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Biomedical subjects

T D Williams

Publications and source records attributed to T D Williams.

At least 73 records · Page 4Linked to original sources

Systemic abnormalities associated with iris/nerve head/choroidal/retinal coloboma.

A case is reported in which large colobomas of the retina and choroid are found bilaterally in a young female who also has a pituitary tumor and mental retardation. Visual field data are presented and correlated with the retinal appearances. Relevant embryology is reviewed, and a table of systemic abnormalities associated with retinal/choroidal colobomas is presented.

Adenoma↗

A potential anti-oxidant protein in a ferrous iron-oxidizing Sulfolobus species.

The production of a 25 kDa protein was greatly increased when a sulfur- and ferrous iron-oxidizing species of Sulfolobus was switched from growth on tetrathionate to growth on ferrous iron. The gene encoding the protein was cloned and sequenced. The predicted amino sequence showed significant similarity to those of the alkyl hydroperoxide reductase/thiol specific anti-oxidant family of proteins that appear to be involved in responses to certain types of oxidative stress.

Amino Acid Sequence↗

Adaptive changes in lipid composition of skeletal sarcoplasmic reticulum membranes associated with aging.

We have undertaken a detailed examination of changes associated with aging in lipid composition and corresponding physical properties of hindlimb skeletal sarcoplasmic reticulum (SR) membranes isolated from young (5 months), middle-aged (16 months), and old (28 months) Fischer strain 344 rats. Silica gel HPLC chromatography was used to separate phospholipid headgroup species. Subsequent reversed-phase HPLC was used to resolve fatty acid chain compositions of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol species. For all three phospholipid pools, significant age-related variations are observed in the abundance of multiple molecular species, particularly those having polyunsaturated fatty acid chains. Using mass spectrometry (fast atom bombardment and tandem techniques) to distinguish ester- from ether-linked phosphatidylethanolamine species, we demonstrate that overall plasmenylethanolamine content is substantially increased with age, from 48 mol% to 62 mol%. A substantial increase is also observed in the single molecular species 18:0-20:4 phosphatidylinositol suggesting implications for signalling pathways. In addition, associated with senescence we find a significant increase in the rigidifying lipid, cholesterol. Despite these changes in lipid composition of different aged animals, the average bilayer fluidity examined at several bilayer depths with stearic acid spin labels, is not altered. Neither do we find differences in the rotational mobility of maleimide spin-labeled Ca(2+)-ATPase, as determined from saturation-transfer electron paramagnetic resonance, which is sensitive to both the fluidity of lipids directly associated with the Ca(2+)-ATPase and to its association with proteins.

Aging↗

Information technology for home care--a promising future.

Home care faces challenges in the automation arena from changing regulations to improved software and hardware. The past has had its ups and downs in relations between agencies and those vendors from whom they must purchase these necessities. What have been the problems? How can agencies avoid them?

Ambulatory Care Information Systems↗

Degradation of O6-benzylguanine in aqueous polyethylene glycol 400 (PEG 400) solutions: concerns with formaldehyde in PEG 400.

The degradation of O6-benzylguanine (BG) in aqueous polyethylene glycol (PEG) 400 solution at room temperature had been investigated using chromatographic and spectrometric methods. The degradation of BG in this solvent appeared to arise from a reaction between BG and formaldehyde. The formaldehyde was present as an impurity in PEG 400 and probably formed through air oxidation of PEG 400. The major product of this reaction was believed to be a methylene-bridged compound containing two BG molecules. This was probably produced via an intermediate imine, a schiff base between one BG molecule and formaldehyde. This degradation reaction was the only observable reaction in the 40% PEG/water solvent (pH 8.0) i.e. degradation of the drug via hydrolysis was minimal under these conditions.

Chromatography, High Pressure Liquid↗

Intraspecific variation in egg size and egg composition in birds: effects on offspring fitness.

