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PubMed2002

kappa-Hefutoxin1, a novel toxin from the scorpion Heterometrus fulvipes with unique structure and function. Importance of the functional diad in potassium channel selectivity.

An important and exciting challenge in the postgenomic era is to understand the functions of newly discovered proteins based on their structures. The main thrust is to find the common structural motifs that contribute to specific functions. Using this premise, here we report the purification, solution NMR, and functional characterization of a novel class of weak potassium channel toxins from the venom of the scorpion Heterometrus fulvipes. These toxins, kappa-hefutoxin1 and kappa-hefutoxin2, exhibit no homology to any known toxins. NMR studies indicate that kappa-hefutoxin1 adopts a unique three-dimensional fold of two parallel helices linked by two disulfide bridges without any beta-sheets. Based on the presence of the functional diad (Tyr(5)/Lys(19)) at a distance (6.0 +/- 1.0 A) comparable with other potassium channel toxins, we hypothesized its function as a potassium channel toxin. kappa-Hefutoxin 1 not only blocks the voltage-gated K(+)-channels, Kv1.3 and Kv1.2, but also slows the activation kinetics of Kv1.3 currents, a novel feature of kappa-hefutoxin 1, unlike other scorpion toxins, which are considered solely pore blockers. Alanine mutants (Y5A, K19A, and Y5A/K19A) failed to block the channels, indicating the importance of the functional diad.

Amino Acid Sequence↗

PubMed2004

Functional identification of three receptor activator of NF-kappa B cytoplasmic motifs mediating osteoclast differentiation and function.

Receptor activator of NF-kappa B ligand (RANKL) and its receptor activator of NF-kappa B (RANK) play pivotal roles in osteoclast differentiation and function. However, the structural determinants of the RANK that mediate osteoclast formation and function have not been definitively identified. To address this issue, we developed a chimeric receptor approach that permits a structure/function study of the RANK cytoplasmic domain in osteoclasts. Using this approach, we examined the role of six RANK putative tumor necrosis factor receptor-associated factor-binding motifs (PTM) (PTM1, ILLMT-REE(286-293); PTM2, PSQPS(349-353); PTM3, PFQEP(369-373); PTM4, VYVSQTSQE(537-545); PTM5, PVQEET(559-564); and PTM6, PVQEQG(604-609)) in osteoclast formation and function. Our data revealed that the RANK cytoplasmic domain possesses three functional motifs (PFQEP(369-373), PVQEET(559-564), and PVQEQG(604-609)) capable of mediating osteoclast formation and function. Moreover, we demonstrated that these motifs play distinct roles in activating intracellular signaling. PFQEP(369-373) initiates NF-kappa B, c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38 signaling pathways and PVQEET(559-564) activates NF-kappa B and p38 pathways in osteoclasts, whereas PVQEQG(604-609) is only capable of activating NF-kappa B pathway. Significantly, the revelation of these functional RANK cytoplasmic motifs has not only laid a foundation for further delineating RANK signaling pathways in osteoclasts, but, more importantly, these RANK motifs themselves represent potential therapeutic targets for bone disorders such as osteoporosis.

Amino Acid Sequence↗

PubMed1997

Correlation of functional independence measure (FIM) and SPECT Iofetamine (I-123) as a predictor of functional return in stroke.

Function following stroke is often measured using the Functional Independence Measure (FIM). Independence occurs when the patient achieves certain levels of functions. SPECT imaging assesses the regional cerebral blood flow (rCBF). Is it possible to correlate the FIM scores with SPECT imaging and predict functional return? We evaluated total of 69 stroke patients with SPECT imaging using Iofetamine (I-123). Patients were scanned within 14-21 days post-stroke. CT scans were evaluated and correlated with the SPECT images. This information was compared with the admission and discharge FIM scores. The rCBF reperfusion changes and region of stroke were evaluated and correlated with discharge functional status. The right parietal areas demonstrated a strong correlation with SPECT and FIM changes as predictors of return of functional living status (p-value = 0.0438). The right parietal area demonstrated an improvement in ambulation (p-value = 0.0578); the right brain correlated with overall improvement in FIM scores and change in SPECT imaging (p-value = 0.0833); the left brain did not exhibit significant values. Our conclusion was that there were trends seen with the predictive value of stroke recovery using SPECT imaging. The current sample number was not large enough to provide an adequate study, especially for the left brain; a larger study is needed. This information could be useful to help determine patient placement for rehabilitation.

