Biomedical subjects

J Chen

Publications and source records attributed to J Chen.

At least 919 records · Page 51Linked to original sources

PubMed2000

Computation of the signal-to-noise ratio of high-frequency magnetic resonance imagers.

A method of computing the signal-to-noise ratio (SNR) in high-frequency magnetic resonance (MR) imaging systems is presented. The method uses a numerical solution to Maxwell's equations which can capture all relevant electrodynamic effects at high B0-field strengths. Using this method, the intrinsic SNR of both volume and surface coils loaded with the human head is calculated as a function of frequency. It is shown that although the available SNR from any point scales favorably with frequency, phase inhomogeneity over the volume of the head may pose a challenge to achieving improved SNR with traditional imaging techniques at high B0-field strengths.

Biomedical Engineering↗

PubMed2000

Wireless clinical alerts for physiologic, laboratory and medication data.

A fully interfaced clinical information system (CIS) contains physiologic, laboratory, blood gas, medication and other data that can be used as the information base for a comprehensive alerting system. Coupled with an event driven rules engine, a CIS can generate clinical alerts which may both prevent medical errors and assist caregivers in responding to critical events in a timely way. The authors have developed a clinical alerting system which delivers alerts and reminders to clinicians in real time via a alphanumeric display pagers. This paper will describe the system, the type and number of alerts generated, and the impact on clinical practice. A major issue remains in measuring the impact of wireless alerts on patient outcomes.

Algorithms↗

PubMed2000

Crystal structures of two mutants (K206Q, H207E) of the N-lobe of human transferrin with increased affinity for iron.

The X-ray crystallographic structures of two mutants (K206Q and H207E) of the N-lobe of human transferrin (hTF/2N) have been determined to high resolution (1.8 and 2.0 A, respectively). Both mutant proteins bind iron with greater affinity than native hTF/2N. The structures of the K206Q and H207E mutants show interactions (both H-bonding and electrostatic) that stabilize the interaction of Lys296 in the closed conformation, thereby stabilizing the iron bound forms.

Amino Acid Substitution↗

PubMed2000

Oophorectomy at the time of surgery for moderate endometriosis: a survey of Australian gynaecologists.

The decision to perform bilateral oophorectomy at the time of surgery for endometriosis is dependent upon many factors, one of which is the opinion of the surgeon concerned. At present there is no consensus on this subject, and in an attempt to document current opinion, we performed a postal survey of all Fellows of RANZCOG living within Australia. The questionnaire presented the Fellow with a clinical scenario describing moderate endometriosis, and then asked him/her to select their preferred option for each of a number of anatomical areas. Out of 1,050 questionnaires, 688 (65.5%) were returned. Analysis of these replies suggests that current opinion supports a conservative approach to surgery, with only 27.5% of Fellows electing to perform a hysterectomy in conjunction with bilateral oophorectomy.

Adult↗

PubMed2000

Postmenopausal hormone therapy and cognitive function in healthy older women.

OBJECTIVE: Accumulating biologic evidence suggests that estrogen is related to cognitive function. Several epidemiologic investigations have reported that hormone therapy may reduce the risk of Alzheimer's disease. However, fewer studies have examined the relation of postmenopausal hormone use to general cognitive function in nondemented older women. Thus, we examined the association of hormone therapy to performance on four cognitive tests among healthy participants of the Nurses' Health Study. DESIGN: Cohort study. SETTING: The Nurses' Health Study, an ongoing prospective cohort study begun in 1976. PARTICIPANTS: From the Nurses' Health Study, 2138 women aged 70-78 years. MEASUREMENTS: From 1995-1999 we administered four cognitive tests (Telephone Interview for Cognitive Status (TICS), immediate and delayed recall of the East Boston Memory Test (EBMT), and verbal fluency) by telephone. Hormone use was ascertained from biennial questionnaires beginning in 1976. Linear and logistic regression models were used to calculate multivariate-adjusted differences in scores and relative risks of a low score for never users compared to current and past hormone users. RESULTS: After adjustment for confounders, neither current nor long-term hormone users demonstrated better performance on an overall measure of cognition (TICS), or on three tests of verbal memory (immediate and delayed recall of the EBMT, immediate recall of the TICS 10-word list) than never users. On the test of verbal fluency, current hormone users scored significantly better than never users (linear regression estimate of the difference in score = 0.78 points, 95% confidence interval (CI) 0.19-0.38, P = .01 for any current use; and 0.91 points, 95% CI 0.28-1.54, P = .005 for > or = 5 years current use). Current hormone users also had a 30% decrease (RR = 0.70, 95% CI 0.45-1.09) in their risk of a low score on the test of verbal fluency. These results were similar for women taking estrogen alone and estrogen combined with a progestin. CONCLUSIONS: Verbal fluency may be enhanced among women taking postmenopausal hormones, however, there is little support for better overall cognitive function in hormone users than nonusers.

