Yoshimitsu Miyahira

Immunosuppressive effect of prolactin‐induced protein: a new insight into its local and systemic role in chronic allergic contact dermatitis

Background  Prolactin‐induced protein (PIP) has been shown to bind to CD4 and is speculated to block CD4–HLA‐DR interaction. However, the immunomodulatory effect of PIP on chronic allergic contact dermatitis (ACD) remains to be elucidated.

Neuronal Differentiation of Ewing's Sarcoma Induced by Cholera Toxin B and Bromodeoxyuridine—Establishment of Ewing's Sarcoma Cell Line and Histochemical Study—

An Ewings sarcoma (ES) cell line was established from a metastatic bone marrow specimen in a patient with advanced disease, and some histochemical characteristics were investigated by neuronal differentiation induced with cholera toxin B (CTB) and bromodeoxyuridine (BrdU). Neuronal differentiation was investigated by the expression of neurofilament and Leu‐7, and glial differentiation was observed by expression of S‐100 protein. Neurofilament (NF) and Leu‐7 were positive in ES cells and these were expressed more intensively by induction with CTB than with BrdU. There was no expression of S‐100 protein in untreated or differentiated ES cells. ES cells became differentiated to neuronal cells with CTB and BrdU, but it was not observed, that ES cells had the potential to differentiate to glial cells. It appears that ES is of more primitive neural origin than neuroblastoma, primitive neuroectodermal tumors and other related neural tumors.

Cytological features of myxoid adrenocortical adenoma with a pseudoglandular component: A case report with differential diagnostic considerations

Myxoid adrenocortical tumors are extremely rare neoplasms with only nine adenomas and eleven carcinomas reported in the literature. They occasionally have a pseudoglandular component resembling metastatic mucinous adenocarcinoma in the adrenal gland. However the cytological features of this unusual tumor have not been previously described. We report here the first cytopathological study of a myxoid adrenocortical adenoma with a pseudoglandular component, contributing especially to the differential diagnosis from metastatic mucinous adenocarcinoma. Two major cytopathological features distinguishing myxoid adrenocortical adenoma from metastatic mucinous adenocarcinoma in the adrenal gland are: (1) the myxoid material is found only in the extracellular space, and not in the cytoplasm; and (2) nuclei are usually located in the central portion of the cytoplasm, and not compressed to the periphery. Careful observation of these cytological features and positive immunoreactivity to Melan A, alpha‐inhibin and synaptophysin can lead to the correct diagnosis. Diagn. Cytopathol. 2008; 36: 576–580.

Ascitic fluid due to type II herpes simplex virus infection: Report of a case with immunocytochemical confirmation

Herpes simplex virus (HSV) infection is usually observed in the oral cavity and external genitals, and HSV peritonitis is extremely rare. Herein, we report a case of type II HSV peritonitis successfully diagnosed by ascitic cytology. A 66‐year‐old Japanese man, who had been treated with steroid inhalation for 5 years due to chronic obstructive pulmonary disease, was suspected to have acute cholecystitis. Laparoscopic cholecystectomy and intraoperative cytological examination of ascitic fluid were performed. Cytological study of ascitic fluid revealed that abundant granular cell debris, degenerative cells and apoptotic bodies were present, as well as some single or multinucleated cells with ground glass nuclei. However, vivid mesothelial cells were rarely seen. Immunocytochemical staining for type II HSV was positive in single or multinucleated cells with ground glass nuclei. Therefore, a diagnosis of type II HSV peritonitis was made. This is the first reported case of type II HSV peritonitis successfully diagnosed by ascitic cytology. This report highlights that the presence of abundant cell debris, degenerative cells and apoptotic bodies, and the absence of vivid mesothelial cells are the key cytological findings to suspect HSV peritonitis, and the diagnosis can be confirmed by careful surveillance for characteristic nuclear findings of single or multinucleated cells. The frequency of opportunistic infection is increased because of the increased numbers of iatrogenic immunocompromised patients as seen in this case, therefore, cytological examination is a useful method for early detection of the causative agent of peritonitis including HSV. Diagn. Cytopathol. 2013;41:354–359.

