bluuebunny/crossref_metadata_2025 huggingface dataset:
037  Experience of Use of Long Pulse Alexandrite Laser for Fresh Facial Traumatic Tattoo
Authors: Naohiro Ishii , Masashi Fukatsu , Yuji Nakanishi
Published: February 2004

Objectives: We devised a method of irradiating a fresh traumatic tattoo with long pulse alexandrite laser in conjunction with the use of a dynamic cooling device (DCD) to minimize the injury of the epidermal layer before the occurrence of pigmentation in the deep layer of the skin, when the wound is not completely epithelialized.

Methods: A 4‐year‐old girl suffered a burn injury and deposition of fuel residues in a diameter of 5 cm on the left cheek by backfire of a motorcycle muffler. The patient was treated with an ointment at a hospital for about 10 days, and then referred to our hospital. On initial visit, removal of foreign bodies was attempted by brushing but with little success. Accordingly, long pulse alexandrite laser treatment was performed four times in total at intervals of about one week. On the initial irradiation DCD was not used, but was used on all subsequent treatments thereafter for the protection of the epidermal layer.

Results: Since remarkable pigment reduction was observed after the laser irradiation, the treatment was stopped. Follow‐up was performed while the lesion was shielded from light.

Conclusion: Since the long pulse alexandrite laser with the DCD conveniently enables continuous irradiation of pigments in a short time while minimizing damage to the epidermis, its therapeutic effect can be expected. However, great care is needed during the treatment to prevent scarring.
039  Observation of Angiogenesis in Granulation Tissue Using the Dressing Material
Authors: Kazuaki Murashita , Hiroko Sinzawa , Akira Takeda , Eiju Uchinuma
Published: February 2004

Aim: It is important to analyze the angiogenesis and the formation of the granulation tissue in understanding the wound healing process. The dressing material is thought that the wound healing is promoted, and understanding the effect of the dressing material. The model which used the dressing material was made, and the angiogenesis in the granulation tissue formation process were compared.

Method: The Sprague‐Dawrey rat's granulation formation model and the model which used the dressing materials were made. The granulation tissue was removed on the 7th day, the 14th day, the 28th day, and the 42nd day. The angiogenesis and the formation of network of newly formed vessels during the granulation tissue formation were observed with Confocal laser scanning microscopy.

Result: The angiogenesis starts from the depths part of the granuration tissue. Afterwards, it progresses superficial part of the granulation tissue, and the network of the blood vessel is formed. In this process, as the model which used the dressing material, the network of the angiogenesis was admitted from early time.
040  The Function of ‘Choke Vessels’ to the Blood Flow: Angiographic and Laser Flow‐Graphic Study on the Rat Flap Model
Authors: Toshiharu Minabe , Katsumata S. , Ogo K. , Taylor G. I.
Published: February 2004

Aim: The ‘choke vessels’, defined by Taylor 1], are reduced‐caliber anastomosing vessels which are normally the barrier in the vasculature. They also have capacity to dilate and increase the blood flow. The aim of this study is to investigate the anatomical and dynamic function of choke vessels.

Study design: The 3‐territory bipedicled flaps were elevated on the back of the Wistar rats 2]. The flaps were directly sutured back in place in the revascularized group (10 animals), and the plastic sheets were underlaid in the non‐revascularized group (10 animals). On the day 3, each flap was converted to the mono‐pedicled flap and was scanned by the laser flow‐graphy and injected for the angiography.

Results: All flaps survived completely. The revascularized flaps showed evenly dilated choke vessels in the 2 choke zones of the flaps and the blood flow from the vascular pedicle covered more than 2 territories. The non‐revascularized flaps showed more remarkable but uneven dilatation of choke vessels between 2 choke zones. The blood flow in non‐revascularized flaps, however, reached only 1 territory, blocked by the first choke zone which dilated less than the other zone.

Conclusions: By dilating, the choke vessels are activated and can have the adverse function of regulating the blood flow, namely, suppression and escalation of the blood flow.
041  New Experimental Animal Model of Pressure Ulcers Using the Originally Designed Skinfold Chamber
Authors: Shinsaku Tsuji , Shigeru Ichioka , Naomi Sekiya , Takashi Nakatsuka
Published: February 2004

It is clear that the interruption of microcirculation is one of the significant factors to the pathophysiology of pressure ulcers. But the relation between them has not sufficiently elucidated yet. We aimed at developing the experimental animal model of pressure ulcers. Using the originally designed skinfold chamber and pressing systems, we visualized interruption, remodeling and angiogenesis of microcirculation dynamically. And such various microcirculatory responses also could be evaluated and recorded chronically. We compared ischemia‐induced injury to ischemia‐reperfusion‐induced injury with this model, and analyzed each reaction of microcirculation quantitatively by measuring the functional capillary density. This model can be useful from the viewpoint of microcirculation.
043  Effects of Early Wound Excision on Hepatic Blood in the Extensively Burned Rat
Authors: Yoshimitsu Nakano , Kazutaka Soejima , Tsukasa Isago , Motohiro Nozaki
Published: February 2004

Aim: Effects of early excision on hepatic blood flow were investigated in burned rats.

Methods: 30% TBSA burned Wistar rats were allocated to four groups, infusion group (n = 13): fluid resuscitation with lactated Ringer’s; early excision group (n = 13): early escherectomy and allogenic skin grafting with fluid resuscitation; burn group (n = 13): burn injury alone without any treatment; sham group (n = 15): sham burn procedure. The hepatic blood flow was measured at 0, 0.5, 1, 2, 3, 6, 12 and 24 hours postburn. At 12 and 24 hours postburn, plasma Endothelin‐1 (ET‐1) and nitric oxide (NO) levels were detected.

