Biomedical subjects

K Young

Publications and source records attributed to K Young.

At least 55 records · Page 3Linked to original sources

PubMed2000

Skeletal muscle contractile and noncontractile components in young and older women and men.

To examine the influences of age, gender, and habitual physical activity level on human skeletal muscle composition, we developed a relatively simple magnetic resonance imaging method for the quantitation of leg anterior compartment contractile and noncontractile content. We studied 23 young (11 women and 12 men, 26-44 yr old) and 21 older (10 women and 11 men, 65-83 yr old) healthy adults. Analysis was by two-factor (age, gender) ANOVA. Physical activity, quantitated by three-dimensional accelerometer worn about the waist for 1 wk, was not different between groups. Men had larger contractile and noncontractile cross-sectional areas (cm(2)) than women, with no gender effect on percent noncontractile area. Young subjects had larger contractile areas and smaller absolute (cm(2)) and relative (percent total) noncontractile areas than older subjects. There was a significant linear relationship between physical activity and percent noncontractile area in older (r = -0.68, P = 0.002) but not young subjects. These data demonstrate a more than twofold increase in the noncontractile content of locomotor muscles in older adults and provide novel support for physical activity as a modulator of this age-related change in muscle composition.

Adult↗

PubMed2000

Adult croup: a rare but more severe condition.

We report the first adult patient with virologically confirmed croup caused by parainfluenza virus type 3 and review 10 cases of adult croup described in the English-language literature. Circumstantial evidence of viral infection was present in only 1 other case, in which there was a rise in antibody titer against influenza B virus. Ten patients (91%) required intensive care support. None of the 11 patients died. A comparison was also made between the 11 adults with croup and 43 children hospitalized with severe croup described in a representative paper published in 1984. Adult croup represents an apparently more severe disease entity than pediatric croup.

Aged↗

PubMed2000

Common and rare ABCA1 variants affecting plasma HDL cholesterol.

Mutations in ABCA1, a member of the ATP-binding cassette family, have been shown to underlie Tangier disease (TD) and familial hypoalphalipoproteinemia (FHA), which are genetic disorders that are characterized by depressed concentrations of plasma high density lipoprotein (HDL) cholesterol. An important question is whether common variants within the coding sequence of ABCA1 can affect plasma HDL cholesterol in the general population. To address this issue, we developed a screening strategy to find common ABCA1 variants. This strategy involved long-range amplification of genomic DNA by using coding sequences only, followed by deep sequencing into the introns. This method helped us to characterize a new set of amplification primers, which permitted amplification of virtually all of the coding sequence of ABCA1 and its intron-exon boundaries with a single DNA amplification program. With these new sequencing primers, we found 3 novel ABCA1 mutations: a frameshift mutation (4570insA, A1484S-->X1492), a missense mutation (A986D) in a TD family, and a missense mutation (R170C) in aboriginal subjects with FHA. We also used these sequencing primers to characterize 4 novel common amino acid variants in ABCA1, in addition to 5 novel common silent variants. We tested for association of the ABCA1 I/M823 variant with plasma HDL cholesterol in Canadian Inuit and found that M823/M823 homozygotes had significantly higher plasma HDL cholesterol compared with subjects with the other genotypes. The results provide proof of principle of the effectiveness of this approach to identify both rare and common ABCA1 genomic variants and also suggest that common amino acid variation in ABCA1 is a determinant of plasma HDL cholesterol in the general population.

ATP Binding Cassette Transporter 1↗

PubMed2000

Dynamic cerebral autoregulation in sick newborn infants.

