ABSTRACT
BACKGROUND: Human papillomavirus type 16 (HPV16)-E6 antibodies are detectable in peripheral blood before diagnosis in the majority of HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), but the timing of seroconversion is unknown. PATIENTS AND METHODS: We formed the HPV Cancer Cohort Consortium which comprises nine population cohorts from Europe, North America and Australia. In total, 743 incident OPSCC cases and 5814 controls provided at least one pre-diagnostic blood sample, including 111 cases with multiple samples. Median time between first blood collection and OPSCC diagnosis was 11.4 years (IQR = 6-11 years, range = 0-40 years). Antibodies against HPV16-E6 were measured by multiplex serology (GST fusion protein based Luminex assay). RESULTS: HPV16-E6 seropositivity was present in 0.4% of controls (22/5814; 95% CI 0.2% to 0.6%) and 26.2% (195/743; 95% CI 23.1% to 29.6%) of OPSCC cases. HPV16-E6 seropositivity increased the odds of OPSCC 98.2-fold (95% CI 62.1-155.4) in whites and 17.2-fold (95% CI 1.7-170.5) in blacks. Seropositivity in cases was more frequent in recent calendar periods, ranging from 21.9% pre-1996 to 68.4% in 2005 onwards, in those with blood collection near diagnosis (lead time <5 years). HPV16-E6 seropositivity increased with lead time: 0.0%, 13.5%, 23.7%, and 38.9% with lead times of >30 years (N = 24), 20-30 years (N = 148), 10-20 years (N = 228), and <10 years (N = 301 cases) (p-trend < 0.001). Of the 47 HPV16-E6 seropositive cases with serially-collected blood samples, 17 cases seroconverted during follow-up, with timing ranging from 6 to 28 years before diagnosis. For the remaining 30 cases, robust seropositivity was observed up to 25 years before diagnosis. CONCLUSIONS: The immune response to HPV16-driven tumorigenesis is most often detectable several decades before OPSCC diagnosis. HPV16-E6 seropositive individuals face increased risk of OPSCC over several decades.
Subject(s)
Antibodies, Viral/blood , Human papillomavirus 16/immunology , Oropharyngeal Neoplasms/diagnosis , Papillomavirus Infections/diagnosis , Squamous Cell Carcinoma of Head and Neck/diagnosis , Adult , Aged , Carcinogenesis/immunology , Case-Control Studies , Female , Follow-Up Studies , Human papillomavirus 16/isolation & purification , Humans , Male , Middle Aged , Oncogene Proteins, Viral/immunology , Oropharyngeal Neoplasms/blood , Oropharyngeal Neoplasms/immunology , Oropharyngeal Neoplasms/virology , Papillomavirus Infections/blood , Papillomavirus Infections/immunology , Papillomavirus Infections/virology , Prospective Studies , Repressor Proteins/immunology , Seroconversion , Squamous Cell Carcinoma of Head and Neck/blood , Squamous Cell Carcinoma of Head and Neck/immunology , Squamous Cell Carcinoma of Head and Neck/virology , Time FactorsABSTRACT
The Sf9 and Sf21 cell lines derived from ovarian tissues of the wide-host-range phytophagous lepidopteran Spodoptera frugiperda are widely used for research and commercial-scale production of recombinant proteins. These cell lines are chronically infected with a rhabdovirus (Sf-RV) that does not cause any overt cytopathic effects. We demonstrate that wild populations of S. frugiperda in the eastern United States and Caribbean are infected with genetically diverse strains of Sf-RV and that this virus is also capable of infecting cells of Spodoptera exigua, Heliothis subflexa, and Bombyx mori Feeding studies demonstrated the ability of S. frugiperda larvae to deposit Sf-RV onto human-consumed vegetables during feeding. Although no evidence for replication in two species of plant cells was detected, subcellular localization studies demonstrated that the Sf-RV nucleocapsid was targeted to plasmodesmata, while two forms of the accessory protein were differentiated on the basis of their ability to localize to nuclei. Collectively, the results from this study suggest that environmental exposure of humans to Sf-RV is likely to be commonplace and frequent, but its inability to replicate in plant or human cells suggests that there is no substantial risk to human health.IMPORTANCE Insect-derived cell lines are widely used commercially for the production of vaccines and protein-based pharmaceuticals. After decades of safe and beneficial use, it was a surprise to the biotechnology industry to discover an endemic rhabdovirus in Sf9 cells. This discovery was made possible only by the substantial advancements in DNA sequencing technologies. Given the public health concerns associated with many rhabdovirus species, several initiatives were undertaken to establish that Spodoptera frugiperda rhabdovirus (Sf-RV) does not pose a threat to humans. Such actions include the generation of cell lines that have been cleared of Sf-RV. Given that Sf9 is derived from a moth whose larvae feed on human-edible foods, we explored the prevalence of Sf-RV in its wild and lab-grown populations, as well as its ability to be deposited on food items during feeding. Collectively, our data suggest that there is no overt risk from exposure to Sf-RV.
