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PubMed2004

[Relationship between line spread function (LSF), or slice sensitivity profile (SSP), and point spread function (PSF) in CT image system.].

In the CT image system, we revealed the relationship between line spread function (LSF), or slice sensitivity profile (SSP), and point spread function (PSF). In the system, the following equation has been reported; I(x,y) = O(x,y) ** PSF(x,y), in which I(x,y) and O(x,y) are CT image and object function, respectively, and ** is 2-dimensional convolution. In the same way, the following 3-dimensional expression applies; I'(x,y,z) = O'(x,y,z) *** PSF'(x,y,z), in which z-axis is the direction perpendicular to the x/y-scan plane. We defined that the CT image system was separable, when the above two equations could be transformed into following equations; I(x,y) = [O(x,y) * LSF(x)(x) ] * LSF(y)(y) and I' (x,y,z) = [ O'(x,y,z) * SSP(z) ] ** PSF(x,y), respectively, in which LSF(x)(x) and LSF(y)(y) are LSFs in x- and y-direction, respectively. Previous reports for the LSF and SSP are considered to assume the separable-system. Under the condition of separable-system, we derived following equations; PSF(x,y)=LSF(x)(x) LSF(y)(y) and PSF' (x,y,z) = PSF(x,y) SSP(z). They were validated by the computer-simulations. When the study based on 1-dimensional functions of LSF and SSP are expanded to that based on 2- or 3-dimensional functions of PSF, derived equations must be required.

Computer Simulation↗
PubMed2004

[Cloning and characterization of a novel human ceg1 gene cDNA].

ceg1 gene was a novel human gene, which was cloned by bioinformatics research and RT-PCR. It was a single exon gene and located on human chromosome 14. The length of the cDNA was 2050 bp. Bioinformatics analysis predicted a 1340 bp complete open reading frame (ORF) which encoded a 446 amino acid protein, containing an EGF-like and CLECT domain. We found that the homologous genes of ceg1 in mouse embryo and chicken embryo were specifically expressed in the brain by in-situ hybridization. The result of RT-PCR of the mature mouse organs showed it was widely expressed in many organs. The result indicates that ceg1 gene may have an essential role in the development of brain and the maintenance of the organs' normal function. The analysis of expression and function profile of ceg1 gene may provide valuable insights into the functions of ceg1 in the development and function of human body.

Amino Acid Sequence↗
PubMed2003

Comparison of the effect of propofol and sevoflurane on the urethral pressure profile in healthy female dogs.

OBJECTIVE: To compare the effects of propofol and sevoflurane on the urethral pressure profile in female dogs. ANIMALS: 10 healthy female dogs. PROCEDURE: Urethral pressure profilometry was performed in awake dogs, during anesthesia with sevoflurane at 1.5, 2.0, and 3.0% end-tidal concentration, and during infusion of propofol at rates of 0.4, 0.8, and 1.2 mg/kg/min. A consistent plane of anesthesia was maintained for each anesthetic protocol. Maximum urethral pressure, maximum urethral closure pressure, functional profile length, and functional area were measured. RESULTS: Mean maximum urethral closure pressure of awake dogs was not significantly different than that of dogs anesthetized with propofol at all infusion rates or with sevoflurane at 1.5 and 2.0% end-tidal concentration. Functional area in awake dogs was significantly higher than in anesthetized dogs. Functional area of dogs during anesthesia with sevoflurane at 3.0% end-tidal concentration was significantly lower than functional area for other anesthetic protocols. Individual differences in the magnitude of effects of propofol and sevoflurane on urethral pressures were observed. CONCLUSIONS AND CLINICAL RELEVANCE: Sevoflurane is an alternative to propofol for anesthesia in female dogs undergoing urethral pressure profilometry. Use of these anesthetics at appropriate administration rates should reliably distinguish normal from abnormal maximum urethral closure pressures and functional areas. Titration of anesthetic depth is a critical component of urodynamic testing.

Anesthetics, Inhalation↗
PubMed2005

FADO: a statistical method to detect favored or avoided distances between occurrences of motifs using the Hawkes' model.

We propose an original statistical method to estimate how the occurrences of a given process along a genome, genes or motifs for instance, may be influenced by the occurrences of a second process. More precisely, the aim is to detect avoided and/or favored distances between two motifs, for instance, suggesting possible interactions at a molecular level. For this, we consider occurrences along the genome as point processes and we use the so-called Hawkes' model. In such model, the intensity at position t depends linearly on the distances to past occurrences of both processes via two unknown profile functions to estimate. We perform a non parametric estimation of both profiles by using B-spline decompositions and a constrained maximum likelihood method. Finally, we use the AIC criterion for the model selection. Simulations show the excellent behavior of our estimation procedure. We then apply it to study (i) the dependence between gene occurrences along the E. coli genome and the occurrences of a motif known to be part of the major promoter for this bacterium, and (ii) the dependence between the yeast S. cerevisiae genes and the occurrences of putative polyadenylation signals. The results are coherent with known biological properties or previous predictions, meaning this method can be of great interest for functional motif detection, or to improve knowledge of some biological mechanisms.

