Surface electromyographic evaluation of the neuromuscular activation of the inspiratory muscles during progressively increased inspiratory flow under inspiratory-resistive loading.

This study aimed to evaluate neuromuscular activation in the scalene and sternocleidomastoid muscles using surface electromyography (EMG) during progressively increased inspiratory flow, produced by increasing the respiratory rate under inspiratory-resistive loading using a mask ventilator. Moreover, we attempted to identify the EMG inflection point (EMGIP) on the graph, at which the root mean square (RMS) of the EMG signal values of the inspiratory muscles against the inspiratory flow velocity acceleration abruptly increases, similarly to the EMG anaerobic threshold (EMGAT) reported during incremental-resistive loading in other skeletal muscles. We measured neuromuscular activation of healthy male subjects and found that the inspiratory flow velocity increased by approximately 1.6-fold. We successfully observed an increase in RMS that corresponded to inspiratory flow acceleration with ρ ≥ 0.7 (Spearman's rank correlation) in 17 of 27 subjects who completed the experimental protocol. To identify EMGIP, we analyzed the fitting to either a straight or non-straight line related to the increasing inspiratory flow and RMS using piecewise linear spline functions. As a result, EMGIP was identified in the scalene and sternocleidomastoid muscles of 17 subjects. We believe that the identification of EMGIP in this study infers the existence of EMGAT in inspiratory muscles. Application of surface EMG, followed by identification of EMGIP, for evaluating the neuromuscular activation of respiratory muscles may be allowed to estimate the signs of the respiratory failure, including labored respiration, objectively and non-invasively accompanied using accessory muscles in clinical respiratory care.

Trends in prevalence of Alzheimer's disease and vascular dementia in a Japanese community: the Hisayama Study.

OBJECTIVE: To examine secular trends in the prevalence of Alzheimer's disease (AD) and vascular dementia (VD) in a general Japanese population. METHOD: Four cross-sectional examinations were conducted among residents of a Japanese community aged >or=65 in 1985, 1992, 1998 and 2005. RESULTS: The age- and sex-adjusted prevalence of all-cause dementia significantly increased with time (6.0% in 1985, 4.4% in 1992, 5.3% in 1998 and 8.3% in 2005; P for trend = 0.002). A similar trend was observed for AD (1.1%, 1.3%, 2.3% and 3.8% respectively; P for trend < 0.001), while the age- and sex-adjusted prevalence of VD and other/unclassified dementia showed J-shaped patterns (for VD: 2.3%, 1.5%, 1.5% and 2.5%, respectively, P for trend = 0.82; for other/unclassified dementia: 2.6%, 1.7%, 1.5% and 2.0%, P for trend = 0.26). The prevalence of AD was likely to increase with time from 1985 to 2005 among subjects aged 75 or older. The ratio of the prevalence of VD to that of AD decreased with time (2.1 in 1985, 1.2 in 1992, 0.7 in 1998 and 0.7 in 2005). CONCLUSION: Our findings suggest that the prevalence of all-cause dementia and AD significantly increased over the past two decades in the general Japanese population.

Incidence and survival of dementia in a general population of Japanese elderly: the Hisayama study.

OBJECTIVE: To estimate the incidence and survival rates of total and cause specific dementia in a general Japanese population. METHODS: A total of 828 subjects without dementia, aged 65 years or over, were followed-up prospectively for 17 years. Dementia was subdivided into cause specific subtypes: namely, Alzheimer's disease (AD), vascular dementia (VD), dementia with Lewy bodies (DLB), combined dementia and other types of dementia. During the follow-up, 275 subjects developed dementia; of these, 251 (91.2%) were evaluated morphologically, with 164 subjected to brain autopsy examination and the remaining 87 to neuroimaging. RESULTS: The incidences of total dementia, AD, VD, DLB, combined dementia and other types of dementia were 32.3 (n = 275), 14.6 (124), 9.5 (81), 1.4 (12), 3.8 (33), and 3.1 (16) per 1000 person years, respectively. The incidences of AD, combined dementia and other types of dementia rose with increasing age, particularly after the age of 85 years, but this tendency was not observed for VD or DLB. The survival curve of dementia cases aged 65-89 years was significantly lower than that of age and sex matched controls (10 year survival rate, 13.6% vs 29.3%; hazard ratio 1.67; 95% confidence interval 1.31 to 2.13). The 10 year survival rates were not significantly different among dementia subtypes. CONCLUSIONS: Our findings suggest that the Japanese elderly population has a high risk for the development of dementia, specifically AD and VD, and once dementia is established, the risk of death is considerable.

