Long-term beneficial effects of lung volume reduction surgery on quality of life in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation, which results in exertional dyspnea and physical disability. Subsequently, those cause a difficulty in performing routine activities of daily living and affect their health-related quality of life (HRQOL). Lung volume reduction surgery (LVRS) has been reported to be an effective treatment for selected patients with advanced COPD to improve pulmonary function, lung mechanics, exercise tolerance, and dyspnea. However, the long-term effects of LVRS on HRQOL have not been fully investigated. Therefore the effects of LVRS on generic and disease-specific HRQOL were assessed in patients with COPD following LVRS for 36 months. Nineteen patients (65.1 +/- 7.0 [mean +/- S.D.] years old) who underwent pulmonary rehabilitation plus LVRS (LVRS group), and 8 patients (67.2 +/- 5.8 years old) who did pulmonary rehabilitation but not LVRS (Medical group) were studied. In both groups, optimal medication was given throughout this period. Generic HRQOL and disease-specific HRQOL were evaluated before rehabilitation, and 3, 12, 24, and 36 months after LVRS. Following LVRS, the generic HRQOL was significantly improved and the disease-specific HRQOL was maintained up to 36 months. In Medical group, disease-specific HRQOL rapidly deteriorated. In conclusion, the long-term effects of LVRS on HRQOL in COPD patients were maintained up to 36 months compared with Medical group. Both generic and disease-specific HRQOL changed differently, suggesting the importance of both assessments especially in long-term follow up.

Development and Validation of an Improved, COPD-Specific Version of the St. George Respiratory Questionnaire.

OBJECTIVE: To produce an improved, COPD-specific version of the St. George respiratory questionnaire (SGRQ-C). METHODS: Five different steps were required: (1) Rasch analysis of the responses of 893 COPD patients to the St. George respiratory questionnaire (SGRQ) identified weaker items to be removed; (2) a scoring algorithm was produced using data from 1,036 patients; (3) validity of the new and original SGRQ was tested using data from the original validation study; (4) responsiveness was tested using data from a previously published trial; and (5) a reworded version (SGRQ-C) that no longer specified the recall period was administered to 63 pulmonary rehabilitation participants. RESULTS: Items were removed due to lack of response (n = 1), misfit to the Rasch model (n = 8), and disordered responses (n = 1). Another six items had disordered responses; this was corrected. Scores from the two versions differed slightly, so the scoring algorithm was revised to produce scores equivalent to the original. Intraclass correlation coefficient (ICCC) for the scores for original and new versions was 0.99. Correlations with other measures of disease were very similar to those obtained with the original. New and original scores for treatment effects were similar: difference, 0.1 +/- 2.7 U (+/- SD). Baseline SGRQ and SGRQ-C scores were similar (ICCC, 0.95; 95% confidence interval, 0.92 to 0.97; mean difference, 0.9 +/- 5.8 U). Change scores were similar (difference, 1.0 +/- 7.3 U). CONCLUSIONS: The SGRQ-C contains the best of the original items, no longer specifies a recall period, and produces scores equivalent to the original.

Reliability and validity of the Korean version of Kidney Disease Quality of Life instrument (KDQOL-SF).

Although the Kidney Disease Quality of Life instrument (KDQOL-SF), which was designed to measure the comprehensive quality of life in patients with end stage renal disease, has been tested and widely administered in many other counties, it has not yet been translated, validated and reported for Korea. The primary purpose of this study was to validate a Korean version of KDQOL-SF and to evaluate its psychometric properties. The study subjects were 164 patients with hemodialysis or continuous ambulatory peritoneal dialysis in university dialysis centers in Korea. In order to investigate the reliability, test-retest reliability and internal consistency reliability were assessed. Both test-retest reliability and internal consistency reliability were found to be high. In order to investigate the construct validation, all the items of the SF-36 scales, an established generic QOL measures, were compared with an overall health rating scale in kidney disease-targeted scale. They found to be highly correlated with each other. Moreover, overall health rating scale was significantly correlated with symptoms/problems, effects of kidney disease, burden of kidney disease, cognitive function (p < 0.001), and quality of social interaction (p < 0.05). These results suggest that the Korean version of KDQOL-SF satisfies its reliability and validity in Korean patients with hemodialysis or continuous ambulatory peritoneal dialysis. This questionnaire provides important and clinically valuable information for understanding the health related quality of life in the Korean patients with dialysis.

