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Biomedical subjects

R Henry

Publications and source records attributed to R Henry.

At least 37 records · Page 2Linked to original sources

Three-dimensional magnetic resonance spectroscopic imaging of histologically confirmed brain tumors.

The goal of this study was to determine whether presurgical metabolite levels measured by 3D MR Spectroscopic Imaging (MRSI) can accurately detect viable cancer within human brain tumor masses. A total of 31 patients (33 exams, 39 pathology correlations) with brain tumors were studied prior to surgical biopsy and/or resection. The 3D MRSI was obtained with a spatial resolution of 0.2 to 1 cc throughout the majority of the mass and adjacent brain tissue using PRESS-CSI localization. Levels of choline, creatine and NAA were estimated from the locations of the resected tissue and normalized to normal appearing brain tissue. The data were correlated with subsequent histologic analysis of the biopsy tissue samples. Although there were large variations in the metabolite ratios, all regions of confirmed cancer demonstrated significant choline levels and a mean choline/NAA ratio of 5.84 + 2.58 with the lowest value being 1.3. This lowest value is greater than 4 standard deviations above the mean (0.52 +/- 0.13) found in 8 normal volunteers. The choline signal intensities in confirmed cancers were significantly elevated compared to normal appearing brain tissue with a mean ratio of 1.71 +/- 0.69. Spectra with no significant metabolite levels were observed in the non-enhancing necrotic core of the tumor masses. The results of this study indicate that 3D MRSI of brain tumors can detect abnormal metabolite levels in regions of viable cancer and grades and can differentiate cancer from necrosis and/or normal brain tissue.

Biomarkers, Tumor↗

Ritonavir: an extraordinary example of conformational polymorphism.

PURPOSE: In the summer of 1998, Norvir semi-solid capsules supplies were threatened as a result of a new much less soluble crystal form of ritonavir. This report provides characterization of the two polymorphs and the structures and hydrogen bonding network for each form. METHODS: Ritonavir polymorphism was investigated using solid state spectroscopy and microscopy techniques including solid state NMR, Near Infrared Spectroscopy, powder X-ray Diffraction and Single crystal X-ray. A sensitive seed detection test was developed. RESULTS: Ritonavir polymorphs were thoroughly characterized and the structures determined. An unusual conformation was found for form II that results in a strong hydrogen bonding network A possible mechanism for heterogeneous nucleation of form II was investigated. CONCLUSIONS: Ritonavir was found to exhibit conformational polymorphism with two unique crystal lattices having significantly different solubility properties. Although the polymorph (form II) corresponding to the "cis" conformation is a more stable packing arrangement, nucleation, even in the presence of form II seeds, is energetically unfavored except in highly supersaturated solutions. The coincidence of a highly supersaturated solution and a probable heterogeneous nucleation by a degradation product resulted in the sudden appearance of the more stable form II polymorph.

Calorimetry, Differential Scanning↗

Absorption of alkalized intravesical lidocaine in normal and inflamed bladders: a simple method for improving bladder anesthesia.

PURPOSE: Pharmacokinetic studies have shown that intravesical lidocaine is not sufficiently absorbed by human bladders to achieve significant serum levels and it only provides a superficial local anesthetic effect. We investigated the pharmacokinetics of alkalized intravesical lidocaine in healthy volunteers and patients with interstitial cystitis to determine a safe dose of buffered lidocaine, the effect of interstitial cystitis on lidocaine uptake and the acute local anesthetic effect on bladder pain in interstitial cystitis. MATERIALS AND METHODS: An initial dose finding study was done in 12 healthy volunteers using 4, 5 and 6 mg./kg. 5% lidocaine buffered with 8.4% sodium bicarbonate. Serial lidocaine levels were measured for 3 hours. Serum measurement was repeated in 12 patients with interstitial cystitis using 5 mg/kg. 5% lidocaine with sodium bicarbonate daily for 2 days. Patients rated pain before and during treatment. RESULTS: Healthy volunteers and patients with interstitial cystitis had similar lidocaine absorption profiles with a peak of 1.06 microg/ml. (range 0.66 to 1.71) and 1.3 (range 0.2 to 2.0) at about 30 minutes. Mean pain score in the interstitial cystitis group decreased from a baseline of 6.0 to 1.8 on day 1 and 0.6 on day 2. There were complaints of urethral discomfort after voiding the buffered lidocaine in each group. CONCLUSIONS: Alkalization provides safe and predictable lidocaine absorption into the bladder, as indicated by therapeutic systemic levels in healthy and inflamed bladders. Furthermore, the decrease in acute pain scores in the interstitial cystitis group indicated a concentration of local anesthetic within the bladder wall that was sufficient to block the sensory neurons within the submucosal plexus.

