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Biomedical subjects

G Mason

Publications and source records attributed to G Mason.

At least 73 records · Page 4Linked to original sources

Vulvitis circumscripta plasmacellularis. A clinicopathologic entity?

Four cases of vulvitis circumscripta plasmacellularis (plasma cell vulvitis) are presented. One case was associated with cutaneous lupus erythematosus and another with a history of desquamative vaginitis. Two patients were postmenopausal, and two were premenopausal. The presenting symptoms were pruritus, tenderness, superficial dyspareunia and vulvar dysuria. The lesions were situated in the introitus in three patients and on the lateral aspect of the labium minus in the fourth and appeared as well-circumscribed, glistening, erythematous patches with a faint orange hue. Histologically, epidermal edema and inflammation, a dense upper dermal band of chronic inflammatory cells, including many plasma cells, dilated capillaries, extravasated red blood cells and hemosiderin deposition, were seen. There was a variable response to local steroid therapy, but one of the postmenopausal patients responded to local estrogen alone. The term vulvitis circumscripta plasmacellularis is useful to describe an idiopathic form of erosive vulvitis with a characteristic clinical and histologic appearance.

Adult↗

1H-[13C] NMR measurements of [4-13C]glutamate turnover in human brain.

A limitation of previous methods for studying human brain glucose metabolism, such as positron emission tomography, is that metabolic steps beyond glucose uptake cannot be studied. Nuclear magnetic resonance (NMR) has the advantage of allowing the nondestructive measurement of 13C distribution in specific carbon positions of metabolites. In this study 1H-[13C] NMR spectroscopy in conjunction with volume localization was used to measure the rate of incorporation of 13C isotope from infused enriched [1-13C]glucose to human brain [4-13C]glutamate. In three studies C4 glutamate turnover time constants of 25, 20, and 17 min were measured in a 21-cm3 volume centered in the region of the visual cortex. Based on an analysis of spectrometer sensitivity the spatial resolution of the method can be improved to < 4 cm3. In conjunction with metabolic modeling and other NMR measurements this method can provide a measure of regional rates of the brain tricarboxylic acid cycle and other metabolic pathways.

Brain↗

Sickle cell retinopathy.

Sickle cell retinopathy was described as early as 1930 and research has been ongoing as to the pathophysiology of the disease, its effects on the eye and successful treatment. Disease stages have been identified and treatment modalities have been established for each stage. Research results and case reports have been published in medical journals available to physicians; however, there are no identifiable publications applicable to the nursing skills required to deal with this disease. Ophthalmic nurses should be knowledgeable of the sickle cell diseases and specifically the resultant retinopathy.

Anemia, Sickle Cell↗

Effects of the food mutagens MeIQx and PhIP on the expression of cytochrome P450IA proteins in various tissues of male and female rats.

The promutagenic 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) found in cooked food are converted to their active forms mainly by cytochrome P450 forms IA1 and IA2. By induction of these isoenzymes the food mutagens could thus influence their own rate of activation. Male and female Wistar rats were given MeIQx, PhIP, beta-naphthoflavone (BNF) or saline i.p. at 50 mg/kg body wt on three consecutive days. On the fourth day the rats were killed and lungs, kidneys, liver and intestines taken. The microsomal fraction from each organ was prepared as well as 9000 g supernatant from the liver. The induction of cytochrome P450IA was measured at the protein level by enzymatic assays (ethoxyresorufin-O-deethylation, Ames' mutagenicity test) and immunoassays (Western blot) and at the pretranslational level by RNA hybridization (Northern blot). The binding affinities of MeIQx, PhIP and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) for the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-receptor were studied by evaluation of the competition with 3H-labelled TCDD for specific binding. Ethoxyresorufin-O-deethylase (EROD) activity was significantly increased in the liver (males 2.1-fold, females 3.3-fold), kidneys (males 2.1-fold, females 1.8-fold) and lungs (males 4.3-fold, females 3-fold) of the MeIQx-treated rats. Furthermore, the levels of cytochrome P450IA proteins were increased in these animals. It was not possible, however, to detect the corresponding mRNA. In the case of the PhIP-treated animals a significantly increased EROD activity (2.7-fold) and an increased cytochrome P450IA protein level were seen only in the male lungs. Only a very weak TCDD-receptor affinity was observed for PhIP, whereas MeIQx or IQ did not appear to compete significantly with [3H]TCDD for binding to the TCDD-receptor. It is concluded that MeIQx is a weak inducer of cytochrome P450IA in several organs of the rat, while PhIP induced these isoenzymes only in the male lungs. More work is needed to clarify the mechanism(s) whereby this induction occurs.

