Differential interactions of phytochrome A (Pr <i>vs.</i> Pfr) with monoclonal antibodies probed by a surface plasmon resonance technique

Natori, Chihoko,Kim, Jeong-Il,Bhoo, Seong Hee,Han, Yun-Jeong,Hanzawa, Hiroko,Furuya, Masaki,Song, Pill-Soon Royal Society of Chemistry 2007 PHOTOCHEMICAL AND PHOTOBIOLOGICAL SCIENCES Vol.6 No.1

<P>Phytochromes are red- and far-red light-reversible photoreceptors for photomorphogenesis in plants. Phytochrome A is a dimeric chromopeptide that mediates very low fluence and high irradiance responses. To analyze the surface properties of phytochrome A (phyA), the epitopes of 21 anti-phyA monoclonal antibodies were determined by variously engineered recombinant phyA proteins and the dissociation constants of seven anti-phyA monoclonal antibodies with phyA were measured using a surface plasmon resonance (SPR)-based resonant mirror biosensor (IAsys). Purified oat phyA was immobilized on the sensor surface using a carboxymethyl dextran cuvette in advance, and the interactions of each chosen monoclonal antibody against phyA in either red light absorbing form (Pr) or far-red light absorbing form (Pfr) at different concentrations were monitored. The binding profiles were analyzed using the FAST Fit program of IAsys. The resultant values of dissociation constants clearly demonstrated the differential affinities between the phyA epitopes and the monoclonal antibodies dependent upon Pr <I>vs.</I> Pfr conformations. Monoclonal antibody mAP20 preferentially recognized the epitope at amino acids 653–731 in the Pr form, whereas mAA02, mAP21 and mAR07/mAR08 displayed preferential affinities for the Pfr's surfaces at epitopes 494–601 (the hinge region between the N- and C-terminal domains), 601–653 (hinge in PASI domain), and 772–1128 (C-terminal domain), respectively. The N-terminal extension (1–74) was not recognized by mAP09 and mAP15, suggesting that the N-terminal extreme is not exposed in the native conformation of phyA. On the other hand, the C-terminal domain becomes apparently exposed on Pr-to-Pfr phototransformation, suggesting an inter-domain cross-talk. The use of surface plasmon resonance spectroscopy offers a new approach to study the surface properties of phytochromes associated with the photoreversible structural changes, as well as for the study of protein–protein interactions of phytochromes with their interacting proteins involved in light signaling events in plants.</P> <P>Graphic Abstract</P><P>This article describes a method, based on a surface plasmon resonance (SPR) technique, for studying surface properties of phytochrome and its protein–protein interactions involved in light signaling events in plants. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=b611077k'> </P>

Poster Session : PS 0333 ; Hematology : Multiple Neoplasms Including Malignant Lymphoma

( Kazuhiko Natori ),( Daisuke Nagase ),( Susumu Ishihara ),( Akiko Sakai ),( Yukitoshiq Toyoda ),( Motohiro Kato ),( Yasunobu Kuraishi ),( Kazuho Arai ),( Haruka Izumi ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: The clinical outcome of the malignant lymphoma improved and longterm survivor increased. In addition, the improvement of the examination technology and available PET/CT, screening ability rose, multiple neoplasms increased drastically last decade. We reviewed multiple neoplasms including the ML which accounted for a major ratio in hematological malignancies. Methods: We were approved privacy policy by the Ethical Review Board. Between January 1988 and December 2013, we reviewed multiple neoplasms including hematological malignancies. The diagnosis of the multiple neoplasms depends on a criteria of Warren & Gates. The defi nition of metachronous type and synchronous type is 6 months interval. Results: During the studied period, 285 cases became the subject of the examination. The multiple neoplasms including the ML was 161 cases in that. Median age was 70 years, male/female ratio was 101/60, double neoplasms were 135 cases, triple neoplasms 24 cases, quadple neoplasms 2 cases. The type of multiple neoplasms, metachrounaous type, synchronous type, were 120 cases, 41 cases respectively. In metachronous double type, all cases were102, and median time of interval was 59 months. The Consist of malignant neoplasms, gastric cancer 39 cases, colon cancer 26 cases, lung cancer 24 cases, hepatocellular carcinoma 13 cases, breast cancer 13 cases, prostate carcinoma 10 cases, and 18 kind of diagnosis 64 cases. On the other hand, kind of malignant lymphoma, Hodgkin`s lymphoma 7 cases, non-Hodgkin`s lymphoma 153 cases, adult T cell lymphoma 1 case. Median overall survival time was 33 months. About double neoplasms, median overall survival time between metachronous and synchronous type, there is signifi cance difference. Conclusions: In metachronous double type, all cases were102, 41 cases out of 102 cases were diagnosed within 5 years. We can discover metachronous multiple neoplasms by serial observations of fi ve years from an initial diagnosis.

