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Biomedical subjects

W F Hughes

Publications and source records attributed to W F Hughes.

At least 19 recordsLinked to original sources
PubMed1998

Alveolar epithelial cell death adjacent to underlying myofibroblasts in advanced fibrotic human lung.

Earlier work from this laboratory showed that abnormal fibroblast phenotypes isolated from fibrotic human lung produce factor(s) capable of inducing apoptosis and necrosis of alveolar epithelial cells in vitro [B. D. Uhal, I. Joshi, A. True, S. Mundle, A. Raza, A. Pardo, and M. Selman. Am. J. Physiol. 269 (Lung Cell. Mol. Physiol. 13): L819-L828, 1995]. To determine whether epithelial cell death is associated with proximity to abnormal fibroblasts in vivo, the spatial distribution of epithelial cell loss, DNA fragmentation, and myofibroblasts was examined in the same tissue specimens used previously for fibroblast isolation. Paraffin sections of normal and fibrotic human lung were subjected to in situ end labeling (ISEL) of fragmented DNA and simultaneous immunolabeling of alpha-smooth muscle actin (alpha-SMA); replicate samples were subjected to electron microscopy and detection of collagens by the picrosirius red technique. Normal human lung exhibited very little labeling except for positive alpha-SMA immunoreactivity of smooth muscle surrounding bronchi and vessels. In contrast, fibrotic human lung exhibited moderate to heavy ISEL of interstitial, cuboidal epithelial, and free alveolar cells. ISEL of the alveolar epithelium was not distributed uniformly but was most intense immediately adjacent to underlying foci of alpha-SMA-positive fibroblast-like interstitial cells. Both electron microscopy and picrosirius red confirmed epithelial cell apoptosis, necrosis, and cell loss adjacent to foci of collagen accumulation surrounding fibroblast-like cells. These results demonstrate that the cuboidal epithelium of the fibrotic lung contains dying as well as proliferating cells and support the hypothesis that alveolar epithelial cell death is induced by abnormal lung fibroblasts in vivo as it is in vitro.

Apoptosis↗
PubMed1997

Mechanisms of liquid flux across pulmonary alveolar epithelial cell monolayers.

Active transport of sodium by pulmonary alveolar epithelial cells (AEC) is believed to be an important component of edema clearance in the normal and injured lung. Data supporting this premise have come from measurements of sodium movement across AEC monolayers or from perfused lung model systems. However, direct measurement of fluid flux across AEC monolayers has not been reported. In the present work, AEC were studied with an experimental system for the measurement of fluid flux (Jv) across functionally intact cell monolayers. Primary adult rat type II alveolar epithelial cells were cultured on 0.8 micron nuleopore filters previously coated with gelatin and fibronectin. Intact monolayers were verified by high electrical resistance (> 1000 omega) at 4-5 d of primary culture. At the same time interval, transmission electron microscopy revealed cells with type I cell-like morphology throughout the monolayer. These were characterized by both adherens and tight junctional attachments. Fluid flux across the monolayers was measured volumetrically over a period of 2 h in the presence of HEPES-buffered DMEM containing 3% fatty acid-free bovine serum albumin. Flux (Jv) was inhibited 39% by 1 X 10(-4) M ouabain (P < 0.01) and 27% by 5 X 10(-4) M amiloride (P < 0.05). These data support the concept that AEC Na+/K(+)-ATPase and Na+ transport systems are important determinants of AEC transepithelial fluid movement in vitro.

Animals↗
PubMed1991

Quantitation of ischemic damage in the rat retina.

In order to determine thresholds for irreversible cellular injury in the rat retina, timed acute no-flow ischemic episodes of 30-180 min duration were produced by elevation of intraocular pressure (IOP) above systolic pressure. Quantitation of irreversible degeneration and cell loss following a 2-week post-ischemic interval was performed by computer-assisted measurements from histologic sections. Alterations of thickness of retinal layers and linear cell density were determined for ischemia of selected durations (30, 60, 80, 90, 120 and 180 min). Different thresholds were evident for inner and outer retinal damage. Neurons of the inner nuclear layers showed extensive loss with episodes at 60 min. Decrease in the thickness of the inner plexiform layer provided the best index of this inner nuclear damage. The outer retina was more resistant, with photoreceptors showing extensive damage only after 90 min in conjunction with pigment epithelial metaplasia and degeneration. Two-hour episodes produced full-thickness degeneration with loss of pigment epithelium and sparing of the peripheral retina. Greater sensitivity of the inner retina suggested problems with restoration of the retinal circulation. Horseradish peroxidase infusions did reveal central microcirculatory defects in retinal wholemounts of some specimens with episodes longer than 60 min. Refinements of the methods resulted in outcomes sufficiently reproducible for quantitative assessment of acute ischemic injury. The rat retina provides an economical basic tissue model of acute ischemic injury affecting neurons, glia, and microvasculature. Quantitation of this injury promises great utility in testing agents with potentially protective effects on acute ischemic injury.

Animals↗
PubMed1989

Enhanced survival of motoneurons in the chick lateral motor column: effects of embryonic skeletal muscle extracts and myoblast-conditioned medium.

