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1.
J Mech Behav Biomed Mater ; 95: 96-102, 2019 07.
Article in English | MEDLINE | ID: mdl-30986757

ABSTRACT

Artificial composites inspired from biological materials such as nacre and bone has a staggered structure of hard inclusions surrounded by a soft interface. These composites possess an excellent combination of strength, toughness and stiffness. These properties depends on a critical value of overlap ratio of inclusions, and hence is one of major parameters in the design of bio-inspired composites. Randomness in material and geometrical parameters could exist in such composites. In this work, the randomness in various parameters are considered, and using probabilistic methods, the critical overlap ratio is found out. This is done for two dimensional, and three dimensional inclusions. For the three dimensional case, due to unavailability of the analytical solution, high dimensional model representation technique in conjunction with finite element analysis is done to find out the critical overlap ratio. To determine the probability of failure for two dimensional as well as three dimensional cases, Monte Carlo Simulation is used. Finally, based on the study a factor of safety is proposed for the critical stress intensity factor which could be used in design to account for uncertainties in the various parameters.


Subject(s)
Biomimetic Materials , Mechanical Phenomena , Finite Element Analysis , Materials Testing , Probability
2.
Sci Rep ; 6: 24292, 2016 Apr 12.
Article in English | MEDLINE | ID: mdl-27068682

ABSTRACT

Sex differences in locomotor performance may precede the onset of sexual maturity and/or arise concomitantly with secondary sex characteristics. Here, we present the first study to quantify the terrestrial locomotor morphology, energetics and kinematics in a species, either side of sexual maturation. In domestic leghorn chickens (Gallus gallus domesticus) sexual maturation brings about permanent female gravidity and increased male hind limb muscle mass. We found that the sexes of a juvenile cohort of leghorns shared similar maximum sustainable speeds, while in a sexually mature cohort maximum sustainable speeds were greater by 67% (males) and 34% (females). Furthermore, relative to that in juveniles of the same sex, the absolute duration of leg swing was longer in mature males and shorter in mature females. Consequently, the proportion of a stride that each limb was in contact with the ground (duty factor) was higher in sexually mature females compared to males. Modulation of the duty factor with the development of secondary sex characteristics may act to minimize mechanical work in males; and minimise mechanical power and/or peak force in females. A greater incremental response of mass-specific metabolic power to speed in males compared to females was common to both age cohorts and, therefore, likely results from physiological sexual dimorphisms that precede sexual maturation.


Subject(s)
Chickens/anatomy & histology , Chickens/growth & development , Locomotion , Sex Characteristics , Animals , Biomechanical Phenomena , Energy Metabolism , Female , Male
3.
Eye (Lond) ; 27(12): 1353-8, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24008929

ABSTRACT

BACKGROUND/AIMS: To estimate the prevalence of myopia based on reduced unaided visual acuity (VA) in Chinese school children over the past 20 years. METHODS: Guangzhou school health authorities have measured VA on Grade 1-12 students from 1988 to 2007 annually, using a LogMAR tumbling E chart. VA is reported as Snellen categories: normal (VA ≥ 6/6), mildly reduced (6/9 < VA <6/6), moderately reduced (6/18 < VA ≤ 6/9), and severely reduced VA (VA ≤ 6/18). RESULTS: In 1988, over 80% of children in Grade 1 (age 6 years) and about 30% in Grade 12 (age 17 years) had normal unaided VA. By 2007, this dropped to only 60% in Grade 1 and about 10% in Grade 12. Conversely, the prevalence of moderately and severely reduced unaided VA increased from 6.2% in Grade 1 and 62.5% in Grade 12 in 1988 to 14.5% in Grade 1 and 84.11% in Grade 12 in 2007. This rate was unchanged from 2003 to 2007 at both the Grade 1 and Grade 12 levels. CONCLUSIONS: In Guangzhou, the prevalence of reduced unaided VA has increased markedly in the past 20 years, but has stabilized in the past few years. This increase may result from environmental changes, such as increased schooling intensity and urbanization.


