Baseline and changes in serum uric acid independently predict 11-year incidence of metabolic syndrome among community-dwelling women.

INTRODUCTION: Metabolic syndrome (MetS) is associated with an increased risk of major cardiovascular events. In women, increased serum uric acid (SUA) levels are associated with MetS and its components. However, whether baseline and changes in SUA predict incidence of MetS and its components remains unclear. METHODS: The subjects comprised 407 women aged 71 ± 8 years from a rural village. We have identified participants who underwent a similar examination 11 years ago, and examined the relationship between baseline and changes in SUA, and MetS based on the modified criteria of the National Cholesterol Education Program's Adult Treatment Panel (NCEP-ATP) III report. RESULTS: Of these subjects, 83 (20.4%) women at baseline and 190 (46.7%) women at follow-up had MetS. Multiple linear regression analysis was performed to evaluate the contribution of each confounding factor for MetS; both baseline and changes in SUA as well as history of cardiovascular disease, low-density lipoprotein cholesterol, and estimated glomerular filtration ratio (eGFR) were independently and significantly associated with the number of MetS components during an 11-year follow-up. The adjusted odds ratios (ORs) (95% confidence interval) for incident MetS across tertiles of baseline SUA and changes in SUA were 1.00, 1.47 (0.82-2.65), and 3.11 (1.66-5.83), and 1.00, 1.88 (1.03-3.40), and 2.49 (1.38-4.47), respectively. In addition, the combined effect between increased baseline and changes in SUA was also a significant and independent determinant for the accumulation of MetS components (F = 20.29, p < 0.001). The ORs for incident MetS were significant only in subjects with age ≥ 55 years, decline in eGFR, and no baseline MetS. CONCLUSIONS: These results suggested that combined assessment of baseline and changes in SUA levels provides increased information for incident MetS, independent of other confounding factors in community-dwelling women.

Interaction between gender and uric acid on hemoglobin A1c in community-dwelling persons.

INTRODUCTION: Higher glycated hemoglobin (Hb) (HbA1c) is significantly associated with an increased risk of cardiovascular disease (CVD). Serum uric acid (SUA) levels are associated with glucose intolerance and type 2 diabetes. Whether gender-specific differences regarding the relationship between SUA levels and HbA1c exist is unknown. AIM: We recruited 1636 (men, 696 aged of 70 ± 10 years; women, 940 aged of 70 ± 9 years) participants and enrolled in the study during their annual health examination from a single community. We investigated the association between SUA levels and HbA1c within each gender. RESULTS: Multiple linear regression analysis showed that in men, SUA (ß = -0.091, p = 0.014) with prevalence of antidiabetic medication (ß = 0.428, p < 0.001) and eGFR (ß = 0.112, p = 0.016) were significantly and negatively associated with HbA1c, and in women, SUA (ß = 0.101, p = 0.002) with prevalence of antidiabetic medication (ß = 0.458, p < 0.001) were significantly and positively associated with HbA1c. Moreover, the interaction between gender and SUA (ß = 0.445, p < 0.001) as well as gender (ß = -0.465, p < 0.001), prevalence of antidiabetic medication (ß = 0.444, p < 0.001), eGFRCKDEPI (ß = 0.074, p = 0.014), and SUA (ß = -0.356, p < 0.001) was a significant and independent determinant of HbA1c. A significant interactive effect of gender and SUA on determinants of HbA1c was noted in patients not on antidiabetic medications, regardless of age, HbA1c, and renal function. CONCLUSIONS: The interaction between gender and SUA was associated with HbA1c independent of other metabolic factors in community-dwelling persons.

Septic arthritis and atopic dermatitis: 2 cases and a review of the recent literature

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A case of wheat-dependent exercise-induced anaphylaxis after specific oral immunotherapy

