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Biomedical subjects

M Kubo

Publications and source records attributed to M Kubo.

At least 37 records · Page 2Linked to original sources
PubMed2004

Effects of hypophysectomy and in vivo administration of ACTH or dexamethasone on the level of ACTH receptor mRNA in adrenal glands and adipose tissues of mice.

OBJECTIVE: In rodents, ACTH induces steroidogenesis in the adrenal cortex and also lipolysis in adipose tissues via the sole specific receptor for ACTH. Up-regulation of the ACTH receptor (ACTH-R) mRNA by ACTH was found to be evident in adrenocortical cells. However, a role of in vivo ACTH on ACTH-R mRNA expression in the adrenal cortex is not well understood. In addition, so far less attention has been also paid to the regulation of ACTH-R expression in adipose tissues. We investigated the effects of hypophysectomy and in vivo administration of ACTH or dexamethasone on the level of ACTH-R mRNA in the adrenal gland and adipose tissues of mice. METHODS: ACTH mRNA in the adrenal glands and epididymal adipose tissues of mice sacrificed 10 days after hypophysectomy or sham operation, and 24 hours after ACTH-Z (2 IU i.m.) or physiological saline solution (PSS) injection, and also 3-days after dexamethasone (300 microg/day i.m.) or PSS administration was analysed by Northern blot, and intensities of autoradiographic bands were quantified. RESULTS: In the adrenal gland, in vivo administration of ACTH-Z significantly increased the level of ACTH-R mRNA to 342% of control values, but in vivo administration of dexamethasone or hypophysectomy induced no significant alteration of ACTH-R mRNA. In adipose tissues, these conditions did not significantly alter the level of ACTH-R mRNA. CONCLUSION: Low circulating ACTH may not be a substantial factor for ACTH-R gene expression in the adrenal gland, but a high level of in vivo ACTH dose up-regulated the expression. A different regulation of ACTH-R gene expression exists in the adrenal cortex and adipose tissues of mice.

Adipose Tissue↗
PubMed2003

Effects of dexamethasone on the pathogenesis of porcine circovirus type 2 infection in piglets.

To investigate the effect of immunosuppression on porcine circovirus type 2 (PCV2) infection, hysterectomy-produced, colostrum-deprived piglets were inoculated with the virus by the intranasal or intraperitoneal route, with or without dexamethasone (DEX) treatment. Eleven piglets aged 8 days were divided into four groups, namely group A (four animals given PCV2), B (three given PCV2 with DEX), C (two given sterile medium with DEX) and D (two given sterile medium). No significant clinical signs were observed. Histopathological and immunohistochemical examination revealed granulomatous inflammation and PCV2 antigen in the lymphoid tissues of group B piglets, but not in the other three groups. Flow cytometric analysis of peripheral blood lymphocytes showed a reduced number of CD4+ T cells in DEX-treated piglets (groups A and C). No differences between groups were observed in respect of the number of B cells, serum IgG concentration, or PCV2 antibody titre. These results indicate that DEX influenced the pathogenic effects of PCV2 infection in lymphoid organs, and that suppression of cell-mediated immunity may play a role in the aetiology of postweaning multisystemic wasting syndrome.

Animals↗
PubMed2003

A novel p63 sterile alpha motif (SAM) domain mutation in a Japanese patient with ankyloblepharon, ectodermal defects and cleft lip and palate (AEC) syndrome without ankyloblepharon.

We present a sporadic case of a Japanese female infant with ectodermal dysplasia, complete cleft lip and palate, severe skin erosions at birth and recurrent scalp infection. She had typical clinical features of ankyloblepharon, ectodermal defects and cleft lip and palate (AEC) syndrome without ankyloblepharon. Histological and immunohistochemical analyses showed reduced granular cell layers and aberrant expression of the p63 protein in the suprabasal keratinocytes. Mutation analysis of the exon 13 of p63 gene revealed a heterozygous in-frame 3-bp insert (c. 538-539 ins TTC) encoding additional amino acid residues (F). This is the first report of sterile alpha motif domain mutation except for single nucleotide transitions.

Abnormalities, Multiple↗
PubMed2003

Risk factors for age related maculopathy in a Japanese population: the Hisayama study.