Aged↗

PubMed2000

Atrioventricular nodal tachycardia occurring during atrial fibrillation.

We describe the case of a 32-year-old woman with palpitations and atrial fibrillation (AF) as the only documented arrhythmia. The patient underwent electrophysiologic study and was found to have inducible AV nodal reentrant tachycardia (AVNRT). During a prolonged episode of AVNRT, AF developed in both atria, but AVNRT persisted. Dissociation of the atria during AVNRT is evidence that the atrium is not necessary in AVNRT. This case also illustrates the utility of an electrophysiologic study in locating a potentially curable arrhythmia as the primary cause of AF in young patients.

Adult↗

PubMed2000

Spatially distributed dominant excitation frequencies reveal hidden organization in atrial fibrillation in the Langendorff-perfused sheep heart.

INTRODUCTION: Atrial fibrillation (AF) is characterized by complex wave propagation, yet periodic excitation suggesting a high degree of organization may be revealed during sustained AF. We provide a systematic quantification of the spatial distribution of dominant frequencies (DFs) of local excitation on the epicardium of the right atrial (RA) free wall and left atrial (LA) appendage of the isolated sheep heart during AF. The data reveal, for the first time, hidden organization, independent of the activation sequences or nature of electrograms. METHODS AND RESULTS: In 13 Langendorff-perfused sheep hearts, AF was induced in presence of 0.1 to 0.6 microM acetylcholine. Video movies (potentiometric dye di-4-ANEPPS) of the RA and LA (>30,000 and >20,000 pixels, respectively) were obtained at 120 frames/sec and a biatrial electrogram was recorded. Spectral analyses were performed on movies with DF maps constructed. During AF, the activity formed stable discrete domains with uniform DFs within each domain. Acceleration of AF increased the number of domains (R = 0.81, P < 0.0001) and the DF variance (R = 0.63, P < 0.001), indicating a decrease in organization. Also, the LA was faster and more homogeneous, with smaller number of DF domains, compared to the RA (P < 0.00001). CONCLUSION: In this model, AF is characterized by multiple domains with distinct DFs on the atrial epicardium. The decrease in domain area with increased rate suggests that AF results from high-frequency impulses that undergo spectral transformations. The LA is generally faster and more organized than the RA, suggesting that the sources for the impulses are localized to the LA.

Animals↗

PubMed2000

Assessment of gastric emptying using a low fat meal: establishment of international control values.

OBJECTIVE: The diagnosis of gastroparesis implies delayed gastric emptying. The diagnostic gold standard is scintigraphy, but techniques and measured endpoints vary widely among institutions. In this study, a simplified scintigraphic measurement of gastric emptying was compared to conventional gastric scintigraphic techniques and normal gastric emptying values defined in healthy subjects. METHODS: In 123 volunteers (aged 19-73 yr, 60 women and 63 men) from 11 centers, scintigraphy was used to assess gastric emptying of a 99Tc-labeled low fat meal (egg substitute) and percent intragastric residual contents 60, 120, and 240 min after completion of the meal. In 42 subjects, additional measurements were taken every 10 min for 1 h. In 20 subjects, gastric emptying of a 99Tc-labeled liver meal was compared with that of the 99Tc-labeled low fat meal. RESULTS: Median values (95th percentile) for percent gastric retention at 60, 120, and 240 min were 69% (90%), 24% (60%) and 1.2% (10%) respectively. A power exponential model yielded similar emptying curves and estimated T50 when using images only taken at 1, 2 and 4 h, or with imaging taken every 10 min. Gastric emptying was initially more rapid in men but was comparable in men and women at 4 h; it was faster in older subjects (p < 0.05) but was independent of body mass index. CONCLUSIONS: This multicenter study provides gastric emptying values in healthy subjects based on data obtained using a large sample size and consistent meal and methodology. Gastric retention of >10% at 4 h is indicative of delayed emptying, a value comparable to those provided by more intensive scanning approaches. Gastric emptying of a low fat meal is initially faster in men but is comparable in women at 4 h; it is also faster in older individuals but is independent of body mass.