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Reduction in superoxide dismutase expression in the epithelial mucosa of eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: Eosinophils generate large amounts of oxidant species. The eosinophil-dominant type of chronic rhinosinusitis (CRS) with nasal polyps is related to more extensive disease and a decreased likelihood of surgical success. Superoxide dismutase (SOD) is the first-line and only antioxidant enzyme that converts superoxide to hydrogen peroxide. METHODS: The patients with CRS with nasal polyps were divided into eosinophilic and noneosinophilic groups. The expression of three isoforms of SOD, intracellular copper-zinc SOD (CuZnSOD), mitochondrial manganese SOD (MnSOD) and extracellular SOD (ECSOD), were examined by enzyme activity assay, immunohistochemistry and quantitative real-time RT-PCR sampled by laser capture microdissection. RESULTS: SOD activity in the eosinophilic and noneosinophilic groups was significantly reduced compared to that of the control groups. Immunostaining of both CuZnSOD and MnSOD in the eosinophilic group was significantly decreased compared with that in the noneosinophilic and control groups. CuZnSOD mRNA of the eosinophilic group was significantly decreased compared with that of the control group, whereas MnSOD mRNA in the eosinophilic group was significantly decreased compared with that in the noneosinophilic and control groups. Neither immunoreactivity nor mRNA of ECSOD was different among the three groups. The degree of epithelial damage and disease severity were inversely correlated with CuZnSOD and MnSOD immunoreactivity. CONCLUSIONS: The reduction in SOD activity and the downregulation of the SOD message are suggested to be related to eosinophil recruitment and epithelial damage of CRS with nasal polyps.

Role of interleukin-17A in the eosinophil accumulation and mucosal remodeling in chronic rhinosinusitis with nasal polyps associated with asthma.

BACKGROUND: Interleukin (IL)-17A is a highly inflammatory cytokine with a robust effect on stromal cells in many tissues. Although IL-17A is known to be associated with inflammatory lung disorders by triggering an accumulation of neutrophils, the effect of IL-17A on the upper airway is still uncertain. The expression of IL-17A and its role were investigated in the nasal polyps of chronic rhinosinusitis associated with asthma. METHODS: IL-17A was detected by immunohistochemistry and quantitative real-time RT-PCR. The cellular source of IL-17A was examined by double staining with EG2, CD4 and neutrophil elastase. The tissue remodeling of the nasal polyps was evaluated by assessing the epithelial damage and basement membrane thickness. RESULTS: Both the immunoreactivity and mRNA of IL-17A were significantly detected in the nasal polyps in comparison with control normal sinus mucosa. The localization of IL-17A expression predominantly coincided with eosinophils and CD4-positive lymphocytes. Furthermore, the number of IL-17A-positive cells correlated with tissue eosinophils, but not with neutrophils. The degree of epithelial damage and basement membrane thickness was dependent on the number of infiltrated IL-17A-positive cells. CONCLUSION: The present study suggests, for the first time, that IL-17A plays an important role in the eosinophil accumulation in the nasal polyps and the remodeling of the nasal polyps of chronic rhinosinusitis associated with asthma.

Postnatal development of the organ of Corti in dominant-negative Gjb2 transgenic mice.

Hereditary hearing loss is one of the most prevalent inherited human birth defects, affecting one in 2000. A strikingly high proportion (50%) of congenital bilateral nonsyndromic sensorineural deafness cases have been linked to mutations in the GJB2 coding for the connexin26. It has been hypothesized that gap junctions in the cochlea, especially connexin26, provide an intercellular passage by which K(+) are transported to maintain high levels of the endocochlear potential essential for sensory hair cell excitation. We previously reported the generation of a mouse model carrying human connexin26 with R75W mutation (R75W+ mice). The present study attempted to evaluate postnatal development of the organ of Corti in the R75W+ mice. R75W+ mice have never shown auditory brainstem response waveforms throughout postnatal development, indicating the disturbance of auditory organ development. Histological observations at postnatal days (P) 5-14 were characterized by i) absence of tunnel of Corti, Nuel's space, or spaces surrounding the outer hair cells, ii) significantly small numbers of microtubules in inner pillar cells, iii) shortening of height of the organ of Corti, and iv) increase of the cross-sectional area of the cells of the organ of Corti. Thus, morphological observations confirmed that a dominant-negative Gjb2 mutation showed incomplete development of the cochlear supporting cells. On the other hand, the development of the sensory hair cells, at least from P5 to P12, was not affected. The present study suggests that Gjb2 is indispensable in the postnatal development of the organ of Corti and normal hearing.

Pharmacokinetic investigation of oral itraconazole in stratum corneum level of tinea pedis.