Journal Article↗
PubMed1989

Functional and neutralization profile of seven overlapping antigenic sites on the HN glycoprotein of Newcastle disease virus: monoclonal antibodies to some sites prevent viral attachment.

We have previously identified five antigenic sites on the hemagglutinin-neuraminidase (HN) glycoprotein of the Australia-Victoria isolate of Newcastle disease virus (Iorio and Bratt, J. Virol. 48, 440-450; Iorio et al., J. Gen. Virol. 67, 1393-1403). Two additional sites (designated 12 and 23) are now described, bringing to a total of seven the number of antigenic sites defined by our panel of neutralizing anti-HN antibodies. Competition antibody binding and additive neutralization assays reveal that each of these newly-identified sites overlaps two previously-defined ones. The seven HN antigenic sites thus form a continuum in the three-dimensional conformation of the molecule. Studies on the inhibition of hemagglutination (HA), neuraminidase (NA) and the attachment of virus to chick cell monolayers have been used to construct a functional profile of each antigenic site. Monoclonal antibodies (mAbs) to three overlapping sites (12, 2 and 23) inhibit HA and NA and prevent viral attachment to chick cell monolayers. These findings are consistent with the domains recognized by these mAbs being close to the NA and receptor-binding sites. MAbs to two other overlapping sites, 14 and 1 (which in turn, overlap site 12), inhibit HA quite effectively, and attachment to a lesser extent. Sites 14 and 1 probably identify a second domain involved in receptor recognition. MAbs to the two remaining sites (3 and 4), though neutralizing, are negative in all three assays, thus recognizing domains not involved in HA or NA or attachment to chick cells.

Animals↗
PubMed2004

Proteomics.

The growing discipline of proteomics is highly relevant in our quest to understand cause/effect relationships between environmental, Physiological, and pathological influences on bodily organ function. We present an overview of the principles and methods in profiling, functional, and structural proteomics and their applications to oncology and others related areas.

Drug Industry↗
PubMed1999

Abnormalities in liver function and coagulation profile following the Fontan procedure.

OBJECTIVE: To investigate liver function and coagulation disorders in patients with a Fontan circulation at different time intervals after surgery. DESIGN: Retrospective analysis of clinical data and cross sectional study relating liver function and coagulation profile to time since surgery, in 28 surviving patients after the modified Fontan procedure. PATIENTS: 20 patients (71%) with atriopulmonary anastomosis, seven (25%) with atrioventricular anastomosis, and one (4%) with total cavopulmonary connection. Follow up ranged from 2.0 to 21.8 years (mean 11.1). RESULTS: Abnormal liver function tests, mainly reflecting cholestasis, were present in 21 patients who had a significantly longer follow up (p < 0.01). Protein synthesis was normal in almost all patients. Coagulation profile showed abnormalities in 22 patients. "Procoagulant" abnormalities-that is, decreased plasminogen and protein C activity-were found in 11 and five patients, respectively. The extent of these abnormalities was less in patients with a longer follow up. Anticoagulant abnormalities were factor V deficiency in 16 patients and factor VII deficiency in 17, resulting in a prolonged prothrombin time in 19 patients. Thirteen patients had both pro- and anticoagulant abnormalities. A prethrombotic state was present in five patients, with a significantly longer mean time interval since surgery (p = 0.05). Thus, although the individual procoagulant indices decreased with increasing time intervals since surgery, a prethrombotic state was found particularly in patients with a long term follow up. CONCLUSIONS: Mild cholestasis was mainly present in Fontan patients with a long duration of follow up. Along with laboratory procoagulant abnormalities indicating a prethrombotic state, anticoagulant abnormalities were also present. The coagulation profile varied at different time intervals after surgery. Thus detailed evaluation should be performed regularly, and the use of anticoagulants should be considered in every patient. Long term prospective studies are needed to evaluate the individual fluctuations of coagulation profile over time following a Fontan procedure.

Adolescent↗
PubMed2002

Optimization of feeding profile for a fed-batch bioreactor by an evolutionary algorithm.

