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Biomedical subjects

L W Chu

Publications and source records attributed to L W Chu.

18 recordsLinked to original sources

Rods are selectively altered by lead: II. Ultrastructure and quantitative histology.

Electroretinographic and cyclic nucleotide metabolism studies have established that low-level lead exposure during early postnatal development results in long-term selective rod deficits. To determine whether there was a corresponding selective rod photoreceptor cell degeneration we examined retinas of adult rats exposed to low-level lead during development using light and electron microscopy. In all retinal regions, a rod but not cone cell degeneration was observed. Overall, 20% of the rod cells were lost. Moreover, two specific regional differences were found. Degeneration was much greater in the inferior (-25%) than superior (-15%) retina and greater in the posterior (-22%) than peripheral (-17%) retina. The latter pattern indicates a central-peripheral gradient of degeneration. Total retinal thickness decreased 15-20%, which reflects cell loss in the outer and inner nuclear layers. Ultrastructurally, the most obvious lead-induced alterations were swollen and disorganized rod outer segments and large accumulations of beta-glycogen particles in rod photoreceptor mitochondria. Glycogen accumulations were heaviest in rod inner segment mitochondria followed by rod axon and synaptic terminal mitochondria. Possible cellular mechanisms of action responsible for these lead-induced retinal alterations include an inhibition of retinal cyclic GMP phosphodiesterase and the resultant elevation of cyclic GMP, an inhibition of intermediary metabolism, and/or an alteration in calcium metabolism. In addition, the thinning of the inner nuclear layers could be due to transneuronal degeneration. As noted in our preceding paper, the first possibility has been demonstrated in rats similarly exposed to lead. These quantitative histological results, in combination with the ERG and biochemical results in the preceding paper, demonstrate that low-level lead exposure during early postnatal development produces long-term selective rod functional deficits and degeneration.

3',5'-Cyclic-GMP Phosphodiesterases

Protection from harmful UV radiation by contact lenses.

Ultraviolet radiation (UVR) has been demonstrated to be harmful to the cornea, the lens and the retina. Recent research has indicated that, in addition to the epithelial trauma found in UVR-induced keratitis, the deeper corneal layers are also involved. Since trauma to keratocytes and endothelial cells can result in permanent damage or cell loss, it is imperative to protect eyes against excessive dosages of UVR. Standard hydrogel contact lenses (Vistamarc normal) and newly developed UV-filtering hydrogel lenses (Vistakon UV-BLOC) were fitted on five rabbits and compared in protection from harmful UVR (300 nm). The eyes that wore the UV-filtering lens maintained normal corneas; however, the eyes that wore the standard hydrogel lens showed pronounced epithelial, stromal and endothelial changes. We concluded that the UV-filtering lens effectively absorbed the hazardous UV radiation while the standard soft lens provided little protection.

Animals

Ultrastructural analysis of corneal exposure to UV radiation.

The primate cornea was exposed to 300 nm UVR with five levels of radiant exposure from 0.08 to 0.6 Jcm-2. All cellular layers of the cornea were damaged at the 0.08 Jcm-2 exposure, and damage became more severe as the exposure level was increased. The corneal cells showed variable response in that essentially normal cells were found among damaged cells. Eight days post-exposure using the 0.6 Jcm-2 level, the epithelium had regained its normal thickness and was populated largely by normal appearing cells; however, the stroma showed damaged keratocytes and the loss of keratocytes. The corneal basement membranes (the epithelial basement membrane and the posterior limiting lamina) and the anterior limiting lamina were not damaged at any exposure level except for an isolated area along the epithelial basement membrane in one cornea. Therefore, one is lead to conclude that basement membranes are unaffected by UVR. The endothelium continued to demonstrate the loss of mitochondria, endoplasmic reticulum and some vacuoles at 8 days after exposure. However, the endothelium appeared to have resumed its physiological function as demonstrated by the reduced stromal oedema. This research gives the first complete description of UV-B induced corneal damage and repair of the full, in-depth cornea of the primate using the EM.

Animals

The efficacy of a UV-blocking soft contact lens in protecting cornea against UV radiation.

Recently, it has been shown that UV keratitis is more serious than previously thought because it is not limited to the corneal epithelium but also involves the stroma and the endothelium. It is, therefore, very important to avoid ultraviolet radiation (UVR) damage, and the purpose of the present study was to examine the ability of a UV absorbing hydrogel lens to filter such wavelengths. Ultrastructural observations of rabbit corneas showed that a regular soft (Vistamarc normal) contact lens offered no protection, and since wearing one adds stress to the cornea it seems possible that the cornea may be more vulnerable to UVR trauma. A UV absorbing soft contact lens (Vistakon UV-BLOC) provided complete protection to all corneal layers. Subepithelial nerve fibres in the traumatized corneas were mostly of normal morphology and may explain why UV keratitis is a very painful experience. It was concluded that a UV absorbing soft contact lenses with acceptable clinical performance may be prescribed on a routine basis.

Animals

Epithelial morphological response to soft hydrogel contact lenses.

