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Biomedical subjects

D W Wilson

Publications and source records attributed to D W Wilson.

At least 109 records · Page 6Linked to original sources

Changes in type II cell populations in monocrotaline pneumotoxicity.

Unlike many other systemically administered pneumotoxicants affecting alveolar septa, Monocrotaline (MCT) does not cause a proliferative type II cell response. To determine whether MCT has an effect that might alter the type II cell response, we determined the numerical density and volume of type II cells in lungs from MCT-treated rats. Morphometric parameters were derived from estimates of nuclear volume based on point and intercept ratios counted in electron micrographs of type II cell profiles. These were combined with point and intercept counts of alveolar septal structures and counts of nuclear profiles per unit area to calculate average cell volume and numerical density of type II cells. Areal densities of type II cell profiles were determined by light microscopic counts of alveolar parenchyma and normalized to the volume of lung parenchyma. Cell volume of type II cells was markedly increased in MCT-treated animals (1.25 X 10(3) microns3) compared with controls (3.4 X 102) microns3). Nuclear diameter of type II cells was similarly increased (8.53 microns in treated animals versus 5.81 microns in controls). The number of type II cells was markedly decreased in treated animals (1.36 X 10(6] cells per cm3 lung parenchyma compared with 7.65 X 10(6) cells per cm3 parenchyma in controls). We conclude that MCT causes marked cellular hypertrophy of type II alveolar epithelial cells and that this hypertrophy is somehow related to a failure to maintain normal cell populations in the lung of MCT-treated rats. We hypothesize that this change is analogous to the hypertrophy and mitotic inhibition that occurs in the liver of animals treated with hepatotoxic pyrrolizidine alkaloids.

Animals↗

Chronobiology in laboratory medicine: principles and clinical applications illustrated from measurements of neutral steroids in saliva.

A number of chronobiological principles, as they pertain to the practice of laboratory medicine, have been discussed. Without doubt, salivary steroid assays are valuable tools for use in clinical studies, not necessarily as a single time-qualified sample but more often as a series of samples that will describe the underlying endocrinological time-structure. It is also important to appreciate that melatonin, certain drugs, and many dietary constituents such as phyto-oestrogens, are among the myriad of substances that can be monitored, and so hold great promise for the chronobiologist interested in the use of saliva as a sampling medium, both in the present and in the future.

Adrenal Glands↗

Potential value of salivary steroids in chronoepidemiological and endocrine-related studies.

Experience from Institute studies has clearly demonstrated the advantages of salivary steroids in clinical endocrinological research and their potential value in chronoepidemiological studies of many kinds that may involve hormones. Of course, the examples and suggestions for areas of research involve many more covariates than those mentioned; but sufficient evidence has been presented to indicate the chronobiological potential of salivary steroid assays in studies of mental health, aggression and behaviour, stress, the endocrine changes occurring from birth to old age and those relating to endocrine cancer. The pioneering studies of Halberg et al (1981) and Haus et al. (1987) have demonstrated the feasibility of carrying out international epidemiological studies as they relate to breast cancer risk and studies of the general population. The potential value of salivary steroid assays in clinical, physiological and epidemiological studies is judged to be considerable.

Chronobiology Phenomena↗

A fusion protein required for vesicle-mediated transport in both mammalian cells and yeast.

A protein sensitive to N-ethylmaleimide catalyses the fusion of transport vesicles with Golgi cisternae in a mammalian cell-free system. By cloning and sequencing its gene from Chinese hamster ovary cells and by use of in vitro assays, we show that this fusion protein is equivalent to the SEC18 gene product of the yeast Saccharomyces cerevisiae, known to be essential for vesicle-mediated transport from the endoplasmic reticulum to the Golgi apparatus. The mechanism of vesicular fusion is thus highly conserved, both between species and at different stages of transport.

Amino Acid Sequence↗

Effects of chronic administration of doxorubicin on myocardial creatine phosphokinase and antioxidant defenses and levels of lipid peroxidation in tissues and plasma of rats.

