bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ubiquinone Synthesis in Mitochondrial and Microsomal Subcellular Fractions of
Pneumocystis
spp.: Differential Sensitivities to Atovaquone
Authors: Basselin Mireille , Hunt Shannon M. , Abdala-Valencia Hiam , Kaneshiro Edna S. 
Published: August 2005

ABSTRACT

The lung pathogen
Pneumocystis
spp. is the causative agent of a type of pneumonia that can be fatal in people with defective immune systems, such as AIDS patients. Atovaquone, an analog of ubiquinone (coenzyme Q [CoQ]), inhibits mitochondrial electron transport and is effective in clearing mild to moderate cases of the infection. Purified rat-derived intact
Pneumocystis carinii
cells synthesize de novo four CoQ homologs, CoQ
7
, CoQ
8
, CoQ
9
, and CoQ
10
, as demonstrated by the incorporation of radiolabeled precursors of both the benzoquinone ring and the polyprenyl chain. A central step in CoQ biosynthesis is the condensation of
p
-hydroxybenzoic acid (PHBA) with a long-chain polyprenyl diphosphate molecule. In the present study, CoQ biosynthesis was evaluated by the incorporation of PHBA into completed CoQ molecules using
P. carinii
cell-free preparations. CoQ synthesis in whole-cell homogenates was not affected by the respiratory inhibitors antimycin A and dicyclohexylcarbodiimide but was diminished by atovaquone. Thus, atovaquone has inhibitory activity on both electron transport and CoQ synthesis in this pathogen. Furthermore, both the mitochondrial and microsomal fractions were shown to synthesize de novo all four
P. carinii
CoQ homologs. Interestingly, atovaquone inhibited microsomal CoQ synthesis, whereas it had no effect on mitochondrial CoQ synthesis. This is the first pathogenic eukaryotic microorganism in which biosynthesis of CoQ molecules from the initial PHBA:polyprenyl transferase reaction has been unambiguously shown to occur in two distinct compartments of the same cell.
Candida albicans
Biofilm-Defective Mutants
Authors: Richard Mathias L. , Nobile Clarissa J. , Bruno Vincent M. , Mitchell Aaron P. 
Published: August 2005

ABSTRACT

Biofilm formation plays a key role in the life cycles and subsistence of many microorganisms. For the human fungal pathogen
Candida albicans
, biofilm development is arguably a virulence trait, because medical implants that serve as biofilm substrates are significant risk factors for infection. The development of
C. albicans
biofilms in vitro proceeds through an early phase, in which yeast cells populate a substrate, an intermediate phase, in which pseudohyphal and hyphal cell types are produced, and a maturation phase, in which continued cell growth is accompanied by accumulation of an extracellular matrix. Here we report the results of a screen for
C. albicans
biofilm-defective mutants, in which homozygous insertions in
NUP85
,
MDS3
,
KEM1
, and
SUV3
were found to block biofilm development. Confocal microscopic examination suggests that
nup85
,
suv3
, and
mds3
mutations cause early-phase arrest, whereas the
kem1
mutation causes intermediate-phase arrest. All of the mutants are defective in hypha production in several media. Analysis of mixed-biofilm development indicates that all of the mutants are defective in the production of hyphae in the context of a biofilm. Because all of the mutants are defective in the retention of cells in the biofilm, we infer that hyphae provide an adherent scaffold that stabilizes the biofilm structure.
The effects of knee-ankle-foot orthoses in the treatment of Duchenne muscular dystrophy: review of the literature
Authors: Bakker J P J , de Groot I J M , Beckerman H , de Jong B A , Lankhorst G J 
Published: August 2005

Objective:A systematic review of the available literature on the effectiveness of knee-ankle-foot orthoses in the treatment of Duchenne muscular dystrophy. Design:A computer search was carried out (MEDLINE 1966–97, CINAHL 1982–97) using the key words muscular dystrophy, rehabilitation, locomotion, braces or orthotic devices. References in relevant publications and nonindexed journals were also examined. Criteria to include and exclude articles were formulated. We used a systematic review procedure to evaluate the literature. Seven methodological criteria were formulated. Results:Thirty articles describing 35 studies met the inclusion criteria for our review, nine studies were selected based on completeness of information on study population, treatment and quantitative presentation of the effect outcome. Operations on the lower limbs were performed on most patients. A concomitant programme of rehabilitation was not described thoroughly. A percentage success of treatment was calculated for eight studies. Median percentage after one year was 75.1, after two years 47.9 and after three years 24.3. The median for the means of independent walking was 24 months, the median for the means of assisted walking was 36.2 months and the median for the means of standing ability was 50.5 months duration. Conclusion: The scientific strength of the studies reviewed is poor. It seems that the use of knee-ankle foot orthoses can prolong assisted walking and standing, but it is uncertain whether it can prolong functional walking. The boys that benefit most have a relatively low rate of deterioration, are capable of enduring an operation and are well motivated.
Inter-rater reliability of the Frenchay Activities Index in patients with stroke and their carers
Authors: Piercy Martina , Carter Judy , Mant Jonathan , Wade Derick T 
Published: August 2005

