The Prediction of Dry Weight for Chronic Hemodialysis Athletes Using a Machine Learning Approach: Sports Health Implications / La predicción del peso seco para atletas en hemodiálisis crónica mediante un enfoque de aprendizaje automático: implicaciones para la salud deportiva

This study seeks to evaluate the ability of machine learning methods to predict the dry weight of chronic hemodialysis athletes. The researcher has reached out to kidney patients who have had to give up sports and athletic careers due to chronic hemodialysis. This paper explores the development of medical prediction algorithms that combine image analysis with numerical data, which is widely used in the field of medicine. This deep learning method is widely employed to enhance the treatment of athletes who have kidney conditions. Regular hemodialysis is crucial for maintaining the health of athletes who have kidney disease. Accurately predicting dry weight is a crucial step in the process of performing hemodialysis. In this context, dry weight refers to the optimal moisture level at which excess water is effectively eliminated from the patient (athletes) through ultrafiltration during hemodialysis. In order to accurately determine the optimal amount of hemodialysis, predicting the correct dry weight is crucial. However, this task is quite challenging and often yields inaccurate results due to the extensive data analysis required by experienced nephrologists. This paper presents a deep learning methodology utilising the Artificial Neural Network (ANN) approach to efficiently address these issues. The proposed method aims to predict dry weight rapidly by analysing image values and clinical data from X-ray images obtained during routine check-ups. The current study has several theoretical and practical implications. This study contributes to the existing literature on chronic hemodialysis and the dry weight of athletes, offering valuable insights to sports health organisations. By doing so, these organisations can effectively prepare to proactively evaluate the atypical health conditions of athletes.(AU)

Effects of aroma self-foot reflexology on peripheral neuropathy, peripheral skin temperature, anxiety, and depression in gynaecologic cancer patients undergoing chemotherapy: A randomised controlled trial.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) can interfere with activities of daily living and can negatively affect symptoms. Thus, this study aimed to develop and implement an aroma self-foot reflexology regimen based on Cox's Interaction Model of Client Health Behaviour (IMCHB) as an intervention that can be self-performed at home and at any time. The effects of aroma self-foot reflexology on peripheral neuropathy, peripheral skin temperature, anxiety, and depression were examined in patients with gynaecologic cancer who were undergoing chemotherapy. METHODS: This randomized controlled trial included 32 experimental and 31 control patients with CIPN. Data were collected using self-reported questionnaires (CIPN assessment tool, HADS). In the experimental group, peripheral neuropathy, peripheral skin temperature, anxiety, and depression were measured before and after aroma self-foot reflexology therapy for 6 weeks. The control group was provided with identical aroma self-foot reflexology training 6 weeks later and underwent the intervention at that time. RESULTS: The intervention resulted in lower levels of symptoms of peripheral neuropathy, less interference with activities (p < .001), and higher peripheral skin temperature level (p < .001). Anxiety and depression decreased in the experimental group (p < .001). The ratio of borderline and definite cases of anxiety and depression did not differ between groups. CONCLUSIONS: An aroma self-foot reflexology intervention can reduce CIPN, anxiety, and depression in gynaecologic cancer patients. Further research is required to assess the effects of differences in the content of the intervention and the effects of various numbers of applications and durations of applications based on each individual patient's condition.

Correlates of Successful Aging in South Korean Older Adults: A Meta-Analytic Review.

The purpose of this study was to examine the factors contributing to achieving successful aging (SA) among the Korean older population and identified the strength of each factor's contribution to SA. We extensively searched 4 Korean and 3 English online databases, extracting a total of 64 studies for the analysis. Finally, 42 associated factors and 347 correlation coefficients were found, which were then categorized into 5 domains: functional, psychological, familial, social, and demographic. The psychological domain had the highest effect size. This was followed, in descending order, by the social, functional and familial, and demographic domains. Importantly, the familial domain, which has not been explored in many existing SA models, emerged as a notable predictor. This study is meaningful in terms of understanding one of the minority older populations more deeply and providing stronger evidence for developing evidence-based intervention programs for Korean older adults.