In the present study, the authors administered 100 mg itraconazole (ITCZ) twice daily for a period of 1 week to six patients with hyperkeratotic type tinea pedis, and examined its efficacy, safety profile, and usefulness. ITCZ concentration in stratum corneum was also measured to examine the mobility of the drug into the affected site of planta pedis. ITCZ concentration in the stratum corneum of the affected part was first detected at 1 week after the completion of administration, gradually increased over time, and peaked at 3 weeks, with the sum of ITCZ and hydroxyitraconazole (OH-ITCZ) amounting to 163.7 ng g(-1) on a average. It then gradually decreased to a total sum of 10.3 ng g(-1) on average at 8 weeks following the completion of administration. When compared with the geometric mean minimum inhibitory concentration (MIC) of ITCZ against fresh clinical isolates of dermatophytes (Trichophyton rubrum) (0.06 microg ml(-1)), the stratum corneum ITCZ concentration in this study was 2.1-fold of the geometric mean MIC at 2 weeks following the completion of administration, and 2.4-fold at 4 weeks. Although ITCZ does not produce therapeutic effectiveness (fungistasis) during the period of administration, it starts appearing at 2 weeks after the completion of administration, and after it peaks out at 3-4 weeks, clinical symptoms started improving. These results suggest that satisfying effects can be achieved in a short-term oral ITCZ at a dose of 100 mg twice daily for a period of 1 week in cases of hyperkeratotic type tinea pedis.

Morphological and functional differentiation of human thyroid cells in collagen gel culture.

OBJECTIVE: Cultured human thyroid cells in collagen gel culture were examined on cell morphology and the production of thyroglobulin (Tg), triiodothyronine (T3) and thyroxine (T4) which are components of functional differentiation. METHODS: Thyroid cells obtained from normal human thyroid tissues (four cases), follicular adenoma tissues (three cases), papillary carcinoma tissues (three cases), and follicular carcinoma tissue (one case), were cultured in collagen gel. Then these cultured cells were observed on cellular morphology and production of Tg, T3 and T4. Moreover, changes in morphological characteristics and production of Tg, T3 and T4 induced by addition of thyroid stimulating hormone (TSH) and epidermal growth factor (EGF) to medium in collagen gel culture were determined. RESULTS: Normal and tumor cells in collagen gel culture formed colonies and follicles with Tg production, similar to in vivo-like three-dimensional cellular structures and functions. Normal thyroid cells stimulated TSH induced more Tg and produced morphological changes, i.e. enlarged follicular lumens and increased the height of follicular cells, but did not promote cell proliferation. Reversely, normal thyroid cells stimulated with EGF promoted cell proliferation, but did not change morphological findings and did not increase production of Tg, T3 and T4. CONCLUSIONS: These findings suggest that collagen gel culture is useful for observing the effects of stimulation by cell growth factor on the morphological and functional differentiation of human thyroid cells.

Unidimensional scale for dementia.

A cognitive test comprising 27 subscales was administered to 262 demented patients and 92 normal subjects. Principal factor analysis followed by varimax and Harris-Kaiser rotation and Guttman's scalogram analysis was performed. The analysis yielded three factors, i.e. "recent memory", "immediate memory or attention" and "remote memory". The relationships between the three-dimensional distribution of the scores and the DSM-IIIR grade of dementia indicated the existence of a continuum of dementia severity. Scalogram analysis showed unidimensionality in the difficulty level of the subscales as well as in the severity of the cases. Thus, the simple summary score can be used as a good measure of the severity of dementia.

The Japan Home-health Apparatus Industrial Association: investigation of home-use electronic sphygmomanometers.

The Japanese Home-health Apparatus Industrial Association is an official independent organization comprising ten departments. That concerned with home electronic sphygmomanometers, which has seven participants from different Japanese manufacturers, has already undertaken and is currently involved in various activities related to voluntary standards for performance validation and quality assurance. Because Japanese companies form a large proportion of manufacturers, these activities are important in terms of autonomic regulation. Although many improvements have been made to home electronic sphygmomanometers, some problems still remain unresolved, especially in terms of measurement reliability and easy operation by lay people. Another aspect of the department's work relates to making proposals on major validation standards, such as those of the Association for the Advancement of Medical Instrumentation, the British Hypertension Society and Comité Européen de Normalisation (CEN). Clinical validation should be discussed in order to define a more accurate standard method of measurement using auscultation and more appropriate criteria that are unaffected by primary blood pressure variation.

Cathepsin L activity and its inhibitor in human otitis media.