The optimal feeding profile of a fed batch process was designed by means of an evolutionary algorithm. The algorithm chromosomes include the real-valued parameters of a profile function, defined by previous knowledge. Each chromosome is composed of the parameters that define the feeding profile: the feed rates, the singular arc parameters and the switching times between the profile states. The feed profile design was tested on a fed-batch process simulation. The accepted profiles were smooth and similar to those derived analytically in other studies. Two selection functions, roulette wheel and geometric ranking, were compared. In order to overcome the problem of model mismatches, a novel optimization scheme was carried out. During its operation the process was sampled, the model was updated and the optimization procedure was applied. The on-line optimization showed improvement in the objective function for relatively low sample times. Choosing the sampling frequencies depends on the process dynamics and the time required for the measurements and optimization. Further study on experiments of fed-batch process demonstrated the use of complex, non-differentiable model and produced improved process performances using the optimal feeding profile.

Algorithms↗
PubMedDate not supplied

The immediate effect of colposuspension on resting and stressed urethral pressure profiles in anaesthetized incontinent bitches.

The aim of this study was to document what changes in the resting and stressed urethral pressure profile occur in the incontinent bitch with urethral sphincter mechanism incompetence (SMI) immediately after colposuspension. Resting and stressed subtracted simultaneous urethral pressure profilometry was performed immediately pre- and postcolposuspension in 26 bitches diagnosed with SMI. All of the urethral pressure profiles were measured in anaesthetized bitches using a standard technique and two orientations of the catheter transducers (dorsal and left). Readable pre- and postoperative urethral pressure profiles were obtained in 20 of the 26 bitches. Subjective and objective evaluation of the profiles showed significant differences in the profiles pre- and postcolposuspension. Immediately postoperatively there were significant (P < .05) increases in functional profile length, maximum urethral closure pressure (MUCP), and distance between the bladder neck and the first negative respiratory peak and stressed spike. There was a significant (P < .001) decrease in the percentage of negative spikes extending below the resting intravesical pressure on the subtracted profile. The pressure transmission profiles were significantly (P < .001) altered by surgery. The findings presented support the hypothesis that colposuspension may restore continence by increasing pressure transmission to the proximal urethra and bladder neck. The results also suggest that immediately after surgery functional urethral length and urethral resistance are increased.

Analysis of Variance↗
PubMedDate not supplied

Cost-effectiveness profiles with an expanding treatment population.

In trying to identify the therapeutic impact of a drug, clinical trials eliminate potentially confounding factors such as comorbidities, poor compliance and treatment errors in diagnosis, dosing, and drug interactions. Elimination of these variables means that attempts to use clinical data as the basis for predicting relative cost-effectiveness are fraught with difficulties. In this article a theoretical framework is proposed, which, for a single drug intervention, examines the relationship between assumed patterns of clinical effectiveness, costs of drug delivery, and the proportion of the prospective patient population being treated. Cost-effectiveness profiles are generated to represent both usual-treatment situations and situations where interventions to reduce misdiagnoses, adverse events, and noncompliance attempt to push clinical effectiveness to a maximum (given the existence of comorbidities). Without data describing effectiveness and cost profiles, and unless strict assumptions are made as to effectiveness and cost functions, profiles of cost-effectiveness cannot be predicted.

Cost-Benefit Analysis↗
PubMed2002

Functional impairment of human T-lymphocytes following PHA-induced expansion and retroviral transduction: implications for gene therapy.

The immune function of retrovirus-mediated gene modified (GM) T cells is critical for a beneficial effect to follow their adoptive transfer into patients. Recent clinical data show that GM T cells expanded with PHA have reduced function in vivo. However, little functional analysis of PHA stimulation is available. Our results show that expansion of T cells with PHA impairs their ability to respond (proliferation, cytotoxicity and IFN gamma and perforin expression) to allogeneic stimulation or viral antigens in vitro. Conversely, CD3/CD28-based protocols can preserve this immune function. Retroviral transduction did not alter the functional profile induced by polyclonal stimulation. We investigated the mechanisms leading to this functional effect, and identified differential effects of PHA and CD3/CD28 on the distribution of CCR7/CD45RA T cell functional subsets, which may explain the functional differences observed. While CD3/CD28 stimulation parallels the lineage differentiation pattern induced by antigens in physiological conditions, PHA induces a skewed distribution of the CCR7/CD45RA functional T cell subsets, with near disappearance of the subpopulations that display the effector phenotype. Overall, this study demonstrates a functional disadvantage for transduction protocols based on PHA, uncovers mechanisms that may explain this functional effect, and provides us with information to design and select transduction protocols with an improved functional outcome.