Adult↗

PubMed2000

Optimization of design and surgical positioning of inflatable penile prostheses.

The interaction between the cylinders of an inflatable penile prosthesis (IPP) and the surrounding tissues during IPP-aided erection may result in local elevated stresses. These stresses may reach values that can obstruct penile blood vessels and cause ischemia and/or stimulate nerves around the operation site, thereby inducing sensations of pain. A new numerical model was used to analyze penile stresses postimplantation of different IPP types, in order to optimize prosthesis design and surgical positioning by enabling minimal stress transfer to dorsal blood vessels and nerves. The results suggest that intraluminal pressures should be maintained at low levels (about 80 kPa) while cylinder thickness and stiffness should be kept just high enough (approximately 15% of the radius and 1000 MPa, respectively) to eliminate deleterious cylinder-tissue contact stresses. Smaller prosthetic cylinders, i.e., occupying about 45% of the cavernosal space, may be advantageous in terms of reducing dorsal stresses, but lower penile rigidity should be expected. A significant decrease of dorsal stresses can also be achieved by encouraging the surgeon to position the cylinders toward the lower part of the corpora. The numerical simulations indicate that circular cylinders may allow greater biomechanical compatibility of the IPP with the penis structure than elliptic ones, and this should be a subject for clinical investigations.

Biomechanical Phenomena↗

PubMed2000

Synthetic modification of prostaglandin f(2alpha) indicates different structural determinants for binding to the prostaglandin F receptor versus the prostaglandin transporter.

Several principles governing the binding of E series prostaglandins to EP receptors have emerged in recent years. The C-1 carboxyl group binds electrostatically to a conserved arginine residue in the seventh transmembrane segment of the receptor. Prostaglandin E analogs involving bioisosteric replacements of the carboxyl group, such as acylsulfonamide, are also active. In addition, structurally similar esters may also exhibit similar affinity, presumably by virtue of hydrogen bonding. Other regions of the substrate molecule appear to bind to other domains of EP receptors, either via hydrophobic interactions or by hydrogen bonding. Less information is available about the structural requirements for substrate binding to FP receptors. Prostanoids also bind to the prostaglandin transporter PGT. In this case, a conserved C-1 carboxyl group is critically important, since C-1 esters exhibit little affinity. Here we examined the binding of chemically diverse PGF(2alpha) structural analogs to the FP receptor and compared these with binding by the PG transporter. PGT recognized a wide range of anionic substituents. In contrast, the carboxylic acid group was essential for optimal binding to the FP receptor, since replacement by larger moieties with a similar pK(a), such as acylsulfonamide and tetrazole, substantially decreased binding affinity. Interestingly, insertion of cyclic substituents in the omega chain increased binding to the FP receptor but reduced affinity for PGT, and substitution for the 15-hydroxyl group produced only a modest reduction in FP receptor binding, but eliminated binding by PGT. Because extracellular PGF(2alpha) may compete for binding between FP receptors and PGT, these findings have implications for designing PGF(2alpha) analogs for treating disease states.

Animals↗

PubMed2000

Molecular characterization of Yarrowia lipolytica and Candida zeylanoides isolated from poultry.