Difference in quality of life according to the severity of malocclusion in Japanese orthodontic patients.

Although quality of life (QOL) assessment is important in dentistry, it has not been fully investigated in orthodontic patients. We investigated the health-related generic QOL (entire body health) and disease specific QOL (oral health) in adult patients with malocclusions at the first visit. One hundred and twenty-seven orthodontic patients and 66 persons with normal occlusion were recruited for the study. The subjects were divided into the three following groups based on their treatment: 61 patients in need of surgical correction (SURG), 66 patients in need of non-surgical correction (NONS), and 66 control subjects with normal occlusion. Their dentofacial morphology was assessed using a specific Severity Score (SS), which was set up originally based on their cephalometric radiographs and their plaster models of arrangement of their teeth. The subjects also completed a generic QOL assessment questionnaire, the SF-36, and two disease-specific QOL instruments. The patients with malocclusions, especially SURG, had lower disease-specific QOL, although the generic QOL was equal to that of control subjects. Furthermore, in patients with the same severity of dentofacial deformities, especially SS 4 and SS 5, the borderline cases of surgical correction and non-surgical correction, there were differences between SURG and NONS in some items of the QOL. The severity of malocclusion evidently plays an important role in patients' choice of treatment, but also QOL appeared to play a significant role. The QOL assessment may contribute to the selection of the best treatment for improving QOL, especially for borderline cases with moderate degrees of orthodontic abnormality.

Construct validity of the Frenchay Activities Index for community-dwelling elderly in Japan.

Many researchers have developed various measures to evaluate the functional status of community-dwelling elderly. The Frenchay Activities Index (FAI) was developed to measure instrumental activities of daily living in stroke populations. The FAI has undergone the most intensive evaluation, but its factor structure has not been examined in Japan. The primary purpose of this study was to investigate the construct validity of the FAI for non-stroke community-dwelling elderly in Japan. The study subjects were 1,323 randomly selected community older residents in Hojo city, Ehime prefecture, the southern part of Japan. In order to investigate the construct validation, we performed factor analyses, i.e., exploratory factor analysis and confirmatory factor analysis. Furthermore, we examined the influences of age and gender on the FAI constructs. In the results, the FAI had a two-factor structure consisting of domestic chores, including washing clothes and preparing meals, and work and leisure, including gardening, driving and outings. Younger age was significantly related to increased performance on both factors. In addition, relative to females, males had a lower performance on the domestic chores and a greater performance on the work and leisure. These results suggest that the FAI satisfies the construct validity in the Japanese community-dwelling elderly. The FAI and its two factors provide important and clinically valuable information for understanding the patterns of functional status in the Japanese community-dwelling elderly.

Expression profile of LIT1/KCNQ1OT1 and epigenetic status at the KvDMR1 in colorectal cancers.

