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Biomedical subjects

S J Phillips

Publications and source records attributed to S J Phillips.

At least 37 records · Page 2Linked to original sources

TTF-2, a new forkhead protein, shows a temporal expression in the developing thyroid which is consistent with a role in controlling the onset of differentiation.

Expression of thyroglobulin (Tg) and thyroperoxidase (TPO) genes in thyroid follicular cells occurs in the mouse at embryonic day (E)14.5. Two transcription factors, TTF-1 and Pax-8, have been implicated in transcriptional activation of Tg and TPO, even though the onset of their expression is at E9.5, suggesting that additional events are necessary for transcriptional activation of Tg and TPO genes. We report in this paper the cloning of TTF-2, a DNA binding protein that recognizes sites on both Tg and TPO promoters. TTF-2 is a new forkhead domain-containing protein whose expression is restricted to the endodermal lining of the foregut and to the ectoderm that will give rise to the anterior pituitary. TTF-2 shows transient expression in the developing thyroid and anterior pituitary. In the thyroid, TTF-2 expression is down-regulated just before the onset of Tg and TPO gene expression, suggesting that this transcription factor plays the role in development of a negative controller of thyroid-specific gene expression.

Amino Acid Sequence↗

Mapping and retinal phenotype of the hugger mutation in the mouse.

Hugger, hug, is a recessively expressed mutation in mice that features mildly abnormal locomotion, not yet explained, and a unique combination of developmental and degenerative retinal abnormalities. Analysis with the efficient MEV linkage testing stock established that hug is on mouse Chr 19 about 14 cM from th centromere, between the microsatellite markers D19Mit28 and D19Mit14. An abnormal retinal phenotype was recognized on the day of birth, when some retinal ganglion cells already lie in abnormal positions in the inner plexiform layer. By postnatal day 18 the number of neurons is reduced in all three cellular layers of the retina. Rod photoreceptor cells develop only rudimentory outer segments, and by 9 months of age, about 75% of the photoreceptor cells have completely disappeared. Similar photoreceptor cell abnormalities are seen in prph2 (formerly rds) homozygotes, which lack the peripherin/rds protein of the rod outer segments, but a mating of the respective homozygotes yielded normal progeny. Rom1, which codes for an outer segment protein similar to peripherin/rds, maps to a more proximal position on Chr 19.

Animals↗

Mapping in the region of Danforth's short tail and the localization of tail length modifiers.

We have used an interspecific backcross to generate a detailed genetic map around the mouse tail and kidney developmental mutation Danforth's short tail (Sd). The map includes 14 simple sequence repeat (SSR) markers and four genes in a 5-cM region encompassing Sd. In addition we have used a DNA pooling approach to carry out a genome scan to localize quantitative trait loci (QTL) that modify the tail length of Sd progeny of the backcross. This has allowed us to identify a major QTL on chromosome 10 in the region of nodal and three other putative tail length QTL on chromosomes 1, 9, and 18.

Alleles↗

Detection of obesity QTLs on mouse chromosomes 1 and 7 by selective DNA pooling.

The inheritance of obesity has been analyzed in an intercross between the lean 129/Sv mouse strain and the obesity-prone EL/Suz mouse strain. The weights of three major fat pads were determined on 4-month-old mice, and the sum of these weights, divided by body weight, was used as an adiposity index. The strategy of selective DNA pooling was used as a primary screen to identify putative quantitative trait loci (QTLs) affecting adiposity index. DNA pools representing the leanest 15% and fattest 15% of the F2 progeny were compared for differential allelic enrichment using widely dispersed microsatellite variants. To evaluate putative QTLs, individual genotyping and interval mapping were employed to estimate QTL effects and assess statistical significance. One QTL affecting adiposity index, which accounted for 12.3% of phenotypic variance in gender-merged data, was mapped to the central region of Chromosome (Chr) 7. The QTL allele inherited from EL conferred increased adiposity. A second QTL that accounts for 6.3% of phenotypic variance was identified on Chr 1 near D1Mit211. At both QTLs, the data are consistent with dominant inheritance of the allele contributing to obesity. The possible relationships between these QTLs and previously described obesity QTLs, major obesity mutations, and candidate genes are discussed.

Adipose Tissue↗

Synthesis and characterization of 8-methoxy-2'- deoxyadenosine-containing oligonucleotides to probe the syn glycosidic conformation of 2'-deoxyadenosine within DNA.

