Yoshimi Nishijima

Hydrocellular foam dressings promote wound healing associated with decrease in inflammation in rat periwound skin and granulation tissue, compared with hydrocolloid dressings

The effects of modern dressings on inflammation, which represent the earliest phase of wound healing, are poorly understood. We investigated the effects of modern hydrocellular foam dressings (HCFs) on wound healing and on the gene expression levels of the inflammatory markers—interleukin (IL)-1β, IL-6, and IL-10—in rat periwound skin and granulation tissue by quantitative reverse transcription-polymerase chain reaction. HCF absorbed significantly higher volume of water than hydrocolloid dressing (HCD) and increased the contraction of wounds. Polymorphonuclear neutrophils were massively infiltrated to the wound edge and boarded between granulation and dermis in the HCD group. IL-1β, IL-6, and IL-10 mRNA levels were significantly decreased in the periwound skin around the wounds and granulation tissue covered with HCF. These findings suggest that HCF may promote wound healing along with decrease in inflammation by reducing gene expression levels of IL-1β, IL-6, and IL-10. Graphic·Abstract HCF promotes wound healing along with decreases in inflammation by reducing gene expression levels of IL-1β, IL-6 and IL-10 in rat periwound skin and granulation tissue.

Primary study on providing a basic system for uterine cervical screening in a developing country: analysis of acceptability of self-sampling in Lao PDR.

BACKGROUND Most developing countries have been unable to implement well-organized health care systems, especially comprehensive Pap smear screening-based programs. One of the reasons for this is regional differences in medical services, and a low-cost portable cervical screening system is necessary. To improve regional discrepancies in cervical screening systems, we investigated the usefulness and acceptability of cervical self- sampling by liquid-based cytology (LBC) for 290 volunteers in the Lao PDR. MATERIALS AND METHODS Following health education with comprehensive documents, cervical self-sampling kits by LBC were distributed in three provincial, district, and village areas to a total of 290 volunteers, who were asked to take cytology samples by themselves. Subsequently, the acceptability of self-sampling was evaluated using a questionnaire. RESULTS The documents were well understood in all three regions. Regarding the acceptability of self-sampling, the selections for subsequent screening were 62% self-sampling, 36% gynecologist-sampling, 1% either method, and 1% other methods. The acceptability rates were higher in the district and the village than in the province. For the relationship between acceptability and pregnancy, the self-sampling selection rate was higher in the pregnancy-experienced group (75%) than in the pregnancy-inexperienced group (60%). For the relationship between selection of self-sampling and experience of screening, the self-sampling selection rate was higher in the screening-inexperienced group (62%) than in the screening-experienced group (52%). CONCLUSIONS Our data show that this new way forward, involving a combination of self-sampling and LBC, is highly acceptable regardless of age, educational background, and residence in rural areas in a developing country.

Intracellular localization of α-tubulin acetyltransferase ATAT1 in rat ciliated cells.

Cilia are microtubule-based hair-like organelles on basal bodies located beneath the cell membrane in various tissues of multicellular animals, and are usually classified into motile cilia and primary cilia. Microtubules are assembled from the heterodimers of α- and β-tubulin. The lysine residue at position 40 (K40) of α-tubulin is an important site for acetylation, and this site is acetylated in the cilium. α-Tubulin N-acetyltransferase 1 (ATAT1) is an acetyltransferase specific to the K40 residue of α-tubulin; however, its intracellular distribution in mammalian tissues remains unclear. In this study, we analyzed ATAT1 localization in rat trachea, oviduct, kidney, retina, testis and the third ventricle of the brain by immunohistochemical techniques using a specific antibody against ATAT1. ATAT1 was distributed to the motile cilia of multiciliated cells of the trachea, third ventricle of the brain and oviduct, and in the primary cilia of the renal medullary collecting duct. ATAT1 also localized to the primary cilia, inner and outer segments of retinal photoreceptor cells, and at the Golgi apparatus of spermatocytes and spermatids of testis. These results indicated that α-tubulin acetylation by ATAT1 at distinct subcellular positions may influence the functional regulation of microtubules and cilia in a variety of ciliated cells.

HSL Attenuates the Follicular Oxidative Stress and Enhances the Hair Growth in ob/ob Mice.

