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Masatoshi Hasegawa

Publications and source records attributed to Masatoshi Hasegawa.

At least 19 recordsLinked to original sources
PubMed2006

Systematic characterization of 2'-deoxynucleoside- 5'-triphosphate analogs as substrates for DNA polymerases by polymerase chain reaction and kinetic studies on enzymatic production of modified DNA.

We synthesized C5-modified analogs of 2'-deoxyuridine triphosphate and 2'-deoxycytidine triphosphate and investigated them as substrates for PCRs using Taq, Tth, Vent(exo-), KOD Dash and KOD(exo-) polymerases and pUC 18 plasmid DNA as a template. These assays were performed on two different amplifying regions of pUC18 with different T/C contents that are expected to have relatively high barriers for incorporation of either modified dU or dC. On the basis of 260 different assays (26 modified triphosphates x 5 DNA polymerases x 2 amplifying regions), it appears that generation of the full-length PCR product depends not only on the chemical structures of the substitution and the nature of the polymerase but also on whether the substitution is on dU or dC. Furthermore, the template sequence greatly affected generation of the PCR product, depending on the combination of the DNA polymerase and modified triphosphate. By examining primer extension reactions using primers and templates containing C5-modified dUs, we found that a modified dU at the 3' end of the elongation strand greatly affects the catalytic efficiency of DNA polymerases, whereas a modified dU opposite the elongation site on the template strand has less of an influence on the catalytic efficiency.

DNA↗
PubMed2006

A prospective study of reduced-dose three-course CHOP followed by involved-field radiotherapy for patients 70 years old or more with localized aggressive non-Hodgkin's lymphoma.

PURPOSE: We conducted a multicenter prospective study to evaluate the efficacy and safety of reduced-dose three-course CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) followed by involved-field radiotherapy for elderly patients with localized aggressive non-Hodgkin's lymphoma. The primary endpoint was compliance with the combined modality. METHODS AND MATERIALS: This study included untreated patients, > or =70 years old, with diffuse aggressive lymphoma, Stage IA or contiguous nonbulky Stage IIA. 80%-CHOP (cyclophosphamide 600 mg/m(2), doxorubicin 40 mg/m(2), vincristine 1.1 mg/m(2), and prednisolone at 80 mg/day for 5 days) was repeated every 3 weeks. After three cycles of chemotherapy, involved-field radiotherapy was performed with a radiation dose of 30-50 Gy in 15-28 fractions. RESULTS: Twenty-four patients with a median age of 75 years (range, 70-84 years) were enrolled. The compliance rate of the protocol study was 87.5% (95% confidence interval [CI], 67.6-97.3). Three patients received only two cycles of chemotherapy because of toxicity or second neoplasm. There were no deaths caused by severe toxicity. The 3-year progression-free and overall survival rates were 83.1% (95% CI, 75.4-90.8) and 82.9% (95% CI, 75.1-90.6), respectively. CONCLUSION: Three-course 80%-CHOP followed by involved-field radiotherapy may be safe for administration to elderly patients over 70 years old. The next step is to evaluate three-course 80%-CHOP and rituximab followed by radiotherapy in elderly patients with localized disease.

Aged↗
PubMed2006

In-vivo visualization of radiation-induced apoptosis using (125)I-annexin V.

BACKGROUND: As apoptosis occurs in tumors within a short time after irradiation, the detection of the frequency of apoptosis may be useful as an indicator of the effect of treatment. For the evaluation of apoptosis under these conditions, tissue extraction from patients is indispensable. AIM: To develop a noninvasive imaging technique to measure and monitor apoptosis in tumor cells caused by X-irradiation using (125)I-radiolabeled annexin V. METHODS: The tumors used were human ependymoblastomas, which were transplanted into nude mice. The tumors were irradiated at 2, 5 or 10 Gy. (125)I-annexin V was administered intravenously 6 h after irradiation. In the 5 Gy irradiation group, the isotope was injected at various time intervals (3, 6 and 12 h) after irradiation. Three hours after the injection, the mice were sacrificed, the tumors were quickly removed and frozen sections were prepared at 6 and 40 microm thickness using a cryomicrotome. In autoradiographic imaging, the tumor-to-muscle ratios were compared in the respective irradiated groups. In addition, apoptosis detection by the in-situ end-labeling (Klenow) assay was conducted on the same sections. The number of Klenow-positive cells was counted in 100 x fields for each section. RESULTS: Both autoradiography and immunohistochemical staining showed a significantly higher frequency of apoptosis in the neoplasms in all irradiated groups than in the control group (P<0.05). Although immunohistochemical staining revealed a peak apoptosis frequency in the 5 Gy irradiated group, autoradiography revealed a peak in the group receiving a lower dose than 5 Gy. When the time from irradiation to annexin injection was varied, both imaging methods showed a peak apoptosis frequency in the group receiving the injection 6 h after irradiation. CONCLUSION: It is possible to predict the effect of treatment in cancer in a noninvasive manner by apoptosis imaging in vivo after radiotherapy.

