Direct Analysis of Ion-Induced Peptide Fragmentation in Secondary-Ion Mass Spectrometry.

Primary-ion-induced fragmentation in organic molecules can strongly influence the results in secondary-ion mass spectrometry (SIMS) of organic and biomolecular samples. In order to characterize this ion-induced fragmentation, oligopeptide samples irradiated in SIMS experiments were investigated by means of desorption/ionization induced by neutral SO2 clusters (DINeC). The latter is a nondestructive desorption method for mass spectrometry of biomolecules, which gives direct access to the fragments induced in the sample. Comparison of TOF-SIMS and DINeC mass spectra revealed qualitative differences between the fragments, which remain in the sample and the fragments sputtered during ion bombardment. The fragmentation strength and its spatial distribution were found to be quantitatively different for Bi1+, Bi3+, and Ar1000+ primary ions, leading to different distributions of the degree of fragmentation in the samples as directly measured by means of DINeC depth profiles.

MMP13 can be a useful differentiating marker between squamous cell carcinoma and benign hyperkeratotic lesions in recessive dystrophic epidermolysis bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe hereditary mechanobullous disease resulting from mutations in the COL7A1 gene, coding for type VII collagen. Patients with RDEB tend to develop squamous cell carcinomas (SCCs) at sites of chronic ulceration or scarring on the whole body. Distinguishing SCC from benign hyperkeratotic lesions is often difficult, not only clinically but also histologically in patients with RDEB. We investigated several matrix metallopeptidase (MMP) subtypes by comparing the DNA amplification microarray findings between evident SCCs and benign hyperkeratotic lesions in the same patient with RDEB. We report that MMP13 was found to be strongly positive in SCCs but negative in benign hyperkeratotic lesions. We found that there is an evident difference in the transitional area between SCCs and benign hyperkeratotic lesions. We propose that MMP13 may be a useful differentiating marker between SCC and benign hyperkeratotic lesions in RDEB.

Lessons from 28 cases of reconstruction by lenticular island pedicle flap at a single institution.

BACKGROUND: Lenticular island pedicle flap (LIPF) has been reported to be one of the most useful techniques for reconstructing middle cheek skin defects. LIPF may have been used all over the world on a daily basis; however, no reports have examined a large number of LIPF cases at a single institution. MATERIALS AND METHODS: A total of 28 cases of reconstruction by LIPF at the Hokkaido University Hospital from 2005 to 2013 were analysed. We examined the tumour type, location, area of defect and presence/absence of antithrombotic treatment and complications, including transient circulatory impairment, damage to facial nerves and eyelid ectropion. RESULTS: We found that nine patients had transiently impaired circulation. This complication was statistically more frequent in the patients without antithrombotic treatment than in the patients with antithrombotic treatment (0/8 vs. 10/20, P = 0.0292; Fisher's exact test). CONCLUSION: We revelled that LIPF have been safely performed even under antithrombotic treatment, so, when patients are taking antithrombotic agents, we should choose LIPF rather than conventional flap including cheek flap, island pedicle flap and so on.

MUC5AC expression correlates with invasiveness and progression of extramammary Paget's disease.

BACKGROUND: Patients with in situ extramammary Paget's disease (EMPD) tend to have a good prognosis, although dermal invasion and metastasis are associated with significantly increased morbidity and mortality. Previous studies have addressed mechanisms underlying the EMPD pathogenesis; however, no molecular markers that reflect invasiveness or progression have been established. OBJECTIVE: This study aims to identify a reliable marker for predicting the risk of invasion and metastasis in EMPD. METHODS: We performed an initial microarray screening for in situ, invasive or metastatic lymph node lesions of EMPD. We analysed 44 specimens from 38 primary EMPD cases by immunohistochemical staining. RESULTS: We found that expressions of MUC5AC directly correlate with invasion and prognosis. Labelling rates of tumour cells were scored by staining intensity on a four-tiered scale (- to 3+) to investigate the correlation between the expression score of these molecular markers and the type of EMPD lesion. All the specimens scored positive (3+) for MUC1 and negative (-) for MUC6. MUC5AC expression was detected in 19 of 44 (43.2%) specimens. Invasive lesions and metastatic lymph nodes tended to express MUC5AC significantly higher than in situ lesions (P < 0.01). MUC2 was positive in 10 specimens (22.7%). There was no significant difference between the degree of MUC2 expression and invasiveness. CONCLUSION: The degree of MUC5AC expression may correlate with the invasiveness and progression of EMPD, and may be a useful marker for identifying high-risk EMPD cases.

