Molecular detection of fungal and bacterial DNA from pustules in patients with palmoplantar pustulosis: special focus on Malassezia species.

BACKGROUND: Palmoplantar pustulosis (PPP) is a distinct, chronic skin disorder characterized by intraepidermal pustules on the palms and soles. It is hypothesized that microorganisms on the skin might induce the symptoms of PPP via inflammatory cell activation. However, the microbiota has not been studied in detail because of the assumption that the pustules in PPP are sterile. AIM: To elucidate the role of microorganisms in pathogenesis of PPP. METHODS: PCR analysis was performed of microbial DNA fragments in the pustules of patients with PPP. The sequence of the D1/D2 LSU 26s rRNA gene and that of the 16S rRNA gene was used for fungal and bacterial DNA detection, respectively. RESULTS: In total, 71 samples were carefully collected from the pustules of patients with PPP. Fungal DNA bands were detected in 68 samples, and fungi including Malassezia spp. were identified in 30 of 71 samples (42.3%). Malassezia restricta was the most frequently encountered fungus (14/71; 19.7%). However, bacterial DNA was not detected by the methods used. Furthermore, identical fungal DNA was not detected in the outer lid of the pustules, suggesting that the fungi detected within the pustule did not derive from contamination via the skin surface. CONCLUSIONS: In the present study, we demonstrated for the first time that certain pustules in patients with PPP contain fungal DNA fragments, especially those of Malassezia spp. Our findings provide new insights on the role of skin microbiota in the pathogenesis of PPP.

Functional analysis of a novel G87V TNFRSF1A mutation in patients with TNF receptor-associated periodic syndrome.

Tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is an autoinflammatory disease that is caused by heterozygous mutations in the TNFRSF1A gene. Although more than 150 TNFRSF1A mutations have been reported to be associated with TRAPS phenotypes only a few, such as p.Thr79Met (T79M) and cysteine mutations, have been functionally analyzed. We identified two TRAPS patients in one family harboring a novel p.Gly87Val (G87V) mutation in addition to a p.Thr90Ile (T90I) mutation in TNFRSF1A. In this study, we examined the functional features of this novel G87V mutation. In-vitro analyses using mutant TNF receptor 1 (TNF-R1)-over-expressing cells demonstrated that this mutation alters the expression and function of TNF-R1 similar to that with the previously identified pathogenic T79M mutation. Specifically, cell surface expression of the mutant TNF-R1 in transfected cells was inhibited with both G87V and T79M mutations, whereas the T90I mutation did not affect this. Moreover, peripheral blood mononuclear cells (PBMCs) from TRAPS patients harboring the G87V and T90I mutations showed increased mitochondrial reactive oxygen species (ROS). Furthermore, the effect of various Toll-like receptor (TLR) ligands on inflammatory responses was explored, revealing that PBMCs from TRAPS patients are hyper-responsive to TLR-2 and TLR-4 ligands and that interleukin (IL)-8 and granulocyte-macrophage colony-stimulating factor (GM-CSF) are likely to be involved in the pathogenesis of TRAPS. These findings suggest that the newly identified G87V mutation is one of the causative mutations of TRAPS. Our findings based on unique TRAPS-associated mutations provide novel insight for clearer understanding of inflammatory responses, which would be basic findings of developing a new therapeutic and prophylactic approach to TRAPS.

Factors related to dissociation between objective and subjective masticatory function in Japanese community-dwelling elderly adults.

