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Papers - Kishi, Kazuo

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Leukemia inhibitory factor regulates microvessel density by modulating oxygen-3 dependent VEGF expression in mice

Kubota Yoshiaki, Hirashima Masanori, Kishi Kazuo, Stewart Colin L., Suda Toshio

Journal of Clinical Investigation 118 ( 7 ) 2393 - 2403 2008.07

ISSN 0021-9738

To meet tissue requirements for oxygen, capillaries must be properly distributed without excess or shortage. In this process, tissue oxygen concentration is well known to determine capillary density via the hypoxia-induced cascade, in which HIFs and VEGF play key roles. However, some additional mechanisms modulating this cascade are suggested to be involved in precise capillary network formation. Here, we showed that leukemia inhibitory factor (LIF) was predominantly expressed in developing endothelium, while its receptor was expressed in surrounding cells such as retinal astrocytes. The retinas of Lif-/- mice displayed increased microvessel density accompanied by sustained tip cell activity, due to increased VEGF expression by astrocytes in the vascularized area. Lif-/- mice resisted hyperoxygen insult in the oxygen-induced retinopathy model, whereas they paradoxically had increased numbers of neovascular tufts. In an in vitro study, LIF inhibited hypoxia-induced VEGF expression and proliferation in cultured astrocytes. Lif-/- mice also exhibited similarly increased microvessel density and upregulated VEGF in various tissues outside the retina. Together, these findings suggest that tissues and advancing vasculature communicate to ensure adequate vascularization using LIF as well as oxygen, which suggests a new strategy for antiangiogenic therapy in human diseases such as diabetic retinopathy and cancer.

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Leukemia inhibitory factor regulates microvessel density by modulating oxygen-dependent VEGF expression in mice

Kubota, Yoshiaki, Hirashima, Masanori, Kishi, Kazuo, Stewart, Colin L., Suda, Toshio

JOURNAL OF CLINICAL INVESTIGATION 118 ( 7 ) 2393 - 2403 2008.07

Research paper (scientific journal), ISSN 0021-9738

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Quantitative evaluation of elderly skin based on digital image analysis

Tanaka, Hiromasa, Nakagami, Gojiro, Sanada, Hiromi, Sari, Yunita, Kobayashi, Hiroshi, Kishi, Kazuo, Konya, Chizuko, Tadaka, Etsuko

SKIN RESEARCH AND TECHNOLOGY 14 ( 2 ) 192 - 200 2008.05

Research paper (scientific journal), ISSN 0909-752X

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Three-dimensional venous anatomy of the dermis observed using stereography

Imanishi, Nobuaki, Kishi, Kazuo, Chang, Hak, Nakajima, Hideo, Aiso, Sadakazu

JOURNAL OF ANATOMY 212 ( 5 ) 669 - 673 2008.05

Research paper (scientific journal), ISSN 0021-8782

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A new dog ear correction technique

Kishi Kazuo, Nakajima Hideo, Imanishi Nobuaki

Journal of Plastic, Reconstructive and Aesthetic Surgery 61 ( 4 ) 423 - 424 2008.04

ISSN 1748-6815

When moving a local flap, a dog ear sometimes appears at the base of the flap. If we try to correct the dog ear primarily, the blood supply to the flap may be disturbed. In such a case, the dog ear is prone to be corrected secondarily. In the present report we show a new technique for correcting a dog ear that enables correction to be done primarily and sufficiently. The principle of the technique is to de-epithelialise the dog ear portion and dig it in to the dermis to preserve the subdermal plexus at the base of the flap intact. This method is useful especially at the base of a transposition flap because the pedicle tends to be narrowed by the conventional correction.

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Rapid, severe repigmentation of congenital melanocytic naevi after curettage and dermabrasion

Kishi K., Matsuda N., Kubota Y., Katsube K. I., Imanishi N., Nakajima T.