Serum levels of resistin and adiponectin in women with periodontitis: the Hisayama study.

Resistin and adiponectin, recently discovered adipokines, are secreted from adipose tissue, with postulated opposing functions in insulin resistance and inflammation. More recently, an abundance of resistin was detected in macrophages, which suggests its important role in inflammation. The aim of this study was to clarify circulating serum adipokine levels in women with periodontitis. Thirty-four women with moderate to severe periodontitis and 42 control individuals with healthy gingiva (50- to 59-year-old women) were selected. The serum level of adipokines was analyzed between groups, along with the obesity index, smoking status, and age. Having periodontitis was significantly associated with an increased level of resistin, both in bivariate (OR, 3.0; 95% CI, 1.2-7.6) and multivariate (adjusted OR, 3.1; 95% CI, 1.1-8.6) analyses. The association of periodontitis with a decreased level of adiponectin did not reach statistical significance. It was concluded that an increased serum resistin level in middle-aged Japanese women with periodontitis may affect systemic health.

Relationship of metabolic syndrome to periodontal disease in Japanese women: the Hisayama Study.

Recent studies have suggested that several systemic conditions--such as obesity, hypertension, hyperlipidemia, and diabetes--are related to periodontitis. The objective of this study was to examine the relationship between periodontitis and 5 components of metabolic syndrome--abdominal obesity, triglyceride level, high-density lipoprotein cholesterol level, blood pressure, and fasting blood sugar level--in 584 Japanese women. In multivariate analyses, persons exhibiting more components of metabolic syndrome had significantly higher odds ratios for a greater pocket depth and clinical attachment loss than did those with no components; the odds ratios for a greater pocket depth and clinical attachment loss of the persons exhibiting 4 or 5 components were 6.6 (95% confidence interval = 2.6-16.4) and 4.2 (95% confidence interval = 1.2-14.8), respectively. These results indicate that metabolic syndrome increases risk of periodontitis, and suggest that people exhibiting several components of metabolic syndrome should be encouraged to undergo a periodontal examination.

Decreasing incidence of lacunar vs other types of cerebral infarction in a Japanese population.

BACKGROUND: There is scant information on secular trends in the incidence and survival of ischemic stroke subtypes. METHODS: The authors established three cohorts of Hisayama residents age > or =40 years in 1961 (1,618 subjects), 1974 (2,038 subjects), and 1988 (2,637 subjects). They followed up with each cohort for 12 years, comparing the incidence and survival rate of ischemic stroke subtypes. Morphologic examinations by autopsy or brain imaging was performed on most of the ischemic stroke cases in all cohorts. RESULTS: The age-standardized incidence of lacunar infarction significantly declined by 59% for men and by 28% for women from the first to the second cohort. It continued to decline by 41% for men, but the decline decelerated for women between the second and third cohort. The age-standardized incidence of atherothrombotic infarction tended to decline from the first to the second cohort, whereas it was sustained between the second and third cohort for both sexes. The age-standardized incidence of cardioembolic infarction was unchanged throughout the cohorts. In these cohorts, mean blood pressure levels among hypertensive subjects and the prevalence of current smoker decreased with time, though the prevalence of hypertension remained stable. The 5-year survival rate after lacunar infarction significantly improved among the cohorts, but those of atherothrombotic and cardioembolic infarction did not. CONCLUSIONS: These data suggest that, in the Japanese population, the incidence of lacunar infarction steadily declined for the last 40 years. The improvement of hypertension control and decreasing prevalence of smoking might be responsible for this trend.

First Report of Pythium aphanidermatum on Basella rubra in Japan.