Activities of Daily Living↗

PubMed1999

Parameters of odontostomatognathic disability: guidelines for evaluation of impaired simple and complex human functions involving the odontostomatognathic functional system.

This paper explores the current status and the future of efforts to establish parameters of disability for the odontostomatognathic functional system ("the teeth, mouth, jaws and related structures as they subserve the functions of mastication, deglutition, digestion, speech, facial expression, respiration, sexual activity, appearance and posture"). Illness, disorders, disease or injuries involving this functional system include a broad spectrum of problems that affect the dental and paradental structures. The dentist is the primary healthcare provider (HP) in the diagnosis, treatment and impairment/disability/handicap status (IDH) decisions. The authors point out that the first stage of establishing parameters of odontostomatognathic disability was accomplished with recognition in the AMA Guides to Evaluation of Permanent Impairment of the temporomandibular joint and the masticatory musculature. The second stage will be the AMA Guides publishing of an objective rating system for functional impairment of the temporomandibular joint and the masticatory musculature. Prior to the third stage of actually establishing parameters of odontostomatognathic disability, the authors suggest that multiple objectives must be accomplished, including: 1. a change in current healthcare terminology; 2. an agreement on the organization of human physiological systems; 3. medical community acceptance of the integrated structures and functions of the odontostomatognathic functional system; and 4. an appreciation of both Level I (joint and muscle dysfunction) and Level II (complex odontostomatognathic dysfunction including problems with mastication, deglutition, digestion, speech, facial expression, respiration, sexual activity, appearance and posture). The authors conclude that once these objectives are met, parameters of odontostomatognathic disability can be established.

American Medical Association↗

PubMed2004

Function and disability in late life: comparison of the Late-Life Function and Disability Instrument to the Short-Form-36 and the London Handicap Scale.

PURPOSE: We evaluated the Late-Life Function and Disability Instrument's (LLFDI) concurrent validity, comprehensiveness and precision by comparing it with the Short-Form-36 physical functioning (PF-10) and the London Handicap Scale (LHS). METHODS: We administered the LLFDI, PF-10 and LHS to 75 community-dwelling adults (> 60 years of age). We used Pearson correlation coefficients to examine concurrent validity and Rasch analysis to compare the item hierarchies, content ranges and precision of the PF-10 and LLFDI function domains, and the LHS and the LLFDI disability domains. RESULTS: LLFDI Function (lower extremity scales) and PF-10 scores were highly correlated (r = 0.74 - 0.86, p > 0.001); moderate correlations were found between the LHS and the LLFDI Disability limitation (r = 0.66, p < 0.0001) and Disability frequency (r = 0.47, p < 0.001) scores. The LLFDI had a wider range of content coverage, less ceiling effects and better relative precision across the spectrum of function and disability than the PF-10 and the LHS. The LHS had slightly more content range and precision in the lower end of the disability scale than the LLFDI. CONCLUSIONS: The LLFDI is a more comprehensive and precise instrument compared to the PF-10 and LHS for assessing function and disability in community-dwelling older adults.

Activities of Daily Living↗

PubMed1970

Studies on thymus function. I. Cooperative effect of thymic function and lymphohemopoietic cells in restoration of neonatally thymectomized mice.