Clinicians' evaluations of older adults sometimes reveal inconsistencies between objective and subjective dental status. This study investigated which factors contribute both to good objective masticatory function (OMF) and the poor subjective masticatory function (SMF) that often becomes a clinical issue. Study participants included 635 elderly community-dwelling Japanese adults who underwent a comprehensive geriatric health examination in 2012. SMF was assessed with a question from the Kihon Checklist on eating difficulties (poor or good). OMF was assessed by a colour-changing gum (poor or good). Also investigated were age, sex, depressive symptoms, instrumental activities of daily living (I-ADLs), number of people who joined the participant at dinner, grip strength, usual walking speed, number of remaining teeth, number of functional teeth and their occlusal force. The group with good OMF and good SMF, defined as group 1, and the group with good OMF but poor SMF, group 2, were compared. Logistic regression analyses confirmed that the number of remaining and functional teeth participants had was statistically unrelated to differences between OMF and SMF. Instead, differences were related to stronger depressive symptoms (OR = 1.67, CI = 1.14-2.44), less ability to conduct I-ADL activities (OR = 0.73, CI = 0.59-0.91), slower usual walking speeds (OR = 0.18, CI = 0.06-0.58) and less occlusal force (OR = 0.99, CI = 0.99-1.00). Depressive symptoms, I-ADLs, and physical function are shown to be significantly related to divergence between objective and subjective masticatory function in elderly Japanese. This suggests that dissociations between objective and subjective dental evaluations of elderly adults indicate need for assessment of their mental and physical function.

An examination of factors related to aspiration and silent aspiration in older adults requiring long-term care in rural Japan.

Swallowing disorders are a growing problem among the elderly in long-term care (LTC), and they can cause aspiration pneumonia. In order to detect swallowing disorders early, simple tools are needed to assess aspiration and silent aspiration (SA). To compile a sample of elderly people requiring LTC, and categorise them as having suspected aspiration and/or SA using simple screening tools. In addition, oral ability, severity of dementia, vital functions and nutritional status were compared in these groups. A total of 393 elderly people in LTC (89 men and 304 women; age ranging from 65 to 100 years) were included in the study. The modified water swallow test, cervical auscultation and cough test were used to assess swallowing function. The participants were categorised as having suspected aspiration and/or SA, and the following assessments were performed: (i) oral ability (lips function, tongue function, rinsing and gargling ability), (ii) dementia severity, (iii) vital functions and (iv) nutritional status. Suspected aspiration was apparent in 50.5% of patients, of which 24.0% had suspected SA. Those with suspected aspiration showed worsened oral ability, dementia severity, vital functions and nutritional status. Similarly, those with suspected SA showed worsened dementia severity, vital functions and nutritional status. Logistic regression analysis revealed that lip closure, lingual movement and rinsing ability were significantly associated with suspected aspiration. Dementia severity was the best predictor of suspected SA. Simple screening tools can be used to identify suspected aspiration and SA, which may facilitate early detection of aspiration pneumonia or swallowing disorder risk.

Angiomyofibroblastoma of the vulva.

BACKGROUND: Angiomyofibroblastoma (AMF) is a rare benign mesenchymal neoplasm that arises in the pelviperial region. CASE: A patient presented with a painless mass in the right vulva. Under the preoperative diagnosis of Bartholin cyst, she underwent a simple tumor excision. Pathological examination revealed an AMF. Immunohistochemical examination showed that tumor cells were positive for estrogen receptor, progesterone receptor, vimentin, and CD34. She has been with no evidence of local recurrence for ten months after surgery. CONCLUSION: AMF of the vulva is a distinctive mesenchymal tumor that is curable with a simple excision.

Updated overall survival results from a randomized phase III trial comparing gefitinib with carboplatin-paclitaxel for chemo-naïve non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002).

BACKGROUND: NEJ002 study, comparing gefitinib with carboplatin (CBDCA) and paclitaxel (PTX; Taxol) as the first-line treatment for advanced non-small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) mutation, previously reported superiority of gefitinib over CBDCA/PTX on progression-free survival (PFS). Subsequent analysis was carried out mainly regarding overall survival (OS). MATERIALS AND METHODS: For all 228 patients in NEJ002, survival data were updated in December, 2010. Detailed information regarding subsequent chemotherapy after the protocol treatment was also assessed retrospectively and the impact of some key drugs on OS was evaluated. RESULTS: The median survival time (MST) was 27.7 months for the gefitinib group, and was 26.6 months for the CBDCA/PTX group (HR, 0.887; P=0.483). The OS of patients who received platinum throughout their treatment (n=186) was not statistically different from that of patients who never received platinum (n=40). The MST of patients treated with gefitinib, platinum, and pemetrexed (PEM) or docetaxel (DOC, Taxotere; n=76) was around 3 years. CONCLUSIONS: No significant difference in OS was observed between gefitinib and CBDCA/PTX in the NEJ002 study, probably due to a high crossover use of gefitinib in the CBDCA/PTX group. Considering the many benefits and the risk of missing an opportunity to use the most effective agent for EGFR-mutated NSCLC, the first-line gefitinib is strongly recommended.

