Biomedical subjects

M S Roy

Publications and source records attributed to M S Roy.

At least 37 records · Page 2Linked to original sources

PubMed1997

Light induces peroxidation in retina by activating prostaglandin G/H synthase.

Prostaglandin G/H synthase (PGHS) has been shown to generate peroxides to a significant extent in the retina and absorbs light at the lower end of the visible spectrum. We postulated that PGHS could be an important initial source of peroxidation in the retina exposed to light, which would in turn alter retinal function. Exposure of pig eyes (in vivo) to light (350 fc/3770 lx) caused after 3 h a 50% increase and by 5 h a 30% decrease in a- and b-wave amplitudes of the electroretinogram (ERG) which were comparable at 380-650 nm and 380-440 nm but were not observed at wavelengths > 450 nm. These effects of light were prevented by free radical scavengers (dimethylthiourea and high-dose allopurinol) and PGHS inhibitors (naproxen and diclofenac), but stable analogs of prostaglandins did not affect the ERG. Both increases and subsequent decreases in ERG wave amplitudes following light exposure in vivo were associated with increases in retinal prostaglandin and malondialdehyde (peroxidation product) levels, which were inhibited by the nonselective PGHS blockers, naproxen and diclofenac. Similar observations were made in vitro on isolated porcine eyecups as well as on retinal membranes exposed to light (250 fc/ 2700 lx) 380-650 nm and 380-440 nm but not at > 500 nm. Both PGHS-1 and PGHS-2 contributed equivalently to light-induced prostaglandin synthesis, as shown after selective PGHS-2 blockers, but mRNA expression of PGHS-1 and 2 was not affected by light. Finally, light stimulated activities of pure PGHS-1 and PGHS-2 isozymes, and these were also shown to produce superoxide radical (detected with fluorogenic spin trap, proxyl fluorescamine). Taken together, data suggest that PGHS- (1 and 2) is activated by short wavelength visible light, and in the retina is an important source of reactive oxygen species which in turn alter retinal electrophysiological function. PGHS thus seems a likely chromophore in setting forth photic-induced retinal injury. Findings provide an explanation for increased sensitivity of the retina to visible light predominantly at the far blue range of its spectrum.

Animals↗

PubMed1997

Retinopathy in haemoglobin C trait.

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Anemia, Sickle Cell↗

PubMed1997

Cone ERG subnormality to red flash in central retinal vein occlusion: a predictor of ocular neovascularisation?

In patients with unilateral central retinal vein occlusion (CRVO), we retrospectively examined whether cone electroretinogram (ERG) subnormality to red flash (ratio of the b-wave amplitude in the CRVO eye to that in the normal fellow eye < 1) found at the time of diagnosis of the CRVO was a predictor of later ocular neovascularisation. Ganzfeld ERG cone and rod responses had initially been obtained in a consecutive series of 21 patients with unilateral CRVO. Patients were re-evaluated 6-55 months later to determine whether ocular neovascularisation had developed. Of the 21 CRVO eyes, 6 (29%) were subnormal to red in the affected compared with the normal fellow eye. At follow-up, all 6 (100%) patients had developed ocular neovascularisation compared with 1 (7%) of the 15 patients who were supernormal to red (p = 0.00013). Cone ERG subnormality to red flash in CRVO eyes compared with normal fellow eyes may be a predictor of later development of ocular neovascularisation.

Adaptation, Ocular↗

PubMed1995

Macular blood flow velocity in sickle cell disease: relation to red cell density.

AIMS/BACKGROUND: While the retinal lesions of sickle cell retinopathy have been well documented, their pathogenesis remains unclear. The purpose of this study was (1) to compare macular blood flow velocity in patients with sickle cell disease and controls, and (2) to determine in sickle cell patients the relation between macular blood flow velocity and red blood cell density. METHODS: Macular blood flow velocity was measured in 18 patients with stable sickle cell disease and 45 normal controls using blue field entoptoscopy. Red blood cell density was determined by the phthalate ester density method. RESULTS: There were no significant differences between patients and controls for leucocyte velocity. However, in the sickle cell patients leucocyte velocity in the macular capillaries was significantly negatively associated with greater range of red blood cell density (p < 0.002 and p < 0.04 for right and left eyes, respectively). CONCLUSION: These results suggest that in sickle cell patients heterogeneity of the density of the red blood cells may slow down macular capillary blood flow.