The human chromosome region 11p15.5 contains a number of maternally and paternally imprinted genes, and the LIT1/KCNQ1OT1 locus acts as an imprinting center in the proximal domain of 11p15.5. Loss of imprinting (LOI) of LIT1 and its correlation with methylation status at a differentially methylated region, the KvDMR1, were investigated in 69 colorectal cancer tissue specimens. LIT1 expression profiles were also examined by RNA-fluorescence in situ hybridization in 13 colorectal cancer cell lines. In 69 colorectal cancer tissue specimens, LOI of LIT1 was observed in nine of the 17 (53%) informative cases. Moreover, LOI of LIT1 was only observed in tumor samples. In the cell lines, methylation status at the KvDMR1 correlated well with LIT1 expression profiles. Loss of expression of LIT1 also correlated with enrichment of H3 lysine 9 (H3-K9) dimethylation and reduction of H3 lysine 4 (H3-K4) dimethylation. Thus, LIT1 expression appears to be controlled by epigenetic modifications at the KvDMR1, although CDKN1C expression, which is considered to be controlled by LIT1, was not associated with epigenetic status at the KvDMR1 in some colorectal cancer cell lines. Therefore, these findings suggest that LOI of LIT1 via epigenetic disruption plays an important role in colorectal carcinogenesis, but it is not necessarily associated with CDKN1C expression.

Validity and utility of the Craig Hospital Inventory of Environmental Factors for Korean community-dwelling elderly with or without stroke.

The social environmental barriers are considered to be important because the "social participation" of people with impairments would be facilitated by the prevention and reduction of environmental barriers. The Craig Hospital Inventory of Environmental Factors (CHIEF) is one of the few scales to assess the environmental barriers. In this study, we developed the Korean version of CHIEF and evaluated its construct validity and utility in a sample of Korean community-dwelling elderly with or without stroke. We evaluated the construct validity of the CHIEF by testing the original five-factor structure using a confirmatory factor analysis in 400 elderly in Seoul, Korea. The utility of the CHIEF was then assessed by examining the relationships between individual characteristics, Barthel Index and perceived environmental barriers, measured by the CHIEF, using a structural equation modeling approach. The confirmatory factor analysis result demonstrated the validity of a second-order factor model of the CHIEF comprising the five factors as first-order factors. The perceived environmental barrier was a second-order factor when provided acceptable fit indices after two modifications. The structural equation modeling indicates that perceived environmental barriers are significantly related to activities of daily life but not age, gender, and the episode of stroke. The CHIEF is useful in measuring environmental factors for Korean older adults with or without stroke.

Narrowed abrogation of the Angelman syndrome critical interval on human chromosome 15 does not interfere with epigenotype maintenance in somatic cells.

Human chromosome 15q11-q13 involves a striking imprinted gene cluster of more than 2 Mb that is concomitant with multiple neurological disorders manifested by Prader-Willi syndrome (PWS) and Angelman syndrome (AS). PWS and AS patients with imprinting mutation have microdeletions, which share a 4.3 kb short region of overlap (SRO) at the 5' end of the paternal SNURF-SNRPN gene in PWS, or on the maternal allele, which shares a 880 bp SRO located at the 35 kb upstream of the SNURF-SNRPN promoter in AS. Recent studies have revealed an essential role of PWS-SRO in the postzygotic maintenance of the appropriate epigenotype on the paternal chromosome. For AS-SRO, however, there is insufficient experimental evidence exists to determine the direct functions. Here we show that the complete deletion of AS-SRO does not cause any anomalies of imprinted gene expression or DNA methylation on the mutated human chromosome 15, further supporting the idea that AS-SRO is dispensable for post implantation imprint maintenance. This implies that AS-SRO is not essential for the robust epigenotype preservation in somatic cells.

Development and construct validation of the Korean competence scale (KCS).

A comprehensive Korean competence scale (KCS) designed for Korean older adults, was developed and its construct validity evaluated. KCS assesses their higher levels of functional competence than activities of daily livings (ADL), necessary for independence in the home and community. The internal structure of the scale was tested using an exploratory and confirmatory factor analysis with two elderly Korean sample groups. As expected, the exploratory factor analysis result demonstrated a three-factor solution comprised of the following three domains: instrumental self-maintenance, intellectual activity, and social role. The confirmatory factor analysis results showed that an acceptable solution could be estimated for a second-order factor model comprised of these factors. These findings provide evidence for the construct validity of the instrument and have implications for future research on factorial invariance.

Discovery of imprinted transcripts in the mouse transcriptome using large-scale expression profiling.

