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H Kume

Publications and source records attributed to H Kume.

At least 19 recordsLinked to original sources

CFTR-Mediated anion conductance regulates Na(+)-K(+)-pump activity in Calu-3 human airway cells.

We studied the role of CFTR in the Na(+)-K(+)-pump activity of Calu-3 human airway cells. To estimate the Na(+)-K(+)-pump activity on the basolateral membrane, the ouabain-sensitive component of the short-circuit current (Isc) was measured after permeabilization of the apical membrane with nystatin, a Na(+) ionophore. The Na(+)-K(+)-pump activity was diminished by a selective CFTR blocker (glybenclamide) or nonspecific Cl(-) channel inhibitors (NPPB and DPC) but not by outwardly rectifying Cl(-) channel blockers (DNDS, DIDS). Augmentation of anion conductance by 8-bromo-cyclic AMP (8Br-cAMP, 1 mM) potentiated the Na(+)-K(+)-pump activity that was reduced by blocking CFTR or by the replacement of Cl(-) with gluconate, a less membrane-permeant anion. The Na(+)-K(+)-pump activity was unaffected by the replacement of Cl(-) with NO(-)(3) that has equal permeability through the CFTR. These results suggest that the anion movement through the CFTR may contribute to the Na(+)-K(+)-pump activity in Calu-3 cells by regulating the rate of Na(+) entry.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Benzo[a]pyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor.

The contribution of the aryl hydrocarbon receptor (AhR) in induction of a battery of xenobiotic-metabolizing enzymes has been studied extensively. However, no direct proof has been obtained that it plays a role in modulating carcinogenesis. To address the question of whether AhR is required for tumor induction, we have investigated the response of AhR-deficient mice to benzo[a]pyrene (B[a]P), a widely distributed environmental carcinogen. B[a]P treatment induced expression of the cytochrome P450 gene Cyp1a1 in the skin and liver of AhR-positive mice bearing +/+ and +/- genotypes and did not induce expression of the cytochrome P450 gene Cyp1a1 in AhR-null mice in either skin or liver. In contrast, Cyp1a2 gene expression was positive in liver irrespective of the presence or absence of the AhR gene, or B[a]P treatment, although its inducibility was lost in the AhR(-/-) mouse. All AhR-positive male mice of both +/+ and +/- genotypes that received subcutaneous injection of B[a]P (2 mg) on the first and the eighth days had developed subcutaneous tumors at the site of injection at the end of the 18-week experiment. In contrast, no tumors were apparent in any of the AhR-deficient mice. Likewise, topical application of B[a]P (200 microg) at weekly intervals to the skin of female mice for 25 weeks produced skin tumors only in the AhR-positive mice. Thus the carcinogenic action of B[a]P may be determined primarily by AhR, a transcriptional regulator of the gene for CYP1A1. The results of the present study provide direct evidence that AhR is involved in carcinogenesis.

Animals↗

Case report. A case of chromoblastomycosis effectively treated with terbinafine. Characteristics of chromoblastomycosis in the Kitasato region, Japan.

A 38-year-old male with history of trauma in the left gluteal region 20 years ago presented with a dark red skin eruption at the traumatized area. It gradually grew to form an erythematous plaque with a well-defined border. Clinical findings and mycological cultures resulted in the diagnosis of chromoblastomycosis due to Fonsecaea pedrosoi. After initial administration of 5-fluorocytosine and local heat an almost complete cure was achieved with terbinafine combined with local heat therapy. A review is given on the chromoblastomycosis cases observed in the Kitasato region in Japan.

Adult↗

Bifonazole (Mycospor cream) in the treatment of moccasin-type tinea pedis. Comparison between combination therapy of bifonazole cream + 10% urea ointment (Urepearl) and occlusive dressing therapy with the same agents.

Moccasin-type tinea pedis(MTTP) is a hardly curable superficial dermatomycosis primarily characterized by hyperkeratosis of the sole. In this study, we compared the usefulness of combination therapy of bifonazole (Mycospor cream) + 10% urea ointment (Urepearl) (overlapping application group = group I) with occlusive dressing therapy with the same agents (group II) in the treatment of MTTP, and obtained the following results. (1) The clinical improvement rate (percentage of "marked improvement" and "moderate improvement") was 60.4% in group I and 83.3% in group II. (2) The mycological eradication rate was 48.7% in group I and 82.1% in group II after 4 weeks of treatment and 90.9 and 96.9%, after 12 weeks of treatment, respectively. (3) The clinical utility rate (percentage of "very beneficial" and "beneficial") was 83.3% in group I and 93.8% in group II. These results indicate the superiority of both combination therapy of bifonazole + 10% urea ointment (overlapping application group) and occlusive dressing therapy with the same agents in terms of efficacy and safety for the treatment of MTTP, and suggest that they can be recommended for treatment of patients for whom it is difficult to use oral antimycotic agents or for patients who fail to respond to oral medications alone.