Absorption↗

February asthma outbreaks in NSW: a case control study.

OBJECTIVES: To investigate individual factors associated with an asthma outbreak among children aged one to 14 years in Sydney in February 1999. METHODS: A case control study was undertaken with cases (n=92) defined as all children admitted to Sydney Children's Hospital for asthma in February 1999. Unmatched controls (n=76) were all children admitted for asthma in the previous three months. We obtained information by a structured telephone survey of parents. Logistic regression analyses were used to determine odds ratios for risk factors for hospital admission. RESULTS: Mean age for hospital admission of 4.7 years for cases and 4.4 years for controls. The presence of one or more siblings reduced the risk of admission during an asthma outbreak (OR=0.59, 95% CI 0.37 to 0.93). Children with older siblings aged 10 to 14 years were also less likely to be admitted (OR=0.3, 95% CI 0.12 to 0.74). An age effect was observed. Other demographic, clinical and environmental characteristics, including smoking, were not associated with admission during the outbreak. CONCLUSIONS: The main findings of this study are the protective effect of siblings and an age-dependent effect in risk of hospital admission during an asthma outbreak. These findings are consistent with an infective cause of the outbreak. IMPLICATIONS: Children without siblings, particularly older siblings, appear to be at highest risk of hospital admission during an asthma outbreak. Environmental and other factors need to be examined to further explain the episodicity of such outbreaks and to determine means of predicting and preventing future episodes.

Adolescent↗

Effect of acute exercise on citrate synthase activity in untrained and trained human skeletal muscle.

Maximal citrate synthase activity (CS) is routinely used as a marker of aerobic capacity and mitochondrial density in skeletal muscle. However, reported CS has been notoriously variable, even with similar experimental protocols and sampling from the same muscles. Exercise training has resulted in increases in CS ranging from 0 to 100%. Previously, it has been reported that acute exercise may significantly affect CS. To investigate the hypothesis that the large variation in CS that occurs with training is influenced by alterations during the exercise itself, we studied CS in human vastus lateralis both in the rested and acutely exercised state while trained and untrained (n = 6). Tissues obtained from four biopsies (untrained rested, untrained acutely exercised, trained rested, and trained acutely exercised) were analyzed spectrophotometrically for maximal CS. Exercise training measured in a rested state resulted in an 18.2% increase in CS (12.3 +/- 0.3 to 14.5 +/- 0.3 micromol x min(-1) x g tissue(-1), P < or = 0.05). However, even greater increases were recorded 1 h after acute exercise: 49.4% in the untrained state (12.3 +/- 0.3 to 18.3 +/- 0.5 micromol x min(-1) x g tissue(-1), P < or = 0.05) and 50.8% in the trained state (14.5 +/- 0.3 to 21.8 +/- 0.4 micromol x min(-1) x g tissue(-1), P < or = 0.05). Ultrastructural analysis, by electron microscopy, supported an effect of acute exercise with the finding of numerous swollen mitochondria 1 h after exercise that may result in greater access to the CS itself in the CS assay. In conclusion, although unexplained, the increased CS with acute exercise can clearly confound training responses and artificially elevate CS values. Therefore, the timing of muscle sampling relative to the last exercise session is critical when measuring CS and offers an explanation for the large variation in CS previously reported.

Adult↗

The water level influence on biomass of Echinochloa polystachya (Poaceae) in the Jurumirim Reservoir (São Paulo, Brazil).

In the Paranapanema River mouth, Jurumirim Reservoir (23 degrees 27'-23 degrees 29'S and 48 degrees 39'-48 degrees 36'W, SP, Brazil), the biomass of E. polystachya was monthly determined with eight quadrats of 0.25 m2 from August 1993 to July 1994. The seasonal variation in biomass was unimodal, with greater biomass from November 1993 to April 1994. The average biomass was 1,933.7 +/- 479.5 gDW.m-2, with a variation along the year from 1,149.0 to 2,755.9 gDW.m-2. The annual variation of aerial green biomass, aerial and aquatic detritus suggest that the main growth period of E. polystachya was from December 1993 to May 1994, with peak between February to March 1994. The data indicate that this macrophyte is adapted to water level variation.

Biomass↗

Changing approaches to asthma management in Australia: effects on asthma morbidity.