Poster Session : PS 0332 ; Hematology : Malignant Lymphoma That Diagnosed from Gastric Biopsy

( Kazuhiko Natori ),( Daisuke Nagase ),( Susumu Ishihara ),( Yukitoshi Toyoda ),( Sakai ),( Motohiro Kato ),( Yasunobu Kuraishi ),( Kazuho Arai ),( Haruka Izumi ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Primary malignant gastrointestinal lymphoma accounts for 1-4% of malignant gastrointestinal tumors. Herein, we report the results of our study on 32 patients diagnosed from biopsy of stomach. Methods: From 2003 to 2012, we intended for 466 patients whom malignant lymphoma. 32 patients were selected. All patients were followed up until death or untile December 2013. Survival was measured from the diagnosis of multiple cancer to time of death or last contact. Results: All cases are 32 cases, gender male 16 cases, female 16 cases. Median age is 68 years, performance status is grade 0 20 cases, grade 1 7 cases, 2 grade 1 case, 3 grade 1 case, grade4 3 cases. Pathological fi ndings, 31 cases are non-Hodgkin`s lymphoma, 1 case is adult T cell lymphoma. Immnochemical stain fi ndings, diffuse laerge B cell type 21 cases, MALT lymphoma 8 cases, T cell lymphoma 1 cases, unknown 1 case. Clinical stage by Ann aobor classifi cation, stage IV is 13 cases, and Lugno classifi cation, L-I 17 cases, L-II-1 1 case, L-II-2 1 case. About therapy, CHOP or CHO therapy 3 cases(because of HBV active infection), rituximab +CHOP therapy 15 cases, Radiation therapy 4 cases, CHOP therapy after radiation therapy 2 cases, CHOP therapy after total gastrectomy 2 cases Eradication alone 1 case, chemotherapy ( CHOP therapy ) after eradication 1 case. Median survival time is not reached, 5 years survival rate is 66. 7%. At last December 2013, surviver is 23 cases, dead is 9 cases. Conclusions: The benefits of surgical treatment include decreased tumor amount by resection of local and regional lymph nodes, and more accurate diagnosis of the disease stage. However, we consider that the disadvantages of the majority of the recent therapies can be avoided by performing endoscopic examination and improving diagnostic imaging.

Poster Session : PS 0331 ; Hematology : Experience of Chemotherapy of Malignant Lymphoma in More Than 90 Years

( Kazuhiko Natori ),( Daisuke Nagase ),( Susumu Ishihara ),( Yukitoshi Toyoda ),( Akiko Sakai ),( Motohiro Kato ),( Yasunobu Kuraishi ),( Kazuho Arai ),( Haruka Izumi ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Though oral infection represented by caries and periodontal disease is the infectious disease that is thought with life-style related diseases generally. Including hematological malignancy, the infectious disease research before taking anticancer drug treatment is important. A potential infectious disease may bring about a fatal infectious disease for bone marrow suppression period. We report it this time about an oral surgery area as a search before treatment of the malignant lymphoma. Methods: In eight years from 2003 to 2012, we intended for a case in newly diagosed malignant lymphoma in our hospital. We reviewed having consultation or not of the oral surgery, treatment contents, having exodontia or not. Results: Among 383 patients, the oral surgery consultation was 271 cases, male female ration was 150/121. T, and the age median was 67years. It was 154 cases that it was judged that treatment was necessary. The case performed exodontia was 53 cases. Among 53 patients, 33 cases were progression stages. Conclusions: With the onset of febril neutropenia, the infectious disease that is not seen occurs with the normal immune status. An oral cavity lesion is a neighborhood of the central nerve system and is in very danger. Fortunately, there was not the case of death for the infection of the oral cavity lesion. However, malignant neoplasms patients has much dentistry treatment, and the exodontia number accounts for the majority, too.