Adult↗

PubMed1995

Alterations in the electroretinogram of newborn piglets by propionic acid-derivative nonsteroidal antiinflammatory drugs but not by indomethacin and diclofenac.

Different nonsteroidal antiinflammatory drugs (NSAID), especially ibuprofen, are being considered as an alternative to indomethacin for use in the newborn and as antipyretics for infants. However, some of these NSAID have been shown to cause visual complications. We therefore studied the effects of different NSAID indomethacin 19.6 mumol/kg (7 mg/kg), diclofenac 15.7 mumol/kg (5 mg/kg), ibuprofen 48 and 194 mumol/kg (10 and 40 mg/kg), naproxen 79 mumol/kg (20 mg/kg), and flurbiprofen 41 mumol/kg (10 mg/kg) on photopic and scotopic electroretinograms (ERG) and retinal prostaglandin E2, prostaglandin F2 alpha, and 6-keto-prostaglandin F1 alpha levels in piglets 1-5 d old. All NSAID decreased retinal prostaglandin levels, but their effects on the ERG were not identical. Indomethacin and diclofenac did not alter the ERG. In contrast, the propionic acid derivatives ibuprofen (the two doses used), naproxen, and flurbiprofen affected the amplitude as well as the implicit time of the ERG under photopic and scotopic conditions. These changes are suggestive of generalized alterations in the function of rods and cones. Prior inhibition of prostaglandin synthesis by indomethacin did not modify the effects of ibuprofen on the ERG. These findings thus show a dissociation between the effects of NSAID on the ERG and prostaglandin synthesis. Because ERG changes are associated with visual alterations, these effects of propionic acid derivatives should be taken into account before considering their use in infants.

Animals↗

PubMed1995

Maturation of binocular pattern visual evoked potentials in normal full-term and preterm infants from 1 to 6 months of age.

The purpose of this study was to evaluate the visual development of preterm infants from 1 to 6 mo of age, using the pattern visual evoked potentials (VEP) in response to three check sizes: 60, 30, and 15 min of arc. Pattern VEP were recorded in 24 full-term and 24 preterm infants (26-36 wk of gestation). The results showed a rapid visual maturation between 1 and 3 mo, followed by a slower progression over the next 3 mo, in both groups. The implicit time of the P100 wave of the pattern VEP was also found to shorten with increasing check sizes. The maturation of pattern VEP in preterm infants was shown to be related to their gestational (or corrected) age rather than their postnatal age. The pattern VEP obtained in response to a 60-min check size in preterm infants aged between 1.5 and 2.5 mo (corrected age) showed a tendency for a faster maturation than those of full-term infants. Our results suggest that within the first 6 mo of age, pattern VEP response is useful to monitor visual development in full-term infants as well as in preterm infants using corrected age.

Age Factors↗

PubMed1994

The use of museum specimens to reconstruct the genetic variability and relationships of extinct populations.

In this review, we discuss the use of DNA from museum specimens to address conservation genetic questions. We provide four examples from our previous studies of the northern hairy-nosed wombat, African wild dog, Ethiopian wolf and red wolf. These species were genetically surveyed using two molecular approaches: first, analysis of short sequences in the mitochondrial genome using species-specific primers, and second, analysis of hypervariable microsatellite loci. The studies demonstrate that museum-derived DNA adds an important dimension to the genetic study of extant populations. Inaccessible populations can be studied, and both the loss of genetic variation and its distribution over space and time can be better understood. Finally, analysis of additional museum material provides definitive evidence for a hybrid origin of the red wolf.

Animals↗

PubMed1994

A new blood-coagulating protease in mitochondrial membranes of rat submaxillary glands. Purification and characterization of protease and its blood-coagulating activity.