Immunological restoration of 45-day old, neonatally thymectomized C3Hf mice by treatment with humoral thymic function (thymoma grafts, thymus or thymoma in diffusion chambers) ranges from 0 to 12% and is difficult to acheive. When small numbers (5-20 x 10(6)) of young adult lymphohemopoietic cells, ineffective by themselves, are given in association with humoral thymic function, a cooperative effect is observed and restoration ranges from 30 to 60%. With a particular cell dosage (20 x 10(6)), effectivity for cooperation with thymic function was the following in decreasing order: spleen, lymph nodes, thoracic duct cells, bone marrow, blood leukocytes, thymus, and Peyer's patch cells. Comparable results were obtained using spleen, thymus, and hemopoietic liver from newborn donors in association with thymic function. For similar cell dosages, newborn thymus cells were more effective than adult thymus in their cooperative effect with thymic function. Dispersed thymus cells in association with young adult bone marrow or newborn hemopoietic liver cells showed no synergism for the cooperative effect with thymic function in the present model. Using hemiallogeneic cells (F(1) hybrid into parent) it was possible to show that restoration was mediated by proliferative expansion of the injected cells. This was indicated by specific tolerance to tissues of the other parental strain and by cellular chimerism, especially of lymphoid tissues, as indicated by chromosome markers and absence of significant numbers of immunocompetent cells of host origin. A population of paritally differentiated cells of hemopoietic origin, termed postthymic, sensitive to humoral activity of the thymus and present in the lymphohemopoietic tissues of adult and newborn mice is postulated to explain our results. These cells are postthymic and thymus dependent in the sense that they already received thymic influence, probably through traffic, and are incapable of self-renewal in absence of the thymus. Sensitivity to humoral activity of the thymus is characterized by proliferative expansion and/or a differentiative process eventually leading to larger numbers of competent cells.

Animals↗

PubMed1970

Studies on thymus function. II. Cooperative effect of newborn and embryonic hemopoietic liver cells with thymus function.

Significant immunological restoration of 45-day old, neonatally thymectomized C3Hf mice was obtained by the cooperation of syngeneic newborn or embryonic hemopoietic liver cells with thymic function. Thymic function or cells alone are almost ineffective or restore approximately 10% of the animals. Newborn liver cells are effective in association with thymus grafts or humoral thymic function (thymoma grafts and thymus or thymomas in diffusion chambers). Embryonic liver cells are ineffective, even in large numbers, when associated with humoral thymic function. On the other hand, embryonic liver cells are effective in the cooperative effect only in association with viable thymus grafts, preferably syngeneic, whether the grafts were placed subcutaneously, intraperitoneally, or under the kidney capsule. Dispersed viable thymic cells are ineffective in association with embryonic liver cells. Cells capable of cooperating with humoral thymic function start to appear to embryonic liver by day 19-21 of gestation and are detectable until day 5-6 postbirth. Embryonic hemopoietic liver cells from 12 to 18 days of gestation contain cells capable of cooperation only with viable free thymus grafts and not with humoral thymic function. A prethymic cell population of partially differentiated cells of hemopoietic origin, insensitive to humoral activity of the thymus but requiring thymic stroma and traffic through the thymus is postulated to explain our results. This population of prethymic cells can become postthymic through this process and eventually develop into competent cells. Postthymic cells are characterized by their sensitivity to humoral activity of the thymus and by their wide distribution in the lymphohemopoietic tissues of newborn and young adult mice.

Animals↗

PubMed1982

In vitro effects of 4-hydroperoxycyclophosphamide on human immunoregulatory T subset function. I. Selective effects on lymphocyte function in T-B cell collaboration.

The alkylating agent cyclophosphamide may suppress or enhance immune responses in vivo but is inactive in vitro unless metabolized by microsomal enzyme activation. 4-hydroperoxycyclophosphamide (4-HC) is a synthetic compound that is spontaneously converted in aqueous solution to the active metabolites. In this report, we examined the in vitro sensitivity of functional human T cell subsets to 4-HC in a polyclonal B cell differentiation assay and in the generation of mitogen-induced suppressor cells for effector B cell function. Con A-induced T suppression of B cell differentiation is completely abrogated by a 1-h pretreatment of T cells at very low concentrations of between 10(-2) and 20 nmol/ml, whereas inducer T cell function is sensitive only to concentrations in greater than 40 nmol/ml. The effects of 4-HC on suppressor T cells appear to occur at concentrations that do not result in DNA cross-linking or decreased blastogenesis. Con A-induced T suppressors are generated from within the OKT4+, OKT8- subset and are sensitive to low-dose 4-HC only before activation, whereas differentiated suppressor cells are resistant to concentrations in greater than 80 nmol/ml. Low-dose 4-HC pretreatment of the B cell population results in abrogation of immunoglobulin secretion when treated B cells are cocultured with unfractionated T cells, however, this effect is completely reversible if pretreated B cells are cocultured with T cells devoid of suppressor activity. These results demonstrate that human presuppressor cells for B-effector function differentiate in response to Con A from the OKT4+, OKT8- subset and are exquisitely sensitive to low concentrations of CYP whereas mature suppressor and inducer functions are resistant to all but very high concentrations in vitro. The differential sensitivity of functional T and B cell subsets to 4-HC in vitro can be a very useful probe in dissecting immunoregulatory interactions with man.

