Cancer of the prostate: endocrine factors.
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Aging↗
Biomedical subjects
D W Wilson
Publications and source records attributed to D W Wilson.
Response of the macaque nasal epithelium to ambient levels of ozone. A morphologic and morphometric study of the transitional and respiratory epithelium.
Although ozone (O3)-induced bronchiolitis has been morphologically characterized, effects of O3 on the upper respiratory tract have not been thoroughly investigated. The purpose of this study was to determine whether exposures to ambient levels of O3 induce lesions in the nasal mucosa. Bonnet monkeys were exposed to 0.00, 0.15, or 0.30 ppm O3 for 6 or 90 days, 8 hours/day. After exposure, nasal mucosa was processed for light and electron microscopy. Quantitative changes were evident in the nasal transitional and respiratory epithelium. At 6 or 90 days of exposure to 0.15 or 0.30 ppm O3 lesions consisted of ciliated cell necrosis, shortened cilia, and secretory cell hyperplasia. Inflammatory cell influx was only present at 6 days of exposure. Ultrastructural changes in goblet cells were evident at 90 days. Ambient levels of O3 can induce significant nasal epithelial lesions, which may compromise upper respiratory defense mechanisms.
Animals↗
Daily salivary progesterone levels in cyclical mastalgia patients and their controls.
Progesterone levels were measured in samples of saliva collected daily throughout the menstrual cycle in patients with pronounced cyclical mastalgia and breast nodularity. A control group matched for age, length of menstrual cycle and parity was also studied. No significant differences in progesterone levels were detected between the two groups for the luteal phase of the cycle. These data indicate that cyclical mastalgia is not associated with significant luteal phase progesterone insufficiency, as demonstrated by salivary levels and, by implication, serum levels of progesterone.
Adult↗
Hepatic pathological changes due to hydroxyalkenals.
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Aldehydes↗
Niacin skin flush is not diagnostic of schizophrenia.
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Administration, Oral↗
Metabolism of aflatoxin B1 in the upper airways of the rabbit: role of the nonciliated tracheal epithelial cell.
Short-term tracheal explant cultures from the rabbit were used to study the metabolism of the carcinogen aflatoxin B1 (AFB1) and to determine the cell types that are susceptible to damage by AFB1 and their relative contents of monooxygenase enzymes. Tracheas were cultured in serum-free medium for 0.5-24 h with 0.7 microM [3H]AFB1, and metabolism was measured by determining the level of binding of the carcinogen to DNA and by the release of metabolites into the medium. The binding of aflatoxin B1 was time dependent and appeared to peak at 12 h in culture. In addition, the metabolites aflatoxicol, aflatoxin M1, and aflatoxin Q1 were produced by the explants. Ultrastructural evaluation of cultured tracheas showed degenerative changes exclusively in nonciliated secretory cells after 4 h in culture. Extensive nonciliated secretory cell necrosis was evident by 12 h. Ciliated cells did not show degenerative changes until 12 h and appeared much more viable after 24-h exposure to AFB1 relative to the nonciliated cells. Tracheal sections stained to demonstrate rabbit lung cytochrome P-450, Forms 2 and 5, and cytochrome P-450 reduced nicotinamide adenine dinucleotide phosphate reductase by an immunoperoxidase technique showed intense staining selectively within nonciliated cells. In total, the data revealed that: (a) rabbit tracheal explants are able to metabolize aflatoxin B1; (b) the nonciliated secretory cell population in this tissue is the target cell for cytotoxicity of this carcinogen; and (c) as is the case in the more distal airways, the nonciliated epithelial cells appear to have a high content of components of the pulmonary cytochrome P-450 monooxygenase system, which may be an important factor in the susceptibility of these cells and this region of the airways to suspected airborne carcinogens.
Aflatoxin B1↗
trans-4-Hydroxy-2-hexenal: a reactive metabolite from the macrocyclic pyrrolizidine alkaloid senecionine.