Summary: We demonstrated enhanced hair regeneration following topical administration of N-(3-oxododecanoyl)-L-homoserine lactone (HSL) in ob/ob mice. The ob/ob mice showed delayed hair regeneration (more than 6 wk) after depilation, which rapidly induced transition to anagen in the hair cycle in wild-type mice. Vehicle and HSL solutions were applied to the depilated dorsal skin of ob/ob mice. The depilated skin of the HSL-treated mice was fully covered with hair, whereas no macroscopic alteration was observed in vehicle-treated group by the fourth week after depilation. Oxidative stress was drastically decreased and the expression of the antioxidative enzymes PON1 and PON3 was increased in the HSL-treated skin with highly proliferative anagen follicles. These results suggest that HSL is a candidate therapeutic agent for alopecia in metabolic syndrome.

Compression-induced HIF-1 enhances thrombosis and PAI-1 expression in mouse skin.

Pressure ulcers result from tissue hypoxia caused by external forces. Thrombosis due to external forces is considered important, and hypoxia inducible factor‐1 (HIF‐1) is a master regulator of pressure ulcer development. To date, however, their causal relationship has not been determined. This study therefore investigated the mutual relationship between thrombosis and HIF‐1 activation in compressed mouse skin, based on a hypothesis that HIF‐1 regulation by plasminogen activator inhibitor‐1 (PAI‐1) enhances thrombosis. Compression of mouse skin significantly increased the numbers of thrombi and HIF‐1α‐positive cells compared with control skin. A thrombosis inhibitor significantly reduced the numbers of HIF‐1α‐positive cells and an HIF‐1 inhibitor significantly inhibited thrombosis in compressed skin tissue, suggesting a mutual relationship between thrombosis and HIF‐1 activation. Compression of mouse skin also enhanced the level of Pai‐1 messenger RNA expression, but this increase was significantly reduced by treatment with an HIF‐1 inhibitor, whereas a thrombosis inhibitor had no effect. These results suggested the involvement of PAI‐1 in HIF‐1‐enhanced thrombosis and that an additional factor participates in regulating Pai‐1 expression in compressed skin. These findings may suggest new strategies in pressure ulcer management.

ATAT1 is essential for regulation of homeostasis-retaining cellular responses in corticotrophs along hypothalamic-pituitary-adrenal axis

The production and secretion of adrenocorticotropin, a proopiomelanocortin (POMC)-derived hormone, by corticotrophs in the anterior pituitary, is regulated by corticotrophin-releasing hormone (CRH) and glucocorticoids. We have previously demonstrated that adrenalectomy induces α-tubulin N-acetyltransferase 1 (ATAT1) expression and α-tubulin acetylation in corticotrophs. However, the regulatory mechanism of ATAT1 expression and the function of acetylated microtubules in corticotrophs are unclear. Here, we analyze the effect of CRH or dexamethasone on Atat1 expression in the mouse corticotroph AtT20 cell line. The expression of Atat1 was increased by CRH and decreased by dexamethasone in AtT20 cells. We examined the effect of Atat1 knockdown on the expression of POMC-associated genes and the dexamethasone-induced nuclear translocation of glucocorticoid receptor (GR) by real-time polymerase chain reaction and Western blot analysis, respectively. Atat1 knockdown resulted in a significant increase in the expression of ACTH-producing genes and decreased the dexamethasone-induced nuclear translocation of GR accompanied with a reduction in α-tubulin acetylation. Atat1 overexpression resulted in a significant increase in α-tubulin acetylation and the dexamethasone-induced nuclear translocation of GR. These results suggest that the acetylated microtubules function as the rail-line for the transportation of GR into the nucleus. We conclude that ATAT1 finely tunes the cellular responses of corticotrophs to hormonal stimulation through an intracellular feedback circuit.

Adrenalectomy facilitates ATAT1 expression and α-tubulin acetylation in ACTH-producing corticotrophs

Microtubules play an important role in the intracellular transport of secretory granules in endocrine cells and in mitosis and the maintenance of cell morphology and are composed of heterodimers of α- and β-tubulin. α-Tubulin N-acetyltransferase 1 (ATAT1), which acetylates the lysine residue at position 40 of α-tubulin, functions not only in stabilizing microtubule structures and forming the primary cilium assembly but also in vesicular trafficking in neurons. However, the localization of ATAT1 and the role of α-tubulin acetylation in endocrine cells in the pituitary are still poorly understood. Corticotrophs in the anterior lobe of the pituitary produce and secrete adrenocorticotropin (ACTH). Although removal of the adrenal gland, a target organ of ACTH, is reported to promote the synthesis and secretion of ACTH in corticotrophs and to induce structural alterations in their organelles, uncertainty remains as to whether the acetylation of α-tubulin is involved in such intracellular events of corticotrophs. We investigate the expression and localization of ATAT1 and the acetylation of α-tubulin in the pituitary of normal and adrenalectomized rats. We find that ATAT1 is localized to the Golgi apparatus of endocrine cells in the anterior lobe of normal pituitary and that the expression levels of ATAT1 and acetylation levels of α-tubulin increase following adrenalectomy. These results agree with the hypothesis that the acetylation of α-tubulin by ATAT1 regulates the intracellular transport of secretory granules in corticotrophs.

