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1.  Predictors of improved functional outcome in elderly inpatients after rehabilitation: a retrospective study 
The number of elderly inpatients has been steadily increasing worldwide. However, the ability to predict the degree of improvement of functional capacity after comprehensive examination of elderly inpatients is still lacking. The purpose of this study was to investigate the predictors of improved functional outcome after rehabilitation of elderly inpatients.
We performed a retrospective cohort study with 1,079 patients (age <70 years: N=331, age ≥70 years: N=748) who had been admitted to Tottori Municipal Hospital. Functional Independence Measure (FIM) scores were measured both at admission and discharge to calculate FIM gain and efficiency. Of these patients, 262 patients had oral examinations on admission. The Mann–Whitney U-test or chi-square test was used for statistical analyses. Conditional logistic regression analysis was used to compute the odds ratio (OR) and 95% confidence interval (CI). Cut-off values of FIM scores to determine if elderly inpatients were able to return home after discharge were determined using a receiver operating characteristic curve.
FIM scores, including FIM gain and efficiency, of elderly patients were significantly lower than those of middle-aged patients. Inability to close the lips and dysfunctional tongue movement, but not the loss of teeth, were correlated with a reduced improvement of FIM scores. Cognitive impairment and aspiration pneumonia, but not cerebrovascular disease, were also correlated with a reduced improvement of FIM scores. Interestingly, FIM scores were significantly lower in patients with both cerebrovascular disease and a loss of posterior occlusion. Factors shown to have a significant impact on the improvement of FIM scores included the stable posterior occlusion (OR: 2.23, 95% CI: 1.2–4.1), closed lips (OR: 5.15, 95% CI: 2.3–11.7), functional tongue movement (OR: 5.74, 95% CI: 3.0–11.0), presence of cognitive impairment (OR: 0.31, 95% CI: 0.17–0.49), and presence of aspiration pneumonia (OR: 0.27, 95% CI: 0.15–0.51).
Age and disorder of oral function may be significant predictors of improved functional capacity after rehabilitation for elderly inpatients.
PMCID: PMC4264602  PMID: 25584025
elderly inpatients; Functional Independence Measure (FIM); oral examination; geriatric disease
2.  Mechanism of interleukin-1α transcriptional regulation of S100A9 in a human epidermal keratinocyte cell line 
Biochimica et biophysica acta  2013;1829(9):954-962.
S100A9 is a calcium-binding protein and subunit of antimicrobial calprotectin complex (S100A8/A9). Produced by neutrophils, monocytes/ macrophages and keratinocytes, S100A9 expression increases in response to inflammation. For example, IL-1α produced by epithelial cells acts autonomously on the same cells to induce expression of S100A8/A9 and cellular differentiation. Whereas it is well known that IL-1α and members of the IL-10 family of cytokines upregulate S100A8 and S100A9 in several cell lineages, the pathway and mechanism of IL-1α-dependent transcriptional control of S100A9 in epithelial cells is not established. Modeled using human epidermal keratinocytes (HaCaT cells), IL-1α stimulated phosphorylation of p38 MAPK and induced S100A9 expression, which was blocked by IL-1 receptor antagonist, RNAi suppression of p38, or a p38 MAPK inhibitor. Transcription of S100A9 in HaCaT cells depended on nucleotides -94 to -53 in the upstream promoter region, based upon use of deletion constructs and luciferase reporter activity. Within the responsive promoter region, IL-1α increased the binding activity of CCAAT/enhancer binding protein β (C/EBPβ). Mutated C/EBPβ binding sequences or C/EBPβ-specific siRNA inhibited the S100A9 transcriptional response. Hence, IL-1α is strongly suggested to increase S100A9 expression in a human epidermal keratinocyte cell line by signaling through the IL-1 receptor and p38 MAPK, increasing C/EBPβ-dependent transcriptional activity.
PMCID: PMC3719387  PMID: 23563247
S100A9; IL-1α; keratinocytes; p38; C/EBPβ
3.  Association of the c.385C>A (p.Pro129Thr) polymorphism of the fatty acid amide hydrolase gene with anorexia nervosa in the Japanese population 
The functional c.385C>A single-nucleotide polymorphism (SNP) in the fatty acid amide hydrolase (FAAH) gene, one of the major degrading enzymes of endocannabinoids, is reportedly associated with anorexia nervosa (AN). We genotyped the c.385C>A SNP (rs324420) in 762 lifetime AN and 605 control participants in Japan. There were significant differences in the genotype and allele frequencies of c.385C>A between the AN and control groups. The minor 385A allele was less frequent in the AN participants than in the controls (allele-wise, odds ratio = 0.799, 95% confidence interval [CI] 0.653–0.976, P = 0.028). When the cases were subdivided into lifetime restricting subtype AN and AN with a history of binge eating or purging, only the restricting AN group exhibited a significant association (allele-wise, odds ratio = 0.717, 95% CI 0.557–0.922, P = 0.0094). Our results suggest that having the minor 385A allele of the FAAH gene may be protective against AN, especially restricting AN. This finding supports the possible role of the endocannabinoid system in susceptibility to AN.