Transition of low-grade to high-grade endometrial stromal sarcoma: a case report.

BACKGROUND: The transition of low-grade endometrial stromal sarcoma (ESS) to high-grade ESS remains a rare clinical event. CASE: A patient presented with abdominal pain and abnormal genital bleeding. She underwent a supracervical hysterectomy with bilateral salpingo-oophorectomy, omentectomy, and resection of peritoneal disseminated lesions. Pathological examination revealed low-grade ESS in the uterus and omentum. Immunohistochemical examination showed immunoreactivity for CD10 and Ki-67 (MIB1) in the uterus and omentum. However, estrogen receptor, progesterone receptor, alpha-SMA, desmin, h-caldesmon, and CAM5-2 were negative. P53 immunoreactivity was noted only in the omental lesion. Despite performing six courses of adjuvant chemotherapy, she recurred in the abdomen. She underwent ileostomy and resection of peritoneal disseminated lesions. Pathology showed high-grade ESS in the recurrent lesion of the ileum, which was characterized by severe cytologic atypia, high mitotic index, multifocal necrosis, increased Ki-67 index, and immunoreactivity for p53. CONCLUSION: Although rare, the transition of low-grade ESS to high-grade ESS may occur and suggests the worsening of the prognosis. Pathological examination and immunohistochemistry are useful for the diagnosis of the transition of low-grade ESS to high-grade ESS.

Association between Oral Frailty and Dietary Variety among Community-Dwelling Older Persons: A Cross-Sectional Study.

OBJECTIVE: To examine the association between the severity of oral frailty (OF), which is one of the comprehensive oral functions evaluated, and dietary variety in community-dwelling older persons. DESIGN: Cross-sectional study. SETTING: Community-based. PARTICIPANTS: A total of 769 community-dwelling older persons aged 65 and over. INTERVENTIONS: We examined basic demographic information, functional status, cognitive status, depressive symptoms, medical history, and oral functions of the participants. MEASUREMENTS: OF was defined by 1-2 and 3 or more of 6 items of oral function evaluation in the pre-oral frailty and oral frailty groups, respectively. Dietary variety was assessed using the dietary variety score (DVS). The participants were categorized into 3 groups for evaluation: those with a low score (0-2), medium score (3-5), and high score (≥6). Ordinal logistic regression analysis was performed to examine the association between OF and DVS. RESULTS: The rate of OF in the participants was 21.6%, and its severity was significantly associated with DVS after adjusting for potential confounders (Pre-OF; adjusted odds ratio [OR] = 1.687, 95% confidence interval [CI] = 1.219-2.335, OF; adjusted OR = 2.857, 95% CI = 1.489-5.484). CONCLUSION: The severity of OF was significantly associated with DVS in community-dwelling older persons. This suggests that DVS may be useful in understanding the effects of OF on the nutritional status. Further longitudinal studies are needed to elucidate the association between OF and DVS.

[Radical surgery using modified open door method for anterior apical tumor].

The approach that should be used for an anterior apical tumor still remains controversial. Since a modified open door method was very useful for the widening of the surgical field in a recent patient with an anterior apical tumor, an outline of this case is reported. The patient was a 66-year-old male with squamous cell carcinoma of the anterior apical region of the right lung (suspected to be invading the thoracic wall, cT3N1M0). After a midline sternal incision with a right unilateral collar incision, the medial half of the right clavicle and a few cm of the right 1st rib on the sternal side were resected to sufficiently expose the area from the right brachiocephalic trunk to around the subclavicular artery and vein, where invasion was suspected. This treatment facilitated widening of the visual field around the site of tumor invasion and made safe right upper lobectomy + combined thoracic wall resection + ND2a possible. In this patient, anterolateral incision at the 4th intercostal level, which is made using the original open door method, could be avoided, probably minimizing surgical invasion.