British Journal of Dermatology 156 ( 6 ) 1251 - 1257 2007.06

ISSN 0007-0963

Background: Curettage and dermabrasion are effective in treating giant congenital melanocytic naevi (GCMN). We report two patients with rapid, severe postoperative repigmentation. To the best of our knowledge this is the first report on the histological features of such patients. Objectives: We wish to call attention to histological features that may cause rapid, severe repigmentation after curettage and dermabrasion of medium to giant CMN. Patients/methods: From 1998 to 2002, we treated 23 patients with medium to giant CMN with curettage and dermabrasion. Patients being treated ranged in age from 1 month to 19 years. Histological samples were taken from the centre of naevi in all patients during surgery. Histological types were 12 intradermal and 11 compound. Follow-up after curettage lasted at least 3 years. Results: Among our 23 patients only two showed repigmentation soon after surgery. Histological sections from these two patients indicated naevoid cells in the deep dermis along hair follicles or sebaceous glands. However, no such pigmented naevoid cells along hair follicles were observed in samples from patients successfully treated with curettage and dermabrasion with less repigmentation. Conclusions: Although we saw only two cases of repigmentation soon after curettage and dermabrasion, we suspect a correlation between pigmented naevoid cells around hair follicles and repigmentation. If histological sections of skin biopsies show pigmented cells along hair follicles in the deep dermis, other treatments such as total skin resection followed by skin grafting or tissue expansion may be better choices than curettage or dermabrasion.

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Distally based greater saphenous venoadipofascial-sartorius muscle combined flap with venous anastomosis

Kishi Kazuo, Nakajima Hideo, Imanishi Nobuaki

Plastic and Reconstructive Surgery 119 ( 6 ) 1808 - 1812 2007.05

ISSN 0032-1052

In reconstruction of the extremities, a distally based flap is useful for covering the distal parts. Distally based flaps are, however, prone to congestion in the peripheral part of the flap, followed by partial necrosis because of insufficient venous drainage caused by resistance of the venous valves. To rescue peripheral congestion of the distally based flap, venous anastomosis is effective so that the venous blood flows in the direction of the venous valve. We applied this idea to a patient who had skin defects around the knee after a wide resection of the skin tumor, and covered them with a distally based greater saphenous venoadipofascial-sartorius muscle combined flap. The whole area of the flap took well without congestion after anastomosis of the vein.

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Molecules involved in the hair cycle

Kishi Kazuo, Kubota Yoshiaki, Nakajima Hideo, Nakajima Tatsuo

Japanese Journal of Plastic and Reconstructive Surgery 50 ( 2 ) 157 - 161 2007.02

ISSN 0021-5228

Macroscopic and histological studies of the subcutaneous adipofascial tissue

Imanishi Nobuaki, Nakajima Hideo, Kishi Kazuo

Japanese Journal of Plastic and Reconstructive Surgery 49 ( 10 ) 1083 - 1088 2006.10

ISSN 0021-5228

The reconstruction of the lower eyelid with V-Y advancement flap

Kishi Kazuo, Nakajima Hideo, Imanishi Nobuaki, Nakajima Tatsuo

Japanese Journal of Plastic and Reconstructive Surgery 49 ( 7 ) 749 - 754 2006.07

ISSN 0021-5228

In lower eyelid reconstruction, we use a V-Y advancement flap from the lower lateral cheek. The technique is simple and the scar after surgery is fine. On the other hand, we recommend supporting the reconstructed flap firmly to prevent ectropion due to either scar contraction or gravity. We use fascia lata fixed to a newly developed screw system that is directly inserted into the lateral orbital rim. By using these techniques, lower eyelids were successfully reconstructed.