Asthma is an important public health issue in Australia and is responsible for significant morbidity and mortality in the community. Recognition of the impact of asthma on the health of Australians, and the apparent failure of new medications to reduce mortality and hospital admission rates resulted in a major review by the stakeholders in asthma care. This led to new approaches to asthma management based on strategic use of asthma medications and the development of the Asthma Management Plan (AMP). The AMP drew together current understanding of asthma to develop a simple stepwise approach to management that could be readily applied in patient management. The National Asthma Campaign (NAC), a coalition of the major stakeholders in asthma care, was launched in 1990 to lead the dissemination of the AMP. In association with other organisations interested in asthma care in Australia, the NAC has developed the AMP, and co-ordinated a decade of education and advocacy about asthma that targeted doctors, health professionals and the general public. These activities have been successful in raising awareness about asthma in the community. However, recent research, while demonstrating the continued uptake of written asthma action plans for asthma and decrease in use of inhaled bronchodilator medications, reported a decrease in use of preventive therapy by people with asthma. These activities have had a sustained impact on asthma-related health outcomes with mortality at the lowest level since 1960 and a decline in hospital readmission rates. This is useful information because there is sound evidence that the prevalence and possibly severity of asthma in children has increased. However, review of management in primary care and among people who present to emergency services with acute asthma suggest that many people continue to manage their asthma poorly. Continued education is needed to build on the progress that has been made. There are opportunities to do this through efforts to integrate general practitioners into the wider health system through the formation of Divisions of General Practice. Recognition of asthma as a health priority area at a national level will help to enhance and maintain awareness of the public health importance of asthma and facilitate the further development of the initiatives begun during the last decade or more.

Asthma↗

Childhood asthma: can computers aid detection in general practice?

BACKGROUND: Childhood asthma remains underdiagnosed in general practice. Computers with a patient interface have the potential to screen children for asthma in a time-efficient manner. AIM: To develop a concise, validated self-report measure that calculates an 'asthma score' that predicts likelihood of asthma and its severity in childhood. DESIGN OF STUDY: Computerised questionnaire survey in general practitioners' (GPs') waiting rooms, followed by a written questionnaire and either bronchial challenge or skin allergy testing at the regional teaching hospital. SETTING: Children between 18 months and 18 years old accompanied by a parent or guardian in five group practices in Newcastle in New South Wales, Australia. METHOD: The responses from both the computerised questionnaire and the written questionnaire were compared with physician assessment of asthma, based on an existing validated questionnaire and clinical tests. RESULTS: Six items were identified to be independently and significantly associated (at P < 0.05) with the presence of asthma and its severity: parent or self-reported asthma, previous diagnosis, wheeze in the past year, physical activity affected by symptoms, night cough in the past year, and visits to a GP in the past year. From the regression model a linear score was derived that indicates whether a child is likely to have asthma and its likely severity. CONCLUSIONS: The asthma score is a valid indicator of asthma and its severity in children in general practice.

Adolescent↗

Analysis of grape ESTs: global gene expression patterns in leaf and berry.

Analysis of 2479 ESTs from Vitis vinifera berry tissue and 2438 from leaf revealed that 1% of the ESTs match to known Vitis proteins, 72% to plant proteins, 11% to non-plant, and 16% had no match (P[N]>0.5). The levels of redundancy were similar in the leaf and berry libraries. Only 12% of the genes matched by the ESTs were common to both libraries indicating marked differences in the genes expressed in the two tissues. The abundance of transcripts with predicted cellular roles in leaf and berry were estimated by classifying the primary BLAST matches to known proteins (score >80) into functional categories. Thirty-six percent of the leaf transcripts were involved in photosynthesis, compared to 3% in the berry. This is a much higher proportion of transcripts involved with a function limited to specialized cells, than was found when transcripts of 33 human tissues were compared using a similar approach, suggesting plant cells may involve their cellular machinery to a greater extent in specialized activities than animal cells. Relatively enhanced expression of specific transcription factors, and genes involved in defense, detoxification, stress response, proteolysis, trafficing, and signal transduction, suggests berry tissue is actively engaged in responding to environmental stimuli.

Journal Article↗

The L18 domain of light-harvesting chlorophyll proteins binds to chloroplast signal recognition particle 43.