Objective: To measure the inter-rater reliability of the interview-administered version of the Frenchay Activities Index (FAI). Design: Comparison of FAI score on the same person when administered by two raters (mean time between interviews 15.2 days). Subjects: Fifty-nine Oxfordshire residents who either had had a stroke (n = 35) or were the main carer (n = 24). Results: The 95% limits of agreement for the FAI totals were –9.9 to +8.4. The kappa statistic for nine of the 15 items showed a good level of agreement between the two research interviews (0.64–0.80). The other six items showed fair or moderate strength of agreement (0.26–0.52). Three items showed significant differences between the two raters p < 0.05 (Wilcoxon's sign paired rank sum test). The mean difference between the total scores was –0.76 (95% confidence interval from –1.98 to 0.46). Spearman's rho correlation coefficient for FAI totals of rater B against A was r(59) = 0.93 (p < 0.001). Conclusion: The FAI is a reliable tool for measuring outcome following stroke. Suggestions are made to strengthen the reliability, and consequently the validity of the measure.
Reliability of tremor measurements using a multidimensional electromagnetic sensor system
Authors: Spyers-Ashby Julia M , Stokes Maria J 
Published: August 2005

Objective: To investigate the reliability of repeated measurements of normal physiological tremor made with a multidimensional measurement system. Equipment: Measurements of postural upper limb tremor at the hand were made in 10 normal subjects using a 3Space Fastrak® (Polhemus, Inc.) which detects movement over six degrees-of-freedom (three of the measurement directions were examined). Data collection: Reliability was assessed for two alternative upper limb postures (arm straight or bent) and data were collected on two days, twice at each session, to determine the repeatability between and within recording sessions. Data analysis: The data were split into segments and subjected to autoregressive (AR) modelling. Three parameters (one for each of the measurement directions examined) were extracted from the models and used as variables for the reliability analysis. Statistical tests: Variation within and between sessions was assessed by finding the median differences between efforts and days for each subject and then finding the overall median value and the corresponding 97.9% confidence intervals for each movement. This produced estimates of the population median value and indicated the precision of the estimates. Results: All the confidence intervals encompassed the zero median difference point indicating that, in the population, this technique would produce repeatable results. For between-efforts comparisons there was some evidence that data collected for the bent arm posture were more repeatable than for a straight arm. Conclusion: Normal physiological tremor can be measured reliably, within and between sessions, using the 3Space Fastrak system.
The Huntingdon Day Hospital Trial: secondary outcome measures
Authors: Burch Sarah , Longbottom Jenny , McKay Maggie , Borland Colin , Prevost Toby 
Published: August 2005

Objective: To compare day hospital to day centre rehabilitation using scales to measure mobility, activities of daily living and quality of life. Design: Single blind randomized controlled trial with home assessments at baseline (twice), six weeks and three months. Setting: Mainly rural health district. Day hospital and social services day centres in market towns. Interventions: Day hospital treatment or day centre rehabilitation by a physiotherapist and two health support workers. Main outcome measures: World Health Organization mobility scale scored with and without aid, Nottingham Extended Activities of Daily Living Scale and Nottingham Health Profile. Subjects: One hundred and five physically disabled older patients living at home referred for day hospital rehabilitation or maintenance before discharge from hospital (66) or referred as outpatients (39). Results: At three months there were no statistically significant differences between rehabilitation at day hospital and day centre for any of the outcome measurements. However, there were significant improvements between baseline and three months for the following subscales [mean change per six-week period (95% confidence interval)]: WHO mobility subscale (with aid) – 0.67 (–0.99,–0.35); Nottingham Health Profile mobility subscale –10 (–15.5,–4.5) Nottingham extended ADL mobility subscale +3.08 (1.78,4.37); Nottingham extended ADL leisure subscale +1.66 (0.96,2.36). Conclusion: There were no differences between day hospital and day centre in the outcomes measured. Day rehabilitation appeared to improve functional ability and mobility and scales reflecting these domains deserve further evaluation as outcome measures in this patient group. However, no improvement in quality of life was observed.
A randomized controlled trial of strapping to prevent post-stroke shoulder pain
Authors: Hanger H C , Whitewood P , Brown G , Ball M C , Harper J , Cox R , Sainsbury R 
Published: August 2005