Results: In the infusion and the burn group, a significant decrease in hepatic blood flow compared with the sham group. In contrast in the early excision group, the hepatic blood flow was not decreased and there was a significant difference from the infusion group at 12 hours postburn. The plasma ET‐1 and NO levels were markedly elevated in the infusion and the burn group at 12 and 24 hours postburn. Whereas in the early excision group, no significant increase either in the plasma ET‐1 or NO levels were found compared with the sham group during experimental period.

Conclusion: The hepatic blood flow decreases after a massive burn injury even with adequate fluid resuscitation. Early excision is helpful in stabilizing the hepatic blood flow without further aggravating the hepatic hemodynamic load. The decrease in plasma ET‐1 and NO levels after early wound excision procedure may be playing a role in improving the hepatic blood flow.
044  The Difference in Virulence between Clinically Recovered Staphylococcus Aureus and an Established Strain Applied to a Skin Ulcer Model
Authors: Masahiro Tachi , Shinichi Hirabayashi
Published: February 2004

Aim: We attempted to establish a rat model by placing gauze on a wound bed. We then used this model to evaluate the virulence of an established strain of Staphylococcus Aureus and a clinical strain isolated from a patient with a wound infection.

Methods: Using a 1.5 × 1.5 cm template, full thickness skin wounds were made through the panniculus carnosus on the backs of rats. A small piece of gauze was placed over each wound. The wound beds were inoculated with 1.5 × 106 cfu of Staphylococcus Aureus from the American Type Culture Collection, or 1.5 × 106 cfu of a clinical isolate. The wounds were debrided every 48 hours and samples taken to the laboratory for quantitative bacteriologic analysis. Specimens were fixed and stained by H/E and Gram staining.

Results: The clinical strain of Staphylococcus Aureus resulted in bacterial counts (cfu per gram of tissue) exceeding 107 on days 2 to 6, while the established stain produced bacterial counts exceeding 107 cfu on days 2 to 4 only. Gram stain analysis revealed that the clinical strain penetrated deep granulation tissue, whereas, the established strain was present in small cell nests at the wound margins.

Conclusion: A clinical strain isolated from a patient showed deeper penetration of the wound bed than an established strain, resulting in prolonged elevation of the bacterial count.
045  Alteration of Integrin Expression in Migrating Epidermal Cells and Fibronectin Distribution in the Dermis with Pressure Ulcers
Authors: Miyoko Kubo , Mika Shinoyama , Kousaku Suenobu , Takahiko Moriguchi
Published: February 2004

Failure of re‐epithelialization characterizes the pathophysiology of chronic wounds. However, the mechanism of this failure has not been fully clarified. During the re‐epithelialization of acute wounds, migrating epidermal cells up‐regulate integrins α5β1, αvβ5, αvβ6 and these integrins play an important role in the re‐epithelialization process. Laminin‐1 is a basement membrane component which appears during the late phase of the re‐epithelialization process. In this study, with 6 specimens from burn patients (acute wounds, control) and 11 specimens from patients with pressure ulcers, we examined the expression of α5β1 in the migrating epidermis, laminin‐1 at the dermal‐epidermal junction and fibronectin in the dermis by an immunohistochemical method. We then compared the findings for α5β1 with histological, laminin‐1 and fibronectin distribution findings. In 8 out of the 11 pressure ulcer specimens, the expression of α5β1 significantly decreased or was negative while it increased in the control. The degree of expression correlated well with histological findings of epidermal elongation over the wound bed. Moreover, fibronectin distribution in all the pressure ulcer specimens decreased considerably while it increased in three out of the six burn specimens. A statistically significant correlation was found between the distance at which the cells were positively stained for α5β1 and the distance at which they were negatively stained for laminin‐1 in both the burn (control) and pressure ulcer specimens. Our data demonstrated that the decrease in α5β1 expression correlated with the failure in re‐epithelialization of chronic wounds (pressure ulcers). It was also suggested that the decrease in fibronectin distribution was responsible for the failure of the re‐epithelialization process.
047  Allogeneic Transplantation of Genetically Modified Primate Embryonic Stem Cells
Authors: Asano T , Hanazono Y , Sasaki K , Ueda Y , Hasegawa M , Ageyama N , Terao K , Kitano Y , Momoeda M , Ozawa K , Harii K
Published: February 2004

Aim: To examine the efficacy and safety of human embryonic stem (ES) cell‐based therapies, allogeneic transplantation of monkey ES cells would be useful. We transplanted genetically marked monkey ES cells into the allogeneic fetus.

Methods and Results: Cynomolgus ES cells were transduced once using a simian immunodeficiency virus‐based lentivirus vector encoding the GFP gene driven by the CMV promoter at 1, 10 and 100 transducing units per cell. Five days posttransduction, 60, 80 and 90% of the cells expressed GFP, respectively, and the expression levels were stable for 5 months. GFP expression was still observed after embryoid‐body formation. The gene‐marked ES cells were transplanted into the cynomolgus fetus in the abdominal cavity (n = 2) or liver (n = 1) after the first trimester. The fetuses were delivered 1 month posttransplantation. Transplanted cell progeny were detected (∼1%) in multiple tissues by quantitative PCR and in situ PCR of the GFP sequence. No teratoma was found in the tissues. Conclusions: Cynomolgus ES cells can be engrafted in the allogeneic fetus. We are now trying to transplant cynomolgus ES cells differentiated to neural or hematopoietic lineage.
S‐I‐05  Increased Levels of Cell Division Cycle 25A Protein in Keloid Lesions
Authors: Ghazizadeh M , Tosa M , Shimizu H , Egawa S , Inoue K , Oguro T , Hirai T , Kawanami O
Published: February 2004

Aim: Keloid lesions develope as a result of abnormal growth of dermal fibroblasts after the injury. On the other hand, cell division cycle (Cdc) 25 is a family of phosphatases that activate the cell cycle regulating cyclin‐dependent kinases. The three members of this family, Cdc25A, Cdc25B, and Cdc25C act in different phases of the cell cycle. In this study, we examined the dgree of expression of these phosphatases in keloid fibroblasts.

