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Biomedical subjects

M J Costello

Publications and source records attributed to M J Costello.

At least 19 recordsLinked to original sources
PubMed2001

Multilamellar bodies as potential scattering particles in human age-related nuclear cataracts.

PURPOSE: To characterize within human age-related nuclear cataracts rare spherical objects covered by multiple membranes, termed multilamellar bodies (MLBs). METHODS: Adult human normal, transparent lenses were obtained from eye bank donors and age-related nuclear cataracts were obtained immediately after extracapsular extraction. Each sample was Vibratome sectioned fresh into 200 microm thick sections that were fixed and embedded for light or electron microscopy. Confocal images were recorded from sections stained with the lipid soluble dye, DiI. RESULTS: Light micrograph montages of the equatorial plane containing the fetal and embryonic nuclei were examined. Rare, but distinct, circular 1-3 microm diameter objects were observed consistently in the cataracts. These objects did not appear to be components of the complex intercellular interfaces. Serial sections indicated that the objects were spherical, or contained a spherical component. For about 20,000 fiber cell cross-sections in each lens, the frequency of MLBs was 10 times higher in cataracts than in the normal lens nuclei. Although extensive searching with the electron microscope was necessary, the size, circular profile and multiple layers of thin (5 nm) membranes easily identified the MLBs. Interiors of the MLBs displayed variable textures. Confocal images indicated that the coverings were enriched in lipid compared to the adjacent plasma membranes. The calculated density of the MLBs in the cataractous nuclei was about 3800/mm3, which represents a volume fraction of 0.00003. CONCLUSIONS: Because the MLBs are large compared to the wavelength of light, display interiors with variable staining textures and have lipid-rich coverings, they appear to be ideal candidates for large scattering particles that may contribute to the forward light scattering in nuclear cataracts.

Aged↗
PubMed2001

Structural evidence of human nuclear fiber compaction as a function of ageing and cataractogenesis.

This study was conducted to quantify structural change associated with human nuclear fiber compaction as a function of ageing and nuclear cataract formation. Normal donor lenses in three age ranges, young (15--25 years), middle-aged (36--46 years) and aged (59--81 years) were compared to each other and to age-related nuclear cataracts (55--81 years) surgically removed by extracapsular extraction. Several structural modifications which occurred as a manifestation of fiber compaction were noted. In the fetal nucleus (FN), the average anterior and posterior fiber angles decreased approximately 20% with age. Additionally, there was a reduction in the thickness of both the anterior and posterior segments of fetal fibers with age. On average, the anterior--posterior (A--P) axis in the embryonic nucleus (EN) decreased 33% with age. The average length of EN fibers decreased significantly (37%) as a function of age. This change in EN fiber length was accomplished by effecting compaction folds along fiber length. By comparison, in nuclear cataracts the anterior and posterior angles of FN fibers were about 12% smaller than comparably aged normal lenses. Similarly, the A--P axis and the length of EN fibers were 13% smaller than age-matched normals. Nuclear fiber compaction in early adulthood was significant and may contribute to the lens hardening and loss of accommodative ability symptomatic of presbyopia. 3D-CAD reconstructions of fiber compaction show how the reduction in the spacing of lateral interdigitations along fiber length causes an increase in the fiber membrane complexity along the A--P axis in relation to fiber cytoplasm as light passes through lenses. These results may explain, at least in part, how an increase in large particle scatter occurs as light is transmitted through fiber membranes, resulting in reduced lens optical quality as a function of age. By extrapolation, the significantly increased compaction of nuclear fibers in age-related nuclear cataracts may be a contributing factor for excessive scatter in nuclear opacification.

Adolescent↗
PubMed1999

Fourier analysis of textural variations in human normal and cataractous lens nuclear fiber cell cytoplasm.