Yeast isolates from raw and processed poultry products were characterized using PCR amplification of the internally transcribed spacer (ITS) 5.8S ribosomal DNA region (ITS-PCR), restriction analysis of amplified products, randomly amplified polymorphic DNA (RAPD) analysis, and pulsed-field gel electrophoresis (PFGE). ITS-PCR resulted in single fragments of 350 and 650 bp, respectively, from eight strains of Yarrowia lipolytica and seven strains of Candida zeylanoides. Digestion of amplicons with HinfI and HaeIII produced two fragments of 200 and 150 bp from Y. lipolytica and three fragments of 350, 150, and 100 bp from C. zeylanoides, respectively. Although these fragments showed species-specific patterns and confirmed species identification, characterization did not enable intraspecies typing. Contour-clamped heterogeneous electric field PFGE separated chromosomal DNA of Y. lipolytica into three to five bands, most larger than 2 Mbp, whereas six to eight bands in the range of 750 to 2,200 bp were obtained from C. zeylanoides. Karyotypes of both yeasts showed different polymorphic patterns among strains. RAPD analysis, using enterobacterial repetitive intergenic sequences as primers, discriminated between strains within the same species. Cluster analysis of patterns formed groups that correlated with the source of isolation. For ITS-PCR, extraction of DNA by boiling yeast cells was successfully used.

Animals↗

PubMed2000

Attachment of Escherichia coli O157:H7 to the surfaces and internal structures of apples as detected by confocal scanning laser microscopy.

Confocal scanning laser microscopy (CSLM) was used to demonstrate the attachment of Escherichia coli O157:H7 transformed with a plasmid encoding for green fluorescent protein (GFP) to the surface and within the internal structures of nonwaxed Red Delicious cv. apples. Apples at 2 or 25 degrees C were inoculated with an E. coli O157:H7 cell suspension at 2 or 25 degrees C. The effect of a negative temperature differential (cold inoculum, warm apple), a positive differential (warm inoculum, cold apple), and no differential (warm inoculum, warm apple), in combination with a pressure differential (atmospheric versus 10,130 Pa), on the attachment and infiltration of cells was determined. CSLM stereo images of external surfaces of apples subjected to all combinations of test parameters showed preferential cellular attachment to discontinuities in the waxy cuticle on the surface and to damaged tissue surrounding puncture wounds, where the pathogen was observed at depths up to 70 microm below the skin surface. Attachment to lenticels was sporadic but was occasionally observed at depths of up to 40 microm. Infiltration through the floral tube and attachment to seeds, cartilaginous pericarp, and internal trichomes were observed in all apples examined, regardless of temperature differential during inoculation. The pressure differential had no effect on infiltration or attachment of E. coli O157:H7. Image analysis to count cells at various depths within tissues was used to quantitatively compare the extent of infiltration into various apple structures as well as the effects of the temperature differential. Puncture wounds harbored greater numbers of the pathogen at greater depths than did other sites examined. Attachment or infiltration of cells was greater on the intact skin and in lenticels, russet areas, and the floral tube of apples inoculated under a negative temperature differential compared to those inoculated under no temperature differential. The results suggest that E. coli O157:H7 attached to internal core structures or within tissues of apples may evade decontamination treatments. Interventions designed to deliver disinfectants to these locations or to remove viable cells of E. coli O157:H7 and other pathogens from apples by other means need to be developed and validated.

Animals↗

PubMed2000

PCR detection of Salmonella enterica serotype Montevideo in and on raw tomatoes using primers derived from hilA.

Salmonellae have been some of the most frequently reported etiological agents in fresh-produce-associated outbreaks of human infections in recent years. PCR assays using four innovative pairs of primers derived from hilA and sirA, positive regulators of Salmonella invasive genes, were developed to identify Salmonella enterica serotype Montevideo on and in tomatoes. Based on examination of 83 Salmonella strains and 22 non-Salmonella strains, we concluded that a pair of hilA primers detects Salmonella specifically. The detection limits of the PCR assay were 10(1) and 10(0) CFU/ml after enrichment at 37 degrees C for 6 and 9 h, respectively. When the assay was validated by detecting S. enterica serotype Montevideo in and on artificially inoculated tomatoes, 10(2) and 10(1) CFU/g were detected, respectively, after enrichment for 6 h at 37 degrees C. Our results suggest that the hilA-based PCR assay is sensitive and specific, and can be used for rapid detection of Salmonellae in or on fresh produce.