The synthesis of 8-methoxy-2'-deoxyadenosine (moA) protected at N6 as an N,N-dimethylformamidine derivative and incorporation of the modified nucleoside into oligodeoxynucleotides via the phosphoramidite method are described. UV thermal denaturation studies were conducted on duplexes containing moA:G, moA:C and moA:T base pairs to determine the thermodynamic stability of duplexes containing moA relative to their adenosine (A)-containing counterparts. In the case of moA:G base pairs the effect of moA substitution is sequence dependent. In A:G mismatch-containing sequences, which have been shown by structural characterization to have a syn conformational preference at the glycosidic bond of A, moA substitution results in stabilization of the duplex. In contrast, in sequences where the A in the A:G mismatch has been shown to prefer the anti conformation moA substitution is destabilizing to the duplex. Thus moA may be a useful probe for investigating the conformational preferences of the N-glycosidic bond of adenosine within DNA. In addition, moA nucleoside is more resistant to acid-catalyzed depurination than previously described 8-bromo-2'-deoxyadenosine, allowing for facile incorporation into oligonucleotides via automated solid phase DNA synthesis.

Base Sequence↗

Typing recombinant inbred mouse strains for microsatellite markers on chromosomes 10, 16, 18, 19, and X.

A total of 57 different microsatellite variants have been typed in one or more of five different sets of recombinant inbred (RI) mouse strains. The present report concentrates on markers for Chromosomes (Chrs) 10, 16, 18, 19 and X. These markers extend the regions swept in these RI strains, provide reference markers for integrating RI and conventional maps, and provide additional estimates of genetic distances. Multilocus maps, based on maximum likelihood analysis of present and previously published RI SDPs on five chromosomes, are presented. Unexpectedly, three microsatellite markers, previously assigned to Chr 10, detected polymorphic fragments mapping to other chromosomes.

Animals↗

PCR-amplification of simple sequence repeat variants from pooled DNA samples for rapidly mapping new mutations of the mouse.

A novel strategy for rapidly mapping new mutations of the mouse is presented and tested. The inbred Mus musculus castaneus strain CAST/Ei is used as a tester stock. Separate DNA pools are made from mutant and wildtype intercross (F2) progeny and analyzed using simple sequence repeat (SSR) variants detected using PCR amplification. Linkage is indicated if the mutant DNA pool is enriched for the mutant-strain SSR allelic fragment in comparison with the wildtype pool and controls. The expected contributions of the tester stock to mutant and wildtype pools as a function of recombination frequency are derived for both intercross and backcross progeny segregating for a recessive mutant gene. The sensitivity and reliability of this method is investigated using arbitrary DNA mixtures and also mutant and wildtype pools from a (CAST/Ei x MEV) intercross segregating for the dilute coat color mutation. It is concluded that linkages as great as 20 cM can be reliably detected by this method provided that sufficient progeny contribute to the pools. A set of 39 SSR variants, resolvable by agarose gel electrophoresis and suitable for pooled-SSR analysis, is identified. These are expected to screen 94% of the autosomal genome in crosses between CAST/Ei and common laboratory strains.

Animals↗

For young jumpers, differences are in the movement's control, not its coordination.

Previous research on the development of jumping has indicated that the coordination of the jump is stable from its inception, but that individual differences lie in the control of the task. The purpose of this study was to examine control in the vertical jump as performed by novice jumpers. Two groups of children who varied in their ability to regulate the takeoff angle were compared on measures of coordination and control. The children's groups were also compared to a group of skilled adults. Both children's groups demonstrated temporal coordination patterns comparable to the adult pattern, though the children were distinguished from the adults on selected spatial (control) measures. The results indicate that a mature pattern of coordination for the jump exists at the earliest stages of the behavior's appearance in the movement repertoire. The novice, however, lacks the ability to precisely control, or tune, the movement to task demands.

Child, Preschool↗

Resuscitation for cardiogenic shock with extracorporeal membrane oxygenation systems.

Between 1975 and 1993, 73 patients in cardiogenic shock were supported by a variety of venoarterial pumping (VAP) systems. There were 64 adults and 9 children. Shock was caused by myocardial infarction (MI) (26), failed percutaneous transluminal coronary angioplasty (PTCA) (25), post open heart surgery (9), viral cardiomyopathy (5), idiopathic cardiomyopathy (2), pulmonary embolism (2), hypothermia (2), and arrhythmia (2). Forty-three patients were treated with percutaneous bypass and 30 by surgical bypass. Resuscitated patients were usually bridged to further therapies such as coronary artery bypass graft (CABG), valve repair or replacement or cardiac transplantation. Overall, 35 patients (48%) survived VAP and additional therapies. We conclude that early application of complete cardiopulmonary support to patients in shock allows resuscitation and corrective therapy with an acceptable salvage rate.