Candidate imprinted transcriptional units in the mouse genome were identified systematically from 27,663 FANTOM2 full-length mouse cDNA clones by expression profiling. Large-scale cDNA microarrays were used to detect differential expression dependent upon chromosomal parent of origin by comparing the mRNA levels in the total tissue of 9.5 dpc parthenogenote and androgenote mouse embryos. Of the FANTOM2 transcripts, 2114 were identified as candidates on the basis of the array data. Of these, 39 mapped to known imprinted regions of the mouse genome, 56 were considered as nonprotein-coding RNAs, and 159 were natural antisense transcripts. The imprinted expression of two transcripts located in the mouse chromosomal region syntenic to the human Prader-Willi syndrome region was confirmed experimentally. We further mapped all candidate imprinted transcripts to the mouse and human genome and were shown in correlation with the imprinting disease loci. These data provide a major resource for understanding the role of imprinting in mammalian inherited traits.

A new imprinted cluster on the human chromosome 7q21-q31, identified by human-mouse monochromosomal hybrids.

We have previously established a series of human monochromosomal hybrids containing a single human chromosome of defined parental origin as an in vitro resource for the investigation of human imprinted loci. Using the hybrids with a paternal or maternal human chromosome 7, we determined the allelic expression profiles of 76 ESTs mapped to the human chromosome 7q21-q31. Seven genes/transcripts, including PEG10 which has previously been reported to be imprinted, showed parent-of-origin-specific expression in monochromosomal hybrids. One of the 6 candidate genes/transcripts, i.e., DLX5 was confirmed to be imprinted in normal human lymphoblasts and brain tissues by a polymorphic analysis. Thus, an imprinted domain has been newly defined in the region of human chromosome 7q21-q31 using human-mouse monochromosomal hybrids.

Predominant maternal expression of the mouse Atp10c in hippocampus and olfactory bulb.

The human chromosome 15q11-q13 region is one of the most intriguing imprinted domains, and the abnormalities inherited are associated with neurological disorders including Prader-Willi syndrome (PWS), Angelman syndrome (AS) and autism. Recently we have identified a novel maternally expressed gene, ATP10C, that encodes a putative aminophospholipid translocase within this critical region, 200 kb distal to UBE3A in an imprinted domain on human chromosome 15. ATP10C, with UBE3A, displayed tissue-specific imprinting with predominant expression of the maternal allele in the brain. In this study, we demonstrated that the mouse homologue, Atp10c/pfatp, showed tissue-specific maternal expression in the hippocampus and olfactory bulb, which overlapped the region of imprinted Ube3a expression. These data suggest that the imprinted transcript of Atp10c in the specific region of CNS may be associated with neurological disorders including AS and autism.

Calcr, a brain-specific imprinted mouse calcitonin receptor gene in the imprinted cluster of the proximal region of chromosome 6.

Expressed sequence tags (ESTs) in the human chromosome 7q21-q31 region were recently used to screen for allelic expression bias in monochromosomal hybrids retaining a paternal or maternal human chromosome 7. Six candidate imprinted genes were identified. In this study, we investigated parent-of-origin-specific expression profiles of their mouse homologues in the proximal region of chromosome 6. An imprinting analysis, using F1 mice from reciprocal crosses between the B6 and JF strains, demonstrated that the mouse calcitonin receptor gene ( Calcr) was expressed preferentially from the maternal allele in brain, whereas no allelic bias was detected in other tissues. Our results indicate that Calcr is imprinted in a tissue-specific manner, with a predominant expression from the maternal allele in the brain.

Identification and characterization of an imprinted antisense RNA (MESTIT1) in the human MEST locus on chromosome 7q32.