Association between Vitamin D Deficiency and Anemia in Patients with End-Stage Renal Disease: A Cross-Sectional Study.

PURPOSE: Despite new treatment strategies, anemia remains the most prevalent complication in patients with end-stage renal disease (ESRD). We investigated whether 25-hydroxyvitamin D [25(OH)D3] deficiency was associated with anemia in ESRD patients. MATERIALS AND METHODS: We reviewed the medical records of 410 ESRD patients who had undergone renal transplantation (RTx) at Yonsei University Health System and who had 25(OH)D3 levels measured at the time of RTx. Patients were divided into two groups based on baseline 25(OH)D3 concentrations: group 1, 25(OH)D3 levels <10 ng/mL; and group 2, 25(OH)D3 levels ≥10 ng/mL. RESULTS: Using multivariate regression models, 25(OH)D3, age, and erythrocyte-stimulating agent (ESA) dose were found to be significantly associated with hemoglobin (Hb) levels [25(OH)D3: ß=0.263, p<0.001; age: ß=0.122, p=0.010; ESA dose: ß=-0.069, p=0.005]. In addition, logistic regression analysis revealed that patients in group 1 had a significantly higher risk for developing anemia (Hb level <10 g/dL) compared to group 2 patients, even after adjusting for potential risk factors for anemia (odds ratio=3.857; confidence interval=1.091-13.632; p=0.036). CONCLUSION: 25(OH)D3 deficiency was significantly associated with anemia in patients with ESRD. Randomized controlled trials are needed to determine whether vitamin D supplementation can improve anemia in these patients.

[Trends in nursing research in Korea: research trends for studies published from the inaugural issue to 2010 in the Journal of Korean Academy of Nursing and the journals published by member societies under Korean Academy of Nursing Science].

PURPOSE: The purpose of this study was to identify trends for studies published in the Journal of Korean Academy of Nursing and journals published by member societies from inaugural issues to 2010. METHODS: A total of 6890 studies were analyzed using descriptive statistics. RESULTS: Quantitative studies accounted for 83.6% while qualitative studies accounted for 14.4%. Most frequently used research designs were quasi-experimental (91.1%) for experimental research and survey (85.2%) for non-experimental research. Most frequent study participants were healthy people (35.8%), most frequent nursing interventions, nursing skills (53.5%), and 39.8% used knowledge, attitude and behavior outcomes for dependent variables. Most frequently used keyword was elderly. Survey studies decreased from 1991 to 2010 by approximately 50%, while qualitative studies increased by about 20%. True experimental research (1.2%) showed no significant changes. Studies focusing on healthy populations increased from 2001-2005 (37.5%) to 2006-2010 (41.0%). From 1970 to 2010, studies using questionnaire accounted for over 50% whereas physiological measurement, approximately 5% only. Experimental studies using nursing skill interventions increased from 1970-1980 (30.4%) to 2006-2010 (64.0%). No significant changes were noted in studies using knowledge, attitude and behavior (39.9%) as dependent variables. CONCLUSION: The results suggest that further expansion of true experimental, qualitative studies and physiological measurements are needed.

DICOM-based intravascular ultrasound signal intensity analysis: an Echoplaque Medical Imaging Bench study.

