of particle number on lung perfusion images: concise communication.

Twelve normal mongrel dogs were injected with decreasing numbers of 99mTc-labeled macroaggreagated albumin particles (99mTc-MAA), and lung images were recorded using both parallel-hole and pinhole collimators. The quality of normal lung images was found to decrease with decreasing numbers of injected radiolabeled particles (from 10,000 to 250 particles per injection). The quality was unaffected by adding carrier MAA. The minimum number of particles compatible with a good-quality image of the normal human lung is approximately 60 radiolabeled particles per gram of lung.

Animals↗