The toxicity of macrocyclic pyrrolizidine alkaloids in the livers of man and animals has been attributed to the formation of reactive pyrroles from dihydropyrrolizines. Now a novel metabolite, trans-4-hydroxy-2-hexenal, has been isolated from the macrocyclic pyrrolizidine alkaloid senecionine, in an in vitro hepatic microsomal system. Other alkenals such as trans-4-hydroxy-2-nonenal have previously been isolated from microsomal systems when treated with halogenated hydrocarbons or subjected to lipid peroxidation. The in vivo pathology caused by trans-4-hydroxy-2-hexenal appears to be identical to that previously attributed to reactive pyrroles. There are similarities between the toxic effects of this alkenal and those of centrilobular hepatotoxins such as CCl4 and other alkenals formed during lipid peroxidation.
Aldehydes↗
A prognostic index for the clinical management of patients with advanced prostatic cancer: a British Prostate Study Group investigation.
Patients with histologically proven carcinoma of the prostate (n = 186) were initially assessed and followed up according to the standardized protocol of the British Prostate Study Group, urologists from which contributed patients to this investigation. These patients were given either endocrine therapy or orchidectomy as first line treatment; the ratio of the number of patients receiving these two treatments was similar in each group of subjects compared for survival. Prognostic indices were derived for all patients and for those classified according to the presence (M1) or absence (M0) of metastases. The prognostic indices were derived from clinical and hormone data obtained at initial presentation. Whereas the degree of tumor differentiation and plasma testosterone concentrations were significant prognostic factors in both M0 and M1 disease, growth hormone was only significant in M1 patients, where age was also of borderline significance; elevated growth hormone, higher Gleason grade, younger age, and lower testosterone indicated a poorer prognosis in M1 patients. These findings indicated the feasibility of selecting a poor prognostic group of patients that may derive benefit from a more aggressive therapy.
Age Factors↗
Analysis of the effects of measured white blood cell entrance times on hemodynamics in a computer model of a microvascular bed.
To quantify the interdependence of capillary leukocyte plugging and microvascular hemodynamics, experimental measurements were made of the time required for lymphocytes and granulocytes to enter a micropipette. Using standard micropipette deformation techniques, entrance times were found to be a function of both cell diameter and pipette diameter, with no significant dependence on aspiration pressure over the differential pressure range of 200-400 Pa. Experimental results were combined with a computer network model to describe changes in red cell distribution and flow rate resulting from the delayed entrance of leukocytes (WBC) into capillaries. The network model is based on geometrical measurements from the capillary bed of a hamster cremaster muscle (Sarelius et al. 1981) and utilizes previous work describing: 1. preferential cell distribution at a bifurcation, 2. increased apparent viscosity due to the presence of red and white cells, and 3. increased velocities of red and white cells relative to blood. Red and white cell positions within the network were computed at discrete time increments, and WBC plugging was simulated by a temporary cessation of flow in vessels of smaller diameter than the white cell. In contrast with previous studies, the increased viscosity due to the presence of WBCs was found to have an insignificant effect on overall network flow rate. Instead, a major flow reduction occurs only when capillaries are plugged by the white cells. At normal physiological concentrations (1,000 RBC/WBC), time-averaged overall network flow is reduced by 4.4%, based on averaged experimentally measured entrance times, and up to 14.8% if maximal entrance times are used.(ABSTRACT TRUNCATED AT 250 WORDS)
Erythrocytes↗
Evaluation of luteal-phase salivary progesterone levels in women with benign breast disease or primary breast cancer.
Salivary progesterone concentrations were determined in premenopausal parous women with a mean age of ca. 40 yr who had a history of either benign breast disease (n = 15) or primary breast cancer (n = 15) and in a group of age-matched healthy women (n = 15). Saliva samples were collected at 09.00 and 21.00 hr daily for one complete menstrual cycle and progesterone concentration was measured by radioimmunoassay. Characteristic luteal-phase progesterone profiles were observed in all subjects in each of the three groups but no statistical intergroup differences could be demonstrated for age-matched subjects in each group. These studies indicated that ovarian dysfunction, as judged from salivary progesterone concentrations, was not apparent in older premenopausal women with a history of benign breast disease or primary breast cancer when compared with age-matched controls.