Animals↗
PubMed2006

Radiation therapy alone for stage I (UICC T1N0M0) squamous cell carcinoma of the esophagus: indications for surgery or combined chemoradiotherapy.

BACKGROUND AND AIM: The aim of this study was to clarify the efficacy and limitations of radiation therapy (RT) for superficial esophageal carcinoma, and to explore the indications for more aggressive therapy, such as combined chemo-radiotherapy. METHODS: Sixty-eight patients with stage I (UICC T1N0M0) esophageal squamous cell carcinoma treated by definitive RT alone were analyzed. Brachytherapy was administered in 36 patients as a boost, and the prescribed doses were 10 Gy (5 Gy x 2 times) at a low dose rate (19 patients) and 9 Gy (3 Gy x 3 times) at a high dose rate (17 patients). Recurrence patterns and survival rates were assessed and the factors predisposing to recurrences after RT were statistically investigated by univariate analysis. RESULTS: The 5-year cause-specific survival rate and the locoregional control rate were 79.9% and 82.1%, respectively. No case of recurrence or disease-related death was observed in any of the patients with mucosal cancer. Among the cases with the cancer invading the submucosa, there were 12 cases with locoregional recurrence and two cases with distant metastases. In cases of submucosal esophageal cancer, the tumor length was the only statistically significant factor predicting locoregional control. The 5-year locoregional control rate in cases with a short length of the tumor ( 5 cm in length was 57.8% (P = 0.036). Patients treated by additional brachytherapy exhibited better cause-specific survival and locoregional control rates than those receiving external RT alone, however, the addition had no statistically significant influence on the outcome. CONCLUSIONS: RT was a successful treatment for stage I esophageal cancer, and the treatment outcome using RT was nearly comparable to that of surgery. However, it is suggested that chemo-radiation should be considered in inoperable cases of submucosal cancer when the tumor is more than 5 cm in length.

Aged↗
PubMed2005

FDG-PET in the detection of recurrence of uterine cervical carcinoma following radiation therapy--tumor volume and FDG uptake value.

PURPOSE: We evaluated the use of positron emission tomography (PET) with fluorine-18-labeled fluoro-2-deoxy-d-glucose (FDG) in follow-up study after radiation therapy in patients with uterine cervical carcinoma. MATERIALS AND METHODS: Thirty-two studies in 25 patients were reviewed. Twenty patients were treated with external beam irradiation and intracavitary brachytherapy, and five with irradiation following initial surgery. Time from initial treatment to FDG-PET was 23.3 (5.2-88.0) months. Rationale for FDG-PET was the presence of symptoms in 6 patients, abnormal serum tumor marker values in 13, abnormal lesions on other diagnostic imaging modalities in 19, and patient request in 2. On visualization of a lesion, the maximum standardized uptake value (maxSUV) of the lesion was calculated, and values over 2.0 were classified as FDG-positive. Maximum tumor diameter and tumor volume in the corresponding disease were estimated by computed tomography (CT) or magnetic resonance imaging (MRI). RESULTS: Sensitivity and specificity of FDG-PET in the detection of recurrent disease were 91.5% (43/47) and 57.1% (4/7), respectively. Four false-negative findings were seen for small lung metastases having a volume less than 1 cm3. Three false-positive cases were a localized pneumonitis, a benign pubic bone fracture, and a fibrosis after interstitial brachytherapy. Sensitivity for extrapelvic lymph node metastases was extremely high (100%); in contrast, sensitivity and specificity for lung and bone lesions were 75.0% (12/16) and 33.3% (1/3), respectively. Regarding tumor volume measurement, good correlation between maxSUV on FDG-PET and tumor volume was obtained (lung metastases, P = 0.03; extrapelvic nodes, P < 0.0001). Within this study, all corresponding lesions over 1 cm3 showed a maxSUV value greater than 2.0. CONCLUSION: FDG-PET is a useful tool for the detection of extrapelvic lesions during the follow-up period after radiation therapy for cervical cancer. This study suggests that FDG uptake is associated with tumor volume, and FDG-PET has limitations in the detection of lesions less than 1 cm3 or microscopic disease. Careful diagnostic agreement between PET and CT/MRI for positive but benign lesions, such as inflammation and bone fracture, remains important.

