研究者詳細 - 尾﨑　敏文

論文 - 尾﨑　敏文

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高悪性軟部腫瘍に対する化学療法の多施設共同研究

川井章, 梅田透, 鬼頭正士, 津金昌一郎, 長谷川匡, 和田卓郎, 伊原公一郎, 平賀博明, 高橋満, 荒木信人, 石井猛, 阿部哲士, 川野壽, 上田孝文, 馬場一郎, 尾崎敏文

日本癌治療学会誌 37 ( 2 ) 219 - 219 2002年9月

Giant cell tumor of the spine. 国際誌

Toshifumi Ozaki, Ulf Liljenqvist, Henry Halm, Axel Hillmann, Georg Gosheger, Winfried Winkelmann

Clinical orthopaedics and related research ( 401 ) 194 - 201 2002年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Six patients with giant cell tumor of the spine had surgery between 1981 and 1995. Three lesions were located in the scrum, two lesions were in the thoracic spine, and one lesion was in the lumbar spine. Preoperatively, all patients had local pain and neurologic symptoms. Two patients had cement implanted after curettage or intralesional excision of the sacral tumor; one patient had a local relapse. After the second curettage and cement implantation, the tumor was controlled. One patient with a sacral lesion had marginal excision and spondylodesis; no relapse developed. Two patients with thoracic lesions had planned marginal excision and spondylodesis; the margins finally became intralesional, but no relapse developed. One patient with a lumbar lesion had incomplete removal of the tumor and received postoperative irradiation. At the final followup (median, 69 months), five of six patients were disease-free and one patient died of disease progression. Two of the five surviving patients had pain after standing or neurologic problems. Although some contamination occurred, planning a marginal excision of the lesion seems beneficial for vertebral lesions above the sacrum. Total sacrectomy of a sacral lesion seems to be too invasive when cement implantation can control the lesion.

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骨肉腫の治療成績過去36年間の症例

伊藤達男, 川井章, 尾崎敏文, 杉原進介, 森本裕樹, 中田英二, 大畑範英, 井上一

日本整形外科学会雑誌 76 ( 6 ) S767 - S767 2002年6月

Characterization of the malignant melanoma of soft-parts cell line GG-62 by expression analysis using DNA microarrays. 国際誌

Karl-Ludwig Schaefer, Daniel H Wai, Christopher Poremba, Eberhard Korsching, Frans van Valen, Toshifumi Ozaki, Werner Boecker, Barbara Dockhorn-Dworniczak

Virchows Archiv : an international journal of pathology 440 ( 5 ) 476 - 84 2002年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

GG-62 is a cell line previously thought to be derived from an atypical Ewing tumor (ET). Reverse-transcriptase polymerase chain reaction revealed an in-frame fusion between the Ewing sarcoma gene ( EWS) codon 325 and the activating transcription factor 1 gene ( ATF1) codon 65 which permits the production of chimeric EWS-ATF1 oncoproteins. We also identified the genomic breakpoint resulting from a reciprocal t(12;22)(q13;q12), which is the hallmark of malignant melanoma of soft parts (MMSP). We applied Affymetrix human cancer G110 arrays to compare the gene expression patterns of GG-62 and other cell lines derived from small blue round cell tumors of childhood. Hierarchical clustering of 463 differentially expressed genes distinguished GG-62 from the ETs, as well as the neuroblastomas, and revealed a cluster of 36 upregulated genes. Several of these genes are involved in signal transduction pathways that may be critical for maintaining cell transformation; some examples are avian erythroblastic leukemia viral oncogene homolog 3 ( ERBB3), neuregulin 1 ( NRG1), fibroblast growth factor 9 ( FGF9), and fibroblast growth factor receptor-1 ( FGFR1). Furthermore, genes near the chromosome-12q13 breakpoint exhibited increased expression of GG-62 including ERBB3, NR4A1 (nuclear receptor subfamily 4, group A, member 1), cyclin-dependent kinase 2 ( CDK2), and alpha 5 integrin ( ITGA5). Altogether our findings demonstrate the MMSP derivation of GG-62 and may shed light on the mechanisms of tumorigenesis in this rare disease.

