Biomedical subjects

D S Williams

Publications and source records attributed to D S Williams.

123 records · Page 7Linked to original sources

PubMed1987

Prevention of rod disk shedding by detachment from the retinal pigment epithelium.

The authors tested whether or not rod outer segment (ROS) disks are shed when the neural retina is detached from the retinal pigment epithelium (RPE). Adult Xenopus were injected with 3H-L-leucine. Later, when the distal disks of their ROSs were labeled with a band of 3H-leucine, their eyes were enucleated. Intact eyecups, eyecups with partially detached retinae, and retinae that were peeled completely away from the RPE were incubated in culture medium. Disk shedding was stimulated by changes in lighting, or the addition of 0.5 mM ouabain. Where the retina was attached, phagosomes in the RPE, and not the ROSs, contained most of the radiolabel. Where there was retinal detachment, ROSs were still heavily radiolabeled near their distal ends. It was concluded that mechanical retinal detachment prevents ROS disk shedding.

Animals↗

PubMed1986

In vitro maintenance of a pure-cone retina.

The retina of the lizard, Sceloporus occidentalis, appears to have only cone photoreceptors. Eyecups from this animal were incubated in media containing Earle's Balanced Salts, supplemented with amino acids and vitamins, and gassed with 5% CO2/95% O2. Under these conditions, good morphology, protein synthesis, and normal cyclic AMP and cyclic GMP levels were maintained for 1-2 days. This in vitro preparation is likely to be useful for pharmacological studies of cone photoreceptors.

Amino Acids↗

PubMed1985

Primaxin in the treatment of acute bacterial pneumonia in adults.

Imipenem (N-Formimidoyl thienamycin) (MK-0787) is a new beta-lactam carbapenem antibiotic. When it is combined with the renal dipeptidase inhibitor cilastatin (MK-0791) the combination is known as primaxin. In this study 28 adult patients (24 males and 4 females) with acute bacterial pneumonia were treated with primaxin. Twenty-one patients were evaluable and 20 (95%) were clinically cured of their pneumonia. Bacteriological cures were demonstrated in 84% of the cases. One patient with a susceptible Pseudomonas aeruginosa failed. Major complications or toxic reactions included antibiotic associated diarrhoea in one patient; hypotension in one patient; increased grand mal seizures in one patient and elevated liver function studies in one patient. Results of this study suggest that primaxin will be useful in the treatment of a variety of serious Gram-positive and Gram-negative pneumonias. The true incidence of possible toxic reactions with this drug is not known at this time and awaits further experience.

Adult↗

PubMed1985

Effect of L-cysteine on the activity of penicillin antibiotics against Clostridium difficile.

We observed elevated MICs of penicillin antibiotics while performing agar dilution susceptibility testing of strains of Clostridium difficile on supplemented brain heart infusion agar, an effect which was completely eliminated by the exclusion of L-cysteine from the medium. L-Cysteine antagonizes the activity of penicillins against C. difficile, most likely by direct inactivation of the antibiotic.

Cephalosporins↗

PubMed1983

Retrospective analysis of plasmid patterns in a study of burn unit outbreaks of infection due to Enterobacter cloacae.

To evaluate the usefulness of plasmid pattern analysis as an epidemiologic tool and to determine the mechanism of resistance to silver sulfadiazine and mafenide acetate, silver sulfadiazine-resistant, mafenide acetate-resistant Enterobacter cloacae isolates from a 1976 outbreak of infections in a burn unit (group I) were analyzed retrospectively. These strains were compared with various E cloacae isolates (groups II-V), including E cloacae isolates from a more recent (1982) burn unit outbreak (group V). Agarose gel electrophoresis (AGE) of DNA isolated from "epidemic" strains of E cloacae revealed a uniform pattern of four plasmid DNA bands, ranging in molecular size from 66 to 2 megadaltons. No such plasmid pattern was seen in silver sulfadiazine-, mafenide acetate-susceptible isolates of E cloacae in groups II, III, and V. Analysis of non-E cloacae coisolates suggested that silver sulfadiazine resistance was associated with the 55-megadalton plasmid. Plasmid pattern analysis easily separated "epidemic" E cloacae isolated in 1976 from those isolated in 1982.