Subject(s)
Myopia/epidemiology , Vision Disorders/epidemiology , Visual Acuity , Adolescent , Asian People , Child , Child, Preschool , China/epidemiology , Female , Humans , Male , Myopia/physiopathology , Prevalence , Vision Disorders/physiopathology , Visual Acuity/physiology
4.
Aust Vet J ; 90(12): 505-9, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23186095

ABSTRACT

Epizootics of sudden death in tammar wallabies (Macropus eugenii) occurred at six research facilities and zoological gardens in New South Wales, Australia, in late 1998 and at one Queensland research facility in March 1999. There were 120 confirmed tammar wallaby deaths during this period; however, population censuses indicated that up to 230 tammar wallabies may have died. The majority of animals died without premonitory signs. A small proportion of wallabies exhibited increased respiratory rate, sat with a lowered head shortly before death or were discovered in lateral recumbency, moribund and with muscle fasciculations. Gross postmortem findings consistently included massive pulmonary congestion, mottled hepatic parenchyma and subcutaneous oedema throughout the hindlimbs and inguinal region. Approximately 30% of the animals examined also had extensive haemorrhage within the fascial planes and skeletal muscle of the hindlimb adductors, inguinal region, ventral thorax, dorsal cervical region and perirenal retroperitoneal area. The tissues of affected animals became autolytic within a short period after death. Bacteriological examination of tissues from 14 animals did not provide any significant findings. Toxicological examination of the gastric and colonic contents of four animals did not reveal evidence of brodifacoume or other rodenticides. Viruses from the Eubenangee serogroup of the Orbivirus genus were isolated from the cerebral cortex of nine, and the myocardium of two, tammar wallabies and the liver and intestine of another tammar wallaby. A similar orbivirus was also isolated from the cerebrospinal fluid of another tammar wallaby that died suddenly. The disease agent appears to be a previously unrecognised orbivirus in the Eubenangee serogroup. This is the first report of epizootics of sudden deaths in tammar wallabies apparently associated with an orbivirus infection.


Subject(s)
Macropodidae/virology , Orbivirus , Reoviridae Infections/veterinary , Animals , Animals, Zoo , Death, Sudden/veterinary , Female , Male , New South Wales/epidemiology , Reoviridae Infections/diagnosis , Reoviridae Infections/mortality
5.
Eye (Lond) ; 26(7): 925-32, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22498798

ABSTRACT

PURPOSE: To establish standardised protocols for vision screening, testability and comparability of three different vision tests were examined in a population-based, cross-sectional sample of preschool children (Sydney Paediatric Eye Disease Study). METHODS: Measurement of presenting monocular distance visual acuity (VA) using the Amblyopia Treatment Study (ATS) HOTV protocol, was attempted by all (1774) children aged≥24 months. In addition, in children aged≥60 months (576), VA was also tested using the logMAR retro-illuminated HOTV or Early Treatment Diabetic Retinopathy Study (ETDRS) linear charts (CSV 1000). Children able to have both eyes tested monocularly were considered. RESULTS: Testability significantly increased with age for all VA tests. The ATS HOTV with an overall testability of 80% (females: 82%, males: 78%) was the most testable of the VA tests (P<0.0001). In children aged <3 years testability was low (≤47%) rising to≥80% in children aged≥3. In children≥60 months, testability was higher for the HOTV (94%) than the ETDRS (59%) chart. In those that did two VA tests, mean difference of the ATS HOTV compared with the HOTV(CSV) was -0.1, and compared with ETDRS was -0.12 (P<0.0001). CONCLUSIONS: Children aged <3 years had poor VA testability, whereas those 3 years and above were highly testable using the ATS HOTV. The HOTV (CSV) retro-illuminated test was appropriate for children aged >5 years, and may be possible in younger children with early educational exposure. When comparing VA measures using these tests, the higher VA attained using the ATS HOTV, needs to be taken into account.


