Kochi University Repository

高橋, 克己

「外来(テュラーテン)叡智(・ヌース)」（νοῦς θύραθεν）：intellectus extrinsecus

小松, 利広

宇高, 惠子

腫瘍特異的ヘルパーＴ細胞の腫瘍内浸潤機構における血管内皮細胞の役割の解明

難波, 利治

谷口, 睦男

村田, 芳博

奥谷, 文乃

椛, 秀人

バゾプレッシンによる副嗅球シナプス可塑性の誘導

Kimiko, Nakajima

Mika, Terao

Ichiro, Katayama

Junji, Takeda

Shigetoshi, Sano

? ?? ?
26.Primary ceramide deficiency in keratinocytes leads to gene alterations linked to dermatitis 
Kimiko Nakajima1), Mika Terao2), Ichiro Katayama2), Junji Takeda3), Shigetoshi Sano1) 
1) Department of Dermatology, Kochi Medical School, 
2) Department of Dermatology, Osaka University Graduate School Medicine, 
3) Department of Social and Enviromental Medicine, Osaka University Graduate School Medicine 
Impaired skin barrier is associated with inflammatory skin disorders including atopic dermatitis (AD). We have 
studied the role of epidermal ceramide by using keratinocytes-specific Sptlc deficient mice (K5.SPT-KO mice), 
which lack serine palmytoltransferase (SPT), a rate-limiting enzyme for ceramide biosynthesis. K5.SPT-KO mice 
exhibited barrier disruption from two weeks of age and developed skin lesions with hyperkeratosis, epidermal 
hyperplasia, and dermal infiltration. To examine whether ceramide deficiency itself affected gene expression 
within keratinocytes, we performed an array analysis on primary cultured keratinocytes of newborn K5.SPT-KO 
mice. Transcriptional profiling revealed that increased expression of thymic stromal lymphopoietin (TSLP, 
ration=4.2), amphiregulin (Areg, 3.2), and aqaporin 3 (AQP3, 3.0). Interestingly, these three molecules are 
associated with the pathogenesis of AD. Since no skin lesion expect for skin dehydration was found in newborn 
KO mice, the up-regulation of these genes in keratinocytes was primary consequences of constitutive ceramide 
deficiency. AQP3, AR and TSLP were increased in the lesional skin of K5.SPT KO mice. Langerhans cells (LCs) 
in the epidermis of K5.SPT KO mice appeared mature and increased numbers of langerin+dendritic cells were 
found in the skin-draining lymph nodes of K5.SPT KO mice. This may be consistent with recent notion that local 
increase of TSLP was directly associated with LC activation. Strikingly, acute barrier disruption by tape stripping 
led to up-regulation of AQP3, AR and TSLP as well as activation of LCs in hairless mice. We suggested that 
primary ceramide deficiency in keratinocytes and barrier disruption resulted in increased expression of AQP3, 
AR, and TSLP, which may contribute to development of atopic dermatitis.   


Primary ceramide deficiency in keratinocytes leads to gene alterations linked to dermatitis

Hideki, Nakajima

Masahito, Tarutani

Ryuji, Morishige

? ?? ?
35.Relationship between Th17 cytokines and adipokines in psoriasis patients 
Hideki Nakajima1) , Kimiko Nakajima1), Masahito Tarutani1), Ryuji Morishige2), Shigetoshi Sano1) 
1) Department of Dermatology, Kochi Medical School 
2) Janssen Pharmaceutical K.K 
 Psoriasis is associated with an increase of Th17 cytokines which are produced by Th17 cells. It is well 
recognized that metabolic syndrome (MS) is prevalent in psoriasis patients, and adipose tissue-related cytokines 
(adipokines) contribute substantially to the pathogenesis of MS and psoriasis. We investigated the statistics of 
various circulating Th17-related cytokines and adipokines in psoriasis patients (n=30) and control subjects (n=30). 
Furthermore, we analyzed the relationship between those cytokines to understand their interaction in psoriasis 
and MS. Our study identified the significant elevation of serum IL-6, IL-21, IL-22, and resistin levels in psoriasis 
patients. Increased serum levels of IL-22 and adiponectin were positively correlated with Psoriasis Area and 
Severity Index (PASI). In contrast, serum high molecular weight (HMW) adiponectin levels were decreased in 
psoriasis and negatively correlated with PASI. The biological effects of adiponectin in psoriasis could be 
dissected on its molecular weight. Our results revealed that there was a strong positive association between 
adiponectin and IL-22 in psoriasis patients. A significant positive relationship was also found between resistin and 
TNF-. Retinol-binding protein-4 (RBP-4) was negatively correlated with IL-6, IL-22 and TNF- in psoriasis. 
Serum levels of adiponectin, resistin and RBP-4 closely correlated with inflammatory cytokines. Th17 cytokines 
and adipokines may represent a novel link between psoriasis and metabolic signals. 