Bacterial Proteins↗

PubMed2000

Enhancement of clearance of bacteria from murine lungs by immunization with detoxified lipooligosaccharide from Moraxella catarrhalis conjugated to proteins.

Moraxella catarrhalis strain 25238 detoxified lipooligosaccharide (dLOS)-protein conjugates induced a significant rise of bactericidal anti-LOS antibodies in animals. This study reports the effect of active or passive immunization with the conjugates or their antiserum on pulmonary clearance of M. catarrhalis in an aerosol challenge mouse model. Mice were injected subcutaneously with dLOS-tetanus toxoid (dLOS-TT), dLOS-high-molecular-weight proteins (dLOS-HMP) from nontypeable Haemophilus influenzae (NTHi), or nonconjugated materials in Ribi adjuvant and then challenged with M. catarrhalis strain 25238 or O35E or NTHi strain 12. Immunization with dLOS-TT or dLOS-HMP generated a significant rise of serum anti-LOS immunoglobulin G and 68% and 35 to 41% reductions of bacteria in lungs compared with the control (P<0.01) following challenge with homologous strain 25238 and heterologous strain O35E, respectively. Serum anti-LOS antibody levels correlated with its bactericidal titers against M. catarrhalis and bacterial CFU in lungs. Additionally, immunization with dLOS-HMP generated a 54% reduction of NTHi strain 12 compared with the control (P<0.01). Passive immunization with a rabbit antiserum against dLOS-TT conferred a significant reduction of strain 25238 CFU in lungs in a dose- and time-dependent pattern compared with preimmune serum-treated mice. Kinetic examination of lung tissue sections demonstrated that antiserum-treated mice initiated and offset inflammatory responses more rapidly than preimmune serum-treated mice. These data indicate that LOS antibodies (whether active or passive) play a major role in the enhancement of pulmonary clearance of different test strains of M. catarrhalis in mice. In addition, dLOS-HMP is a potential candidate for a bivalent vaccine against M. catarrhalis and NTHi infections.

Animals↗

PubMed2000

Self-assembly of the Agrobacterium tumefaciens VirB11 traffic ATPase.

The Agrobacterium tumefaciens VirB11 ATPase is a component of a type IV transporter dedicated to T-DNA delivery to plant cells. In this study, we tested a prediction from genetic findings that VirB11 self-associates in vivo. A chimeric protein composed of VirB11 fused to the DNA binding domain of lambda cI repressor protein formed dimers, as shown by immunity of Escherichia coli to lambda superinfection. An allele encoding VirB11 fused at its C terminus to the green fluorescent protein (GFP) exerted strong negative dominance when synthesized in wild-type A. tumefaciens cells. Dominance was suppressed by overproduction of native VirB11, suggestive of titrating or competitive interactions between VirB11 and VirB11::GFP. In support of the titration model, a complex of native VirB11 and VirB11::GFP was recovered by precipitation with anti-GFP antibodies from detergent-solubilized A. tumefaciens cell extracts. VirB11 was shown by cI repressor fusion and immunoprecipitation assays to interact with VirB11 derivatives encoded by (i) 11 dominant negative alleles, (ii) recessive alleles bearing codon substitutions or deletions in the Walker A nucleotide binding motif, and (iii) alleles corresponding to the 5' and 3' halves of virB11. Further immunoprecipitation studies showed a hybrid protein composed of the N-terminal half of VirB11 fused to GFP interacted with mutant proteins exerting dominant effects and with a recessive Walker A deletion mutant (Delta GKT174-176). By contrast, a hybrid protein composed of the C-terminal half fused to GFP interacted with mutants exerting dominant effects but not the Walker A mutant protein. Together, these studies establish that VirB11 assembles as homomultimers in vivo via domains residing in each half of the protein. Furthermore, ATP binding appears to be critical for C-terminal interactions required for assembly of productive homomultimers.