Basella rubra L. (Indian spinach, Japanese name Tsurumurasaki) is cultivated worldwide as an ornamental and its aerial parts are consumed as a vegetable and health food. A severe rot of leaves, stems, and roots was found on B. rubra cv. Midori grown in a commercial field at Naruto-City (34°11'N, 134°36(E) in Tokushima Prefecture, Japan from May to September 2004. More than 50% of approximately 2,100 plants in the field were destroyed by the disease. Soft, black lesions appeared initially at the base of the stems in 2- to 5-month-old plants and enlarged gradually upward and downward within 2 days after plant injury caused by heavy rainfall. A fluffy, white mass of mycelium appeared on the surface of lesions under moist conditions. A Pythium species was routinely isolated from rotted stems and roots and identified as Pythium aphanidermatum (Edson) Fitzpatrick on the basis of its morphology on a grass leaf water culture (2). Characteristics of isolate OPU743 (NBRC No. 101556, MAFF No. 239847) included hyphae as much as 10 µm wide, terminal oogonia 17.8 to 28.8 µm in diameter, and monoclinous or diclinous antheridia 8.8 to 10.9 µm wide, either terminal or intercalary, with one or rarely two per oogonium. Oospores were aplerotic, 13.5 to 22.6 µm in diameter. Sporangia were terminal or occasionally intercalary, and either inflated filamentous hyphae or complexes of swollen hyphal branches were present in cultures. Cardinal temperatures for growth on potato carrot agar were 10°C minimum, 37°C optimum, and 40°C maximum with a daily radial growth rate of 32.9 mm at 25°C. Pathogenicity tests were conducted on potted 3-month-old B. rubra (cv. Midori). A wound (1 mm deep and 5 mm long made by a razor) on the surface of the stem of the plant was inoculated with an 8-mm-diameter agar disk of isolate OPU743 (grown at 25°C for 48 h on potato dextrose agar) attached to a stem of the plant using a paraffin film. The inoculated plants were placed in transparent plastic bags and kept in a growth chamber at 24 to 26°C with continuous light (82 to 126 µmol·m-2·s-1). The experiment was done four times with three plants in each experiment. The same number of plants was used for the noninoculated control. Dark brown rot of stems and leaves developed on 66.7% of inoculated plants within 2 days after inoculation. P. aphanidermatum reisolated from diseased tissues was morphologically identical to the original isolate OPU743. Noninoculated control plants showed no symptoms. P. aphanidermatum has been described on B. rubra in Brazil (1), but has not been reported from other regions of the world. To our knowledge, this is the first report of P. aphanidermatum on B. rubra in Japan. References: (1) C. F. Robbs. A Lavoura 74:43, 1972. (2) A. J. Van Der Plaats-Niterink. Stud. Mycol. 21:1, 1981.

Cricoarytenoid arthritis with rheumatoid arthritis and systemic lupus erythematosus.

A 56-year-old woman with rheumatoid arthritis (RA) suddenly developed severe respiratory distress and laryngeal stridor, which required endotracheal intubation. She had had RA for 12 years, which had been controlled well with prednisolone (3 mg/day) at the orthopedic clinic. Laryngoscopy revealed cricoarytenoid arthritis. She was finally diagnosed as having overlap syndrome with RA and systemic lupus erythematosus. She was given high dose corticosteroids that improved her clinical symptoms and laryngoscopic findings. She represents the first patient with overlap syndrome who developed an acute airway obstruction due to cricoarytenoid arthritis.

CD56-Positive cutaneous lymphoma with multicentric Castleman's disease-like systemic manifestations.

We report a 55-year-old Japanese male with CD56+ cutaneous lymphoma. The patient had multiple cervical lymphadenopathy, a red nodule on his neck, and parotid gland nodularity. Histologic features of the biopsied cervical lymph node showed follicular hyperplasia with numerous plasma cells. A biopsied skin specimen of the nodule on his neck demonstrated dense infiltration of atypical large lymphocytes into the dermis. Immunohistochemical study of this specimen revealed CD3+, CD4+, and CD56+ expression in the majority of neoplastic cells. Polymerase chain reaction assays for the detection of Epstein-Barr virus sequences were positive for lymph node and skin DNA. Laboratory examinations showed polyclonal gammopathy, pancytopenia, and high serum interleukin-6 levels. These clinical and histological findings resembled those of multicentric Castleman's disease.