Animals↗

Do all melanomas come from "moles"? A study of the histological association between melanocytic naevi and melanoma.

Histological examination of 1101 melanomas (990 superficial spreading and 111 nodular melanomas) from 1098 people revealed that 23.3% showed an associated melanocytic naevus. Of these, 56.5% were classified histologically as common acquired, 37.7% as dysplastic and 5.8% as congenital. Of the superficial spreading melanomas, 25.7% showed an associated naevus. By contrast, only 2.7% of nodular melanomas showed histological evidence of a coexisting naevus. When the superficial spreading melanomas were analysed by level, the presence of a naevus varied from 31.3% of level I melanomas to 21.3% of level IV melanomas. When thickness was measured, an associated naevus was found in 27.0% of superficial spreading melanomas less than 1.0 mm thick, and 14.8% of melanomas with a thickness of 1.0 mm or greater. These data suggest that most melanomas do not arise in pre-existing naevi, and accordingly public educational programs for the early detection of melanoma should focus on looking for changes in previously normal skin as well as in pre-existing moles.

Female↗

Solute concentrations of the pulmonary epithelial lining fluid of anesthetized rats.

Uncertainty persists concerning the best method of estimating the volume and solute concentrations of the pulmonary epithelial lining fluid (ELF) recovered during bronchoalveolar lavage (BAL). In the present study, measurements were made of the BAL-to-plasma concentration ratios of a variety of solutes in an anesthetized rat model. One minute after an intravenous injection of labeled Na+ and urea, 5 ml of isotonic mannitol, saline, or glucose were injected into the trachea and an initial aliquot of the BAL was immediately removed. Initial BAL-to-plasma concentration ratios of urea, Na+, Cl-, Ca2+, and total protein were similar (ranging from 0.013 to 0.017) after BAL with mannitol, but albumin and transferrin ratios were approximately 60% lower and K+ ratios were five times greater. Lavage with saline yielded BAL-to-plasma urea concentration ratios similar to those obtained with mannitol lavage. The BAL-to-plasma specific activity of urea was about twice that of Na+, indicating that urea diffused into the ELF more rapidly than Na+ during the 70 s that elapsed between the time the radioactive urea and Na+ were injected into the circulation and the time when lavage was complete. Subsequent lavage samples also indicated that urea rapidly diffuses into the fluid-filled lungs. These experiments suggest that isotonic mannitol may be a useful solution for lavage, because it allows use of Na+ and perhaps Cl- as additional indicators of ELF dilution by BAL.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of a very low calorie diet on weight, thyroid hormones and mood.

Changes in weight, thyroid hormones and mood were examined in 15 obese (113 kg) women over an 18-week period. After 4 weeks of a 1200 kcal/day diet, patients were randomly assigned to one of two dietary conditions: very low calorie diet (VLCD) (n = 8) or balanced deficit diet (BDD) (n = 7). VLCD patients consumed 400 kcal/day for 8 weeks and then gradually returned to a 1200 kcal/day diet. BDD patients consumed 1200 kcal/day for the entire 18 weeks. Differences in weight losses between the conditions were statistically significant only during the consumption of the VLCD. Serum T3 decreased by as much as 66 percent in VLCD patients during consumption of the 400 kcal/day diet, whereas rT3 increased by as much as 27 percent. T3 increased when patients were realimented with a 1000 kcal/day balanced diet but remained a significant 22 percent below baseline at the end of the study. BDD patients also showed marked reductions in T3, as great as 40 percent, so that the differences between the two conditions were not statistically significant. Multiple regression analyses, collapsing across conditions (n = 15), indicated that weight loss at week 12 and baseline T3 accounted for 63 percent of the variance in the change in T3 at week 12. Patients in both conditions showed improvements in mood. Changes in depression were not associated with changes in serum T3.