Objective: To determine whether strapping the shoulder in hemiplegic stroke patients: (1) prevents the development, or reduces the severity, of shoulder pain, (2) preserves range of movement in the shoulder, and (3) improves the functional outcomes for the arm and patient overall. Design: A prospective, randomized, single-blind controlled trial of shoulder strapping versus no strapping. Setting: Care of the elderly wards in a teaching hospital, Christchurch, New Zealand. Subjects: All patients admitted with an acute hemiplegic stroke, who had persisting weakness of shoulder abduction. Intervention: The treatment group had their affected shoulder strapped for six weeks from randomization in addition to standard physiotherapy. Main outcome measures: All subjects were assessed at entry (week 0), at end of the treatment phase (week 6) and two months later (week 14). A visual analogue scale (VAS) was used to assess shoulder pain severity whereas shoulder range of movement to the point of pain (SROMP) assessed passive range of movement and pain. Functional Independence Measure (FIM), Motor Assessment Scale (MAS) and Rankin Disability Index measured functional outcomes. Results: Ninety-eight subjects participated (49 strapped, 49 controls). Intention to treat analysis showed no significant difference in pain, range of movement or functional outcomes after the intervention phase or at the final assessment. However there were trends for less pain at six weeks (VAS, p = 0.11) and better final upper limb function (MAS, p = 0.16) in strapped patients. Skin reactions were uncommon (6.1%). The presence of neglect or sensory loss, but not subluxation, at baseline was independently associated with poor outcome. Range of movement was lost early (mean difference SROMP between hemiplegic and contralateral shoulders at baseline = 15.2° (95% CI 10.9–19.5)) and continued throughout the study. Shoulder strapping did not alter the rate at which range of movement was lost. Conclusions: No significant benefit with shoulder strapping was demonstrated and reasons for this are discussed. Range of movement in the hemiplegic shoulder is lost very early and any preventive treatments need to begin within the first 1–2 days after a stroke.
Computer recording of standard tests of visual neglect in stroke patients
Authors: Potter Jonathan , Deighton Tony , Patel Mehool , Fairhurst Michael , Guest Richard , Donnelly Nick 
Published: August 2005

Objective: To determine whether a computer-based method for recording standardized assessment of neglect identifies abnormalities in the ‘process’ as well as in the ‘outcome’ of such tasks. Design: Prospective sequential assessment of patients admitted to a stroke rehabilitation unit. Subjects: All consecutive patients with right-sided cerebrovascular accident confirmed on computerized tomography (CT) scan including 30 patients with neglect, 57 patients without neglect. An age-matched control group of 13 subjects. Intervention: All patients were tested using the standard Rivermead Behavioural Inattention Test (BIT) and by computer recording of two standard tests for assessing neglect (line bisection and Albert's test). Age-matched controls were tested using computer recording of the two standard tests. Main outcome measures: Neglect was defined using the BIT with a cut-off score of 129. Computer recording measured the ‘outcome’ of tasks, i.e. the deviation from midline and omissions in cancellation, as well as the ‘process’ of tasks, i.e. time between cancellations, components of cancellation time including premovement, movement and drawing time, and the starting point for cancellation. Results: The computer recording identified significant differences in ‘outcome’ and ‘process’ which distinguished neglect from non-neglect patients. There were significant differences between non-neglect patients and age-matched controls with regard to ‘process’ measures but not with regard to ‘outcome’ measures. Conclusions: Computer recording of standard tests for assessing neglect identifies novel impairments with regard to the process of carrying out tasks. These impairments may be used to investigate changes in neglect with time, the response of neglect to treatment and to explore further the neuropsychological changes associated with neglect in stroke patients.
The Relationship between Parity and Bone Mineral Density in Women Characterized by a Homogeneous Lifestyle and High Parity
Authors: Streeten Elizabeth A. , Ryan Kathleen A. , McBride Daniel J. , Pollin Toni I. , Shuldiner Alan R. , Mitchell Braxton D. 
Published: August 2005