Subject(s)
Host Specificity/physiology , Rhabdoviridae/physiology , Spodoptera/virology , Animals , Cell Line , Humans , Insecta/virology , Larva/metabolism , Larva/virology , Plants/virology , Recombinant Proteins/metabolism , Rhabdoviridae/metabolism , Sf9 Cells , Spodoptera/metabolism , Viral Proteins/metabolismABSTRACT
BACKGROUND: Serious cardiac valve disease and left ventricular hypertrophy occur in most untreated older children with severe mucopolysaccharidosis type I. Although it is assumed that early intervention prevents these processes, evaluation of cardiac findings in these infants has not yet been reported. METHODS: We reviewed echocardiograms of 13 untreated infants < 1 year of age with severe mucopolysaccharidosis type I who had undergone evaluation for hematopoietic cell transplantation. We recorded left ventricular chamber dimensions, septal and posterior wall thicknesses, ventricular function, and aortic sinus diameters. We evaluated mitral and aortic valves for increased thickness, regurgitation, and stenosis. RESULTS: Average age (7M, 6F) was 221 (range 25-347) days. Left ventricular chamber dimension was ≥2 SD of normal in 3/13; wall thicknesses were ≥2 SD of normal in 2/13 infants. Systolic function was normal. Mitral valves were thickened in all infants; mitral regurgitation was present in 9/13, but significant in only three infants. Aortic valves were thickened in 10/13, but no infant had significant aortic regurgitation. Neither mitral nor aortic stenosis occurred. Aortic roots were dilated to ≥2 SD of normal in 5/13. CONCLUSIONS: Characteristic cardiac features of severe mucopolysaccharidosis type I can be seen in infancy. Mitral and aortic valve thickening are nearly universally present, even in the youngest infants. In 20-30 % of infants, other abnormalities such as left ventricular dilation, increased wall thickness, and mild mitral/aortic regurgitation may occur. Aortic root dilation is a frequent finding. Early intervention with enzyme replacement therapy may minimize the incidence and severity of cardiac findings in these infants. SUMMARY: Serious cardiac valve disease and left ventricular hypertrophy occur in most untreated older children with severe mucopolysaccharidosis type I. Although it is assumed that early intervention prevents these processes, evaluation of cardiac findings in these infants has not yet been reported. In our study of 13 infants with severe untreated MPS I < 1 year of age, mitral and aortic valve thickening was nearly universally present and aortic root dilation was frequent. Despite this, we found a lower incidence of left ventricular hypertrophy and both a lower incidence and milder expression of mitral and aortic valve dysfunction than previously reported in older children. These findings suggest that earlier intervention, including neonatal screening, may be of benefit to children with severe MPS I.