Subject(s)
Vision Disorders/diagnosis , Vision Screening/methods , Visual Acuity , Australia , Child, Preschool , Cross-Sectional Studies , Female , Humans , Male , Reproducibility of Results
6.
J Hum Hypertens ; 26(6): 350-6, 2012 Jun.
Article in English | MEDLINE | ID: mdl-21614023

ABSTRACT

Very few studies have explored links between physical activity, sedentary behaviours and blood pressure (BP) in early adolescence. We aimed to assess the association between a range of sedentary activities (screen time, television (TV) viewing, computer usage, video game usage and time spent in homework or reading) and BP in schoolchildren. Eligible year-7 students (2353/3144, mean age 12.7 years) from a random cluster sample of 21 Sydney schools were examined during 2003-2005. Parents and children completed detailed questionnaires of activity. BP was measured using a standard protocol and high BP was defined using published guidelines. Height and weight were measured, and body mass index (BMI) calculated. After adjusting for age, sex, ethnicity, parental education, height, BMI and time spent in physical activity, each hour per day spent in screen time, watching TV and playing video games was associated with a significant increase in diastolic BP of 0.44 (P=0.0001), 0.99 (P<0.0001) and 0.64 mm Hg (P=0.04), respectively. In contrast, each hour per day spent reading was associated with a decrease of 0.91 (P=0.01) and 0.69 mm Hg (P=0.02) in systolic and diastolic BP, respectively. Our results indicate that addressing different types of sedentary activities could be a potentially important strategy to reduce the prevalence of elevated BP in children.


Subject(s)
Blood Pressure , Exercise , Body Mass Index , Child , Child Behavior , Female , Humans , Male , Reading , Sedentary Behavior , Television
7.
Br J Ophthalmol ; 93(8): 997-1000, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19211608

ABSTRACT

AIM: To investigate the relationship of outdoor activities and myopia in Singapore teenage children. METHODS: Teenage children (1249 participants), examined in the Singapore Cohort study Of Risk factors for Myopia (SCORM), during 2006 were included in analyses. Participants completed questionnaires that quantified total outdoor activity, and underwent an eye examination. RESULTS: The mean total time spent on outdoor activity was 3.24 h/day. The total outdoor activity (h/day) was significantly associated with myopia, odds ratio 0.90 (95% CI 0.84 to 0.96) (p = 0.004), after adjusting for age, gender, ethnicity, school type, books read per week, height, parental myopia, parental education and intelligence quotient. In addition, the total time spent outdoors was associated with significantly less myopic refraction (regression coefficient = 0.17; CI 0.10 to 0.25, p<0.001) and shorter axial length (regression coefficient -0.06 (CI -0.1 to -0.03, p<0.001). Total sports was also significantly negatively associated with myopia (p = 0.008) but not indoor sports (p = 0.16). CONCLUSIONS: Participants who spent more time outdoors were less likely to be myopic. Thus, outdoor activity may protect against development of myopia in children, supporting recent Australian data. As near work did not predict outdoor activity, this can be viewed as an independent factor and not merely the reciprocal of near work.


Subject(s)
Leisure Activities , Myopia/prevention & control , Sports/statistics & numerical data , Adolescent , Age Factors , Child , Female , Humans , Male , Myopia/epidemiology , Sex Factors , Singapore/epidemiology , Time Factors , Young Adult
8.
Eye (Lond) ; 22(5): 649-56, 2008 May.
Article in English | MEDLINE | ID: mdl-17277756

ABSTRACT

PURPOSE: To examine the prevalence of refractive error and distribution of ocular biometric parameters among major ethnic groups in a population-based sample of 11-15-year-old Australian children. METHODS: The Sydney Myopia Study examined 2353 students (75.3% response) from a random cluster-sample of 21 secondary schools across Sydney. Examinations included cycloplegic autorefraction, and measures of corneal radius of curvature, anterior chamber depth, and axial length. RESULTS: Participants mean age was 12.7 years (range 11.1-14.4); 49.4% were female. Overall, 60.0% of children had European Caucasian ethnicity, 15.0% East Asian, 7.1% Middle Eastern, and 5.5% South Asian. The most frequent refractive error was mild hyperopia (59.4%, 95% confidence interval (CI), 53.2-65.6), defined as spherical equivalent (SE) +0.50 to +1.99 D. Myopia (SE-0.50 D or less) was found in 11.9%, 95% (CI 6.6-17.2), and moderate hyperopia (SE> or =+2.00 D) in 3.5%, 95% (CI 2.8-4.1). Myopia prevalence was lower among European Caucasian children (4.6%, 95% CI 3.1-6.1) and Middle Eastern children (6.1%, 95% CI 1.3-11.0) than among East Asian (39.5%, 95%, CI 25.6-53.5) and South Asian (31.5%, 95%, CI 21.6-41.4) children. European Caucasian children had the most hyperopic mean SE (+0.82 D) and shortest mean axial length (23.23 mm). East Asian children had the most myopic mean SE (-0.69 D) and greatest mean axial length (23.86 mm). CONCLUSION: The overall myopia prevalence in this sample was lower than in recent similar-aged European Caucasian population samples. East Asian children in our sample had both a higher prevalence of myopia and longer mean axial length.