Chloroplast signal recognition particle (cpSRP) is a novel type of SRP that contains a homolog of SRP54 and a 43-kDa subunit absent from all cytoplasmic SRPs but lacks RNA. It is also distinctive in its ability to post-translationally interact with light-harvesting chlorophyll proteins (LHCP), hydrophobic proteins synthesized in the cytoplasm and targeted to the thylakoid via the stroma. LHCP integration into thylakoid membranes requires the two subunits of cpSRP, cpFtsY, GTP, and the membrane protein ALB3. It had previously been shown that the L18 domain, an 18-amino acid peptide between the second and third transmembrane domains, and a hydrophobic domain are required for interaction with cpSRP. In the present study we used a pull-down assay, with cpSRP43 or cpSRP54 fused to glutathione-transferase, to study interactions between cpSRP43, cpSRP54, LHCP, and cpFtsY. cpFtsY was not observed to form significant interactions with any of the proteins even in the presence of nonhydrolyzable GTP analogs. Our data indicate that cpSRP43 binds to the L18 domain, that cpSRP54 binds to the hydrophobic domain, and that LHCP and cpSRP54 independently bind to cpSRP43. These data confirm that the novel post-translational interaction between LHCP and cpSRP is mediated through binding to cpSRP43.

Amino Acid Sequence↗

A novel precursor recognition element facilitates posttranslational binding to the signal recognition particle in chloroplasts.

Signal recognition particles (SRPs) in the cytosols of prokaryotes and eukaryotes are used to target proteins to cytoplasmic membranes and the endoplasmic reticulum, respectively. The mechanism of targeting relies on cotranslational SRP binding to hydrophobic signal sequences. An organellar SRP identified in chloroplasts (cpSRP) is unusual in that it functions posttranslationally to localize a subset of nuclear-encoded thylakoid proteins. In assays that reconstitute thylakoid integration of the light harvesting chlorophyll-binding protein (LHCP), stromal cpSRP binds LHCP posttranslationally to form a cpSRP/LHCP transit complex, which is believed to represent the LHCP form targeted to thylakoids. In this investigation, we have identified an 18-aa sequence motif in LHCP (L18) that, along with a hydrophobic domain, is required for transit complex formation. Fusion of L18 to the amino terminus of an endoplasmic reticulum-targeted protein, preprolactin, led to transit complex formation whereas wild-type preprolactin exhibited no ability to form a transit complex. In addition, a synthetic L18 peptide, which competed with LHCP for transit complex formation, caused a parallel inhibition of LHCP integration. Translocation of proteins by the thylakoid Sec and Delta pH transport systems was unaffected by the highest concentration of L18 peptide examined. Our data indicate that a motif contained in L18 functions in precursor recruitment to the posttranslational SRP pathway, one of at least four different thylakoid sorting pathways used by chloroplasts.

Amino Acid Sequence↗

Chloroplast Oxa1p homolog albino3 is required for post-translational integration of the light harvesting chlorophyll-binding protein into thylakoid membranes.

Multiple sorting pathways operate in chloroplasts to localize proteins to the thylakoid membrane. The signal recognition particle (SRP) pathway in chloroplasts employs the function of a signal recognition particle (cpSRP) to target light harvesting chlorophyll-binding protein (LHCP) to the thylakoid membrane. In assays that reconstitute stroma-dependent LHCP integration in vitro, the stroma is replaceable by the addition of GTP, cpSRP, and an SRP receptor homolog, cpFtsY. Still lacking is an understanding of events that take place at the thylakoid membrane including the identification of membrane proteins that may function at the level of cpFtsY binding or LHCP integration. The identification of Oxa1p in mitochondria, an inner membrane translocase component homologous to predicted proteins in bacteria and to the albino3 (ALB3) protein in thylakoids, led us to investigate the potential role of ALB3 in LHCP integration. Antibody raised against a 50-amino acid region of ALB3 (ALB3-50aa) identified a single 45-kDa thylakoid protein. Treatment of thylakoids with antibody to ALB3-50aa inhibited LHCP integration, whereas the same antibody treatment performed in the presence of antigen reversed the inhibition. In contrast, transport by the thylakoid Sec or Delta pH pathways was unaffected. These data support a model whereby a distinct translocase containing ALB3 is used to integrate LHCP into thylakoid membranes.

Arabidopsis↗

Informed consent for labour epidurals: what labouring women want to know.