Dynamic localization of α-tubulin acetyltransferase ATAT1 through the cell cycle in human fibroblastic KD cells

Acetylation of α-tubulin is a well-studied posttranscriptional modification, which is mostly catalyzed by α-tubulin N-acetyltransferase (ATAT1). ATAT1 possibly affects various cellular functions related with microtubules, such as intracellular transport, cell motility, cilia formation, and neuronal signaling. Here, we analyzed the subcellular localization of immunolabeled ATAT1 in human fibroblast KD cells through the cell cycle using confocal laser scanning microscopy. ATAT1 dramatically changed its localization through the cell cycle, depending on the mitotic phase. In interphase, immunolabeled ATAT1 was observed in centrioles, nuclei, and basal bodies if the cells projected primary cilia. ATAT1 was intensely detected as clusters in the nuclei in the G1–G2 phase. In telophase, ATAT1 colocalized with chromatids and spindle poles, and ultimately migrated to the daughter nucleus, newly synthesized centrioles, and midbody. The nucleolus is a core region of ribosomal RNA transcription, and the midbody is associated with severing and depolymerizing of microtubules in the stembody. The specific distributions of ATAT1 through the cell cycle suggest multiple functions of ATAT1, which could include acetylation of microtubules, RNA transcription activity, severing microtubules, and completion of cytokinesis.

Expression and localization of forkhead box protein FOXJ1 in S100β-positive multiciliated cells of the rat pituitary

S100β-positive cells exist in the marginal cell layer (MCL) of the adenohypophysis and follicle structure in the parenchyma of anterior lobe (ALFS) in pituitary. They have multiple functions as phagocytes or cells that regulate hormone secretion. Majority of S100β-positive cells in the adenohypophysis express sex determining region Y-box 2 protein (SOX2), a stem cell marker; therefore, S100β/SOX2 double positive cells are also considered as one type of stem/progenitor cells. MCL and ALFS are consisting of morphologically two types of cells, i.e., multiciliated cells and non-ciliated cells. However, the relationship between the S100β-positive cells and multiciliated cells in the pituitary is largely unknown. In the present study, we first immunohistochemically verified the feature of multiciliated cells in MCL and ALFS. We then examined the expression patterns of FOXJ1, an essential expression factor for multiciliated cell-differentiation, and SOX2 in the S100β-positive multiciliated cells by in situ hybridization and immunohistochemistry. We identified anew the S100β/SOX2/FOXJ1 triple positive multiciliated cells, and revealed that they were dispersed throughout the MCL and ALFS. These results indicate that the MCL and ALFS are consisting of morphologically and functionally distinct two types of cells, i.e., S100β/SOX2 double positive non-ciliated cells and S100β/SOX2/FOXJ1 triple positive multiciliated cells.

Pleomorphic rhabdomyosarcoma arising in the anterior mediastinum: A case report with cytological features of imprint and liquid-based cytology specimens: CYTOLOGICAL FEATURES OF MEDIASTINAL PLEOMORPHIC RHABDOMYOSARCOMA

We herein report the cytological features of a very rare case of pleomorphic rhabdomyosarcoma arising in the anterior mediastinum on imprint and liquid‐based cytology (LBC) specimens. A 58‐year‐old man had an approximately 10‐cm tumor in the anterior mediastinum as shown on computed tomography. Thymectomy with complete resection of the left lung was performed. The fresh cut surface of the tumor was used to prepare imprint and LBC specimens. The imprint specimens showed four types of tumor cells dispersed on a background of hemorrhage, necrosis, and mucus. On the other hand, only two types of tumor cells (spindle‐shaped and spiderweb cells) were scattered or present in clusters in the LBC specimens. Immunocytologically, both of these cell types were positive for desmin and myoglobin, negative for pan‐keratin and epithelial membrane antigen. Cytological and immunocytological features are useful for the correct diagnosis of pleomorphic rhabdomyosarcoma, and LBC specimens show clearer results than do imprint specimens. Diagn. Cytopathol. 2017;45:333–338.