Administration, Topical↗

Serum itraconazole and hydroxyitraconazole concentrations and interaction with digoxin in a case of chronic hypertrophic pachymenigitis caused by Aspergillus flavus.

A patient treated with itraconazole (ITCZ) under the diagnosis of Aspergillus flavus-induced chronic hypertrophic pachymeningitis is presented. The reason for the successful cure of this patient was investigated by the pharmacokinetic analysis of serum levels of ITCZ. Concurrently administered digoxin was also investigated for its drug-drug interaction. The patient (a 75-year-old male) developed ophthalmopathy, and was diagnosed as having A. flavus hypertrophic pachymeningitis by pachymeninx biopsy. After admission, he was treated with FLCZ, AMPH, 5-FC and MCZ. The infection tended to subside with the AMPH administration. Since renal insufficiency was induced by AMPH and the other antifungal drugs were ineffective, daily administration of 200 mg of ITCZ was initiated, and the inflammatory signs and symptoms gradually subsided. The symptoms did not recur during the 36 months of itraconazole treatment after discharge, and it was concluded that ITCZ was effective for A. flavus hypertrophic pachymeningitis. Pharmacokinetic parameters of ITCZ and OH-ITCZ as follows: ITCZ: Cmax 93.2 ng/ml, T1/2 beta 11 hours, AUC0-24 999 ng.h/ml, OH-ITCZ: Cmax 159.4 ng/ml, T1/2 beta 16. 2 hours, AUC0-24 of 1391 ng.h/ml. Both ITCZ and OH-ITCZ reached steady states seven days after administration began. The ITCZ and OH-ITCZ levels in serum collected 36 months after the initiation of administration were 452.9 ng/ml and 1233.6 ng/ml, respectively. Cmax and AUC0-24 of ITCZ and OH-ITCZ on the second day were markedly lower than those in healthy adults reported by Oguchi et al., and hypoalbuminemia observed at administration on that day was considered the most probable cause. It was assumed that the most plausible reason for a successful cure even at a low dose of ITCZ was the increase of distribution to tissue by the increase of the unbound form. Digoxin was concurrently given to this patient at 0. 125 mg/day, but the blood digoxin level was not elevated. Consideration of the blood level of albumin is believed to be important for evaluating the blood concentration of ITCZ.

Aged↗

[Sarcoidosis with primary acute cavitation exacerbated by bronchial asthma].

A 22-year-old woman complaining of blurred vision visited our hospital in March 1995 and was given a diagnosis of uveitis. Chest X-ray and computed tomographic (CT) films demonstrated bilateral hilar lymphadenopathy (BHL), diffuse granular shadows in both lung fields, and a cavity with a thin, smooth wall in the right upper lung field. Because histopathologic findings from transbronchial lung biopsy specimens of the lung and cavity tissues disclosed sarcoid granuloma, the diagnosis was sarcoidosis with primary cavitation, which is very rare for this disease. Although BHL disappeared without medication, in November the patient experienced dyspnea due to attacks of bronchial asthma that had been in remission for a long period. Treatment with inhalation of becromethazone propionate markedly alleviated her symptoms. In May 1998, follow-up chest CT films demonstrated that the cavity had disappeared. This case suggested that sarcoidosis leads to a deterioration of asthma control, a conclusion supported by previous reports.

Adult↗

Norbin, a neurite-outgrowth-related protein, is a cytosolic protein localized in the somatodendritic region of neurons and distributed prominently in dendritic outgrowth in Purkinje cells.

Distribution of norbin protein in rats was characterized by immunohistochemical study. It was distributed not only in whole brain but also in peripheral nervous system. The protein was localized in the somata, except for nuclei, and dendrites of neurons. Subcellular fractionation revealed that norbin is a cytosolic protein. Prominent distribution was observed in dendrites of dendritic outgrowth in Purkinje cells. Norbin should play a role in somatodendritic functions of neurons.

Animals↗

VHL gene inactivation in an endolymphatic sac tumor associated with von Hippel-Lindau disease.