PURPOSE: To determine A) what a labouring woman expects to hear about epidural analgesia before consenting, B) if she feels able to understand the risks and thereby assess if we are obtaining informed consent. METHODS: Sixty actively labouring women were surveyed immediately after requesting an epidural. Demographic, labour, epidural and consent information were included in the questionnaire. Answers were categorical (yes/no, multiple choice) or scored on a scale from 0 to 10 (visual analogue scale). RESULTS: The majority of parturients wanted all potential epidural complications but not their incidences disclosed in the consent process. However, a discussion of risks would not dissuade women from consenting to an epidural in the majority of cases. Labouring women have a moderate understanding of epidural risks. The ability to understand risks was not affected by labour pain, anxiety, opioid premedication, duration of labour pain, desire for an epidural, previous epidural experience, level of education or age. CONCLUSION: This prospective survey characterizes what 60 reasonable labouring women wanted to know about labour epidural analgesia. Parturients wanted all risks of epidural analgesia disclosed in the informed consent process. The majority of women did not want the incidences quoted. This study suggests that labouring patients are as able to give informed consent as are other members of our patient population.

Adult↗

Validation of the ISAAC video questionnaire (AVQ3.0) in adolescents from a mixed ethnic background.

BACKGROUND: The International Study of Asthma and Allergies in Childhood (ISAAC) has developed an international version of the asthma video questionnaire (AVQ3.0) to measure asthma prevalence. This questionnaire has not been validated in adolescents from a mixed ethnic background. OBJECTIVE: The aims of this study were to compare the video questionnaire with a written questionnaire in the detection of airway hyperresponsiveness to hypertonic saline in a population of adolescents from a mixed ethnic background, and to establish the repeatability and psychometric properties of the asthma video questionnaire. METHODS: The study was conducted in four secondary schools in Sydney, an area with a high proportion of people from a non-English speaking background. Four hundred and seventy-five students from schools 1 and 2 completed the video questionnaire and a subgroup of these students (n = 170) completed the written questionnaire and a hypertonic saline inhalation challenge. Reproducibility of the questionnaire was evaluated by administering the questionnaire to a subsample of students 2 weeks later. The psychometric properties of the video questionnaire were examined in 852 students at two other schools (schools 3 and 4). RESULTS: One hundred and sixty-nine students aged 13.5 (sd 1.3) years completed both written and video questionnaires, and the hypertonic saline challenge. The students had widely different cultural backgrounds including Asian, South Pacific, Middle Eastern, European and African countries. There was good agreement between the questionnaires for wheeze (kappa 0.42). Questions on the video questionnaire concerning wheezing had good sensitivity (90%) and specificity (68%) for airway hyperresponsiveness to hypertonic saline. The video questionnaire was reproducible (kappa 0.82), had good internal consistency (Cronbach's alpha 0.81) and each question pertained to a single construct explaining 58% of the variance in total score. CONCLUSION: This study has validated the international version of the ISAAC video questionnaire against airway hyperresponsiveness to hypertonic saline in adolescents from a mixed ethnic background, and identified that the questionnaire has good psychometric properties. The ISAAC video has proved to be a valuable tool for the assessment of asthma prevalence in populations of ethnic diversity.

Adolescent↗

Microsatellite analysis of genetic structure in the mangrove species Avicennia marina (Forsk.) Vierh. (Avicenniaceae).

The level of genetic variation throughout the entire worldwide range of the mangrove species Avicennia marina (Forsk.) Vierh. was examined using microsatellite markers. Three microsatellite loci detected high levels of allelic diversity (70 alleles in total), essential for an accurate estimation of population genetic parameters. The informativeness of the microsatellite loci tended to increase with increasing average number of repeats. The levels of heterozygosity detected for each population, over all loci, ranged from 0.0 to 0.8, with an average of 0.407, indicating that some populations had little or no genetic variation, whereas others had a large amount. Populations at the extremes of the distribution range showed reduced levels of heterozygosity, and significant levels of inbreeding. This is not unexpected as these populations may be subject to founder effects and environmental constraints. The presence of genetic structure was tested in A. marina populations using three models: (i) a single panmictic model; (ii) the discrete subpopulation model; and (iii) the isolation by distance model. The discrete subpopulations model was supported by the overall measures of population differentiation based on the infinite alleles model (F-statistics), and the stepwise mutation model (R statistics). In addition, an analysis of molecular variance (AMOVA), using both theoretical models, found that most of the variation was between populations (41-71%), and within individuals in the total population (31-49%). There was little variation among individuals within populations (0-10%). There was no significant isolation by distance. The high levels of genetic differentiation observed among populations of A. marina may be due to environmental and ecological factors, particularly past sea level and climatic changes.

Alleles↗