Biomedical subjects

J Song

Publications and source records attributed to J Song.

At least 91 records · Page 5Linked to original sources

PubMed2001

Porteus Maze performance following traumatic brain injury in children.

To investigate planning in traumatically brain injured children, the authors gave the Porteus Maze Test (PMT; S. D. Porteus, 1959) to 276 pediatric patients who had sustained a traumatic brain injury (TBI) at least 3 years previously. Sensitivity of the PMT to TBI severity, age at test, and volume of focal brain lesions detected by magnetic resonance imaging was also studied. The Peabody Picture Vocabulary Test-Revised (L. M. Dunn & L. M. Dunn, 1981) was also administered as a control measure. Results indicated that the PMT was highly sensitive to TBI severity and to volume of circumscribed prefrontal lesions. In contrast to the PMT data, receptive vocabulary was related to injury severity but not to discrete prefrontal lesions. Implications for mechanisms of cognitive deficit after TBI in children are discussed.

Adolescent↗

PubMed2001

Bag1-Hsp70 mediates a physiological stress signalling pathway that regulates Raf-1/ERK and cell growth.

Survival after stress requires the precise orchestration of cell-signalling events to ensure that biosynthetic processes are alerted and cell survival pathways are initiated. Here we show that Bag1, a co-chaperone for heat-shock protein 70 (Hsp70), coordinates signals for cell growth in response to cell stress, by downregulating the activity of Raf-1 kinase. Raf-1 and Hsp70 compete for binding to Bag1, such that Bag1 binds to and activates Raf-1, subsequently activating the downstream extracellular signal-related kinases (ERKs). When levels of Hsp70 are elevated after heat shock, or in cells conditionally overexpressing Hsp70, Bag1-Raf-1 is displaced by Bag1-Hsp70, and DNA synthesis is arrested. Mutants Bag1C204A and Bag1E208A, which cannot bind Hsp70, constitutively activate Raf-1/ERK kinases but are unaffected by Hsp70; consequently neither Bag1-Raf-1 nor DNA synthesis is negatively affected during heat shock. Likewise, mutants Hsp70F245S, Hsp70R262W and Hsp70L282R, which retain chaperone activity but do not bind to Bag1, fail to repress Bag1 activation of Raf-1/ERK kinase. We propose that Bag1 functions in the heat-shock response to coordinate cell growth signals and mitogenesis, and that Hsp70 functions as a sensor in stress signalling.

Animals↗

PubMed2001

An evaluation of the change in electrocardiographic P-wave variables after acute caffeine ingestion in normal volunteers.

BACKGROUND: Caffeine's effect on supraventricular dysrhythmias is poorly understood, and establishing a marker to predict atrial fibrillation may help to explain supraventricular dysrhythmias caused by caffeine. OBJECTIVE: To evaluate the effects of caffeine (mean 6.1 mg/kg) on maximum P-wave duration and P-wave dispersion in normal volunteers. METHOD: A randomised, double-blind, placebo-controlled, crossover study in 10 healthy volunteers at least 17 years of age at the University of Connecticut. Participants abstained from caffeinated products for at least 2 days before study initiation and were randomly allocated on different days to receive placebo or caffeine 400 mg. For each of the study phases, a baseline 12-lead electrocardiogram (ECG) was performed and a subsequent 12-lead ECG was performed 3 h after ingesting the study drug. RESULTS: No significant changes were found within intra- or intergroup comparisons for any P-wave variables measured. CONCLUSION: Single dose caffeine (400 mg) does not affect average P-wave duration, maximum P-wave duration or P-wave dispersion in normal individuals.

Adult↗

PubMed2001

Regulation of catalase-peroxidase (KatG) expression, isoniazid sensitivity and virulence by furA of Mycobacterium tuberculosis.