BACKGROUND: Most intravascular ultrasound (IVUS) data are stored digitally using the Digital Imaging and Communications in Medicine (DICOM) standard. This allows random access to studies and improves on the major limitation of conventional grayscale IVUS. METHODS: We harvested 129 coronary arteries from 43 autopsied cases. Grayscale IVUS and virtual histology-IVUS imaging were performed beginning 30 mm distal to the ostium of each coronary artery. Grayscale IVUS was processed; and the signal intensity was determined from DICOM-stored images using a new Medical Imaging Bench system (Echoplaque-MIB). We compared 436 regions of interest. The accuracy rate was expressed using the interpolation method and 95% confidence interval (CI). RESULTS: Patients' mean age was 49±9 years and 82% were men. Four patients succumbed to sudden cardiac death and 39 to noncardiac death. Grayscale IVUS signal intensity of dense calcium was 215±21.1 (95% CI: 207-223), that of fibrotic plaque was 75±17.8 (95% CI: 72-79), and that of fibrofatty plaque was 55±11.3 (95% CI: 52-59); however, the signal intensity of the necrotic core was between fibrotic plaque and dense calcium of 161±27.4 (95% CI: 153-168). Using the interpolation method, the cutoff values were as follows: fibrofatty plaque 0-65, fibrotic plaque 66-105, necrotic core 106-187, and dense calcium of at least 188. Overall, MIB grayscale had a 78.1% sensitivity and a 91.9% specificity versus histopathology. CONCLUSION: Plaque characterization using DICOM-based grayscale IVUS signal intensity analysis may improve on the major limitation of conventional grayscale IVUS: its inability to assess plaque composition.

Replication of a microsatellite genome-wide association study of Behcet's disease in a Korean population.

OBJECTIVE: Behçet's disease is one of the major aetiologies of uveitis causing blindness in Asian countries. A genome-wide association study identified six microsatellite markers as disease susceptibility loci for Japanese patients with Behçet's disease. To confirm our recent results, these microsatellite markers were examined in a Korean population as a replication study. METHODS: Study participants included 119 Behçet's disease patients and 141 controls. All were enrolled in Korea. Association between the six reported microsatellite markers (D3S0186i, D6S0014i, D6S0032i, 536G12A, D12S0645i and D22S0104i) and Behçet's disease was analysed. HLA-B was genotyped by sequence-based typing methods. RESULTS: A microsatellite marker located near the HLA-B region demonstrated significant association with Behçet's disease (P = 0.028). The genotype and phenotype frequencies of the HLA-B*51 gene were significantly increased in patients (23.1 and 39.5%, respectively) compared with healthy controls (11.2 and 20.1%, respectively; P < 0.001). CONCLUSION: Microsatellite analysis revealed that the HLA-B*51 gene was strongly associated with Behçet's disease in a Korean population.

Mannose-binding lectin 2 gene haplotype analysis in Korean patients with ankylosing spondylitis.

Mannose-binding lectin (MBL) serum levels or genetic polymorphisms are known to be associated with autoimmune diseases. We investigated MBL2 genetic polymorphisms in 95 patients with ankylosing spondylitis (AS) and in 252 healthy controls. MBL2 promoter polymorphisms at -550 (H/L), -221 (Y/X), +4 (P/Q), and exon polymorphisms at codon 52 (Arg/Cys), 54 (Gly/Asp, or A/B), and 57 (Gly/Glu) were investigated using polymerase chain reaction and restriction fragment length polymorphism. Genetic polymorphisms were analyzed using SPSS (ver 12.0) and Haploview (ver 4.2). MBL2 single-nucleotide polymorphisms (SNPs) were not significantly different between patients with AS and controls. By haplotype analysis, LYPB frequency was significantly lower in AS (10.7% vs. 21.3%, OR 0.441, 95% CI: 0.266-0.733, P value = 0.001, Pc value = 0.008). The frequency of LYPA (15.4% vs. 9.2%, OR 1.802, 95% CI: 1.097-2.961, P value = 0.019, Pc value = 0.101) and HYPB (3.5% vs. 0.8%, OR 4.457, 95% CI: 1.289-15.409, P value = 0.011, Pc value = 0.060) tended to be higher in AS. Clinical characteristics of AS were not associated with any MBL2 SNP or haplotype. In summary, haplotypes of MBL2 genetic polymorphisms were found to be associated with AS, which suggests that MBL2 genetic polymorphisms may play a role during the development of AS.