Tissue and plasma levels of thiobarbituric acid reactive substances (TBARS) were measured in rats treated chronically with doxorubicin. In addition, heart creatine phosphokinase and antioxidant defenses were examined. Male rats received doxorubicin (DXR) 2 mg/kg or vehicle weekly subcutaneously for 13 weeks and were sacrificed at 14 and 19 weeks, 1 and 6 weeks after the last dose, respectively. Histological evaluation in DXR-treated rats at 14 and 19 weeks found significant and progressive cardiac and renal lesions as compared to controls. Heart TBARS were unchanged from controls. Plasma and kidney levels of TBARS were elevated above controls at both 14 and 19 weeks. Lung levels of TBARS were significantly elevated above controls at 14 weeks. Liver levels of TBARS were elevated at 19 weeks. Heart creatine phosphokinase activity was significantly depressed from controls at both 14 and 19 weeks. Heart glutathione peroxidase and superoxide dismutase activities were unchanged from controls. Heart glutathione, glutathione reductase, glucose-6-phosphate dehydrogenase, and catalase were elevated above controls at both 14 and 19 weeks. The lack of change in heart TBARS suggests that changes in TBARS in other organs may be secondary processes. The depression of creatine phosphokinase suggests that levels of adenosine triphosphate may be insufficient to sustain the myocardial function and this may partly be responsible for DXR-induced cardiac myopathy.

Animals↗

Energetics of kayaking.

The metabolic cost of paddling at low speeds (v) was measured from oxygen uptake (VO2) and anaerobic glycolysis in an annular pool or calculated from submaximal VO2 measured at higher speeds when the kayaker was assisted in overcoming water resistance. Also calculated were the total drag (D) and the net mechanical efficiency (e). Each of the above variables was determined in male (n = 17) and female (n = 7) kayakers ranging in experience from beginners to elite. The VO2 increased with v to a peak of approximately 3.4 l.min-1 (80%-100% of peak VO2 during running) in men and of approximately 2.8 l.min-1 in women, while at higher speeds the additional energy was accounted for by anaerobic glycolysis. In all subjects the energy cost to paddle a given distance (C) increased according to a power function with increasing v. The C was lower for the elite male paddlers than for the unskilled group, while that for elite women was slightly less than that for the elite men. Also the rates of increase of C appeared to be inversely proportional to the subjects' skill. Total D for elite men increased from approximately 15 to 60 N over a range of speeds from 1 to 2.2 m.s-1 while those of unskilled men and skilled women for the same speed range were 10-20 N greater and slightly less, respectively. The e increased linearly, but at a different rate, with increases in v for the unskilled and the elite kayakers (males and females) being 4.2% and 6%, respectively, at v = 1.2 m.s-1.

Adult↗

Progressive inflammatory and structural changes in the pulmonary vasculature of monocrotaline-treated rats.

The progression of changes in the bronchus-associated and intraacinar pulmonary arteries of rats treated with a single dose of monocrotaline (60 mg/kg) was evaluated by quantitative light and electron microscopy. The relative volume of vessel wall components was normalized to the surface area of the adventitial sheath. An increased relative volume of media was evident in intraacinar pulmonary arteries by 4 hr post-treatment. This increase may represent vascular smooth muscle contraction. Significant increases in adventitial mononuclear inflammatory cells were evident by 8-16 hr post-treatment in intraacinar pulmonary arteries and veins but not until 14 days post-treatment in major, bronchus-associated pulmonary arteries. Inflammatory cell influxes were associated with increased relative volume of adventitia, largely due to increased extracellular space. By 22 days posttreatment, there was right ventricular hypertrophy and a marked mononuclear vasculitis in major and intraacinar pulmonary arteries as well as intraacinar veins (confirmed as such by vascular perfusion of carbon/gelatin). There was increased relative medial volume in both major and intraacinar pulmonary arteries associated with increased extracellular matrix composed largely of collagen. Intraacinar veins developed intimal plaques of smooth muscle in a collagenous matrix. We conclude that (1) adventitial inflammation precedes morphologic evidence of medial changes in monocrotaline-induced pulmonary hypertension, (2) involvement of intraacinar arteries precedes that of major bronchus associated arteries, and (3) both pulmonary arteries and veins are involved in monocrotaline-induced pulmonary vascular disease in the rat.

Animals↗

Progesterone concentrations in samples of saliva from adolescent girls living in Britain and Thailand, two countries where women are at widely differing risk of breast cancer.

Menstrual-cycle patterns of salivary progesterone concentration were obtained for 131 and 245 adolescent girls up to 4 years postmenarche living in Britain and Thailand respectively. These patterns were graded on a scale of 1 (little or no activity) to 5 (activity similar to that exhibited by the mature premenopausal woman) and the frequency of these grades within groups of girls from each centre was analysed. The major finding was that British girls exhibited a predominance of higher grades of progesterone activity when compared with their Thai counterparts (n = 2 x 58) when matched for chronological and gynaecological ages (P approximately 0.002). This was particularly so for the girls from these two matched groups in the gynaecological age range 2-4 years (P approximately 0.03). The major contribution to this significant difference between the two groups is attributed to the greater effect of chronological age on progesterone secretion in the British girls (P approximately 0.03) compared with the Thai girls (P approximately 0.29). These findings may have implications for facilitating our understanding of the reason for the differing risk of breast cancer in women in both countries.