AIMS: To examine the risk factors for age related maculopathy (ARM) in a sample Japanese population. METHODS: In 1998, a cross sectional community survey was conducted among residents of Hisayama. A total of 596 men and 886 women living in Hisayama, Japan, aged 50 years or older consented to participate in the study. Each participant underwent a comprehensive examination that included an ophthalmic examination. The presence of ARM was determined by grading from fundus examination by indirect ophthalmoscopy, slit lamp examination, and colour fundus photographs. Using these cross sectional data, logistic regression analyses were performed to determine the risk factors for ARM. The following 10 possible risk factors were used: age, cataract, hypertension (history), hypertension (history or examination), diabetes, hyperlipidaemia, current smoker, alcohol intake, BMI, and WBC. RESULTS: ARM was detected in 19.5% of men and 14.9% of women. Men were found to have a significantly higher prevalence of ARM than women. Multiple logistic regression analysis showed that age and hypertension (history or examination) were significantly associated with ARM in men, whereas only age was a significant risk factor for ARM in women. CONCLUSIONS: This study suggests that higher age and male sex are relevant risk factors for ARM in Japan. In addition, hypertension is a relevant risk factor in men.

Age Distribution↗
PubMed2003

Induction of apoptosis in HL-60 cells treated with medicinal herbs.

In order to develop a new apoptosis inducer, we screened 22 crude drugs for their apoptosis-inducing activity. It was found that Glycyrrhiza uralensis, Cynomorium songaricum, Eucommia ulmoides, Phellodendron amurense, Cinnamomum cassia and Paeonia lactiflora induced the death of HL-60 cells. To investigate the mechanism of apoptosis induced by these six crude drugs, the mitochondrial transmembrane potential and the activity of caspase-3 were measured. Reduced mitochondrial transmembrane potentials within 12 hours after the administration of Glycyrrhiza uralensis, Cynomorium songaricum, Phellodendron amurense and Paeonia lactiflora, and within 24 hours after the administration of Eucommia ulmoides and Cinnamomum cassia were observed. All of the six apoptosis-inducing crude drugs increased caspase-3 activity within 12-36 hours after administration. After further examining the apoptosis-inducing activity of berberine, palmatine, panelofuroline and glycyrrhizin, which were the ingredients obtained from Phellodendron amurense, Glycyrrhiza uralensis and Paeonia lactiflora, it was found that only berberine could induce apoptosis. From these results, it was concluded that the apoptosis induced by the six crude drugs (Glycyrrhiza uralensis, Cynomorium songaricum, Eucommia ulmoides, Phellodendron amurense, Cinnamomum cassia and Paeonia lactiflora) occurred via the mitochondrial route and that the apoptosis-conducting mechanism acted through a cascade involving caspase-3.

Antineoplastic Agents, Phytogenic↗
PubMed2002

Characterization and identification of Oya virus, a Simbu serogroup virus of the genus Bunyavirus, isolated from a pig suspected of Nipah virus infection.

A virus, named Oya virus, was isolated in Vero cell cultures from the lungs of a pig suspected of Nipah virus infection. The virus was revealed as a spherical enveloped RNA virus with a diameter of 79 nm. For identification of Oya virus, RT-PCR was performed. A common primer set for S-RNA of the Simbu serogroup of the genus Bunyavirus was able to amplify a cDNA from Oya virus RNA. The sequence data of the product revealed that the partial gene of Oya virus S-RNA segment had 65-70% homology with published cDNA sequences of Simbu serogroup viruses. The phylogenetic analysis of the data showed that the Oya virus is grouped in Simbu serogroup, but is genetically distinct from the serogroup viruses that have been analyzed molecularly. Serological surveys revealed that the virus distributed widely and densely in Malaysia.

Animals↗
PubMed2002

Antipruritic and antinociceptive effects of Chenopodium album L in mice.