Adult↗

Heaven can wait.

The apparently unlimited demand for health care, finite supply of resources, the internal social market and continuous technological advances have given rise to increasing concern about the performance of health services. We examine an important measure of health care performance--avoidable mortality. Studies extending the scope of avoidable mortality and other outcome indicators are discussed. Although avoidable mortality is limited to providing a warning signal of possible health care deficiencies and is not an appropriate measure for all types of intervention, it still provides us with one of the best guides to the performance of health services.

Adolescent↗

Coronary angioplasty for acute myocardial infarction in a hospital without cardiac surgery.

We evaluated, retrospectively, the hospital records of 100 consecutive patients with acute myocardial infarction who underwent emergency coronary angiography and percutaneous transluminal coronary angioplasty between January 1984 and August 1990. Intracoronary streptokinase (250,000 to 1 million units) was administered to 46 of these patients. Reperfusion was achieved in 82 patients, 8 of whom died in the hospital within 30 days. Angioplasty failed in 18 patients. Six were managed medically and survived, 7 survived emergency coronary bypass surgery at a nearby facility, and 5 died. The overall mortality rate was 13%. No facilities for open-heart surgery were available at our hospital; however, surgical back-up was available at another hospital, 0.5 miles away. No death was related to the transfer of a patient or to the unavailability of an in-house cardiac surgery facility. The American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures has written guidelines for cardiac surgical back-up for percutaneous transluminal coronary angioplasty. These guidelines strongly recommended that an experienced cardiovascular surgical team be available for emergency surgery in the institution as a back-up for all angioplasty procedures. Our study shows, however, that with careful case selection, emergency angioplasty for acute myocardial infarction can be performed safely with good results in a setting without on-site cardiac surgery facilities.

Aged↗

A longitudinal study of intralimb coordination in the first year of independent walking: a dynamical systems analysis.

Using a dynamical systems approach, we examined the development of intralimb coordination over the first year of independent walking. The segmental motion of the thigh and shank and their intralimb coordinative relationship were modeled dynamically as a system of coupled limit cycles. To test the predictions of such a dynamic model in the development of intralimb coordination, 3 infants were filmed from the onset of their first upright independent walking steps, and weekly for the next month and then every month thereafter until they had been walking for 1 year. 3 adults also were included for comparison. Analysis of the kinematic data derived from the film revealed that at the emergence of walking, the limit cycle system displayed instability in several aspects. With walking experience, however, the limit cycle regime became more attractive, such that by 3 months of walking the infants appeared to have found an adult-like stable coordinative relationship between the 2 segments. This pattern of instability followed by stability is consistent with the transitional behaviors of dynamical systems. Several potential control parameters are discussed that might contribute to the stabilization of the walking behavior. The utility of employing a dynamical systems approach for understanding developing behavioral systems is discussed.

Female↗

Benefits of combined balloon pumping and percutaneous cardiopulmonary bypass.

Sixteen patients (2 women, 14 men) aged 29 to 72 years with continued cardiogenic shock during intraaortic balloon pumping (IABP) had additional treatment with percutaneous cardiopulmonary bypass (PBY). Cause of cardiogenic shock was myocardial infarction in 7 (3 survived), failed percutaneous transluminal coronary angioplasty requiring emergency coronary artery bypass grafting in 5, postoperative aortic valve replacement in 1, postoperative emergency coronary artery bypass grafting in 1, after cardiac transplantation in 1, and bridging to transplantation in 1. Mean blood pressure with PBY and IABP combined was 75 mm Hg versus 60 mm Hg with IABP off. Percutaneous cardiopulmonary bypass flows ranged from 0.8 to 2.1 L/min with a mean flow of 1.3 L/min. Time on IABP ranged from 24 hours to 1 week. Time on IABP to PBY ranged from 1 to 20 hours, and time on PBY ranged from 65 minutes to 20 hours. Ten of 16 (63%) were successfully weaned, and 3 died after weaning. Seven of 16 (44%) survive. Combined IABP with PBY appears to be a better therapy than either one individually. Staging the therapy as the balloon first in and last out appears to be a good methodology.

Adult↗