Publications by authors named "Komai A"

Background: Obstructive sleep apnoea (OSA) is a common disease with breathing disturbances during sleep. Sulthiame (STM), a carbonic anhydrase (CA) inhibitor, was recently shown to reduce OSA in a significant proportion of patients. CA activity and hypoxia-inducible factor (HIF)-1α are two potential biomarkers reported in severe OSA and hypoxia.

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White adipocyte adiponectin exocytosis is triggered by cAMP and a concomitant increase of cytosolic Ca potentiates its release. White adipose tissue is richly innervated by sympathetic nerves co-releasing noradrenaline (NA) and ATP, which may act on receptors in the adipocyte plasma membrane to increase cAMP via adrenergic receptors and Ca via purinergic receptors. Here we determine the importance of NA and ATP for the regulation of white adipocyte adiponectin exocytosis, at the cellular and molecular level, and we specifically detail the ATP signalling pathway.

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Circulating levels of the adipocyte hormone adiponectin are typically reduced in obesity, and this deficiency has been linked to metabolic diseases. It is thus important to understand the mechanisms controlling adiponectin exocytosis. This understanding is hindered by the high complexity of both the available data and the underlying signaling network.

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  • The study examines how resistin, an adipose hormone linked to metabolic diseases, is regulated in mouse fat cells.
  • Resistin is secreted from white adipocytes in rodents but produced by different cell types in humans.
  • The research finds that increased cAMP and calcium levels stimulate resistin release, which is significantly reduced in fat cells from obese and diabetic mice, suggesting a connection with adiponectin in their secretion process.
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Exocytosis, the fusion of vesicles with the plasma membrane, can be measured with the patch-clamp technique as increases in membrane capacitance. Here we provide detailed information on how to monitor white adipocyte exocytosis using this method. We describe how to isolate the stromal vascular fraction of cells (SVF) within adipose tissue and how to differentiate SVF and cultured 3T3-L1 cells into adipocytes suitable for patch-clamp studies.

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Adiponectin is a hormone secreted from white adipocytes and takes part in the regulation of several metabolic processes. Although the pathophysiological importance of adiponectin has been thoroughly investigated, the mechanisms controlling its release are only partly understood. We have recently shown that adiponectin is secreted via regulated exocytosis of adiponectin-containing vesicles, that adiponectin exocytosis is stimulated by cAMP-dependent mechanisms, and that Ca and ATP augment the cAMP-triggered secretion.

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Background: Although many new disease entities of autoimmune bullous disease (AIBD) have recently been recognized, satisfactory immunological diagnostic methods and comprehensive classifications for various AIBDs have not been established.

Objectives: To identify immunological diagnostics and comprehensive classifications for AIBDs.

Methods: We selected and examined 4774 patients with various AIBDs from our cohort of 5063 patients with difficult AIBDs, whose sera and information were sent for our diagnostic method from other institutes in either Japan or other countries over the last 19 years.

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  • The study explored how adiponectin release is regulated in healthy versus metabolically diseased states, using specialized lab techniques to measure secretion.
  • Epinephrine and β-adrenergic receptor activation effectively increased adiponectin release in normal cells but not in those from obese or type 2 diabetic mice, indicating a dysfunction in this process.
  • The research suggests that lower expression of β-adrenergic receptors and Epac1 in obese cells contributes to a condition termed "catecholamine resistance," impairing proper adiponectin secretion.
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We investigated the effects of temperature on white adipocyte exocytosis (measured as increase in membrane capacitance) and short-term adiponectin secretion with the aim to elucidate mechanisms important in regulation of white adipocyte stimulus-secretion coupling. Exocytosis stimulated by cAMP (included in the pipette solution together with 3 mM ATP) in the absence of Ca2+ (10 mM intracellular EGTA) was equal at all investigated temperatures (23°C, 27°C, 32°C and 37°C). However, the augmentation of exocytosis induced by an elevation of the free cytosolic [Ca2+] to ~1.