The ethanolic extract from the fruits of Chenopodium album L. (FCAL), orally administered at doses of 100-400 mg/kg, dose-dependently inhibited scratching behavior induced by 5-HT (10 micro g per mouse, s.c.) or compound 48/80 (50 micro g per mouse, s.c.) in mice. But it failed to affect hind paw swelling induced by 5-HT or compound 48/80 in mice at doses of 100 and 200 mg/kg and only showed a relatively weak inhibition on the swelling at a higher dose of 400 mg/kg. In addition, FCAL (200 and 400 mg/kg) significantly attenuated the writhing responses induced by an intraperitoneal injection of acetic acid and the inflammatory pain response induced by an intraplantar injection of formalin in mice. At a dose of 400 mg/kg, it also inhibited the neurogenic pain response of formalin test. In conclusion, FCAL possesses antipruritic and antinociceptive activities and the antinociceptive effects are not secondary to anti-inflammatory effects. The findings support evidence for the clinical use of FCAL to treat cutaneous pruritus.

Analgesics↗
PubMed2002

Decreased MMP-9 activity in the serum of patients with diffuse cutaneous systemic sclerosis.

Matrix metalloproteinase-9 (MMP-9) and its inhibitor, tissue inhibitors of metalloproteinases-1 (TIMP-1) are involved in tissue inflammation and fibrotic processes. We previously reported an elevated serum TIMP-1 level in patients with systemic sclerosis (SSc). We measured serum TIMP-1 and active MMP-9 levels in 62 patients with SSc, 10 patients with rheumatoid arthritis (RA) and 15 normal controls using a modified enzyme-linked immunosorbent assay. The active MMP-9 level in the serum of the patients with RA or SSc was not significantly different from that of controls. Serum MMP-9 activity in patients with diffuse cutaneous SSc was significantly decreased compared with that of limited cutaneous SSc or normal controls. The MMP-9 activity and modified-Rodnan total skin thickness score in patients with SSc were negatively correlated. Serum MMP-9 activity and TIMP-1 level in patients with SSc were not correlated. Serum MMP-9 activity might be a useful indicator of disease activity, especially skin severity, in SSc patients.

Adolescent↗
PubMed2002

Articular cartilage degradation and de-differentiation of chondrocytes by the systemic administration of retinyl acetate-ectopic production of osteoblast stimulating factor-1 by chondrocytes in mice.

OBJECTIVE: Vitamin A derivatives are widely used therapeutic agents for the treatment of dermatological and rheumatological disorders. Long-standing administration of these drugs, in turn, causes skeletal changes including ossification of ligaments, premature fusion of epiphyses and abnormalities of modeling. Recent in vitro experiments have further suggested that retinoid treatment of cultured chondrocytes may cause apoptotic cell death. The present study aims to address detailed cartilage changes associated with in vivo administration of vitamin A derivatives. METHODS: Retinyl acetate was administrated to experimental mice, C3H-Heston, for more than 12 months. Modified morphometry on the articular cartilage and fluorescent labeling of the subchondral bone were carried out to address the changes in the articular cartilage and subchondral bone. In order to address the detailed chondrocytes phenotypes, electron microscopy was carried out. Since findings of these studies suggested that biological properties of the cartilage matrix might be altered, the present study also immunolocalized functional matrix molecules, type I collagen and osteoblast-stimulating factor-1 (OSF-1). RESULTS: Histomorphometry demonstrated that retinoid administration lead to progressive atrophy of the articular cartilage with concomitant proliferation of subchondral bone. Furthermore, detailed light and electron microscopy suggested that the subchondral bone proliferates into the degenerating cartilage. The affected articular cartilage also resembled that of osteoarthritis in terms of ectopic type I collagen production. Furthermore, the affected articular cartilage produced a developmentally regulated matrix molecule, osteoblast-stimulating factor-1 (OSF-1) that is normally expressed in both the fetal cartilage and the epiphyseal growth plate cartilage but not in the articular cartilage. CONCLUSION: The present results indicate that the systemic retinoid administration may alter the biological properties of the articular cartilage.

Adjuvants, Immunologic↗
PubMed2002

Clinical significance of serum surfactant protein D (SP-D) in patients with polymyositis/dermatomyositis: correlation with interstitial lung disease.