ABSTRACT
California Assembly Bill AB487 mandates that all practicing physicians are required to obtain 12 h of Continuing Medical Education in Pain Management and End of Life Care before the year 2006 in order to renew their state license to practice medicine. In order to determine the effectiveness of this bill in influencing the practice of medicine, we conducted the first of five planned annual Pain Management seminars and utilized physician questionnaires to determine possible practice changes as a result of this seminar. Eighty-one physicians representing 17 multiple specialties of medicine enrolled in this seminar. The topics included: management of malignant and non-malignant pain, pharmacology and management of side effects of opiate and non-opiate analgesics, and adjunctive therapies including depression management and spirituality issues. Physicians were asked to respond to an immediate post-seminar questionnaire and were subsequently queried 4 months following the conference. Fifty-one out of 81 physician registrants responded to an immediate post-attendance questionnaire, and 31 responded to the 4-month follow-up questionnaire. Responses included: [Please see text]. This audience represents the most motivated group of practitioners electing to receive Pain Management Education long before the mandated deadline. Sixty-seven percent expressed an interest in changing their practice following this intensive educational experience. Ninety percent responding to the follow-up evaluation indicated that their practices had changed, suggesting that this seminar series is effective in altering physician practice patterns (supported by Cancer Center Support Grant CA 33572 and Sarnat Foundation).
Subject(s)
Analgesics, Non-Narcotic/therapeutic use , Analgesics, Opioid/therapeutic use , Education, Medical, Continuing , Pain/drug therapy , Practice Patterns, Physicians' , California , Follow-Up Studies , HumansABSTRACT
OBJECTIVES: To assess the cost-effectiveness of outpatient (at home) cervical ripening with isosorbide mononitrate (IMN) prior to induction of labour. DESIGN: Economic evaluation was conducted alongside a randomised placebo controlled trial (the IMOP trial). SETTING: Large UK maternity hospital. POPULATION: A total of 350 nulliparous women with a singleton pregnancy, cephalic presentation > or = 37 weeks gestation, requiring cervical ripening prior to induction of labour. INTERVENTIONS: Isosorbide mononitrate (n = 177) or placebo (n = 173) self-administered vaginally at home at 48, 32 and 16 hours prior to the scheduled time of admission for induction. RESULTS: Mean health service costs between the period of randomisation and discharge for mother and infant were 1254.86 pound sterling in the IMN group and 1242.88 pound sterling in the placebo group, generating a mean cost difference of 11.98 pound sterling (bootstrap mean cost difference 12.86 pound sterling; 95%CI: -106.79 pound sterling, 129.39 pound sterling) that was not statistically significant (P = 0.842). The incremental cost per hour prevented from hospital admission to delivery was 7.53 pound sterling. At the notional willingness to pay threshold of 100 pound sterling per hour prevented from hospital admission to delivery, the probability that IMN is cost-effective was estimated at 0.67. This translated into a mean net monetary benefit of 98.13 pound sterling for each woman given IMN. CONCLUSIONS: Although the probability that IMN is cost-effective approaches 0.7 at seemingly low willingness to pay thresholds for an hour prevented from hospital admission to delivery, our results should be viewed in the light of the clinical findings from the IMOP trial.