Methods: Primary cultures of keloid and adjacent normal dermal fibroblasts (n = 4) as well as frozen and paraffin‐embedded keloid and normal dermal tissues (n = 12 and n = 17 respectively) were examined by Western blot and immunohistochemical analyses for the expressions of Cdc25A, Cdc25B, Cdc25C and phosphorylated Cdk2.

Results: Cdc25A protein levels were frequently increased in keloid fibroblasts as compared to the adjacent normal‐appearing fibroblasts or different normal dermal fibroblasts. In contrast, Cdc25B and Cdc25C were none or rarely expressed. The incrased levels of Cdc25A were associated with lower levels of its substrate, Cdk2, in a phosphorylated or inactive form.

Conclusions: Taken together, our data show that Cdc25A protein levels increase in keloid fibroblasts and this increase may be sufficient to activate its substrate, Cdk2, and accelerate the cell cycling. These results may have implication for the development of strategies to silence Cdc25A activity after the wound healing as a therapeutic modality for the keloid lesions.
S‐II‐01  Dynamics of Myenteric Nerves after Transection of the Muscle Coat of the Rat Small Intestine; the Involvement of Glial Cell Line‐Derived Neurotrophic Factor (GDNF) and its Receptor (Ret) in their Growth
Authors: Yoshiaki Takahashi , Tsuyoshi Noguchi , Yuzo Uchida , Hiroshi Shimoda
Published: February 2004

The present immunohistochemical study was designed to investigate the manner of the myenteric nerve regeneration and expression of glial cell line‐derived neurotrophic factor (GDNF) and its signaling receptor (Ret) in nerves after transection of the muscle coat in the rat small intestine. The enteric neurons and enteroglial cells were immunohistochemically determined using antibodies against protein gene product 9.5 and S‐100 protein, respectively. The neuronal sprouts issued from the severed nerve stumps 12 h after the operation, and thereafter extended into the lesion. The proximal portions of outgrowing neuronal fibers were gradually enveloped by regenerating enteroglial cells to become thick nerve bundles. The regrowing neurons and their associated enteroglial cells developed into an irregular network in the myectomized area on postoperative day 5. The elongation of the regrowing nerves was conspicuously accelerated from postoperative day 3 in accordance with the regrowing neurons started to associate with the enteroglial cells. Under normal conditions, faint immunoreactivity for GDNF and Ret was selectively localized in the enteroglial cells and neurons within the myenteric ganglia, respectively. Following myectomy, the both immunoreactivities were significantly intensified in the nerve stumps and ganglia proximal to the lesion. The regenerating enteroglial cells closely associated with the regrowing neurons in the lesion exhibiting a dense immunoreaction to GDNF, whereas the neuronal fibers were richly supplied with reaction products of Ret in their entire course. The present findings suggest that the enteroglial cells, contacting with regrowing neurons, may promote the myenteric nerve regeneration in the rat small intestine, via the GDNF‐Ret signaling system.
S‐II‐03  A Study of Wound Healing in Chronic Hemodyalsis Patients after Abdominal Operation
Authors: Itikawa H , Tanaka S , Ikeno T , Ozaki K , Matida M
Published: February 2004

Aim: This paper reports on the delay in wound healing of chronic hemodyalysis patients who under‐went abdominal surgery. Methods: The subjects were 19 hemodyalysis patients who had had elective abdominal operations and 20 hemodyalysis patients who had undergone emergency abdominal surgery. For all subjects, we retroactively investigated the incidence of wound complications and the differences in postoperative values for TP, ALB, RBC and HGB between the wound‐complication group and the no‐ wound‐complication group. Results: In the elective‐surgery group, the incidence of wound complications was 21%, including one suture failure, one wound deficiency and three wound infections. No patients died. In the emergency‐surgery group, the incidence of wound complications was 40%, with two suture failures, four wound deficiencies and two wound infections. The postoperative death rate was 20%. There was no significant difference in TP, ALB, RBC, or HGB between the wound‐complication group and the non‐complication group in either the elective or the emergency surgery group. Conclusions: In hemodyalysis patients, pre‐and postoperative infection had a great influence on wound healing.
S‐III‐01  A Case of Skin Trouble Around the Ileostomy Improved by Application of bFGF Spray
Authors: Nobuyo Suzuki , Junichi Nakamura , Takayuki Asao , Hiroyuki Kuwano
Published: February 2004

The content of the effluent from an ileostomy is high‐volume, liquid, and contains proteolytic enzymes. It is crucial to maintain a stoma appliance that protects the surrounding skin. This is an interesting report of a 74‐year‐old female who present bladder carcinoma and underwent total cystectomy, ileal conduit, low anterior resection of the rectum and loop ileostomy for covering the anastomosis at July 7, 2002. After surgery, the stoma was depressed in fatty abdomen and resulted in the trouble surrounding skin. The erosion around stoma was not healed easily. We applied bFGF spray to the erosion around the ileostomy. One week later, an ostomy appliance was able to apply longer, because of reducing exudates from the erosion.

