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Biomedical subjects

A B Taylor

Publications and source records attributed to A B Taylor.

At least 19 recordsLinked to original sources
PubMed2006

Extracranial metastases of a glioblastoma multiforme to the pleura, small bowel and pancreas.

Extracranial metastases of glioblastoma multiforme (GBM) are rare and usually occur in the context of recurrent intracranial GBM. We present a 39-year-old man with histologically confirmed GBM. The patient remained well for nearly 2 years, with no signs of recurrent tumour. He then presented with distant recurrence within the brain at the same time as developing pneumonia and epigastric pain. A computed tomography scan of the patient's abdomen and chest showed several intra-abdominal masses, including one in the head of the pancreas as well as a separate mass at the base of the left lung. A computed tomography-guided biopsy of the pancreatic mass demonstrated histological appearances identical to those of the original GBM. This unusual case raises the possibility of a link between prolonged survival with GBM and the occurrence of extracranial disease.

Adult↗
PubMed2001

Crystal structures of mitochondrial processing peptidase reveal the mode for specific cleavage of import signal sequences.

BACKGROUND: Mitochondrial processing peptidase (MPP) is a metalloendopeptidase that cleaves the N-terminal signal sequences of nuclear-encoded proteins targeted for transport from the cytosol to the mitochondria. Mitochondrial signal sequences vary in length and sequence, but each is cleaved at a single specific site by MPP. The cleavage sites typically contain an arginine at position -2 (in the N-terminal portion) from the scissile peptide bond in addition to other distal basic residues, and an aromatic residue at position +1. Mitochondrial import machinery recognizes amphiphilic helical conformations in signal sequences. However, it is unclear how MPP specifically recognizes diverse presequence substrates. RESULTS: The crystal structures of recombinant yeast MPP and a cleavage-deficient mutant of MPP complexed with synthetic signal peptides have been determined. MPP is a heterodimer; its alpha and beta subunits are homologous to the core II and core I proteins, respectively, of the ubiquinol-cytochrome c oxidoreductase complex. Crystal structures of two different synthetic substrate peptides cocrystallized with the mutant MPP each show the peptide bound in an extended conformation at the active site. Recognition sites for the arginine at position -2 and the +1 aromatic residue are observed. CONCLUSIONS: MPP bound two mitochondrial import presequence peptides in extended conformations in a large polar cavity. The presequence conformations differ from the amphiphilic helical conformation recognized by mitochondrial import components. Our findings suggest that the presequences adopt context-dependent conformations through mitochondrial import and processing, helical for recognition by mitochondrial import machinery and extended for cleavage by the main processing component.

Amino Acid Sequence↗
PubMed2001

Measurement of scapular asymetry and assessment of shoulder dysfunction using the Lateral Scapular Slide Test: a reliability and validity study.

BACKGROUND AND PURPOSE: The Lateral Scapular Slide Test (LSST) is used to determine scapular position with the arm abducted 0, 45, and 90 degrees in the coronal plane. Assessment of scapular position is based on the derived difference measurement of bilateral scapular distances. The purpose of this study was to assess the reliability of measurements obtained using the LSST and whether they could be used to identify people with and without shoulder impairments. Subjects. Forty-six subjects ranging in age from 18 to 65 years (X=30.0, SD=11.1) participated in this study. One group consisted of 20 subjects being treated for shoulder impairments, and one group consisted of 26 subjects without shoulder impairments. METHODS: Two measurements in each test position were obtained bilaterally. From the bilateral measurements, we derived the difference measurement. Intraclass correlation coefficients (ICC [1,1]) and the standard error of measurement (SEM) were calculated for intrarater and interrater reliability of the difference in side-to-side measures of scapular distance. Sensitivity and specificity of the LSST for classifying subjects with and without shoulder impairments were also determined. RESULTS: The ICCs for intrarater reliability were .75, .77, and .80 and .52, .66, and .62, respectively, for subjects without and with shoulder impairments in 0, 45, and 90 degrees of abduction. The ICCs for interrater reliability were .67, .43, and .74 and .79, .45, and .57, respectively, for subjects without and with shoulder impairments in 0,45 and 90 degrees of abduction. The SEMs ranged from 0.57 to 0.86 cm for intrarater reliability and from 0.79 to 1.20 cm for interrater reliability. Using the criterion of greater than 1.0 cm difference, sensitivity and specificity were 35% and 48%, 41% and 54%, and 43% and 56%, respectively, for 0, 45, and 90 degrees of abduction. Sensitivity and specificity based on the criterion of greater than 1.5 cm difference were 28% and 53%, 50% and 58%, and 34% and 52%, respectively, for the 3 scapular positions. CONCLUSION AND DISCUSSION: Our results suggest that measurements of scapular positioning based on the difference in side-to-side scapular distance measures are not reliable. Furthermore, the results suggest that sensitivity and specificity of the LSST measurements are poor and that the LSST should not be used to identify people with and without shoulder dysfunction.