Adult↗
Disseminated infection associated with corticosteroid therapy after transduodenal sphincteroplasty.
Treatment with oral prednisolone appears to have precipitated an episode of ascending cholangitis in an asymptomatic 55-year-old patient. He had undergone a Pólya partial gastrectomy, a cholecystectomy and a sphincteroplasty 19, 6 and 2 years earlier, respectively. The cholangitis was complicated by septicaemia with six different enteric organisms including aerobes and anaerobes. He developed liver and lung abscesses, and an indolent Pseudomonas aeruginosa septic arthritis of both hip joints. The patient eventually made a complete recovery, but required surgical replacement of both hips.
Ampulla of Vater↗
Relationships between the circadian rhythms of TSH, prolactin and cortisol in surgically treated microprolactinoma patients.
Pharmacological doses of glucocorticoids inhibit TSH release both in vivo and in vitro and since the circadian rhythms of TSH and cortisol show a reciprocal relationship, the hypothesis has been advanced that changes in cortisol levels may be a primary determinant of circadian TSH changes. We have tested this hypothesis by studying the relationship between circadian cortisol and TSH rhythms in subjects before and during blockade with metyrapone. Seven patients were studied during their routine post-operative assessment following selective transethmoidal adenomectomy for microprolactinomas. PRL levels were restored to normal (less than 420 mU/l) in all patients by surgery (pre-op: 930-2752 mU/l, post-op: 33-376 mU/l) and the patients also had normal pituitary function in other respects. Blood was sampled hourly for 24 h before and on the third day of treatment with metyrapone (250 mg, 2 hourly). In order to compare circadian rhythms, hormonal data were subjected to cosinor analysis which involved fitting of the data with a cosine function using the method of least squares. The 6% cross reactivity of the cortisol antibody with 11-deoxycortisol was taken into account during the calculation of results. All subjects showed a normal cortisol rhythm which was strikingly blunted during metyrapone treatment. Group mean (+/- SD) TSH mesors, amplitudes and acrophases for control and metyrapone treated subjects were 1.5 +/- 0.26, 1.29 +/- 0.48; 0.46 +/- 0.26, 0.23 +/- 0.13 and -49 degrees +/- 9.8 degrees; -62 degrees +/- 2.7 degrees respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Characterization of profiles of salivary progesterone concentrations during the luteal phase of fertile and subfertile women.
Salivary progesterone concentrations were measured in daily samples collected between 08.00 and 09.00 h throughout the menstrual cycle of women with a history of fertility. The luteal-phase salivary progesterone profiles in these normally menstruating, healthy women were characterized using a computer program based on a cumulative sum procedure. This method of statistical analysis led to the development of a 'progesterone boundary diagram', the inner and outer domains of which distinguished between the profiles of salivary progesterone considered compatible with fertility, and those observed in subfertile women attending an infertility clinic.
Adolescent↗
The use of salivary steroids to monitor circadian rhythmicity on expeditions in the arctic.
The circadian variation in salivary cortisol concentration was investigated in four men during a traverse on foot, of the Greenland ice cap and of salivary cortisol and testosterone on a summer expedition to Spitzbergen. In both instances circadian rhythmicity was demonstrated both before leaving the U.K. and throughout the expedition. The acrophase of the rhythms followed the changes in activity patterns on both expeditions although there was a dissociation between the cortisol and testosterone following an acute 8 hr phase shift in Spitzbergen. The mesor of cortisol in both instances tended to be higher than in the U.K. but the difference was never statistically significant. This work demonstrates the feasibility of using salivary steroid concentrations to investigate their circadian rhythmicity in circumstances where frequent blood sampling would be precluded.