Mutual dependence of murine fetal cutaneous regeneration and peripheral nerve regeneration

Kishi Kazuo, Ohyama Kyoji, Satoh Hiroko, Kubota Yoshiaki, Tanaka Takara, Imanishi Nobuaki, Nakajima Hideo, Kawamura Kohki, Nakajima Tatsuo

Wound Repair and Regeneration 14 ( 1 ) 91 - 99 2006.01

ISSN 1067-1927

Mammalian fetal cutaneous wounds made at certain developmental stages show complete regeneration. It is reported that wound healing in both adult and fetal skin is disrupted by denervation. Furthermore, fetal cutaneous regeneration has unique aspects such as epidermal wrinkle texture regeneration and dermal regeneration that depend on developmental stage. Therefore, we have examined the relationship of fetal cutaneous regeneration with denervation. We made cutaneous wounds on fetal mice at various developmental time points including embryonic days (E)13, E15, and E17, and compared the regenerating patterns of peripheral nerves in the skin. We found that when the fetuses are wounded at an early stage of development, peripheral nerves regenerate quicker than at later stages of development when peripheral nerve regeneration is delayed. Next, we denervated the intercostal nerves and made wounds at the denervated sites on E13 and E15. We found that epidermal wrinkling and dermal regeneration were disrupted by denervation. These findings indicate that components of fetal cutaneous regeneration and peripheral nerve regeneration are mutually dependent.

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Skin reconstitution in SCID mice

Kishi Kazuo, Kubota Yoshiaki, Katsube Kenichi, Satoh Hiroko, Shimizu Yusuke, Imanishi Nobuaki, Nakajima Hideo, Nahajima Tatsuo

Japanese Journal of Plastic and Reconstructive Surgery 48 ( 9 ) 979 - 984 2005.09

ISSN 0021-5228

In fetal regenerative wound healing, dermal mesenchymal cells directly migrate into the wound and regenerate the dermal structure. On the contrary, loose fascial cells beneath the dermis construct scar tissue in the late stage of development. We co-transplanted fetal epidermal cells and dermal or loose fascial mesenchymal cells onto a skin defect in SCID mice to evaluate the regenerative activity of their skin. The cells used for transplantation were obtained from fetal C57b1 mice on embryonic day 17, and suspended enzymatically. Four weeks after the transplantation, almost normal skin was regenerated in the animals that were transplanted with dermal and epidermal cells. Conversely, scar-like tissue was constructed in the animal wounds into which loose fascial and epidermal cells were transplanted. We found it useful to use this model to evaluate the cutaneous regenerative activity of various cells.

Our revised classification of skin flaps and opinion for 2004 classification of skin flaps

Nakajima Hideo, Iwanishi Nobuaki, Kishi Kazuo

Japanese Journal of Plastic and Reconstructive Surgery 48 ( 7 ) 745 - 755 2005.07

ISSN 0021-5228

Vascular systems of the flaps are constructed of following elements; i) types of blood circulation in the flaps, ii) vessel types of vascular pedicles, iii) separation points of vascular pedicles. The blood circulation of flaps is constructed of the dermal vascular system and the subdermal vascular system. Based on the combination of these elements, skin flaps can be categorized into the thin cutaneous flap, the split thickness cutaneous flap, and the full thickness cutaneous flap. The blood circulation in the deep fascia itself is poor, and thus the deep fascia does not contribute to the blood supply of the cutaneous flaps. Accordingly, the cutaneous flaps containing the whole subcutaneous adipose layer without deep fascia is basically similar to the fasciocutaneous flap. However, we categorized the former as full thickness cutaneous flap to prevent the confusion of terminology. From the clinical aspects, perforating vessels that construct the vascular pedicles were categorized into 6 types based on the vascular pattern from the source vessel to the dermal plexus. These six types of perforating vessels can be simplified as follows: 1) direct cutaneous vessels, 2) accompanying vessels, 3) muscular artery perforators, 4) septal perforators.