Diffuse large B-cell lymphoma associated with skin, muscle and cranial nerve involvement.

The present case, a 75-year-old man with extranodal B-cell lymphoma showed facial hemiplegia, paresthesia and cutaneous manifestations. He was initially diagnosed as having a facial paralysis of unknown etiology. One month after the original diagnosis, erythematous indurated plaques developed on his left cheek and nose. A skin biopsy from the plaque on his cheek showed dense infiltrates of large lymphocytes with irregularly shaped nuclei and prominent nucleoli in the dermis and subcutaneous tissue. The lymphocytes were positive for L26 and CD79a. A diagnosis of diffuse large B-cell lymphoma was made. A muscle biopsy from facial muscle in the area of the erythematous plaque showed massive destruction of the muscle tissues by the lymphomatous infiltrates. Furthermore, electrodiagnostic study showed peripheral cranial nerve palsies, involving the left facial and trigeminal nerves. We conclude that diffuse large B-cell lymphoma may develop symptoms such as facial hemiplegia and paresthesia prior to cutaneous manifestations. Diffuse large B-cell lymphoma must be considered as one of the important causes of palsies of cranial nerves at the peripheral level.

Evaluation and treatment of shoulder subluxation in hemiplegia: relationship between subluxation and pain.

Shoulder subluxation in hemiplegic patients has been recognized as a difficult problem to manage. In the study contained herein, our aims are to evaluate shoulder subluxation, to clarify if shoulder subluxation causes pain, and to discuss the treatment of shoulder subluxation. The study included 75 hemiplegic patients with shoulder subluxation. Each patient was evaluated for the degree of shoulder pain, motor recovery of the upper limb, and shoulder range of motion. Some indexes for evaluating subluxation were measured with radiographs of the shoulders. Arthrograms of the affected shoulder joint were taken in 23 patients. The following results were found: (1) shoulder pain was significant more frequently in left hemiplegia; (2) vertical disparity was strongly correlated with discrepancy of the descendant ratio; (3) severe inferior subluxation had a tendency to show medial displacement of the humeral head; (4) there were correlations between shoulder pain and shoulder range of motion, especially external rotation; (5) adhesive changes in the arthrograms were seen in most subjects. These results indicate that there is no relation between shoulder subluxation and pain, and adhesive capsulitis is a main cause of shoulder pain. We conclude that correct positioning and shoulder range of motion exercises are advisable in hemiplegic patients with shoulder subluxation.

Silent nucleotide substitution in the sterol 27-hydroxylase gene (CYP 27) leads to alternative pre-mRNA splicing by activating a cryptic 5' splice site at the mutant codon in cerebrotendinous xanthomatosis patients.

A functionally silent nucleotide substitution of the sterol 27-hydroxylase gene (CYP 27), identified in two families with cerebrotendinous xanthomatosis (CTX), was confirmed to cause alternative pre-mRNA splicing of the gene. Full-length RT-PCR analysis of the CYP 27 gene in a patient from one of the CTX families revealed one major and an additional faint band. Sequence analysis of the cloned RT-PCR product showed three species of cDNA: 3' terminal 13 bp of exon 2 deleted cDNA, exon 2 skipped cDNA, and full-length cDNA with a functionally silent G to T mutation at codon 112 (GGG 112Gly to GGT 112Gly). Only a single base change was identified by genomic DNA sequence analysis of the CYP 27 gene in the patient: T replaced G at the third position of codon 112, 13 bp upstream from the 3' terminus of exon 2. Transfection of constructed minigenes, with or without the mutation, confirmed that this silent mutation resulted in alternative pre-mRNA splicing by activating a cryptic 5' splice site around the mutant codon. The mutation was also identified in two patients from another CTX family, with a compound heterozygous pattern of A for G substitution at codon 372, a mutation reported previously by our group. The results elucidate a novel molecular basis for the CTX and suggest the significance of a silent nucleotide substitution with regard to pre-RNA splicing.

Genomic organization and alternative splicing of human PACE4 (SPC4), kexin-like processing endoprotease.