1. There is little unequivocal evidence to date in support of a positive relationship between egg size and offspring fitness in birds. Although 40 studies (of 34 species) have considered the effect of variation in egg size on chick growth and/or survival up to fledgling only 12 studies have controlled for other characters potentially correlated both with egg size and offspring fitness. Of these only two have reported a significant residual effect of egg size on chick growth (in the roseate tern and European blackbird) and three a residual effect on chick survival (all in seabirds: common tern, lesser black-backed gull and kittiwake). 2. More consistent evidence exists, though from fewer studies, for a positive relationship between egg size and offspring fitness early in the chick-rearing period; chick growth and chick survival being dependent on egg size in 8 of 10 studies and 4 of 5 studies respectively. It is suggested that the most important effect of variation in egg size might be in determining the probability of offspring survival in the first few days after hatching. 3. Egg size explains on average 66% of the variation in chick mass at hatching (n = 35 studies) but only 30% of the variation in chick body size (n = 18). When effects of hatching body size are controlled for chick mass remains significantly correlated with egg size, though the reverse is not true. This supports the hypothesis that large eggs give rise to heavier chicks at hatching, i.e., chicks with more nutrient (yolk) reserves, rather than structurally larger chicks. 4. Egg composition increased isometrically with increasing egg size in about half the studies so far reported (n equals approximately 20). However, in seabirds, and some passerines, larger eggs contain disproportionately more albumen, whilst in some waterfowl percentage yolk content increases with increasing egg size. Changes in albumen content largely reflect variation in the water content of eggs, but changes in yolk content involve variation in lipid content, and therefore in egg 'quality.' The adaptive significance of variation in egg composition is considered; females may adjust egg composition facultatively to maximise the benefits to their offspring of increased reproductive investment. 5. Considerations for future research are discussed with particular emphasis on experimental studies and the application of new techniques.

Animals↗

Glutathione- and glutathione-S-transferase-dependent oxidative desulfuration of the thione xenobiotic diethyldithiocarbamate methyl ester.

Oxidative desulfuration of diethyldithiocarbamate methyl ester (DDTC-Me), a thione xenobiotic and a metabolite of disulfiram, was studied. Using a rat liver microsomal incubation system, DDTC-Me was oxidized at the thionosulfur group, forming DDTC-Me sulfine. Only minimal desulfuration of DDTC-Me to S-methyl-N,N-diethylthiolcarbamate (DETC-Me) occurred. Desulfuration of DDTC-Me increased 4-fold when the microsomal incubation was supplemented with reduced glutathione (GSH) and increased 8-fold when both GSH and glutathione-S-transferase (EC 2.5.1.18) were added. Similar results were obtained using a simplified system containing DDTC-Me sulfine, GSH, and glutathione-S-transferase. This suggested that DDTC-Me sulfine is a stable intermediate formed before DDTC-Me is desulfurated to DETC-Me. This unprecedented desulfuration process can be explained as follows. GSH attacks the oxithiirane isomer of DDTC-Me sulfine, resulting in ring opening followed by loss of glutathione hydrodisulfide, which is reduced by GSH to oxidized glutathione and H2S. GSH can also reduce DDTC-Me sulfine to DDTC-Me. This mechanism is supported by in vitro studies. An approximately 1:1 stoichiometry was observed for the formation of H2S and DETC-Me. A 1:1 stoichiometry was also observed for the consumption of DDTC-Me sulfine, formation of DETC-Me plus DDTC-Me, and formation of oxidized glutathione. Glutathione hydrodisulfide was trapped by derivatization in situ using 4-vinylpyridine. Oxidative desulfuration of a series of dithiocarbamate esters also followed a similar mechanism.

Aldehyde Dehydrogenase↗

Exchangeable GTP binding site of beta-tubulin. Identification of cysteine 12 as the major site of cross-linking by direct photoaffinity labeling.