Is the platysma flap musculocutaneous? Angiographic study of the platysma

Imanishi Nobuaki, Nakajima Hideo, Kishi Kazuo, Chang Hak, Aiso Sadakazu

Plastic and Reconstructive Surgery 115 ( 4 ) 1018 - 1024 2005.04

ISSN 0032-1052

Background: The platysma flap has often been used for reconstructions of the head and neck, but the arterial anatomy of the platysma itself has not been clarified. Methods: The anterolateral neck skin in five sides of four fresh cadavers that had been injected systemically with a lead oxide-gelatin mixture was elevated and divided into three layers: the skin with adipofascial tissue over the platysma, the platysma, and the adipofascial tissue under the platysma. Radiographs were taken of each specimen using the soft x-ray system. Results: The anterolateral neck skin was chiefly supplied by branches of the submental, facial, superior thyroid, transverse cervical, and occipital arteries, and it was found that the vasculature of the arterial branches can be classified into three groups. In all of the groups, the arterial branches penetrated the platysma and did not run long in the platysma layer. The platysma was supplied by only small vessels from the arterial branches. Furthermore, there was little connection between the vascular plexus of the platysma and that of the skin layer with adipofascial tissue above the platysma and the platysma located in the subcutaneous tissue. Conclusions: The platysma flap should be considered fasciocutaneous rather than musculocutaneous. Therefore, the platysma flap should usually be elevated with the deep adipofascial tissue under the platysma. Flap survival is threatened if it is elevated without the adipofascial tissue under the muscle as with a usual musculocutaneous flap.

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The fetal dermal but not loose fascial mesenchymal cells possess regenerative activity of dermal structure

Kishi Kazuo, Katsube Kenichi, Satoh Hiroko, Imanishi Nobuaki, Nakajima Hideo, Nakajima Tatsuo

Cell Transplantation 14 ( 9 ) 709 - 714 2005

ISSN 0963-6897

Fetal skin possesses a regenerative activity until certain developmental stages. However, the origin of cells that regenerate dermis after wounding has not been clarified yet. In the present study we located the origin of cells that reconstruct fetal dermal structure by histological examination and by marking cells in the loose fascia. Next we evaluated the regenerative activity of fetal dermal mesenchymal cells by cotransplanting with fetal epidermal cells onto the skin defect of scid mice. We conclude that fetal dermal mesenchymal cells but not loose fascial cells possess regenerative activity even on the environment in scid mice.

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Tissue engineering of skeletal muscle in collagen gel

Kishi Kazuo, Satoh Hiroko, Tanaka Takara, Kubota Yoshiaki, Koyama Taroh, Imanishi Nobuaki, Nakajima Hideo, Nakajima Tatsuo

Japanese Journal of Plastic and Reconstructive Surgery 47 ( 9 ) 1001 - 1005 2004.09

ISSN 0021-5228

In order to construct functional skeletal muscle in vitro for tissue engineering, cell alignment followed by the fusion of skeletal muscle cells, and the construction of basement membrane are needed. Of the various means used to align skeletal muscle cells, the mechanical load method is the most popular. In the present paper, we describe the history of attempts to align skeletal muscle cells in vitro and the construction of basement membrane. We then describe the challenges we faced to achieve skeletal muscle tissue engineering in type I collagen gel by co-culturing various types of cells including skeletal muscle cells, fibroblasts, endothelial cells, and fetal rat anterior horn cells.

Transplanted mesenchymal stem cells are effective for skin regeneration in acute cutaneous wounds

Satoh Hiroko, Kishi Kazuo, Tanaka Takara, Kubota Yoshiaki, Nakajima Tatsuo, Akasaka Yoshikiyo, Ishii Toshiharu

