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Biomedical subjects

G Moore

Publications and source records attributed to G Moore.

At least 127 records · Page 7Linked to original sources

Water movement in the rabbit eye.

The intraocular distribution of topically applied D2O was quantified using deuterium nuclear magnetic resonance (NMR) spectroscopy. D2O appeared in all tissues with the highest concentration in the aqueous humor (1.2 M); however, it rapidly dissipated from the eye. Surface coil NMR spectroscopy on D2O-treated eyes in vivo showed that the flow pattern was best described by a single exponential decay plus a constant. This suggests that the D2O flow consisted of a flow component representing vascular circulation (with a flow rate constant of 0.101 min-1), and a reservoir-like component. Topical D2O in conjunction with the surface-coil NMR technique can be used to examine the movement of water in the anterior segment of the living eye.

Animals↗

A family of retrotransposons and associated genomic variation in wheat.

A family of related retroelements was characterized in the genomes of some Graminease species. The structure of these retroelements indicates that they are retrotransposons containing reading frames with sequence similarity to the polyproteins of copia and Ty. This family of retroelements (termed WIS-2) occurs in the genomes of barley, wheat, rye, oats, and Aegilops species. Ongoing genomic variation both within individual plants of a wheat variety and within and between varieties of wheat is associated with some members of the WIS-2 family.

Amino Acid Sequence↗

BIS 1, a major component of the cereal genome and a tool for studying genomic organization.

We report the cloning and characterization of an element (BIS 1) in barley. Related sequences were also found in wheat and rye genomes. BIS 1-related sequences may be some of the more frequent of the complex repeats in the barley genome, and their dispersion throughout the barley genome suggests that they are capable of both mobility and amplification. BIS 1 sequences have been used to study the gross structure of the barley genome. These studies indicate that the genome may be formed from larger genomic structures of tens of kilobases which may be repeated. Surprisingly, these studies also show that these large genomic structures also occur in similar proportions and at similar size distribution in the wheat genome.

Blotting, Southern↗

Pharmacokinetic and pharmacodynamic comparison of metoprolol CR/ZOK once daily with conventional tablets once daily and in divided doses.

Four studies of identical design, each on 18 young healthy subjects, were undertaken to study the pharmacokinetics and beta 1-receptor blockade at steady state after a once daily dose (od) of 100, 200, 300 and 400 mg of metoprolol CR/ZOK (a new controlled release preparation) in comparison with 100 mg dosages (od, bid, tid and qid, respectively) of conventional metoprolol tablets (CT). All studies were of randomized three-way crossover design with 7-day double-blind treatment periods separated by 7-day single-blind washout periods. A number of predose plasma concentrations and assessments of beta 1-blockade were made during the study and a full pharmacokinetic and pharmacodynamic study was performed on day 7. The maximal plasma concentration, Cmax, was significantly lower after metoprolol CR/ZOK compared to CT after all doses--the most pronounced difference being observed after the 100 mg dose when both preparations were given once daily (145 nmol/L vs 606 nmol/L) and the least difference after the 400 mg dose when metoprolol CT was given every 6 hours (837 nmol/L vs 1111 nmol/L). The maximal plasma concentration occurred later after metoprolol CR/ZOK than CT in all studies (median 2.5-4.1 hours vs 1.0-1.2 hours). The trough plasma concentration, Cmin, was significantly higher after 100 mg metoprolol CR/ZOK compared to CT dosed once daily; CminS were comparable between the two preparations in the 200 mg and 300 mg studies and lower after metoprolol CR/ZOK in the 400 mg study (278 nmol/L vs 469 nmol/L). In all four studies the AUCs were significantly lower after metoprolol CR/ZOK compared to CT with the mean relative bioavailability being approximately similar (73-84%). All metoprolol treatments produced a statistically significant beta 1-blockade (measured as percent reduction of exercise induced tachycardia) throughout the whole day compared to placebo except in the 100 mg study where the effect of once daily CT did not differ from placebo during the last 6 hours. Consequently, a significantly higher beta 1-blockade was observed after metoprolol CR/ZOK compared to CT in this latter period. The maximum beta 1-blockade (Emax) after CR/ZOK 100 mg was significantly lower than after CT 100 mg once daily (12.6% vs 23.3%) but when CT was given in divided doses from 200 to 400 mg daily, Emax did not differ between the two formulations. Once daily administration of 100 mg of both products resulted in a significantly higher beta 1-blockade 24 hours after dosing with CR/ZOK compared to CT, but when CT was taken in divided doses this difference between the treatments was less pronounced.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Acute inhalation toxicity of soman and sarin in baboons.