Adult↗
PubMed2000

Mechanism of the phenylpyruvate tautomerase activity of macrophage migration inhibitory factor: properties of the P1G, P1A, Y95F, and N97A mutants.

Phenylpyruvate tautomerase (PPT) has been studied periodically since its activity was first described over forty years ago. In the last two years, the mechanism of PPT has been investigated more extensively because of the discovery that PPT is the same protein as the immunoregulatory cytokine known as macrophage migration inhibitory factor (MIF). The mechanism of PPT is likely to involve general base-general acid catalysis. While several lines of evidence implicate Pro-1 as the general base, the identity of the general acid remains unknown. Crystal structures of MIF with the competitive inhibitor (E)-2-fluoro-p-hydroxycinnamate bound in the active site and that of the protein complexed with the enol form of a substrate, (p-hydroxyphenyl)pyruvate, suggest that Tyr-95 is the only candidate in the vicinity that can function as a general acid catalyst. Although Tyr-95 is nearby the bound inhibitor and substrate, it is not within hydrogen bonding distance of either ligand. In this study, Tyr-95 was mutated to phenylalanine, and the kinetic and structural properties of the Y95F mutant were determined. This alteration produces a fully active enzyme, which shows no significant structural changes in the active site. The results indicate that Tyr-95 does not function as the general acid catalyst in the reaction catalyzed by wild-type PPT. The mechanism of PPT was studied further by constructing and characterizing the kinetic properties of two mutants of Pro-1 (P1G and P1A) and one mutant of Asn-97 (N97A). The mutation of Asn-97, a residue implicated in the binding of the phenolic hydroxy group of the keto and enol isomers of (p-hydroxyphenyl)pyruvate and of (E)-2-fluoro-p-hydroxycinnamate affects only the binding affinity of the inhibitor. However, the mutations of Pro-1 have a profound effect on the values of k(cat) and k(cat)/K(m) and clearly show that Pro-1 is a critical residue in the reaction. The results are discussed in terms of a mechanism in which Pro-1 functions as both the general acid and the general base catalyst.

Catalytic Domain↗
PubMed1999

Crystal structure of macrophage migration inhibitory factor complexed with (E)-2-fluoro-p-hydroxycinnamate at 1.8 A resolution: implications for enzymatic catalysis and inhibition.

Macrophage migration inhibitory factor (MIF) exhibits dual activities. It acts as an immunoregulatory protein as well as a phenylpyruvate tautomerase. To understand better the relationship between these two activities and to elucidate the structural basis for the enzymatic activity, a crystal structure of a complex between murine MIF and (E)-2-fluoro-p-hydroxycinnamate, a competitive inhibitor of the tautomerase activity, has been determined to 1.8 A resolution. The structure is nearly superimposable on that of the free protein indicating that the presence of the inhibitor does not result in any major structural changes. The inhibitor also confirms the location of the active site in a hydrophobic cavity containing the amino-terminal proline. Within this cavity, the inhibitor interacts with residues from adjacent subunits. At the back of the cavity, the side-chain carbonyl oxygen of Asn-97' interacts with the phenolic hydroxyl group of the inhibitor while at the mouth of the cavity the ammonium group of Lys-32 interacts with a carboxylate oxygen. The other carboxylate oxygen of the inhibitor interacts with Pro-1. The hydroxyl group of Tyr-95' interacts weakly with the fluoro group on the inhibitor. The hydrophobic side chains of five active-site residues (Met-2, Ile-64, Met-101, Val-106, and Phe-113) and the phenyl moiety of Tyr-95' are responsible for the binding of the phenyl group. Further insight into the enzymatic activity of MIF was obtained by carrying out kinetic studies using the enol isomers of phenylpyruvate and (p-hydroxyphenyl)pyruvate. The results demonstrate that MIF processes the enol isomers more efficiently than the keto isomers primarily because of a decrease in Km. On the basis of these results, a mechanism is proposed for the MIF-catalyzed tautomerization reaction.