The sick newborn infant is vulnerable to brain injury and impaired cerebral autoregulation is thought to contribute to this. Coherent averaging is a method of measuring the dynamic cerebral autoregulatory response that is particularly suitable for neonates. We used this method in combination with a measure of the gradient of the cerebral blood flow velocity (CBFV) response following transient blood pressure (BP) peaks to study dynamic autoregulation in infants undergoing intensive care. Term and preterm infants at high risk of neurologic injury were compared with a control group of infants, also undergoing intensive care. Simultaneous video-EEG, CBFV (using transcranial Doppler), and arterial blood pressure measurements were obtained intermittently during a study period of at least 2 h. Cerebral autoregulatory response curves were constructed for high risk and control groups. Intact cerebral autoregulation produces a characteristic response consisting of a brief period when CBFV follows arterial blood pressure but quickly returns to baseline value. An impaired autoregulatory response shows CBFV mirroring the arterial blood pressure curve closely. Thirteen high-risk infants, who also had seizures (10 term and 3 preterm) and 12 control infants (6 term and 6 preterm) were studied. Autoregulation was absent in high-risk term and preterm infants. It was also absent in preterm control infants. Term, neurologically healthy infants undergoing intensive care have an intact autoregulatory response. The constant passive response seen in high-risk infants may reflect the severity of the underlying neurologic disease.

Blood Flow Velocity↗

PubMed2000

Popular cinema and lesbian interpretive strategies.

In its examination of the relationship between popular film and lesbian viewing practices, this study attempts to more fully elucidate current ideas around audience engagement and forms of cultural reception. Drawing on 15 in-depth interviews conducted in Western Canada in 1996, the results clearly demonstrate the existence of active lesbian viewers, whose interpretations of popular film are intimately informed by lesbian-specific life experiences and cultural competencies. Although the social conditions which create the need for resistant viewing are themselves oppressive, subversion of mainstream film holds out some possibility of empowerment for lesbian viewers.

Art↗

PubMed2000

Is visual thinking "imageless thought"?

Two measures of visual problem solving ability and two measures of visual-imaging ability were administered to 99 subjects. Scores on the Emergent Patterns Test, a problem-solving test which requires subjects to think about specific combinations of visual icons and to identify the emergent patterns, did not correlate significantly with scores on either the Vividness of Visual Imagery Questionnaire or the Brightness of Visual Imagery Measure. Scores on the Block Visualization Test, which requires subjects to think about blocks being painted and diced and to answer questions about the resulting pieces of block, did not correlate significantly with the scores on the Vividness of Visual Imagery Questionnaire and correlated negatively with the scores on the Brightness of Visual Imagery Measure. The three nonsignificant correlations support nineteenth century arguments that vivid imagers tend to construct sensory representations of unconscious visual thoughts, whereas "imageless thinkers" tend not to. The one negative correlation further may suggest that the conscious construction of visual imagery can sometimes interfere with the underlying processes of unconscious visual thinking.

Humans↗

PubMed2000

Tacrolimus (FK 506) induced thrombotic thrombocytopenic purpura after ABO mismatched second liver transplantation: salvage with plasmapheresis and prostacyclin.

We report the course of thrombotic thrombocytopenic purpura (TTP) in a patient receiving tacrolimus (FK506) immunosuppression for an ABO mismatched second liver graft. A Chinese woman with fulminant hepatitis-B reactivation failed a living-related orthotopic liver transplantation (OLT) due to portal vein thrombosis. An ABO mismatched cadaveric OLT (group A to O) was performed, with peri-operative plasmapheresis to reduce anti-A hemagglutinin titers. On day 30, she developed fever, hemolysis, thrombocytopenia and neurologic dulling. Prominent microangiopathic features in peripheral blood film, and characteristic brain lesions on magnetic resonance imaging confirmed TTP. She responded initially to intensive plasmapheresis with cryosupernatant replacement, and withdrawal of FK506. An attempted reintroduction of FK506 for threatened rejection led to TTP exacerbation. This was controlled with prolonged plasmapheresis and a ten-day infusion of prostacyclin. Immunosuppression was changed to mycophenolate mofetil. By day 53, the peripheral film and lactate dehydrogenase level had returned to baseline and plasmapheresis was stopped.

ABO Blood-Group System↗

PubMed2000

Parkinson's disease revisited.