Adult baboons (Papio sp.; 8-12 kg) were anesthesized with sodium pentobarbital (20 mg/kg iv). The animals were instrumented for measurement of mean blood pressure (MBP), pulmonary artery pressure (PAP), ECG, arterial and mixed venous blood gases, lung volumes, lung pressures, and efferent phrenic nerve activity. Bronchoalveolar lavage (BAL) was performed. Studies were done prior to exposure, at intervals during the first 4 hr postexposure, and at 4 and 28 days after exposure. Control animals received a sham exposure to 2-propanol (N = 5). Soman (pinacolyl methylphosphonofluoridate) at 13.14 micrograms/kg (2 X LD50) was vaporized into the upper airway in a second group of animals (N = 5), and sarin (isopropyl methylphosphonofluoride) 30 micrograms/kg (2 X LD50) was vaporized into a third group of animals (N = 4). Controls showed no change in any parameter either immediately after diluent exposure or during the monitoring period. Soman and sarin produced a decline in MBP and bradyarrhythmias that were reversed with atropine. Apnea occurred in all soman- and sarin-exposed animals within 5 min postexposure, and was associated with absence of phrenic nerve signal. Ventilation was mechanically supported until the animal could maintain normal arterial blood gases during spontaneous breathing. BAL studies revealed an increase in total white cell population and neutrophils at 4 hr in all three groups. There were signs of impaired hemodynamics and persistent lung injury for 4 days that resolved by 28 days after exposure. In conclusion, inhalation of soman and sarin in the baboon is associated with cardiac arrhythmias, development of apnea, and a significant decrease in MBP. Inhalation exposure also resulted in a persistent influx of neutrophils and hypoxemia.

Administration, Inhalation↗

Helping postacute traumatically brain injured clients return to work: three case studies.

This paper presents three case studies of individuals who had sustained a severe brain injury and who are clients of a return to work programme emphasizing a supported employment approach. The case studies illustrate the types of interventions which are utilized, including job placement; job site and off-site training, advocacy, and compensatory strategies; and ongoing assessment and maintenance of social and productive gains in order to assist with job retention. The results of the case studies may be generalized to the population of brain injury survivors who require intensive and long-term intervention and support in order to return to employment.

Adult↗

Adenocarcinoma of the colon occurring with intussusception in an adolescent.

Hydrostatic reduction of intussusception is definitive therapy in most infants with this abnormality. In the older child, adolescent, and adult, a polyp or tumor is often present. Operative intervention should be considered earlier in the clinical course both to relieve the intussusception and to define the nature of the lead point.

Adenocarcinoma↗

Multiple tandem 18-kb sequences clustered in the region of the acute promyelocytic leukemia breakpoint on chromosome 17.

This paper describes the cloning of an 18-kb sequence present in approximately 30 copies on chromosome 17. Most of these are clustered in the region of the breakpoint associated with acute promyelocytic leukemia (APL). These copies map both above and below the breakpoint, and pulsed field gel analysis indicates that the majority of these sequences lie within a region of approximately 2 megabases. The organization of these sequences appears to be that of large imperfect palindromes.

Animals↗

Polysplenia and jejunal atresia with agenesis of the dorsal mesentery.

Polysplenia syndrome has been well described. It is associated with gastrointestinal atresia in patients with situs inversus abdominus; however, it appears that this case represents the first occurrence of polysplenia with jejunal atresia having agenesis of the dorsal mesentery and partial situs inversus abdominus.

Abnormalities, Multiple↗

Dorsal dislocation of four metacarpophalangeal joints.

We report the case of a 23-year-old man who fell from a third-floor window and injured his left hand. Physical examination and radiographic evaluation revealed open dorsal metacarpophalangeal dislocation of four fingers. The index finger dislocation was reduced in the emergency department, and the other three fingers responded to closed reduction during surgery. The patient made an uneventful recovery without complications. Metacarpophalangeal dislocations are unusual, with multiple dislocations rarely described.

Accidental Falls↗

Utilisation of acute hospitals by age and sex in Australia, 1985.

This paper provides estimates of the utilisation rates of acute care (short-stay) hospitals, by age and sex, for the Australian population. Separation and bed-day rates per 1000 persons for public, Repatriation and private hospitals in 1985 have been estimated by age group, for each sex, in each State and Territory in Australia. The Australian Base Grant, negotiated between the Commonwealth, States and Territories in the new Medicare Agreements, distributes funds for the care and treatment of Medicare patients in public hospitals. The national bed-day utilisation rates reported in this article, have been used as the basis for population weights to allocate these funds. This paper presents the data and methods used to derive these weights, and examines the differences between them and the actual State and Territory utilisation patterns in 1985. The impact of population ageing on the overall utilisation rates for acute hospitals in Australia is examined.

Adolescent↗

Linkage analysis of chromosome 17 markers in British and South African families with neurofibromatosis type I.