Subject(s)
Biometry , Refraction, Ocular/physiology , Refractive Errors/ethnology , Adolescent , Child , Cornea/pathology , Cross-Sectional Studies , Ethnicity , Female , Humans , Male , New South Wales/epidemiology , Prevalence , Refractive Errors/epidemiology
9.
Eye (Lond) ; 22(4): 496-502, 2008 Apr.
Article in English | MEDLINE | ID: mdl-17384576

ABSTRACT

AIMS: To report prevalence of amblyopia and long-term impact of its treatment on vision in a population-based sample of 12-year-old Australian children. METHODS: Logarithm of minimum angle of resolution (logMAR) visual acuity (VA) was measured in 2353 children (response rate 75.3%); visual impairment was defined as VA<6/12. Amblyopia was defined using various criteria of best-corrected VA, together with an amblyogenic factor and absence of significant organic pathology. Corroborative historical data on previous diagnosis and treatment were obtained from parental questionnaires. RESULTS: Forty-four children (1.9%) were diagnosed with amblyopia, unilateral in 40 and bilateral in four. Isolated anisometropia was the most frequent cause (41%), followed by strabismus (25%), combined anisometropia and strabismus (23%), and high ametropia (9%). Myopia, hyperopia, and astigmatism were present in 28, 51, and 44% of amblyopic children, respectively, compared to 12, 4, and 9% of non-amblyopic children. Mean best-corrected VA in amblyopic eyes was 44.5 logMAR letters (Snellen equivalent 6/9), range: 11-60 letters. Most children with amblyopia (84%) had been treated. Only 27% were visually impaired in their amblyopic eye. CONCLUSIONS: This report documents a low amblyopia prevalence in a population of 12-year-old Australian children. Amblyopic visual impairment was infrequent in this sample despite absence of mandatory vision screening.


Subject(s)
Amblyopia/complications , Vision Disorders/etiology , Amblyopia/epidemiology , Amblyopia/physiopathology , Anisometropia/complications , Anisometropia/epidemiology , Child , Female , Humans , Male , New South Wales/epidemiology , Prevalence , Strabismus/complications , Strabismus/epidemiology , Vision Disorders/epidemiology , Vision Disorders/physiopathology , Visual Acuity
10.
Br J Ophthalmol ; 90(5): 597-601, 2006 May.
Article in English | MEDLINE | ID: mdl-16622090

ABSTRACT

AIM: To study the distribution of anisometropia and aniso-astigmatism in young Australian children, together with clinical and ocular biometry relations. METHOD: The Sydney Myopia Study examined 1765 predominantly 6 year old children from 34 randomly selected Sydney schools during 2003-4. Keratometry, cycloplegic autorefraction, and questionnaire data were collected. RESULTS: Spherical equivalent (SE) anisometropia (> or =1 dioptre) prevalence was 1.6% (95% confidence interval (CI) 1.1% to 2.4%). Aniso-astigmatism (>or =1D) prevalence was 1.0% (CI: 0.6% to 1.6%). Both conditions were significantly more prevalent among moderately hyperopic (SE > or =2.0D) than mildly hyperopic (SE 0.5-1.9D) children. Myopic children (SE < or =-0.5D) had higher anisometropia prevalence. Neither condition varied by age, sex, or ethnicity. In multivariate analyses, anisometropia was significantly associated with amblyopia, odds ratio (OR) 29, (CI: 8.7 to 99), exotropia (OR 7.7, CI: 1.2 to 50), and neonatal intensive care unit (NICU) admission (OR 3.6, CI: 1.1 to 12.6). Aniso-astigmatism was significantly associated with amblyopia (OR 8.2, CI: 1.4 to 47), maternal age >35 years (OR 4.0, CI: 1.3 to 11.9), and NICU admission (OR 4.6, CI: 1.2 to 17.2). Anisometropia resulted from relatively large interocular differences in axial length (p<0.0001) and anterior chamber depth (p = 0.0009). Aniso-astigmatism resulted from differences in corneal astigmatism (p<0.0001). CONCLUSION: In this predominantly 6 year old population, anisometropia and aniso-astigmatism were uncommon, had important birth and biometry associations, and were strongly related to amblyopia and strabismus.