Adult↗
PubMed2005

Results of radiation monotherapy for primary central nervous system lymphoma in the 1990s.

PURPOSE: Results of radiation therapy for primary central nervous system lymphoma (PCNSL) were poor in the 1970-1980s, with most reported 5-year survival rates being less than 10%. To investigate whether the prognosis of PCNSL patients treated by radiation alone remains still poor, we investigated the results of radiation monotherapy in the 1990s. METHODS AND MATERIALS: We collected data on 132 patients with histologically proven PCNSL treated by radiation alone in the 1990s from three nationwide or regional multiinstitutional studies conducted by the Japanese Society for Therapeutic Radiology and Oncology (JASTRO) Lymphoma Study Group or the Chubu Radiation Oncology Group. Follow-up data were updated as far as possible. Eleven patients who did not complete planned radiotherapy were included. The data were analyzed in relation to patient and tumor characteristics. The median patient age was 63 years, and the World Health Organization performance status (PS) was 3 or 4 in 40% of the patients. Multiple tumors were seen in 34%. Whole-brain irradiation with or without focal boost was used in 92%. The median radiation dose to the tumor site was 50 Gy (range, 8-74 Gy). RESULTS: For all 132 patients, the median survival time was 18 months and the 5-year survival rate was 18.0%. For 62 patients with PS 0-3 and aged 16-65 years (i.e., those eligible for the European Organization for Research and Treatment of Cancer 20962 study), the median survival was 26 months and 5-year survival was 24%. The 5-year survival was 25% for patients 63 years old or younger, and 9.8% for those older than 63 years (p = 0.0005). The 5-year survival was 22% for patients with PS 0-2 and 13% for those with PS 3 or 4 (p = 0.0040). Multivariate analysis confirmed the negative influence of higher age on patient prognosis. CONCLUSIONS: The results of radiation monotherapy for PCNSL appear to have improved as compared with those reported previously. The results of new treatment should be evaluated in light of this finding. Since most prospective studies on the combined treatment exclude poor PS and high-age patients, the 5-year survival rate of 30% may not be regarded as a marked improvement over radiation alone.

Adolescent↗
PubMed2005

Expansion of repertoire of modified DNAs prepared by PCR using KOD Dash DNA polymerase.

Thymidine analogues bearing a variety of functional groups at the C5-position via an amino-linker arm were prepared and the substrate activity for PCR using thermophilic KOD Dash DNA polymerase was examined. The enzyme accepted the thymidine analogues bearing pyridine, imidazole, biotin, a cationic-charged guanidinium, a cationic-charged amino, mercaptopyridyl and phenanthrolne groups at the C5-position, forming the corresponding PCR product. However, a thymidine analogue bearing a carboxyl group at the C5-position was a poor substrate and the corresponding PCR products could not be obtained. The thymidine analogue bearing a mercapto group was also a poor substrate for the enzyme, because it dimerized by disulfide linkage under PCR conditions. The enzyme hardly accepts the thymidine analogues with a negatively-charged carboxyl group or a bulky group as a substrate. KOD Dash DNA polymerase, having a broader substrate specificity than any other DNA polymerase, will expand the variety of modified DNAs that can be prepared by PCR.

Amines↗
PubMed2005

Attenuation of chronic thermotolerance by KNK437, a benzylidene lactam compound, enhances thermal radiosensitization in mild temperature hyperthermia combined with low dose-rate irradiation.