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Infiltration of sarcomas into the hip joint: comparison of CT, MRI and histologic findings in 67 cases. 国際誌

Toshifumi Ozaki, Marc Putzke, Horst Bürger, Georg Gosheger, Winfried Winkelmann, Norbert Lindner

Acta orthopaedica Scandinavica 73 ( 2 ) 220 - 6 2002年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

We analyzed the incidence, route, and characteristics of hip joint infiltration in pelvic or proximal femoral sarcomas. 67 patients with a sarcoma that originated around the hip joint (50 pelvic and 17 femoral) were included in this study. Preoperative CT and MRI were matched with the histological findings in tumor specimens. Tumor infiltration into the hip joint was suspected on the basis of preoperative imaging in 29 patients due to articular cartilage disruption, diffuse signal changes in the acetabulum or femoral neck, signs of a tumor in the joint, or markedjoint effusion. Of these 29 patients, 15 showed tumor invasion on histological examination. 12 of 31 chondrosarcomas, none of 12 Ewing's sarcomas, and 3 of 24 osteosarcomas infiltrated into the hip joint (p = 0.008). 10 of 26 low-grade sarcomas and 5 of 41 high-grade sarcomas infiltrated into the hip joint (p = 0.02). The joint infiltration rate of the chondrosarcomas was related to their size. Of 10 tumors originating in the acetabulum, 9 penetrated through or around the osseous-ligamentous junction and one through the acetabular cartilage. In 5 proximal femur lesions, all infiltrated the joint through the femoral neck, 3 of them also through the ligamentum teres.

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Osteoid osteoma and osteoblastoma of the spine: experiences with 22 patients. 国際誌

Toshifumi Ozaki, Ulf Liljenqvist, Axel Hillmann, Henry Halm, Norbert Lindner, Georg Gosheger, Winfried Winkelmann

Clinical orthopaedics and related research ( 397 ) 394 - 402 2002年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Osteoblastomas and osteoid osteomas of the spine are relatively rare bone-forming tumors. Between 1980 and 1999, nine patients with osteoid osteoma and 13 patients with osteoblastoma had surgery for their tumors. Four tumors were in the cervical spine, six tumors were in thoracic spine, 10 tumors were in the lumbar spine, and two tumors were in the sacrum. The average duration between onset of pain and surgery was 16.6 months in 12 patients treated in the 1980s and 8.6 months in 10 patients treated in the 1990s. Seventeen patients had scoliosis. In nine of 10 patients with magnetic resonance imaging scans, high signal intensity areas in the muscles and bone around the lesion were seen. Two of nine patients with osteoid osteoma and nine of 13 patients with osteoblastoma had neurologic disorders before treatment. All patients had open resection of the lesions. Two patients with osteoid osteoma had relapse because of incomplete resection, necessitating a second excision. In 16 of 17 patients with preoperative spinal deformity, the deformity improved during followup. With development of modern imaging techniques, exact surgical planning may become possible; however, in some cases, intraoperative complete resection of the lesion still is difficult.

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Implantation of hemipelvic prosthesis after resection of sarcoma. 国際誌

Toshifumi Ozaki, Christiane Hoffmann, Axel Hillmann, Georg Gosheger, Norbert Lindner, Winfried Winkelmann

Clinical orthopaedics and related research ( 396 ) 197 - 205 2002年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Twelve adult patients with pelvic sarcoma had implantation of a hemipelvic prosthesis. Eight patients had hemipelvic resection, and four patients had acetabulopubic resection. The implanted prosthesis was a special Vitallium prosthesis, which was specially designed for each patient with the aid of a computer. At a median followup of 57 months, eight patients were free of disease. In four patients with local relapse, two had additional resection, one had hindquarter amputation, and one was observed. In three patients with deep infection, the prosthesis was removed; however, one patient had hindquarter amputation. One patient had dislocation of the hip and prosthesis loosening. Overall survival of patients was 70%, and the survival of prostheses was 42%. In eight patients, the functional evaluation showed that the average functional score with the prosthesis was 11.6 (39%) and without the prosthesis the functional score was 7.0 (23%). Implantation of a megaprosthesis seems to indicate a high complication rate and a poor functional result after hemipelvic resection.