Variations in cytoplasmic texture of human normal and cataractous lenses were investigated with Fourier analysis. Fixed Vibratome sections of six normal transparent human lenses (age range 55-72 years) and six nuclear cataractous lenses (age range 66-89 years) were examined using transmission electron microscopy. Images were taken of the fiber cell cytoplasm and examined using linear optical density scans, Fourier transforms and autocorrelation analysis. The cytoplasm of normal human lenses was found to be smooth and homogeneous. Radially-averaged plots of Fourier transforms revealed a broad band of intensity over the range of 15-50 nm. Four of the six cataracts also had homogeneous cytoplasm without substantial density variations. Fourier transforms and radially-averaged plots were similar to those of the normal, although slightly lower in intensity for components</=20 nm. Two of the six cataracts had a slightly granular or textured cytoplasm that showed significant density variations. Fourier transforms and radially-averaged plots revealed significant intensity in the range>/=200 nm. Autocorrelation analysis supported the data obtained by Fourier transforms. Radially-averaged plots of the autocorrelation resultant displays detected only small structural units in the normal and non-textured cataractous cytoplasm, whereas larger structural units were detected in the textured cataractous cytoplasm. The appearance of the textured cataractous cytoplasm suggests that redistribution or loss of protein may be the cause of density variations in these types of cataracts. Importantly, these results indicate that some nuclear cataracts do not contain spatial fluctuations in the cytoplasm large enough to cause significant light scattering. The data suggest that nuclear cataractogenesis is a multi-factorial process involving minor alterations in cellular structure.

Aged↗
PubMed1997

Light microscopic variation of fiber cell size, shape and ordering in the equatorial plane of bovine and human lenses.

PURPOSE: A rapid means was sought to visualize and quantify the cross-sectional areas of fiber cells, the variations of cell area, and the regularity of packing in the equatorial plane of normal adult bovine and normal aged human lenses. METHODS: Vibratome sections of bovine and human lenses were fixed, embedded in LR White resin, and sectioned for light microscopic observation. Image analysis was performed to determine the cross-sectional areas of fiber cells in selected nuclear regions. RESULTS: Examination of bovine lenses revealed a pattern of cell size and shape in each region that was similar to that recently reported for normal human lenses (1). In the equatorial plane of bovine lenses, average cross-sectional areas were 20 +/- 6 micron2 in the adult nucleus, 43 +/- 19 micron2 in the fetal nucleus, and 63 +/- 61 micron2 in the embryonic nucleus. Light microscopy of human lenses was consistent with our previous electron microscopic observations. Moreover, in both bovine and human lenses, the distribution of cell sizes and the number of cell layers was readily available for each region. Overviews of the equatorial plane demonstrated a gradual improvement in the regular packing of radial cell columns proceeding from the relatively disordered embryonic and fetal nuclei through the well-ordered adult nucleus to the highly regular cortical region. CONCLUSIONS: Light microscopy revealed the highly irregular packing and large average size of cells in the embryonic nucleus and the gradual reduction in size and progressive improvements in regularity of packing in the outer layers. The methods used here have the advantage of rapidly giving a continuous view of the fiber cell structure and arrangement which is not available using electron microscopy.

Aged↗
PubMed1996

Distribution and type of morphological damage in human nuclear age-related cataracts.

The distribution and type of fiber cell damage was evaluated in human age-related nuclear cataracts and in aged normal (non-cataractous) lenses. Ten age-related nuclear cataracts (53 to 89 years old) and four normal lenses (59 to 67 years old) were examined by electron microscopy of fixed Vibratome sections. Images from the adult, juvenile, fetal and embryonic nuclear regions were compared. Each cataractous lens contained a central region of increased light scattering which involved the embryonic and fetal regions with progressively less involvement in the juvenile and adult nuclear regions. Some damaged fiber cells were observed in all specimens, although damage was minor and infrequent in the normal lenses. Degeneration of single or groups of fiber cells was noted in all the adult nuclei of the cataractous lenses, becoming less frequent in the juvenile nuclei. The types of damage included localized voids, multilamellar membrane aggregates, globular bodies, enlarged cells and regions of highly convoluted membranes. The fetal and embryonic nuclei of the cataractous lenses exhibited rare and minor morphological defects, and were virtually identical to the equivalent regions of the normal aged lenses. Examination of cell interfaces in opaque regions of cataractous lenses revealed that the oldest fiber cells sustained apparent membrane loss. Extracellular spaces in the embryonic, fetal and juvenile regions of the cataractous lenses often contained dense deposits, presumably cytoplasmic material lost from adjacent fibers. The results indicate that the region of greatest nuclear opacity, located in the lens center, does not contain any significant cellular damage. This suggests that older fiber cells respond differently to pathological and senescent changes than younger cells made after fetal development. The observed loss of membranes and cytoplasmic material from the oldest fiber cells may be a contributory mechanism in the formation of age-related human nuclear cataracts.