PURPOSE: We investigated whether the attenuation of chronic thermotolerance by KNK437, a heat shock protein inhibitor, can modify the effect of thermal radiosensitization in mild temperature hyperthermia (MTH) combined with low dose-rate irradiation (LDRI). MATERIALS AND METHODS: The human lung adenocarcinoma cell line A549 was simultaneously exposed to LDRI with MTH at 41 degrees C and KNK437 at a dose of 100 microM. Cell survival was estimated by a clonogenic assay. Cell cycle change during treatment was analyzed by flow cytometry. Expression levels of the heat shock proteins hsp72, hsp27 and heat shock factor 1 (HSF-1) were measured by Western blotting. RESULTS: KNK437 inhibited the expression of inducible hsp72 and hsp27, but produced no change in the mobility shift of HSF-1. The cytotoxicity of LDRI was enhanced by MTH. The survival curve for LDRI + MTH revealed no development of chronic thermotolerance up to 48 h. Simultaneous LDRI and KNK437 treatment also resulted in enhanced cell killing. The radiosensitizing effect of KNK437 was enhanced by simultaneous exposure of the cells to MTH. Flow cytometry analysis of cell cycle progression demonstrated marked G2 arrest and mild G1 arrest with LDRI alone, but mild G1 arrest with MTH alone, and mild G2-M, S-phase accumulation with KNK437 alone. The marked G2 arrest caused by LDRI was partially suppressed by the addition of MTH, and was also suppressed by KNK437 treatment. CONCLUSIONS: Exposure of A549 cells to KNK437 caused inhibition of hsp72 and hsp27 expression. The addition of KNK437 increased not only thermosensitivity to MTH, but also radiosensitivity to LDRI. KNK437 also enhanced the MTH-induced radiosensitization under these experimental conditions.

Adaptation, Physiological↗
PubMed2005

Clinical outcomes and prognostic factors for patients with early esophageal squamous cell carcinoma treated with definitive radiation therapy alone.

GOALS AND BACKGROUND: There are great differences between treatment methods for early-stage esophageal cancer in institutions. Radiation therapy has been considered to be an effective modality as organ-preserving treatment of the disease. The aim of this study is to assess the effect and limitation of radiation therapy on patients with early esophageal cancer. STUDY: The subjects were 38 patients with stage I (T1N0M0) squamous cell carcinoma of the esophagus who had received definitive radiation therapy alone. Eleven tumors were assessed within the mucosal layer, whereas 27 tumors showed submucosal invasion by examination using endoscopic ultrasound. All patients were treated with more than 60 Gy using a conventional daily fractionation dose at 2 Gy. An additional boost with brachytherapy was performed for 20 patients, and the prescribed doses were 10 Gy (5 Gy x 2 times) with low dose rate (8 patients) and 9 Gy (3 Gy x 3 times) with high dose rate (12 patients). Outcomes and prognostic factors, including the efficacy of intraluminal brachytherapy, were investigated. RESULTS: The cause-specific survival rate and the local control rate at 5 years were 82.6% and 86.3%, respectively. Recurrences were noted in 8 patients with submucosal cancer, but no recurrence was observed in patients with mucosal cancer. In the present study, tumor length was a statistically significant prognostic factor for cause-specific survival (P = 0.018) and tumor depth tended toward statistical significance (P = 0.073). In 27 patients with submucosal cancer, the tumor length was also statistically significant for the survival (P = 0.032). The 5-year cause-specific survival rates for the short tumor group and the long tumor group were 85.7% and 55.6%, respectively. On the other hand, the use of intraluminal brachytherapy had no significant effect on patient survival. CONCLUSION: Radiation therapy is very effective for early esophageal squamous cell carcinoma with tumor length less than 5 cm, but other treatment modalities, including chemoradiotherapy especially for inoperable patients, should be considered for submucosal cancer with a tumor length of 5 cm or more.

Aged↗
PubMed2004

Expression of hypoxic-inducible factor 1alpha predicts metastasis-free survival after radiation therapy alone in stage IIIB cervical squamous cell carcinoma.