A novel splice site mutation in NCSTN underlies a Japanese family with hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic follicular occlusive disease with characteristic recurrent draining sinuses, skin abscesses and disfiguring scars, mainly involving the axilla, groin, perianal and perineal regions. While most HS cases are nonfamilial, familial cases showing autosomal dominant inheritance have been reported. Recently, loss-of-function mutations in the genes encoding γ-secretase have been identified as a cause of familial HS in the Chinese and British populations. OBJECTIVES: To identify mutations in the genes encoding γ-secretase in Japanese patients with familial and nonfamilial HS. METHODS: Two affected and three unaffected individuals from a Japanese family with familial HS and nine patients with nonfamilial HS were recruited. We conducted mutation analysis of the γ-secretase genes in Japanese patients with familial and nonfamilial HS. RESULTS: A novel splice site mutation in the nicastrin gene NCSTN, one of the six key component genes encoding γ-secretase, was identified in the patients with familial HS. Neither unaffected individuals in the family nor 100 ethnically matched control alleles carry this mutation. None of the nine patients with nonfamilial HS carry nonsense, frameshift or splice site mutations in this gene. CONCLUSIONS: A novel splice site mutation, c.582+1delG, in NCSTN was identified in the familial patients with HS. We also reveal for the first time that a γ-secretase gene mutation is not linked to the development of nonfamilial HS. These results would further pave the way to a better understanding of the contribution of γ-secretase and other genes to the pathogenesis of HS and to the development of a new therapeutic strategy for HS.

[Long-term results of aortic root replacement with a composite graft].

We analyzed the long-term results of aortic root replacement with a composite graft. Since 1992, 127 patients had undergone aortic root replacement with a composite graft. There were 92 men and 35 women with a mean age of 56.5 years. There were 69 patients with annuloaortic ectasia, 17 aortic dissections, and 41 ascending aortic dilatation due to aortic valve disease. Marfan syndrome was diagnosed in 19 patients. As surgical procedure, button technique was used in 90 patients, Cabrol technique in 11, and Piehler technique in 26. Open distal anastomosis was performed in 82 patients to avoid clamp injury of rest aorta. Early mortality was 3.1% and no major morbid events had occurred. Follow-up was completed in 95.9% of the patients and the mean follow-up period was 6.1 years. Actuarial survival at 5, 10, and 15 years was 86.2%, 83.4%, and 83.4%, respectively. Actuarial freedom from aortic valve reoperation at 10 and 15 years was 99.2% and 95.7%, respectively. The results of aortic root replacement with a composite graft were excellent. This procedure should be the 1st choice for surgical treatment of the aortic root disease.

Usefulness of real-time tissue elastography for detecting lymph-node metastases in squamous cell carcinoma.

We report a case of invasive SCC arising from multiple lesions of Bowen's disease with right inguinal lymph-node metastasis. Assessment of superficial lymph-node involvement by real-time tissue elastography before surgery was found to be more useful than other noninvasive conventional methods. Histologically, the metastatic tumour cells were located asymmetrically in a small section of the cortical area of the right node, and this result was comparable with the elastographic findings. Additionally, we found that the presence of an asymmetrical cortical area with high elasticity should be included in the determination of metastatic involvement in small lymph nodes. It has high predictive values in the differentiation of benign and malignant superficial lymph nodes in patients with clinically node-negative skin cancer. More cases are needed to validate this efficiency in differentiating benign from malignant lymph-node status, but if confirmed, it may have an important role in the diagnosis of high-risk cutaneous squamous cell carcinoma.

A severe and refractory case of anti-p200 pemphigoid resulting in multiple skin ulcers and scar formation.

Anti-p200 pemphigoid is a recently described autoimmune blistering skin disease that is characterized by the presence of autoantibodies against an unidentified 200-kDa dermal autoantigen. Most of the previous cases have been successfully treated using mild-to-moderate immunosuppressive therapies, which resulted in a good prognosis. We report here a severe and refractory case of anti-p200 pemphigoid that developed in a 53-year-old woman, in which blisters led to multiple skin ulcers, followed by severe scar formation. In the present case, methylprednisolone pulse therapy was effective enough to reduce the disease activity.

Usefulness of thermography techniques for evaluating the disease activity in Kimura's disease.

Kimura's disease (KD) is a rare, chronic inflammatory disorder predominantly affecting the head and neck. A case of KD in a 30-year-old man is reported. Thermography was useful for evaluating the activity of the condition.

Extensive proliferative nodules in a case of giant congenital naevus.

The rare presence of proliferative nodules in cases of giant congenital naevus can, in some cases, be potentially misdiagnosed as neonatal melanoma. We report here a case of multiple, proliferative nodules found in a giant congenital naevus lesion in a female neonatal patient diagnosed with neurocutaneous melanosis. Our initial clinical observations of this case suggested the possibility of primary cutaneous neonatal melanoma or skin metastasis from a melanoma in the meninges or elsewhere in the central nervous system. However, histological examination revealed no sign of melanoma, abnormal mitosis, necrosis or any malignant change. Pagetoid arrays of naevus cells in the junctional zone and myxoid changes present in a significant portion of the dermis led to the diagnosis of proliferative nodules. Distinct histological patterns seen in the proliferative nodules in our neonatal patient were useful to differentiate between benign pigmented nodular lesions in a giant congenital naevus and malignant melanoma, and reduced the chance of misdiagnosis.