OBJECTIVE: To determine the clinical significance of serum surfactant protein D (SP-D) levels in patients with polymyositis/dermatomyositis (PM/DM). METHODS: Serum SP-D levels were assayed using a sensitive enzyme-linked immunosorbent assay in 59 patients with PM/DM and in 29 healthy controls. RESULTS: The serum level of SP-D was significantly higher in patients with PM/DM than in healthy controls (mean+/-S.D. 61.7+/-122.6 vs 31.0+/-12.4 ng/ml, P < 0.01). The serum SP-D level in patients with interstitial lung disease (ILD) was significantly higher than in those without ILD (118.7+/-220.2 vs 38.7+/-21.0 ng/ml, P < 0.001). Serum level of SP-D was correlated with the presence of ILD. The incidences of decreased vital capacity (%VC) and of decreased diffusing capacity of carbon monoxidase (%DLCO) were also significantly greater in patients with an elevated SP-D level than in those with a normal level (64 vs 7%, P < 0.02; 73 vs 27%, P < 0.01). Moreover, the serum SP-D level was inversely correlated with %VC (r=-0.452, P < 0.01) and %DLCO (r=-0.349, P < 0.05). CONCLUSION: The serum SP-D level may be a useful marker for ILD in patients with PM/DM.

Adult↗
PubMed2002

Anti-U5 snRNP antibody as a possible serological marker for scleroderma-polymyositis overlap.

OBJECTIVE: To determine the prevalence of the anti-U5 small nuclear ribonucleoprotein (snRNP) antibody in patients with systemic sclerosis. METHODS: Sera from 281 patients with systemic sclerosis, including 10 patients with overlapping polymyositis, were assayed using RNA immunoprecipitation and protein immunoprecipitation. RESULTS: Only one serum sample showed precipitation of U5 snRNA with scarce precipitation of U2, U1, U4 and U6 snRNAs. In addition, the serum precipitated a 200 kDa protein. The serum was from a 35-yr-old Japanese male patient with overlapping systemic sclerosis and polymyositis accompanied by large-cell lung carcinoma. The clinical appearance was similar to that of a case reported previously. CONCLUSION: The presence of the anti-U5 snRNP antibody in serum may be specific for scleroderma-polymyositis overlap syndrome.

Adult↗
PubMed2002

Dermatitis herpetiformis in Japan: an update.

BACKGROUND: Although dermatitis herpetiformis (DH) is a relatively common disease in Caucasian populations, it is rare in Asian populations including the Japanese. We encountered a Japanese case of DH which showed granular IgA and C3 deposits in the papillary dermis and which was associated with gluten-sensitive enteropathy but no HLA-B8/DR3/DQ2. OBJECTIVE: The purpose of this study is to describe the characteristics of Japanese DH cases, since most of them have been reported in Japanese language and dermatologists outside Japan are not familiar with the characteristics of Japanese DH. METHODS: We have reviewed all 34 Japanese DH cases reported previously. RESULTS: We found several features of Japanese DH compared with Caucasian DH, such as a high frequency of the fibrillar pattern, rarity of gluten-sensitive enteropathy and an absence of the HLA-B8/DR3/DQ2 haplotype. CONCLUSION: There might be significant differences in pathophysiology between Caucasian and Japanese DH cases.

Biopsy, Needle↗
PubMed2001

A mutant form of JAB/SOCS1 augments the cytokine-induced JAK/STAT pathway by accelerating degradation of wild-type JAB/CIS family proteins through the SOCS-box.

Cytokines exert biological functions by activating Janus tyrosine kinases (JAKs), and JAK inhibitors JAB (also referred to as SOCS1 and SSI1) and CIS3 (SOCS3) play an essential role in the negative regulation of cytokine signaling. We have found that transgenic (Tg) mice expressing a mutant JAB (F59D-JAB) exhibited a more potent STAT3 activation and a more severe colitis than did wild-type littermates after treatment with dextran sulfate sodium. We now find that there is a prolonged activation of JAKs and STATs in response to a number of cytokines in T cells from Tg mice with lck promoter-driven F59D-JAB. Overexpression of F59D-JAB also sustained activation of JAK2 in Ba/F3 cells. These data suggested that F59D-JAB up-regulated STAT activity by sustaining JAK activation. To elucidate molecular mechanisms related to F59D-JAB, we analyzed the effects of F59D-JAB on the JAK/STAT pathway using the 293 cell transient expression system. We found that the C-terminal SOCS-box played an essential role in augmenting cytokine signaling by F59D-JAB. The SOCS-box interacted with the Elongin BC complex, and this interaction stabilized JAB. F59D-JAB induced destabilization of wild-type JAB, whereas overexpression of Elongin BC canceled this effect. Levels of endogenous JAB and CIS3 in T cells from F59D-JAB Tg-mouse were lower than in wild-type mice. We propose that F59D-JAB destabilizes wild-type, endogenous JAB and CIS3 by chelating the Elongin BC complex, thereby sustaining JAK activation.