Mycobacterium tuberculosis has two genes for ferric uptake regulator orthologues, one of which, furA, is situated immediately upstream of katG encoding catalase-peroxidase, a major virulence factor that also activates the prodrug isoniazid. This association suggested that furA might regulate katG and other genes involved in pathogenesis. Transcript mapping showed katG to be expressed from a strong promoter, with consensus -10 and -35 elements, preceding furA. No promoter activity was demonstrated downstream of the furA start codon, using different gene reporter systems, indicating that furA and katG are co-transcribed from a common regulatory region. The respective roles of these two genes in the isoniazid susceptibility and virulence of M. tuberculosis were assessed by combinatorial complementation of a Delta(furA-katG) strain that is heavily attenuated in a mouse model of tuberculosis. In the absence of furA, katG was upregulated, cells became hypersensitive to isoniazid, and full virulence was restored, indicating that furA regulates the transcription of both genes. When furA alone was introduced into the Delta(furA-katG) mutant, survival in mouse lungs was moderately increased, suggesting that FurA could regulate genes, other than katG, that are involved in pathogenesis. These do not include the oxidative stress genes ahpC and sodA, or those for siderophore production.

Animals↗

PubMed2001

Validity and sensitivity to change of the extended Glasgow Outcome Scale in mild to moderate traumatic brain injury.

Using a structured outcome interview, this study addressed the validity and sensitivity to change of the Glasgow Outcome Scale (GOS) and the Extended GOS (GOSE) in a prospective study of patients who sustained mild (n = 30) to moderate (n = 13) traumatic brain injury (TBI) or general trauma (n = 44). The patients were recruited from the emergency center or inpatient units of Ben Taub General Hospital and invited to participate in follow-up examinations at 3 and 6 months. Using a series of functional outcome measures, assessment of affective status, and neuropsychological tests as criteria, the validity of the GOSE generally exceeded the GOS. Analysis of the outcome data for the patients who completed both the 3-month and 6-month assessments disclosed that the GOSE was more sensitive to change than the GOS. Comparison of the 3-month outcome data disclosed that the GOSE and GOS scores did not differ for the TBI and general trauma groups. These findings lend further support for utilization of the GOSE in clinical trials when it is based on a structured interview.

Adult↗

PubMed2001

Longitudinal outcome of verbal discourse in children with traumatic brain injury: three-year follow-up.

PURPOSE: This study compared changes in discourse ability between two groups of children age 5 to 10 years after brain injury: those with severe traumatic brain injury (TBI) and those with mild/moderate injury over 3-year follow-up testing. MATERIALS AND METHODS: Forty-three children with TBI were recruited from a larger research project examining cognitive and linguistic recovery after injury. Twenty-two of these patients had severe injuries and 21 sustained mild/moderate injuries. All children were presented an ordered sequence of pictures and asked to verbally produce a story/narrative discourse. Each child was then asked to produce a lesson relating to the story. RESULTS: The severe group performed significantly worse than the mild/moderate group when performance across all four discourse domains was considered. Both groups improved across time on selected discourse measures. Qualitative analysis suggested that the severe group showed differential rates of improvement across the individual discourse variables over the 3-year interval. CONCLUSIONS: Severe TBI can have a pernicious effect on discourse abilities in children years after injury compared with children with mild/moderate injuries. The major caveat is that the discourse measures must be sufficiently challenging when used to assess older children and children with milder forms of TBI.

Analysis of Variance↗

PubMed2001

Lumbosacral plexopathy in gunshot wounds and motor vehicle accidents: comparison of electrophysiologic findings.

OBJECTIVE: To characterize the differences between injuries to the lumbosacral (LS) plexus caused by gunshot wounds (GSW) and motor vehicle crashes (MVC) with regard to the location and extent of involvement. DESIGN: A retrospective review of electrophysiologic data from an electromyography laboratory of a county hospital. Nineteen patients with GSW and ten patients with MVC diagnosed by electromyography with an LS plexopathy were included in the study. Injuries were categorized by the number of anatomic quadrants of the LS plexus: upper anterior, upper posterior, lower anterior, and lower posterior. Comparison of upper vs. lower portions and bilaterality of LS plexus involvement was also made. Statistical analyses were performed with two-tailed Fisher's exact and general association tests. RESULTS: Lower portions of the plexus were involved more frequently in patients with MVC compared those observed in patients with GSW. Upper portions of the LS plexus were more involved compared with the lower portions in patients with GSW injuries. More sections of the plexus were involved in patients with MVC compared with those in patients with GSW. CONCLUSIONS: Compared with patients with MVC, patients with GSW had a greater chance of involvement of the upper portion of the plexus. The reverse was true for the lower portion. Hopefully this information will aid the electromyographer and rehabilitation team in the diagnosis and treatment of traumatic plexopathies caused by different etiologies.