Parkinson's disease (PD) is a neurodegenerative disorder that affects an estimated 1 million persons in the United States each year. Although PD has been studied for almost 50 years, several shortcomings in management still exist. Symptom management, addressing movement disorders, psychological aspects, sexual dysfunction, and gastrointestinal concerns may all affect the person with PD.

Antiparkinson Agents↗

PubMed2000

Thyroid cancer: patients' experiences of receiving iodine-131 therapy.

PURPOSE/OBJECTIVES: To enhance understanding of the experiences and educational needs of patients receiving iodine-131 (131I) therapy for the treatment of thyroid cancer. DESIGN: Qualitative design using interpretive description. SETTING: A 24-bed oncology/acute-care medical unit in a large tertiary hospital in western Canada. SAMPLE: 5 men and 22 women (18-80 years of age) who have received 131I therapy in the past two years. METHODS: Unstructured focus group and telephone interviews and field notes. Interviews were tape-recorded, transcribed verbatim, and subjected to thematic analysis. FINDINGS: Researchers elicited four major themes from the analysis: (a) recognizing the totality of the cancer experience, (b) being isolated, (c) recognizing the totality of the treatment experience, and (d) understanding barriers to treatment. CONCLUSIONS: Healthcare providers require a better understanding of thyroid disease and the treatment and side effects of 131I therapy. Furthermore, educational programs are required to adequately prepare nurses and patients for future care. IMPLICATIONS FOR NURSING PRACTICE: A need exists to improve the care and education provided to patients receiving 131I therapy. In particular, recognition of the totality of the cancer experience and the need for both staff and patient education were illustrated. If nurses are to provide comprehensive cancer care, both psychosocial and physical needs must be addressed and fulfilling these needs requires a collaborative approach among patients, nurses, and other healthcare professionals.

Administration, Oral↗

PubMed1999

Inhibition of IMP-1 metallo-beta-lactamase and sensitization of IMP-1-producing bacteria by thioester derivatives.

IMP-1 metallo-beta-lactamase is a transferable carbapenem-hydrolyzing enzyme found in some clinical isolates of Pseudomonas aeruginosa, Serratia marcescens and Klebsiella pneumoniae. Bacteria that express IMP-1 show significantly reduced sensitivity to carbapenems and other beta-lactam antibiotics. A series of thioester derivatives has been shown to competitively inhibit purified IMP-1. As substrates for IMP-1, the thioesters yielded thiol hydrolysis products which themselves were reversible competitive inhibitors. The thioesters also increased sensitivity to the carbapenem L-742,728 in an IMP-1-producing laboratory stain of Escherichia coli, but will need further modification to improve their activity in less permeable organisms such as Pseudomonas and Serratia. Nonetheless, the thioester IMP-1 inhibitors offer an encouraging start to overcoming metallo-beta-lactamase-mediated resistance in bacteria.

Bacteria↗

PubMed1999

Computer model for cryosurgery of the prostate.

The objective of this study was to devise an interactive tool to assist in cryoablation therapy through computer modeling, simulation, and visualization. CryoSim, a software package, accepts a set of acquired and processed three-dimensional ultrasound images, then models heat diffusion (formation of the iceball) based on numerical approximation of the heat equation and knowledge of the thermal properties of the underlying tissues. Results of cryoexperiments were found to be significantly similar to those generated by CryoSim. Therefore, CryoSim provides a viable technique for predicting the outcome of cryosurgery, and establishes a platform for future automation of cryosurgery.

Animals↗

PubMed1999

Spectral simulations incorporating gradient coherence selection.

Computer-aided methods can considerably simplify the use of the product operator formalism for theoretical analysis of NMR phenomena, which otherwise becomes unwieldy for anything but simple spin systems and pulse sequences. In this report, two previously available programming approaches using symbolic algebra (J. Shriver, Concepts Magn. Reson. 4, 1-33, 1992) and numerical simulation using object-oriented programming (S. A. Smith, T. O. Levante, B. H. Meier, and R. R. Ernst, J. Magn. Reson. A 106, 75-105, 1994) have been extended to include the use of gradient operators for simulation of spatially localized NMR spectroscopy and gradient coherence selection. These methods are demonstrated using an analysis of the response of an AX(3) spin system to the STEAM pulse sequence and verified with experimental measurements on lactate.