After direct photoaffinity cross-linking of [3H]GTP to the beta-subunit of tubulin, followed by tryptic digestion and alkaline phosphatase treatment, we employed cis-diol-specific boronate gel chromatography and reversed-phase high-pressure liquid chromatography to purify a peptide containing most of the covalently bound radioactivity. The sequence of this peptide corresponded to that of residues 3-19 of beta-tubulin. Residue 10 of the peptide, which is Cys-12 in beta-tubulin, could not be identified. The fast atom bombardment mass spectrum of this peptide showed the presence of a predominant species with a molecular mass of 2022 kDa (2021 kDa for the 12C variant), which is 255 Da greater than the molecular mass of the peptide. Fast atom bombardment collision-activated decomposition mass spectrometry analysis produced fragments which are consistent with the beta(3-19) peptide but having a unit of mass of 358 at position 12. Thermolysin digestion of the tryptic peptide restricted the cross-linking site to the 9-amino acid sequence, I(L)QAGQXGNQ. The molecular mass of this peptide was 1174 kDa, which is equal to the mass of the beta(7-15) peptide containing an extra group of mass 255. To explain the molecular masses of the two labeled peptides, which are 26 atomic mass units less than expected, a mechanism of photolabeling is proposed that involves opening of the guanine ring and loss of the C-6 carbonyl function as CO2.

Affinity Labels↗

Plasma prolactin during the breeding season in adult and immature macaroni (Eudyptes chrysolophus) and gentoo (Pygoscelis papua) penguins.

Plasma prolactin levels were measured in free-living breeding adult and immature (pre-breeding) macaroni (Eudyptes chrysolophus) and gentoo (Pygoscelis papua) penguins at Bird Island, South Georgia (54 degrees S, 38 degrees W). Macaroni and gentoo penguins first breed at 5-6 and 2 years of age, respectively. In adult birds, of both species, prolactin was low (< 1.0 microgram. liter-1) during the courtship period and then increased during early (gentoo) to mid (macaroni) incubation (to 3.9-4.7 and 2.4-3.5 micrograms.liter-1, respectively), remaining elevated until the creche period, by which time continuous nest attendance by the adults had ceased. This pattern is similar to that seen in other altricial species and is consistent with delayed onset of brood patch development and full incubation efficiency, which has been previously reported in penguins. Adult female macaroni penguins showed a marked, but transient, increase in prolactin concentrations within 24 hr of the first egg being laid (from 1.7 to 7.0 micrograms.liter-1), plasma levels decreasing following clutch completion (to prelaying levels) before increasing again during incubation. Elevated plasma prolactin levels occurred in all age classes of immature (nonbreeding) birds in both macaroni (1- to 5 year-olds) and gentoo (1-year-olds) penguins. However, compared to that in adult birds, the increase in prolactin was more transient in immatures, a smaller proportion of immatures had detectable prolactin levels at each stage of the breeding cycle, and, at least in 1- and 2-year-olds, absolute levels of prolactin were lower.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Reproductive endocrinology of macaroni (Eudyptes chrysolophus) and gentoo (Pygoscelis papua) penguins. I. Seasonal changes in plasma levels of gonadal steroids and LH in breeding adults.

Changes in plasma luteinizing hormone (LH), testosterone, oestradiol, and progesterone were measured throughout the breeding and molt cycle in free-living male and female macaroni (Eudyptes chrysolophus) and gentoo (Pygoscelis papua) penguins, at Bird Island, South Georgia (54 degrees S, 38 degrees W). These two species are sympatric but have a markedly different breeding cycle. In macaroni penguins plasma levels of all hormones, except LH in males, were significantly elevated at the time of arrival at the breeding colony. In both species and sexes plasma LH, testosterone (males), and estradiol (females) levels were highest during nest-building and postcopulation, coincident with the period of frequent agonistic interactions in males and egg-formation in females. Elevated testosterone levels occurred in females of both species during the postcopulation period and may be associated behaviourally with both sexes being involved in nest defence. Male birds also had elevated estradiol levels. Following copulation, plasma levels of LH, testosterone, and estradiol decreased to basal levels in both sexes and species and, except for a transient increase in testosterone in male macaroni penguins, remained low through to the end of molt. There was no associated rise in LH or testosterone during premolt and early molt despite a further period of agonistic and social interaction, suggesting that birds were in a photorefractory state at this time. Plasma progesterone showed a pattern of variation different from that of the other hormones. In both species and sexes, plasma levels were elevated between arrival and early chick-rearing and then decreased slowly to low levels during molt.