CD28 Antigens↗
PubMed1999

T-cell responses in rheumatoid arthritis: systemic abnormalities-local disease.

One manifestation of rheumatoid arthritis (RA) is a destructive inflammation of the joint, but many other organs can be targeted by this disease, classifying it as a truly systemic disorder. Accordingly, pathogenic models have to account for the multiorgan character of RA. This article proposes that the primary abnormalities in RA lie in the assembly of the T-cell pool and in the maintenance of T-cell homeostasis. Evidence has accumulated that the repertoire of CD4 T cells in RA patients is distinct and includes a high frequency of disease-relevant T cells. Emergence of T cells with self-aggressive potential could indicate a failure of negative selection in the thymus. Also, the turnover of mature T cells in the periphery is altered in RA patients with a sharp contraction in diversity. Loss of diversity results from the replacement of rare T-cell specificities by multiplying T-cell clones. Large clonal T-cell populations in RA patients acquire a distinct phenotype (CD4+CD28null) and functional profile (overproduction of interferon-gamma, cytotoxicity), giving them the ability to function as proinflammatory cells. Optimal conditions for T-cell stimulation are encountered in the synovium, where ectopic lymphoid tissue with germinal centers is formed. Considering the systemic nature of RA, therapeutic strategies suppressing synovial inflammation while ignoring systemic abnormalities could lack the potential of a curative intervention.

Arthritis, Rheumatoid↗
PubMedDate not supplied

Senior Team Assessment and Referral Program--STAR.

BACKGROUND: Although comprehensive geriatric assessment has been found to improve health and function and decrease hospital admissions, most such programs are staff-intensive and take many hours or even days. The Senior Team Assessment and Referral Program (STAR) was developed to address these two issues by using a short but comprehensive outpatient health appraisal that required only a few health professionals to complete. METHODS: Six hundred forty-nine Kaiser Permanente health plan members aged 65 years or older who received their health care at the Kaiser Permanente Medical Center, San Jose, Calif, were randomly selected during the first 12 months of the study and invited by mail to participate in STAR. Of those members contacted, 326 agreed to join the study. A nurse practitioner evaluated the health, functional, and social status of each STAR participant at an office visit once each year for the next 3 years and provided case management for those participants found to be frail or in danger of becoming frail. A control group of 764 elderly (aged 65 years and older) Kaiser members with characteristics similar to those of the STAR participants was drawn from Kaiser Permanente health plan members in San Jose. They continued to receive usual medical care throughout the study. A medical-functional profile was developed to stratify each STAR participant's overall health and functional status at each visit and case management contact. The results were entered on a grid that was used as a tracking tool throughout the study. Utilization of medical services, changes in health and function, and effects of STAR interventions on participant health behaviors were measured, and primary care physician and participant satisfaction was assessed. RESULTS: Although short-term utilization of medical services increased in the STAR group, health, function, and health behaviors improved as a result of STAR interventions. Ninety-three percent of the STAR participants described a satisfactory experience, and 71 percent were very satisfied. Sixty-five percent of primary care physicians who responded to a satisfaction questionnaire found something useful for their patients in the STAR assessment. CONCLUSIONS: STAR offers an efficient, minimally staff-intensive model for evaluating the health, functional, and social status of the 65-year-old and older age-group and intervening when they are frail or at risk of becoming frail. The improved health, function, and healthy behaviors in STAR participants and the high satisfaction rates among participants and physicians suggest that STAR would be a useful addition to the health care environment.

Aged↗
PubMed1991

Selectivity profile of the novel muscarinic antagonist UH-AH 37 determined by the use of cloned receptors and isolated tissue preparations.

1. Functional in vitro experiments were carried out to determine the antimuscarinic potencies of the pirenzepine derivative UH-AH 37 (6-chloro-5,10-dihydro-5-[(1-methyl-4-piperidinyl)acetyl]-11H-dibenzo- [b,e] [1,4] diazepine-11-one hydrochloride) at M1 muscarinic receptors of rabbit vas deferens, M2 receptors of rat left atria and M3 receptors of rat ileum. Furthermore, N-[3H]-methylscopolamine competition binding experiments were performed to obtain its affinities for the five cloned human muscarinic receptors (m1-m5) stably expressed in CHO-K1 cells. Pirenzepine served as a reference drug throughout all experiments. 2. In all preparations used, UH-AH 37 interacted with muscarinic receptors in a fashion characteristic of a simple competitive antagonist. 3. In the functional studies, UH-AH 37, like pirenzepine, showed high affinity for M1 (pA2 8.49) and low affinity for M2 muscarinic receptors (pA2 6.63). In contrast to pirenzepine, UH-AH 37 also displayed high affinity for M3 receptors (pA2 8.04). 4. In agreement with its functional profile, UH-AH 37 bound with highest affinity to m1 (pKi 8.74) and with lowest affinity to m2 receptors (pKi 7.35). Moreover, it showed a 7 fold higher affinity for m3 (pKi 8.19) than for m2 receptors, whereas pirenzepine bound to both receptors with low affinities. 5. The binding affinity of UH-AH 37 for m4 and m5 receptors (pKi 8.32 for both receptors) was only ca. 2.5 fold lower than that for m1 receptors, while the corresponding affinity differences were 6 and 13 fold in case of pirenzepine. 6. In conclusion, the receptor selectivity profile of UH-AH 37 differs clearly from that of its parent compound, pirenzepine, in both functional and radioligand binding studies, the major characteristics being its pronounced M2 (m2)/M3 (m3) selectivity. UH-AH 37 thus represents a useful tool for the further pharmacological characterization of muscarinic receptor subtypes.