Subject(s)
Anisometropia/epidemiology , Astigmatism/epidemiology , Amblyopia/complications , Anisometropia/complications , Anisometropia/pathology , Astigmatism/complications , Astigmatism/pathology , Australia/epidemiology , Birth Weight , Child , Developmental Disabilities/complications , Epidemiologic Methods , Ethnicity , Exotropia/complications , Eye/pathology , Female , Humans , Hyperopia/complications , Infant, Newborn , Infant, Premature , Male , Maternal Age , Multiple Birth Offspring
12.
Ann Acad Med Singap ; 33(4): 541-3; author reply 543; discussion 544, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15344259
13.
Science ; 293(5530): 657-60, 2001 Jul 27.
Article in English | MEDLINE | ID: mdl-11474103

ABSTRACT

Planning and decision-making can be improved by access to reliable forecasts of ecosystem state, ecosystem services, and natural capital. Availability of new data sets, together with progress in computation and statistics, will increase our ability to forecast ecosystem change. An agenda that would lead toward a capacity to produce, evaluate, and communicate forecasts of critical ecosystem services requires a process that engages scientists and decision-makers. Interdisciplinary linkages are necessary because of the climate and societal controls on ecosystems, the feedbacks involving social change, and the decision-making relevance of forecasts.


Subject(s)
Ecosystem , Forecasting , Agriculture , Animals , Decision Making , Disease Outbreaks , Ecology , Epidemiology , Humans , Policy Making , Population Growth , Stochastic Processes
14.
J Manipulative Physiol Ther ; 22(8): 523-9, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10543582

ABSTRACT

OBJECTIVE: To determine to what degree chiropractic clinics are complying with the Americans with Disabilities Act (ADA), which mandates that health care clinics be accessible to the disabled. METHODS: A survey was developed and mailed to 200 chiropractic clinics in Orange and Los Angeles counties. The survey asked about the essential necessities for health care clinics to be accessible to the wheelchair-bound, the blind, and the deaf. It also sought to discover how many disabled patients these clinics were treating and the attitudes of practitioners and staff toward this population. RESULTS: The response rate was 50.5%. Accessibility for the wheelchair-bound was high. Accessibility for the blind was limited by a lack of Braille signs. Accessibility to the deaf was limited by lack of telecommunications device for the deaf or use of sign language interpreters. Most clinics were treating few or no disabled patients and did not perceive a need to become more accessible. CONCLUSION: There appears to be poor compliance with the ADA in chiropractic clinics in Los Angeles and Orange counties. Although data are lacking, it appears likely that the disabled population is being underserved by the chiropractic profession. Education for chiropractors on the rights and needs of the disabled population is necessary to give this group equal access to chiropractic health care.


Subject(s)
Chiropractic/statistics & numerical data , Disabled Persons , Health Services Accessibility/statistics & numerical data , Attitude of Health Personnel , Blindness , California , Deafness , Health Care Surveys , Humans , Surveys and Questionnaires , Wheelchairs
15.
Aust N Z J Ophthalmol ; 25 Suppl 1: S61-3, 1997 May.
Article in English | MEDLINE | ID: mdl-9267628

ABSTRACT

In the cat optic nerve a lesion was induced by brief application of pressure. It selectively blocked impulse conduction in large diameter fibres of the retinal ganglion cells. Electrophysiological examination of single optic axons several weeks later demonstrated a gross alteration of the visual properties of the affected BT/Y ganglion cells. It is suggested that the alteration of receptive field properties may reflect the cellular and dendritic response to distant focal injury of the axon.