Adolescent↗

Immunocytochemical localization of estrogen receptor in human breast tissue.

An immunocytochemical assay for the measurement of estrogen receptor (ER-ICA; Abbott Diagnostics) has been evaluated in 163 human breast carcinomas. Specific binding was observed in the nuclei of 111 of 163 (68%) tumors. An excellent correlation was observed between the ER-ICA and the estrogen receptor enzyme immunoassay. A significant relationship was observed between ER-ICA status and percentage of ER-ICA negative cells, histological grade of malignancy, and mitotic activity of the tumors. A significant correlation was also observed between ER-ICA status and age at mastectomy with 50% of patients with ER-ICA positive breast tumors presenting with their disease over 60 years of age. No association was observed with either tumor size or patient nodal status. Examination of the proportion of negative cells within tumors revealed a trend for the acquisition of poor prognostic features to be associated with an increase in the negative cell population. Data on the recurrence free interval of these patients showed a significant recurrence free advantage in ER-ICA positive patients, particularly those whose tumors contained low numbers of negative cells.

Adult↗

Extranuclear gene expression in yeast: evidence for a plasmid-encoded RNA polymerase of unique structure.

Strains of the yeast Kluyveromyces lactis that produce killer-toxin have been found to contain two linear dsDNA plasmids, k1 (8.9 Kb) and k2 (13.4 Kb). The four transcribed open reading frames of plasmid k1 contain no recognisable yeast nuclear expression signals. Moreover, a toxin subunit gene fused with the lacZ gene of Escherichia coli is not detectably expressed when introduced to K.lactis or Saccharomyces cerevisiae on a nuclear vector, even when native k1 and k2 are present in the cell. This and other evidence is consistent with the hypothesis that k1 and k2 reside in an extranuclear location, and do not utilise the nuclear RNA polymerases I, II or III for transcription of their genes. Sequencing of plasmid k2, which is thought to encode factors necessary for the maintenance or expression of k1, reveals an open reading frame predicted to encode a 974 amino acid polypeptide with homology to several DNA-directed RNA polymerases. We suggest that this is a component of a novel plasmid-specific extranuclear gene expression system.

Amino Acid Sequence↗

Tracheobronchial epithelium of the sheep: IV. Lectin histochemical characterization of secretory epithelial cells.

Conventional histochemical characterization of the mucus secretory apparatus is often difficult to reconcile with the biochemical analysis of respiratory secretions. This study was designed to examine the secretory glycoconjugates in airways using lectins with biochemically defined affinities for main sugar residues of mucus. We used five biotinylated lectins--DBA (Dolichos biflorus) and SBA (Glycine max) for N-acetyl galactosamine (galNAc), BSA I (Bandeiraea simplicifolia) and PNA (Arachis hypogea) for galactose (gal), and UEA I (Ulex europeus)--for detection of fucose (fuc) in HgCl2-fixed, paraffin-embedded, serially sectioned trachea, lobar and segmental bronchi and bronchioles of nine sheep. Lectins selectively localized the carbohydrate residues in luminal secretions, on epithelial cell surfaces, and in secretory cells. In proximal airways, the major carbohydrate residues in luminal secretions, cell surfaces, goblet cells, and glands were fuc and gal-NAc. PNA reacted mainly with apical granules of less than 10% of goblet cells, and gal residues were only detected in some of the mucous cells and on basolateral cell surfaces. Distal airways contained sparse secretion in the lumen, mucous cells contained weakly reactive fuc and gal-NAc, and the epithelial surfaces of Clara cells contained gal. Sugars abundant in the airway secretions were also the major component of cells in glands. We conclude that there is a correlation between specific sugar residues in secretory cells, glycocalyx, and luminal secretions in proximal and distal airways. This suggests that lectins may be used to obtain information about airway secretory cell composition from respiratory secretions.

Animals↗

In vitro evidence of cellular adaptation to ozone toxicity in the rat trachea.

