Mapping of a New Deformation Region around

We performed the first direct mass measurements of neutron-rich scandium, titanium, and vanadium isotopes around the neutron number 40 at the RIKEN RI Beam Factory using the time-of-flight magnetic-rigidity technique. The atomic mass excesses of ^{58-60}Sc, ^{60-62}Ti, and ^{62-64}V were measured for the first time. The experimental results show that the two-neutron separation energies in the vicinity of ^{62}Ti increase compared to neighboring nuclei. This shows that the masses of Ti isotopes near N=40 are affected by the Jahn-Teller effect. Therefore, a development of Jahn-Teller stabilization appears below the Cr isotopes, and the systematics in Sc, Ti, and V isotopes suggest that ^{62}Ti is located close to the peak of the Jahn-Teller effect.

Expansion and further delineation of the SETD5 phenotype leading to global developmental delay, variable dysmorphic features, and reduced penetrance.

Diagnostic exome sequencing (DES) has aided delineation of the phenotypic spectrum of rare genetic etiologies of intellectual disability (ID). A SET domain containing 5 gene (SETD5) phenotype of ID and dysmorphic features has been previously described in relation to patients with 3p25.3 deletions and in a few individuals with de novo sequence alterations. Herein, we present additional patients with pathogenic SETD5 sequence alterations. The majority of patients in this cohort and previously reported have developmental delay, behavioral/psychiatric issues, and variable hand and skeletal abnormalities. We also present an apparently unaffected carrier mother of an affected individual and a carrier mother with normal intelligence and affected twin sons. We suggest that the phenotype of SETD5 is more complex and variable than previously presented. Therefore, many features and presentations need to be considered when evaluating a patient for SETD5 alterations through DES.

Magic Nature of Neutrons in

We perform the first direct mass measurements of neutron-rich calcium isotopes beyond neutron number 34 at the RIKEN Radioactive Isotope Beam Factory by using the time-of-flight magnetic-rigidity technique. The atomic mass excesses of ^{55-57}Ca are determined for the first time to be -18650(160), -13510(250), and -7370(990) keV, respectively. We examine the emergence of neutron magicity at N=34 based on the new atomic masses. The new masses provide experimental evidence for the appearance of a sizable energy gap between the neutron 2p_{1/2} and 1f_{5/2} orbitals in ^{54}Ca, comparable to the gap between the neutron 2p_{3/2} and 2p_{1/2} orbitals in ^{52}Ca. For the ^{56}Ca nucleus, an open-shell property in neutrons is suggested.

Diagnosis and treatment of bone metastasis: comprehensive guideline of the Japanese Society of Medical Oncology, Japanese Orthopedic Association, Japanese Urological Association, and Japanese Society for Radiation Oncology.

Diagnosis and treatment of bone metastasis requires various types of measures, specialists and caregivers. To provide better diagnosis and treatment, a multidisciplinary team approach is required. The members of this multidisciplinary team include doctors of primary cancers, radiologists, pathologists, orthopaedists, radiotherapists, clinical oncologists, palliative caregivers, rehabilitation doctors, dentists, nurses, pharmacists, physical therapists, occupational therapists, medical social workers, etc. Medical evidence was extracted from published articles describing meta-analyses or randomised controlled trials concerning patients with bone metastases mainly from 2003 to 2013, and a guideline was developed according to the Medical Information Network Distribution Service Handbook for Clinical Practice Guideline Development 2014. Multidisciplinary team meetings are helpful in diagnosis and treatment. Clinical benefits such as physical or psychological palliation obtained using the multidisciplinary team approaches are apparent. We established a guideline describing each specialty field, to improve understanding of the different fields among the specialists, who can further provide appropriate treatment, and to improve patients' outcomes.

Radiation therapy for superficial esophageal cancer: a comparison of radiotherapy methods.

PURPOSE: A comparison of treatment outcomes in response to various methods of radiotherapy for superficial esophageal cancer (SEC) was carried out for a large series of patients. METHODS AND MATERIALS: During the period from March 1987 to November 1998, 147 patients with superficial esophageal cancer received definitive radiation therapy at nine radiotherapy institutions in Japan. Fifty-five patients were treated with external radiation therapy alone, 69 with high-dose-rate intracavitary radiation therapy with or without external radiation therapy, and 23 with low-dose-rate intracavitary radiation therapy and external radiation therapy. RESULTS: The 5-year survival rates for mucosal and submucosal cancer patients were 62% and 42%, respectively. The 5-year cause-specific survival rates for mucosal and submucosal cancer patients were 81% and 64%, respectively (p = 0.013). There was no statistically significant difference in the survival rates for either mucosal or submucosal cancer patients between treatment groups. Metastasis was observed only in submucosal cancer patients. Esophageal ulcers developed only in patients who received intracavitary radiation therapy, and were especially common in patients treated with a fraction size of 5 Gy or more. CONCLUSIONS: The use of intracavitary radiation therapy does not influence the survival or local control rate of SEC. Optimal radiotherapy methods for SEC should be determined by a randomized clinical trial.