Subject(s)
Optic Nerve/physiopathology , Retinal Ganglion Cells/physiology , Visual Fields , Visual Pathways/physiopathology , Visual Perception/physiology , Animals , Axons/physiology , Cats , Electric Stimulation , Electrophysiology/methods , Pressure
16.
Aust N Z J Ophthalmol ; 25 Suppl 1: S91-3, 1997 May.
Article in English | MEDLINE | ID: mdl-9267638

ABSTRACT

A glaucoma screening device based on the visibility of the spatial frequency doubled (FD) illusion will be marketed by Welch Allyn Ltd in the next year (ANU Patients (Australia) 611,585, (USA) 5,065,767 and application PL 3130). An underlying assumption of the method is that retinal processes are being tested. To test this assumption we compared the visibility of the FD illusion over a range of conditions and in the same spatial locations as a multi-region pattern electroretinogram (PERG). Grating speed and contrast were good predictors of the psychometric functions and PERG amplitude and phase.


Subject(s)
Electroretinography , Retina/physiology , Space Perception/physiology , Humans , Pattern Recognition, Visual , Predictive Value of Tests , Random Allocation , Retinal Ganglion Cells/physiology
17.
Aust N Z J Ophthalmol ; 25 Suppl 1: S94-7, 1997 May.
Article in English | MEDLINE | ID: mdl-9267639

ABSTRACT

It has been proposed that the spatial frequency doubled (FD) illusion may originate from Y-like non-linear retinal ganglion cells. If the contrast of multi-frequency stimuli is increased, Y cells show a phase advance in the self-sum frequencies but not in other output frequencies. We looked for these effects with a multi-region pattern electroretinogram (PERG) displaying the sum of two temporal frequencies in each visual field location. Regional variation was found in the recorded sum and difference frequencies. The results indicate that PERG signals become dominated by responses from Y-like cells when the FD illusion is seen.


Subject(s)
Electroretinography , Retina/physiology , Contrast Sensitivity/physiology , Humans , Pattern Recognition, Visual , Photic Stimulation , Regression Analysis , Retinal Ganglion Cells/physiology , Visual Pathways/physiology
18.
Proc Natl Acad Sci U S A ; 94(10): 4925-30, 1997 May 13.
Article in English | MEDLINE | ID: mdl-9144166

ABSTRACT

Steroids produced locally in brain (neurosteroids), including dehydroepiandrosterone (DHEA), influence cognition and behavior. We previously described a novel cytochrome P450, Cyp7b, strongly expressed in rat and mouse brain, particularly in hippocampus. Cyp7b is most similar to steroidogenic P450s and potentially could play a role in neurosteroid metabolism. To examine the catalytic activity of the enzyme mouse Cyp7b cDNA was introduced into a vaccinia virus vector. Extracts from cells infected with the recombinant showed NADPH-dependent conversion of DHEA (Km, 13.6 microM) and pregnenolone (Km, 4.0 microM) to slower migrating forms on thin layer chromatography. The expressed enzyme was less active against 25-hydroxycholesterol, 17beta-estradiol and 5alpha-androstane-3beta,17beta-diol, with low to undetectable activity against progesterone, corticosterone, and testosterone. On gas chromatography and mass spectrometry of the Cyp7b metabolite of DHEA the retention time and fragmentation patterns were identical to those obtained with authentic 7alpha-hydroxy DHEA. The reaction product also comigrated on thin layer chromatography with 7alpha-hydroxy DHEA but not with 7beta-hydroxy DHEA; when [7alpha-3H]pregnenolone was incubated with Cyp7b extracts the extent of release of radioactivity into the medium suggested that hydroxylation was preferentially at the 7alpha position. Brain extracts also efficiently liberated tritium from [7alpha-3H]pregnenolone and converted DHEA to a product with a chromatographic mobility indistinguishable from 7alpha-hydroxy DHEA. We conclude that Cyp7b is a 7alpha-hydroxylase participating in the synthesis, in brain, of neurosteroids 7alpha-hydroxy DHEA, and 7alpha-hydroxy pregnenolone.