Hydrogel (HEMA) contact lenses of increased thickness were worn by owl monkeys (Aotus tivergatus) under open and closed eye conditions to study ultrastructurally the corneal epithelial response to increased stress. The 0.07 mm thick lens with a calculated Dk/L of 4.2-2.2 caused an epithelial thinning without oedema. This thinning was due to a loss of superficial cells and a flattening of the remaining ones. Factors in the mechanism of epithelial thinning without oedema may include anoxia, trauma, lid pressure, and lens weight. The 0.4 mm thick lens offers negligible gas transmission in the closed eye, and after 48 hours much of the epithelium was stripped, while oedema and degenerative cytoplasmic changes were prominent in areas of surviving cells. In such areas the thickness of the epithelium was reduced to one or two layers of cells. The basement membrane was in all experiments unharmed by hydrogel contact lens wear. The epithelial innervation was maintained in all corneas except those of the closed eye, and finding correlates well with the good corneal touch threshold in soft contact lens wearers.

Animals

Ultrastructural observations on (pseudo-) exfoliation of the lens capsule: a re-examination of the involvement of the lens epithelium.

One lens each from 2 separate patients suffering from pseudoexfoliation and one lens from a normal eye were examined ultrastructurally. The normal lens capsule was internally lamellar in places and externally of a somewhat reduced electron density but otherwise of a homogeneous appearance and free of inclusions. Observations on the abnormal lenses revealed an electron dense and mainly granular but sometimes fibrillar material along the surface of the peripheral one-third of the capsule. Material of similar ultrastructural appearance was also found deeper in the capsule and in the immediately underlying epithelium. Since the capsule close to the pole of the lens was completely free of these abnormal inclusions and the underlying epithelium also lacked this material, it is concluded that the lens epithelium is a source of the surface debris in pseudoexfoliation. These findings therefore support previous authors who proposed a lenticular involvement in this disease. The present study does, however, not rule out the possibility of a uveal contribution of abnormal material but disputes its exclusive involvement in this disease, as has previously been postulated. Build-up of exfoliated material close to the capsular surface caused an apparent peeling of the lens capsule. It is therefore concluded that the anomalous lenses suffered from a true exfoliative process that may be more correctly termed 'exfoliation of the lens capsule.'

Epithelium

Corneal epithelial response of the primate eye to gas permeable corneal contact lenses: a preliminary report.

The comparative corneal epithelial effects of rigid gas permeable and soft contact lenses are reported in the present preliminary study using two bush baby monkeys (Galago senegalensis). Both types of lenses produced early cell death among the surface squamous cells while internally the epithelium and its nerve fibers remained normal. Sporadically small abnormal groups of cells involving two to three of the surface layers were observed in both the hard and soft lens wearing corneas. It was concluded that this represented superficial punctate keratitis (SPK). Small superficial intracellular epithelial cysts with membranous contents were infrequently noted in the gas permeable lens wearing cornea and it is suggested here that they were mild forms or precursors of those seen clinically in human corneas. Since the gas permeable lens met the corneal oxygen requirement it is postulated that the traumatic effect of the rigidity of the lens caused the cystic formation to occur. The relative hypoxia induced by the soft contact lens resulted in a mild superficial epithelial edema.

Animals

Rabbit eye exposure to broad-spectrum fluorescent light.

Two F40CW fluorescent lamps mounted in an EYS-2404 fixture and 300 nm, 5 nm waveband UV radiation were used to expose pigmented rabbit eyes. The results of the exposures to the eye were evaluated with the biomicroscope, ophthalmoscope, light microscope and electron microscope. The following conclusions were reached: The adverse ocular responses to fluorescent radiation exposure were due to long-duration, broadband radiation. These reactions were more generalized for fluorescent exposures when the cornea and lens are compared to UV exposures. The differences between the levels of threshold exposure needed to cause damage for the fluorescent source and UV radiation were attributed to exposure duration and the rate of delivery of the radiation. Corneal and lenticular damage was mild when compared with UV 300 nm exposures, and the threshold occurred after 8 h to 12 h of exposure. The effect of the radiation was to interfere with the normal functions of the cell while changes to the inert materials in the tissues was secondary to injury to the cell. The damage was mild in the corneal epithelium, somewhat more severe in the corneal endothelium, but minimal in the corneal stroma. Early retinal changes were found after 8 h of exposure to the fluorescent source. These induced changes were evident in the neural retina as spaces and were assumed to represent oedema. The retinal oedema was initially found only in the receptor cell, outer nuclear and nerve fibre layers. Many vacuoles or spaces were located in the junctional area between the ganglion cell and nerve fibre layers while smaller spacing occurred also within the nerve fibre layer. Twelve h of exposure to the fluorescent source produced a further increase in the oedema in the retina. The outer segments of the receptor cells appear to disintegrate and significant open spaces are evident among the inner and outer segments of the receptors. The inner plexiform layer shows an increased number of spaces within and among the neural elements, and the mitochondria appeared to be undergoing changes. The 20-h and longer exposure induced severe changes affecting all layers of the retina. These changes include massive retinal oedema with degenerative signs in all retinal neurons. A sympathetic reaction of the unexposed, contralateral eye occurred as the result of the damage to the exposed eye. Minimal sympathetic responses to the cornea and the lens began at exposure durations at or above 12 h, while the retina showed the sympathetic reaction beginning at 8 h.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Cerebral tissue response to electrode implantation.