Clinical characteristics of TIMP2, MMP2, and MMP9 gene polymorphisms in colorectal cancer.

BACKGROUND AND AIM: Genetic variations and the expression profile of matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) are involved in the invasion and metastasis of colorectal cancer. METHODS: The gene profiles of TIMP2 and MMP were assayed from 333 colorectal cancer using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: TIMP2-418*G/*G, TIMP2 303*G/*G and MMP9-1562*C/*C were more frequent in patients than in controls (P = 0.020, P < 0.0001 and P < 0.044, respectively). Frequency of TIMP2-418*G/*G was higher in patients with metastasis than in those without metastasis, and that of TIMP2 303*G/*G was higher in patients with rectal cancer than in those with colon cancer (P = 0.008 and P =0.022, respectively). TIMP2-303*A/*A and MMP2-1575*G/*G were less frequent in patients than in controls (P = 0.001 and P = 0.005, respectively). The TIMP2-418*G303*G haplotype was more frequent (P < 0.0001) and MMP2-1575*G-735*C haplotype was less frequent in patients than in controls (P= 0.005). CONCLUSION: Specific single-nucleotide polymorphism in TIMP2 and MMP appeared to be associated with tumorigenesis and biological behavior in colorectal cancer, which is expected be further verified in a larger cohort in the future.

The role of Qa-2, the functional homolog of HLA-G, in a Behcet's disease-like mouse model induced by the herpes virus simplex.

BACKGROUND: It has been suggested that the HLA-G molecule is a genetic risk factor for Behcet's disease (BD). In this study, we evaluated the level of Qa-2, a murine nonclassical class I MHC molecule and possible functional homolog of HLA-G, to determine if it was associated with various symptoms of BD-like mice. In addition, we investigated siRNA (small interfering RNA) treatment to determine if it inhibited Qa-2 expression, thereby changing the symptoms of mice. METHODS: RNA interference (RNAi) and vector transfection were employed to manipulate gene expression in vivo in mice. siRNA (small interfering RNA) or Qa-2 expression vector was applied to inhibit or up-regulate Qa-2 expression, respectively. RESULTS: The Qa-2 levels in granulocytes were lower in BD-like mice than in normal controls. The silencing of Qa-2 by intravenous injection of siRNA (500 nmol/mouse, 4 times at 3-day intervals) specifically reduced the Qa-2 levels and worsened the BD-like symptoms. CONCLUSIONS: Silencing Qa-2 by injecting siRNA into mice resulted in deterioration of symptoms in BD-like mice.

Association of TLR4 polymorphisms with Behcet's disease in a Korean population.

OBJECTIVES: HLA-B51 is strongly associated with Behçet's disease (BD) in any ethnic background. We recently reported that another gene, Toll-like receptor-4 (TLR4) is also implicated in BD in a Japanese population. To confirm these results, we investigated polymorphisms in the TLR4 gene in Korean patients with BD. METHODS: In this study, 119 patients with BD and 141 healthy controls were enrolled; every participant was a Korean. Nine single nucleotide polymorphisms previously detected in TLR4 by direct sequencing were analysed for an association with BD. RESULTS: The most frequent haplotype, TAGCGGTAA, was significantly increased in HLA-B*51-positive BD patients (49.5%), compared with healthy control participants [32.3%; P = 0.029; odds ratio (OR) = 2.01; 95% CI 1.25-3.23]. This haplotype was also significantly increased in BD patients with arthritis (48.2%; P = 0.003; OR = 1.96; 95% CI 1.26-3.26). There were no significant differences in the allele and genotype frequencies of patients and controls for each single nucleotide polymorphism. CONCLUSIONS: The haplotype of TLR4 may increase the risk for developing BD and the complication of arthritis in the Korean population.