Relationship between Th17 cytokines and adipokines in psoriasis patients

青木, 早苗

山脇, 京子

藤田, 倫子

乳がん治療経験者の性生活に対する戸惑い

Sabah A.,  Bhatti

Ryoji, Hirota

Narufumi, Suganuma

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55.Validation of Protein Microarray for Diagnosis of  Mesothelin in asbestos exposed workers 
Sabah A. Bhatti1), Ryoji Hirota1), Narufumi Suganuma1)
1)Environmental Medicine, Kochi Medical School. 
Background
Mesothelin is a tumor differentiation antigen that is normally present on the mesothelial cell lining the pleura, 
peritoneum and pericardium. Mesothelin is over expressed in several cancers; the protein could be exploited as 
tumor marker. Identification of tumor markers for mesothelioma might prove useful diagnosis as well as for 
monitoring tumor in response to therapy and for screening at high risk individuals.  
Objective
In the present research study we aimed to measure N-ERC mesothelin by protein microarray.  
Methods 
After the initial development and validation of protein array, the plasma samples were collected from asbestos 
exposed workers. The samples were printed onto nitrocellulose membrane glass plate using micro caster arrayer 
system and incubated at 37oC for overnight. After incubation, samples were blocked with protein array blocking 
buffer and incubate at 25 oC for 2 hours with gentle agitation insuring that mixing occurred. The plates were 
placed into zip-lock bags to avoid evaporation. Each slide was washed five times with washing buffer in the 
chamber with gentle agitation, incubated for five minutes, and completely dried with nitrogen gas. HRP 
conjugated antibody was applied on dried slides and incubated for 2 hours at 25 oC .The slides were washed again 
five times and dried completely with nitrogen gas. Finally, substrate solution was applied on each slide and 
signals were detected with CCD camera. The protocols and procedure were kept constant in each case. 
Results 
The results showed that a high correlation exist between concentration and intensity. The graph shows correlation 
between different concentrations of mesothelin plasma samples and the intensity of signals and figure shows the 
spots of plasma samples. 
y = 3E+06x + 911625
R2 = 0.97
0 0.5 1 1.5
0
1000000
500000
1500000
2000000
2500000
3000000
3500000
4000000
4500000
Concentration (ng/ml)
In
te
ns
ity


Validation of Protein Microarray for Diagnosis of Mesothelin in asbestos exposed workers

Nalandu,  Roger Ngatu

Maiko K., Okajima

? ?? ?
56.Identification of Bioactive Compounds from Vernonia amygdalina leaf and their Anti-allergic activity in 
patients with atopic/eczema dermatitis 
Nlandu Roger Ngatu1), Maiko K. Okajima2) , Ryoji Hirota1) , Narufumi Suganuma1)
1)Department of Environmental Medicine, Kochi Medical School, 
2)Department of Materials Science, Japan Advanced Institute of Science and Technology. 
Objectives
Atopic dermatitis (AD), a relapsing skin disorder characterized by severe itching and impair- ment of quality of 
life, affects 10–20% of children and 3-5% of adults worldwide. Vernonia amygdalina (VAM) is a plant which leaf 
extracts have antioxidant, antitumor activities in experimental studies. We previously demonstrated that VAM 
extracts display anti-inflammatory effects in animal model of atopic dermatitis. The present study aimed to 
analyze the main chemical compounds from the leaf extracts and their anti-allergic effects in patients with AD 
and allergic contact dermatitis (ACD). 
Methods
HPLC analysis of the aqueous (VAM1) and alcoholic (VAM2) extracts was performed in order to identify their 
main components. Gas chromatography mass spectrometry (GC-MS) showed lipid contents of each extract. A 
clinical trial was conducted that included 63 students suffering from mild to moderate AD or ACD. They were 
randomly assigned one of the following treatments: VAM1, VAM2, dexamethasone (steroid) or vaseline. The 
severity of the disease was evaluated using the “eczema area severity index” (EASI) scoring system. The 
evaluation of skin symptoms and signs was performed once a week for a total of four weeks. Hematological, 
immunological assays and markers of hepatic function (ALT, ASAT) assays were performed in representative 
patients. Signed informed consent were obtained from patients’ parents. 
Results 
HPLC analysis showed that VAM1 mainly contains polyphenols (flavonoids), alkaloids and saponins; while 
VAM2 comprised terpenes and carotenoids. In addition, GC-MS analysis revealed that this species of VAM has 
different chemical composition as compared with the plant from the western and southern regions of Africa. 
VAM 1 mainly contains various inositols (87%); however, for VAM2, aliphatic acids such (as hexadecanoic acid, 
octadecanoic acid) represent 61%. Regarding anti-inflammatory compounds, the most active isolated terpene 
from the plant is vernodalin and, on the other side, the most active flavonoid is dicaffeoyl- quinic acid. Regarding 
the clinical trial, dexamethasone, VAM1 and VAM2 displayed a good anti-itch effect as compared with Vaseline 
(p<0.001, t test). In addition, the anti-itch effect of VAM2 was greater than that of dexamethasone (p<0.05). A 
marked improvement of EASI score was observed in dexamethasone, VAM1 and VAM2-treated patients (vs. 
Vaseline; p<0.001 by t test), with dexamethasone having a slightly higher proportion of patients clinically cured 
within five weeks of treatment (82%), followed by VAM2 (79%) and VAM1 (76%). 
Conclusion
This is the very first conducted clinical study on VAM, which displayed an anti-allergic activity similar to that of 
dexamethasone; this suggests that VAM may possibly serve as alternative therapeutic agent for atopic/eczema 
dermatitis syndrome. Detailed results will be discussed during the research meeting. 


Identification of Bioactive Compounds from Vernonia amygdalina leaf and their Anti-allergic activity in patients with atopic/eczema dermatitis

卯城, 光

加藤, 元海

耕作放棄地における生後１年未満のヤギの放牧と除草効果

岡, 拓矢

ヒトにおける体重と体組成の変動パターンおよび体脂肪率に変化を与える要因

Kōchi University

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