PMCID: PMC4113271  PMID: 25077173
Anandamide; cannabinoid 1 receptor; eating disorder; endocannabinoid
4.  Using the mood disorder questionnaire and bipolar spectrum diagnostic scale to detect bipolar disorder and borderline personality disorder among eating disorder patients 
BMC Psychiatry  2013;13:69.
Screening scales for bipolar disorder including the Mood Disorder Questionnaire (MDQ) and Bipolar Spectrum Diagnostic Scale (BSDS) have been plagued by high false positive rates confounded by presence of borderline personality disorder. This study examined the accuracy of these scales for detecting bipolar disorder among patients referred for eating disorders and explored the possibility of simultaneous assessment of co-morbid borderline personality disorder.
Participants were 78 consecutive female patients who were referred for evaluation of an eating disorder. All participants completed the mood and eating disorder sections of the SCID-I/P and the borderline personality disorder section of the SCID-II, in addition to the MDQ and BSDS. Predictive validity of the MDQ and BSDS was evaluated by Receiver Operating Characteristic analysis of the Area Under the Curve (AUC).
Fifteen (19%) and twelve (15%) patients fulfilled criteria for bipolar II disorder and borderline personality disorder, respectively. The AUCs for bipolar II disorder were 0.78 (MDQ) and 0.78 (BDSD), and the AUCs for borderline personality disorder were 0.75 (MDQ) and 0.79 (BSDS).
Among patients being evaluated for eating disorders, the MDQ and BSDS show promise as screening questionnaires for both bipolar disorder and borderline personality disorder.
PMCID: PMC3599106  PMID: 23443034
Bipolar disorder; Borderline personality disorder; Eating disorder; Comorbidity; Screening scale
5.  Regulation of antimicrobial peptide expression in human gingival keratinocytes by interleukin-1α 
Archives of oral biology  2011;56(8):761-767.
In the oral cavity, mucosal keratinocytes resist bacterial infection, in part, by producing broad-spectrum antimicrobial peptides (AMPs) including defensin, adrenomedullin and calprotectin. Epidermal keratinocyte expression of many AMPs increases in response to interleukin-1α (IL-1α). IL-1α is produced by epidermal keratinocytes and regulates cell differentiation. To better understand innate immunity in the oral cavity, we sought to determine how IL-1α might regulate expression of AMPs by human gingival keratinocytes (HGKs) using DNA microarray and western blot analyses. HGKs from three subjects expressed eleven AMPs, including S100A7, S100A8, S100A9, S100A12, secretory leukocyte protease inhibitor, lipocalin 2 (LCN2), cystatin C and β-defensin 2. Of the expressed AMPs, S100A7, S100A12 and LCN2 were up-regulated by IL-1α (inducible AMPs); the other AMPs were considered to be constitutive. Human gingival keratinocytes, therefore, express constitutive and IL-1α-inducible AMPs to provide a rapid and robust innate response to microbial infection.
PMCID: PMC3412402  PMID: 21316034
antimicrobial peptide; gingival keratinocyte; interleukin-1α; microarray analysis; analysis
6.  Cross-cultural study of conviction subtype Taijin Kyofu: proposal and reliability of Nagoya-Osaka diagnostic criteria for social anxiety disorder 
Conviction subtype Taijin-Kyofu (c-TK) is a subgroup of mental disorder characterized by conviction and strong fear of offending others in social situations. Although the concept of c-TK overlaps with that of social anxiety disorder (SAD), patients with c-TK often may not be diagnosed as such within the current DSM-IV criteria. We propose the Nagoya-Osaka Criteria to amend this situation. This study examined the cross-cultural inter-rater reliability of the proposed criteria. 18 case vignettes of patients with a variety of complaints focused around social anxieties were collected from 6 different countries, and diagnosed by 13 independent raters from various nationalities according to the original DSM-IV and the expanded criteria. The average agreement ratio for the most frequent diagnostic category in each case was 61.5% with DSM-IV and 87.6% with the modified DSM-IV with Nagoya-Osaka Criteria (p<0.001). These findings indicate that the Nagoya-Osaka Criteria for SAD can improve inter-rater reliability of SAD.
PMCID: PMC2953949  PMID: 18414125
Social Phobia; Taijin Kyofu; Reliability; Diagnostic and Statistical Manual of Mental Disorders; Cross-Cultural Comparison
7.  Periodontal Tissue Regeneration Using Fibroblast Growth Factor -2: Randomized Controlled Phase II Clinical Trial 
PLoS ONE  2008;3(7):e2611.
The options for medical use of signaling molecules as stimulators of tissue regeneration are currently limited. Preclinical evidence suggests that fibroblast growth factor (FGF)-2 can promote periodontal regeneration. This study aimed to clarify the activity of FGF-2 in stimulating regeneration of periodontal tissue lost by periodontitis and to evaluate the safety of such stimulation.