Subject(s)
Ambulatory Care/economics , Cervical Ripening/drug effects , Home Care Services/economics , Isosorbide Dinitrate/analogs & derivatives , Labor, Induced , Nitric Oxide Donors/economics , Cost-Benefit Analysis , Female , Health Care Costs/statistics & numerical data , Hospitalization/statistics & numerical data , Humans , Isosorbide Dinitrate/economics , Labor, Induced/economics , Pregnancy , Prenatal Care/economics , Prenatal Care/statistics & numerical dataABSTRACT
Because of the dynamic nature of many managed habitats, proper evaluation of conservation efforts calls for models that take into account both spatial and temporal habitat dynamics. We develop a metapopulation model for successional-type systems, in which habitat quality changes over time in a predictable fashion. The occupancy and recruitment of the predatory saproxylic (dependent on dead wood) beetle Harminius undulatus was studied in a managed boreal forest landscape, covering 24,449 ha, in central Sweden. In a first step, we analyzed the beetle's occupancy pattern in relation to stand characteristics, and the amounts of present and past habitat in the surrounding landscape. Managed forest is suitable habitat when > or =60 years old, and immediately after cutting, but not between the ages of 10 and 60 years. The observed occupancy of H. undulatus was positively correlated with the stand's age as habitat. We used a metapopulation model to predict the current probability of occurrence in each forest stand, given the spatiotemporal distribution of suitable forest stands during the last 50 years. Metapopulation parameters were estimated by matching predicted spatial distributions with observed spatial distributions. The model predicted observed spatial distributions better than a similar model that assumed constant habitat quality of each forest stand. Thus, metapopulation models for successional-type systems, such as dead wood dependent organisms in managed forest landscapes, should include habitat dynamics. An estimated 82% of the landscape-wide recruitment took place in managed stands, which covered 87% of the forest area, in comparison with 18% in unmanaged stands, which covered 13% of the forest area. Among the managed stand types, > or =60-year-old stands and 3-7-year-old clear-cuttings contributed to 79% of the total recruitment while 8-59-year-old stands only contributed 3%. The results suggest the following guidelines to improve conditions for H. undulatus and other species with similar habitat requirements: (1) the proportion of the landscape constituted by younger stands should not be allowed to grow too large, (2) the rotation period of managed stands should not be allowed to be too short, and (3) dead wood should be retained and created at final cutting.
Subject(s)
Coleoptera/physiology , Ecosystem , Forestry , Models, Theoretical , Trees , Animals , Conservation of Natural Resources , Larva/physiology , Plant Bark/parasitology , Population Density , SwedenABSTRACT
Rapidity distributions of protons from central 197Au+197Au collisions measured by the E895 Collaboration in the energy range from (2-8)A GeV at the Brookhaven AGS are presented. Longitudinal flow parameters derived using a thermal model including collective longitudinal expansion are extracted from these distributions. The results show an approximately linear increase in the longitudinal flow velocity,
ABSTRACT
TheGuilty Knowledge Test (GKT) has been used extensively to model deception. An association between the brain evoked response potentials and lying on the GKT suggests that deception may be associated with changes in other measures of brain activity such as regional blood flow that could be anatomically localized with event-related functional magnetic resonance imaging (fMRI). Blood oxygenation level-dependent fMRI contrasts between deceptive and truthful responses were measured with a 4 Tesla scanner in 18 participants performing the GKT and analyzed using statistical parametric mapping. Increased activity in the anterior cingulate cortex (ACC), the superior frontal gyrus (SFG), and the left premotor, motor, and anterior parietal cortex was specifically associated with deceptive responses. The results indicate that: (a) cognitive differences between deception and truth have neural correlates detectable by fMRI, (b) inhibition of the truthful response may be a basic component of intentional deception, and (c) ACC and SFG are components of the basic neural circuitry for deception.
Subject(s)
Cerebral Cortex/physiology , Deception , Gyrus Cinguli/physiology , Magnetic Resonance Imaging , Adult , Dominance, Cerebral/physiology , Female , Guilt , Humans , Lie Detection , Male , Middle Aged , Nerve Net/physiology , Truth DisclosureABSTRACT
We report a particle source imaging analysis based on two-pion correlations in high multiplicity Au+Au collisions at beam energies between 2A and 8A GeV. We apply the imaging technique introduced by Brown and Danielewicz, which allows a model-independent extraction of source functions with useful accuracy out to relative pion separations of about 20 fm. The extracted source functions have Gaussian shapes. Values of source functions at zero separation are almost constant across the energy range under study. Imaging results are found to be consistent with conventional source parameters obtained from a multidimensional Hanburg-Brown-Twiss analysis.