Imprinted gene(s) on human chromosome 7 are thought to be involved in Russell-Silver syndrome (RSS), based on the fact that approximately 10% of patients have maternal uniparental disomy of chromosome 7. However, involvement of the known imprinted genes (GRB10 at 7p12, PEG10 at 7q21.3 and MEST at 7q32) in RSS has yet to be established. To screen for new imprinted genes, we are initially using somatic cell hybrids containing a paternal or maternal human chromosome 7. Transcripts located between D7S530 and D7S649 (a 1.5 Mb interval encompassing MEST ) were subjected to RT-PCR analysis using somatic cell hybrids. One transcript named MESTIT1 (for MEST intronic transcript 1) reproducibly showed paternal-specific expression. Upon further analysis, we found MESTIT1 to be (1) paternally (and not maternally) expressed in all fetal tissues and fibroblasts examined, (2) to be located in an intron of one of the two isoforms of MEST but transcribed in the opposite direction, (3) to be composed of at least two exons without any significant open reading frame, and (4) to exist as a 4.2 kb transcript in many fetal and adult tissues. We could also identify two isoforms of the mouse Mest gene as observed in humans, but it is still unknown if a murine ortholog of MESTIT1 exists. We also examined the imprinting status of MEST isoforms as a first step in assessing whether MESTIT1 might influence the allelic expression pattern of the sense transcript. MEST isoform 1 was determined to be exclusively expressed from the paternal allele in all fetal tissues and cell lines examined, whereas MEST isoform 2 was only preferentially expressed from the paternal allele in a tissue/cell-type-specific manner. Our results suggest that MESTIT1 is a paternally expressed non-coding RNA that may be involved in the regulation of MEST expression during development. MESTIT1 (also known as PEG1-AS) is now the third independent transcript (with MEST and COPG2IT1) identified at human chromosome 7q32 demonstrating paternal chromosome-specific expression.

Molecular genetic studies of human chromosome 7 in Russell-Silver syndrome.

Russell-Silver syndrome (RSS) is a form of congenital short stature characterized by severe growth retardation and variable dysmorphic features. In some RSS individuals, alterations in imprinted genes may be involved because approximately 7% of sporadic patients have been observed to have maternal uniparental disomy (mUPD) of chromosome 7. RSS patients with structural abnormalities of chromosome 7 have also been described. In these individuals the chromosome rearrangement could disrupt the balance of imprinted genes, contribute to a recessive form of RSS, or lead to haploinsufficiency of a crucial developmental gene product. Because the mechanism and molecular defects on chromosome 7 causing RSS are still unknown, we tested our collection of 77 RSS families for mUPD7 and were able to identify three new cases. We also characterized two RSS patients with de novo cytogenetic abnormalities involving the short arm of chromosome 7. One had a partial duplication [46, XX, dup(7)(p12 p14)] and the second contained a paracentric inversion [46, XY, inv(7)(p14 p21)]. Fluorescence in situ hybridization (FISH) mapping revealed that the breakpoints on 7p14 were localized to the same novel gene, C7orf10, which encompasses >700 kb of DNA. We also identified other transcription units from this immediate region, but all seem to be biallelically expressed when using a somatic cell hybrid assay.

Asb4, Ata3, and Dcn are novel imprinted genes identified by high-throughput screening using RIKEN cDNA microarray.

Genes differentially expressed between parthenogenetic and androgenetic embryos are candidates for the identification of imprinted genes, which are expressed specifically from the maternal or paternal allele. To search for genes differentially expressed between parthenogenetic and androgenetic embryos, we used the RIKEN full-length enriched mouse cDNA microarray. The 25 candidates obtained included 8 known imprinted genes (such as IgfII, Snrpn, and Neuronatin) and 3 new ones--Asb4 (ankyrin repeat and SOCS box-containing protein 4), Ata3 (amino acid transport system A3), and Decorin--which were confirmed by using normal diploid embryos from the reciprocal F1 crosses of B6 and JF1 mice. The 25 candidates also included genes that showed no imprinting-associated expression in normal diploid embryos. We describe a feasible high-throughput method of screening for novel imprinted genes by using the RIKEN cDNA microarray.