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Expression analysis of pediatric solid tumor cell lines using oligonucleotide microarrays. 国際誌

Daniel H Wai, Karl-Ludwig Schaefer, Alexander Schramm, Eberhard Korsching, Frans Van Valen, Toshifumi Ozaki, Werner Boecker, Lothar Schweigerer, Barbara Dockhorn-Dworniczak, Christopher Poremba

International journal of oncology 20 ( 3 ) 441 - 51 2002年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

We identified patterns of differentially-expressed genes in cell lines derived from several pediatric solid tumors. Affymetrix Human Cancer G110 Arrays, carrying 1,700 cancer-associated genes, were applied to a panel of 11 cell lines originating from Ewing tumors (ETs), neuroblastomas, and malignant melanoma of soft parts. Hierarchical clustering clearly differentiated these 3 entities and revealed groups of 75, 102, and 36 gene probe-sets exhibiting tumor-type specific up-regulation in these cell lines, respectively. Whereas ET lines demonstrated increased expression of microtubule-associated protein tau (MAPT), protein phosphatase 1 regulatory subunit 1A (PPP1R1A), NIMA (never in mitosis gene a)-related kinase 2 (NEK2), and cyclin D1 (CCND1), neuroblastoma samples exhibited high expression of wingless-type mouse mammary tumor virus integration site family member 11 (WNT11), Drosophila frizzled homolog 2 (FZD2), and adenomatous polyposis coli (APC) which are involved in regulating free beta-catenin levels. These genes likely maintain tumor-specific characteristics and participate in key downstream regulatory mechanisms. We also correlated the expression levels of up-regulated genes in ETs with their chromosomal localization and compared these data to the comparative genomic hybridization profiles of the cell lines. We demonstrate that gains of genetic material contribute essentially to differential gene expression.

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Osteosarcoma of the spine: experience of the Cooperative Osteosarcoma Study Group. 国際誌

Toshifumi Ozaki, Silke Flege, Ulf Liljenqvist, Axel Hillmann, Günter Delling, Mechthild Salzer-Kuntschik, Heribert Jürgens, Rainer Kotz, Winfried Winkelmann, Stefan S Bielack

Cancer 94 ( 4 ) 1069 - 77 2002年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Due to the low incidence rate, the optimal strategy for the treatment of patients with spinal osteosarcoma is unknown. METHODS: Twenty-two patients with osteosarcoma of the spine (15 with tumors of the sacrum and 7 with tumors at other sites) who received chemotherapy according to the Cooperative Osteosarcoma Study Group protocol were analyzed. Six patients presented with metastasis, and 16 patients had no evidence of metastasis at the time of entry into the protocol. Of 12 patients who underwent excision of their tumors, 2 patients underwent wide excision, 3 patients underwent marginal excision, and 7 patients underwent intralesional excision. Eight patients received irradiation: Six patients received conventional radiotherapy only, one patient received neutron beam therapy, and one patient received samarium-153-ethylene diamine tetramethylene phosphonate therapy. Follow-up ranged between 24 months and 105 months (median, 47 months). RESULTS: The median survival was 23 months, and three patients have survived without disease for > 6 years. Patients with primary metastases (P = 0.004), large tumors (P = 0.010), and sacral tumors (P = 0.048) had lower overall survival compared with patients who had no metastasis, small tumors, and nonsacral tumors, respectively. There was a significant difference in overall survival between 5 patients who underwent either wide or marginal surgery and 17 patients who underwent either intralesional surgery or no surgery (P = 0.033). Among 17 patients who underwent no surgery or intralesional surgery, overall survival tended to be better in 7 patients who received irradiation compared with the overall survival in 10 patients who did not receive irradiation (P = 0.059). CONCLUSIONS: Patients with metastases, a large tumors, and sacral tumors had a poor prognosis in the current study with small numbers of patients. Wide or marginal excision of the tumor improved survival. Patients with osteosarcoma of the spine should be treated with a combination of chemotherapy and at least marginal excision for those with surgically accessible tumors. Postoperative radiotherapy may be beneficial.