Animals↗
PubMed1998

Crystal structure of 4-oxalocrotonate tautomerase inactivated by 2-oxo-3-pentynoate at 2.4 A resolution: analysis and implications for the mechanism of inactivation and catalysis.

The crystal structure of 4-oxalocrotonate tautomerase (4-OT) inactivated by the active site-directed irreversible inhibitor 2-oxo-3-pentynoate (2-OP) has been determined to 2.4 A resolution. The structure of the enzyme covalently modified at Pro-1 by the resulting 2-oxo-3-pentenoate adduct is nearly superimposable on that of the free enzyme and confirms that the active site is located in a hydrophobic region surrounding Pro-1. Both structures can be described as a trimer of dimers where each dimer consists of a four-stranded beta-sheet with two antiparallel alpha-helices on one side. Examination of the structure also reveals noncovalent interactions between the adduct and two residues in the active site. The epsilon and eta nitrogens of the guanidinium side chain of Arg-39" from a neighboring dimer interact respectively with the C-2 carbonyl oxygen and one C-1 carboxylate oxygen of the adduct while the side chain of Arg-61' from the same dimer as the modified Pro-1 interacts with the C-1 carboxylate group in a bidentate fashion. An additional interaction to the 2-oxo group of the adduct is provided by one of the two ordered water molecules within the active site region. These interactions coupled with the observation that 2-oxo-3-butynoate is a more potent irreversible inhibitor of 4-oxalocrotonate tautomerase than is 2-OP suggest that Arg-39" and the ordered water molecule polarize the carbonyl group of 2-OP which facilitates a Michael reaction between Pro-1 and the acetylene compound. On the basis of the crystal structure, a mechanism for the enzyme-catalyzed reaction is proposed.

Binding Sites↗
PubMed1997

Relative growth, ontogeny, and sexual dimorphism in gorilla (Gorilla gorilla gorilla and G. g. beringei): evolutionary and ecological considerations.

Gorillas are the largest and among the most sexually dimorphic of all extant primates. While gorillas have been incorporated in broad-level comparisons among large-bodied hominoids or in studies of the African apes, comparisons between gorilla subspecies have been rare. During the past decade, however, behavioral, morphological, and molecular data from a number of studies have indicated that the western lowland (Gorilla gorilla gorilla) and eastern mountain (Gorilla gorilla beringei) subspecies differ to a greater extent than has been previously believed. In this study I compare patterns of relative growth of the postcranial skeleton to evaluate whether differences between subspecies result from the differential extension of common patterns of relative growth. In addition, patterns of ontogeny and sexual dimorphism are also examined. Linear skeletal dimensions and skeletal weight were obtained for ontogenetic series of male and female G.g. gorilla (n = 315) and G.g. beringei (n = 38). Bivariate and multivariate methods of analysis were used to test for differences in patterns of relative growth, ontogeny, and sexual dimorphism between sexes of each subspecies and in same-sex comparisons between subspecies. Results indicate males and females of both subspecies are ontogenetically scaled for postcranial proportions and that females undergo an earlier skeletal growth spurt compared to males. However, results also indicate that the onset of the female growth spurt occurs at different dental stages in lowland and mountain gorillas and that mountain gorillas may be characterized by higher rates of growth. Finally, data demonstrate lowland and mountain gorilla females do not differ significantly in adult body size, but mountain gorilla males are significantly larger than lowland gorilla males, suggesting mountain gorillas are characterized by a higher degree of sexual dimorphism in body size. Thus, although lowland and mountain gorillas do not appear to have evolved novel adaptations of the postcranium which correlate with differences in locomotor behavior, the present investigation establishes subspecies differences in ontogeny and sexual dimorphism which may be linked with ecological variation. Specifically, these findings are evaluated in the context of risk aversion models which predict higher growth rates and increased levels of sexual dimorphism in extreme folivores.

Animals↗
PubMed1997

Scapula form and biomechanics in gorillas.