Association between Oral Frailty and Nutritional Status among Community-Dwelling Older Adults: the Takashimadaira Study.

OBJECTIVES: Recently, the concept of oral frailty, defined as accumulated deficits in oral health, has been introduced in Japan. However, data about its association with nutritional status are limited. Thus, this cross-sectional study aimed to investigate the association between oral frailty and malnutrition among community-dwelling older adults. DESIGN: Cross-sectional study. SETTING: Community. PARTICIPANTS: One thousand and fifty-four individuals (428 men and 626 women, mean age: 77.0 years) from the Takashimadaira Study. MEASUREMENTS: Based on a multifaceted oral health assessment, oral frailty was defined as greater than or equal to three of the following components: (1) low number of remaining teeth, (2) decreased masticatory performance, (3) reduced articulatory oral motor skill, (4) low tongue pressure, and difficulties in (5) eating and (6) swallowing. The nutritional status was evaluated using the Mini Nutritional Assessment®-Short Form (MNA®-SF) and serum albumin. An ordinal logistic regression model was used to evaluate the association between oral frailty and nutritional status. RESULTS: Oral frailty was observed in 217 (20.4%) participants. After adjusting for potential confounders, the participants with oral frailty had higher odds of more severe malnutrition evaluated using MNA®-SF (adjusted odds ratio: 2.17; 95% confidence interval: 1.58-2.98) and serum albumin level (adjusted odds ratio: 1.59; 95% confidence interval: 1.10-2.31). CONCLUSION: Oral frailty was associated with nutritional status among Japanese older adults. Maintaining comprehensive oral health and function may be effective for malnutrition prevention in community-dwelling older adults. However, further studies must be conducted to validate the generalizability of the results of the current study.

Association of Dietary Variety and Appetite with Sleep Quality in Urban-Dwelling Older Japanese Adults.

OBJECTIVES: Although it has been shown that specific foods and nutrients are associated with sleep quality, few studies have examined the association of dietary variety and appetite with sleep quality in older adults. DESIGN AND SETTING: A cross-sectional study was conducted that examined the association of dietary variety and appetite with sleep quality in Japanese adults aged ≥70 years who resided in the metropolitan area of Tokyo, Japan. PARTICIPANTS: Data were collected in two steps: a mailed interview survey and an on-site survey. Those who responded to the surveys and met the inclusion criteria were included. MEASUREMENTS: Dietary variety, appetite, and sleep quality were assessed using a Dietary Variety Score (DVS), Council on Nutrition Appetite Questionnaire (CNAQ) score, and sleep efficiency, respectively. The sleep efficiency is the ratio of sleep duration to total time in bed (retiring time-awakening time). We defined the individuals with a sleep efficiency less than 75% as having poor sleep quality. RESULTS: Mean DVS and CNAQ score were 3.8 and 29.6 points, respectively. The rate of individuals with poor sleep quality was 11.7%. In the fully adjusted model, the odds ratios (OR) for low sleep efficiency in the middle and highest group categories of the DVS were 0.83 (95% confidence interval [CI], 0.54-1.29) and 0.50 (95% CI, 0.28-0.90), respectively, in reference to the lowest group category (p for trend = 0.023). The OR for low sleep efficiency in the middle and highest group categories of the CNAQ score were 0.73 (95% CI, 0.47-1.14) and 0.54 (95% CI, 0.30-0.96), respectively, in reference to the lowest group category (p for trend = 0.031). CONCLUSIONS: The higher DVS and CNAQ scores were significantly associated with higher sleep efficiency. Thus, dietary variety and good appetite might help maintain good sleep quality in urban-dwelling older Japanese adults.

Self-Feeding Ability as a Predictor of Mortality Japanese Nursing Home Residents: A Two-Year Longitudinal Study.

