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Biomedical subjects

N Shikama

Publications and source records attributed to N Shikama.

At least 19 recordsLinked to original sources

Localized aggressive non-Hodgkin's lymphoma of the nasal cavity: a survey by the Japan Lymphoma Radiation Therapy Group.

PURPOSE: To clarify the role of radiotherapy and chemotherapy in the treatment of patients with localized aggressive non-Hodgkin's lymphomas (NHL) originating in the nasal cavity. METHODS AND MATERIALS: The survey, administered at 25 Japanese institutes in 1998, enabled us to collect the clinical data for 787 patients with localized aggressive NHL who were treated between 1988 and 1992. RESULTS: There were 42 patients (5%) with nasal lymphomas. Twelve of these patients received radiotherapy alone, and 30 were treated with a combination of radiotherapy and chemotherapy. The median radiation dose was 47 Gy (22-66). Twelve patients were reviewed histopathologically according to REAL (Revised European-American Classification of Lymphoid neoplasms) classification. T-cell or natural killer (NK) cell lymphomas were detected in 9 patients (75%), and diffuse large B-cell lymphomas in 3 (25%). The 5-year overall and disease-free survival (DFS) rates of all patients were 57% and 59%, respectively. The 5-year DFS rate for the 30 patients treated with the combined therapy was 64% and that for the 12 patients treated with radiotherapy alone was 46% (p = 0.021). For the 34 patients with stage-modified International Prognostic Index (m-IPI) 0-1, the 5-year DFS rates of those treated with the combined therapy and radiotherapy alone were 68% and 45%, respectively (p = 0.020), but there was no difference in DFS rate among the two groups of patients with m-IPI 2-3. The 5-year local control rates of the patients who received >46 Gy (n = 22) and < or =46 Gy (n = 20) were 95% and 76% (p = 0.087), respectively. There was no significant difference among the 5-year DFS rates (62% vs. 67%) and local control rates (87% vs. 100%) of the patients with T-cell or NK-cell lymphoma and diffuse large B-cell lymphoma. CONCLUSIONS: Patients with nasal lymphomas (m-IPI 0-1) should be treated with combined therapy. For the patients with high risk (m-IPI 2-3), the effectiveness of combined therapy was not clarified because of the small number of the patients. A high radiation dose >46 Gy may need to be used to achieve good local control.

Adolescent↗

Alternating chemoradiotherapy for nasopharyngeal cancer using cisplatin and 5-fluorouracil: a preliminary report of phase II study.

Alternating chemoradiotherapy was performed in 35 patients with locally advanced nasopharyngeal cancer. The median duration of follow-up was 20 months, and the 2-year progression free and overall survival rates were 83% (95% confidence interval: 66~101%) and 94% (95% CI: 84~105%), respectively. This method may be useful in treating nasopharyngeal cancer.

Adenocarcinoma↗

Control of gene expression and the cell cycle.

The pRb tumour suppressor protein is an essential component of the cell-cycle clock, integrating both positive and negative signals for cellular growth and proliferation with the transcription machinery. pRb exerts its tumour suppression function by both antagonizing and synergizing with downstream effectors, such as E2F. pRb has two modes of action, it can inactivate E2F transcription activity or it can assemble an active repression complex with E2F. Apart from E2F, pRb interacts with various factors to promote cellular differentiation. The differentiation properties of pRb are likely to contribute partly to its tumour suppressor function. It is also clear that pRb is a master regulator for transcription. It can both activate and repress transcription in a context-dependent manner. pRb interacts directly with histone acetyltransferase, histone deacetylases and SWI/SNF proteins, all of which are classes of proteins involved in chromatin remodelling. Last, but not least, pRb regulates transcription driven by all three polymerases, thereby integrating the cell-cycle clock with the biosynthetic capacity of the cell in controlling cellular proliferation and growth.

Animals↗

A case of POEMS syndrome with high concentrations of interleukin-6 in pericardial fluid.

The POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy of various forms, monoclonal gammopathy, skin changes) is a rare multisystem disorder of unknown pathogenesis. Overexpression of proinflammatory cytokines has been implicated in the pathogenesis of POEMS syndrome, however, it is not known whether there is an association between abnormalities in cytokines and pericardial fluid. We present a case of POEMS syndrome with high concentrations of interleukin-6 (IL-6) in pericardial fluid. In our patient, pericarditis developed into cardiac tamponade, and the concentration of IL-6 in pericardial fluid was remarkably elevated compared with that in serum (1760 vs. 6.57 pg mL(-1)). We suggest that IL-6 is associated with the progression or maintenance of pericarditis as a result of POEMS syndrome.

Adult↗

Ulcer in the gastric tube for esophageal replacement: a comparison of 12 esophageal cancer patients with or without postoperative radiotherapy.

BACKGROUND AND AIMS: Ulcer in the gastric tube for esophageal replacement, which was caused by peptic factors or postoperative radiotherapy (Rx), are occasionally reported. The aim of this study was to clarify the clinicopathologic features of the ulcers in the gastric tube. METHODS: In 62 patients with a reconstructed gastric tube, after esophagectomy for esophageal cancer, esophagogastroduodenoscopy was performed. Ulcers of the gastric tube were detected in 12 patients: six with postoperative Rx and six without Rx. The 12 patients with gastric tube ulcers (GU-group) were reviewed and compared to the remaining 50 patients without ulcers of the gastric tube (Control-group). Clinicopathologic features of gastric tube ulcers were compared between the patients with and without Rx. RESULTS: There was no difference in any parameter between the patients of the GU- and Control-groups. Comparing the patients of the GU-group with and without Rx, the ulcers of the gastric tube in the patients without Rx were frequently located in the lower part of the gastric tube (P = 0.067), detected in a later period after surgery (P = 0.055), associated with cervical esophagitis (P = 0.03), and less associated with gastritis (P = 0.03). In three patients of the GU-group without Rx, Helicobacter pylori was detected in the gastric tube. Two of the three patients had a history of peptic ulcers before surgery, and had recurrence of the gastric tube ulcers. CONCLUSIONS: Gastric tube ulcers without postoperative Rx may have different characteristics compared to those induced by Rx.

Endoscopy, Digestive System↗

Coronary flow reserve in angiographically normal coronary arteries with one-vessel coronary artery disease without traditional risk factors.

AIMS: Reduced coronary flow reserve has been reported in patients with traditional risk factors, in particular hyperlipidaemia, despite angiographically normal coronary arteries. However, it is recognized that traditional risk factors do not explain the presence of coronary atherosclerosis in a large proportion of patients. The aim of this study was to assess whether coronary flow reserve is preserved in the myocardium supplied by normal coronary arteries in patients with one-vessel coronary artery disease without traditional risk factors. METHODS AND RESULTS: Positron emission tomography using [13N]ammonia was performed at baseline and after intravenous dipyridamole administration (0.56 mg x dl(-1)over 4 min) in 30 subjects: six patients with ischaemia on effort, no myocardial infarction, and isolated left anterior descending coronary artery stenosis without traditional risk factors (coronary artery disease patients without risk factors, aged 59+/-13), five patients with ischaemia on effort, no myocardial infarction, and isolated left anterior descending coronary artery stenosis with multiple risk factors (coronary artery disease patients with risk factors, aged 69+/-7), 11 age-matched controls (aged 58+/-6), and eight healthy young volunteers (aged 34+/-4). Myocardial blood flow calculated in the myocardium supplied by normal coronary arteries in the coronary artery disease patients was compared with those of the two control groups. Coronary flow reserve was defined as the ratio of hyperaemic blood flow after dipyridamole infusion to baseline blood flow. Although coronary flow reserve in the coronary artery disease patients with risk factors was significantly lower than that in the age-matched controls (1.62+/-0.37, 2.58+/-0.71, P=0.0428), coronary flow reserve in the coronary artery disease patients without risk factors was similar to that in the age-matched controls (2.54+/-0.17 vs 2.58+/-0.71, P=ns). CONCLUSION: Coronary flow reserve is preserved in regions supplied by angiographically normal coronary arteries with one-vessel coronary artery disease without traditional risk factors.