Base Sequence↗
PubMed2001

Absolute stereostructures of novel norcadinane- and trinoreudesmane-type sesquiterpenes with nitric oxide production inhibitory activity from Alpinia oxyphylla.

Novel 14-norcadinane-type sesquiterpenes, oxyphyllenodiols A and B, and 11,12,13-trinoreudesmane-type sesquiterpenes, oxyphyllenones A and B, were isolated from the methanolic extract of kernels of Alpinia oxyphylla. The absolute stereostructures of these norsesquiterpenes were determined on the basis of physicochemical and chemical evidence. In addition, oxyphyllenodiol A and oxyphyllenone A were found to inhibit the NO production in lipopolysaccharide-activated macrophages.

Animals↗
PubMed2001

CIS3/SOCS3/SSI3 plays a negative regulatory role in STAT3 activation and intestinal inflammation.

Immune and inflammatory systems are controlled by multiple cytokines, including interleukins (ILs) and interferons. These cytokines exert their biological functions through Janus tyrosine kinases and signal transducer and activator of transcription (STAT) transcription factors. We recently identified two intrinsic Janus kinase (JAK) inhibitors, JAK binding protein (JAB; also referred to as suppressor of cytokine signaling [SOCS1]/STAT-induced STAT inhibitor [SSI1]) and cytokine-inducible SH2 protein (CIS)3 (or SOCS3/SSI3), which play an essential role in the negative regulation of cytokine signaling. We have investigated the role of STATs and these JAK inhibitors in intestinal inflammation. Among STAT family members, STAT3 was most strongly tyrosine phosphorylated in human ulcerative colitis and Crohn's disease patients as well as in dextran sulfate sodium (DSS)-induced colitis in mice. Development of colitis as well as STAT3 activation was significantly reduced in IL-6-deficient mice treated with DSS, suggesting that STAT3 plays an important role in the perpetuation of colitis. CIS3, but not JAB, was highly expressed in the colon of DSS-treated mice as well as several T cell-dependent colitis models. To define the physiological role of CIS3 induction in colitis, we developed a JAB mutant (F59D-JAB) that overcame the inhibitory effect of both JAB and CIS3 and created transgenic mice. DSS induced stronger STAT3 activation and more severe colitis in F59D-JAB transgenic mice than in their wild-type littermates. These data suggest that hyperactivation of STAT3 results in severe colitis and that CIS3 plays a negative regulatory role in intestinal inflammation by downregulating STAT3 activity.

Animals↗
PubMed2001

IL-4-mediated development of TGF-beta1-producing cells from naïve CD4(+) T cells through a STAT6-independent mechanism.

Transforming growth factor-beta1 (TGF-beta1) is an inhibitory cytokine increasingly recognized as a key factor for immuno-regulation. The function of IL-4 in the regulation of TGF-beta1 production from T cells has been reported previously; however, the precise molecular mechanism still remains to be elucidated. For a better understanding of the mechanism involved in regulation, we have investigated a relationship between the STAT6-dependent pathway and TGF-beta1 production from naïve T cells. TCR crosslinking initiates TGF-beta1 production in CD4(+) T cells, and IL-4-mediated signaling enhances the TGF-beta1 production from naïve CD4(+) T cells. The IL-4-mediated up-regulation of TGF-beta1 production from naïve CD4(+) T cells is elicited in STAT6-deficient (STAT6 KO) mice, but not in IL-4 receptor-deficient (IL-4R KO) mice. These results clearly demonstrate that a STAT6-independent pathway is working in IL-4-mediated enhancement of TGF-beta1 production from naïve CD4(+) T cells. Moreover, the addition of IL-4 showed no additive effect on TGF-beta1 promoter-mediated transcription stimulated by TCR. Therefore, we hypothesize that the IL-4-mediated signaling does not work directly on the transcription of the TGF-beta1 gene, but rather regulates the expansion of TGF-beta1-secreting T cells.

Animals↗