OBJECTIVES: To examine the ability of different elements of the Self-Feeding Assessment Tool for Elderly with Dementia (SFED) to predict mortality risk in nursing home residents. DESIGN AND SETTING: Data from 387 residents in five nursing homes for the elderly in Japan were obtained using a baseline survey. This measure's ability to predict mortality risk was examined over a two-year observation period. Participants and Measurement: Demographic information (sex, age, height, weight, medical history) on 387 initial participants was gathered. A total of 10 individuals were excluded from the analysis because of the inability to eat by mouth at baseline, while 36 were excluded owing to missing mortality data during the observation period. The resulting 341 residents were divided into a death group or survival group according to whether they were still alive after two-year observation period. In addition to basic information and the SFED, the baseline survey included the Barthel Index (BI), Clinical Dementia Rating (CDR), and Mini Nutritional Assessment-Short Form (MNA®-SF). The ability of SFED to predict time-to-event mortality was examined using Cox proportional hazards regression analysis, including other measures associated with mortality as confounding variables. RESULTS: In total, 129 participants (37.8%) died during the observation period, and their mean SFED score was significantly lower than that of surviving ones (11.1 ± 6.7 vs. 15.0 ± 5.6, P<0.001). SFED score was significantly associated with two-year mortality in the Cox proportional hazards regression analysis after adjusting for sex, age, medical history, BI, CDR, and MNA®-SF (hazard ratio = 0.941, 95% confidence interval = 0.898-0.985, P = 0.010). Additionally, three SFED categories were significantly associated with mortality risk: movement ("able to eat without dropping food"), concentration ("able to maintain attention to meal"), and safety ("able to swallow without choking, with no change in vocal quality after eating"). CONCLUSIONS: Self-feeding ability as measured by SFED score was associated with long-term mortality in elderly living in nursing homes. Accordingly, adjusting feeding assistance based on regular SFED-based assessments may help maintain self-feeding ability and enhance quality of life in this population, as well as providing evidence for end-of-life care options and greatly improving care quality.

Safety of Elderly Living Kidney Donors: 2 Cases of Donors Older Than 80 Years: A Case Report.

Much controversy exists over the performance of elderly living donor kidney transplantation. We report the safety of 2 cases of elderly living kidney donations in our hospital. CASE 1: An 82-year-old man was a living kidney donor for his 56-year-old son. The donor suffered from hypertension, but has successfully managed his blood pressure with only one medication. His serum creatinine was 0.7 mg/dL and inulin clearance was 122.5 mL/min, which met the usual criteria for living kidney donors. This was his son's secondary kidney transplantation, and no other donors existed. CASE 2: An 80-year-old woman was a living kidney donor for her 45-year-old son. Her serum creatinine was 0.61 mg/dL and inulin clearance was 71.7 mL/min, which met the marginal kidney donor criteria. In both cases, we determined that the donor kidney function was acceptable. Though we explained the risks of the transplantation thoroughly, the patients' strong will to offer a kidney to their family member did not change. We decided to carry out the transplantation. At the time of publication, nearly 2 years have passed since the transplantation, but both donors and recipients are doing well. In the future, it seems more likely that the number of elderly living donor kidney transplantation will rise. On one hand, there is no absolute contraindication for elderly donors, while on the other hand, the criteria for a living kidney donor must be strictly examined. Furthermore, careful observation of both donors and recipients after transplantation is required.

Frailty Severity and Dietary Variety in Japanese Older Persons: A Cross-Sectional Study.

Providing older person individuals with an appropriate intervention at the time of frailty onset is important to prevent the progression of the condition and the need for long-term care. However, the proper timing of starting nutritional and dietary interventions for frail older person subjects has not been fully elucidated. Therefore, in this cross-sectional study, we aimed to clarify the association between frailty and dietary variety among older persons in Japan. We surveyed sex, age, body height, body weight, body mass index, serum albumin level, dietary variety, and nutritional intake indexes in 747 community-dwelling older person individuals who underwent a comprehensive health examination in October 2014. Frailty was determined using the Kihon Checklist (25 questions). Kihon Checklist is widely used to assess frailty in Japan, and their physical, cognitive and social function was evaluated. After excluding those who did not complete the Kihon Checklist and those who required long-term care, frailty status was analyzed in 665 older person individuals. The numbers and percentages of frail, pre-frail and robust older persons were found to be 77 (11.6%), 182 (27.4%) and 406 (61.0%) respectively. Significant differences among robust, pre-frail, and frail subjects were observed in terms of age, serum albumin level, alcohol consumption, smoking, and history of diabetes. Among the nutrition-related indexes, only the dietary variety showed a significant difference. The results of ordinal logistic regression analysis showed a significant association between frailty and sex, age, smoking status, diabetes, and dietary variety score. Dietary variety was significantly associated with the progression of frailty among older persons in the community.