Tissue response to platinum electrodes was assessed after an eight-day implantation period. The regions of study included the cortical areas at the opercular gyri and at the sulcus parieto-occipitalis externus, as well as the sub-cortical white matter in these cases. Perivascular and intraparenchymal hemorrhagic lesions as well as edematous changes characterized both by extensive intra and extracellular swelling were noted. Numerous phagocytic elements and degenerative strucutres were present at the electrode/parenchymal interface. Tissue alterations were asymmetrical as observed both around and at the tip of the implanted electrode. The parenchymal alterations extended from 0.2mm to 3.5mm distance from the electrode path/parenchymal interface. Greater tissue involvement was found in the subcortical white matter as compared to the adjacent cortical gray matter.

Animals

Cerebral tissue response to reserpine: a morphological study.

The acute influence of reserpine injection on cerebral tissue was studied in baboon and rat models. Five h after the infusion of reserpine, bilateral cortical areas were found to contain perivascular changes only, whereas basal ganglia regions contained advanced oedematous responses. Mitochondrial swelling was commonly found in the latter regions, as were loci containing microvascular crenation with accompanying pericytic changes.

Animals

Acute tissue response to cerebral ischemia in the gerbil. An ultrastructural study.

The Mongolian gerbil, because of the uniqueness of the anatomical features of its circle of Willis, has become an increasingly useful model in the study of cerebrovascular disease. The present work defines acute changes at the ultrastructural level following ischemic insult. The pathomorphological responses include initial astrocytic involvement and, when the degree of insult is increased, a progression of morphological changes is evident in neuronal and other parenchymal elements. Animals with vessels occluded for more than 3 hr without neurological signs suggestive of ischemia exhibited limited perivascular edema. Contralateral changes (perivascular astrocytic) were observed in the basal ganglia at 24 hr in animals with neurological deficit. Astrocytic and basal ganglia susceptibility to ischemia was consistent with previous findings in primate models. An additional association was found in that limited edematous involvement could exist in animals without neurological deficit but neuronal changes were only present in animals with signs of ischemic neurological deficit.

Animals

Acute ultrastructural changes in the middle cerebral artery due to the injury and ischemia of surgical clamping.

Ultrastructural changes in the zone of clamping of the middle cerebral artery of the squirrel monkey are described after application of a surgical clip. The experimental model utilized has been widely applied to the study of cerebral ischemia and possibly has relevance to clamps applied to the cerebral vessels during neurosurgical treatment of patients with cerebrovascular disorders. The earliest changes within the arterial wall were found in the smooth muscle (media) and accompanying fasciculi of nerves. Changes within the nerve bundles were sufficiently advances following 4 hours of vascular clipping to suggest temporary or permanent impairment of neurogenic innervation of the cerebral vessels distal to the trunk of the vessel clipped.

Animals

Mitochondrial abnormalities in progressive ophthalmoplegia.

A clinically diagnosed case of progressive external ophthalmoplegia was biopsied and ultrastructurally evaluated. The disease was found to be characterized by numerous giant mitochondria. The intramitochondrial changes consisted of either swirls of cristae or of paracrystalline structures which were in apposition with the membranes of the cristae. The internal structure of the paracrystalline units consisted of parallel bands of material which were aligned in the same plane as the membranes of the related cristae.

Humans

The ultrastructure of the middle cerebral artery and its associated nerve fibers in the squirrel monkey and baboon.

This study describes the ultrastructural characteristics of the middle cerebral artery and its related neural elements in the squirrel monkey and baboon. The cytoarchitecture of the M-1 segment as well as that of the smaller extracerebral and intracerebral vessels is comparable in both animals. Smooth muscle elements are occasionally found within the intimal lining. The nerve bundles associated with vessels contain fewer myelinated fibers as the vessel diameter decreases. The cytological relationship between the neural structures and the smooth muscle cells are discussed.

Animals

Morphological responses of cerebral tissues to temporary ischemia.

The ultrastructural responses of cerebral tissue following temporary periods (1/2, 1,2,3, or 4 hour) of right, middle cerebral artery, (MCA) occlusion were studied acutely after a 3 day or 7 day interval following the removal of the MCA clip. Cortical and basal ganglia tissues for each ischemic duration were compared at 3 post-occlusive periods (acute, 3 days, 7 days). With the short periods of ischemic insult (1/2, 1, 2, 3, and 4 hour), the temporal and insular cortex contained no greater changes in the 7 day group than in the 3 day group. The basal ganglia were more susceptible to MCA occlusion as indicated by more marked cytological changes and/or necrosis in all intervals of ischemia.

Acute Disease