The difficulty to maintain the good status surrounding skin with ileostomy was higher up with increasing meal and activities of diary living. The application of bFGF spray advanced the healing skin erosion. It is useful for caring the skin trouble with ileostomy.
S‐III‐02  Construction and Management of Loop Ileostomy
Authors: Tomonori Hamada , Haruhiko Naitoh , Tatsuya Orimo , Hirohumi Adachi , Hiroshi Shiroto , Keishi Kondoh , Masami Ogita
Published: February 2004

Aim: The aim of this study was to determine the morbidity associated with both construction and reversal of loop ileostomies.

Methods: Thirty‐three patients who had loop ileostomies constructed and 31 of these same patients who had their loop ileostomies reversed between 1994 and 2001 were reviewed.

The loop ileostomies were constructed in round‐shaped (2.5∼3 cm in diameter) like a end ileostomy and everted to produce a 2∼3 cm stoma without a rod

Results: The average size of ileostomies was 28 × 29 × 25(hight)mm. Five patients had complications arising from ileostomy construction including 4 parastomal irritation, 1 ileus, and 1 stomal ulcer. All complications improved with conservative management. Mean time to ileostomy reversal was 78 days. Of 31 patients who had loop ileostomies reversed, 10 patients had staple closure (functional end‐to‐end anastomosis with ENDO GIA 45). Nine patients had complications associated with reversal including 6 small bowel obstruction due to anastomotic stenosis(anastomotic edema), 1 leakage and 2 SIRS. Of these 9 patients, 2 required surgical intervention. One patient suffered leakage required reanastomosis, one for SIRS required reconstruction of loop ileostomy. Of 6 patients developed small bowel obstruction, 3 required long intestinal tube decompression. All patients improved with conservative management. 10 patients who had their loop ileostomies closed by functional end‐to‐end anastomosis had no bowel obstruction and other complications.

Conclusions: Defunctioning loop ileostomy is associated with low morbidity. We recommend a defunctioning ileostomy as the procedure of choice for temporary fecal diversion, and functional end‐to‐end anastomosis in reversal of ileostomies.
S‐III‐03  Long‐Term Clinical Outcomes of a New Colostomy Technique
Authors: Yuichiro Kiduka , Yoshiaki Tai , Yojiro Inoue , Kensuke Kiyokawa , Toshihiko Yamauchi
Published: February 2004

Aim: Quality of Life (QOL) of patients after cancer surgery has become more important as success rate of surgical treatment has been improved. Anal sphincter preservation has been concerned in treatment for colon cancer, in particular rectum cancer. However, in order for patients to become cancer free, colostomy is the essential treatment. In usual stoma, skin contacts directly with colon membrane, and this sometimes induces (i) skin troubles around the stoma (e.g., ulcer, abscess, fistula), and (ii) constriction, collapse, perforation, hernia or obstruction of the colon. The skin troubles are the complications that are unavoidable only through the improvement and control of the equipment because the skin directly touches to the stool. Therefore, preventive measures should be employed at colostomy. For this purpose, a new colostomy technique was applied from the point of plastic and reconstruction surgery.

Methods: In order to reduce the duration and area of direct contact with stool, local flap and split‐thickness skin grafting are applied. Colon is pull out to the abdominal wall by using the usual surgical procedure. The stoma is kept at a certain height from the abdominal wall by using the flap and the graft.

Results: To date, the longest follow‐up period is 8 years and 7 months. Frequency of skin problems due to direct contact with stool was reduced, infection and constriction on and around the stoma have been prevented, and defecation became able to be better managed.
S‐IV‐02  C2C12 Cells Differente in Three Dimensional Culture in Collagen Gel
Authors: Tanaka T , Kishi K , Sato H , Nakajima H , Nakajima T
Published: February 2004

Aim: The movements of the cell population are different between 2‐D culture and 3‐D culture. From the observation of morphology of skeletal muscle cell 3‐D culture, We expect that skeletal muscle cells differentiation is accelerate in the collagen gel 3‐D culture, and the proliferation is suppressed. The purpose of this study is to investigate the difference between 2‐D culture and 3‐D culture of C2C12 cells.

Methods: C2C12 skeletal muscle cells are incubated following three difference conditions for 48 hours, plastic dish 2‐D culture, collagen coated dish 2‐D culture and collagen gel 3‐D culture. The culture medium is Dulbecco's modified Eagle medium containing 10% fetal bovine serum and 1% penicillin/streptomycin. Collagens are removed by collagenase treatment and cells are homogenized. After centrifugation the top clear layer is used for CPK assay and protein development analysis by Western blotting

Results: After 48 hour incubation, we observed cell morphology by a phase contract microscope. Cell fusion was observed in collagen gel 3‐D culture. The fusion cells have many nucleus in the cytoplasm called synthetium. But in plastic dish 2‐D culture and in collagen coated dish 2‐D culture synthetiums were not observed and cells were mononuclear and monolayer. Cell prolieration was suppressed in collagen gel 3‐D culture. CPK activity was five times activated in collagen gel 3‐D culture than in plastic dish 2‐D culture.