An integral membrane protease was solubilized and purified to homogeneity from rat submaxillary mitochondria. The purified enzyme could coagulate rabbit plasma. The molecular mass of the enzyme is 22 kDa on SDS-polyacrylamide gel electrophoresis under reducing conditions and 24 kDa on gel filtration on a Sephadex G-100 column. Its isoelectric point is 4.2-4.25. Enzyme activity is strongly inhibited by diisopropyl fluorophosphate, soybean trypsin inhibitor, benzamidine, aprotinin, and antipain, suggesting the enzyme as a serine protease. Its pH optimum for activity is 8.5. Zn2+ is strongly inhibitory; at 1 mM concentration it produced 72% inhibition. The enzyme is active toward different synthetic substrates (p-nitroanilide derivatives) containing Arg at the P1 position with blocked NH2 terminus. Kcat/Km was highest with the substrate N-Bz-Pro-Arg-pNa (where Bz is benzoyl and pNA is paranitroanilide). The purified enzyme coagulates rabbit plasma in a dose-dependent manner. Plasma coagulation by the enzyme is completely blocked in the presence of aprotinin or soybean trypsin inhibitor, suggesting that protease activity is required for this coagulation reaction. Antibody raised against the purified enzyme inhibits the plasma coagulation initiated by the enzyme. The enzyme can correct the prolonged clotting time of factor X-deficient human plasma but is unable to convert purified fibrinogen to fibrin clots, indicating factor Xa-like activity of the enzyme. The enzyme has the ability to activate prothrombin. Several properties of the enzyme distinguish it from other reported submaxillary proteases.

Amino Acid Sequence↗

PubMed1994

Human strabismus: evaluation of the interhemispheric transmission time and hemiretinal differences using a reaction time task.

Experimentally induced strabismus in visually immature cats leads to abnormal development of the posterior corpus callosum. This, in turn, should lead to abnormal interhemispheric integration of unilaterally presented visual information. To test whether strabismus produces deficits in the human commissural visual system, the interhemispheric transmission time (ITT) was compared in strabismic and normal subjects. Simple unimanual reaction times (RT) were tested in 30 subjects in response to a lateralized target presented monocularly at 4 degrees and 35 degrees nasally and temporally from the fovea along the horizontal meridian. This method was also used to examine the effect of strabismus on the central and peripheral portions of each hemiretina. The results showed that in strabismic subjects with or without amblyopia, the ITT did not differ significantly from normals at both eccentricities. In non-amblyopic strabismic patients, RTs in the central and peripheral portions of hemiretina were comparable to normals. However, a reduced speed of response was found in the central visual field (4 degrees) in the amblyopic eye. Our results suggest that the ITT is normal in strabismic subjects and that the longer RTs in the central portion of the nasal and temporal hemiretina of the amblyopic eye may be associated with the severe amblyopic condition.

Adolescent↗

PubMed1994

Patterns of differentiation and hybridization in North American wolflike canids, revealed by analysis of microsatellite loci.

Genetic divergence and gene flow among closely related populations are difficult to measure because mutation rates of most nuclear loci are so low that new mutations have not had sufficient time to appear and become fixed. Microsatellite loci are repeat arrays of simple sequences that have high mutation rates and are abundant in the eukaryotic genome. Large population samples can be screened for variation by using the polymerase chain reaction and polyacrylamide gel electrophoresis to separate alleles. We analyzed 10 microsatellite loci to quantify genetic differentiation and hybridization in three species of North American wolflike canids. We expected to find a pattern of genetic differentiation by distance to exist among wolflike canid populations, because of the finite dispersal distances of individuals. Moreover, we predicted that, because wolflike canids are highly mobile, hybrid zones may be more extensive and show substantial changes in allele frequency, relative to nonhybridizing populations. We demonstrate that wolves and coyotes do not show a pattern of genetic differentiation by distance. Genetic subdivision in coyotes, as measured by theta and Gst, is not significantly different from zero, reflecting persistent gene flow among newly established populations. However, gray wolves show significant subdivision that may be either due to drift in past Ice Age refugia populations or a result of other causes. Finally, in areas where gray wolves and coyotes hybridize, allele frequencies of gray wolves are affected, but those of coyotes are not. Past hybridization between the two species in the south-central United States may account for the origin of the red wolf.

Alleles↗

PubMed1994

Molecular genetics of the most endangered canid: the Ethiopian wolf Canis simensis.

