Clinical comparison of human and canine atopic dermatitis using human diagnostic criteria (Japanese Dermatological Association, 2009): proposal of provisional diagnostic criteria for canine atopic dermatitis

Atopic dermatitis (AD) is a common skin disease encountered in both humans and dogs. Canine AD can be used in the analysis of naturally occurring AD; however, details of clinical comparison have been lacking. The purpose of this study is to compare those clinical features using the human diagnostic criteria (Japanese Dermatological Association, 2009). Fifty-one dogs with canine AD were evaluated by the human criteria. Prior to this study, canine AD was basically diagnosed by the fulfillment of two authentic canine AD criteria and a positive reaction against Dermatophagoides farinae in serum immunoglobulin E levels and/or in intradermal tests. Among the human AD criteria items, behavior corresponding to pruritus was observed in all 51 dogs. Skin lesions corresponding to eczematous dermatitis were seen in 50 dogs, and symmetrical distribution of skin lesions was noted in all 51 dogs. A chronic or chronically relapsing course was observed in 50 dogs. Based on these results, the concordance rate for the criteria was 96% (49/51). Differential diagnoses of AD were also investigated in the same manner. The concordance rate for the criteria was 0% (0/69) in scabies, 2% (1/50) in pyoderma, 0% (0/50) in demodicosis, 0% (0/9) in cutaneous lymphoma, 0% (0/2) in ichthyosis, 25% (2/7) in flea allergy, 48% (24/50) in seborrheic dermatitis and 75% (3/4) in food allergy. Canine AD is thus indicated as a valuable counterpart to human AD in clinical aspects. In addition, the human AD criteria could be applicable, with some modification, as provisional diagnostic criteria for canine AD.     

Prevalence of dermatological disorders in Japan: a nationwide, cross-sectional, seasonal, multicenter, hospital-based study

To clarify the prevalence of skin disorders among dermatology patients in Japan, a nationwide, cross-sectional, seasonal, multicenter study was conducted in 69 university hospitals, 45 district-based pivotal hospitals, and 56 private clinics (170 clinics in total). In each clinic, information was collected on the diagnosis, age, and gender of all outpatients and inpatients who visited the clinic on any one day of the second week in each of May, August, and November 2007 and February 2008. Among 67,448 cases, the top twenty skin disorders were, in descending order of incidence, miscellaneous eczema, atopic dermatitis, tinea pedis, urticaria/angioedema, tinea unguium, viral warts, psoriasis, contact dermatitis, acne, seborrheic dermatitis, hand eczema, miscellaneous benign skin tumors, alopecia areata, herpes zoster/postherpetic neuralgia, skin ulcers (nondiabetic), prurigo, epidermal cysts, vitiligo vulgaris, seborrheic keratosis, and drug eruption/toxicoderma. Atopic dermatitis, impetigo, molluscum, warts, acne, and miscellaneous eczema shared their top-ranking position in the pediatric population, whereas the most common disorders among the geriatric population were tinea pedis, tinea unguium, psoriasis, seborrheic dermatitis, and miscellaneous eczema. For some disorders, such as atopic dermatitis, contact dermatitis, urticaria/angioedema, prurigo, insect bites, and tinea pedis, the number of patients correlated with the average high and low monthly temperatures. Males showed a greater susceptibility to some diseases (psoriasis, erythroderma, diabetic dermatoses, inter alia), whereas females were more susceptible to others (erythema nodosum, collagen diseases, livedo reticularis/racemosa, hand eczema, inter alia). In conclusion, this hospital-based study highlights the present situation regarding dermatological patients in the early 21st century in Japan.     

Beneficial effect of a diet containing heat-killed Lactobacillus paracasei K71 on adult type atopic dermatitis

The purpose of this study was to investigate the clinical effect of a supplementary diet containing heat-killed lactic acid bacterium Lactobacillus paracasei K71 (LAB diet) on adult patients with atopic dermatitis (AD). A randomized, double-blind, placebo-controlled study was conducted in 34 adult type AD subjects who were treated with conventional topical corticosteroid and tacrolimus. LAB diet or placebo was added over 12 weeks. The primary end-point was the clinical severity of AD which was evaluated by a severity scoring system proposed by the guideline of the Japanese Dermatological Association. The effect was also secondarily evaluated by itch scores of visual analog scales (VAS), quality-of-life (QOL) impairment scores of Skindex 16 and consumption amounts of topical therapeutics. Data on these four assessment variables were collected at baseline and at week 4, 8 and 12. Within the study population, the skin severity scores were significantly decreased from baseline at week 8 (P<0.05) and at week 12 (P<0.01) in the LAB diet group but not in the placebo group. Influence of LAB diet on itch scores or QOL impairment scores was not evident. The consumption of topical therapeutics in the placebo group was 1.9-times greater in total amount compared with the corresponding value in the LAB diet group during the intervention period, although there was no significant difference. No LAB diet- or placebo-related adverse events were observed. We concluded that the LAB diet may have some benefits as a complementary therapy for adult AD patients who are managed with the conventional treatment.     