The authors present a case of endolymphatic sac tumor, a rare adenomatous tumor of the temporal bone, in a patient with von Hippel-Lindau (VHL) disease. Sequencing and microsatellite analysis of DNA samples from the tumor showed a 1-base pair deletion in exon 1 of the VHL gene and loss of heterozygosity at chromosome 3p25.5, the locus for the VHL gene. The results indicate that VHL gene inactivation contributed to the oncogenesis of endolymphatic sac tumor and provide molecular genetic proof that this tumor is associated with VHL disease.

Adult↗

Tetracyclines reduce Na+/K+ pump capacity in Calu-3 human airway cells.

We studied the effect of tetracyclines on the Na+/K+ pump activity in Calu-3, a human airway cell line. To estimate Na+/K+ pump capacity on the basolateral membrane, an ouabain-sensitive component of the short-circuit current (Isc) was measured in the presence of nystatin, an ionophore of Na+. The application of ouabain (1 mM) to the basolateral solution completely inhibited the Isc generated by adding nystatin (50 microM) to the apical solution. Tetracycline (TC), minocycline (MC), or demethylchlortetracycline (DC) at 0.5 mM applied to the apical but not to the basolateral solution also decreased the nystatin-induced Isc. Neither phlorizin- nor diphenylamine-2-carboxylic acid-sensitive Isc was affected by TC, MC, or DC. These results indicate that tetracyclines may permeate only through the apical membrane with the result that the Na+/K+ pump's capacity for Na+ extrusion should be suppressed without a decrease in Cl- transport.

Anti-Bacterial Agents↗

Case report. Kerion Celsi effectively treated with terbinafine. Characteristics of kerion Celsi in the elderly in Japan.

A 75-year-old non-working male living in Sagamihara, Kanagawa Prefecture, had erythematous plaques with scales associated with follicular pustules in the head area extending from the occipital to right temporal regions about 1 month prior to his initial visit, when hair loss increased. The diagnosis was kerion Celsi. Trichophyton rubrum was isolated from scales and tissues taken from lesions in the head. Histopathological examinations showed irregular epidermal thickening with dense cell infiltration from the dermis to subcutaneous adipose tissues. Granulomatous reactions involving neutrophils, histiocytes and giant cells were seen mainly in the hair follicles. Periodic acid-Schiff (PAS) and Grocott-positive microbial elements were detected in the horny layer, and inside and outside the hair follicles. Pustules disappeared 1 week after starting the oral treatment with terbinafine (125 mg day-1). A cure was achieved 2 weeks after starting the treatment, with only slight scales remaining. No recurrence has been observed to date. Terbinafine was thought to be very effective and safe for kerion Celsi. We reviewed 27 cases of kerion Celsi reported in patients, aged at least 70 years, in Japan and found that the major characteristics of this disease in Japan include the following: (1) female cases outnumber male cases; (2) the causative organism was T. rubrum in 14 of 27 patients (51.9%); and (3) topical application of steroids often induces this disease in patients with superficial tinea capitis.

Administration, Oral↗

Surgical treatment of renal cell carcinoma associated with Budd-Chiari syndrome: report of four cases and review of the literature.

AIMS: Renal cell carcinoma is sometimes associated with inferior vena caval tumour thrombus, but occlusion of hepatic veins by the tumour thrombus causing liver dysfunction, the so-called Budd Chiari syndrome, is relatively uncommon. There are only a few reports in the literature which discuss this condition. METHODS: Four cases admitted to our hospital over a 7-year period and eight cases reported in detail in the English and the Japanese literature were included in this study. They are classified into two groups: mild/silent, without liver failure, and severe, with liver failure. RESULTS: Five patients were classified as mild/silent and seven as severe. Clinical manifestations were mild in the former cases and acute in the latter. Surgery was performed in four of the former cases but only in one case of the latter cases. CONCLUSIONS: In mild cases, surgical treatment seems to avoid imminent hepatic failure effectively and should be performed as soon as possible. In such cases Budd Chiari syndrome in itself does not affect the prognosis. In severe cases, however, surgical treatment is very difficult and risky due to the existing hepatic failure.

Adult↗

Epidemiology of visceral mycoses: analysis of data in annual of the pathological autopsy cases in Japan.