B-Lymphocytes↗

PubMed1982

Immune response gene function correlates with the expression of an Ia antigen. II. A quantitative deficiency in Ae:E alpha complex expression causes a corresponding defect in antigen-presenting cell function.

A series of experiments were performed to explore the role of complementing major histocompatability complex (MHC)-linked immune response Ir genes in the murine T cell proliferative response to the globular protein antigen pigeon cytochrome c. The functional equivalence of I-E-subregion-encoded, structurally homologous E(a) chains from different haplotypes bearing the serologic specificity Ia.7 was demonstrated by the complementation for high responsiveness to pigeon cytochrome c of F(1) hybrids between low responder B 10.A(4R) (I-A (k)) or B 10.S (I-A(8)) mice and four low responder E(a)- bearing haplotypes. Moreover, this Ir gene function correlated directly with both the ability of antigen-pulsed spleen cells from these same F(1) strains to stimulate pigeon cytochrome c-primed T cells from B10.A or B10.S(9R) mice, and with the cell surface expression of the two-chain Ia antigenic complex, A(e):E(a), bearing the conformational or combinatorial determinant recognized by the monoclonal anti-Ia antibody, Y-17. The B 10.PL strain (H-2(u)), which expresses an Ia.7-positive I-E- subregion-encoded E(a) chain, failed to complement with B10.A(4R) or B10.S mice in the response to pigeon cytochrome c. However, (B10.A(4R) x B10.PL)F(1) and (B10.S x B10.PL)F(1) mice do express A(k)(e):E(u)(a) and A(8)(e):E(u)(a) on their cell surface, although in reduced amounts relative to A(k,s)(e):E(k,d,p,r)(a) complexes found in corresponding F(1) strains. This quantitative difference in Ia antigen expression correlated with a difference in the ability to present pigeon cytochrome c to B 10.A and B 10.S(9R) long-term T cell lines. Thus, (B10.A(4R) x B10.PL)F(1) spleen cells required a 10-fold higher antigen dose to induce the same stimulation as (B10.A(4R) x B10.D2)F(1) spleen cells. In addition, the monoclonal antibody, Y-17, which reacts with A(e):E(a) molecules of several strains, had a greater inhibitory effect on the proliferative response to pigeon cytochrome c of B10.A T cells in the presence of (B10.A(4R) X B10.PL)F(1) spleen cells than in the presence of (B10.A(4R) X B10.D2)F(1) spleen cells. These functional data, in concert with the biochemical and serological data in the accompanying report, are consistent with the molecular model for Ir gene complementation in which appropriate two-chain Ia molecules function at the antigen-presenting cell (APC) surface as restriction elements. Moreover, they clearly demonstrate that the magnitude of the T cell proliferative response is a function of both the concentration of nominal antigen and of the amount of Ia antigen expressed on the APC. Finally, the direct correlation of a quantitative deficiency in cell surface expression of an Ia antigen with a corresponding relative defect in antigen-presenting function provides strong independent evidence that the I-region-encoded Ia antigens are the products of the MHC-linked Ir genes.

Animals↗

PubMed1997

Cytokine-induced cytotoxic function expressed by lymphocytes of the innate immune system: distinguishing characteristics of NK and LAK based on functional and molecular markers.