Animals↗

Reproductive endocrinology of macaroni (Eudyptes chrysolophus) and gentoo (Pygoscelis papua) penguins. II. Plasma levels of gonadal steroids and LH in immature birds in relation to deferred sexual maturity.

Plasma levels of LH, testosterone, estradiol, and progesterone were measured, during the breeding season, in adult and immature macaroni (Eudyptes chrysolophus) and gentoo (Pygoscelis papua) penguins, at Bird Island, South Georgia (54 degrees S, 38 degrees W), in relation to deferred sexual maturity. Macaroni penguins do not breed until 6-8 years of age whereas gentoo penguins first breed at 2 years of age. Plasma LH was elevated in 3- to 5-year-old macaroni penguins, but not in 1- to 2-year-old birds nor 1-year-old gentoos. However, 1 year olds of both species responded to an injection of exogenous LH-RH by increasing LH secretion. Some individual 3-, 4-, and 5-year-old macaroni penguins had circulating testosterone levels within the range of peak values in adults, suggesting that in males, gonads were physiologically mature several years in advance of the age of first breeding. One year old macaroni penguins had elevated progesterone levels and basal estradiol levels, but in 2-4 year olds plasma levels of both progesterone and estradiol were low. This does not support the hypothesis that high progesterone levels "block" ovarian maturation in immature penguins. Immature gentoo penguins showed a different pattern of hormone secretion. Plasma testosterone was low in all breeding periods, but estradiol levels increased to a peak during the incubation period, 4 weeks later than peak values occurred in adults. In both species, therefore, deferred sexual maturity was associated with delayed and/or reduced secretion of LH and gonadal steroids.

Animals↗

Identification and quantitation of tetrapeptide deamidation products by mass spectrometry.

A method to quantify asparagine (Asn), aspartate (Asp) and isoaspartate (isoAsp) residues in small peptides by fast atom bombardment mass spectrometry (FAB-MS) was developed. Discrimination of isoAsp from Asp residues was accomplished by selective derivatization of isoAsp residues in acetic anhydride, D2O and pyridine. Deuteration occurred at any carbon adjacent to a free alpha-carboxyl group, through a transient oxazalone intermediate, allowing the isoAsp side chain and the C-terminus to incorporate deuterium. Thus, isoAsp-containing peptides incorporate one more deuterium than peptides with Asp and two more than Asn peptides. FAB CID-MS spectra of the Asn tetrapeptide, Thr-Asn-Ser-Tyr, were used to confirm the position of deuteration to the C-terminal residue. FAB and FAB CID-MS spectra demonstrated that the 1 amu shift in mass was not caused by derivatization induced deamidation of the Asn residue. FAB-MS spectra of deuterated peptide standards and mixtures containing deamidation products were obtained over the molecular ion region and deconvoluted using non-deuterated control spectra. Deuterium incorporation values for the Asn, Asp and iosAsp containing peptide standards were 80% mono-deuterated peptide, 95% mono-deuterated peptide and 63% di-deuterated peptide, respectively. IsoAsp to Asp ratios in an unknown mixture were obtained by a least-squares minimization of the difference between the unknown deuterated mixture and the isotopic envelopes from the deuterated standards. The mixture was found to contain 85% isoAsp peptide by FAB-MS, which agreed well with 81% isoAsp peptide when assayed by reversed-phase LC.