Expression of genes involved in repair of DNA double-strand breaks in normal and tumor tissues.

BACKGROUND: DNA double-strand breaks (DSB) are the major lethal lesions induced by ionizing radiation. The capability for DNA DSB repair is crucial for inherent radiosensitivity of tumor and normal cells. DNA-PKcs, Ku 70, Ku 85, Xrcc4, and Nbs1 play a critical role in DNA DSB repair. METHODS: We immunohistochemically investigated the expression of DNA-PKcs, Ku 70, Ku85, Xrcc4, and Nbs1 in 134 specimens from various normal and tumor tissues with different radiosensitivity. RESULTS AND CONCLUSION: Immunopositivity to Ku70, Ku85, DNA-PKcs, Xrcc4, and Nbs1 was found in all tumor tissues examined. The staining for Ku70, Ku85, and DNA-PKcs was nuclear; but, for Xrcc4 and Nbs1, it was nuclear and cytoplasmic. There were no apparent differences in the expression of these five proteins among cancerous tissues and the corresponding normal tissues. No apparent differences in nuclear staining intensity were detected in the expression of these five proteins among tumor tissues with different radiosensitivity, although non-Hodgkins' lymphoma (B or T cell) tended to show a lower expression than the others. The stromal cells generally expressed these five proteins at much lower frequency than either tumor or epithelial cells in both tumor and normal tissues.

Accelerated radiotherapy for T1, 2 glottic carcinoma: analysis of results with KI-67 index.

PURPOSE: Hyperfractionated and accelerated radiotherapy without a split was performed to improve the local control probability of early glottic carcinomas. We analyzed the results of this regimen by using the Ki-67 index. METHODS AND MATERIALS: Over a 12-year period, 85 T1N0M0 glottic cancers and 50 T2N0M0 glottic cancers were treated with conventional fractionation (CF) from 1984 to 1989 and with accelerated fractionation (AF) since 1990. The CF program consisted of five daily fractions of 2 Gy per week, for a total of 64 Gy. The AF program consisted of 1.72 Gy per fraction, two fractions per day, 5 days a week, for a total of 55 or 58 Gy. The specimens, taken before radiotherapy, were immunohistochemically stained with anti-Ki-67 antibody. RESULTS: The 5-year local control probability for T1 tumors was 79.6 +/- 6.9% with CF treatment, whereas with AF it was 86.9 +/- 5.6%. For T2 tumors it was 62.7 +/- 12.2% with CF, whereas it was 74.7 +/- 7.8% with AF. The difference between CF and AF did not reach the point of statistical significance. However, when T1 tumors had a Ki-67 index lower than 50%, the local control rate achieved with AF was significantly better than that with CF (p = 0.018). When the tumors had a Ki-67 index that was 50% or more, there was no difference in the local control rate between CF and AF, whether they were T1 or T2. The peak mucosal reactions at the larynx and/or hypopharynx were much more severe and appeared at smaller doses and earlier in AF than in CF. The patients with AF showed no severe late complications. CONCLUSIONS: AF could not obtain statistically significant improvement in local control probability of T1 or T2 glottic carcinomas.

Prognostic factors of nasopharynx tumors investigated by MR imaging and the value of MR imaging in the newly published TNM staging.