Animals↗
PubMed2005

Features of developmental functions and autistic profiles in children with fragile X syndrome.

BACKGROUND: In this study, we investigated the developmental functions and autistic profiles in children with Fragile X syndrome (FXS). In addition, we established the relationships between developmental and autistic profiles in these children. METHODS: The medical records of 12 children with FXS, aged 2 to 7 years, were collected. Fifteen children with autism, without FXS, who were age- and sex-matched were selected as the comparison group. All children underwent assessments of developmental functions according to the Chinese Child Development Inventory (CCDI), and autistic profiles according to the Childhood Autism Rating Scale (CARS). Differences in genders between the two groups were determined with the Fisher's exact test. Differences in developmental functions (CCDI) and autistic profiles (CARS) between the two groups were compared using Mann-Whitney U test and Bonferroni adjustment. The Spearman's rho correlation was used to determine the relationship of developmental functions and autistic profiles. RESULTS: All developmental functions in children with FXS were better than those with autism except for gross motor, fine motor and expressive language functions. Children with FXS had the worst expressive language function (56% Development Quotient, DQ) as compared with other developmental functions (> 70% DQ). The major difference between the children with FXS and those with autism was personal social function with a difference of 33% DQ. The average total CARS score were lower in children with FXS (average score, 28) than children with autism (average score, 34). Spearman's correlation demonstrated the CARS total score were negatively correlated with all developmental functions, except for gross motor function. CONCLUSIONS: Our findings suggest that the FXS children had multifaceted and disproportional development patterns in motor, speech and social domains when compared with the autism children without FXS. The developmental functions were inversely correlated with autistic profiles. Therefore, when applying comprehensive assessment, we were able to identify the special developmental features in children with FXS.

Autistic Disorder↗
PubMed2002

Tuning of membrane properties regulates subliminal synapses in dorsal horn neurons of intact rats.

Functional plasticity in receptive field properties underlies the mechanism whereby spinal dorsal horn neurons encode changes in pain sensitivity following peripheral injury. Activation of "silent" or subliminal excitatory synapses was hypothesized to account for this injury-induced neural plasticity. To better characterize the mechanisms governing subliminal inputs, we adapted whole-cell patch clamp to the study of dorsal horn neurons in intact, anesthetized rats. In this report we show that the membrane properties of spinal cells correlate to functional class defined by action potential responses to cutaneous stimuli. In addition, we report the discovery of a novel "silent" population of neurons with solely subliminal excitatory inputs at rest that can be activated by membrane depolarization. Finally, an induced change in baseline membrane potential to a level nearer that of a different functional class results in a corresponding change in the responses to cutaneous stimuli of a given cell to that of the new functional class. In summary our findings suggest that biophysical membrane properties are key factors determining the functional profile of spinal neurons. The rapid change of such properties may regulate the function of silent synapses in spinal neurons and underlie rapid development of neural plasticity.

Action Potentials↗
PubMed1975

Quantitative assays of human monocyte-macrophage function.

Monocyte-macrophages are required for the development of cell mediated immunity to a variety of microorganisms and tumors. Quantitative assays of human monocyte-macrophage function would be most useful in the evaluation of cell mediated immune function in man. Five quantitative assays are described that provide a human monocyte-macrophage function profile. These assays parallel the physiologic steps necessary for monocyte-macrophages to function as phagocytes: 1) chemotaxis, 2) opsonization, 3) phagocytosis, 4) phagocytosis-induced metabolic stimulation and 5) destruction of foreign material. Application of these quantitative assays will allow detection and dissection of disorders of monocyte-macrophage function in man.

Adult↗