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Incidence and mechanisms of infiltration of sarcomas in the shoulder. 国際誌

Toshifumi Ozaki, Marc Putzke, Robert Rödl, Winfried Winkelmann, Norbert Lindner

Clinical orthopaedics and related research ( 395 ) 209 - 15 2002年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

The intraarticular infiltration of sarcomas around the shoulder was analyzed. Of 58 sarcomas located around the shoulder, which were treated between 1993 and 1998, 15 osteosarcomas, 12 chondrosarcomas, and one Ewing's sarcoma that abutted the shoulder were selected. Radiologic images of 28 tumors were analyzed and compared with pathologic examinations. In 17 of 28 sarcomas (15 in the proximal humerus and two in the scapula), joint infiltration was suspected radiologically because of the existence of a tumor mass probably inside the joint or disruption of the joint surface and protrusion of the tumor. Seven of 17 tumors with radiologically positive and zero of 11 tumors with radiologically negative findings showed histologically positive findings for tumor inside the joint. Four of 11 osteosarcomas and three of four chondrosarcomas of the proximal humerus showed histologic findings of joint infiltration. Pericapsular extension was seen in two patients, direct articular spread with a pathologic fracture was seen in two patients, direct articular spread was seen in one patient, direct articular spread with pericapsular extension was seen in one patient, and pericapsular extension with a pathologic fracture was seen in one patient. The current study showed that pericapsular or direct articular infiltration into the glenohumeral joint is a phenomenon in sarcoma around the shoulder. Exact assessment of tumor existence inside the joint can be difficult in osteosarcoma and chondrosarcoma, so abnormal radiologic findings should be regarded as proof of existence of tumor, and extraarticular wide resection should be planned.

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当科で経験した小児骨肉腫の治療成績

大畑範英, 川井章, 尾崎敏文, 森本裕樹, 井上一

中部日本整形外科災害外科学会雑誌 45 ( 6 ) 969 - 970 2002年

上腕骨近位転移性骨腫瘍に対する人工骨頭置換術の治療成績

森本裕樹, 川井章, 尾崎敏文, 杉原進介, 井上一

中部日本整形外科災害外科学会雑誌 45 ( 6 ) 961 - 962 2002年

Reconstruction of the proximal humerus with the clavicle after tumor resection: A case report

T. Ozaki, H. Hashizume, T. Kunisada, A. Kawai, K. Nishida, S. Sugihara, H. Inoue

Clinical Orthopaedics and Related Research 385 170 - 175 2001年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Lippincott Williams and Wilkins

Reconstruction of the proximal humerus after resection for tumor and modification of the clavicular transposition procedure is described in which the blood supply of the clavicle is preserved and the clavicle is used to bridge the defect. An 11-year-old boy presented with shoulder pain, and the diagnosis was osteosarcoma of the right proximal humerus. After resection of the sarcomatous proximal humerus, the clavicle was released with its periosteum remaining intact, and the clavicle was rotated downward around the acromioclavicular joint. A vascularized fibula supplemented the reconstruction in trying to gain length of the arm. The acromioclavicular joint and the vascular supply of the clavicle were preserved. Internal fixation from the clavicle and the fibula to the distal humerus was made with an AO plate and screws. Muscles around the proximal humerus were reattached to the clavicle. Range of motion of the shoulder was 80° flexion, 85° abduction, 30° external rotation, and 90° internal rotation. Although the postoperative followup is relatively short, only 2 years, the functional advantages of this operation over other forms of reconstruction can be observed.

DOI： 10.1097/00003086-200104000-00026

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A reverse transcriptase-polymerase chain reaction assay in the diagnosis of soft tissue sarcomas

N Naito, A Kawai, M Ouchida, T Dan'ura, Y Morimoto, T Ozaki, K Shimizu, H Inoue

CANCER 89 ( 9 ) 1992 - 1998 2000年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY-LISS