The world's most endangered canid is the Ethiopian wolf Canis simensis, which is found in six isolated areas of the Ethiopian highlands with a total population of no more than 500 individuals. Ethiopian wolf populations are declining due to habitat loss and extermination by humans. Moreover, in at least one population, Ethiopian wolves are sympatric with domestic dogs, which may hybridize with them, compete for food, and act as disease vectors. Using molecular techniques, we address four questions concerning Ethiopian wolves that have conservation implications. First, we determine the relationships of Ethiopian wolves to other wolf-like canids by phylogenetic analysis of 2001 base pairs of mitochondrial DNA (mtDNA) sequence. Our results suggest that the Ethiopian wolf is a distinct species more closely related to gray wolves and coyotes than to any African canid. The mtDNA sequence similarity with gray wolves implies that the Ethiopian wolf may hybridize with domestic dogs, a recent derivative of the gray wolf. We examine this possibility through mtDNA restriction fragment analysis and analysis of nine microsatellite loci in populations of Ethiopian wolves. The results imply that hybridization has occurred between female Ethiopian wolves and male domestic dogs in one population. Finally, we assess levels of variability within and between two Ethiopian wolf populations. Although these closely situated populations are not differentiated, the level of variability in both is low, suggesting long-term effective population sizes of less than a few hundred individuals. We recommend immediate captive breeding of Ethiopian wolves to protect their gene pool from dilution and further loss of genetic variability.

Animals↗

PubMed1993

The ovine corticotropin-releasing hormone-stimulation test in type I diabetic patients and controls: suggestion of mild chronic hypercortisolism.

We examined hypothalamic-pituitary-adrenal (HPA) axis function in insulin-dependent diabetic outpatients (N = 22) and age-, sex-, and weight-matched normal controls (N = 22). The evaluation included measurements of 9:00 AM fasting plasma cortisol and cortisol-binding globulin (CBG) levels, 24-hour urinary free cortisol (UFC) excretion, and plasma corticotropin and cortisol responses to intravenously administered ovine corticotropin-releasing hormone ([CRH] 1 microgram/kg given as a bolus at 8:00 PM). Diabetic patients had significantly elevated 9:00 AM plasma cortisol levels (mean +/- SE, 300.7 +/- 99.3 v 237.3 +/- 99.3 nmol/L, P < .04), higher 24-hour UFC excretion (313.2 +/- 112.6 v 244.2 +/- 69.3 nmol/24 h, P < .02), and greater cortisol responses to CRH infusion (time-integrated values: 49,408.2 +/- 11,289.8 v 40,217.9 +/- 7,228.6 nmol/L.120 min, P < .004; peak cortisol values: 529.7 +/- 107.6 v 438.7 +/- 77.3 nmol/L, P < .002) than controls. UFC excretion values were positively correlated with both 5-year averaged hemoglobin A1c level (P = .03) and total number of insulin units administered per day (P = .03). These results suggest that insulin-dependent diabetic outpatients have mild chronic hypercortisolism, which might influence the control of the disease and play a role in the development of its chronic complications.

Adrenocortical Hyperfunction↗

PubMed1993

Prevention of postasphyxial increase in lipid peroxides and retinal function deterioration in the newborn pig by inhibition of cyclooxygenase activity and free radical generation.

Free radicals have been implicated in the development of injury to the immature retina. Asphyxia increases free radicals as well as prostaglandins (PG) in neural tissues. We assessed whether in the retina the cyclooxygenase pathway contributes to free radical formation after oxidative insults such as asphyxia, which in turn disrupts retinal function. Newborn pigs were treated with either saline, ibuprofen (194 mumol/kg i.v.), or allopurinol (1 mmol/kg i.v.), and retinal malondialdehyde (MDA), hydroperoxides, PGE2 and PGF2 alpha levels, and the amplitudes and implicit times of the a- and b-waves of the full-field electroretinogram were measured before and 1 h after a 5-min period of asphyxia. In saline-treated animals, asphyxia caused a marked increase (p < 0.01) in MDA, hydroperoxides, PGE2, and PGF2 alpha concentrations in the retina. This was associated with a significant decrease (p < 0.01) in the b-wave amplitude measured under scotopic and photopic conditions and an increase in the b-wave implicit times. Ibuprofen and another cyclooxygenase inhibitor, indomethacin (28 mumol/kg i.v.), decreased PGE2 and PGF2 alpha levels and prevented the increase in MDA and hydroperoxides after asphyxia. Allopurinol maintained low concentrations of MDA and hydroperoxides after asphyxia. Both ibuprofen and allopurinol prevented the postasphyxial changes in the b-wave amplitude and diminished the delay in implicit time observed after asphyxia in saline-treated pigs. Our findings suggest that in the retina after asphyxia free radicals appear to originate primarily from the cyclooxygenase pathway and contribute to the deterioration in retinal electrophysiologic function of the newborn animal. Cyclooxygenase inhibitors, like free radical scavengers, may protect retinal function from deteriorating after oxidative stresses.