Cell Transplantation 13 ( 4 ) 405 - 412 2004

ISSN 0963-6897

Mesenchymal stem cells (MSCs) possess the capacity for site-specific differentiation of cell types in response to cues provided by different organs. This phenomenon suggests that MSCs participate in cutaneous wound regeneration. However, there are no prior reports on the influence of the local application of MSCs on cutaneous wound regeneration. To examine the effects of MSCs on wound regeneration, we cultured bone marrow cells of the femur of rats and treated the plastic adherent cells with a differentiation medium to induce differentiation. After treatment, we found that the bone marrow-derived plastic adherent cells possessed myogenesis, chondrogenesis, and adipogenesis capabilities, indicating that these cells are MSCs. The bone marrow-derived plastic adherent cells were injected intradermally into the skin of rats, and linear full-thickness incisional wounds were made immediately through the injected area. At 14 days after operation, wounds transplanted with bone marrow-derived plastic adherent cells had healed with very fine scars. Collagen architecture was thick and appeared to be similar to normal dermis. Histomorphologic scale analysis demonstrated significant differences between the control and the wounds transplanted with bone marrow-derived plastic adherent cells. These results indicate that transplanted MSCs can respond quite normally to wound healing and regenerate dermal structure.

Anatomical study of subcutaneous adipofascial tissue

Nakajima Hideo, Imanishi Nobuaki, Minabe Toshiharu, Kishi Kazuo, Aiso Sadakazu

Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery 38 ( 5 ) 261 - 266 2004

ISSN 0284-4311

The subcutaneous adipofascial tissue over the entire body was radiographically and macroscopically investigated in 20 fresh and embalmed cadavers. The subcutaneous adipofascial tissue was made up of two adipofascial layers. Because the superficial layer forms a solid structure and is thought to protect against external forces, the adipofascial system formed by the solid structure was named the "protective adipofascial system (PAFS)". Because the deep layer forms a mobile layer and is thought to lubricate musculoskeletal movement, the adipofascial system formed by the mobile structure was named "lubricant adipofascial system (LAFS)". By classifying subcutaneous adipofascial tissue by its functional characteristics, we found we could understand the subcutaneous adipofascial structure over the entire body well.

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Nasal reconstruction by thin forearm flap

Nakajima Hideo, Imanishi Nobuaki, Kishi Kazuo, Sasaki Katsumi

Japanese Journal of Plastic and Reconstructive Surgery 46 ( 9 ) 891 - 900 2003.09

ISSN 0021-5228

It is theoretically possible to thin a forearm flap by clarifying the subcutaneous adipofascial structure and vasculature of the forearm, and a thin forearm flap has been developed accordingly based on the anatomy. In our report, we discussed indications for thin flap usage from a point of view which considers reconstruction of skin, bone and mucosal defects. Our first choice for thin forearm flap usage utilizes the two skin paddles and the radial bone for reconstructing whole defects of the nose. With this method, the donor site, if possible, is covered with the VAF flap using the basilic vein and its accompanying arteries after elevating the flap.

Expression of bone morphogenetic proteins during mandibular distraction osteogenesis in rabbits

Yazawa Masaki, Kishi Kazuo, Nakajima Hideo, Nakajima Tatsuo

Journal of Oral and Maxillofacial Surgery 61 ( 5 ) 587 - 592 2003.05

ISSN 0278-2391

Purpose: We examined the expression pattern of bone morphogenetic proteins (BMPs) during mandibular distraction osteogenesis in rabbits and also investigated the mechanism of membranous bone distraction. Materials and Methods: Twenty-three rabbits underwent mandibular distraction (protocol; no latency period, a 1-week distraction at 0.5 mm/d, and a 2-week consolidation period). Samples were collected at 3, 5, and 7 days of distraction and at 1-week and 2-week consolidation. We prepared undecalcified fresh-frozen sections and immunohistochemically evaluated the expression of BMPs 2 through 8. Results: Both endochondral ossification and intramembranous ossification were observed. The expression of BMPs 2, 4, 5, and 6 was observed continuously from the beginning of distraction. BMP-7 was expressed weakly. The expression of BMP-3 was not observed conspicuously during distraction but was strongly expressed at 1- and 2-week consolidation. Conclusion: The expression pattern of BMPs during membranous bone distraction was similar to that during long bone distraction, but it differed from the expression pattern of long bone distraction in that the expression of BMPs was maintained for 2 weeks after the completion of distraction.

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