Burns↗

PubMed1982

Photoreceptor membrane shedding and assembly can be initiated locally within an insect retina.

Photoreceptors of locust compound eyes add new receptor membrane at dusk and shed membrane at dawn. When part of an eye is masked before dusk, premature assembly of new membrane is initiated in the masked ommatidia but not in the adjacent unmasked ommatidia. Similarly, masking some ommatidia just before dawn prevents normal shedding only in the masked ommatidia. Therefore, the shedding and assembly phases of photoreceptor membrane turnover can be initiated by a change in the state of illumination of individual ommatidia.

Animals↗

PubMed1982

The local deletion of a microvillar cytoskeleton from photoreceptors of tipulid flies during membrane turnover.

The distal regions of the photoreceptor microvilli of tipulid flies are shed to extracellular space during membrane turnover. Before abscission, the microvillar tips undergo a transformation: they become deformed, and after conventional fixation for electron microscopy are relatively electron-lucent compared to the stable, basal microvillar segments. We now show that the electron-lucent segment is an empty bag of membrane whose P-face after freeze-etch preparation appears as densely particulate as the remainder of the microvillus. Transformation is achieved by the local deletion of a microvillar cytoskeleton which consists of a single, axial filament linked to the plasma membrane by side-arms. The filament may be partially preserved by the chelation of Ca2+; the provision of a divalent cation (Mg2+ or Ba2+) stabilizes the side-arms during subsequent fixation, as has been shown previously for the rhabdomeral cytoskeleton of blowflies. Incubation of the isolated retina in the presence of 0.25 mM Ca2+ at room temperature for 10-20 min causes proteolysis of the cytoskeleton which is blocked by as little as 0.5 mM of the thiol protease inhibitors Ep-475 and Ep-459. Loss of the cytoskeleton is accompanied by deformation of all regions of the microvilli. Local deletion of the cytoskeleton from the transformed zone of the normal rhabdom is sufficient to explain deformation of the microvillar tips, but not their subsequent abscission. The intimate association between a Ca2+-activated thiol protease and the cytoskeleton implied by the great rapidity of proteolysis calls for a reassessment of published studies of membrane turnover by radioautography, and of the nature of light-induced damage to arthropod photoreceptor membranes.

Animals↗

PubMed1982

Rhabdom size and photoreceptor membrane turnover in a muscoid fly.

The cross-sectional area of rhabdomeres in the compound eye of the blowfly, Lucilia, was found to remain constant under 12 h light/12 h dark cyclic lighting, and 10 days constant light or darkness. It was reduced only slightly during 3 h light after 10 days darkness (by 21%), or on exposure to 2 h darkness + 1.5 h light after 10 days light (by 10%). Morphological evidence indicates that shedding of photoreceptor membrane during turnover is achieved by an extracellular route, and by pinocytosis from the bases of the microvilli. The photoreceptor membrane shed by both mechanisms appears to accumulate in multivesicular bodies. The amount of photoreceptor membrane shedding, as indicated by numbers of multivesicular bodies, is constant throughout the day and night on cyclic lighting, decreases in constant darkness, but returns to its normal level after an exposure to 3 h light subsequent to 10 days darkness.

Animals↗

PubMed1982

Ommatidial structure in relation to turnover of photoreceptor membrane in the locust.