PURPOSE: To examine the usefulness of MR imaging for predicting local control of nasopharyngeal carcinoma (NPC) and the value of MR imaging in the newly published fifth edition of the TNM classification. METHODS AND MATERIALS: We studied 29 patients with NPC with MR imaging and CT before and after treatment. Staging was done according to the fourth and newly published fifth editions of the International Union Against Cancer (UICC) staging system. The radiotherapy protocol was designed to deliver 66 to 68 Gy to the primary tumor and clinically involved nodes. RESULTS: MR proved better than CT at identifying obliteration of the pharyngobasilar fascia, invasion of the sinus of Morgagni, through which the cartilaginous portion of the eustachian tube and the levator veli palatini muscle pass, invasion of the skull base, and metastases to lymph nodes in the carotid and retropharyngeal spaces. All seven patients without invasion of the pharyngobasilar fascia had local control. The local control rates of patients with invasion of the skull base were not good (60 to 73%). There was no apparent relationship between tumor volume determined by T1-weighted MR images and local control when the tumor volume was more than 20 cc. The newly published N staging system appears to successfully identify the high-risk group for distant metastasis as N3. In our series, four of five patients with N3 disease developed distant metastases. CONCLUSION: Deep infiltration of the tumor is a more important prognostic factor in NPC than tumor volume. Since the newly published T staging system requires a search for tumor invasion into soft tissue such as parapharyngeal space and bony structures, MR imaging may be indispensable for the newly published NPC staging system.

Radiotherapy for Kimura's disease: the optimum dosage.

PURPOSE: To evaluate retrospectively the optimum dosage of irradiation for Kimura's disease. METHODS AND MATERIALS: Twenty patients with Kimura's disease were treated with radiotherapy. The sex ratio was 19 males to 1 female. The mean ages at onset, initial treatment, and radiotherapy were 26.2, 29.5, and 32.2 years, respectively. Radiotherapy was mainly applied for residual or recurrent tumors. The eosinophil count increased by more than 10% in 18 of the 20 patients. In most instances, irradiation was given through a single field with dosages ranging from 20 to 44 Gy. RESULTS: At the completion of radiotherapy, a marked response in tumor size was noted in all cases. The minimum follow-up was 48 months. Local control was obtained in 23 of 31 lesions (74.1%). At dosages of < or =25 Gy, 26-30 Gy, and > 30 Gy, local control was obtained in 2 of 8 (25.0%), 9 of 10 (90.0%), and 12 of 13 sites (92.3%), respectively. CONCLUSIONS: Radiotherapy is an effective treatment for Kimura's disease. This strongly suggests that no surgical procedure other than a biopsy should be carried out. The radiation field should be limited to the lesion and swelling of the adjacent lymph nodes as much as possible, with a optimum dosage of 26-30 Gy regardless of tumor size.

Simultaneous development of insulin dependent diabetes mellitus and alopecia areata universalis.

Alopecia areata universalis developed gradually over nine months in a 25-year-old woman. When her scalp hairs were totally lost and other body hair began to fall out, the symptoms of insulin dependent diabetes mellitus, an organ-specific autoimmune disease, developed rapidly and progressed to diabetic coma. Alopecia did not regress after the metabolic state improved following insulin therapy. Biopsy of the scalp skin revealed significant reduction of the total number of hair bulbs and prominent lymphocyte infiltration into the remaining hair follicles. Insulin dependent diabetes mellitus and alopecia areata universalis are both thought to be related to the autoimmune mechanism and sometimes coexist. However, simultaneous development of these two disorders is extremely rare.

Clinical studies of immunohistochemical staining of DNA-dependent protein kinase in oropharyngeal and hypopharyngeal carcinomas.

PURPOSE: DNA-dependent protein kinase (DNA-PK), a serine/threonine kinase composed of p470 catalytic subunit (DNA-PKcs) and p85/p70 heterodimer (Ku antigen), is considered a critical enzyme in the repair of the DNA double-strand breaks (DSB) that are the major lethal lesions induced by ionizing radiation. We investigated the expression of DNA-PK subunits in human tumors. MATERIALS AND METHODS: We examined immunohistochemically the biopsy specimens of 44 patients with oropharyngeal carcinoma and 32 patients with hypopharyngeal carcinoma who had been treated with radiotherapy. RESULTS: Immunopositivity to Ku85 and DNA-PKcs was found in all patients. The staining of Ku85 and DNA-PKcs was nuclear, with none of the normal epithelial cells or malignant cells exhibiting cytoplasmic or membrane immunoreactivity. Normal epithelial cells were all stained intensely. In tumors, intense nuclear staining of DNA-PKcs was seen in 75 of 76 tumors, while that of Ku85 was seen in all 76 patients. The radiation responses of a primary tumor that was stained weakly with DNA-PKcs were excellent. CONCLUSION: Our results suggest the possibility of predicting the intrinsic radiosensitivity of human tumors in clinics able to perform immunohistochemical analysis of DNA-PK.

Establishment and characterization of monoclonal antibodies to carbohydrate antigens on peanut agglutinin receptor glycoprotein of gastric cancer KATO-III.