Adult↗

Ligand-dependent interaction of the dioxin receptor with target DNA.

Wild type and nuclear transfer deficient mouse hepatoma cell lines were used to study the specific DNA binding of a dioxin inducible factor. This factor interacts with XRE only after dioxin treatment and is absent in receptor mutant containing cells even after treatment. Thus, evidence is provided to substantiate the claim that the dioxin receptor is involved in the specific DNA interaction with dioxin response enhancer elements. It is also shown that the molybdate stabilised dioxin-receptor interacts with hsp90 suggesting that, in similarity to the glucocorticoid receptor, the dioxin receptor is kept in a non-transformed state in the absence of ligand.

Animals↗

Development and validation of in vitro induction assays for toxic halogenated aromatic mixtures: a review.

Halogenated aromatic industrial compounds, typified by the polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls (PCBs) have been identified as residues in almost every component of the global ecosystem. Risk assessment of the complex mixtures of halogenated aromatics found in environmental samples is complicated by analytical problems and the lack of toxicological information on individual compounds and mixtures. Research in our laboratory has focused on the development and vadidation of the in vitro aryl hydrocarbon hydroxylase (AHH) induction assay in rat hepatoma H-4-II E cells in culture for quantitating individual toxic halogenated aryl hydrocarbons and their mixtures. For several PCB, PCDD, PCDF congeners, their mixed bromo/chloro analogs and reconstituted mixtures there was an excellent linear correlation between their -log ED50 values for AHH induction in rat hepatoma cells and their -log ED50 values for in vivo hepatic microsomal AHH induction, inhibition of body weight gain and thymic atrophy in the rat. It has also been shown for selected compounds that there was a good correlation between their in vitro AHH induction potencies and their effects in guinea pigs (AHH induction, inhibition of body weight gain) and mice (immunotoxicity). This assay system has been utilized to quantitative the "2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents" present in extracts from diverse sources including fly ash from a municipal incinerator and pyrolyzed brominated flame retardants which contain a complex mixture of halogenated dibenzo-p-dioxins and dibenzofurans.

Animals↗

Organ-specific effects of long term feeding of 2,3,7,8-tetrachlorodibenzo-p-dioxin and 1,2,3,7,8-pentachlorodibenzo-p-dioxin on I-compounds in hepatic and renal DNA of female Sprague-Dawley rats.

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent hepatocarcinogen, and 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PCDD) on liver and kidney DNA of female Sprague-Dawley rats were investigated by 32P-post-labeling assay. The compounds were administered by gavage [1 microgram/kg/week in corn oil (5 ml/kg)] to the animals for up to 6 months. No exposure-related 32P-labeled spots indicative of TCDD or PCDD covalent DNA adducts were noted on the chromatograms of kidney or liver DNA nucleotides from the rats exposed to the toxins for 2 and 6 months. Corn-oil treated control animals exhibited the characteristic tissue- and age-specific patterns of 32P-labeled I-spots in liver and kidney DNA which are associated with specific DNA modifications of unknown origin and function. Treatment with either TCDD or PCDD resulted in a substantial reduction of the levels of I-compounds in liver, a target organ for TCDD carcinogenesis. After 6 months of exposure to TCDD the reductions in the amounts of individual hepatic I-compounds ranged from 37 to 77% and decreased levels were also observed after 2 months of treatment. It was apparent that PCDD was not as effective as TCDD in reducing hepatic I-compound levels and this corresponded with the lower aryl hydrocarbon receptor binding activity of the former compound. In contrast, TCDD and PCDD did not cause any significant decrease of I-compounds in the kidney which is not a site of TCDD-mediated carcinogenicity in female Sprague-Dawley rats. Whether I-compound deficiency contributes to TCDD-mediated hepatocarcinogenesis (e.g. by facilitating DNA replication) needs to be investigated.