Adult↗

Fulminant Mycoplasma pneumoniae pneumonia.

A 64-year-old woman, who was previously in good health was admitted because of progressive respiratory distress. Her chest radiograph revealed bilateral widespread alveolar infiltrates. She was given a diagnosis of pneumonia caused by Mycoplasma pneumoniae serologically, acute respiratory distress syndrome, and disseminated intravascular coagulation. She died of multiple organ failure despite intensive therapy with mechanical ventilation, intravenous erythromycin and corticosteroids, continuous hemodiafiltration, and plasma exchange. Although Mycoplasma pneumoniae infection is usually a benign self-limited disease, this case emphasizes its potentially serious nature even in normal healthy individuals.

Adrenal Cortex Hormones↗

Evaluation of central nervous system involvement in nasal lymphomas.

OBJECTIVES: To clarify the usefulness of evaluating central nervous system (CNS) involvement in patients with nasal lymphomas at the initial staging procedure, and of CNS prophylaxis for patients with clinical stage I/II. PATIENTS AND METHODS: We retrospectively reviewed 43 patients with nasal lymphomas who had been treated from 1973 through 1999. The staging procedure included mainly computed tomography (CT), ultrasonography, gallium scintigraphy, upper gastrointestinal study, magnetic resonance (MR) imaging, and bone marrow biopsy. Forty-two patients received radiotherapy, and 25 patients received chemotherapy. All 38 patients with stage I/II were not subjected to CNS prophylaxis. RESULTS: Four patients demonstrated CNS involvement at the staging procedure. MR imaging demonstrated the tumor had directly infiltrated the skull base in 3 patients, but CT demonstrated CNS infiltration in only one patient. In another patient, cerebrospinal fluid (CSF) cytologic analyses demonstrated CNS involvement, but MR imaging and CT did not. These 4 patients complained of frontonasal pain and/or cerebral nerve dysfunction. No patient with stage I/II developed CNS relapse. CONCLUSIONS: MR imaging and CSF cytologic analyses should be performed at the initial staging of nasal lymphomas, especially in patients with frontonasal pain and/or cerebral nerve dysfunction. Patients with stage I/II might not need CNS prophylaxis.

Adult↗

Functional interaction between nucleosome assembly proteins and p300/CREB-binding protein family coactivators.

The p300/CREB-binding protein (CBP) family of proteins consists of coactivators that influence the activity of a wide variety of transcription factors. Although the mechanisms that allow p300/CBP proteins to achieve transcriptional control are not clear, it is believed that the regulation of chromatin is an important aspect of the process. Here, we describe a new level of p300-dependent control mediated through the functional interaction between p300/CBP and members of the family of nucleosome assembly proteins (NAP), which includes NAP1, NAP2, and TAF1. We find that NAP proteins, which have previously been implicated in the regulation of transcription factor binding to chromatin, augment the activity of different p300 targets, including p53 and E2F, through a process that is likely to involve the physical interaction between p300 and NAP. NAP proteins can form oligomers, and the results show that NAP proteins can bind to both core histones and p300 coactivator proteins, perhaps in a multicomponent ternary complex. We also provide data in support of the idea that histones can influence the interaction between p300 and NAP protein. These results argue that NAP is a functionally important component of the p300 coactivator complex and suggest that NAP may serve as a point of integration between transcriptional coactivators and chromatin.

Adenovirus E2 Proteins↗

[Non-randomized study on the effects of preoperative radiotherapy and daily administration of low-dose cisplatin against those of radiotherapy alone for oral cancer--effects on local control, control of metastases, and overall survival].