Several molecular events are now identifiable during the activation, recognition, and killing by natural killer (NK) cells that are distinct from those differentiated in response to cytokines during the generation of lymphokine-activated killer (LAK) cells or during lymphocyte proliferation. Because LAK and MHC-unrestricted killing activities also include the prototypic NK targets as part of their broad recognition spectra, accurate identification of the complete function being studied is critical. In many publications, past and present, only NK-sensitive target cells were used (K562, Molt-4, others), and, therefore, the results do not necessarily indicate whether the effectors are NK or have differentiated into LAK cells. Such a consideration becomes critical when the effectors are grown in interleukin-2 (IL-2), and an attempt is made to define receptor recognition, signal transduction pathways, and specificity at the molecular level. In some instances, effector cells are likely to have stopped, therefore merely expressing NK activity, and have also acquired LAK function. The identified receptors may not have been unique to NK cells or NK function. Not until the targets employed are also confirmed to be NK sensitive, and the effectors do not kill NK-resistant targets can the results of molecular studies be proposed to represent aspects unique to NK. Reports of the use of IL-2-expanded NK clones are most likely providing data concerning the biology of LAK and not of classic NK. The classic NK activity surveying our blood apparently performs an important function, including the ability to respond rapidly to certain cytokines and to acquire additional functions and receptors for use in destroying a vast array of target cells. It is critical for scientists to appreciate the functional distinctions and to identify the molecules and pathways unique to each of these curious cytolytic systems.

Biomarkers↗

PubMed2005

Functional dysconnectivity in schizophrenia associated with attentional modulation of motor function.

It is not known whether there is a core abnormality that occurs in all cases of schizophrenia. The cognitive dysmetria hypothesis proposes that there is such an abnormality which is characterized cognitively by a disruption in control and coordination processes, and functionally by abnormal inter-regional connectivity within the cortico-cerebellar-thalamo-cortical circuit (CCTCC). In the current study, we used functional MRI (fMRI) to investigate these two key aspects of the hypothesis. Since patients with schizophrenia show deficits in attention which have been characterized extensively using the continuous performance task (CPT) and since functional imaging studies have also demonstrated that this task engages the CCTCC, we used this task to investigate whether two patient groups with distinct symptom profiles would show functional dysconnectivity within this network. Three groups of subjects participated in the study: healthy volunteers (n = 12), schizophrenia patients with both negative and positive symptoms (n = 11) and schizophrenia patients with primarily positive symptoms (n = 11). Patient groups were matched for age of illness onset and medication, and to the control group for age, gender and handedness. Subjects were scanned using fMRI whilst they performed a modified version of the CPT, involving both degraded and non-degraded stimuli. Stimulus degradation has been shown to produce decrements in sensitivity, which is thought to reflect increased demands on the limited capacity of visual attention. Between-group comparisons revealed that patients with schizophrenia, irrespective of symptomatology, showed attenuation of the anterior cingulate and cerebellar response to stimulus degradation in comparison with control subjects. We also observed disruptions of inter-regional brain integration in schizophrenia. A task-specific relationship between the medial superior frontal gyrus and both anterior cingulate and the cerebellum was disrupted in both patient groups in comparison with controls. In addition, patients with negative symptoms showed impaired behavioural performance, and abnormal task-related connectivity between anterior cingulate and supplementary motor area. These findings are consistent with theoretical accounts of schizophrenia as a disorder of functional integration, and with the cognitive dysmetria hypothesis, which posits a disconnection within the CCTCC as a fundamental abnormality in schizophrenia, independent of diagnostic subtype. Furthermore, these data show evidence of additional functional deficits in patients with negative symptoms, deficits which may explain the accompanying attentional impairment.

Adult↗

PubMed1996

Both loss-of-function and gain-of-function mutations in snf define a role for snRNP proteins in regulating Sex-lethal pre-mRNA splicing in Drosophila development.

The Drosophila snf gene encodes a protein with functional homology to the mammalian U1A and U2B" snRNP proteins. Studies, based on the analysis of three viable alleles, have suggested a role for snf in establishing the female-specific splicing pattern of the sex determination switch gene, sex-lethal. Here, we show that the non-sex-specific lethal null allele is required for female sex determination, arguing against the formal possibility that the viable alleles disrupt a function unrelated to snf's wild-type function. Moreover, we find snf is required for normal cell growth and/or survival, as expected for a protein involved in a cell-vital process such as RNA splicing. We also show that of the three viable alleles only one, snfJA2, is a partial loss-of-function mutation. The other two viable alleles, snf1621 and snfe8H, encode antimorphic proteins. We find the antimorphic proteins are mislocalized and correlate their mislocalization with their molecular lesions and mutant phenotypes. Finally, we provide genetic evidence that the antimorphic alleles interfere with the autoregulatory splicing function of the Sex-lethal protein. Based on these studies we suggest a model in which the snRNP protein, Snf, functions with Sex-lethal to block recognition of the regulated male-specific exon.