The virtual histology intravascular ultrasound appearance of newly placed drug-eluting stents.

Intravascular ultrasound (IVUS) is used before and after intervention and at follow-up to assess the quality of the acute result as well as the long-term effects of stent implantation. Virtual histology (VH) IVUS classifies tissue into fibrous and fibrofatty plaque, dense calcium, and necrotic core. Although most interventional procedures include stent implantation, VH IVUS classification of stent metal has not been validated. In this study, the VH IVUS appearance of acutely implanted stents was assessed in 27 patients (30 lesions). Most stent struts (80%) appeared white (misclassified as "calcium") surrounded by red (misclassified as "necrotic core"); 2% appeared just white, and 17% were not detectable (compared with grayscale IVUS because of the software-imposed gray medial stripe). The rate of "white surrounded by red" was similar over the lengths of the stents; however, undetectable struts were mostly at the distal edges (31%). Quantitatively, including the struts within the regions of interest increased the amount of "calcium" from 0.23 +/- 0.35 to 1.07 +/- 0.66 mm(2) (p <0.0001) and the amount of "necrotic core" from 0.59 +/- 0.65 to 1.31 +/- 0.87 mm(2) (p <0.0001). Most important, because this appearance occurs acutely, it is an artifact, and the red appearance should not be interpreted as peristrut inflammation or necrotic core when it is seen at follow-up. In conclusion, acutely implanted stents have an appearance that can be misclassified by VH IVUS as "calcium with or without necrotic core." It is important not to overinterpret VH IVUS studies of chronically implanted stents when this appearance is observed at follow-up. A separate classification for stent struts is necessary to avoid these misconceptions and misclassifications.

Molecular basis of complement factor I (CFI) polymorphism: one of two polymorphic suballeles responsible for CFI A is Japanese-specific.

Isoelectric focusing has revealed that human complement factor I (CFI) is controlled by two polymorphic alleles, CFI(*)A and CFI(*)B, and a few rare variant alleles. In this study the molecular basis of the CFI polymorphism was investigated in 174 Japanese. The CFI(*)A was divided into two suballeles, CFI(*)As (R201S) and CFI(*)Ah (R406H). CFI(*)Aj, a rare variant allele originating from CFI(*)Ah, had an additional mutation (R502L). The distribution of these three mutations and two registered SNPs was investigated in a total of 2,471 individuals in 20 populations from various areas, and six haplotypes were observed. Haplotype H3, which is characterized by CFI(*)As, was found only in Far East populations: the frequencies were about 0.03 in the main island of Japan and lower than 0.01 in Okinawa and Korea. Haplotype H5, characterized by CFI(*)Ah, prevailed almost exclusively in East Asians and was observed at the highest frequencies in southern Chinese Han and Thais. CFI(*)Ah must have arisen in a southeastern part of Asia and thereafter have spread to neighboring populations.

Cardiovascular and hematopoietic defects associated with Notch1 activation in embryonic Tie2-expressing populations.

Notch signaling is critical for the development and maintenance of the cardiovasculature, with loss-of-function studies defining roles of Notch1 in the endothelial/hematopoietic lineages. No in vivo studies have addressed complementary gain-of-function strategies within these tissues to define consequences of Notch activation. We developed a transgenic model of Cre recombinase-mediated activation of a constitutively active mouse Notch1 allele (N1ICD(+)) and studied transgene activation in Tie2-expressing lineages. The in vivo phenotype was compared to effects of Notch1 activation on endothelial tubulogenesis, paracrine regulation of smooth muscle cell proliferation, and hematopoiesis. N1ICD(+) embryos showed midgestation lethality with defects in angiogenic remodeling of embryonic and yolk sac vasculature, cardiac development, smooth muscle cell investment of vessels, and hematopoietic differentiation. Angiogenic defects corresponded with impaired endothelial tubulogenesis in vitro following Notch1 activation and paracrine inhibition of smooth muscle cells when grown with Notch1-activated endothelial cells. Flow cytometric analysis of hematopoietic and endothelial precursor populations demonstrated a significant loss of CD71(+)/Ter119(+) populations with an active N1ICD(+) allele and a corresponding increase in c-Kit(+)/CD71 and Flk1(+) populations, suggesting a developmental block during the transition between c-Kit- and Ter119-expressing erythroblasts. Cardiovascular lineages are sensitive to an imbalance in Notch signaling, with aberrant activation reflecting a vascular phenotype comparable to a loss-of-function Notch1 mutation.