Aged↗
PubMed1996

The impact of sewage sludge exposure on the reproduction of the sand goby, Pomatoschistus minutus.

Adult sand gobies were exposed to 0.1% sewage sludge for 19 weeks prior to the end of spawning. Exposure to sewage sludge had a significant effect on male mortality rates but no significant effects on the gonadosomatic index of males or females. There were no major effects of sludge exposure on testes androgen content or on testes release of androgens after in vitro gonadotrophin stimulation. Fecundity and the number of larvae produced were not significantly affected by the sludge exposure. There was a tendency for eggs and larvae from sludge-exposed females to have a higher mortality rate. At a population level, however, there was a major reduction in the number of eggs and larvae produced in the sludge-exposed population which reflected a failure of some females to spawn. Of the larvae produced, 60-70% from sludge-exposed parents were lighter and had a larger yolk-sac volume compared to larvae from non-exposed parents which may have indicated impaired yolk utilisation.

Journal Article↗
PubMed1996

Fiber cell morphology and cytoplasmic texture in cataractous and normal human lens nuclei.

PURPOSE: The goal of this study was to compare the ultrastructure of the oldest cells in opaque and transparent human lenses. METHODS: Age-related nuclear cataracts, late-onset diabetic nuclear cataracts and normal aged lenses were examined by transmission electron microscopy. Cross-sectional profiles of fiber cells in the embryonic, fetal and juvenile nuclear regions were obtained to facilitate direct comparisons between lens regions and between sample groups. Image analysis was performed to determine cross-sectional areas of fiber cells in each region. RESULTS: The average cross-sectional area increased approximately sixfold from the outer to the inner nuclear regions in all lenses measured. In each nuclear region, fiber cells displayed a characteristic size, shape, arrangement and type of interdigitations which were consistently seen in all the lenses examined. Some lenses had more complex interdigitations than others. Gap junctions were identified as pentalamellar structures having 16 nm width and appeared identical throughout the nuclei of both normal and cataractous lenses. The cytoplasm of all lenses was smooth and free of large density variations. However, the cytoplasm of some cataractous lenses appeared more granular in texture than noncataractous lenses. Cellular degeneration, debris or large cellular defects were not seen in the cores of cataractous lens nuclei. CONCLUSIONS: These results indicate that only minor ultrastructural differences exist between the oldest fiber cells in normal and cataractous lenses, and that the presence of extensive cellular damage and disruptions is not necessary for the generation of nuclear opacities in aged lenses. Our observations suggest that light scattering sufficient for vision impairment may involve structural alterations much smaller than previously proposed.

Aged↗
PubMed1996

Morphology of the normal human lens.

PURPOSE: To provide a quantitative, morphologic description of differentiated lens fiber cells in all regions of aged normal human lenses. METHODS: Transparent normal human lenses (age range, 44 to 71 years) were examined with correlative transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Vibratome sections allowed examination of internal structures, whereas dissected whole lenses revealed surface characteristics. Additionally, image analysis was used to measure cross-sectional areas of fiber cells. RESULTS: Approximate regional dimensions (percentage of diameter and thickness, respectively) were determined for whole lenses: cortex 16%, 17%; adult nucleus 24%, 21%; juvenile nucleus 12%, 9%; fetal nucleus 45%, 49%; and embryonic nucleus 3%, 4%. Cortical cells were irregularly hexagonal, and the average cross-sectional area measured 24 +/- 9 microns2. Adult nuclear cells were flattened with intricate membranous interdigitations and an area of 7 +/- 2 microns2. Juvenile nuclear cells had an area of 14 +/- 5 microns2. Fetal nuclear cells were rounded with an area of 35 +/- 22 microns2. Embryonic nuclear cells also were rounded and had a variable area of 80 +/- 68 microns2. Fiber cell cytoplasm in all lens regions appeared smooth in texture and homogeneous in staining density. CONCLUSIONS: Both TEM and SEM are necessary to obtain a complete description of fiber cells. Cross-sections of fibers give new insights into the lamellar organization of the lens, indicating that each region has characteristic cell shapes and sizes. Furthermore, average dimensions were used to demonstrate that the number of cells and approximate growth rates vary significantly between adjacent regions.