Alleles↗

PubMed2001

Prevalence [correction of prevalance] of functional blindness, visual impairment, and related functional deficits among elderly Mexican Americans.

BACKGROUND: This report describes the prevalence and correlates of functional blindness and visual impairment among older Mexican Americans, using data on 2800 respondents from the Hispanic Established Populations for the Epidemiological Study of the Elderly. METHODS: Bivariate and multivariate logistic regression analyses were used to examine the associations between corrected bilateral distant vision and sociodemographic characteristics, selected health conditions, self-reported health status, health care utilization, and functional dependence on the basis of assistance needed for basic and instrumental activities of daily living (ADLs). RESULTS: Using a modified Snellen test for distance visual acuity, 5% of older Mexican Americans were found to be functionally blind, and 13.5% were found to be visually impaired. Vision loss was significantly associated with older age, lower education, hypertension, diabetes, poor self-rated health, and hospitalization during the year prior to the interview. Over 50% of functionally blind subjects required assistance with at least one basic ADL, compared with 15% of those who were visually impaired and 8% of those who were not visually impaired. CONCLUSIONS: The prevalence of functional blindness in this sample of elderly Mexican Americans was higher than reported for the general elderly population, yet they also have higher rates of adequate vision because of the low prevalence of visual impairment. The results suggest a need for more research on the prevalence and impact of functional blindness and visual impairment on the health of older Mexican Americans.

Age Factors↗

PubMed2001

Severity of upper and lower extremity functional limitation: scale development and validation with self-report and performance-based measures of physical function. WHAS Research Group. Women's Health and Aging Study.

OBJECTIVES: To better understand disablement and transitions from impairment to disability, discrete valid measures of functional limitation are needed. This study reports the development and criterion-related validity of scales that quantify severity of upper and lower extremity functional limitation. METHODS: Data are from 3,635 cognitively intact community-dwelling women aged 65 years and older and 1,002 moderately to severely disabled participants in the Women's Health and Aging Study. Scales assessing severity of upper and lower extremity functional limitation were constructed from commonly available questions on functional difficulty. Criterion-related validity was evaluated with self-report and performance-based measures. RESULTS: The upper and lower extremity scales range from 0 to 6 and 0 to 9, respectively. Scale scores were well distributed in the disabled group and discriminated limitations in the broader community. For both scales, rates of difficulty for all ADL and IADL increased (p<.001) with increasing severity score, and percent able and mean performance on respective upper and lower extremity tasks decreased (p<.01). DISCUSSION: These scales, constructed from commonly used self-report measures of function, provide discrete measures of upper and lower functional limitation. Because these scales are distinct from measures of disability and impairment, their use should facilitate increased understanding of the disablement process.

Activities of Daily Living↗

PubMed1999

Condition severity and psychosocial functioning in pre-adolescents with spina bifida: disentangling proximal functional status and distal adjustment outcomes.

OBJECTIVE: To examine relations between condition severity and psychosocial functioning in 70 8- and 9-year-old pre-adolescents with spina bifida by testing several direct, indirect, and mediated effects models for proximal functional status and distal adjustment outcomes. METHODS: Proximal functional status outcomes (e.g., degree of involvement in activities, scholastic competence, athletic competence, attentional problems) and distal adjustment outcomes (e.g., behavior problems, social competence) were assessed with mother, father, and teacher report. Severity variables included spinal lesion level, spina bifida classification, shunt status, ambulation status, number of shunt surgeries, and two severity composites. RESULTS: Condition severity was associated with the proximal functional status outcomes across parent and teacher report. In contrast, no significant relationships were found between the severity parameters and distal adjustment outcomes. Findings supported a proximal effects model of condition severity as well as an indirect effects model (e.g., presence of a shunt-->less scholastic competence-->less social competence) and were consistent with recent theoretical formulations (e.g., Wallander & Varni, 1995). CONCLUSIONS: Disentangling proximal functional status outcomes and distal adjustment outcomes is critical in studies of condition severity and psychosocial functioning. We discuss clinical implications.

Adaptation, Psychological↗

PubMed1996

Pulmonary function measures as predictors and correlates of cognitive functioning in later life.