Amino Acid Sequence↗

Haemodynamic and neurohumoral response in heart failure produced by rapid ventricular pacing.

OBJECTIVE: The aim was to determine the exact sequence of hormone changes during the progression of fluid retention in a canine model of "congestive cardiac failure" induced by rapid right ventricular pacing, and during recovery when pacing is stopped. METHODS: Rapid ventricular pacing at a rate of 250 pulses.min-1 was used in six mongrel dogs with implanted right ventricular pacemakers. Right heart haemodynamics were measured by means of Swan Ganz catheterisation, allowing flow measurement by thermodilution and pressure measurement by external manometry. Plasma renin activity, arginine vasopressin, and atrial natriuretic factor were assayed on venous blood samples by radioimmunoassay. Noradrenaline was assayed by high pressure liquid chromatography. RESULTS: The onset of rapid pacing was accompanied by a fall in cardiac output and a rise in pulmonary arterial, pulmonary capillary wedge, and right atrial pressures. Noradrenaline and atrial natriuretic factor rose. Plasma renin activity showed an initial fall followed by a rise, and arginine vasopressin was unchanged in the first 8 h. When rapid pacing was continued for a further 35 d, clinical signs of fluid retention appeared by day 28, by which time cardiac output had fallen, and central pressures risen further. Atrial natriuretic factor peaked at around 14 d whereas plasma renin activity, arginine vasopressin, and noradrenaline tended to reach a plateau at about d 20 and then to show further increases as clinical signs of fluid retention appeared; this was most marked with plasma renin activity. Cessation of pacing at d 35 caused a rapid reversal (increase) of cardiac output but a more gradual reversal (decrease) of right heart pressures over 5 d; only wedge pressure returned to base line. Arginine vasopressin and plasma renin activity fell rapidly to around 40% of the final pacing levels and reached basal values after 8 h and 48 h respectively. Noradrenaline fell after 8 h and reached basal levels in 5 d. Atrial natriuretic factor fell quickly by 60% after 8 h but remained above basal levels for 5 d. At the end of pacing, body weight fell rapidly in conjunction with a large diuresis. CONCLUSIONS: These findings are compatible with a major role of one or more of renin, vasopressin, and noradrenaline in the pathophysiology of the fluid retention of heart failure; the manifestations are not counteracted by the rise in atrial natriuretic factor.

Animals↗

Position of the fovea centralis with respect to the optic nerve head.

Examination of the ocular fundus via indirect ophthalmoscopy gives the clinician an impression of foveal position relative to the nerve head. In some patients, the fovea appears to be in an unusual position (i.e., ectopic): it may appear to be higher or lower than expected, or closer to or farther from the nerve head. There is little published quantitative information on this subject. The purpose of this study was to examine foveal position in a group of normal adult eyes, so that clinicians and other researchers will be able to determine on a more objective basis whether or not a given patient shows foveal ectopia. Using ocular fundus photographs for 446 normal adult eyes, we found the foveal center to be, on average, 6.11 degrees +/- 3.32 degrees below a horizontal line bisecting the nerve head. For a smaller sample of 66 eyes, we found the average distance between the nerve head and foveal centers to be 4.93 +/- 0.33 mm (right eye) and 4.88 +/- 0.36 mm (left eye). Correlations of these data for right and left eyes are also examined. Nerve head data for the group of 66 right eyes were also analyzed to yield dimensions of a best-fitting ellipse: the mean minor axis was 1.75 +/- 0.2 mm; the mean major axis 1.95 +/- 0.2 mm. Ectopia (heterotopia) of the fovea has been found in association with chorioretinitis, fibrous traction bands, and/or colobomas of the choroid and optic nerve (including anomalous insertion of the optic nerve), microcephalus, and microphthalmia. A number of separate cases with anomalous nerve heads and/or foveal positions are discussed in this paper.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