Adult↗
Deferoxamine injection does not affect bleomycin-induced lung fibrosis in rats.
Bleomycin is an antineoplastic agent that causes a dose-related lung fibrosis that limits its therapeutic effectiveness. It has been proposed that the cellular toxicity and antitumor effects of bleomycin occur by formation of O2-Fe(II)-bleomycin complexes that degrade DNA and release O2- and OH radicals that attack other cellular components. Twice daily injections of the iron chelator deferoxamine were utilized in an attempt to ameliorate bleomycin-induced lung fibrosis. They failed to diminish bleomycin-induced lung inflammation and fibrosis in rats.
Animals↗
Endocrine factors in the treatment of prostatic cancer.
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Buserelin↗
The tracheobronchial epithelium of the bonnet monkey (Macaca radiata): a quantitative ultrastructural study.
Since there are major differences between the airway epithelium of man and that of common laboratory species, the tracheobronchial epithelium of the bonnet macaque was characterized to evaluate its usefulness as a model for study of human conducting airways. This study compared the light microscopic, scanning electron microscopic, and ultrastructural appearance of epithelium from the posterior membranous and anterior cartilaginous trachea and mainstem bronchus. Population densities, epithelial volumetric densities, and frequency distributions of cross-sectional areas of nuclei were determined for cell types present on electron micrographs. Four epithelial cell types were distinguished by ultrastructural criteria. Basal cells were 31% of the population and were similar to those described in other species. Ciliated cells were also similar to those of other species and composed 41% of the population; their nuclei were larger than those of other cell types. Mucous goblet cells had large numbers of secretory granules with electron-dense cores and a lucent periphery. They were only 8% of the population by nuclear count but composed 20% of the epithelial volume. The fourth cell type had multiple small vesicles containing small amounts of granular material and was termed a "small mucous granule cell." Small mucous granule cells (16% of the population) were present in greater numbers than mucous goblet cells but were a smaller proportion of the epithelial volume (8%). While population densities of cell types determined from transmission electron micrographs did not vary between sample sites, scanning electron microscopy demonstrated longitudinal streaks of secretory cells in the posterior trachea suggesting that regional differences in epithelial organization exist. We conclude that the macaque extrapulmonary airway epithelium differs from published descriptions of laboratory rodents in both cell types present and relative abundance of those cell types. Although detailed quantitative studies of human extrapulmonary airways are not available, the primate airways resemble those of man in both the types of cells present and the complexity of pseudostratification.
Animals↗
Metabolism, DNA binding, and cytotoxicity of aflatoxin B1 in tracheal explants from Syrian hamster.
Metabolism, DNA binding and cytopathological effects of aflatoxin B1 (AFB1) were studied in isolated tracheal explants from Syrian golden hamsters. Explants were exposed to 0.1, 0.5 and 1.0 microM [14C]AFB1 in Dulbeccos's modified Eagle medium for 24 h, then analyzed for AFB1-DNA binding and AFB1 metabolism. Binding (pmol AFB1/mg DNA) was dose-related (16.3 +/- 1.9 to 180.8 +/- 16.1) and analysis of the culture medium revealed the metabolic conversion products aflatoxicol (AFL) and aflatoxin Q1 (AFQ1). Ultrastructural analysis of sections of tracheal epithelium revealed degenerative changes primarily in the non-ciliated epithelial cells. Autoradiographic analysis of the same treated explants, however, showed no discernible distribution of label with respect to either cell type or cell location, with the exception of increased grain densities overlying vacuoles containing dark droplets. In addition, S9 prepared from hamster trachea was shown to activate AFB1 to mutagens detectable by Salmonella typhimurium TA 98, but was approximately 70 times less active on a per mg protein basis than was S9 prepared from hamster liver. These results demonstrate the metabolic capabilities of tracheal epithelial cells in the activation of AFB1, thus indicating that AFB1 present in respiratory particles may be activated by pulmonary mixed-function oxidases, posing a hazard to those exposed.
Aflatoxin B1↗