Clinical features and mutational survey of NPHS2 (podocin) in Japanese children with focal segmental glomerulosclerosis who underwent renal transplantation

Abstract:  Recurrent FSGS is a major challenge in the field of nephrology. To clarify the role of NPHS2 defects in the pathogenesis of FSGS recurrence, we sequenced all eight exons of NPHS2 in 11 Japanese pediatric FSGS patients with or without post-transplant recurrence. All patients had biopsy-proven primary FSGS, had no family history of renal diseases or consanguinity, were steroid-resistant, and received living-related renal transplantation. The mean age at onset was 5.0 ± 3.1 yr and mean age at renal transplantation was 10.4 ± 4.1 yr. Mutational analysis of NPHS2 was performed using polymerase chain reaction and direct sequencing. We found a synonymous T/C polymorphism at alanine 318 (GC C to GC T ) in seven of 11 patients but no other causative NPHS2 mutations. FSGS recurred immediately after transplant in seven patients, while the remaining four patients had no recurrence for 3.2–5.8 yr. There were no differences between recurrent and non-recurrent patients in the onset age and the interval from onset to ESRD. In conclusion, we detected no causative NPHS2 mutations in Japanese pediatric FSGS patients with or without post-transplant recurrence. Further studies on the involvement of other genes are required to better understand recurrent FSGS.     

Expression of milk fat globule epidermal growth factor-VIII may be an indicator of poor prognosis in malignant melanoma

Background Milk fat globule epidermal growth factor‐VIII (MFG‐E8) is a secreted protein that binds phosphatidylserine and promotes apoptotic cell ingestion by phagocytes, mediating the immune tolerance and maintenance of homeostasis. A recent study has shown that MFG‐E8 expression in human melanoma is increased with tumour progression; however, the effect of its expression on patient survival has not yet been clarified. Objective To analyse MFG‐E8 expression in melanoma, and to determine whether it can serve as a marker for diagnosis, tumour progression and/or prognosis. Methods MFG‐E8 expression was examined by immunohistochemistry in 60 primary melanomas, 22 metastatic lesions and 30 benign naevi. The following clinicopathological variables were evaluated: age, gender, histological type, tumour site, Breslow thickness, Clark’s level, the presence or absence of ulceration and tumour‐infiltrating lymphocytes, and survival periods. Statistical analyses were performed to assess associations and melanoma‐specific survival. Results MFG‐E8 expression was significantly higher in primary and metastatic melanoma than in naevus. Furthermore, it increased according to tumour progression and metastasis. Patients with MFG‐E8 expression in primary tumours had significantly shorter survival periods than those without MFG‐E8 expression. Univariate and multivariate analyses revealed that MFG‐E8 expression was a statistically significant and independent prognostic factor. Conclusion MFG‐E8 expression may serve as a tumour progression marker and can predict an unfavourable prognosis in patients with melanoma.     

Hematopoietic progenitor kinase 1, mitogen-activated protein/extracellular signal-related protein kinase kinase kinase 1, and phosphomitogen-activated protein kinase kinase 4 are overexpressed in extramammary Paget disease

The c-Jun amino-terminal kinase (JNK) pathway seems to play important roles in the pathogenesis of several tumors, but its significance in extramammary Paget disease (EMPD) has not been investigated yet. The purpose of the study was to investigate the potential contribution of the JNK-associated molecules, such as hematopoietic progenitor kinase 1 (HPK1), mitogen-activated protein/extracellular signal-related protein kinase kinase kinase1 (MEKK1), transforming growth factor-β activated kinase 1 (TAK1), and phosphomitogen-activated protein kinase kinase 4 (p-MKK4) to the development of EMPD. Thirty-five paraffin-embedded EMPD specimens were subjected to immunohistochemical staining for HPK1, MEKK1, TAK1, and p-MKK4. All the 35 EMPD, including 13 dermal invasive EMPD and 2 lymph node metastasis, showed cytoplasmic overexpression of HPK1, MEKK1, and p-MKK4. The expression (%positive cells) of HPK1, MEKK1, and p-MKK4 in EMPD (92.3% ± 8.6%, 92.9% ± 8.6%, and 92.7% ± 7.4%, respectively) were significantly higher than in normal eccrine sweat gland cells (51.6% ± 10.4%, 44.7% ± 11.7%, 0% ± 0%). In addition, the expression of HPK1-, MEKK1-, and p-MKK4 in invasive EMPD was significantly higher than in noninvasive EMPD. Meanwhile, the expression of TAK1 was basically low and no significantly different between EMPD and normal controls. In conclusion, these results indicate that JNK pathway may play a role in the pathogenesis of EMPD.     