Conclusions: We suggest skeletal muscle cells C2C12 are activate differentiation by collagen gel 3‐D culture.
S‐IV‐03  Ectopic Bone Formation Accelerated by Human Mesenchymal Stem Cells and Osteogenic Cytokines via Nutrient Vessel Injection in Nude Rat
Authors: Fukui M , Akita S , Akino K
Published: February 2004

Critically larger bone and skin defects often lack the enough nutrient blood supply to induce normal wound healing. Additionally, deteriorated environment such as poor vascularity due to the hard fibrosis after irradiation or extensive tissue loss due to the highly damaged tissue or severe bacterial contamination, leads to finding another donor sites or another methods to repair. Potential free vascularized flaps are widely accepted for reconstruction purpose, however, the donor‐site morbidity is sometimes concerned and its clinical application may be limited. Tissue engineered tissues are now most actively investigated and partially clinically appropriate for use. In order to assist the bone wound healing, the human mesenchymal stem cells (hMSCs), wrapped with the abdominal fascial flap, which is nutrient of superficial epigastric vascular systems in bone, and the full‐thickness dorsal defect covered by artificial skin substitute as a carrier in skin, are used as cell source with potential differentiation with specific cytokines in a nude rat model for eliminating T cell immunity. The hMSCs and osteogenic cytokines such as bone morphogenetic protein‐2 (BMP‐2) and basic fibroblast growth factor (bFGF) were intra‐arteriallly injected and incubated for 10 minutes and then the gelatin‐carrier were wrapped with the abdominal superficial fascia and investigated for the subsequent experiments. The heterotopic bone formation was most significantly observed in 4 weeks after injection and this may be used clinically to enhance the compromised bone healing.
S‐IV‐04  A Vascularized Artificial Bone Graft Using the Periosteal Flap and Porous Hydroxyapatite; Basic Research and Preliminary Clinical Application
Authors: Akiko Hirata M.D. , Yu Maruyama M.D. , Kiyoshi Onishi M.D. , Akiteru Hayashi M.D. , Michio Saze M.D. , Emi Okada M.D.
Published: February 2004

Aim: Vascularized periosteum has an ability of new bone formation, and porous hydroxyapatite (HA) has an property of bone conduction. A basic research was performed to investigate the possibility of making a “hybrid” vascularized artificial bone from porous HA integrated with the vascularized periosteum.

Materials & methods: A latissimus dorsi musculoperiosteal flap was raised in rabbit. In one group, HA blocks (porosity; 55%, dimension; 8 × 4 × 2 mm) were ligatened to the cambium layer of periosteum and muscle, and in the other group HA blocks combined with rhBMP‐2 were apllied in the same manner. HA blocks were removed 4, 8 and 12 weeks after the operation and were examined histologically. This method was applied preliminarily to 5 patients who needed bony repair of anterior chest, midface, and mandible.

Results: Osteogenesis was observed within the pores of the blocks over the course of time. In rhBMP‐2 group, osteogenesis progressed rapidly to the same extent as in without rhBMP‐2 group. In clinical cases, postoperative bone scintigraphy demonstrated radioactive uptake into HA implants, and biopsy revealed bone neogenesis into the pores of HA.

Conclusions: Our basic research and preliminary clinical applications suggested that the possibility of making the hybrid type of vascularized artificial bone preparation with HA using this method. This will enable less invasive procedure and custom‐made reconstruction without the need of vascularized autogeneous bone grafts.
P‐I‐01  Treatment of Skin Defects and Skin Ulcers with bFGF Preparation
Authors: Akihiro Ogino , Kiyoshi Onishi , Hiroko Yoshida , Yu Maruyama
Published: February 2004

Abstract: On 11 patients with skin defect and refractory ulcer, treatment was conducted using bFGF preparations. Good granulation, epithelialization and reduction of ulcer were observed in all patients by once‐daily spraying of this product after washing the topical region. This preparation is a drug developed aiming at the basic fibroblast‐proliferating factor playing an important role in the wound healing process in the body and expecting the therapeutic effects on refractory skin ulcer. Although there are some restrictions including the tropical conditions such as infection and adherence of necrosed tissues and careful administration to the patients with a past history of malignant tumor, its good therapeutic effects were expected in the patients ineffective with other drugs, and this product was evaluated to be useful from the viewpoint of QOL, such as shortening of treatment period, reduction of cost and low invation.
P‐I‐04  Treatment for Limb Ulcer with Severe Ischemia: Therapeutic Angiogenesis by Autologous Transplantation of Bone‐Marrow
Authors: Teiji Okazaki
Published: February 2004

Aim: Limb ulcer due to severe ischemia often needs revascularization. In our hospital, the result of lower extremity bypass surgery for these patients is satisfactory, however, indication of this procedure is limited pathologically and technically. We recently have demonstrated a possibility of efficacy of therapeutic angiogenesis by autologous bone marrow cell transplantation for severe ischemic ulcer of extremity.

Methods: Eight patients (9limbs; 3limbs with arteriosclerosis obliterans, 6limbs with Buerger's disease) with ischemic ulcer of lower and/or upper extremity were treated with implantation of autologous bone marrow mononuclear cell into ischemic skeletal muscles. Four weeks after transplantation, efficacy of this procedure were evaluated by Visual Ana log Scale, angiography and Laser Doppler Flow Analysis (LDFA).

Results: In 4 out of 9 limbs, the ulcers healed dramatically. Seven limbs revealed angiographically improvement and icrease of blood flow by LDFA.