Tumor necrosis factor alpha small interfering RNA decreases herpes simplex virus-induced inflammation in a mouse model.

BACKGROUND: Anti-TNFalpha antibodies have been used for treating inflammation in patients. But, more effective and safer drugs need to be developed for improved future therapeutic use. OBJECTIVES: To inhibit the expression of TNFalpha, we used small interfering RNAs (siRNAs) to reduce over expression of TNFalpha in vitro in cell cultures and in an in vivo Behcet's disease-like (BD) mouse model for amelioration of chronic inflammation. METHODS: TNFalpha siRNA was injected intraperitoneally twice with a 1-week interval. To compare the efficacy of TNFalpha siRNA versus an anti-TNFalpha antibody, Infliximab and Etanercept were administered to symptomatic mice with inflamed tissue. RESULTS: Intraperitoneal delivery of TNFalpha siRNA effectively decreased BD symptoms in 18 of 32 cases (56.3%). Scrambled siRNA treatment decreased BD symptoms in 2 of 19 cases (10.5%). Infliximab was effective in 11 of 27 cases (40.7%) and Etanercept was also effective in 9 of 25 cases (36.0%) at the end of the second week after treatment. TNFalpha siRNA reduced serum levels of TNFalpha (1.57 +/- 0.43pg/ml), compared to levels in mice not injected (84.02 +/- 24.59pg/ml) (p<0.01) or scramble injected (118.89 +/- 20.08pg/ml) (p<0.01). After single injection of TNFalpha siRNA, improvement of BD symptoms showed at 9 +/- 7th day on an average, contrary, in Infliximab injected group, improvement was apparent at 15 +/- 4th day after injection (p<0.05). CONCLUSION: We show that siRNAs can be employed to inhibit cytokine gene expression in an in vivo disease mouse model. This inhibition may, therefore, be attributed to the improvement of inflammatory symptoms.

Matrix metalloproteinase-9 promoter polymorphisms in Korean patients with systemic lupus erythematosus.

To investigate the association between functional promoter polymorphisms of matrix metalloproteinase-9 (MMP-9) and systemic lupus erythematosus (SLE), we analyzed MMP-9 promoter -1562 C>T and MMP-9 -90 (CA)(n) repeat polymorphisms in 135 Korean SLE patients (mean age, 34.7 years; 124 female and 11 male) and in 135 gender- and age-matched healthy controls (mean age, 35.4 years). Clinical and laboratory findings were collected during the follow-up period (mean, 63.5 months; range, 3-252 months), and Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Indexes were calculated. The levels of total MMP-9 were measured in sera of SLE patients and controls by enzyme-linked immunoabsorbent assay. The serum levels of MMP-9 in SLE patients were significantly lower than those of controls (mean +/- standard error of the mean, 1421.6+/-177.4 vs 3731.4+/-441.4 ng/ml, p=1.2 x 10(-5) by t test). Both functional polymorphisms were under the Hardy-Weinberg equilibrium state except (CA)(n) repeat polymorphisms in SLE patients (p=2.6 x 10(-5) by chi(2) goodness-of-fit test). The distribution of the MMP-9 promoter polymorphisms or haplotypes was not significantly different in SLE patients and controls. However the frequency of alleles with low numbers of CA repeats (n<21, 11.9% vs 7.0%, p=0.06 by the chi(2) test; odds ratio=1.78, 95% confidence interval=0.99-3.20) and the prevalence of low CA repeats homozygote tended to be higher in patients than in controls (5.2% vs 0.7%, p=0.07 by logistic regression, odds ratio=7.29, 95% confidence interval=0.88-60.10) in the recessive model. No relationship was found between MMP-9 polymorphisms and clinical features or damage as indicated by SLICC/ACR Damage Index in the study subjects. These results suggest that genetic polymorphisms of the MMP-9 promoter regions are not associated with the development of SLE in Korea.