Immunosuppressive Effect of Prolactin-Induced Protein

Prolactin-induced protein (PIP) has been shown to bind to CD4 and is speculated to block CD4-HLA-DR interaction. However, the immunomodulatory effect of PIP on chronic allergic contact dermatitis (ACD) remains to be elucidated. The aim of this work was to define the role of PIP during the immunoresponse. Using an oxazolone-induced mouse chronic ACD model, expression of PIP was immunohistologically examined. Furthermore, effects of continued exposure of a peptide mimicking the major binding site of PIP (amino acids 106-132) for CD4 was examined in a mouse chronic ACD model. We clarified that keratinocytes and dermal infiltrating cells are positively stained with anti-PIP antibody. The PIP peptide significantly downregulated oxazolone-induced mouse ACD compared to the controls. We also found that inflammation of PIP-non-applied control ear was also suppressed in a synchronized manner in the late phase of the PIP peptide applied mouse. These findings suggest that PIP might have an immunosuppressive effect in mouse chronic ACD.

Effect of Prolactin-Induced Protein on Human Skin: New Insight into the Digestive Action of This Aspartic Peptidase on the Stratum Corneum and Its Induction of Keratinocyte Proliferation

Human prolactin-induced protein (PIP) is a major protein found in exocrine fluids such as saliva and sweat. Intriguingly, PIP possesses residues (human PIP (hPIP): PIP (29-63)) that display similarity to the aspartic peptidase candidapepsin. Here, we aimed to determine the effect of PIP as a protease on normal skin structure. Using an adhesive tape-stripping technique, we applied hPIP peptide on the corneocytes of normal-appearing facial skin from infants with eczema and healthy infants and then analyzed the morphological structure of corneocytes with Nile Red fluorescence. We also repeatedly applied the hPIP peptide onto the surface of a three-dimensional (3-D) human skin model and then analyzed any changes to the stratum corneum and epidermis using light microscopy and scanning electron microscopy. In both infant groups, a decrease in hydrophobic lipids from the cornified envelope was observed after treatment with hPIP. The peptide hPIP appeared to digest the fine structure of the stratum corneum and induce a proliferation of epidermal keratinocytes within the 3-D human skin model. Our results suggest that aspartic peptidase of PIP found in sweat or saliva deteriorates the skin barrier in a de novo manner, which potentially leads directly to the proliferation of epidermal keratinocytes without any external antigenic factors.

A case of pulmonary blastoma

背景:肺芽腫は胎児肺の腺様期に類似した上皮性部分と問葉性部分から構成されるまれな腫瘍で上皮成分は異型性が弱いのが通例である. 今回, われわれは上皮成分に多形性の強調されたbiphasic pulmonary blastomaの症例を経験したので報告する。症例:80歳, 男, 肺炎にて入院中, 右上肺部にmass lesionの増大を認めたため, 胸腔鏡下右肺上葉の部分切除術を施行した. 術中迅速時の捺印細胞診では腺癌様細胞と肉腫様細胞が混在して認められたことから, 癌肉腫の可能性が考えられた. しかし, 組織所見で紡錘形細胞が束状に配列する像や多形性に富む横紋筋肉腫の像が複雑に混じり合うなかに胎児肺類似の腺管上皮が増生する像が認められたことから肺芽腫と診断された.結論:肺芽腫は肺腫瘍としてはきわめてまれな腫瘍であるが, 増殖能力が高く, 腺管上皮や間葉系成分の性格によっては予後が異なってくる. 細胞や組織形態のみならず, 免疫学的所見も参考にしながら, より詳細に腫瘍細胞の性格を捉えて診断していくことが重要である.