Conclusions: Our findings suggest that therapeutic angiogenesis by autologous bone marrow cell transplantation is an effective and safty strategy for patient with peripheral arterial disease. We considered that it is more effective to Buerger's disease than arteriosclerosis obliterans.
P‐I‐05  Flap Repairs for Incurable Lower Leg Ulcers
Authors: Isao Koshima  , Yuzaburo Nanba  , Tetsuya Tsutsui  , Yoshio Takahashi  , Seiko Itoh
Published: February 2004

Incurable ulcer in the lower legs means avascular skin defects exposing bone and osteomyelitis which cannot be repaired even with skin grafting. A total of 151 patients with incurable ulcers were operated with flaps; 60 cases of traumatized avascular defects, 20 diabetic ulcers, 17 osteomyelitis, 14 malignant tumors, 5 arterial obstructions, and 5 arteriovenous malformations, and others. A total of 61 island flaps were used; 20 posterior tibial perforator flaps, 7 saphenous flaps, 7 peroneal flaps, 4 anterior tibial flaps, 4 malleolar perforator flaps, 4 medialis pedis flaps, and others. In addition, a total of 82 free flaps using microvascualr anastomosis were sued; 24 flow‐through anterior thigh flaps, 13 flow‐throuh thoracodorsal artery perforator flaps (or latissimus dorsi MC flap), 8 paraumbilical (or deep inferior epigastric artery ) perforator flap, 6 saphenous venous flaps, 7 combined flaps, and 24 others. In conclusions, small ulcers could be repaired with minimal invasive methods including local perforator flaps and small muscle flaps under local anesthesia. Free flow‐through flaps and free bypass flaps (for diabetic gangrene with ASO), and combined osteocutaneous flaps (for massive segmental defects after resecting advanced carcinoma) are indicated for large ischemic defects.
P‐II‐02  Leukemia Inhibitory Factor Gene and Vascular Endothelial Growth Factor Protein can Module Embryonic Fibroblastic Differentiation via GP130‐STAT and MAPK Signal Transduction Pathways
Authors: Akita S , Akino K , Fukui M
Published: February 2004

The combined application of cytokines on embryonic fibroblasts and dermal substitute were extensively studied for optimal skin defect coverage. Signalling of combined treatment of leukemia inhibitory factor (LIF) and vascular endothelial factor (VEGF) were elucidated and subsequently the in vivo applications of both were tested in an artificial dermal substitute. Mouse embryonic fibroblast cells, BALB‐3T3, were stably transfected with mouse full length LIF cDNA and added to various doses of VEGF for detection of signalling interaction. LIF‐transfected cells and VEGF treatment were tested with pig‐tendon derived collagen dermal substitute in the backs of BALB/c male mice for 14 days. LIF‐transfected cells as well as vector‐transfected fibroblasts significantly proliferated by 1, 10, or 100 nM VEGF on days 3 and 5. LIF‐transfected cells showed rapid phosphorylation of STAT 3 from 1 minute to 60 minutes after VEGF treatment, while vector‐transfected cells failed to induce such phosphorylation after VEGF treatment. Erk MAP kinase phosphorylation was observed from 1 to 15 minutes in LIF‐transfected and 10 nM of VEFG and 1 to 30 minutes in LIF‐transfected and 100 nM VEFG treatments. In in vivo analyses, LIF‐transfected embryonic fibroblasts with 50 μg of VEGF markedly enhanced collagen I expression and CD 34 angiogenic marker on days 7 and 14. LIF transfection induced constitutive STAT signaling and enhanced phosphorylated‐Erk MAP kinase with exogenous VEGF. In vivo study revealed that the combined application of LIF‐transfection of embryonic fibroblasts with an angiogenic factor such as VEGF in the template of an artificial dermis.
P‐II‐04  Early Phase Regulation of Human Mesenchymal Stem Cells and the Unique Profile of the Proliferation by Bone Morphogenetic Protein‐2
Authors: Akino K , Mineta T , Fukui M , Akita S
Published: February 2004

Human mesenchymal stem cells (hMSCs) obtained from a single donor of the iliac crest, was further investigated for the cell proliferation, cell cycle profiles, gene expressions and the ultrastructures by electron microscopy. The hMSCs significantly increased the cell number by day 2 after by treatment of bone morphogenetic protein (BMP)‐2 alone, or basic fibroblast growth factor (bFGF) alone or combination of both in the serum‐free condition (P < 0.01). The hMSCs demonstrated the remarkable proliferation cell nuclear antigen notably at day 1 and pituitary tumor transforming gene all through the experiment, suggesting the cell cycle progression by BMP‐2 treatment as well as the strong cellular nuclear BrdU expression by immunocytochemistry. The fluorescence‐activated cell sorter also demonstrated the similar pattern of the cell cycle progression between BMP‐2 treatment in the serum‐free and 10 % fetal bovine serum treatment. The BMP‐2 treated hMSCs demonstrated the heterochromatin in the nucleus, suggesting the cell differentiation and the well‐developed granular endoplasmic reticulums, indicating the protein production. The hMSCs successfully proliferate, the cell cycle is progressed, and the cell ultrastructure morphology suggest the remarkable nuclear and of granular endoplasmic reticulum induction by BMP‐2 treatment in the serum‐free condition.
P‐II‐05  Effects of BMP‐2 Gene and bFGF Protein Combined with Porous Hydroxyapatite on Bone Formation
Authors: Ichiro Ono , Toshiharu Yamashita , Haiying Jin , Yoshinori Ito , Hirobumi Hamada , Masanori Nakasu , Tetsunori Ogawa , Kowichi Jimbow
Published: February 2004