BACKGROUND. Many types of sarcomas are characterized by specific chromosomal translocations that result in the production of novel chimeric genes. Detection of these fusion genes could be a sensitive molecular diagnostic assay. However, to the authors' knowledge there have been few systemic comparisons between the current histopathologic diagnosis and the presence or absence of particular fusion genes in patients with adult soft tissue sarcomas (STSs).
METHODS. Total RNA was extracted from 75 cases of STS and analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) assay for the detection of a variety of fusion transcripts. The results of the molecular assay were compared with standard histopathologic diagnoses.
RESULTS. Of the 18 tumors diagnosed as synovial sarcoma, 17 (94%) expressed SYT-SSX chimeric transcripts. AU nine myxoid liposarcomas were positive for FUS-CHOP fusion transcripts. Of the four cases of Ewing sarcoma, two had an EWS-FLI1 fusion transcript and one had an EWS-ERG fusion transcript. A clear cell sarcoma had a EWS-ATF1 fusion transcript. None of 19 cases of malignant fibrous histiocytoma nor 3 leiomposarcomas contained a fusion transcript. Three cases with an initial diagnosis other than synovial sarcoma expressed a SYT-SSX fusion transcript. A review of the slides and additional examination showed that a diagnosis of synovial sarcoma was appropriate for these cases. There was a trend for biphasic synovial sarcoma to contain the SYT-SSX1 fusion.
CONCLUSIONS, The authors believe RT-PCR assay for the detection of a specific fusion gene provides a useful tool for confirmation of the diagnosis of adult STS in diagnostically difficult cases and in retrospective studies. (C) 2000 American Cancer Society.

DOI： 10.1002/1097-0142(20001101)89:9<1992::AID-CNCR16>3.0.CO;2-R

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Expression of connective tissue growth factor in cartilaginous tumors 査読

Toshihiko Shakunaga, Toshifumi Ozaki, Nobuya Ohara, Koji Asaumi, Takeshi Doi, Keiichiro Nishida, Akira Kawai, Tohru Nakanishi, Masaharu Takigawa, Hajime Inoue

Cancer 89 ( 7 ) 1466 - 1473 2000年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND. Connective tissue growth factor (CTGF) predominantly is expressed in hypertrophic chondrocytes and its specific receptors are demonstrated on chondrocytic cells. Therefore, CTGF may be involved in the proliferation and/or differentiation of cartilage cells. In the current study, CTGF expression was examined both in chondrosarcoma and enchondroma to clarify the relation between the expression of CTGF and the grade of malignancy. METHODS. The expression of CTGF and proliferating cell nuclear antigen (PCNA) were analyzed immunohistochemically in 34 cartilaginous tumor specimens. Eighteen tumors were determined to be chondrosarcoma including 8 Grade 1 tumors, 6 Grade 2 tumors, and 4 Grade 3 tumors. The percentage of CTGF positive and PCNA positive cells was quantified using at least 500 cells. RESULTS. CTGF was expressed in 70.1% of enchondroma cells, 84.0% of Grade 1 chondrosarcoma cells, 53.7% of Grade 2 tumor cells, and 26.8% of Grade 3 tumor cells (ρ = -0.501
P = 0.0053). In chondrosarcoma cases, CTGF expression was correlated closely with tumor grade (ρ = -0.920
P = 0.0001). There was a strong correlation between PCNA expression and tumor grade (ρ = 0.907
P &lt
0.0001) and a strong negative correlation between CTGF and PCNA expression (ρ = -0.493
P = 0.0061). In chondrosarcoma cases, patients with high expression of CTGF (≥ 30%) showed higher overall survival compared with those with low expression (&lt
30%) (P = 0.004). CONCLUSIONS. The current study revealed a correlation between the histologic grade of chondrosarcoma and prognosis, and the concomitant association between CTGF immunostaining and tumor grade and prognosis. Therefore, immunohistochemical staining with CTGF is a useful procedure for assessing the tumor grade anti clinical course in patients with chondrosarcoma. (C) 2000 American Cancer Society.