Computer Simulation↗

PubMed1999

Balanced biosynthesis of major membrane components through regulated degradation of the committed enzyme of lipid A biosynthesis by the AAA protease FtsH (HflB) in Escherichia coli.

The suppressor mutation, named sfhC21, that allows Escherichia coli ftsH null mutant cells to survive was found to be an allele of fabZ encoding R-3-hydroxyacyl-ACP dehydrase, involved in a key step of fatty acid biosynthesis, and appears to upregulate the dehydrase. The ftsH1(Ts) mutation increased the amount of lipopolysaccharide at 42 degrees C. This was accompanied by a dramatic increase in the amount of UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase [the IpxC (envA) gene product] involved in the committed step of lipid A biosynthesis. Pulse-chase experiments and in vitro assays with purified components showed that FtsH, the AAA-type membrane-bound metalloprotease, degrades the deacetylase. Genetic evidence also indicated that the FtsH protease activity for the deacetylase might be affected when acyl-ACP pools were altered. The biosynthesis of phospholipids and the lipid A moiety of lipopolysaccharide, both of which derive their fatty acyl chains from the same R-3-hydroxyacyl-ACP pool, is regulated by FtsH.

ATP-Dependent Proteases↗

PubMed1999

Mobile elements carrying ermF and tetQ genes in gram-positive and gram-negative bacteria.

Bacteroides spp. conjugative transposon Tn5030 is 150 kb which includes a 43 kb characterized region containing a number of defined genes and an open reading frame (ORF). The 43 kb region is organized with the ORF1 immediately upstream from the ermF gene, coding for an rRNA methylase, then an unknown 20 kb region downstream followed by the tetQ gene (coding for a ribosomal protection protein) then the rteA and rteB genes. The role of ORF1 is unclear; rteA is a putative sensor and rteB a regulator. Thirty-seven (62%) of 60 isolates, representing one gram-positive anaerobic and 13 gram-negative anaerobic species, co-transferred the ermFand tetQ genes to an unrelated Enterococcus faecalis recipient. We used the polymerase chain reaction to show the linkage between ORF1, ermF, tetQ, rteA and rteB. Our data suggest that the ORF1 gene product may participate in the transfer of the ermF gene with or without the ORF1-rteB region and has homology to bacterial transposases. Isolates that co-transferred the ermF and tetQ genes carried and transferred the rteB gene, suggesting that the rteB gene product may be important in transfer of the 43 kb ORF1-rteB region to E. faecalis. The rteB gene product is not required when ermF is transferred independently of tetQ.

Bacterial Proteins↗

PubMed1999

In vitro activities of the potent, broad-spectrum carbapenem MK-0826 (L-749,345) against broad-spectrum beta-lactamase-and extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli clinical isolates.

An important mechanism of bacterial resistance to beta-lactam antibiotics is inactivation by beta-lactam-hydrolyzing enzymes (beta-lactamases). The evolution of the extended-spectrum beta-lactamases (ESBLs) is associated with extensive use of beta-lactam antibiotics, particularly cephalosporins, and is a serious threat to therapeutic efficacy. ESBLs and broad-spectrum beta-lactamases (BDSBLs) are plasmid-mediated class A enzymes produced by gram-negative pathogens, principally Escherichia coli and Klebsiella pneumoniae. MK-0826 was highly potent against all ESBL- and BDSBL-producing K. pneumoniae and E. coli clinical isolates tested (MIC range, 0.008 to 0.12 microgram/ml). In E. coli, this activity was associated with high-affinity binding to penicillin-binding proteins 2 and 3. When the inoculum level was increased 10-fold, increasing the amount of beta-lactamase present, the MK-0826 MIC range increased to 0.008 to 1 microgram/ml. By comparison, similar observations were made with meropenem while imipenem MICs were usually less affected. Not surprisingly, MIC increases with noncarbapenem beta-lactams were generally substantially greater, resulting in resistance in many cases. E. coli strains that produce chromosomal (Bush group 1) beta-lactamase served as controls. All three carbapenems were subject to an inoculum effect with the majority of the BDSBL- and ESBL-producers but not the Bush group 1 strains, implying some effect of the plasmid-borne enzymes on potency. Importantly, MK-0826 MICs remained at or below 1 microgram/ml under all test conditions.