Abstract
Context: We reported previously that Old Order Amish (OOA) women have fewer hip fractures and higher bone mineral density (BMD) than non-Amish Caucasian women.
Objective: The objective of this study was to determine whether the high parity characteristic of OOA women contributes to their relative bone health. Previous data on the long-term effects of parity on BMD have yielded conflicting results with few data from very high parity populations. This observational study included participants in the Amish Family Osteoporosis Study, begun in 1997 to identify genetic and clinical determinants of osteoporosis in the OOA. We measured BMD by dual-energy x-ray absorptiometry at the spine, hip, and distal radius in 424 parous OOA women aged 40 and older (mean age, 57.7 ± 12 yr; mean parity, 7.6 ± 2.9).
Results: Increasing parity was associated with later menopause (P = 0.001) and modestly, but not significantly, higher body mass index (BMI) (P = 0.09). Increasing parity was associated with higher BMD at the total hip and trochanter (age-adjusted P = 0.02 and 0.03), no longer statistically significant after accounting for BMI. Among women aged 50–59 yr, parity was strongly associated with BMD even after accounting for age and BMI (age-adjusted P = 0.02), although this was not true for women younger than 50 or at least 60 yr old.
Conclusions: We conclude that high parity is associated with increased hip BMD in OOA women, largely mediated by higher BMI. The parity-hip BMD association remained statistically significant after accounting for age and BMI only in women aged 50–59 yr, partially explained by a later menopausal age with high parity. The benefit of high parity on BMD appeared to be lost soon after the menopausal transition, and, therefore, these data provide evidence of neither a detrimental nor beneficial effect of high parity on long-term bone health.
Mutation at Cleavage Site of Insulin-Like Growth Factor Receptor in a Short-Stature Child Born with Intrauterine Growth Retardation
Authors: Kawashima Yuki , Kanzaki Susumu , Yang Fan , Kinoshita Tomoe , Hanaki Keiichi , Nagaishi Jun-ichi , Ohtsuka Yoshihiko , Hisatome Ichirou , Ninomoya Haruaki , Nanba Eiji , Fukushima Toshiaki , Takahashi Shin-Ichiro 
Published: August 2005

Context: Mouse knockout models have clearly demonstrated the critical importance of IGF-I and IGF receptor type 1 (IGF-IR) for embryonic growth as well as postnatal growth.Objective: We hypothesized that mutations of IGF-IR gene might predispose to short stature in children born with intrauterine growth retardation (IUGR).Patients: Twenty-four children with unexplained IUGR (birth weight &lt; −1.5 sd) and short stature (&lt;−2.0 sd) were screened for abnormalities of the IGF-IR gene.Methods: Direct DNA sequencing was used to identify IGF-IR gene mutations. Unprocessed IGF-IR proreceptor in fibroblasts was detected by immunoblot analysis. Functions of mutated IGF-IR in fibroblasts were evaluated by IGF-I binding, and IGF-I-stimulated DNA synthesis and β-subunit autophosphorylation.Results: We found the following results: 1) a heterozygous mutation (R709Q) changing the cleavage site from Arg-Lys-Arg-Arg to Arg-Lys-Gln-Arg was identified in a 6-yr-old Japanese girl (case 1) and her mother who also had IUGR with short stature (case 2); 2) fibroblasts from case 2 contained more IGF-IR proreceptor protein (189 ± 26% of normal) and less mature β-subunit protein (63 ± 12%); 3) [125I]IGF-I binding to fibroblasts from case 2 was reduced, compared with normal control (0.61 ± 0.16 × 106vs. 1.14 ± 0.12 × 106 sites per cell; P &lt; 0.05); and 4) both IGF-I-stimulated [3H]thymidine incorporation and IGF-IR β-subunit autophosphorylation were low in fibroblasts from case 2, compared with those of control (P &lt; 0.05).Conclusions: These findings strongly suggest that this mutation leads to failure of processing of the IGF-IR proreceptor to mature IGF-IR and causes short stature and IUGR.
l-Folic Acid Supplementation in Healthy Postmenopausal Women: Effect on Homocysteine and Glycolipid Metabolism
Authors: Villa Paola , Perri Concetta , Suriano Rosanna , Cucinelli Francesco , Panunzi Simona , Ranieri Micaela , Mele Cristina , Lanzone Antonio 
Published: August 2005