Nine markers from the pericentromeric region of chromosome 17 were typed in 16 British and five South African families with neurofibromatosis type 1 (NF1). The markers--p17H8, pHHH202, and EW204--were linked to NF1 at recombination fractions less than 1%. No evidence of locus heterogeneity was detected. Inspection of recombinant events in families informative for several markers suggests that the NF1 gene is located between the markers EW301 (cen-p11.2) and EW206 (cen-q12) and possibly distal to pHHH202 (q11.2-q12).

Chromosomes, Human, Pair 17↗

Construction of a genetic map of human chromosome 17 by use of chromosome-mediated gene transfer.

We used somatic-cell hybrids, containing as their only human genetic contribution part or all of chromosome 17, as donors for chromosome-mediated gene transfer. A total of 54 independent transfectant clones were isolated and analyzed by use of probes or isoenzymes for greater than 20 loci located on chromosome 17. By combining the data from this chromosome-mediated gene transfer transfectant panel, conventional somatic-cell hybrids containing well-defined breaks on chromosome 17, and in situ hybridization, we propose the following order for these loci: pter-(TP53-RNP2-D17S1)-(MYH2-MYH1)-D17Z 1-CRYB1-(ERBA1-GCSF-NGL)-acute promyelocytic leukemia breakpoint-RNU2-HOX2-(NGFR-COLIAI-MPO)-GAA-UM PH-GHC-TK1-GALK-qter. Using chromosome-mediated gene transfer, we have also regionally localized the random probes D17S6 to D17S19 on chromosome 17.

Animals↗

Molecular approaches to dysmorphology.

The biochemical and physiological defects underlying human dysmorphic syndromes can now be approached using techniques of molecular biology. The genetic component of the causation of the dysmorphology can be studied in isolation from the environmental component by using large, rare families which exhibit the same phenotype as more complex multifactorial disorders, but inherit the mutation in a monogenic fashion. Such an analysis starts with the determination of linkage to a gene probe, followed by the use of newer techniques of molecular biology to enable cloning and sequencing of the mutated gene. Analysis of the gene product by amino acid sequence homology to other known proteins, and tissue specific expression, may place the defect within the cascade of events associated with development and differentiation. Once cloned, the gene can also be manipulated in transgenic laboratory animals and the effect of its mutation studied directly. The use of techniques of molecular biology to study the genetic aspects of dysmorphic syndromes will allow insight to be gained both into normal fetal development and into the causes of congenital malformations.

Animals↗

The application of molecular genetics to detection of craniofacial abnormality.

Congenital malformations such as secondary cleft palate can be exclusively monogenic or polygenic, but most cases have a multifactorial origin involving both environmental and genetic factors, making genetic analysis difficult. The new techniques of molecular genetics have allowed the successful chromosomal localization of mutant genes in disorders that show a simple Mendelian segregation, whether autosomal dominant (e.g. Huntington's disease), autosomal recessive (cystic fibrosis) or X-linked (Duchenne muscular dystrophy). Recently, a large Icelandic family (over 280 members) with X-linked secondary cleft palate and ankyloglossia (tongue-tied) has been used as a model to localize the mutant gene associated with this craniofacial clefting. The gene has been sub-chromosomally localized to Xq13-q21.1, using anonymous probe DXYS1; a LOD score of 3.07 was obtained. We are preparing cosmid libraries from DNA from mouse cell lines containing only the relevant part of the human X chromosome, introduced by chromosome-mediated gene transfer. Cosmids that contain human X-chromosome sequences will be isolated and analysed for overlapping sequences and RFLPs (restriction fragment length polymorphisms) and the regions further defined by pulsed-field gel electrophoresis and the identification of coding sequences. This should give data on the location and structure of a gene involved in the craniofacial development of the human palatine shelves. This gene, and its protein product, will identify one component of the pathway that causes nonfusion of the palate. In the long term, the understanding of the expression of this sex-linked gene for secondary cleft palate and ankyloglossia will provide a model for the molecular identification of other genes regulating processes in craniofacial development whose expression is hidden in phenotypic, polygenic complexity.

Cleft Palate↗

Progress towards construction of a total restriction fragment map of a human chromosome.

We present an approach to the construction of an overlapping restriction fragment map of a single human chromosome. A genomic cosmid library genome was constructed from a mouse-human hybrid cell line containing chromosome 17 as its only human genetic component. Cosmids containing human inserts were isolated by hybridisation to a human Alu sequence. DNAs from ninety-six randomly chosen cosmids were digested with either EcoRI or HindIII, end-labelled with 35S-dATP and analysed using agarose gel electrophoresis. Comparison of the restriction fragment patterns revealed two pairs of overlapping clones, that were confirmed by cross-hybridization of the overlapping fragments. The two pairs of cosmids both mapped to human chromosome 17, as shown by hybridization to a panel of somatic cell hybrids. These data demonstrate that the generation of an overlapping cosmid map along a human chromosome is feasible, representing an intermediate step towards the complete sequencing of a human chromosome.

Animals↗