Poster Session : PS 0328 ; Hematology : Metachronous Double Cancer Included B-Cell Chronic Lymphocytic Leukemia and Pancreatic Cancer That Diagnosed After Progression of Diabetes

( Kazuhiko Natori ),( Daisuke Nagase ),( Susumu Ishihara ),( Akiko Sakai ),( Motohiro Kato ),( Yasunobu Kuraishi ),( Kazuho Arai ),( Haruka Izumi ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Among the gastrointestinal cancers, pancreatic cancer has the poorest prognosis. It is important to diagnose patients when the pancreatic cancer is still operable, which remains the only effective procedure. The initial manifestations of pancreatic cancer include abnormal glucose tolerance and onset of diabetes. Methods: We experienced a patient with B-cell chronic lymphocytic leukemia (B-CLL) who was diagnosed with pancreatic cancer after progression of diabetes. Results: A 74-year-old man was diagnosed with B-cell chronic lymphocytic leukemia and was followed up at our outpatient department. In March 2011, he suffered from deterioration of diabetes (HgbA1c: 7. 6%) and underwent detailed examination. After examination, patient was diagnosed with Stage IV pancreatic cancer and is treated with gemcitabine monotherapy. Conclusions: The incidence of diabetes and abnormal glucose tolerance complicated with pancreatic cancer is relatively high. It has been shown that diabetes correlates positively with the risk of onset of pancreatic cancer. However, it has also been demonstrated that diabetes is the result rather than the risk factor of pancreatic cancer onset. Although abnormal glucose tolerance and diabetes onset are important as the initial manifestations of pancreatic cancer. It is necessary to diagnose patients in the early stage of pancreatic cancer, when it is still operable. In comparison with the conventional risk factors of smoking and diabetes, a family history of pancreatic cancer and various hereditary syndromes are much superior risk factors. Patients with pancreatic cancer who have at least 2 fi rst-degree relatives are considered to have familial pancreatic cancer.

Poster Session:PS 0224 ; Gastroenterology : HBV Infection Screening for Malignant Lymphoma

( Kazuhiko Natori ),( Susumu Ishihara ),( Daisuke Nagase ),( Akiko Sakai ),( Motohiro Kato ),( Yasunobu Kuraishi ),( Kazuho Arai ),( Haruka Izumi ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Malignant lymphoma(ML) is the ninth place cause of death in Japan and chemotherapy(CTx) is fi rst choice. Side effect of CTx, rituximab, reactivation of the Hepatitis B type virous(HBV) is serious problem. We reviewed the situation of the HBV infection check of patients that was performed CTx. Methods: We intended for patient which ML was diagnosed in our hospital from January 2003 to December, 2012. The pretreatment HBV check factor is hepatitis B surface antigen(HBsAg), hepatitis B surface antibody(anti-HBs), antihepatitis B core antibody(anti-HBc). When either anti-HBs or anti-HBc is positive, we measure viral amount by HBV-DNA Taqman. In the case of HBV check is imcomplete, additional HBV check followed as much as possible. We reviewed positive rate of HBsAg, anti-HBs, anti-HBc. Also we investigated HBV reactivation rate of R+CTx. Results: All cases were 446 cases, about type of malignant lymphoma, Hodgkin`s lymphoma(HL) 39 cases, non-Hodgkin`s lymphoma(NHL) 401 cases, Adult T cell Lymphoma( ATL) 6 cases. Among 446 patients, 411 cases received CTx or CTx+radiation therapy(RTx). HBsAg was examined in all cases, anti-HBs, anti-HBc was 351 cases, 261 cases respectively. The case searched three factors before CTx was 150 cases. 30 cases were searched HBV-DNA Taqman that indicated anti-HBs and/or anti-HBc were positive. In theses cases, treatment needed situation were 5 cases. These 5 cases treated by entecavir and after 2 weeks, CTx performed. The case that already given an antiviral drug with HBsAg positive for treatment was 4 cases. 107 cases were searched anti-HBs, anti-HBc or either after CTx. 2 cases was revealed to have needed the administration of antiviral drug. HBV reactivation rate was 0%. Conclusions: Only 2 cases needed therapy for HBV infection that were revealed after CTx. We do check in all cases and try for safe chemotherapy especially rituximab including regimen.