Cisplatin is a known radiation modifier. Our previous study suggested that daily administration of low-dose cisplatin enhanced the efficacy of radiotherapy against primary oral squamous carcinoma. In this paper, we follow the patients who participated in the previous study and survey the benefit of combination low-dose cisplatin in improving local control, prevention of metastases, and overall survival. This study included patients with surgically resectable advanced oral tumors. Ten patients underwent preoperative radiotherapy of 30-40 Gy/15-20 days with concomitant daily administration of low-dose cisplatin (5 mg/body or 5 mg/m2). Ten other patients received external radiotherapy alone. All patients then underwent a planned radical tumor resection. No significant difference was see in loco-regional control rates (primary: 86 vs. 88%, neck: 83 vs. 78% at 48 months) or incidence of metastasis (70 vs. 64%) between the two groups. Nor was there a significant difference in the overall survival rate (60 vs. 66%). The results of this study suggest that the concomitant use of daily administration of low-dose cisplatin with preoperative radiation brings no statistically significant benefit in improving local control and survival rate in patients with advanced resectable oral cancer.

Adult↗

Prognostic utility of myocardial blood flow assessed by N-13 ammonia positron emission tomography in patients with idiopathic dilated cardiomyopathy.

Previous studies in patients with idiopathic dilated cardiomyopathy (IDC) have suggested that myocardial perfusion is impaired and spatially heterogeneous in such cases. Our objective was to identify any association between an abnormality in myocardial perfusion and the prognosis of patients with IDC. We collected data on N-13 ammonia positron emission tomography (PET) studies performed in 26 patients with IDC (9 nonsurvivors, 17 survivors) and in 8 normal control subjects. Regional myocardial blood flow (rMBF) was quantified using N-13 ammonia positron emission tomography and the Simple flow model. The spatial heterogeneity of myocardial perfusion was assessed by calculating the coefficient of variance of rMBF. Mean rMBF of the survivors was significantly lower (0.54 +/- 0.13 ml/min/g) than that of control subjects (0.66 +/- 0.06 ml/min/g) (p = 0.03 vs control), but did not differ significantly between nonsurvivors (0.58 +/- 0.15 ml/min/g) and control subjects. The coefficient of variance of rMBF was significantly higher in nonsurvivors than in either survivors or control subjects (0.24 +/- 0.08 vs 0.15 +/- 0.08, p = 0.007, and 0.16 +/- 0.05, p = 0.03, respectively). The probability of 3-year survival (Kaplan-Meier method) was 33.0% in subjects whose coefficient of variance of rMBF was above the median compared with 90.0% in subjects whose coefficient of variance of rMBF was below the median (p = 0.01). The probability of 3-year survival did not differ among subjects whose mean rMBF was above versus below the median (61.5% vs 62.9%, respectively). The results suggest that the prognosis of patients with IDC is associated with the spatial heterogeneity of myocardial perfusion, not with initial absolute rMBF.

Adult↗

Radiotherapy following mastectomy: indication and contraindication of chest wall irradiation.

PURPOSE: To determine in which cases radiotherapy of the chest wall following mastectomy is indicated, based on the local recurrent rate in patients with locally advanced breast cancer. METHODS AND MATERIALS: From 1984 until 1994, 105 patients who had four or more histopathologically confirmed axillary nodes metastases, or T3-4Nany, were subjected to mastectomy and were administered radiotherapy postoperatively using the hockey-stick field, which included the ipsilateral supraclavicular fossa and internal mammary nodes, except the chest wall. Median age was 51 years old (range, 23 to 82 years old). Eighty-five patients underwent radical mastectomy, 18 modified radical mastectomy, and 2 extended radical mastectomy. Fraction size was 2 Gy/day, the weekly fraction size was 10 Gy and the total dose ranged from 44 Gy to 54 Gy (median 50 Gy). Seventy-four patients were administered adjuvant chemotherapy, and 61 patients were administered hormone therapy. RESULTS: The 5-year disease-free survival rates of the whole study population were 66%. The 5-year chest wall recurrence rates were 10%. The 5-year chest wall recurrence rates of the patients who had no vascular invasion (n = 19) and the patients who had definite vascular invasion (n = 38) were 0% and 24%, respectively (p = 0.036). All the patients who presented chest wall recurrence had four or more axillary nodes metastases. Nine of the 10 patients who presented chest wall recurrence had definite vascular invasion, while there was no information about vascular invasion for the remaining patient. Factors such as age, pathological subtypes, tumor location, estrogen receptors, extent of resection, chemotherapy, and hormone therapy did not influence the development of chest wall recurrence. CONCLUSION: Among patients with breast cancer who have four or more positive axillary nodes or T3-4Nany, those who have no vascular invasion or less than 4 axillary nodes metastases do not need to be subjected to chest wall irradiation after radical mastectomy.