PURPOSE: Hypoxia-inducible factor-1alpha (HIF-1alpha) is an intrinsic marker of tumor hypoxia. It has been considered that the hypoxic status reduces radiosensitivity, but the role of HIF-1alpha in advanced cervical carcinoma is still unclear. The objective of this study was to clarify the impact of HIF-1alpha, human papillomavirus (HPV), and other molecular factors, such as p53, bax, bcl-2, and their correlations on the outcome of patients with Stage IIIB cervical carcinoma in radiation therapy. METHODS AND MATERIALS: We analyzed 38 patients with FIGO Stage IIIB squamous cell carcinoma of the cervix treated with radiation therapy alone. All patients received the combination therapy of external beam irradiation and low-dose-rate intracavity brachytherapy. The tumor expressions of HIF-1alpha, p53, bax, and bcl-2 were examined by immunohistochemical staining of the pretreatment paraffin embedded specimens. HPV infection was also detected by polymerase chain reaction. The effects of these parameters on clinical outcomes were analyzed by univariate analysis. RESULTS: Of 38 patients, high expression of HIF-1alpha, p53, bax, and bcl-2 were seen in 17 (45%), 22 (58%), 15 (39%), and 15 (39%) patients, respectively, and 28 patients (74%) showed positive infection with HPV. There was a significant positive correlation between high HIF-1alpha expression and disease recurrence (p < 0.05). Furthermore, HIF-1alpha had a significant correlation with the recurrence-free survival rate (p = 0.04). No statistical correlation was noted between high HIF-1alpha expression and the local control rate (p = 0.17), whereas the HIF-1alpha status predicted distant metastasis with strong significance (p = 0.03). Conversely, other factors demonstrated no impact on the clinical outcome. CONCLUSIONS: The present results suggest that HIF-1alpha is an important prognostic factor, especially for predicting future metastasis after radiation therapy for patients with Stage IIIB squamous cell carcinoma of the cervix.

Aged↗
PubMed2004

Primary central nervous system lymphoma in Japan 1995-1999: changes from the preceding 10 years.

PURPOSE: Previously, we conducted a nationwide survey of primary central nervous system lymphoma (PCNSL) treated between 1985 and 1994 in Japan. In the present study, we conducted further investigations of PCNSL patients treated between 1995 and 1999 to clarify possible changes with time in the clinical features, treatment, and outcome of this disease. METHODS: Thirteen Japanese institutions were surveyed, and data on 101 patients with histologically-confirmed PCNSL were collected. These data were compared with those of 167 patients treated at the same institutions between 1985 and 1994. RESULTS: Regarding patient and tumor characteristics, the proportion of patients with good performance status (PS) was significantly higher in the group treated during 1995-1999 than in that treated during 1985-1994, but other characteristics were not significantly different. Regarding treatment, more patients in the more recent period (66%) received systemic chemotherapy than those in the preceding period (53%, P = 0.049). For all patients, including those who did not complete radiotherapy, the median survival time was 17 months and 30 months in patients treated between 1985 and 1994 and those treated between 1995 and 1999, respectively, and the 5-year survival rate was 15% versus 31% (P = 0.0003). In both patient groups, higher age and tumor multiplicity were associated with poor prognosis in multivariate analysis. In patients treated between 1995 and 1999, those who received systemic chemotherapy showed significantly better prognosis than those who did not (P = 0.0049), but the difference was not significant in multivariate analysis (P = 0.23). CONCLUSIONS: The high survival rates observed in the present survey are comparable with those of recent prospective studies employing intensive chemoradiotherapy. The improvement in prognosis appeared to result, at least in part, from the increase in the proportion of patients with better PS. Since the clinical feature and treatment outcome of patients with PCNSL can thus change with the era, historical control data should not be used in comparing different treatment modalities.

Adolescent↗
PubMed2004

CT-fluoroscopy guided interstitial brachytherapy with image-based treatment planning for unresectable locally recurrent rectal carcinoma.