ABSTRACT
A previous investigation by our laboratory linked cellulose acetate degradation with adverse health effects in hemodialysis patients. To establish the accumulation of degradation products with time, a Monte Carlo model of degradation kinetics was developed. The model tracks changes in a population of molecules representative of the dialyzer membrane during the degradation process. The degradation calculation is a two step process: First, the model uses a random number to select an individual polymer molecule out of the population, and then a second random number is used to identify a site on the selected molecule for the degradation reaction to occur. After the reaction calculation, the resulting degraded molecules are redistributed into the population. The course of the reaction is determined by recalculating the molecular weight averages in the changing population as the calculations proceed. The model was validated using gel permeation chromatography molecular weight results and total acetyl content measurements on dialyzers stored up to 13.3 years after manufacture. It was found that the degradation reactions can be accurately modeled as random events and that the chain scissions and deacetylation events occur at constant rates. The shelf life of these devices was estimated using the model predictions and animal test results.
Subject(s)
Cellulose , Cellulose/analogs & derivatives , Kidneys, Artificial , Membranes, Artificial , Cellulose/adverse effects , Cellulose/chemistry , Drug Stability , Humans , In Vitro Techniques , Kidneys, Artificial/adverse effects , Models, Chemical , Molecular Weight , Monte Carlo Method , Safety , Time FactorsABSTRACT
OBJECTIVE: Neuropsychological studies have shown that deficits in verbal episodic memory in schizophrenia occur primarily during encoding and retrieval stages of information processing. The current study used positron emission tomography to examine the effect of schizophrenia on change in cerebral blood flow (CBF) during these memory stages. METHOD: CBF was measured in 23 healthy comparison subjects and 23 patients with schizophrenia during four conditions: resting baseline, motor baseline, word encoding, and word recognition. The motor baseline was used as a reference that was subtracted from encoding and recognition conditions by using statistical parametric mapping. RESULTS: Patients' performance was similar to that of healthy comparison subjects. During word encoding, patients showed reduced activation of left prefrontal and superior temporal regions. Reduced left prefrontal activation in patients was also seen during word recognition, and additional differences were found in the left anterior cingulate, left mesial temporal lobe, and right thalamus. Although patients' performance was similar to that of healthy comparison subjects, left inferior prefrontal activation was associated with better performance only in the comparison subjects. CONCLUSIONS: Left frontotemporal activation during episodic encoding and retrieval, which is associated with better recognition in healthy people, is disrupted in schizophrenia despite relatively intact recognition performance and right prefrontal function. This may reflect impaired strategic use of semantic information to organize encoding and facilitate retrieval.
Subject(s)
Frontal Lobe/physiopathology , Schizophrenia/physiopathology , Temporal Lobe/physiopathology , Tomography, Emission-Computed/statistics & numerical data , Verbal Learning/physiology , Adult , Female , Frontal Lobe/blood supply , Frontal Lobe/diagnostic imaging , Humans , Male , Memory/physiology , Neuropsychological Tests/statistics & numerical data , Oxygen Radioisotopes , Psychomotor Performance/physiology , Regional Blood Flow , Schizophrenia/diagnosis , Schizophrenia/diagnostic imaging , Temporal Lobe/blood supply , Temporal Lobe/diagnostic imaging , WaterABSTRACT
Directed flow measurements for Lambda hyperons are presented and compared to those for protons produced in the same Au+Au collisions (2A, 4A, and 6A GeV; b<5-6 fm). The measurements indicate that Lambda hyperons flow consistently in the same direction but with smaller magnitudes. A strong positive flow [for Lambdas] has been predicted in calculations which include the influence of the Lambda-nucleon potential. The experimental flow ratio Lambda/p is in qualitative agreement with expectations (approximately 2/3) from the quark counting rule at 2A GeV but is found to decrease with increasing beam energy.