The relation between pulmonary function and cognitive functioning was investigated in a cohort of 3,036 Japanese-American men living in Hawaii. Pulmonary function, as indicated by forced expiratory volume in 1 second (FEV1), was measured at the baseline examination from 1965 to 1968. Cognitive function was assessed by the Cognitive Abilities Screening Instrument (CASI) test at least 23 years later (1991-1993). Baseline FEV1 was significantly correlated with follow-up CASI score (r = 0.22, p = 0.0001). Although the strength of the association was reduced by controlling for the effects of other factors, stepwise multiple linear regression showed that FEV1 during middle age was a significant predictor of CASI in later life, after taking into account the effects of age, education, stroke, sedentary job activity, nonmanual occupation, height, generation, and Japanese speaking ability. The mean CASI value was significantly greater for men whose FEV1 exceeded 2.8 liter compared with those whose FEV1 levels were in the lowest (<2.5 liters) quartile. Furthermore, the test on the effect of interaction between FEV1 and age was statistically significant (p = 0.0024), with subjects less than 55 years of age at the baseline examination showing a stronger direct association of FEV1 with CASI than the men aged 55 or older. These findings suggest that pulmonary function impairment may be associated with cognitive function impairment in later life.

Aged↗

PubMed2006

Measuring functioning in patients with hand osteoarthritis--content comparison of questionnaires based on the International Classification of Functioning, Disability and Health (ICF).

OBJECTIVE: When selecting a questionnaire, researchers and clinicians need to know whether or not a questionnaire covers the relevant outcomes. The aim of this study was to analyse and compare the content of questionnaires that have been used to assess functioning in patients with hand osteoarthritis (OA) based on the International Classification of Functioning, Disability and Health (ICF). METHOD: Questionnaires were identified in a structured literature search. All concepts included in the items of the questionnaires were linked to the ICF categories according to the 10 established linking rules by two health professionals. The degree of agreement between the two health professionals was determined by means of kappa statistic. On the basis of the linking, the content of the instruments was compared. For each concept, it was examined whether functioning is measured on the level of activity or participation or both activity and participation. Indicators for content density, content diversity and the percentage of linked ICF categories addressing participation were calculated. RESULTS: Health Assessment Questionnaire, AUSCAN, Cochin scale, FIHOA, SACRAH and AIMS2-SF were analysed. The result of the kappa statistic for agreement between the two investigators was 0.74. 163 concepts were identified in the 113 items of all instruments, which were then linked to seven ICF categories of the component body functions, 45 categories of the component activities and participation and six categories of the component environmental factors. AUSCAN and SACRAH had the lowest and AIMS2-SF showed the highest diversity ratio and the highest percentage of linked ICF categories that addressed participation. CONCLUSION: When selecting instruments for comprehensive measurements of functioning in hand OA, researchers and clinicians are advised to include both one instrument with a low diversity ratio (for disease-specific aspects) and another instrument with a high diversity ratio (for broader aspects of functioning including some aspects of participation).

Activities of Daily Living↗

PubMed1996

The effects of sevoflurane and isoflurane anesthesia on renal tubular function in patients with moderately impaired renal function.

Increasing evidence indicates that sevoflurane anesthesia does not impair renal function in healthy patients despite higher concentrations of plasma inorganic fluoride. However, whether sevoflurane further affects renal tubular function in patients with impaired renal function is not known. We compared the effect of sevoflurane anesthesia with that of isoflurane anesthesia on renal tubular function in patients with moderately impaired renal function. Fourteen patients with creatinine clearance between 10 and 55 mL/min were anesthetized with either sevoflurane or isoflurane using a semiclosed circuit system. Plasma inorganic fluoride concentrations and urine N-acetyl-beta-D-glucosaminidase (NAG), gamma-glutamyltranspeptidase (gamma-GTP), and beta 2-microglobulin (beta 2MG) excretions were measured up to post-anesthetic day 14. Although both the peak plasma inorganic fluoride concentrations and the areas under the curve of plasma inorganic fluoride concentration versus time were significantly greater in the sevoflurane group than in the isoflurane group, urine NAG, gamma-GTP, and beta 2MG excretions per day did not differ between the two groups. These results indicate that sevoflurane and isoflurane may have similar effects on the renal tubules in patients with moderately impaired renal function.

Acetylglucosaminidase↗