Accidents, Traffic↗

PubMed2001

Lifetime and novel psychiatric disorders after pediatric traumatic brain injury.

OBJECTIVE: To assess lifetime and current psychiatric disorders at least 1 year after traumatic brain injury (TBI) in children and adolescents. METHOD: Forty-six youths who sustained a TBI between the ages of 6 through 15 years were evaluated at least 1 year post-TBI to identify the presence of lifetime and/or novel psychiatric disorders. Semistructured interviews of the parent and child and standardized parent self-report rating instruments were used. RESULTS: Attention-deficit/hyperactivity disorder and depressive disorders were the most common lifetime and novel diagnoses. A wide variety and high rate of novel psychiatric disorders were identified; 74% of these disorders persisted in 48% of the injured children. Internalizing disorders were more likely to resolve than externalizing disorders. Both interviews and parent ratings were sensitive to current externalizing behaviors; interviews more often detected internalizing disorders, whereas parent ratings also identified cognitive difficulties. CONCLUSIONS: Findings were generally consistent with previous research demonstrating the high rate of novel psychiatric disorders following pediatric TBI. Psychiatric interviews were sensitive in identifying both lifetime and novel disorders.

Attention Deficit Disorder with Hyperactivity↗

PubMed2001

A model of dynamic side-chain--side-chain interactions in the alpha-lactalbumin molten globule.

Proteins in the molten globule state contain high levels of secondary structure, as well as a rudimentary, nativelike tertiary topology. Thus, the structural similarity between the molten globule and native proteins may have a significant bearing in understanding the protein-folding problem. To explore the nature of side-chain--side-chain interactions in the alpha-lactalbumin (alpha-LA) molten globule, we determined the effective concentration for formation of the 28--111 disulfide bond in 14 double-mutant proteins, each containing two hydrophobic core residues replaced by alanine. We compared our results with those of single-alanine substitutions using the framework of double-mutant cycle analysis and found that, in the majority of cases, the effects of two alanine substitutions are additive. Based on these results, we propose a model of side-chain-side-chain interactions in the alpha-LA molten globule, which takes into consideration the dynamic nature of this partially folded species.

Alanine↗

PubMed2001

Mycobacterial FurA is a negative regulator of catalase-peroxidase gene katG.

In several bacteria, the catalase-peroxidase gene katG is under positive control by oxyR, a transcriptional regulator of the peroxide stress response. The Mycobacterium tuberculosis genome also contains sequences corresponding to oxyR, but this gene has been inactivated in the tubercle bacillus because of the presence of multiple mutations and deletions. Thus, M. tuberculosis katG and possibly other parts of the oxidative stress response in this organism are either not regulated or are controlled by a factor different from OxyR. The mycobacterial FurA is a homologue of the ferric uptake regulator Fur and is encoded by a gene located immediately upstream of katG. Here, we examine the possibility that FurA regulates katG expression. Inactivation of furA on the Mycobacterium smegmatis chromosome, a mycobacterial species that also lacks an oxyR homologue, resulted in derepression of katG, concomitant with increased resistance of the furA mutant to H2O2. In addition, M. smegmatis furA::Km(r) was more sensitive to the front-line antituberculosis agent isonicotinic acid hydrazide (INH) compared with the parental furA+ strain. The phenotypic manifestations were specific, as the mutant strain did not show altered sensitivity to organic peroxides, and both H2O2 and INH susceptibility profiles were complemented by the wild-type furA+ gene. We conclude that FurA is a second regulator of oxidative stress response in mycobacteria and that it negatively controls katG. In species lacking a functional oxyR, such as M. tuberculosis and M. smegmatis, FurA appears to be a dominant regulator affecting mycobacterial physiology and intracellular survival.