Carbapenems↗

PubMed1999

Lysophosphatidic acid-induced calcium mobilization and proliferation in kidney proximal tubular cells.

Patients with proteinuria tend to develop progressive renal disease with proximal tubular cell atrophy and interstitial scarring. It has been suggested that the nephrotoxicity of albuminuric states may be due to the protein molecule itself or by lipids, such as lysophosphatidic acid (LPA), that albumin carries. LPA was found to cause a transient increase in intracytoplasmic free Ca2+ ([Ca2+]i) in opossum kidney proximal tubule cells (OK) that was maximal at 100 microM LPA and was dose dependent with an EC50 of 2.6 x 10(-6) M. This Ca2+ mobilization was from both internal stores and across the plasma membrane and was pertussis toxin (PTX) insensitive. Treatment of OK cells with 100 microM LPA for 5 min was found to cause a twofold increase in [3H]thymidine incorporation and a three- to fivefold increase over control after 24 h. This was highly PTX sensitive and insensitive to pretreatment with the tyrosine kinase inhibitors genistein and herbimycin A. These findings may be of significance in the progression of renal disease and indicate the potential importance of lipids in modulating proximal tubule cell function and growth.

Animals↗

PubMed1998

Characterization of human and rat brain myristoyl-CoA:protein N-myristoyltransferase: evidence for an alternative splice variant of the enzyme.

Using 5'-rapid amplification of cDNA ends, we have identified an extended 5'-end of mRNA coding for human myristoyl-CoA:protein N-myristoyltransferase (NMT). PCR using primers based on this new 5'-sequence and reverse primers within the currently accepted coding sequence of the enzyme resulted in the identification of a novel splice variant of NMT. In vitro translation of these cDNAs resulted in the production of proteins with apparent molecular masses of 63 kDa and 48 kDa. Immunoprecipitation of NMT from human cell lines and immunoblotting of a range of rat tissues has identified proteins with molecular masses corresponding to those derived from these cDNAs, and provided evidence that their relative abundance differs among tissues. Our results provide evidence that this enzyme exists in different forms resulting from alternative splicing of the mRNA.

Acyltransferases↗

PubMed1998

Analysis of BR96 binding sites for antigen and anti-idiotype by codon-based scanning mutagenesis.

We performed a scanning mutagenesis study of heavy chain complementarity-determining region (CDR) residues to identify how mutations affected binding of the anti-carcinoma mAb BR96 to Ag, Lewis Y, and to an anti-Id Ab (anti-Id). By ELISA, we demonstrated that the anti-Id bound close to the Ag binding site of BR96, but the anti-Id and Ag sites were not identical. Immunoblot analysis and screening of light and heavy chain CDR libraries with multiple mutations in each CDR suggested that the heavy chain had greater involvement in anti-Id binding. We then analyzed contributions of individual residues in the heavy chain CDRs to binding of Ag and anti-Id. In a filamentous phage vector containing BR96 V region sequences, mutations were introduced by codon-based mutagenesis at single positions within the three heavy chain CDRs. The resulting libraries of Fab fragments had all amino acids represented at a CDR position. We evaluated the expressed Fabs for binding to Ag and anti-Id by plaque lift assay. We identified the positions with mutations that had the greatest negative effect on binding to the anti-Id and to Ag and analyzed them on the basis of the BR96 x-ray structure. The residues most important for binding to the anti-Id were located in heavy chain CDR1 and CDR2 and were peripheral to the residues within the Lewis Y binding pocket.

Animals↗