ABSTRACT
Toll-like receptors (TLRs) have been shown to participate in the recognition of pathogens by the innate immune system, but it is not clear how a restricted family of receptors has the capacity to recognize the wide spectrum of TLR stimuli known to exist. We report here that two members of the TLR family, TLR2 and TLR6, together coordinate macrophage activation by Gram-positive bacteria and the yeast cell-wall particle, zymosan. TLR6 and TLR2 both are recruited to the macrophage phagosome, where they recognize peptidoglycan, a Gram-positive pathogen component. By contrast, TLR2 recognizes another component, bacterial lipopeptide, without TLR6. The requirement for TLR cooperation is supported by the finding that TLR2 needs a partner to activate tumor necrosis factor-alpha production in macrophages. Dimerization of the cytoplasmic domain of TLR2 does not induce tumor necrosis factor-alpha production in macrophages, whereas similar dimerization of the TLR4 cytoplasmic domain does. We show that the cytoplasmic domain of TLR2 can form functional pairs with TLR6 or TLR1, and this interaction leads to cytokine induction. Thus, the cytoplasmic tails of TLRs are not functionally equivalent, with certain TLRs requiring assembly into heteromeric complexes, whereas others are active as homomeric complexes. Finally, we show that TLR6, TLR2, and TLR1 are recruited to macrophage phagosomes that contain IgG-coated erythrocytes that do not display microbial components. The data suggest that TLRs sample the contents of the phagosome independent of the nature of the contents, and can establish a combinatorial repertoire to discriminate among the large number of pathogen-associated molecular patterns found in nature.
Subject(s)
Drosophila Proteins , Immune System/immunology , Membrane Glycoproteins/metabolism , Receptors, Cell Surface/metabolism , Animals , Base Sequence , CHO Cells , Cricetinae , DNA Primers , Fungi/immunology , Fungi/pathogenicity , Gram-Positive Bacteria/immunology , Gram-Positive Bacteria/pathogenicity , Mice , Molecular Sequence Data , Toll-Like Receptor 1 , Toll-Like Receptor 2 , Toll-Like Receptor 4 , Toll-Like Receptor 6 , Toll-Like ReceptorsABSTRACT
Acyl-CoA dehydrogenase (ACAD) defects in isoleucine and valine catabolism have been proposed in clinically diverse patients with an abnormal pattern of metabolites in their urine, but they have not been proved enzymatically or genetically, and it is unknown whether one or two ACADs are involved. We investigated a patient with isolated 2-methylbutyrylglycinuria, suggestive of a defect in isoleucine catabolism. Enzyme assay of the patient's fibroblasts, using 2-methylbutyryl-CoA as substrate, confirmed the defect. Sequence analysis of candidate ACADs revealed heterozygosity for the common short-chain ACAD A625 variant allele and no mutations in ACAD-8 but a 100-bp deletion in short/branched-chain ACAD (SBCAD) cDNA from the patient. Our identification of the SBCAD gene structure (11 exons; >20 kb) enabled analysis of genomic DNA. This showed that the deletion was caused by skipping of exon 10, because of homozygosity for a 1228G-->A mutation in the patient. This mutation was not present in 118 control chromosomes. In vitro transcription/translation experiments and overexpression in COS cells confirmed the disease-causing nature of the mutant SBCAD protein and showed that ACAD-8 is an isobutyryl-CoA dehydrogenase and that both wild-type proteins are imported into mitochondria and form tetramers. In conclusion, we report the first mutation in the SBCAD gene, show that it results in an isolated defect in isoleucine catabolism, and indicate that ACAD-8 is a mitochondrial enzyme that functions in valine catabolism.