Adult↗

A novel cofactor for p300 that regulates the p53 response.

The ability of p53 to function as a transcription factor is instrumental in facilitating the response to cellular stress, and p300/CBP proteins, which act as coactivators for diverse transcription factors, participate in regulating p53 activity. We report a novel cofactor for p300 that facilitates the p53 response by augmenting p53-dependent transcription and apoptosis. JMY and p300 associate in physiological conditions, and, during the cellular stress response, the p300/JMY complex is recruited to activated p53. The bax gene is efficiently activated by JMY, and protein isoforms that arise through alternative splicing alter the functional outcome of the p53 response. The results provide compelling evidence that the p300/JMY coactivator complex plays a central role in facilitating the p53 response.

Apoptosis↗

Functional interplay between p53 and E2F through co-activator p300.

Both E2F and p53 are sequence specific transcription factors that regulate early cell cycle progression. The pathway of control mediated through E2F governs the transition from G1 into S phase whereas p53 in response to genotoxic stress can facilitate cell cycle arrest or apoptosis. The mechanisms which influence the outcome of p53 induction are not clear, although transcription of the p53 target gene, encoding the cdk-inhibitor p21(Waf1/Cip1), correlates with p53-mediated cell cycle arrest. Here using a combination of biochemical and functional assays we identify p300 as a co-activator required for p53-dependent transcriptional activation of Waf1/Cip1. Furthermore, we show that the cdk-inhibitor p21(Waf1/Cip1) autoregulates in a positive fashion transcription through modulating the activity of the p53/p300 complex, whilst negatively regulating the activity of E2F by preventing cdk-dependent phosphorylation of pRb. Consistent with a role for p21(Waf1/Cip1) in the autoregulation of p53-dependent transcription, p300 augments the ability of p53 to cause G1 arrest and, conversely, cells undergoing p53-dependent apoptosis are rescued by p300. Thus, our data suggest that the ability of p300 to interact with p53 influences the physiological consequence of p53 activation. From previous studies it is known that cells expressing aberrant levels of E2F-1 can undergo p53-dependent apoptosis. In addition, we find that E2F-1 can cause apoptosis in p53-/- tumour cells and further p300, which also functions as a co-activator for the E2F/DP heterodimer, enhances the apoptotic activity of E2F-1. In conditions where E2F-1 and p53 co-operate in apoptosis E2F-1 can effectively compete for p300, causing a reduction in p53-dependent transcription. Thus, a functional interaction between p300 and either p53 or E2F-1 has a profound impact on early cell cycle progression, specifically in regulating the contrasting outcomes of cell cycle arrest and apoptosis. These results suggest a critical role for p300 in integrating and co-ordinating the functional interplay between the pathways of growth control mediated by E2F and p53.

Binding Sites↗

Experiences of 23 patients > or = 90 years of age treated with radiation therapy.