Subject(s)
17-alpha-Hydroxypregnenolone/metabolism , Brain/enzymology , Cytochrome P-450 Enzyme System/metabolism , Dehydroepiandrosterone/analogs & derivatives , Steroid Hydroxylases , 17-alpha-Hydroxypregnenolone/analogs & derivatives , Animals , Cytochrome P-450 Enzyme System/biosynthesis , Cytochrome P450 Family 7 , DNA, Complementary , Dehydroepiandrosterone/metabolism , Genetic Vectors , HeLa Cells , Hippocampus/enzymology , Humans , Kinetics , Mice , Rats , Recombinant Proteins/biosynthesis , Recombinant Proteins/metabolism , Substrate Specificity , Transfection , Vaccinia virus
19.
J Biol Chem ; 270(50): 29739-45, 1995 Dec 15.
Article in English | MEDLINE | ID: mdl-8530364

ABSTRACT

hct-1 (hippocampal transcript) was detected in a differential screen of a rat hippocampal cDNA library. Expression of hct-1 was enriched in the formation but was also detected in rat liver and kidney, though at much lower levels; expression was barely detectable in testis, ovary, and adrenal. In liver, unlike brain, expression was sexually dimorphic; hepatic expression was greatly reduced in female rats. In mouse, brain expression was widespread, with the highest levels being detected in corpus callosum; only low levels were detected in liver. Sequence analysis of rat and mouse hct-1 cDNAs revealed extensive homologies with cytochrome P450s (CYPs), a diverse family of heme-binding monooxygenases that metabolize a range of substrates including steroids, fatty acids, and xenobiotics. Among the CYPs, hct-1 is most similar (39% at the amino acid sequence) to cholesterol 7 alpha-hydroxylase (CYP7) and contains a postulated steroidogenic domain present in other steroid-metabolizing CYPs but clearly represents a type of CYP not previously reported. Genomic Southern analysis suggests that a single gene corresponding to hct-1 is present in mouse, rat, and human. hct-1 is unusual in that, unlike all other CYPs described, the primary site of expression is in the brain. Similarity to CYP7 and other steroid-metabolizing CYPs may argue that hct-1 (CYP7B) plays a role in steroid metabolism in brain, notable because of the documented ability of brain-derived steroids (neurosteroids) to modulate cognitive function in vivo.


Subject(s)
Brain/enzymology , Cytochrome P-450 Enzyme System/biosynthesis , Liver/enzymology , Steroid Hydroxylases , Amino Acid Sequence , Animals , Base Sequence , Blotting, Southern , Cholesterol 7-alpha-Hydroxylase/chemistry , Corpus Callosum/enzymology , Cytochrome P-450 Enzyme System/chemistry , Cytochrome P-450 Enzyme System/genetics , Cytochrome P450 Family 7 , DNA, Complementary , Female , Gene Expression , Gene Library , Hippocampus/enzymology , Humans , In Situ Hybridization , Male , Mice , Molecular Sequence Data , Organ Specificity , RNA, Messenger/analysis , RNA, Messenger/biosynthesis , Rats , Rats, Inbred Strains , Sequence Homology, Amino Acid , Sex Characteristics , Substrate Specificity , Transcription, Genetic
20.
J Virol Methods ; 55(3): 303-7, 1995 Nov.
Article in English | MEDLINE | ID: mdl-8609196

ABSTRACT

The usefulness of identification of hepatitis C virus (HCV) genotype has recently been investigated for the clinical management of patients infected by HCV. In the present study, the HCV genotype infecting 127 patients was determined by two different methods: HCV genotyping using a dot-blot assay with type-specific probes derived from the 5'-UTR of HCV genome and HCV serotyping using an ELISA system in which type-specific antibodies against the NS4 region were detected. Overall, a good correlation of the two methods was observed, the main discrepancy being 4 patients with sequence-confirmed HCV-2 (2 cases) and HCV-3 (2 cases) genotypes recognized as HCV-1 by serotyping. Mixed infections were not detected by either method. In 19 PCR negative sera, in which the HCV genotype could not be evaluated, no particular serotype profile was observed. In conclusion, the molecular and serological techniques are almost equivalent in determining the viral type, although in individual cases, especially in PCR negative patients, the clinical meaning of the serotyping result remains to be determined.


Subject(s)
Enzyme-Linked Immunosorbent Assay/methods , Hepacivirus/classification , Hepatitis C Antibodies/blood , Hepatitis C/virology , Immunoblotting/methods , Serotyping/methods , Base Sequence , DNA, Viral/blood , DNA, Viral/genetics , Genotype , Hepacivirus/genetics , Hepacivirus/immunology , Hepacivirus/isolation & purification , Hepatitis C/blood , Hepatitis C/immunology , Hepatitis C Antibodies/immunology , Humans , Molecular Sequence Data , Sensitivity and Specificity , Viral Nonstructural Proteins/immunology
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