Subject(s)
Amino Acid Metabolism, Inborn Errors/enzymology , Amino Acid Metabolism, Inborn Errors/genetics , Isoleucine/metabolism , Oxidoreductases Acting on CH-CH Group Donors , Oxidoreductases/deficiency , Valine/metabolism , Alternative Splicing/genetics , Amino Acid Metabolism, Inborn Errors/metabolism , Amino Acid Sequence , Animals , Base Sequence , COS Cells , Child, Preschool , Consanguinity , DNA Mutational Analysis , Enzyme Stability , Exons , Female , Heterozygote , Humans , Introns , Male , Mitochondria/enzymology , Mitochondria/metabolism , Mutation/genetics , Oxidoreductases/genetics , Oxidoreductases/metabolism , Pakistan , Protein Transport , Sequence Deletion/genetics , TransfectionABSTRACT
PURPOSE/OBJECTIVES: To evaluate quality of life (QOL) and cost outcomes of advanced practice nurses' (APNs') interventions with women diagnosed with breast cancer. DESIGN: Randomized clinical trial. SETTING: Integrated healthcare system in a midwestern suburban community. SAMPLE: 210 women with newly diagnosed breast cancer with an age range of 30-85 years. METHODS: The control group (n = 104) received standard medical care. The intervention group (n = 106) received standard care plus APN interventions based on Brooten's cost-quality model and the Oncology Nursing Society's standards of advanced practice in oncology nursing QOL was measured using the Functional Assessment of Cancer Therapy, Mishel Uncertainty in Illness Scale and Profile of Mood States at seven intervals over two years. Information about costs (charges and reimbursement) was collected through billing systems. MAIN RESEARCH VARIABLES: Uncertainty, mood states, well-being, charges, and reimbursement. FINDINGS: Uncertainty decreased significantly more from baseline in the intervention versus control group at one, three, and six months after diagnosis (p = 0.001, 0.026, and 0.011, respectively), with the strongest effect on subscales of complexity, inconsistency, and unpredictability. Unmarried women and women with no family history of breast cancer benefited from nurse interventions in mood states and well-being. No significant cost differences were found. CONCLUSIONS: APN interventions improved some QOL indicators but did not raise or lower costs. IMPLICATIONS FOR NURSING PRACTICE: The first six months after breast cancer diagnosis is a critical time during which APN interventions can improve QOL outcomes. More research is necessary to define cost-effective interventions.
Subject(s)
Breast Neoplasms/nursing , Health Care Costs , Nurse Clinicians , Outcome Assessment, Health Care , Quality of Life , Adaptation, Psychological , Adult , Affect , Aged , Aged, 80 and over , Analysis of Variance , Breast Neoplasms/economics , Breast Neoplasms/psychology , Cost-Benefit Analysis , Female , Humans , Middle Aged , Midwestern United States , Nurse Clinicians/economics , Regression AnalysisABSTRACT
Evidence of bilateral prefrontal activation during memory encoding and retrieval has increased attention given to anatomical subdivisions within the prefrontal cortex. The current study examined anterior and inferior aspects of the prefrontal cortex to determine their degree of functional and hemispheric overlap during encoding and recognition. Cerebral blood flow of 25 healthy volunteers was measured using PET (15)O-water methods during four conditions: resting baseline, sequential finger movement, word encoding, and word recognition. Resting and motor images were averaged to provide a single reference that was subtracted from encoding and recognition using statistical parametric mapping (SPM96). Memory conditions were also subtracted from each other to identify differences in regional activity. Subjects performed well (86% correct) and had a slightly conservative response bias. Baseline subtraction from encoding revealed focal activation of left inferior prefrontal cortex (area 45) without significant contralateral activation. Recognition minus baseline subtraction produced a focal right anterior prefrontal activation (areas 9 and 10) that was not present in the left hemisphere. Bilateral effects were seen in area 45 during recognition. Subtraction of memory tasks from each other did not reveal any areas of greater activity during encoding. However, the recognition task produced greater activation in right area 9 extending into the anterior cingulate. Greater activity during recognition was also observed in left insula and bilateral visual integration areas. These results are discussed in relation to the prevailing model of prefrontal hemispheric asymmetry during episodic memory.