Poster Session : PS 0338 ; Hematology : The Multiple Neoplasms Consist of Colon Cancer and Hematological Malignancy

( Kazuhiko Natori ),( Susumu Ishihara ),( Daisuke Nagase ),( Yukitoshi Toyoda ),( Akiko Shibuya ),( Motohiro Kato ),( Yasunobu Kuraishi ),( Kazuho Arai ),( Haruka Izumi ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Colon cancer accounts for number of cases, a superior of the cause of death like gastric cancer, lung cancer. Wereport aggregates the multiple neoplasms including hematological malignancy and colon cancer. Methods: In the case that hematologic malignancy was diagnosed in our hospital by 1988 from 2013, The multiple cancer including colon cancer and the hematologic malignancy was 45 cases. So we reviewed and reported. Results: All cases are 45 cases, including female 14 cases, male 31cases, synchronous type 15 cases, metechronous type 30 cases. Multiple neoplasms consist of double cancer 33 cases, triple cancer 11 cases, quadrop cancer 1case. The median interval period in double cancer is 58 months. Hematological malignancy consist of non-Hodgkin`s lymphoma 24 cases, Hodgkin`s lymphoma 1 case, myelodysplastic syndrome 6 cases, chronic myelogeneou leukemia 3 cases, multiple myeloma 5 cases, macroglobrinemia 2 cases, acute lymphoblastic leukemia 3 cases, acute myelogeneous leukemia 2 case. Chronic lymphocytic leukemia 1 case. The sites of colon cancer studied 41 cases and results were that ascending colon 7cases, transverous colon 3cases, descending colon 2cases, sigmoid colon 9cases, rectum 8 cases. In a double cancer, 12 cases were preceding colon cancer and 9 cases were preceding hematological malignancy, an interval of the colon cancer precedence cases, the median time was 83M, hematological malignancy precedence cases was 42M. Median survival time is 15M, about cause of death, 21 cases still alive and 24 cases are dead. In 24 cases, hematological malignancy 17 cases, colon cancer 7 cases. Conclusions: In the case of hematological malignancy precedence case, 4 of 9 colon cancer occurred within three years. We should take attention about incidence of other malignancies, particularly those that occur from gastrointestinal tract and serious observation about distant metastasis site, such as liver and lung.

Poster Session : PS 0336 ; Hematology : Hodgkin`s Lymphoma in Our Hospital

( Kazuhiko Natori ),( Daisuke Nagase ),( Susumu Ishihara ),( Akiko Sakai ),( Motohiro Kato ),( Yasunobu Kuraishi ),( Kazuho Arai ),( Haruka Izumi ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: In Japan, ML is hematological malignancies with much number of cases. non-Hodgkin`s lymphoma(NHL) is more than 90%. There is extremely little number of patients Hodgkin`s lymphoma(HL). In Europe, the rarion between NHL and HL, is almost half and half. So we paid attention to HL and examined. Methods: We intended for patient which ML was diagnosed in our hospital from January 2003 to December, 2012. We studied and reported 38 cases about age, gender, pathological fi ndings, therapy, median survival time, 5 years survival rate. Survival was measured from the diagnosis of multiple cancer to time of death or last contact. Results: All cases were 38 cases, gender ration was male 23 cases, female 16 cases. Median age was 45 years, pathological fi ndings, L-D 1 case, L-P 1 case, L-R 6 cases, MC 15 cases, PHL 1 case, NS 14 cases. About clinical stage, I was 5 cases, II was 15 cases, III was 10 cases, IV was 7 cases. Adult patients were 25 cases, elderly patients were 13 cases. About therapy, more than 65 years old that assumed Bleomycine skipped. ABVD therapy performed 26 cases, ABVD therapy + RTx 1 case, AVD therapy 8 cases, C-MOPP therapy 3 cases. Median survival time was 84 months, and 5 years survival rate was 79. 6%. About age, less than 60 years group did not reach median survival time, median survival time of more than 60 years group was 76 months. There is no signifi cant difference between 2 group. 29 cases were survivor and death cases were 9 cases. Cause of death, 8 cases due to original disease, 1 case another reason( because of lung cancer). Conclusions: HL is good prognosis disease in hematological malignancies, but in more than 60 years patients, there is many problem.