Bacterial Proteins↗

PubMed2001

Transmembrane domain (TM) 9 represents a novel site in P-glycoprotein that affects drug resistance and cooperates with TM6 to mediate [125I]iodoarylazidoprazosin labeling.

The multidrug resistant cell line DC-3F/ADII was obtained by stepwise selection for growth in actinomycin D (ActD). Compared with parental cells, it displays high resistance to ActD and vincristine and low resistance to colchicine and daunorubicin. These cells overexpress a form of P-glycoprotein (Pgp1) containing a double mutation, I837L and N839I, in transmembrane domain (TM) 9; when transfected into DC-3F, this mutation confers the DC-3F/ADII phenotype. We have shown previously that another cell line, DC-3F/ADX, also displays this phenotype and overexpresses a mutant form of Pgp1 containing a double mutation in TM6 (G338A, A339P). Hence, mutations in TM9 and TM6 are independently capable of conferring the same cross-resistance phenotype. The TM6 mutations inhibit the ability of cyclosporin A to reverse cross-resistance and to block labeling of the protein by [125I]iodoarylazidoprazosin (IAAP), whereas the TM9 mutations do not show similar effects. A chimeric protein containing both pairs of mutations confers twice the level of resistance to ActD than expected from the sum of the individual mutations, but it cannot be labeled to detectable levels with [125I]IAAP. Thus, TM9 represents a novel site that cooperates with TM6 to mediate drug resistance and [125I]IAAP labeling.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

Silencing of oxidative stress response in Mycobacterium tuberculosis: expression patterns of ahpC in virulent and avirulent strains and effect of ahpC inactivation.

Intracellular pathogens such as Mycobacterium tuberculosis are able to survive in the face of antimicrobial products generated by the host cell in response to infection. The product of the alkyl hydroperoxide reductase gene (ahpC) of M. tuberculosis is thought to be involved in protecting the organism against both oxidative and nitrosative stress encountered within the infected macrophage. Here we report that, contrary to expectations, ahpC expression in virulent strains of M. tuberculosis and Mycobacterium bovis grown in vitro is repressed, often below the level of detection, whereas expression in the avirulent vaccine strain M. bovis BCG is constitutively high. The repression of the ahpC gene of the virulent strains is independent of the naturally occurring lesions of central regulator oxyR. Using a green fluorescence protein vector (gfp)-ahpC reporter construct we present data showing that repression of ahpC of virulent M. tuberculosis also occurred during growth inside macrophages, whereas derepression in BCG was again seen under identical conditions. Inactivation of ahpC on the chromosome of M. tuberculosis by homologous recombination had no effect on its growth during acute infection in mice and did not affect in vitro sensitivity to H2O2. However, consistent with AhpC function in detoxifying organic peroxides, sensitivity to cumene hydroperoxide exposure was increased in the ahpC::Km(r) mutant strain. The preservation of a functional ahpC gene in M. tuberculosis in spite of its repression under normal growth conditions suggests that, while AhpC does not play a significant role in establishing infection, it is likely to be important under certain, as yet undefined conditions. This is supported by the observation that repression of ahpC expression in vitro was lifted under conditions of static growth.

Animals↗

PubMed2001

Mapping of Mycobacterium tuberculosis katG promoters and their differential expression in infected macrophages.