Methodology/Principal Findings
We used recombinant human FGF-2 with 3% hydroxypropylcellulose (HPC) as vehicle and conducted a randomized double-blinded controlled trial involving 13 facilities. Subjects comprised 74 patients displaying a 2- or 3-walled vertical bone defect as measured ≥3 mm apical to the bone crest. Patients were randomly assigned to 4 groups: Group P, given HPC with no FGF-2; Group L, given HPC containing 0.03% FGF-2; Group M, given HPC containing 0.1% FGF-2; and Group H, given HPC containing 0.3% FGF-2. Each patient underwent flap operation during which we administered 200 µL of the appropriate investigational drug to the bone defect. Before and for 36 weeks following administration, patients underwent periodontal tissue inspections and standardized radiography of the region under investigation. As a result, a significant difference (p = 0.021) in rate of increase in alveolar bone height was identified between Group P (23.92%) and Group H (58.62%) at 36 weeks. The linear increase in alveolar bone height at 36 weeks in Group P and H was 0.95 mm and 1.85 mm, respectively (p = 0.132). No serious adverse events attributable to the investigational drug were identified.
Although no statistically significant differences were noted for gains in clinical attachment level and alveolar bone gain for FGF-2 groups versus Group P, the significant difference in rate of increase in alveolar bone height (p = 0.021) between Groups P and H at 36 weeks suggests that some efficacy could be expected from FGF-2 in stimulating regeneration of periodontal tissue in patients with periodontitis.
Trial Registration NCT00514657
PMCID: PMC2432040  PMID: 18596969
8.  Psychological and weight-related characteristics of patients with anorexia nervosa-restricting type who later develop bulimia nervosa 
Patients with anorexia nervosa-restricting type (AN-R) sometimes develop accompanying bulimic symptoms or the full syndrome of bulimia nervosa (BN). If clinicians could predict who might change into the bulimic sub-type or BN, preventative steps could be taken. Therefore, we investigated anthropometric and psychological factors possibly associated with such changes.
All participants were from a study by the Japanese Genetic Research Group for Eating Disorders. Of 80 patients initially diagnosed with AN-R, 22 changed to the AN-Binge Eating/Purging Type (AN-BP) and 14 to BN for some period of time. The remaining 44 patients remained AN-R only from the onset to the investigation period. Variables compared by ANOVA included anthropometric measures, personality traits such as Multiple Perfectionism Scale scores and Temperament and Character Inventory scores, and Beck Depression Inventory-II scores.
In comparison with AN-R only patients, those who developed BN had significantly higher current BMI (p < 0.05) and maximum BMI in the past (p < 0.05). They also scored significantly higher for the psychological characteristic of parental criticism (p < 0.05) and lower in self-directedness (p < 0.05), which confirms previous reports, but these differences disappeared when the depression score was used as a co-variant. No significant differences were obtained for personality traits or depression among the AN-R only patients irrespective of their duration of illness.
The present findings suggest a tendency toward obesity among patients who cross over from AN-R to BN. Low self-directedness and high parental criticism may be associated with the development of BN by patients with AN-R, although the differences may also be associated with depression.
PMCID: PMC2275291  PMID: 18267038
9.  Inhibition of Osteoblastic Cell Differentiation by Lipopolysaccharide Extract from Porphyromonas gingivalis 
Infection and Immunity  1999;67(6):2841-2846.
Lipopolysaccharide from Porphyromonas gingivalis (P-LPS), an important pathogenic bacterium, is closely associated with inflammatory destruction of periodontal tissues. P-LPS induces the release of cytokines and local factors from inflammatory cells, stimulates osteoclastic-cell differentiation, and causes alveolar bone resorption. However, the effect of P-LPS on osteoblastic-cell differentiation remains unclear. In this study, we investigated the effect of P-LPS extract prepared by the hot-phenol–water method, on the differentiation of primary fetal rat calvaria (RC) cells, which contain a subpopulation of osteoprogenitor cells, into osteoblastic cells. P-LPS extract significantly inhibited bone nodule (BN) formation and the activity of alkaline phosphatase (ALPase), an osteoblastic marker, in a dose-dependent manner (0 to 100 ng of P-LPS extract per ml). P-LPS extract (100 ng/ml) significantly decreased BN formation to 27% of the control value and inhibited ALPase activity to approximately 60% of the control level on days 10 to 21 but did not affect RC cell proliferation and viability. P-LPS extract time-dependently suppressed the expression of ALPase mRNA, with an inhibitory pattern similar to that of enzyme activity. The expression of mRNAs for osteocalcin and osteopontin, matrix proteins related to bone metabolism, was markedly suppressed by P-LPS extract. Furthermore, P-LPS extract increased the expression of mRNAs for CD14, LPS receptor, and interleukin-1β in RC cells. These results indicate that P-LPS inhibits osteoblastic-cell differentiation and suggest that LPS-induced bone resorption in periodontal disease may be mediated by effects on osteoblastic as well as osteoclastic cells.
PMCID: PMC96590  PMID: 10338489

Results 1-9 (9)