In the compound eye of the locust, Locusta, the cross-sectional area of the rhabdoms increases at "dusk" by 4.7-fold due to the rapid assembly of new microvillar membrane, and decreases at "dawn" by a corresponding amount as a result of pinocytotic shedding from the microvilli. The rhabdoms at night have more and longer photoreceptor microvilli than rhabdoms during the day. The orientations of the six rhabdomeres that comprise the distal rhabdom also change. The density of intramembrane particles on the P-face of the microvillar membrane, putatively representing mostly rhodopsin molecules, or aggregates thereof, does not change. An alteration in the size of the ommatidial field-stop, produced by the primary pigment cells, is concomitant with the change in rhabdom size. At night the increase in size of the field-stop must widen the angular acceptance of a rhabdom, increasing the capture of photons from an extended field. Conversely, during the day, when photons are more abundant, its decrease must narrow the acceptance angle, increasing angular resolution. Because of the presence of this field-stop, the optics of the ommatidium would not be greatly affected if the rhabdom were to remain always at its night size. It is argued, therefore, that the variable-size rhabdom must have resulted from some demand other than that of light/dark adaptation. Changes in size and organisation of the rhabdoms in response to various light regimes indicate that: (1) Rapid shedding of photoreceptor membrane is induced by the onset of light, but shedding also occurs slowly in darkness during the day. (2) Microvillar assembly is initiated by the onset of darkness, but also occurs at the normal time of dusk without a change in ambient lighting, provided there has been some light during the day. Therefore, both shedding and assembly of microvillar membrane are affected by the state of illumination, but also appear to be under some endogenous control.

Animals↗

PubMed1981

Twisted rhabdomeres in the compound eye of a tipulid fly (Diptera).

The individual rhabdomeres of the outer retinular cells (R 1-6) in the tipulid fly, Ptilogyna, twist about their long axes. Proximally, the rhabdoms become partitioned off by processes from the retinular cells, so that the basal region of each rhabdomere is enclosed in a "pocket" formed by its own cell (Fig. 2). This organisation of the rhabdom enables each rhabdomere to twist while supported within its own retinular cell, and while the cell itself maintains its orientation with respect to the entire ommatidium. Theory predicts that the rhabdomeral twisting should significantly reduce the polarisation sensitivity of R 1-6, but have little effect on the efficiency with which unpolarized light is absorbed.

Animals↗

PubMed1980

Extracellular shedding of photoreceptor membrane in the open rhabdom of a tipulid fly.

The compound eyes of the Australia tipulid fly, Ptilogyna, shed the bulk of their rhabdomeral membrane to extracellular space during turnover. The rhabdomeres of the retinulae lie in a common extracellular space (ECS), which is subdivided in the proximal retina. Before dawn, a distal region of the microvilli in each rhabdomere differentiates and becomes less electron-dense after conventional fixation. The differentiated region then dilates and develops an irregular profile. A few hours after dawn, the transformed tips break off and form a detritus in the ECS. The degraded membrane is internalised back into the retinula cells by mass endocytosis. Retinulae develop pseudopodia at sites bordering the ECS and engulf the membrane detritus, which comes to lie first of all in vacuoles within the receptor cells and then forms very large multivesicular bodies. The latter transform to multilamellar and residual bodies and are, presumably, lysed. Surrounding these secondary lysosomes are rough endoplasmic reticulum and smooth tubular systems, tentatively considered on comparative grounds to provide hydrolases. The literature concerning the ultrastructure of compound eyes offers a small number of instances where extracellular shedding can be suspected for morphological reasons. Attention is drawn to analogies with the shedding of photoreceptor membranes in vertebrate retinae.

Animals↗

PubMed1980

Ca++-induced structural changes in photoreceptor microvilli of Diptera.

When the compound eyes of the fly Lucilia are fixed for electron microscopy with glutaraldehyde in common buffer solutions, artefactual whorls are liable to be formed from the photoreceptor microvilli. The whorls result from two factors: (i) a prolonged time interval prior to osmication, such as the "overnight" primary fixation or wash at 4 degrees C commonly used in studies of compound eyes; (ii) as little as 1-2 mM Ca++ in the primary fixative and wash solutions. Osmication after short (1h) glutaraldehyde fixation at 4 degrees C, or omission of Ca++ and addition of 2 mM EGTA, prevent whorl-formation. In the tipulid fly Ptilogyna, similar artefacts are produced, but are confined to the distal zone of the microvilli that sheds during turnover.

Animals↗

PubMed1980

The posterior median eyes of the dinopid spider Menneus.