Muscle-derived factors have shown neurotrophic effects in culture, but their possible effects on the maintenance of embryonic motoneurons have not been demonstrated in vivo. Soluble extracts derived from embryonic chick muscle, or medium conditioned by chick myoblasts, were instilled onto the chorioallantoic membrane (CAM) between the 5th and 11th days of incubation. Counts of the lumbar lateral motor column (LMC) at embryonic day 12 revealed modest but significant increases (12-15%) in motoneuron number for these experimental groups as compared with control treatments. The results suggest that sustaining effects of muscle-derived factors on motoneurons may be demonstrated on the developing LMC by the simple expedient delivery via the CAM, and that these factors can modify the normal program of cell death occurring during this critical period of development.

Animals↗
PubMed1984

Subclavian artery occlusion 42 years after mastectomy and radiotherapy.

Left subclavian artery occlusion developed in a patient 42 years after a left radical mastectomy and radiotherapy. The vascular supply was successfully reconstructed by a graft from the right subclavian artery to the left brachial artery. Clinical and experimental evidence has demonstrated that radiotherapy can damage large vessels [2,4,5]. It is our contention that radiotherapy was the causative factor in the case of subclavian artery occlusion reported herein.

Aged↗
PubMed1981

Lymphocyte-induced corneal neovascularization: a morphologic assessment.

Lymphocytes obtained from mesenteric lymph nodes of rabbits were stimulated in vitro by concanavalin A and injected into the corneas of allogeneic hosts. Controls were nonstimulated, killed, or autogeneic lymphocytes injected into the contralateral corneas. The stimulated cells were significantly better inducers of neovascular growth. Histologic observations of the vascularized corneas showing marked mononuclear reactions at the limbus, coupled with the requirement of allogenicity, suggest that there was immunologic recognition of the implanted cells. Stimulated allogeneic blast cells may amplify this host recognition by their elaboration of lymphokines or enhanced antigenicity. The apparent importance of allogenicity for the induction of vessel growth in these experiments may be significant in the pathogenesis tumor-induced or graft-related corneal neovascularization.

Animals↗
PubMed1979

Suppressive effects of indomethacin on thermally induced neovascularization of rabbit corneas.

In 16 rabbits with bilateral corneal burns, indomethacin was administered topically to one eye on each day after the lesion was made to determine the effect of a prostaglandin inhibitor on the corneal neovascular response to experimental thermal burns. Comparison of the two eyes showed a reduction of both hyperemia and neovascularization in indomethacin-treated eyes during the first five days after injury. Histologic observations during this period showed a reduction in polymorphonuclear cell infiltration in the treated corneas. Inhibition of prostaglandin synthesis by indomethacin apparently led to a reduction in the inflammatory response and the subsequent corneal neovascularization.

Animals↗
PubMed1979

A comparison of cancer occurrence in allergic and nonallergic populations.

Patients with significant allergy were surveyed with regard to the incidence of malignancy and a control group of nonallergic individuals was similarly reviewed. In the allergic population of 500 persons in the cancer-bearing age group, there were 12 malignancies, while the nonallergic group of 421 individuals had 14 malignancies. The Chi-squared test of these data gives a value of 0.75, which indicates that there is no significant difference in the incidence of malignancy in the allergic and nonallergic groups. As one would expect, the test of independence between age, cancer and allergy using the Chi-squared statistic is rejected.

Adult↗
PubMed1976

Corneal transplant for therapy of primary corneal dystrophies.

Penetrating corneal transplants for primary corneal dystrophies such such as keratoconus and Fuchs dystrophy, and for hereditary dystrophies such as granular, lattice, and macular have an excellent prognosis of 95% or more for a clear graft and good vision in the series presented. These dystrophies are rarely associated with corneal vascularization, unless induced by silk sutures, knots of sutures, exudate, or repeated operations. Accordingly, the incidence of homograft rejection is reduced. However, there is a slower rate of healing, especially with nylon sutures which should not be removed for at least six months. The use of steroids, especially with intensive administration topically or over a long period of time, subconjunctival injection of repository forms, or theoretically at least, systemic administration, can be followed by posterior subcapsular lens opacities which may remain stationary if medication is stopped. Unfortunately, within several years the hereditary dystrophies may slowly develop a recurrence of the dystrophy in the graft requiring reoperation.

Age Factors↗
PubMed1974

Pathology of the pigment epithelium and retina in rabbits poisoned with lead.

Multifocal lesions of the retinal pigment epithelium were observed in rabbits fed a diet contaning 0.5% lead subacetate for periods of up to 2 years. Groups of pigment epithelial cells became congested with a lipofuscin pigment which was apparently derived from phagosomes of rod outer segments. Lipofuscin granules displaced melanin granules from the apical surface of the retinal pigment epithelial cells and resulted in conspicuous brown pigmentation of these cells in albino animals. Migration of macrophages and pigment epithelial cells into the subretinal space was common in affected areas. This pathology was not observed in the pigment epithelium of the ora serrata, or ciliary body. At the latest time periods, the abnormal lipofuscin pigmentation subsided, and degeneration of photoreceptors occurred. The pathogenesis of the lesions is discussed.

Animals↗