Effect of Systematic Conversion to Generic Mycophenolate Mofetil (MMF) in Kidney Transplantation: A Single-Center Clinical Experience from Japan.

INTRODUCTION: Recently, more and more generic drugs have been used for immunosuppressive drugs in the field of organ transplantation. Some reports have indicated that blood concentration of most generic drugs is difficult to maintain stability, and it may cause the difference in graft survival of transplanted organs between original drugs and generic drugs. In this article, we report the cases could not maintain blood concentration of generic drugs of mycophenolate mofetil (MMF). RESULTS: In 4 cases out of 5 cases that we had to change original MMF to generic MMF, there were cases that blood concentration level was not stabilized. There were possibility that the lowered blood concentration level of MMF caused a rejection, in two cases. Mean MMF trough level was decreased from 3.6 ± 1.9 µg/mL to 0.6 ± 0.4 µg/mL. Due to the early detection, it did not become severe or failure of graft function, however, we cannot deny the possibilities that side effects were increased and rejection rose. In these cases, we discontinued to use the generic drugs thereafter due to unstable plasma concentration of MMF. DISCUSSION: Some reports have indicated that failure to maintain plasma concentration of MMF leads to rejection. Therefore, maintenance of effective plasma concentration and prevention of rejection are essential to long-term graft survival in kidney transplant. CONCLUSION: Generic drug formulations may exhibit differences in effects and absorption compared to the brand-name drug. If the generic drug should be used, patients should be closely monitored.

Dual Gas Treatment With Hydrogen and Carbon Monoxide Attenuates Oxidative Stress and Protects From Renal Ischemia-Reperfusion Injury.

BACKGROUND: Hydrogen (H2) and carbon monoxide (CO) gas are both reported to reduce reactive oxygen species and alleviate tissue ischemia-reperfusion (I-R) injury. The present study was conducted to evaluate the effects of a mixture of H2 gas and CO gas (dual gas) in comparison with hydrogen gas (H2: 2%) alone on I-R renal injury (composition of dual gas; N2: 77.8%; O2: 20.9%; H2: 1.30%; CO: 250 parts per million). METHODS: Adult male Sprague-Dawley rats (body weight 250-280 g) were divided into 5 groups: (1) sham operation control, (2) dual gas inhalation (dual treatment) without I-R treatment, (3) I-R renal injury, (4) H2 gas alone inhalation (H2 treatment) with I-R renal injury, and (5) dual treatment with I-R renal injury. I-R renal injury was induced by clamping the left renal artery and vein for 45 minutes followed by reperfusion, and then contralateral nephrectomy was performed 2 weeks later. Renal function was markedly decreased at 24 hours after reperfusion, and thereafter the effects of dual gas were assessed by histologic examination and determination of the superoxide radical, together with functional and molecular analyses. RESULTS: Pathologic examination of the kidney of I-R rats revealed severe renal damage. Importantly, cytoprotective effects of the dual treatment in comparison with H2 treatment and I-R renal injury were observed in terms of superoxide radical scavenging activity and histochemical features. Rats given dual treatment and I-R renal injury showed significant decreases in blood urea nitrogen. Increased expression of several inflammatory cytokines (tumor necrosis factor-α, interleukin-6, intracellular adhesion molecule-1, nuclear factor-κB, hypoxia inducible factor-1α, and heme oxygenase-1) was attenuated by the dual treatment. CONCLUSIONS: Dual gas inhalation decreases oxidative stress and markedly improves I-R-induced renal injury.