Intracellular pathogenic bacteria, including Mycobacterium tuberculosis, frequently have multitiered defense mechanisms ensuring their survival in host phagocytic cells. One such defense determinant in M. tuberculosis is the katG gene, which encodes an enzyme with catalase, peroxidase, and peroxynitritase activities. KatG is considered to be important for protection against reactive oxygen and nitrogen intermediates produced by phagocytic cells. However, KatG also activates the front-line antituberculosis drug isoniazid, hence rendering M. tuberculosis exquisitely sensitive to this compound. In this context, katG expression represents a double-edged sword, as it is an important virulence determinant but at the same time its activity levels determine sensitivity to INH. Thus, it is important to delineate the regulation and expression of katG, as this not only can aid understanding of how M. tuberculosis survives and persists in the host but also may provide information of relevance for better management of INH therapy. Here, we report the first extensive analysis of the katG promoter activity examined both in vitro and in vivo. Using S1 nuclease protection analysis, we mapped the katG mRNA 5' ends and demonstrated that two promoters, P(1)furA and P(1)katG, control transcription of katG. The furA and katG genes are cotranscribed from P(1)furA. Both P(1)furA and P(1)katG promoters show induction upon challenge with hydrogen peroxide and cumene hydroperoxide. Studies carried out using the transcriptional fusions P(1)furA-gfp, P(1)katG-gfp, and P(1)furA-P(1)katG-gfp confirmed the existence of two katG promoters. In addition, we showed that both promoters are expressed in vivo during intracellular growth of virulent M. tuberculosis H37Rv. P(1)furA is induced early upon infection, and P(1)katG becomes active only upon extended growth in macrophages. These studies delineate the transcriptional organization of the furA-katG region and indicate differential regulation in vivo of the two katG promoters. These phenomena most likely reflect the differing demands at sequential stages of the infection cycle and may provide information for improved understanding of host-pathogen interactions in tuberculosis and for further optimization of INH chemotherapy.

Bacterial Proteins↗

PubMed2001

Overexpression of Na+/Ca2+ exchanger alters contractility and SR Ca2+ content in adult rat myocytes.

The functional consequences of overexpression of rat heart Na+/Ca2+ exchanger (NCX1) were investigated in adult rat myocytes in primary culture. When maintained under continued electrical field stimulation conditions, cultured adult rat myocytes retained normal contractile function compared with freshly isolated myocytes for at least 48 h. Infection of myocytes by adenovirus expressing green fluorescent protein (GFP) resulted in >95% infection as ascertained by GFP fluorescence, but contraction amplitude at 6-, 24-, and 48-h postinfection was not affected. When they were examined 48 h after infection, myocytes infected by adenovirus expressing both GFP and NCX1 had similar cell sizes but exhibited significantly altered contraction amplitudes and intracellular Ca2+ concentration ([Ca2+]i) transients, and lower resting and diastolic [Ca2+]i when compared with myocytes infected by the adenovirus expressing GFP alone. The effects of NCX1 overexpression on sarcoplasmic reticulum (SR) Ca2+ content depended on extracellular Ca2+ concentration ([Ca2+]o), with a decrease at low [Ca2+]o and an increase at high [Ca2+]o. The half-times for [Ca2+]i transient decline were similar, suggesting little to no changes in SR Ca2+-ATPase activity. Western blots demonstrated a significant (P < or = 0.02) threefold increase in NCX1 but no changes in SR Ca2+-ATPase and calsequestrin abundance in myocytes 48 h after infection by adenovirus expressing both GFP and NCX1 compared with those infected by adenovirus expressing GFP alone. We conclude that overexpression of NCX1 in adult rat myocytes incubated at high [Ca2+]o resulted in enhanced Ca2+ influx via reverse NCX1 function, as evidenced by greater SR Ca2+ content, larger twitch, and [Ca2+]i transient amplitudes. Forward NCX1 function was also increased, as indicated by lower resting and diastolic [Ca2+]i.

Adenoviridae↗

PubMed2001

Behavioural assessment for HIV prevention: a model programme design.

This paper describes a model HIV prevention programme for relief agencies working in extremely impoverished or socially disrupted areas. A detailed behavioural inventory is proposed to assess: sexual behaviours, traditional cutting procedures, midwifery practices, the availability of injectables and injection equipment in local markets, the use of intoxicants, sex workers, prisons, military behaviours, community beliefs, and the performance of the community health infrastructure. The needs of AIDS orphans and the stigmatizations of person's with AIDS are also assessed. This assessment also examines who has authority to address these issues and what measures of programme assessment could be used for each programme area. The model is currently being tested in south Sudan.

HIV Infections↗

PubMed2001

Genetic variations of cholesterol ester transfer protein gene in Koreans.