In this study, the bone defects created on animal cranium which treated by BMP gene (cDNA plasmid) and bFGF protein introduced with porous HAP and the bone formation was analyzed histpathologically. The bone defect of 1.2 cm in the diameter was made on rabbit's cranium and HAP pellets of exactly 1.0 cm in diameter were implanted after completion of hemostasis. The amount of the bone formation was compared with or without the presence of the BMP‐2 cDNA plasmid. In addition, simultaneous administration of bFGF containing solution with or without BMP gene were performed to analyze the effect of combined use of them. The bone formation was vigorously observed in the cranial defect in the groups, which received the BMP‐2 gene with HAP at three weeks after the operation, and complete ossification was observed at 9 weeks after the operation. In the HAP which containing BMP‐2 gene implanted group, although it revealed that new bone formation was evident surrounding the HAP pellets at three weeks after the operation, the inducted bone tissue did not fill to the entire pores of the HAP pellets even at 9 weeks after the operation which condition was improved by coadministration of bFGF with BMP gene. Those results show that at the BMP gene therapies the bone formation in the pores of the HAP pellet was promoted by coadministration of bFGF. It is possible the effects of the administration of the BMP‐2 gene will be improved, from the above‐mentioned result, through coadministration of bFGF and BMP gene.
001  Treatment of Hypertrophic Scar with the Silicone Cushion
Authors: Yasuyoshi Tosa , Tsutsumi K. , Satoh K. , Hosaka Y. , Wada K. , Fujimura D. , Satoh N. , Morita M.
Published: February 2004

Aim: Various treatments for hypertrophic and keloid scars have been attempted including electron beam irradiation, local triamcinolone injection, oral tranilast administration, use of silicone sheets, and compression therapy using splints. Among them, we have been attempting silicone cushion patching on hypertrophic scar.

Methods: Twenty cases (10 males, 10 females) with hypertrophic scar were treated with silicone cushion. Scar surfaces were kept in contact with silicone cushion for as long periods of time as possible every day. Results were assessed in scores using objective findings (redness, bulging, induration) and subjective symptoms (itching, spontaneous pain, tenderness).

Results: As for objective findings, redness remained unchanged in one case, but bulging and induration were found improved in all cases. As for subjective symptoms, itching and tenderness were found improved in all cases and clinical course considered proving usefulness of the treatment was obtained.

Conclusions: Silicone cushions have highly viscous silicone oil enclosed in the silicone pack designed to generate negative charge electrostatic fields. Generation of adequate and sustaining electrostatic fields is important for useful clinical effect to exhibit on hypertrophic scar recession. Generation of negative charge electrostatic fields was confirmed on potential determination data with an electrostatic field meter as well.
003  Gene Expression Profiles Following Electron Irradiation of Cultured Keloid and Normal Skin Fibroblasts by cDNA Microarray Analysis
Authors: Tosa M , Ghazizadeh M , Shimizu H , Hirai T , Kawanami O , Hyakusoku H
Published: February 2004

Aim: When surgery with postoperative superficial electron irradiation is applied, the recurrence rate of keloid lesion has been found to be <30%. In this study, we assessed the molecular changes underlying the effect of electron irradiation by differential global gene expression analyses of both cultured keloid and normal skin fibroblasts.

Materials and Methods: Primary cultured fibroblasts from 4 active keloids and their adjacent normal dermal tissues were irradiated at a calibrated dosage of 15 Gy with 6 MeV electron beam generated by a linear accelerator. Corresponding paired non‐irradiated cells were used as control. RNA isolated from the collected cells was labeled with 33P, hybridized to the cDNA microarray gene filters and analyzed.

Results: After irradiation, the gene expression profiles of keloid and normal skin fibroblasts were closely similar. Electron irradiated keloid fibroblasts showed suppressed levels of collagen typeI (alpha2), collagen typeVI (alpha1), matrix metalloproteinase 2, fibronectin 1, insulin‐like growth factor binding protein 3, alpha‐1‐antichymotorypsin and heparan glucosaminyl 1 as compared with their non–irradiated counterparts.

Conclusions: Downregulation of matrix synthesis and upregulation of protease inhibitors and apoptosis promoting genes by electron irradiation may inhibit keloid development. This mode of therapy appears to exert a positive effect toward lowering the recurrence rate of keloid formation.
004  Postoperative Electron‐Beam Irradiation‐Thirteen Years’ Experience and Future Prospects in our Hospital‐
Authors: Rei Ogawa , Hiko Hyakusoku , Tuguhiro Miyashita , Atsushi Tateno
Published: February 2004

Purpose and Methods: Between 1988 and 2000, 378 cases of keloids were treated and the therapeutic outcomes were evaluated. For this study, 147 keloids in 129 patients were selected.

Results: The overall recurrence rate was 32.7%. Analysis of the therapeutic outcomes showed that the recurrence rates in the sites with high stretch tension, such as the chest wall, and the scapular and suprapubic regions were statistically higher than in sites without high tension, such as the neck, earlobes and lower limbs (p = 0.0017).

Discussion: The results suggested that keloid sites with a high risk of recurrence should be treated with escalated radiation doses. However in our experience, pigmentation increases when the radiation dose is increased. Additionally, pigmentation can be suppressed by the following methods: 1. reducing the one‐time dose of irradiation while keeping the total dose unchanged; 2. lengthening the irradiation interval. Therefore we made a new protocols and provide further insights into the treatment: Total 20 Gy (4 days): Anterior chest wall, Scapular region and Suprapuvic region; Total 10 Gy (2 days): Ear lobe; Total 15 Gy (3 days): Others.
005  Acceleration of Wound Healing in Healing‐Impaired db/db Mice with a Photoclosslinkable Chitosan Hydrogel Containing Fibroblast Growth Factor‐2
Authors: Kiyohaya Obara , Masayuki Ishihara , Toshiaki Ishizuka , Yuichi Ozeki , Tadaaki Maehara , Akira Kurita
Published: February 2004

Aim: The purpose of the present study has been to assess possibilities of the FGF‐2 incorporated chitosan hydrogel as a dressing for wound occlusion and healing acceleration in healing‐impaired db/db mice.