Adenosine Triphosphatases↗

PubMed2000

Evaluation of a combination rapid immunoassay for detection of Giardia and Cryptosporidium antigens.

A combination cassette format nonenzymatic rapid immunoassay for detection of Giardia and Cryptosporidium antigens was evaluated by using 556 patient stool specimens from three clinical laboratories. This assay (Genzyme Diagnostics Contrast Giardia/Cryptosporidium), which can be used with fresh or formalin-fixed specimens, had unadjusted sensitivities and specificities of 96.1 and 98.5% for Giardia and 100 and 98.7% for Cryptosporidium, respectively, in this study.

Animals↗

PubMed2000

Transcriptional regulation of the Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor gene.

The Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8, open reading frame (ORF) K9 encodes a viral interferon regulatory factor (vIRF) that functions as a repressor for interferon-mediated signal transduction. Consequently, this gene is thought to play an important role in the tumorigenicity of KSHV. To understand the molecular mechanisms underlying vIRF expression, we studied the transcriptional regulation of this gene. Experiments using 5' rapid amplification of cDNA ends and primer extension revealed that vIRF had different transcriptional patterns during the latent and lytic phases. The promoter region of the minor transcript, which was mainly expressed in uninduced BCBL-1 cells, did not contain a canonical TATA box, but a cap-like element and an initiator element flanked the transcription start site. The promoter of the major transcript, which was mainly expressed in tetradecanoyl phorbol acetate-induced BCBL-1 cells, contained a canonical TATA box. A luciferase reporter assay using a deletion mutant of the vIRF promoter and a mutation in the TATA box showed that the TATA box was critical for the lytic activity of vIRF. The promoter activity in the latent phase was eight times stronger than that of the empty vector but was less than 10% of the activity in the lytic phase. Therefore, KSHV may use different functional promoter elements to regulate the expression of vIRF and to antagonize the cell's interferon-mediated antiviral activity. We have also identified a functional domain in the ORF 50 protein, an immediate-early gene product that is mainly encoded by ORF 50. The ORF 50 protein transactivated the vIRF and DNA polymerase promoters in BCBL-1, 293T, and CV-1 cells. Deleting one of its two putative nuclear localization signals (NLSs) resulted in failure of the ORF 50 protein to localize to the nucleus and consequently abrogated its transactivating activity. We further confirmed that the N-terminal region of the ORF 50 protein included an NLS domain. We found that this domain was sufficient to translocate beta-galactosidase to the nucleus. Analysis of deletions within the vIRF promoter suggested that two sequence domains were important for its transactivation by the ORF 50 protein, both of which included putative SP-1 and AP-1 binding sites. Competition gel shift assays demonstrated that SP-1 bound to these two domains, suggesting that the SP-1 binding sites in the vIRF promoter are involved in its transactivation by ORF 50.

Base Sequence↗

PubMed2000

Activation of transcription of the human cytomegalovirus early UL4 promoter by the Ets transcription factor binding element.

The human cytomegalovirus (HCMV) early UL4 promoter has served as a useful model for studying the activation of early viral gene expression. Previous transient-transfection experiments detected cis-acting elements (the NF-Y site and site 2) upstream of the transcriptional start site (L. Huang and M. F. Stinski, J. Virol. 69:7612-7621, 1995). The roles of two of these sites, the NF-Y site and site 2, in the context of the viral genome were investigated further by comparing mRNA levels from the early UL4 promoter in human foreskin fibroblasts infected by recombinant viruses with either wild-type or mutant cis-acting elements. Steady-state mRNA levels from the UL4 promoter with a mutation in the NF-Y site were comparable to that of wild type. A mutation in an Elk-1 site plus putative IE86 protein binding sites decreased the steady-state mRNA levels compared to the wild type at early times after infection. Electrophoretic mobility shift assays and antibody supershifts detected the binding of cellular transcription factor Elk-1 to site 2 DNA with infected nuclear extracts but not with mock-infected nuclear extracts. The role of cellular transcription factors activated by the mitogen activated protein kinase/extracellular signal-regulated kinase pathway in activating transcription from early viral promoters is discussed.

Base Sequence↗