OBJECTIVE: We examined cathepsin L activity, expression of cystatin A, and copper- and zinc-containing superoxide dismutase in human chronic otitis media. The relationships of our findings to clinical findings (e.g., grade of bone destruction) were also studied. DESIGN: Retrospective basic and clinical study. SETTING: Department of Otolaryngology and First Department of Biochemistry, Kinki University School of Medicine, Osaka, Japan. METHOD: The human middle ear tissues evaluated in this study were surgically obtained from seven patients with cholesteatoma epithelium, three patients with granulation tissues in cholesteatoma, three patients with granulation tissues in noncholesteatoma, and three patients with intact mucous membrane of the middle ear. MAIN OUTCOME MEASURES: Cathepsin L activities in cholesteatoma epithelium, granulation tissues in cholesteatoma, or granulation tissues in noncholesteatoma were measured using Barrett's method. Cystatin A expressions were observed by Western blot analysis. Copper- and zinc-containing superoxide dismutase in cholesteatoma was examined immunohistochemically. RESULTS: Mean cathepsin L activity was higher in diseased tissues than in intact mucous membranes of the middle ear. Granulation tissues with high cathepsin L activity resulted in extensive bone destruction in both cholesteatomas and noncholesteatomas of the middle ear. All cases with intact mucous membrane of the middle ear exhibited no expression of cystatin A. Seven of 10 cases with diseased tissues expressed cystatin A in cholesteatoma epithelium, granulation tissues in cholesteatoma, or granulation tissues in noncholesteatoma. No relationships were found between cystatin A expression and grade of cathepsin L activity. Copper- and zinc-containing superoxide dismutase was more strongly positive in cholesteatoma epithelium regions than in granulation tissues. CONCLUSION: These results suggest that copper- and zinc-containing superoxide dismutase in cholesteatoma epithelium prevents complications by suppressing cathepsin L activity.

Distinct aggregation of beta- and gamma-chains of the high-affinity IgE receptor on cross-linking.

The high-affinity IgE receptor (FcepsilonRI) on mast cells and basophils consists of a ligand-binding alpha-chain and two kinds of signaling chains, a beta-chain and disulfide-linked homodimeric gamma-chains. Crosslinking by multivalent antigen results in the aggregation of the bound IgE/alpha-chain complexes at the cell surface, triggering cell activation, and subsequent internalization through coated pits. However, the precise topographical alterations of the signaling beta- and gamma-chains during stimulation remain unclarified despite their importance in ligand binding/signaling coupling. Here we describe the dynamics of FcepsilonRI subunit distribution in rat basophilic leukemia cells during stimulation as revealed by immunofluorescence and immunogold electron microscopy. Immunolocalization of beta- and gamma-chains was homogeneously distributed on the cell surfaces before stimulation, while crosslinking with multivalent antigen, which elicited optimal degranulation, caused a distinct aggregation of these signaling chains on the cell membrane. Moreover, only gamma- but not beta-chains were aggregated during the stimulation that evoked suboptimal secretion. These findings suggest that high-affinity IgE receptor beta- and gamma-chains do not co-aggregate but for the most part form homogenous aggregates of beta-chains or gamma-chains after crosslinking.

IgA pemphigus: a case report and its characteristic clinical features compared with subcorneal pustular dermatosis.

We report a case of IgA pemphigus. A 35-year-old woman had vesiculopustular eruptions on her scalp, trunk, and extremities. Histologic examination showed a subcorneal pustule containing numerous neutrophils without acantholysis. Direct immunofluorescence revealed IgA deposits in the intercellular space throughout the epidermis, more intense in superficial layers and less intense in lower layers. The titer of circulating IgA antibodies was 1:160 in normal human skin as a substrate. Skin lesions responded to dapsone. The IgA autoantibody from this patient did not react with desmogleins or desmocollins when immunoblotting, enzyme-linked immunosorbent assay, or complement DNA transfection was used. We consider the characteristic clinical features that favor the diagnosis of IgA pemphigus rather than classic subcorneal pustular dermatosis as follows: (1) the lesions involve the scalp and/or face, and (2) the distribution of the lesions is more widespread.

Nasal mupirocin treatment of pharynx-colonized methicillin resistant Staphylococcus aureus: preliminary study with 10 carrier infants.

BACKGROUND: Nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection in infants has become a serious concern and a new means of preventing the transmission of MRSA in the community needs to be considered. METHODS: We performed nasal mupirocin treatment on 10 infants who were MRSA-positive either in the nose or the pharynx and evaluated the effect of mupirocin on the eradication of MRSA. RESULTS: Eradication of MRSA from the nose was successful in two cases and eradication from the pharynx in six (66.6%) of nine cases. The number of treatments required to achieve eradication varied; within three courses for nose carriers and from one to seven courses for pharynx carriers. Eradication was unsuccessful even after five to seven treatments in three pharynx-limited carriers. CONCLUSIONS: These data suggest that the effect of nasal mupirocin treatment on pharynx-colonized MRSA is limited and that repetitive treatment is necessary in some cases. However, in view of the possibility of preferential pharyngeal colonization of Staphylococcus aureus in infancy, nasal mupirocin treatment deserves further evaluation for eradication not only of nose- but also of pharynx-colonized MRSA.