The data on visceral mycoses that had been reported in the Annual of the Pathological Autopsy Cases in Japan from 1969 to 1994 by the Japanese Society of Pathology were analyzed epidemiologically. The frequency of visceral mycoses among the annual total number of pathological autopsy cases increased noticeably from 1.60% in 1969 to a peak of 4.66% in 1990. Among them, the incidences of candidiasis and aspergillosis increased the most. After 1990, however, the frequency of visceral mycoses decreased gradually. Until 1989, the predominant causative agent was Candida, followed in order by Aspergillus and Cryptococcus. Although the rate of candidiasis decreased by degrees from 1990, the rate of aspergillosis increased up to and then surpassed that of candidiasis in 1991. Leukemia was the major disease underlying the visceral mycoses, followed by solid cancers and other blood and hematopoietic system diseases. Severe mycotic infection has increased over the reported 25-year period, from 6.6% of the total visceral mycosis cases in 1969 to 71% in 1994. The reasons for this decrease of candidiasis combined with an increase of aspergillosis or of severe mycotic infection might be that (i) nonsevere (not disseminated) infections were excluded from the case totals, since they have become controllable by antifungal drugs such as fluconazole, but (ii) the available antifungal drugs were not efficacious against severe infections such as pulmonary aspergillosis, and (iii) the number of patients living longer in an immunocompromised state had increased because of developments in chemotherapy and progress in medical care.

AIDS-Related Opportunistic Infections↗

Inhibition of beta-adrenergic desensitization by KCa channels in human trachealis.

We examined the reduced responsiveness to beta-adrenergic receptor agonists (beta-agonists) after exposure to beta-agonists, and the mechanisms underlying this phenomenon in isolated human tracheal smooth muscle, using isometric tension records to test the hypothesis that repeated inhalation of beta-agonists leads to reduced responsiveness to beta-agonists. The inhibitory effects of isoproterenol (ISO) on contraction by spasmogens participating in asthma attacks diminished markedly after continuous exposure to ISO (0.0003 to 3 microM) for 45 min; moreover, when ISO was repeatedly applied for 10 min to tissues precontracted by methacholine every 30 min, the relaxant effects of ISO gradually attenuated after these repeated applications. In contrast, reduced beta-adrenergic relaxation after continuous and repeated exposure to agonists did not occur when tissues were preincubated with 2 microg/ ml cholera toxin (CTX), which irreversibly activates guanosine triphosphate (GTP)-binding protein (Gs) coupled with beta-adrenergic receptors, for 6 h. However, the CTX inhibition disappeared in the presence of iberiotoxin, a selective inhibitor of large conductance Ca2+-activated K+ (KCa) channels. Our results demonstrate that continuous and repeated exposure to beta-agonists leads to beta-adrenergic desensitization, and that activation of KCa channels by Gs prevents this desensitization.

Adjuvants, Immunologic↗

Adrenomedullin inhibits ovalbumin-induced bronchoconstriction and airway microvascular leakage in guinea-pigs.

Human adrenomedullin is a potent vasodilator with bronchodilation properties. The effects of adrenomedullin on antigen-induced bronchoconstriction and airway microvascular leakage in guinea-pigs was investigated. The portion of the adrenomedullin molecule possessing these pulmonary active profiles was also examined, using two truncated adrenomedullin molecules: adrenomedullin (1-25) and adrenomedullin (22-52). Four weeks after sensitization with ovalbumin (0.1 mg x k(-1)), the guinea-pigs were anaesthetized and mechanically ventilated. Respiratory resistance, dynamic compliance and arterial blood pressure were monitored. Airway microvascular leakage was evaluated by extravasation of 20 mg x kg(-1) Evans blue into airway interstitial tissue. In order to enhance the pulmonary effects of adrenomedullin, the active production of endogenous nitric oxide was inhibited by coadministration of a nitric oxide synthase inhibitor, L-N(G)-nitroarginine methethyl ester (10 mg x kg(-1)). Intravenous pretreatment with adrenomedullin (10, 30 and 100 microg x mL(-1)) dose-dependently inhibited ovalbumin-induced bronchoconstriction and airway microvascular leakage in all airway segments. Inhaled adrenomedullin (100 microg.mL(-1), 1 min) also significantly inhibited pulmonary changes induced by ovalbumin inhalation (3 mg x mL (-1) , 3 min). These pulmonary profiles of adrenomedullin were enhanced by inhibiting the active production of endogenous nitric oxide. In conclusion, adrenomedullin has inhibitory effects on antigen-induced microvascular leakage and bronchoconstriction in guinea-pigs. These beneficial effects strongly related to its unique ring structure and N-terminal segment, making it a potential anti-asthma.

Adrenomedullin↗