Context: Hyperhomocysteinemia as well as alterations of glycemic and lipidic metabolism are recognized as risk factors for cardiovascular diseases.
Objective: The aim of this study was to examine the effect of l-folic acid supplementation on homocysteine (Hcy) and related thiols, such as cysteine (Cys) and Cys-glycine (Cys-Glyc) pathways and their relationship to glucose, insulin, and lipidic metabolism in normoinsulinemic postmenopausal women.
Design: This study was a randomized placebo, not double-blind, trial.
Setting: The study was performed in an academic research center.
Patients or Other Participants: Twenty healthy postmenopausal women were selected. No patient was taking drugs known to affect lipid or glucose metabolism.
Intervention(s): Patients underwent two hospitalizations before and after 8 wk of l-acid folic (7.5 mg/d) or placebo administration. The glycemic metabolism was studied by an oral glucose tolerance test and a hyperinsulinemic euglycemic clamp. Hcy metabolism was studied by a standardized oral methionine-loading test.
Main Outcome Measure(s): Hcy, Cys, and Cys-Glyc, basally and after a methionine loading test, were measured. Basal insulin, glucose, and peptide C levels as well as area under the curve for insulin, area under the curve for peptide, hepatic insulin extraction, and metabolic index were assayed. The total cholesterol, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol levels and the cholesterol/HDL and LDL/HDL ratios were also measured.
Results: The total basal Hcy concentration and the plasma postmethionine loading Hcy values were significantly decreased (P &lt; 0.01) in l-folic acid-treated patients, whereas postmethionine loading Cys-Glyc levels were markedly increased (P &lt; 0.02). Furthermore, l-folic acid intake induced a significant improvement in carbohydrate metabolism through an increase in fractional hepatic insulin extraction (P &lt; 0.05) and peripheral insulin sensitivity (P &lt; 0.02) in normoinsulinemic women. HDL levels considerably increased, inducing an improvement in other atherosclerotic indexes, such as cholesterol/HDL and LDL/HDL ratios (P &lt; 0.03).
Conclusions: These results show that folic acid supplementation lowers plasma Hcy levels and improves insulin and lipid metabolism, reducing the risk of cardiovascular disease.
Soluble fms-Like Tyrosine Kinase 1 Is Increased in Preeclampsia But Not in Normotensive Pregnancies with Small-for-Gestational-Age Neonates: Relationship to Circulating Placental Growth Factor
Authors: Shibata Eiji , Rajakumar Augustine , Powers Robert W. , Larkin Robert W. , Gilmour Carol , Bodnar Lisa M. , Crombleholme William R. , Ness Roberta B. , Roberts James M. , Hubel Carl A. 
Published: August 2005

Context: An excess of the soluble receptor, fms-like tyrosine kinase 1 (sFlt-1) may contribute to maternal vascular dysfunction in women with preeclampsia by binding and thereby reducing concentrations of free vascular endothelial growth factor and placental growth factor (PlGF) in the circulation. The putative stimulus for increased sFlt-1 during preeclampsia, placental hypoxia due to poor perfusion, is common to both preeclampsia and idiopathic intrauterine growth restriction. However, the latter condition occurs without maternal vascular disease.
Objective: We asked whether, as with preeclampsia, sFlt-1 is increased and free PlGF is decreased in villous placenta and maternal serum of normotensive women with small-for-gestational-age (SGA) neonates.
Study Design: This was a case-control study using banked samples. Groups of women with SGA neonates (birth weight centile &lt; 10th) and women with preeclampsia were matched to separate sets of normal pregnancy controls based on gestational age at blood sampling (serum) or gestational age at delivery (placenta).
Results: sFlt-1 levels were higher in preeclamptics than controls (serum, P &lt; 0.0001; placental protein, P = 0.03; placental mRNA, P = 0.007) but not increased in SGA pregnancies. PlGF was lower in both preeclampsia (serum, P &lt; 0.0001; placental protein, P = 0.05) and SGA (serum, P = 0.0008; placental protein, P = 0.03) compared with their controls. PlGF in preeclampsia and SGA groups did not differ.
Conclusions: These data are consistent with a role for sFlt-1 in the maternal manifestations of preeclampsia. In contrast to preeclampsia, sFlt-1 does not appear to contribute substantially to decreased circulating free PlGF in SGA pregnancies in the absence of a maternal syndrome.