High-speed screening and quantitative SAR analysis of human ABC transporter ABCG2 for molecular modeling of anticancer drugs to circumvent multidrug resistance.

The transport mechanism-based molecular design strategy would provide an effective tool for rationalized chemotherapy against tumors. To develop a platform for molecular modeling to circumvent multidrug resistance, we established new methods of high-speed screening for human ABCG2-drug interactions, quantitative structure-activity relationship (QSAR) analysis, and quantum chemical calculation for lead optimization.

ROM7/BEM4 encodes a novel protein that interacts with the Rho1p small GTP-binding protein in Saccharomyces cerevisiae.

The RHO1 gene encodes a homolog of the mammalian RhoA small GTP-binding protein in the yeast Saccharomyces cerevisiae. Rho1p is localized at the growth site and is required for bud formation. The RHO1(G22S, D125N) mutation is a temperature-sensitive and dominant negative mutation of RHO1, and a multicopy suppressor of RHO1(G22S, D125N), ROM7, was isolated. Nucleotide sequencing of ROM7 revealed that it is identical to the BEM4 gene (GenBank accession number L27816), although its physiological function has not yet been reported. Disruption of BEM4 resulted in the cold- and temperature-sensitive growth phenotypes, and cells of the deltabem4 mutant showed abnormal morphology, suggesting that BEM4 is involved in the budding process. The temperature-sensitive growth phenotype was suppressed by overexpression of RHO1, ROM2, which encodes a Rho1p-specific GDP/GTP exchange factor, or PKC1, which encodes a target of Rho1p. Moreover, glucan synthase activity, which is activated by Rho1p, was significantly reduced in the deltabem4 mutant. Two-hybrid and biochemical experiments revealed that Bem4p directly interacts with the nucleotide-free form of Rho1p and, to lesser extents, with the GDP- and GTP-bound forms of Rho1p, although Bem4p showed neither GDP/GTP exchange factor, GDP dissociation inhibitor, nor GTPase-activating protein activity toward Rho1p. These results indicate that Bem4p is a novel protein directly interacting with Rho1p and is involved in the RHO1-mediated signaling pathway.

Relationship between Sensory Perception and Frailty in a Community-Dwelling Elderly Population.

BACKGROUND: Aging anorexia, defined as loss of appetite and/or reduced food intake, has been postulated as a risk factor for frailty. Impairments of taste and smell perception in elderly people can lead to reduced enjoyment of food and contribute to the anorexia of aging. OBJECTIVE: To evaluate the relationship between frailty and taste and smell perception in elderly people living in urban areas. DESIGN: Data from the baseline evaluation of 768 residents aged ≥ 65 years who enrolled in a comprehensive geriatric health examination survey was analyzed. Fourteen out of 29-items of Appetite, Hunger, Sensory Perception questionnaire (AHSP), frailty, age, sex, BMI, chronic conditions and IADL were evaluated. AHSP was analyzed as the total score of 8 taste items (T) and 6 smell items (S). Frailty was diagnosed using a modified Fried's frailty criteria. RESULTS: The area under the receiver operator curves for detection of frailty demonstrated that T (0.715) had moderate accuracy, but S (0.657) had low accuracy. The cutoffs, sensitivity, specificity and Youden Index (YI) values for each perception were T: Cutoff 26.5 (YI: 0.350, sensitivity: 0.639, specificity: 0.711) and S: Cutoff 18.5 (YI: 0.246, sensitivity: 0.690, specificity: 0.556). Results from multiple logistic regression models, after adjusting for age, sex, IADL and chronic conditions showed that participants under the T cutoff were associated with exhaustion and those below the S cutoff were associated with slow walking speed. The adjusted logistic models for age, sex, IADL and chronic conditions showed significant association between T and frailty (OR 2.81, 95% CI 1.29-6.12), but not between S and frailty (OR 1.73, 95% CI 0.83-3.63). CONCLUSIONS: Taste and smell perception, particularly taste perception, were associated with a greater risk of frailty in community-dwelling elderly people. These results suggest that lower taste and smell perception may be an indicator of frailty in old age.