Adult↗
PubMed1993

Morphological changes in human nuclear cataracts of late-onset diabetics.

The ultrastructure of human diabetic lens nuclei is described for the first time. Two cataractous lenses from late-onset diabetics were examined using transmission electron microscopy to determine the type and distribution of cellular disruptions. The diabetic lens nuclei were compared to a transparent nucleus from a normal human lens. Cellular damage to the exterior region of the diabetic lens nuclei was extensive, especially at the cortical-nuclear interface. Areas of lens fiber condensation as well as areas of cytoplasmic loss were observed in the outer nucleus. Morphological defects commonly seen in this region included: multilamellar membrane aggregates, voids where cytoplasmic material was lost, deposits in the extracellular spaces, density variations between adjacent fiber cells, and heterogeneously staining globules. The opaque central regions of the nuclei displayed relatively little cell damage, but fiber cells were very irregular in shape and packing. The ultrastructure of inner nuclear fiber cells was comparable to that seen in the normal lens and in age-related nuclear cataracts in non-diabetics. It appears that the effect of hyperglycemia on lens fiber cells is dependent on their age and stage of differentiation.

Aged↗
PubMed1993

Ultrastructure of fiber cells and multilamellar inclusions in experimental diabetes.

PURPOSE: The goal of this ultrastructural study was to examine fiber cell shape and intercellular junctions during the early stages of fiber cell breakdown and edema in diabetic rabbit lenses. METHODS: Lens abnormalities were recorded with a slit lamp. Between 6-10 mo after drug treatment, diabetic lenses and untreated control lenses were freshly enucleated and sectioned with a vibrating knife microtome. The thick tissue sections were chemically fixed and processed for thin-section electron microscopy. RESULTS: Alloxan-induced diabetes in albino rabbits produced clinically apparent cataracts as soon as 1 mo after the animals became hyperglycemic. The cataracts displayed cortical fluid-filled vacuoles in the equatorial region and at the cortex-nucleus interface, white specks scattered throughout the cortex, and posterior subcapsular cataracts. Fiber cells just deeper than the large cortical vacuoles had oval or spindle-shaped cross sections. Multilamellar inclusions, not reported previously for diabetic lenses, were observed at or near the fiber cell interfaces and were composed of concentric or spiral rings of plasma membrane-bound cytoplasmic processes. Undulating membranes were present throughout most of the multilamellar inclusions. Transparent lenses from untreated controls did not have such multilamellar bodies or extensive membrane undulations in cells at the same distance from the lens surface. CONCLUSIONS: Fiber cells respond to the diabetic insult differently depending on their stage of differentiation and age. The observed changes are consistent with the hypothesis that hyperglycemia accelerates the formation of age-related changes in fiber cells.

Alloxan↗
PubMed1992

Structural characterization of ordered arrays of sn-glycerol-3-phosphate acyltransferase from Escherichia coli.

Overproduction of the sn-glycerol-3-phosphate acyltransferase in Escherichia coli leads to incorporation of this integral membrane protein into ordered tubular arrays within the cell. Freeze-fracture-etch shadowing was performed on suspensions of partially purified tubules and whole bacteria. This procedure revealed the presence of ridges and grooves defining a set of long-pitch left-handed helical ridges. The long-pitch helices represented chains of acyltransferase dimers. Tubules observed within the cell were often closely packed, with an apparent alignment of grooves and ridges in adjacent tubules. Fracture planes passing through the tubules indicated the presence of a bilayer structure, with some portion of the enzyme being associated with the membrane. The major portion of the enzyme extended from the hydrophilic surface, forming a large globular structure that, in favorable views, displayed a central cavity facing the cytoplasm. Computer analysis of shadowed tubules revealed that the left-handed helices were six stranded, with a pitch of 1,050 A (105.0 nm) and a spacing of 75 A (7.5 nm) between acyltransferase dimers along the chains. Analysis of the predicted secondary structure failed to reveal obvious transmembrane segments, suggesting that very little of the protein was inserted into the bilayer.

Cytoplasm↗
PubMed1992

A novel method of sterilizing orthodontic instruments.