PACE4 (paired basic amino acid cleaving enzyme) is a member of a family of the mammalian kexin-like proprotein convertases containing a subtilisin-like catalytic domain. Previously we reported seven isoform mRNAs of PACE4 that vary in size and 3'-coding sequence [A. Tsuji et al. (1994) Biochem. Biophys. Res. Commun. 200, 943-950; K. Mori et al. (1997) J. Biochem. 121, 941-948]. To determine the origin of these isoforms, the entire human PACE4 gene has been isolated as a set of overlapping genomic DNA fragments, and analyzed by restriction enzyme digestion and nucleotide sequence determination. The human PACE4 gene spans at least 250 kb and is distributed over 25 exons that range in size from 39 to 1,422 base pairs. Human PACE4 gene is the largest kexin-like proprotein convertase gene reported to date. The most striking feature of its genomic structure is the size of the introns and the number of exons, although the general organization of signal peptide, propeptide, and catalytic domains, which are conserved in this family, is very similar to that reported for other kexin-like protease genes. The structural analysis of PACE4 genomic DNA indicates that multiple PACE4 transcripts are produced as a consequence of alternative RNA splicing events, including exon skipping, and differences in the usage of the inner 5'-splicing donor and polyadenylation sites. A major transcriptional start site was detected 314 bp upstream from the ATG translational start site by primer extension analysis. Sequence analysis of the 5'-flanking region revealed that PACE4 gene lacks TATA and CCAAT boxes in the proximal upstream region of the start site, although potential binding sites for several transcription factors including SP1, AP1, AP2, PEA3, Ets-1, GHF (growth hormone factor)-1, CREB (cyclic AMP response element binding protein), and basic helix-loop-helix proteins, were present. An unusual sequence of six tandem repeats of a nonadecamer (GGCCTGGGGGTTCACCTGC) containing an E box is found in the 5'-flanking region. These results suggest that PACE4 is not a constitutive gene product and its expression is regulated by various transcription factors.

Bowen's disease: statistical study of a 10 year period.

According to histological records, a total of 74 patients were diagnosed with Bowen's disease (B.d.) between 1 January 1984 and 31 December 1993 at the Department of Dermatology of Kitasato University. There was slight female predominance (36 male, 38 female), and 73% of the patients were older than 60 years; the mean age was 66.8 years. Fifteen patients had multiple (two-five) lesions. In 13 patients, other benign skin lesions were also found. Arsenic exposure as etiologic factor could have been present in 2 cases. Only 3 patients had other associated malignant tumors, which does not confirm the paraneoplastic nature of B.d. One-fifth of the lesions were on sun-exposed areas (head, neck and hands). Although we excluded invasive carcinomas from our statistical study, we mention the 8 invasive carcinomas developing from B.d. in that period. Histopathological classification of B.d. is uncommon. Classifying our cases by Darier's histopathological classification, 63.3% of them belonged to the lenticular type. The malignant potential of different histopathological types of B.d. needs further investigation.

Inhibitory effect of magnesium L-ascorbyl-2-phosphate (VC-PMG) on melanogenesis in vitro and in vivo.

BACKGROUND: An inhibitory effect of ascorbic acid (AsA) on melanogenesis has been described. However, AsA is quickly oxidized and decomposed in aqueous solution and thus is not generally useful as a depigmenting agent. OBJECTIVE: Our purpose was to examine the effect on pigmentation of magnesium-L-ascorbyl-2-phosphate (VC-PMG), a stable derivative of AsA. METHODS: Percutaneous absorption of VC-PMG was examined in dermatomed human skin, and its effect on melanin production by mammalian tyrosinase and human melanoma cells in culture was also measured. A 10% VC-PMG cream was applied to the patients. RESULTS: VC-PMG suppressed melanin formation by tyrosinase and melanoma cells. In situ experiments demonstrated that VC-PMG cream was absorbed into the epidermis and that 1.6% remained 48 hours after application. The lightening effect was significant in 19 of 34 patients with chloasma or senile freckles and in 3 of 25 patients with normal skin. CONCLUSION: VC-PMG is effective in reducing skin hyperpigmentation in some patients.