PURPOSE: To present 23 patients > or = 90 years old treated with radiotherapy, and to retrospectively evaluate the results of radiotherapy and tolerance in these patients. METHODS AND MATERIALS: The clinical records of 27 patients over 90 years of age who were treated with radiotherapy at the Department of Radiology, Shinshu University Hospital, and eight affiliated general hospitals from 1990 until 1995 were reviewed. The strategy of radiotherapy was individually planned depending on the stage of the disease and performance status (PS) of the patient; however, it was not modified, based solely on chronologic age. The overall survival rate and disease-free survival rate were determined using the Kaplan-Meier method. The Radiation Therapy Oncology Group scoring criteria of acute and late reactions of radiation therapy were used. RESULTS: This group of patients accounted for 0.37% of all patients treated with radiotherapy in these hospitals. Of these, 23 patients in whom cancer was pathologically confirmed and whose follow-up data were available for retrospective analysis were included in the final evaluation of data. The age of the 23 patients ranged from 90 to 96 years (median 93). Tumor was untreated and in the early stage in five patients, locoregionally advanced in 13, recurrent in four, and systemic in one. Definitive radiation therapy was administered in 12 patients (13 sites), preoperative intent in one, and palliative intent in 10. The period of observation ranged from 2.5 to 6 years (median 18 months). Seven patients were alive for 15-67 months. Fourteen patients died because of intercurrent diseases or senility associated with active cancer, and two because of senility without evidence of cancer. The overall and relapse-free survival rates were 65% and 30% at 1 year and 30% and 21% at 2 years, respectively. Definitive radiation therapy was completed in 13 of 13 patients (100%), and local control was attained in 9 of 13 patients at 6 months (62%). Palliative radiation therapy was completed as intended in 7 of 11 (64%), and effects of palliation were observed in 9 of 11 patients (81%). Acute dermatitis, mucositis, pharyngitis, esophagitis, and cystitis of grade 2-3 related to the definitive radiation therapy were tolerable for the patients with good PS. It took 3-7 weeks (median 5) for acute moist desquamation of six lesions of skin cancer to heal. Depending on the radiation doses, grade 1-2 atrophy of skin and telangiectasia were documented for eight patients followed up for more than 1 year. A brief description of representative case is presented. CONCLUSION: Patients older than 90 years with good PS may tolerate the acute effects of radiotherapy administered according to conventional fractionation schedules. Definitive radiation therapy should be considered, when applicable, even for patients older than 90 years.

Aged↗

Mucosa-adhesive water-soluble polymer film for treatment of acute radiation-induced oral mucositis.

PURPOSE: To examine the usefulness and safety of a mucosa-adhesive water-soluble polymer film (AD film) containing anesthetics and antibiotics for the treatment of acute radiation-induced oral mucositis. MATERIALS AND METHODS: To prepare AD films, 600 mg of hydroxy-propyl-cellulose was dissolved in ethyl alcohol, and mixed with a solution containing tetracaine, ofloxacine, miconazole, guaiazulene, and triacetin. The gel obtained was dried to form 30 translucent round sheets (20 mg per sheet) of 7.5 cm in diameter and 0.2 mm in thickness. The AD film showed excellent adhesive and coating properties when placed on wet oral mucosa. From 1993 to 1994, we used the AD film in 25 patients with acute radiation-induced oral mucositis, in an attempt to alleviate their pain and prevent secondary oral infection. All patients had received definitive radiotherapy for oral carcinoma. Intensity and duration of oral pain from mucositis, relief rates at rest and while eating, and presence of bacterial and/or fungal infection were compared with those of 27 patients treated with topical anesthetics (viscous lidocaine, Xylocaine and/or general systemic analgesics from 1990 to 1992 (NonAD Group). RESULTS: The intensity of oral pain was the same in the two groups. The mean duration of pain of the AD film Group (10 days) was significantly shortened compared with the NonAD Group (15 days). The rates of complete pain relief at rest and while eating of the AD film Group were statistically higher than those of the NonAD Group: 82% vs. 44%, and 68% vs. 22%, respectively. No secondary bacterial or fungal infections were observed in the AD film Group, whereas 4 cases of documented infections were found in the NonAD Group. No acute or chronic adverse effects of AD film were observed during the 3-year follow-up period. The rates for local control of oral carcinoma and overall survival, at the end of the follow-up period, were 96% and 87% for the AD film Group vs. 92% and 85% for the NonAD Group, respectively. CONCLUSION: The AD film, containing topical anesthetics and antibiotics, proved useful to alleviate pain due to acute radiation-induced oral mucositis, maintain good peroral feeding, and prevent secondary oral infections, without inducing adverse reactions.

Administration, Buccal↗