An absence of cholesterol ester transfer protein (CETP, protein; CETP, gene) results in an increase of the apolipoprotein AI levels and a decrease in the low density lipoprotein (LDL) levels. Thus, the CETP polymorphism is important in the assessment of risk of atherosclerosis. This study was conducted to elucidate the genotype distributions of the CETP polymorphism and association with plasma lipid levels in Koreans. The genotypes of the TaqI A and B polymorphic loci were associated with plasma triglyceride levels in the control and coronary artery disease (CAD) groups. There was linkage disequilibrium between TaqI A and B loci in the control group (chi2 = 5.58, p < 0.05). Association studies of the CETP polymorphism have been carried out mainly with Caucasian populations; however, the results have not been consistent among different populations. A possible explanation for this diversity among populations may be differences in genetic backgrounds, which may be more important than environmental factors. We discuss the reasons for the incompatibility of the CETP polymorphism among populations.

Alleles↗

PubMed2001

Hematologic and chemical changes observed during and after cardiac arrest in a canine model--a pilot study.

STUDY OBJECTIVE: To evaluate the effect of cardiac arrest and cardiopulmonary resuscitation (CPR) on blood chemistry in a canine model. DESIGN: Evaluative canine animal study. SETTING: Animal laboratory accredited by the Association for Assessment and Accreditation of Laboratory Animals. SUBJECTS: Twenty-six adult mongrel dogs. INTERVENTION: The dogs underwent an episode of induced fibrillatory cardiac arrest for 3 minutes followed by 10 minutes of standard CPR. Blood samples were taken at baseline (before cardiac arrest), after 10 minutes of ventricular fibrillation, and 10 minutes after successful resuscitation for determination of blood chemistries and hematologic parameters. MEASUREMENTS AND MAIN RESULTS: Glucose, blood urea nitrogen, serum creatinine, sodium, potassium, chloride, calcium, phosphorus, uric acid, alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, protein, albumin, cholesterol, triglycerides, iron, white blood cell count, red blood cell count, and hematocrit were measured. Significant changes (p<0.05) in values obtained during CPR versus baseline values were noted for all laboratory parameters except blood urea nitrogen, chloride, and alkaline phosphatase. Eighteen dogs achieved return of spontaneous circulation (ROSC); their laboratory values were obtained after CPR. Significant changes (p<0.05) after ROSC compared with baseline were noted for all laboratory values except chloride, blood urea nitrogen, uric acid, alkaline phosphatase, glucose, potassium, calcium, triglycerides, iron, red blood cell count, and hematocrit. CONCLUSION: Results indicate that significant changes in blood chemistries and hematologic parameters occur during and after CPR. Clinicians should note these normal laboratory parameter changes when interpreting laboratory data in patients who experience cardiac arrest.

Animals↗

PubMed2001

An evaluation of the hemostatic effects of hydrophilic, alcohol, and lipophilic extracts of notoginseng.

STUDY OBJECTIVE: To compare the hemostatic effects of hydrophilic, alcohol, or lipophilic extract of notoginseng with those of the control and placebo. DESIGN: Hemorrhagic rat model. SETTING: Hartford Hospital, Hartford, Connecticut; animals were housed at the Hartford Hospital animal facility. ANIMALS: Sixty-two male Wistar rats. Intervention. Administration of placebo (wheat flour), and alcohol, hydrophilic (water), and lipophilic (hexane) extracts of notoginseng. METHODS: Rats were divided into five groups, and their tails were transected 5 mm from the tip. Group 1 received no treatment (control), group 2 received placebo, group 3 received alcohol extract, group 4 received hydrophilic extract, and group 5 received lipophilic extract. Total bleeding time was determined and compared among the groups. MAIN RESULTS: Bleeding time was shorter for the placebo group than the control group (p=0.035). The alcohol extract group had the shortest bleeding time, which was significantly shorter than that of the control (p<0.0001), placebo (p=0.0124), and lipophilic extract groups (p=0.002). The hydrophilic extract group had a shorter bleeding time than the control group (p=0.0058) and showed a trend toward shorter bleeding time than the lipophilic extract group (p=0.068). CONCLUSIONS: The alcohol extract of notoginseng results in the shortest bleeding time and provides better hemostatic effects than no treatment, placebo treatment, and treatment with lipophilic extract.

Animals↗