The posterior median (pm) eyes of the dinopid spider Menneus unifasciatus L. Koch are described and compared with the pm eyes of Dinopis, which are highly specialised for night vision. The lenses of Menneus have F-numbers of 0.72 compared to 0.58 in Dinopis, the distance between receptors is ca. 4.0 microns compared to 20-22 microns for Dinopis, and image quality is matched to receptor spacing. The lens of Menneus is simple, while that of Dinopis comprises two components of different refractive indices (Blest and Land 1977). Receptive segments of the pm eyes of Dinopis are hexagonal in transverse section and those of adjacent cells are tightly contiguous, allowing the possibility of both optical and electrical coupling (Blest 1978). Receptive segments of Menneus are separated from each other by glial processes containing little pigment, and each segment possesses two rhabdomeres on opposite faces of the cell. Rhabdomere volumes undergo a daily cycle similar to that described for Dinopis, but of relatively minor extent. It is shown that the pm eye of Dinopis could have evolved from that of Menneus by a simple series of transformations, and that a gain of two logarithmic units of sensitivity can be attributed to changes in optical design alone.

Animals↗

PubMed1978

Application of stereotactic principles to the treatment of trigeminal neuralgia.

The application of neuroanatomical and neurophysiological principles to the functional surgery of the trigeminal nerve is discussed. Particular attention has been directed toward correlating the three-dimensional anatomical features of the trigeminal nerve and the surrounding structures to the two-dimensional radiograph of this same region. In this regard, 20 trigeminal nerves, including the surrounding neurovascular structures from 10 cadaver sphenoid blocks, were examined. Measurements of the third, fourth and sixth cranial nerves in relation to the profile of the clivus were made from lateral radiographs of the sphenoid blocks. The position of the internal carotid artery in relation to these structures was also noted. These neurovascular relationships are of clinical importance when using the percutaneous thermocoagulation technique for the treatment of trigeminal neuralgia.

Electrocoagulation↗

PubMedDate not supplied

A multicenter comparative study of the in vitro activity of fleroxacin and other antimicrobial agents.

The in vitro activity of fleroxacin was determined by broth microdilution against 2,079 recent bacterial isolates and compared to the activities of ciprofloxacin, ofloxacin, lomefloxacin, cefaclor, cefuroxime, cefixime, ceftriaxone, amoxicillin/clavulanate, trimethoprim/sulfamethoxazole (TMP-SMX), and, as appropriate, erythromycin and oxacillin. Most Enterobacteriaceae were inhibited by the quinolones at a concentration of < or = 1 microgram/ml; MIC90s of fleroxacin, ciprofloxacin, ofloxacin, and lomefloxacin were 0.25, 0.5, 1 and 1 micrograms/ml, respectively. Fleroxacin was 2-fold more active than ciprofloxacin against Providencia stuartii and Serratia marcescens. Aside from the quinolones, ceftriaxone and TMP-SMX were the most active antibiotics against the Enterobacteriaceae, with MIC90s of 8 and 16 micrograms/ml, respectively. Ciprofloxacin was more active against Pseudomonas aeruginosa than the other quinolones, while fleroxacin was more active against Stenotrophomonas maltophilia: 17.7, 11.2, 20.0, and 22.4% of P. aeruginosa were resistant to fleroxacin, ciprofloxacin, ofloxacin, and lomefloxacin, respectively. Moraxella catarrhalis and Haemophilus influenzae were uniformally susceptible to all antibiotics tested, as were the majority of oxacillin-susceptible staphylococci. The MIC90s of the quinolones and of the beta-lactam antibiotics for oxacillin-resistant staphylococci were 8- to 256-fold higher than for oxacillin-susceptible staphylococci. The beta-lactam antibiotics, TMP-SMX, and erythromycin were more active than the quinolones against streptococci; all antibiotics were poorly active against enterococci. Fleroxacin is active against a broad range of gram-negative bacilli and against oxacillin-susceptible staphylococci and should prove useful for such infections. However, its use cannot be recommended for infections due to oxacillin-resistant staphylococci, streptococci, or enterococci.

Anti-Bacterial Agents↗