PURPOSE: The aim of the study is to develop high-dose-rate (HDR) conformal interstitial brachytherapy by means of combined CT-fluoroscopy guidance with CT-based treatment planning for locally recurrent rectal carcinoma. METHODS AND MATERIALS: Brachytherapy needle insertion was guided with a helical CT scanner providing continuous fluoroscopy reconstruction. A video monitor placed adjacent to the CT gantry simultaneously allowed the operator to see the process of needle insertion. Final CT images were transferred by an online system to the treatment-planning computer, which reconstructed the implant needles and organ contours. The doses in planning target volume were normalized and geometrically optimized. The patients received a brachytherapy dose at 5 Gy twice daily with a hypofractionated accelerated schedule at a total dose of 30-50 Gy with or without external radiation therapy. Eighteen patients were treated with this procedure. RESULTS: Ten to thirty-six needles (average, 17.3) were successfully placed to the planning target volume in each patient. The average time for CT fluoroscopy was 357 seconds for each procedure. No accident was seen at needle insertion, but 2 patients developed incomplete peroneal nerve palsy after needle removal, but gradually recovered. CT-based treatment planning was faster and more accurate than projection reconstruction with conventional radiograms. Analysis of the dose volume histogram showed conformal dose distribution to the target, while avoiding normal structures. CONCLUSION: CT fluoroscopy guidance ensures safety and increases the accuracy of needle placement in brachytherapy. Conformal high-dose-rate (HDR) interstitial brachytherapy with CT-based treatment planning is a method worth considering for locally recurrent rectal cancer.

Adenocarcinoma↗
PubMed2004

Screening of modified DNA aptamers that recognize DNA secondary structure.

We attempted to utilize in vitro selection techniques to develop modified DNA aptamers that are specific for DNA secondary structure including a single-mismatch base pair. For the selection, two kinds of random modified DNA library were prepared by an enzymatic method using modified 2'-deoxynucleoside 5'-triphosphates and KOD Dash DNA polymerase: one library consists of modified DNA including amino functionality and another consists of modified DNA including both hydroxypropynyl and guanidium functionalities.

Aptamers, Nucleotide↗
PubMed2003

Treatment results of radiotherapy for malignant lymphoma of the orbit and histopathologic review according to the WHO classification.

PURPOSE: To analyze the results of radiotherapy (RT) for malignant lymphoma of the orbit and to evaluate them compared with the World Health Organization (WHO) classification published in 2001. METHODS AND MATERIALS: The data from 29 patients with malignant lymphoma of the orbit treated with RT at Gunma University Hospital between 1978 and 2001 were retrospectively analyzed. Pathologic slides from 23 cases were available and were reviewed by a hematopathologist according to the WHO classification. The original and reviewed diagnoses, patient characteristics, treatment results, and complications were analyzed. In principle, patients with low-grade or indolent lymphoma were treated with RT alone, using 30 Gy as the tumor dose. Survival data were calculated using the Kaplan-Meier method. RESULTS: One case that proved to be a pseudotumor was excluded from evaluation. Of the 28 cases, 25 were Stage IAE, 1 was Stage IIAE, and 2 were Stage IVAE. The median follow-up was 71 months. According to the original classification and the Working Formulation, the 5- and 10-year overall survival rate of patients with low-grade lymphoma was 94% and 73%, respectively. The corresponding rates for those with intermediate-grade lymphoma were 67% and 67% (p = 0.15). In contrast, the WHO classification showed a significant difference in the survival curves. The 5- and 10-year overall survival rate of patients with mucosa-associated lymphoid tissue (MALT) lymphoma was 100% and 88%, respectively; for diffuse large B-cell patients, the rates were both 0% (p < 0.001). In patients with MALT lymphoma, one local and four distant relapses developed; two of them >10 years after initial treatment. All of the relapsed MALT lymphomas were controlled by salvage therapy. CONCLUSION: Excellent local control and survival can be achieved for patients with orbital MALT lymphoma using RT alone. A precise histopathologic diagnosis using the WHO classification and long-term follow-up for >10 years is recommended.

Adult↗
PubMed2003

Cis,cis,cis-1,2,4,5-cyclohexanetetracarboxylic acid and its dianhydride.

cis,cis,cis-1,2,4,5-Cyclohexanetetracarboxylic acid, C(10)H(12)O(8), (I), contains a mirror plane and the cyclohexane ring exhibits a chair conformation. Two crystallographically independent hydrogen bonds form R(2)(2)(14), R(2)(2)(16) and R(4)(4)(16) ring motifs, and propagation of these two hydrogen bonds along the c and b axes generates C(2)(2)(16) and C(2)(2)(7) chains. cis,cis,cis-1,2:4,5-Cyclohexanetetracarboxylic dianhydride, C(10)H(8)O(6), (II), was prepared by the reaction of (I) with acetic anhydride. The cyclohexane ring of (II) exhibits a boat conformation and the dihedral angle between the two anhydro rings is 117.5 (1) degrees.

Journal Article↗