Allopurinol↗

PubMed1992

Silanized silica bound trypsin as analytical probe.

Trypsin immobilized by covalent coupling to silanized silica shows significant activity (30-38%) and greater thermostability as compared to soluble trypsin. Proteolytic processing of albumin at varying periods suggest that the enzyme matrix can be used efficiently for limited proteolysis. Repeated use of the immobilized enzyme in protein digestion produces similar products as seen by electrophoretic analysis. Also, digestion of albumin by the immobilized enzyme follows similar pattern as that by soluble enzyme. The enzyme matrix can be easily removed from the incubation mixture. The results indicate the possibility of the immobilized enzyme for its effective application as analytical tool in peptide mapping and limited proteolytic processing.

Electrophoresis, Polyacrylamide Gel↗

PubMed1992

Pyroglutamate aminopeptidase in rat submaxillary gland.

A significant amount of pyroglutamate aminopeptidase (PGAP) activity was found to be present in 27,000 x g supernatant of rat submaxillary gland, maximum activity being at pH 6.5. EDTA stimulated the enzyme activity by 95% at pH 8.0 while at pH 6.5 it did not have any significant effect. On comparison of its properties submaxillary PGAP appears to be different from brain, pituitary and other reported PGAPs. Submaxillary PGAP could also catalyze efficiently the formation of cyclo (His-Pro) from TRH. Cyclo (His-Pro) formation by submaxillary enzyme was more pronounced than that by liver PGAP.

Animals↗

PubMed1992

Ocular findings and visual evoked potential response in the Prader-Willi syndrome.

It has recently been suggested that aberrant misrouting of retino-geniculate-cortical (RGC) projections, a finding previously noted only in albinism, may be an additional feature of the Prader-Willi syndrome. To determine the prevalence of ocular abnormalities in patients with the syndrome and to look for evidence of misrouted RGC projections by means of testing of the pattern-onset visual evoked potential (VEP) response, we examined 12 patients with Prader-Willi syndrome, 8 albino subjects and 5 healthy control subjects. Ocular findings in the first group included telecanthus (in five subjects), strabismus, nystagmus, foveal hypoplasia, visual field defects and cataract. However, the VEP asymmetry typically seen in albinism was not noted in any of the patients with Prader-Willi syndrome. Our findings do not support previous claims of abnormal optic nerve fibre decussation in Prader-Willi syndrome.

Adolescent↗

PubMed1991

Color vision and age in a normal North American population.

Color vision is known to change with age. We conducted the Farnsworth-Munsell (FM) 100-Hue and the Lanthony Desaturated Panel D-15 (DD-15) tests in 115 normal North American subjects aged 5-81 years to obtain age-specific norms for these procedures. For each test, color discrimination was best between the ages of 20 and 50 years. Both increasing age and the occurrence of lens changes were significantly associated with increasing 100-Hue error scores. Age-specific norms for the 100-Hue test were comparable with those obtained by Verriest in a European population, but such norms for the DD-15 test are problematic. Our data indicate somewhat greater variability in the DD-15 than in the 100-Hue test.

Adolescent↗

PubMed1990

The oscillatory potentials in response to stimuli of photopic intensities delivered in dark-adaptation: an explanation for the conditioning flash effect.

Previous studies reported that the oscillatory potentials (OPs) evoked to the first flash of a series were always smaller than those produced by the later flashes. This conditioning flash effect (CFE) was suggested to arise from rod inhibition of cone-mediated OPs. We investigated this CFE with the use of two stimulus intensities: 10 cd sec m-2 and 1 cd sec m-2. While the highest intensity did yield the previously reported CFE, the dimmest intensity did not. Our results further indicated that with the brightest stimulus, there is a significant increase in the interpeak interval of the OPs, while dimmest stimuli failed to reveal a similar marked increase. We also noted a significant correlation between the frequency domain of the OPs (as estimated with the interpeak interval) and the amplitude of the OPs (individual or collective: SOPs). Our results would also suggest that the observed CFE could result from a cone inhibition of rod-mediated OPs.

Adaptation, Ocular↗