Aging↗

Lack of acute d-amphetamine effects on thyrotropin release.

Case reports have suggested that amphetamine abuse causes excessive secretion of thyrotropin (TSH) and thyroxine (T4). Such an amphetamine-induced effect might be noradrenergic-mediated in the hypothalamus. The current controlled study examined oral d-amphetamine effects on the hypothalamic-pituitary-thyroid axis in normal humans. No acute effects were seen on TSH, T3 or T4 levels. d-Amphetamine elevated cortisol levels at 180 min, as previously reported.

Adult↗

Regional variation in the response of cerebral ornithine decarboxylase to electroconvulsive shock.

Levels of ornithine decarboxylase activity were measured in brain regions and in adrenal glands of adult male rats exposed to electroshock. Five hours after shock at levels causing transient loss of consciousness and fore and hindlimb tonic extensor seizures, major increases in ornithine decarboxylase activity were found in adrenals, hippocampus, brain stem, frontal cortex, and cerebellum, but striatal levels were unchanged. These increases were reversed by 24 h after electroshock. When lower levels of shock, which caused no loss of consciousness, were also used, a clear dose-response relationship of shock intensity and ornithine decarboxylase activity was found for hippocampus and brain stem. The ornithine decarboxylase response in brain increased with higher shock levels. However, the changes of ornithine decarboxylase in adrenal glands were maximal at intermediate, and diminished at maximal shock values, as were levels of circulating testosterone. These data suggest a differing role for cerebral and adrenal ornithine decarboxylase in the mature rat. The brain enzyme may be primarily related to metabolic repair processes, whereas adrenal ornithine decarboxylase may function in the activation of secretion.

Adrenal Glands↗

Polybrominated dibenzo-p-dioxins and related compounds: quantitative in vivo and in vitro structure-activity relationships.

The effects of structure on the in vitro receptor binding affinities, aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) induction potencies in rat hepatoma cells were determined for the following compounds: 2-bromo-, 2,7/2,8-dibromo-, 2,3,7-tribromo-, 2,4,6,8/1,3,7,9-tetrabromo-, 2,3,7,8-tetrabromo-, 1,3,7,8-tetrabromo-, 1,2,3,7,8-pentabromo-, 1,2,4,7,8-pentabromo-, 2,3-dibromo-7,8-dichloro-, 2,8-dibromo-3,7-dichloro- and 2-bromo-3,7,8-trichlorodibenzo-p-dioxin. The structure-activity relationships (SARs) for the polybrominated dibenzo-p-dioxins (PBDDs) were comparable for both in vitro responses: the most active compounds were substituted only in the lateral 2,3,7 and 8 position and the addition of non-lateral or removal of lateral halogen substituents reduced the activity of the resultant compound. The biologic and toxic effects of 2,3,7,8-tetrabromo-, 1,3,7,8-tetrabromo-, 1,2,4,7,8-pentabromo-1,2,3,7,8-pentabromo-, 2-bromo-3,7,8-trichloro- and 2,3-dibromo-7,8-dichlorodibenzo-p-dioxin on several receptor-mediated responses (thymic atrophy, body weight loss, hepatic microsomal AHH and EROD induction) were determined in a dose-response fashion in immature male Wistar rats. A comparison of the ED50 values for the in vivo responses demonstrated that the SARs for the PBDDs and brominated polychlorinated dibenzo-p-dioxins were comparable to those observed for in vitro receptor binding and AHH induction. Moreover, there was an excellent linear correlation between the -log EC50 (in vitro AHH induction) vs. the in vivo -log ED50 (thymic atrophy) and -log ED50 (body wt loss) correlation coefficient, r = 0.97 for all 2 correlations).

Animals↗