Adaptation to prolonged ozone (O3) exposure occurs in the tracheal epithelium of rats and is marked by the presence of ciliated cells with uniform short cilia but is not accompanied by shifts in cell populations, altered characteristics of epithelial secretory cell products, increased cell turnover, or elevated tracheal superoxide dismutase activity. The purpose of this study was to test the hypothesis that adaptation is a result of alterations intrinsic to epithelial cells or to the cells and their matrix, and not due to systemic or neural influences. Rats were preexposed to either filtered air (FA) or 0.96 ppm O3 for 8 hr/night for 60 days, and then their tracheae were removed and exposed to 3 ppm O3 in an explant culture system where behavioral, nasal, exudative, and secretory product influences can be eliminated. After exposure to 3 ppm O3 in vitro, quantitative electron microscopic evaluation demonstrated that the epithelia from the FA preexposure group had significantly more necrotic cells and sloughed cells and fewer ciliated cells than the epithelia from the O3 preexposure group. Thus previous exposure to ozone in vivo induces a change in tracheal epithelium which confers resistance to ozone-induced injury in the explant exposure system.

Adaptation, Physiological↗

The response of the rat tracheal epithelium to ozone exposure. Injury, adaptation, and repair.

Although acute ozone (O3) exposure injures tracheal epithelium, the response of the tracheal epithelium to prolonged O3 exposure, and the degree of repair following cessation of exposure have not been previously reported. The purpose of this experiment was to characterize the morphologic response of rat tracheal epithelium to acute (3 days) and prolonged (60 days) exposure to 0.96 ppm O3 as well as to evaluate repair in a 7- and 42-day post-60-day exposure period. Quantitative light- and electron-microscopic evaluation and thymidine labeling indices showed that after 3 days of O3 exposure there was ciliary damage, cell necrosis, an increased density of intermediate cells, and an elevated thymidine labeling index. Following 60 days of exposure, the only major change from controls was the presence of ciliated cells with uniformly short cilia. Tracheal superoxide dismutase levels did not differ between control and 60-day exposure groups. Our findings suggest that the tracheal epithelium adapts to prolonged ozone exposure with the exception of cilia formation in ciliated cells. Complete epithelial recovery occurred by 42 days after exposure.

Animals↗

Nonolfactory surface epithelium of the nasal cavity of the bonnet monkey: a morphologic and morphometric study of the transitional and respiratory epithelium.

The purpose of the present study was to characterize ultrastructurally the nonolfactory nasal epithelium of a nonhuman primate, the bonnet monkey. Nasal cavities from eight subadult bonnet monkeys were processed for light microscopy, and scanning and transmission electron microscopy. Nonolfactory epithelium covered the majority of the nasal cavity and consisted of squamous (SE), transitional (TE), and respiratory epithelium (RE). Stratified SE covered septal and lateral walls of the nasal vestibule, while ciliated pseudostratified RE covered most of the remaining nasal cavity. Stratified, nonciliated TE was present between SE and RE in the anterior nasal cavity. This epithelium was distinct from the other epithelial populations in abundance and types of cells present. TE was composed of lumenal nonciliated cuboidal cells, goblet cells, small mucous granule (SMG) cells, and basal cells, while RE contained ciliated cells, goblet cells, SMG cells, basal cells, and cells with intracytoplasmic lumina lined by cilia and microvilli. TE and RE contained similar numbers of total epithelial cells and basal cells per millimeter of basal lamina. TE was composed of more SMG cells but fewer goblet cells compared to RE. We conclude that nonolfactory nasal epithelium in the bonnet monkey is complex with distinct regional epithelial populations which must be recognized before pathologic changes within this tissue can be assessed adequately.

Animals↗

Internal quality control in clinical chemistry: a teaching review.

This survey introduces the subject of internal quality assessment from a historical point of view, presents a unified approach to notation, concepts and definitions, and describes briefly those quality control procedures that are used most commonly in clinical chemistry. It is not the aim of this report to comment on all the individual contributions made in this field, but rather to concentrate on the principles. Particular emphasis is centered around assessment criteria to compare the efficiencies of selected control procedures for monitoring analyte concentrations in biological fluids. The question of whether to compare control schemes by means of average run lengths, run length distribution functions or average cost functions is considered. A rationalized approach based on the comparison of optimal procedures, using average run length, is adopted.

Chemistry, Clinical↗

Steroid hormone concentrations in relation to patient prognosis and prostate tumour grade.

Survival of patients who received endocrine therapy as first-line treatment for their prostatic cancer was statistically analysed in relation to several parameters, primary tumour stage, metastatic status, age, pretreatment plasma hormone concentrations and Gleason grade. Prognostic indices were derived for both M0 and M1 patients in which Gleason grade and plasma testosterone concentrations were significant prognostic factors. In the M1 patients growth hormone values were also significant and to a lesser degree age. The relationship of Gleason grade to testosterone, growth hormone, prolactin, the gonadotrophins and age was also analysed. No significant differences in any of these hormones was noted with increasing Gleason grade but the age of patients with Grade 5 tumours was significantly lower.

Carcinoma↗