DOI： 10.1002/1097-0142(20001001)89:7<1466::AID-CNCR8>3.0.CO;2-G

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Synovial sarcoma with a large hematoma in the inguinal region 査読

N Naito, T Ozaki, T Kunisada, A Kawai, T Dan'ura, Y Morimoto, H Inoue

ARCHIVES OF ORTHOPAEDIC AND TRAUMA SURGERY 120 ( 9 ) 533 - 534 2000年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER-VERLAG

We report the case of a patient with synovial sarcoma and a large hematoma of the inguinal region. The patient underwent tumor resection of the lower 2/3 of the acetabulum after preoperative chemotherapy. Twenty-four months after surgery, she is alive without any relapse and can walk without support.

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CD44 expression in soft tissue sarcomas

Kahara N, Ozaki T, Doi T, Nishida K, Kawai A, Shibahara M, Inoue H

Virchows Arch 436 ( 6 ) 574 - 578 2000年6月

Giant schwannoma of the back 査読

Eiichi Takada, Toshifumi Ozaki, Toshiyuki Kunisada, Yoshiaki Harada, Hajime Inoue

Archives of Orthopaedic and Trauma Surgery 120 ( 7-8 ) 467 - 469 2000年

Ｋｏｔｚ（ＫＭＦＴＲ）人工関節を用いた膝周囲骨腫ようの治療成績

遠藤裕介, 川井章, 尾崎敏文, 内藤訓子, 杉原進介, 井上一

中国・四国整形外科学会雑誌 12 ( 2 ) 399 - 402 2000年

記述言語：日本語出版者・発行元：The Chugoku-Shikoku Orthopaedic Association

This report was based on our clinical results of 7 patients who were treated with Kotz knee arthoplasty from 1990 to 1998. Primary bone tumors were 5 osteosarcomas, 1 malignant fibrous histiocytoma, and 1 giant cell tumor. The average age at the time of operation was 22 years (11∼47) and the average duration of follow-up was 43 months. The clinical results were estimated by ISOLS system. Rizolli X-ray method was applied to evaluate the condition of the stem. At the latest review, the average of ISOLS score was 24 (80%). On X-rays, 4 cases were classified as stage A. The other 3 cases were calssified as stage B, C, and D respectively. The X-ray of the case scored as stage D was taken only 6 months after the operation. All patients were able to walk without any assistance. These results were satisfactory.

DOI： 10.11360/jcsoa1989.12.399

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Imaging assessment of the responses of osteosarcoma patients to preoperative chemotherapy: Angiography compared with thallium-201 scintigraphy 査読

Toshiyuki Kunisada, Toshifumi Ozaki, Akira Kawai, Shinsuke Sugihara, Kohji Taguchi, Hajime Inoue

Cancer 86 ( 6 ) 949 - 956 1999年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND. Assessment of the responses of osteosarcoma patients to preoperative chemotherapy is of clinical importance. The purpose of this study was to estimate the accuracy of angiography and thallium-201 scintigraphy, compared with histology, in assessing the responses of patients with osteosarcoma to preoperative chemotherapy. METHODS. Nineteen patients with osteosarcoma who were diagnosed between 1992 and 1997 were studied. The findings of angiography and thallium-201 scintigraphy before and after preoperative chemotherapy were compared with the percentage of necrosis of tumor cells and the response grade as determined histologically. Quantitative analysis of the isotopic uptake by thallium-201 scintigraphy before and after chemotherapy, defined as the alteration ratio, was correlated with the percentage of tumor necrosis. RESULTS. Angiography yielded a sensitivity of 88%, a specificity of 73%, and a predictive accuracy of positive test of 70%, whereas thallium-201 scintigraphy achieved 88%, 100%, and 100%, respectively. Both angiographic and scintigraphic assessment showed a significant correlation with response grade as determined histologically (P &lt
0.05 and P &lt
0.0003, respectively). The alteration ratio of thallium-201 scintigraphy showed a strong, highly significant correlation with the percentage of tumor necrosis (P &lt
0.0001). CONCLUSIONS. A change in the tumor uptake of thallium- 201 scintigraphy after preoperative chemotherapy can predict the tumor necrosis in osteosarcoma precisely. Thallium scintigraphy is a noninvasive technique and seems to be more useful than angiography in assessing the response of osteosarcoma to preoperative chemotherapy.

DOI： 10.1002/(SICI)1097-0142(19990915)86:6<949::AID-CNCR9>3.0.CO;2-H

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