Methods: Mutant diabetic mice, C57BL/KsJ db/db, and their normal littermates (db/+) were used in this study. After full thickness‐round wound (about 100 mm2) were prepared on the back of each mouse, the FGF‐2 containing chitosan hydrogel was added onto the wound of each mouse and was irradiated with UV light. Similar full thickness‐round wound were also prepared as controls without any trearment. The changes in wound area of mice were measured. The skin including the wound was removed from each mouse for histological examination.

Results: For the db/db mice treated with the FGF‐2‐incorporated chitosan hydrogel, healing was faster than only chitosan hydrogel‐treated and control wounds. On the other hand, the incorporated FGF‐2 in the chitosan hydrogel did not show a stimulatory effect on the wound healing of db/+ mice. The vascularity of wound areas of db/db mice on day 4, evaluated immunohistochemically with anti‐murine CD34, was markedly increased in FGF‐2‐incorporated chitosan hydrogel‐treated wound.

Conclusion: FGF‐2‐incorporated chitosan hydrogel may become accepted as an occlisuve dressing for healing impaired wound managemant.
Industrial Location Modeling: Extending the Random Utility Framework*
Authors: Guimarães Paulo , Figueiredo Octávio , Woodward Douglas
Published: February 2004

Abstract.  Given sound theoretical underpinnings, the random utility maximization‐based conditional logit model (CLM) serves as the principal method for applied research on industrial location decisions. Studies that implement this methodology, however, confront several problems, notably the disadvantages of the underlying Independence of Irrelevant Alternatives (IIA) assumption. This paper shows that by taking advantage of an equivalent relation between the CLM and Poisson regression likelihood functions one can more effectively control for the potential IIA violation in complex choice scenarios where the decision maker confronts a large number of narrowly defined spatial alternatives. As demonstrated here our approach to the IIA problem is compliant with the random utility (profit) maximization framework.
Tradeoffs between Local Taxes and Government Spending as Determinants of Business Location*
Authors: Gabe Todd M. , Bell Kathleen P.
Published: February 2004

Abstract.  This paper investigates the effects of local fiscal policy on the location decisions of 3,763 establishments that began operations in Maine between 1993 and 1995. Empirical results, estimated from Poisson and negative binomial regression models, indicate that businesses favor municipalities that spend high amounts on public goods and services, even when these expenditures are financed by an increase in local taxes. This suggests that a local fiscal policy of reduced government spending, to balance a tax cut, may attract fewer new businesses than a policy featuring additional spending and higher taxes.
Regional Externalities And Growth: Evidence From European Regions*
Authors: López‐Bazo Enrique , Vayá Esther , Artís Manuel
Published: February 2004

Abstract. This paper models externalities of production across regional economies. Under the assumption that knowledge diffuses without political or administrative barriers, we derive externalities that affect the steady state and the process of growth of each economy. The empirical counterpart of the reduced form equation summarizing the process of growth allows us to test for the presence of regional spillovers and to measure their magnitude. Our results for a sample of European regions show that spillovers are far from negligible, are robust to the consideration of variables within each region, and may cause nondecreasing returns at the spatial aggregate level. The paper also relates previous empirical evidence on spatial dependence in growth studies to the externalities modeled here.
Environmental Externalities, Median Voters, and the Multicentric City*
Authors: Hyok‐Joo Rhee
Published: February 2004

Abstract.  This paper presents a new theory of the formation of a multicentric city and shows an example where median voters prevail in the social choice of land use patterns. To be specific, environmental externalities of work zones give an incentive to voters to form multiple subcenters in a city even in the absence of agglomeration economies. In addition, the land use pattern chosen closely follows the median voter's preferences under appropriately structured choice process. In this demonstration, zoning is as much the mechanism by which the internal structure of a city is organized as it is the one used to organize the metropolitan fabric of local governments in the Tiebout‐Oates‐Hamilton system.
The Dynamics and Volatility of Commercial and Residential Property Prices: Theory and Evidence*
Authors: Kan Kamhon , Kwong Sunny Kai‐Sun , Leung Charles Ka‐Yui
Published: February 2004

Abstract.  This article investigates the dynamics of property prices and their interaction with output growth in a general equilibrium model. Closed form solutions and testable hypotheses are derived from a mildly restricted version of the model. The testable hypotheses are broadly supported empirically. In particular, (1) the volatility of commercial property prices is higher than that of residential property prices, (2) each of the lagged, contemporary, and forward commercial property prices is positively correlated with residential property prices, (3) the contemporaneous covariance between the two property prices is larger than the lagged covariance, and (4) output growth is positively correlated with both property prices. These results are consistent with simulations results that are based on a more general specification of the model.
Understanding the Shortcomings of Commodity‐based Technology in Input–Output Models: an Economic‐Circuit Approach
Authors: De Mesnard Louis
Published: February 2004

Abstract.  The Make‐Use Model serves as a basis for most national accounting systems as the System of National Accounts (SNA) and is acknowledged as the most suitable model for interregional analysis. Two hypotheses are traditionally made featuring either industry‐based technologies (IBT) or commodity‐based technologies (CBT). While industry‐based technologies can be easily interpreted in terms of a demand‐driven economic circuit, it will be shown that: (1) commodity‐based technologies cannot be interpreted as a demand‐driven economic circuit because this involves computing the inverse of a matrix (the matrix of industry output proportions), which is either impossible or generates negative terms; (2) the only way to obtain a plausible explanation of CBT is to convert it into a supply‐driven model. This provides a new reason for rejecting CBT: either IBT is adopted but violates Kop Jansen and ten Raa's axioms, or CBT is chosen but must be converted into a poor or unrealistic supply‐driven model.