Eight mouse monoclonal antibodies, GOM-1, GOM-2, GOM-3, GOM-5, GOM-6, GOM-7, GOM-8 and GOM-9 were established that recognized carbohydrate antigens on the human gastric cancer cell line KATO-III. Their binding specificities were studied by enzyme-linked immunosorbent assay, cellular enzyme-linked immunosorbent assay, flow cytometry analysis and thin layer chromatography immunostaining. All these monoclonal antibodies bound to peanut agglutinin receptor glycoproteins and neutral glycolipids extracted from KATO-III cells, but they could be divided into three groups, namely GOM-1, -3, -9 group, GOM-5 and GOM-2, -6, -7, -8 group. GOM-3 specifically bound to the Le(a) structure, Gal beta 1-3 (Fuc alpha 1-4) GlcNAc beta 1-, and GOM-5 specifically bound to the Lec structure, Gal beta 1-3GlcNAc beta-. GOM-2 showed specific binding to KATO-III, but little or no binding to various other cell lines examined or to normal human leukocytic cells. It also did not bind to the synthetic glycoconjugates tested, carrying 10 different terminal sugar chains including T, Tn, Le(a), Lec and Le(x) structures. The binding specificity of GOM-2 was also different from those of the monoclonal antibodies anti-Le(x), anti-Leb and anti-Ley. These results suggest that GOM-2 recognizes a new carbohydrate antigen on KATO-III cells that is distinct from Le(a), Leb, Lec, Le(x), Ley, T and Tn structures.

[Comparative study on the assay for IgE antibodies specific for Chamaecyparis obtusa pollen between AlaSTAT and CAP-RAST].

Titers of IgE antibody specific for the pollen of Chamaecyparis obtusa (C. obtusa) were determined by AlaSTAT and CAP-RAST in 221 patients with Japanese cedar pollinosis. IgE antibody to C. obtusa tested positive by CAP-RAST at a higher rate (80.5%) than by AlaSTAT (52.6%). The results obtained from the two assays were compared with those from intradermal skin test. CAP-RAST had a higher sensitivity than that of AlaSTAT. Because the two methods showed no differences in the determination of IgE antibody specific for Cryptomeria japonica, the above differences between AlaSTAT and CAP-RAST are surmised to be ascribable to the differences of C. obtusa antigen used in the both assays.

[The countermeasure to pollinosis by a web site of Internet].

For the countermeasure to pollinosis, we opened "the web site of pollinosis by allergic group of otorhinolaryngology, Jikei Medical School" and provided the information of pollinosis for patients in the web site of internet from the spring of 1997. In the web site we kept to be informed of the pollen forecast, daily dispersed pollens, and medical information being renewed frequently of prevention and therapy for pollinosis. For the principle of therapy, we adopted the guideline for allergic rhinitis which was produced by Japan Allergic Societies and recommended visitors to get standard therapy for pollinosis. Consequently, the web site was accessed up to 160,000 times by the summer of 1999 and we received 204 medical questions by e-mail and answered to these all mails. We then made a questionnaire study after 3 each pollen seasons and received over 200 answers which showed that our fresh information was useful to decrease symptoms of pollinosis. These results show that information by web site seems to be useful for the countermeasure to pollinosis and will be more important to support medical treatment in hospitals in future.

[Measurement of superior thyroid artery dynamics in cases of solitary thyroid tumor and its clinical evaluation].

Thyroid blood flow related with thyroid function is of great importance in diagnosing thyroid gland disease. However, there has no report on such observations of thyroid blood flow dynamics, especially non-invasively and quantitatively. In this study new developed ultrasound duplex scanning system was used to measure the superior thyroid blood flow and analyze the hemodynamics in 105 cases of solitary thyroid tumors, including 30 cases of thyroid cancers. Superior thyroid blood flows on afferent portion obviously increased both in benign and malignant tumor cases, but clear difference between them could not be found. On the other hand, in concern with the blood flows on inafferent portions, malignant thyroid tumor cases showed remarkable increase with statistical difference. The blood flow ratio between afferent and inafferent portions was considered to distinguish between benign and malignant thyroid tumors as quantitative criteria. The assumption that the tumors whose blood flow rate was below 3.0 is malignant led the fine result that accuracy was 79.8%, sensitivity; 71.5%, specificity; 81.5%. This quantitative criterion requires no surgical technique, therefore, this is useful for the tissue characterization of thyroid tumors.