A range of orthodontic instruments was artificially inoculated with a mixed culture of representatives of the oral microflora and a marker bacterium and subjected to dry heat sterilization using a glass bead sterilizer. The shortest time which would guarantee total sterilization of the functional parts of the instruments was thirty seconds.

Dental Instruments↗
PubMed1992

Cellular architecture in age-related human nuclear cataracts.

Age-related or senile human nuclear cataracts were examined using electron microscopy of thin sections prepared from thick vibrating-knife microtome sections of nuclei extracted by extracapsular surgery. The use of extended aldehyde-tannic acid fixation of 80-120-microns thick vibrating-knife microtome sections overcame the difficult problem of preserving the hardened nuclear core of aged lenses. Comparisons were made between a typical nuclear cataract, containing a central opacity and a transparent rim, and a more advanced, or mature, completely opaque nuclear cataract. The typical nuclear cataract contained no obvious cell disruption, cellular debris, or objects that readily could explain the central opacity. The fiber cells had intact uniformly stained cytoplasms with well-defined plasma membrane borders and gap junctions. The transparent rim and the nuclear core appeared similar, except that fiber cells in the nucleus were more condensed with more elaborate intercellular interdigitations. The mature cataract showed various types of cell disruption in the perimeter but not in the core of the nucleus. These disruptions were globules, vacuoles, multilamellar membranes, and clusters of highly undulating membranes. Because these potential scattering centers were not found in the nuclear core, they probably were not the sole cause of the observed opacity. Other potential scattering centers found throughout the mature cataract nucleus included variations in staining density between adjacent cells, enlarged extracellular spaces between undulating membrane pairs, and protein-like deposits in the extracellular space. Similar features, although less pronounced, were present in the typical nuclear cataract. It was concluded that massive cell disruption is not essential to the formation of a central nuclear opacity. Subtle structural changes, especially small fluctuations in protein density between adjacent cells and alterations of the membranes and the extracellular space, probably contribute significantly to the central opacities in human nuclear cataracts.

Aged↗
PubMed1991

Immunocompetence as a measure of the biological effects of sewage sludge pollution in fish.

1. Dab, Limanda limanda, exposed to nominal concentrations of 0 (control), 0.0032% (low) and 0.032% (high) sewage sludge in seawater for 12 weeks, were assessed for their immunological competence. 2. No effect upon total blood leucocyte and erythrocyte numbers was found, although significantly fewer thrombocytes were seen in the high-exposure group. 3. A decreased serum protein level was found in the high exposure group, but lysozyme and immunoglobulin levels showed non-significant differences between the groups. 4. Melano-macrophage centres were also affected in the high-exposure dab, which had increased numbers in the spleen and kidney. No effect upon spleen weights or oxygen free radical production by splenocytes was noted. However, oxygen free radical production by kidney leucocytes was inhibited in the low-exposure dab.

Animals↗
PubMed1990

Regional neurotransmitter responses after acute and chronic electroconvulsive shock.

Regional neurotransmitter changes after acute and chronic electroconvulsive shock (ECS) were studied using the technique of repeated microdialysis. Microdialysis was carried out on alternate sides of the brains of anaesthetised rats before and during the first and the eighth ECS or sham (control) treatments. Extracellular fluid release of monoamines and their metabolites was measured in the frontal cortex, striatum and nucleus accumbens using HPLC with electrochemical detection. The first ECS produced selective regional responses, shown by increased concentrations of noradrenaline (NA) and dopamine (DA) in frontal cortex, by unchanged DA content in striatum, and by a small rise in NA and a fall in DA concentrations in nucleus accumbens. Concentrations of metabolites increased after ECS in all regions studied, and for homovanillic acid and dihydroxyphenylacetic acid, the temporal pattern of these changes did not resemble that of DA. Comparison of neurotransmitter responses as per cent of baseline release after the first and eighth ECS treatments showed they were identical. Basal release of monoamines and metabolites before the first ECS or sham treatment was similar in all regions studied. Prior to the eighth treatment, basal release of NA in the frontal cortex and DA in the striatum was elevated in the ECS-treated animals, while basal release of NA in the nucleus accumbens was reduced in both ECS- and sham-treated animals. These data suggest that acute and chronic ECS have different and region-specific effects on neurotransmitter release, although the overall pattern of these responses is not changed by chronic treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