Korean older adults' perceptions of the aging process.

This qualitative study was conducted to describe Korean older adults' perceptions of the aging process. A total of 18 Korean older adults were interviewed, and a grounded theory approach was used to analyze the interview data. The participants were found to perceive aging as a process of Generating, Expressing, and Transforming of Growing Futility. The degree to which they perceived their Growing Futility depended on the actions and interactions of a set of conditional structures. This study revealed five patterns of Korean older adults' perception of the aging process. These findings allow for the possibility of a more refined theoretical development for the aging process, especially when a comparative study becomes available through cross-cultural qualitative research.

Allele frequencies of a SNP and a 27-bp deletion that are the determinant of earwax type in the ABCC11 gene.

Allele frequencies for a SNP (rs17822931) and a 27-bp deletion that are the determinant of earwax type in the ABCC11 gene were investigated in seven Japanese, one Korean, and one German populations. The SNP will be useful as one of ancestry information markers, because it showed marked difference in frequencies between Asian and European populations.

OCA2 481Thr, a hypofunctional allele in pigmentation, is characteristic of northeastern Asian populations.

Asians as well as Europeans have light skin, for which no genes to date are known to be responsible. A mutation, Ala481Thr (c.G1559A), in the oculocutaneous albinism type II (OCA2) gene has approximately 70% function of the wild type allele in melanogenesis. In this study, the distribution of the mutation was investigated in a total of 2,615 individuals in 20 populations from various areas. OCA2 481Thr prevailed almost exclusively in a northeastern part of Asia. The allele frequency was highest in Buryat (0.24) in Mongolia and showed a north-south downward geographical gradient. These findings suggest that OCA2 481Thr arose in a region of low ultraviolet radiation and thereafter spread to neighboring populations.

Heat shock protein 70 alters the endosome-lysosomal localization of huntingtin.

Huntington's disease is caused by CAG trinucleotide expansions in the gene encoding huntingtin. N- terminal fragments of huntingtin with polyglutamine produce aggregates in the endosome-lysosomal system, where proteolytic fragments of huntingtin is generated. Heat shock protein 70 (HSP70) prevents the formation of protein aggregates, but the effect of HSP70 on the huntingtin in the endosome-lysosomal system is unknown. This study was to determine whether HSP70 alters the distribution of huntingtin in endosome-lysosomal system. HSP70 expressing stable cells (NIH/3T3 or cerebral hybrid cell line A1) were generated, and mutant [(CAG)(100)] huntingtin was transiently overexpressed. Analysis of subcellular distribution by immunocytochemistry or proteolysis cleavage by Western blotting was performed. 18 CAG repeat wild type [WT; (CAG)(18)] huntingtin was used as a control. Cells with huntingtin showed patterns of endosome-lysosomal accumulation, from a "dispersed vacuole (DV)" type into a coalescent "perinuclear vacuole (PV)" type over time. In WT huntingtin, HSP70 increased the cells with the PV types that enhanced the proteolytic cleavage of huntingtin. However, HSP70 reduced cells of the DV and PV types expressing mutant huntingtin, that result in less proteolysis than that of control. In addition, intranuclear inclusions were formed only in mutant cells, which was not affected by HSP70. These results suggest that HSP70 alters the distribution of huntingtin in the endosome- lysosomal system, and that this contributes to huntingtin proteolysis.