Poster Session : PS 0330 ; Hematology : Experience of Chemotherapy of Malignant Lymphoma in More Than 90 Years

( Kazuhiko Natori ),( Susumu Ishihara ),( Daisuke Nagase ),( Yukitoshi Toyoda ),( Akiko Sakai ),( Motohiro Kato ),( Yasunobu Kuraishi ),( Kazuho Arai ),( Haruka Izumi ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Chemotherapy of the elderly person was common practice. Clinical outcome is force to equal an adult. However, a patient 90 years or older has a high risk of chemotherapy. We report our experience with two patients of malignant lymphoma 90 years or older. Methods: In periods from 2003 to 2013, patients whom malignant lymphoma was diagnosed in our hospital, we extracted a case 90 years or older. We reviewed gender, clinical stage, chemotherapy, dosage, clinical outcome, and prognosis. Results: Case 1: 91-year-old male, fi rst manifestation was systemic lymphadenopathy, Sufferings from dyspnea, he became the hospitalization. Pleural effusion was revealed, after lymph node biopsy, he was diagnosed non-Hodgkin`s lymphoma diffuse large B cell (NHL DLBCL). We performed chemotherapy by his strong wish. After 3 course of R-CHOP (dosage 50%), he achieved partial remission and was able to return to the house. He died after a diagnosis in 13 months. Case 2: 90-year-old female, fi rst manifestation was dysfunction of artifi cial denture, she had a checkup in dentistry. At the time dentist discovered a mass lesion and performed biopsy. Diagnosis was NHL DLBCL, and she was referred and had performed chemotherapy our hospital. After 6 course of R-CHOP (dosage 65%), she achieved complete remission and he still alive. Conclusions: It is got enough cinical outcome from even a case 90 years or older bychemotherapy. However, drug reduction criteria are not established that are indispensable for safe chemot

Poster Session : PS 0327 ; Hematology : Multiple Neoplasms Including Myelodysplastic Syndrome

( Kazuhiko Natori ),( Susumu Ishihara ),( Daisuke Nagase ),( Akiko Sakai ),( Motohiro Kato ),( Yasunobu Kuraishi ),( Kazuho Arai ),( Haruka Izumi ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: The myelodysplastic syndrome is blood stem cell disease and in many cases, have cytogenetic abnormality. And myelodysplastic syndrome has characteristic that there is defi ection in elderly. But progress of therapy and supporting therapy improved a prognosis. The possibility that a survivor had the second malignancy rise. we reviewed multiple neoplasms including the myelodysplastic syndrome and we report. Methods: In the case that hematologic malignancy was diagnosed in our hospital from 1988 to 2012, we intended for double cancer 271 cases including hematological malignancy. We reviewed 43 multiple neoplasms including the myelodysplastic syndrome. The examination factors are type of the hematological malignancy, treatment, gender, interval with the second cancer. Results: All cases are 43 cases, including male 29 cases, female 14 cases, type of multiple neoplasms, double 40 cases, triple 3 cases, kind of multiple neoplasms, metachronous 31 cases, synchronous 12 cases. The malignancies to constitute multiple neoplasms with myelodysplastic syndrome are gastric cancer 11 cases, esophangeal carcinoma 5 cases, breasr cancer 3 case, multiple myeloma 6 cases, non-Hodgkin`s lymphoma 3 cases, colon cancer 5 cases, lung cancer 4 cases, renal carcinoma 2 cases, urinary bladder carcinoma 2 cases, prostate carcinoma 1 case, thyroid cancer 1 case, pharyngeal cancer 1 case, laryngeal cancer 1 case, angiosarcoma 1 case. On the other hand, acute myelogeneous leukemia, therapy-related leukemia are11 cases, de novo myelodysplastic syndrome 32 cases. Conclusions: The survivors by the fi rst cancer therapy are paid attention to therapy- related myelodysplastic syndrome.