Gorillas are generating renewed interest as mounting evidence from field and molecular studies strongly suggests the western lowland (Gorilla gorilla gorilla) and eastern mountain (Gorilla gorilla beringei) gorillas are considerably more distinct than has previously been accepted. Schultz (1927, 1930, 1934) was one of the earliest investigators to document morphological differences between the two groups, noting differences in pedal, limb and scapular morphology. These differences led Schultz to conclude that while lowland gorillas retained some features suited to an arboreal habitat, the mountain gorilla had evolved into a specialized terrestrial quadruped. In particular, he noted that mountain gorillas exhibited lower values for the scapular index, higher values for ratios of infraspinous fossa vs. scapula length and spine length vs. scapula length and variability in the extent of curvature of the vertebral border. However, Schultz' observations were based upon small sample sizes of mostly adult specimens. This study extends Schultz' preliminary work by assessing, with appreciably larger sample sizes, patterns of relative growth of the scapula in these two subspecies of Gorilla. Scapula measurements were obtained for ontogenetic series of G.g. gorilla (n = 366) and G. g. beringei (n = 43). Statistical analyses reveal mountain gorillas exhibit significantly (P < 0.05) greater spine lengths and scapula breadths and smaller scapula lengths than lowland gorillas of comparable superior border lengths. However, at comparable body weights, mountain gorillas exhibit significantly shorter spines and superior borders than lowland gorillas. These differences in scapula proportions are evaluated in the context of biomechanical predictions regarding scapula form and locomotion.

Animals↗
PubMed1996

Myelodysplasia associated with Turner syndrome.

PURPOSE: This study reports the association of myelodysplasia with Turner syndrome. PATIENT AND METHODS: An 11-year-old girl with Turner syndrome was found to have mild macrocytic anemia that persisted during 2 years. RESULTS: Examination of the bone marrow revealed dyserythropoietic features with multinucleation consistent with refractory anemia. Levels of hemoglobin F were also markedly elevated (57%). She also had transient neutropenia and thrombocytopenia, as well as abnormal platelet function studies. The hematopoietic abnormalities were mild and may have been missed were she not followed for her hypertension and aortic coarctation. CONCLUSIONS: Myelodysplastic syndromes in children are frequently associated with chromosomal abnormalities, but an association with Turner syndrome has not been previously described. This could be due to the fact that mild hematopoietic abnormalities in these patients may not be investigated.

Anemia↗
PubMed1995

Effects of ontogeny and sexual dimorphism on scapula morphology in the mountain gorilla (Gorilla gorilla beringei).

Scapular measurements were obtained from growth series of the sexually dimorphic mountain gorilla (Gorilla gorilla beringei). Juveniles, subadults, and adults were compared to determine if scapula morphology varies with age. Analyses reveal significant (P < 0.05) differences in scapula form for shape ratios of length vs. breadth, length vs. infraspinous fossa length, and length vs. spine length. Males and females were also compared to determine if sexual dimorphism in scapula morphology is a consequence of differential extension of common patterns of relative growth. Analyses reveal that scapula proportions are ontogenetically scaled. Data indicate that male scapulae grow at a faster rate and for a longer duration than females. Results of comparisons of males and females suggest that unique adaptations to different ecological niches have not evolved between the sexes despite sexual differences in frequency of patterns of locomotor behavior. By contrast, age-related variation in scapula morphology may be linked to differences in locomotor behavior during ontogeny.

Age Factors↗
PubMed1991

Prognostic features of children with idiopathic dilated cardiomyopathy.

The presenting features and long-term outcome of 39 children (median age 6.5 months, range 1 day to 16 years) with idiopathic dilated cardiomyopathy (IDC) were reviewed to help determine the appropriate management of these patients. Four outcome groups were identified: those who died, improved, had IDC resolved or received transplants. Presenting clinical features of age, sex, race, congestive heart failure, cardiomegaly, and degree of systolic ventricular dysfunction did not predict final outcome. Left ventricular hypertrophy on the electrocardiogram was seen significantly more often in children who improved than in those who died or in whom IDC resolved (p = 0.002). A rhythm disturbance was also seen more often in those who died than in those who survived (p = 0.025). Of 36 patients treated medically, 12 (33%) died, 15 (42%) improved and 9 (25%) resolved. Eighteen of 26 (69%) patients presenting at age less than or equal to 2 years survived, whereas 6 of 10 patients greater than 2 years survived. There were no differences based on age at presentation, in the time to death or time of follow-up. Three patients received orthotopic heart transplants, 1 of whom died from graft failure. Thus, no clinical feature including age at presentation consistently predicts ultimate outcome in children with IDC.