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  • The study investigated how cAMP, calcium ions (Ca(2+)), and ATP influence exocytosis and the release of adipokines in white adipocytes, particularly using 3T3-L1 cells.
  • Exocytosis occurred without intracellular Ca(2+), provided cAMP was present, but plateaued after about 10 minutes, likely due to vesicle depletion.
  • Inclusion of ATP and elevated Ca(2+) significantly enhanced the duration and rate of cAMP-triggered exocytosis, and similar stimulation was observed using the Epac agonist, while inhibiting PKA did not affect the process.
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Famciclovir is a guanine analog antiviral drug used commonly for herpes zoster. Efficacy of famciclovir treatment has been reported to be comparable to valacyclovir treatment. Both of these medications reduce the time to complete cessation of zoster-associated pain including post-herpetic neuralgia, as compared to acyclovir.

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Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous disease, associated with neoplasia, which has characteristic clinical, histological and immunological features. While respiratory epithelial involvement has been described in several cases, lesions in the colon epithelium have never been reported. We describe a 57-year-old Japanese woman with PNP who had many aphthae-like erosions on the colon epithelium, in addition to typical mucocutaneous PNP lesions.

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Cicatricial pemphigoid (CP) is an autoimmune bullous disease accompanied by mucosal lesions. The majority of patients with CP have autoantibodies against BP180. Anti-laminin 5 (epiligrin) CP is relatively rare.

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A 35-year-old Japanese woman had recurrent, pruritic, vesicular lesions on the face, neck and upper back as well as erosive lesions of the oral cavity and genitalia. The skin and mucosal lesions healed without scarring upon the systemic administration of corticosteroid and azathioprine. Direct immunofluorescence revealed linear deposits of IgG, IgA and C3 at the cutaneous basement membrane zone.

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Pemphigus is an autoimmune mucocutaneous bullous disease characterized by autoantibodies against the cell surfaces of epidermal keratinocytes. Six cases with deposition of both IgG and IgA on keratinocyte cell surfaces have been reported in the recent literature. We provisionally termed these cases IgG/IgA pemphigus.

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Noise can have a beneficial effect on sensory neurological systems, enhancing detection of small afferent signals and thereby improve efferent neural responses. We hypothesized whether a similar mechanism would facilitate impaired neural transmission associated with neurological disease, and tested whether addition of external noise to baroreceptor signaling could improve blunted autonomic efferent responses to a postural challenge in patients with primary autonomic failure (PAF). Five PAF patients were tested, one in duplicate and another triplicate, for their transient responses of heart rate (measured from electrocardiographic RR intervals; RRIs) and systolic (SBP) and diastolic (DBP) blood pressures to either 30 degrees or 60 degrees head-up tilt, with and without continuous application of beat-to-beat Gaussian white noise to the carotid sinus baroreceptors.

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The runoff characteristics of major ionic species from a stream in a forested watershed were investigated during two rain events. The values of EC and the concentrations of alkalinity, anions and cations, except for NO3-, decreased according to the increase of discharge, and showed a sharp lower peak. On the other hand, the concentrations of NO3- and K+ indicated an opposite change.

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We describe four patients with generalized scaly and pustular skin lesions showing extensive neutrophilic infiltration in the subcorneal region of the epidermis. Immunofluorescence, immunoblot and enzyme-linked immunosorbent assay analyses detected IgG antibodies reacting exclusively with desmoglein 1, the pemphigus foliaceus antigen. This study indicates that pemphigus foliaceus may show prominent neutrophilic pustular skin lesions.

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Background: There are a number of reports of pemphigus with clinical shifting between pemphigus foliaceus (PF) and pemphigus vulgaris (PV). On the other hand, a novel enzyme-linked immunosorbent assay (ELISA) against recombinant baculoproteins of desmoglein 1 (Dsg1) (PF antigen) and Dsg3 (PV antigen) has been established and found to be extremely sensitive and specific.

Objectives: To characterize the change in the antibody profiles in a series of pemphigus cases with mixed features of PF and PV by various methods, including the novel ELISA.

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Objective: To examine the frequency of antidesmoglein 1 (Dsg1) and antidesmoglein 3 (Dsg3) IgA autoantibodies in IgA pemphigus.

Design: We developed an enzyme-linked immunosorbent assay against recombinant Dsg1 and Dsg3 to detect IgA autoantibodies.

Patients: Twenty-two patients with IgA pemphigus were studied.

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Cicatricial pemphigoid (CP) is a chronic subepidermal bullous dermatosis which primarily involves the mucous membranes. The oral cavity and the eye are most frequently involved. Since extension of the lesion into the pharynx and esophagus causes sore throat and dysphagia and progressive ocular lesions may cause blindness, early and valid diagnosis is very important.

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