Validation study of a health risk appraisal model and endoscopic screening for early esophageal cancer in men in specialized hospitals

Background

This study was designed to validate a health-risk appraisal (HRA) model for identifying Japanese men in specialized hospitals who were at high risk for esophageal cancer on the basis of their past and present facial flushing reactions after drinking alcohol, drinking and smoking status, and intake of vegetables and fruit.

Methods

We prospectively studied men 50 years or older with no history of head and neck cancer or esophageal cancer who presented at Kitasato University Hospital to undergo endoscopic examination from January 2011 to March 2013. The subjects responded to an HRA questionnaire before examination.

Results

Among the 164 patients enrolled, 157 were eligible for analysis. The median HRA score was 3 in patients aged 70–90 years and 6 in those aged 50 to 69 years. Early esophageal cancer was diagnosed on endoscopic examination in 3 subjects (1.9%, 3/157). Among 70 patients 70–90 years of age, 18 (25.7%, 18/70) had an HRA score of 7 or higher, and early esophageal cancer was detected in 2 (11.1%, 2/18) of these patients. Early esophageal cancer was not detected in 87 patients 50–69 years of age. Early esophageal cancer was detected in a 70-year-old patient with an HRA score of 2 who had no history of drinking alcohol or smoking.

Conclusions

Our results suggest that an HRA questionnaire is useful for identifying persons 70 years or older who are at high risk for alcohol-related esophageal cancer in specialized hospitals.

     

Relationships of alcohol dehydrogenase 1B (<Emphasis Type="Italic">ADH1B</Emphasis>) and aldehyde dehydrogenase 2 (<Emphasis Type="Italic">ALDH2</Emphasis>) genotypes with alcohol sensitivity,drinking behavior and problem drinking in Japanese older men

Objectives

Many East Asians have the genetic polymorphisms rs1229984 in alcohol dehydrogenase 1B (ADH1B) and rs671 in aldehyde dehydrogenase 2 (ALDH2). Here we analyzed the relationships of the two genotypes with alcohol sensitivity, drinking behavior and problem drinking among older and younger men living in rural areas of Japan.

Methods

The subjects were 718 Japanese men aged 63.3 ± 10.8 (mean ± SD), categorized into the older (≥65 years, n = 357) and younger (<65 years, n = 361) groups. Facial flushing frequency, drinking behavior and positive CAGE results were compared among the genotypes using Bonferroni-corrected χ² test and a multivariate logistic regression analysis adjusting for age, BMI and lifestyle factors.

Results

The frequency of ‘always’ facial flushing among the ADH1B*1/*2 carriers was significantly lower than that among the ADH1B*2/*2 carriers in the older group (P < 0.01). The alcohol consumption (unit/day) in the ADH1B*1/*2 carriers tended to be higher compared with that in the ADH1B*2/*2 carriers among the older group (P = 0.050). In the younger group, no significant differences in alcohol sensitivity and drinking habits were generally found among the ADH1B genotypes. The ADH1B*1/*1 genotype tended to be positively associated with problem drinking in the older group (P = 0.080) but not in the younger group. The ALDH2 genotypes consistently and strongly affected the alcohol sensitivity, drinking behavior and problem drinking in both the younger and older group.

Conclusions

We for the first time observed a significant difference in alcohol sensitivity between ADH1B*1/*2 and ADH1B*2/*2 in older men aged 65 and above.

     

内皮素受体B在黑素瘤中的表达及内皮素3对黑素瘤细胞A375的体外促生长效应

目的 研究内皮素受体B（ETR－B）在人恶性黑素瘤中的表达及内皮素3对黑素瘤细胞A375的体外促生长效应。方法 采用免疫组化SP法检测ETR－B在黑素瘤组织中的表达，用RT-PCR法检测ETR－B基因在人恶性黑素瘤细胞A375和SK－mel－1中的表达，用MTT比色法检测不同浓度内皮素3对黑素瘤细胞A375的体外促增殖活性。结果 ETR-B在41例恶性黑素瘤和23例色素痣中的阳性率分别为78.05%和8.69%，两组间差异有统计学意义，P < 0.05。15例原位和26例Ⅰ ~ Ⅳ期恶性黑素瘤ETR-B阳性表达率分别为53.33%和92.31%，两组比较，P < 0.05。13例转移性恶性黑素瘤（Ⅲ ~ Ⅳ期）中ETR-B阳性表达率100%，28例未转移者（0 ~ Ⅱ期）的阳性表达率为67.86%，两组比较，P < 0.05。ETR－B基因在人恶性黑素瘤细胞A375和SK－mel－1中均有表达；内皮素3对黑素瘤细胞A375在体外具有很强的促增殖作用，且促增殖能力呈内皮素3浓度依赖性。结论 内皮素3/ETR－B在促黑素瘤细胞生长中有重要作用