Subject(s)
Brain/diagnostic imaging , Brain/physiology , Pattern Recognition, Visual/physiology , Prefrontal Cortex/physiology , Reading , Tomography, Emission-Computed , Adult , Cerebrovascular Circulation/physiology , Female , Humans , Male , Middle Aged , Prefrontal Cortex/diagnostic imaging , Reference Values , Subtraction Technique , Verbal Behavior/physiologyABSTRACT
Mutations that cause accumulation or rapid degradation owing to protein misfolding are a frequent cause of inherited disease in humans. In Escherichia coli, Clpp protease is one of the components of the protein quality control system that handles misfolded proteins. In the present study, we have characterized the mouse Clpp cDNA sequence, the organization of the mouse gene, the chromosomal localization, and the tissue-specific expression pattern. Moreover. the cellular localization and processing of mouse Clpp was studied by overexpression in transfected eukaryotic cells. Our results indicate that mouse and human Clpp have similar roles, and they provide the molecular basis for establishing a Clpp knockout mouse and to study its phenotype, thereby shedding light on a possible role of Clpp in human disease.
Subject(s)
Adenosine Triphosphatases/genetics , Adenosine Triphosphatases/metabolism , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Animals , Base Sequence , Chromosome Mapping/veterinary , DNA Primers , DNA, Complementary , Endopeptidase Clp , Exons , Humans , Introns , Mice , Mice, Inbred C57BL , Molecular Sequence Data , Recombinant Proteins/genetics , Recombinant Proteins/metabolismABSTRACT
PURPOSE: We evaluated a method of estimating detrusor pressure at home in patients with myelomeningocele who perform clean intermittent catheterization to empty the bladder. MATERIALS AND METHODS: Patients with myelomeningocele who perform clean intermittent catheterization underwent cystometry. At home they determined bladder pressure before draining a full bladder and after partial draining with the bladder almost empty. Home estimate of detrusor pressure was calculated using the formula, full bladder pressure - almost empty bladder pressure. RESULTS: A total of 4 boys and 5 girls with a mean age plus or minus standard deviation of 9.6+/-7.9 years who were enrolled in our study made 16.9+/-15.2 home bladder pressure and volume recordings weekly each during a mean of 5.8+/-4.3 months. Mean bladder capacity determined at home was significantly greater than cystometric capacity (354+/-185 versus 250+/-146 ml.). At a mean home and cystometric volume of 190+/-110 ml. full bladder pressure at home was not significantly different from cystometric vesical pressure (31.0+/-8.8 versus 27.5+/-7.5 cm. water). At a mean volume of 23+/-15 ml. mean home almost empty bladder pressure was not significantly different from cystometric abdominal pressure at full and almost empty volumes (14.1+/-5.5 versus 17.0+/-7.4 and 15.5+/-5.8 cm. water). Mean home estimate of detrusor pressure was not significantly different from cystometric detrusor pressure (17.0+/-6.3 versus 10.2+/-9.2 cm. water). CONCLUSIONS: Estimation of detrusor pressure at home is reliable and accurate in patients who perform clean intermittent catheterization. These pressure determinations may be used as a baseline for rapid identification of changes in bladder function.
Subject(s)
Meningomyelocele/physiopathology , Urinary Bladder/physiopathology , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Male , Pressure , Urodynamics , Urology/methodsSubject(s)
Acyl-CoA Dehydrogenases/genetics , Fetal Diseases/enzymology , Lipid Metabolism, Inborn Errors/enzymology , Prenatal Diagnosis , Acyl-CoA Dehydrogenase, Long-Chain , Acyl-CoA Dehydrogenases/deficiency , DNA , Female , Fetal Diseases/diagnosis , Fetal Diseases/genetics , Humans , Lipid Metabolism, Inborn Errors/diagnosis , Lipid Metabolism, Inborn Errors/genetics , PregnancyABSTRACT
To develop an effective, coordinated, and integrated process for patient education in primary care, the Department of Veterans Affairs, Western New York Healthcare System, launched a process action team. The interdisciplinary team utilized a variety of methods, including flowcharts, cause-and-effect diagrams, and variance matrices. The team developed, implemented, and analyzed a data collection plan involving chart reviews, staff interviews, and patient-staff surveys. An improvement plan was initiated in collaboration with staff. The results highlight the importance of using a data collection plan to understand the causes of problems as well as the need for staff involvement.