Arrhythmias, Cardiac↗
PubMed1991

1991 best hospitals. A guide to the best.

The 45 hospitals identified as the giants in their specialties are profiled below. Beyond size and daily room rates, you'll find special features from kosher menus to schooling for young patients. The ratio of nurses to beds is one measure of how much TLC you can expect. (Because the ratio reflects full-time employment, the number of nurses per bed on any 8-hour shift will be about one third of that indicated.) Phone numbers are provided so you can follow up with your own questions.

Fees and Charges↗
PubMed1991

Doppler echocardiographic evaluation of streptokinase lysis of thrombosed right-sided St. Jude Medical valves in patients with congenital heart defects.

Four episodes of St. Jude Medical prosthesis leaflet thrombosis were serially evaluated by two-dimensional and Doppler echocardiography during treatment with streptokinase. Three patients aged 4, 11, and 24 years with congenital heart disease had St. Jude Medical valves in pulmonary positions (two cases) for tetralogy of Fallot and in the tricuspid position (one case). The duration of thrombosis was not known in any patient. Leaflet immobility and its resolution were demonstrated by echocardiography and were confirmed fluoroscopically. Continuous wave Doppler echocardiography showed abnormal stenotic gradients in thrombosed valves that were reduced after thrombolysis. These studies demonstrate the utility of two-dimensional and Doppler echocardiography in serial evaluation of prosthetic pulmonary and tricuspid valve thrombosis during thrombolysis.

Adult↗
PubMed1991

Effects of perinatal alcohol exposure and dietary calcium supplements on skeletal and dental growth in rats.

Osteoporosis, hypocalcemia and skeletal size reduction are all common correlates of perinatal alcohol exposure. The present study assesses the effects of dietary calcium supplements on reversing perinatal alcohol-induced osteopenia. One hundred and twenty-nine offspring from Fisher 344 rats received 14% v/v alcohol in tap water from conception to weaning or 3 months of age followed by dietary calcium supplements (230 mg/kg/day) to 6 months of age. Significant group effects (p less than 0.001) were noted for all 12 dental and skeletal dimensions measured. Results suggest that calcium therapy following perinatal alcohol exposure may ameliorate alcohol-induced osteopenia in exposed offspring.

Alcohol Drinking↗
PubMed1990

Real-time, automated, interactive cardiac electrophysiology testing.

We describe a new automated interactive system that performs all of the functions required for complete evaluation of the intracardiac conduction system, for inducing, terminating and analyzing tachydysrhythmias, and for locating and characterizing accessory atrioventricular (AV) connections and ectopic foci. In the first year of operation, the system was used to conduct 210 electrophysiology studies. These ranged from simple postoperative evaluation of the conduction system to complete tachycardia studies during pharmacological manipulation of the patient. Patient age at time of catheterization ranged from 6 days to 70 years, with median age of 8 years and 7 months. Advantages accruing from automated electrophysiology testing with this system included great precision and accuracy of timing measurements, flexibility in designing and implementing pacing protocols, and rapid management of induced or spontaneous dysrhythmias. Significant savings of time and labor were achieved by computer generation of reports and graphs as opposed to manual data extraction and plotting. The single most significant advantage is the ability of the system to provide information on a real-time basis, permitting the electrophysiologist to analyze, modify, extend or curtail the procedure.

Adolescent↗
PubMed1989

Perceived needs of families with children who have chronic health conditions.

Parents of children with a wide variety of chronic health conditions (N = 910) were surveyed about their use of health services, out-of-pocket expenses for health care and related items, and ratings of the importance of health and support services. The financial burden on this middle-class, insured sample was substantial, with about half indicating some out-of-pocket expenses for travel, parking fees, drugs and medication, bills after insurance payments, and doctor charges. The commonalities found in parents' reporting of important services needed support the use of a noncategorical approach to program planning and policy development for children with special health care needs.

Child↗