Technical innovation in radiation therapy (RT) such as stereotactic irradiation, intensity modulated RT, image-guided RT, and brachytherapy using remote controlled after-loading system have made it possible to deliver ideally distributed radiation dose to the target with great accuracy, while sparing the adjacent organs at risk. As a result, tumor control rate by RT improved markedly and became excellent alternative to surgery for asymptomatic or mildly symptomatic brain tumors, early stage lung cancer, and low-risk prostate cancer. In locally advanced stage of cancer, randomized controlled trials established the chemoradiation therapy as a standard treatment option for patients with head and neck cancer, lung cancer, esophageal cancer, and cervical cancer. RT is also a valuable treatment for palliation of local symptoms caused by cancer with consistently high response rates. Minimally invasive therapy has come to be emphasized its needs in the background of increased tendency of elderly patients with cancer, and advances in conformal dose delivery technique raise the RT at a more important position in cancer therapy. However, adequate number of RT profession is indispensable to utilize highly-sophisticated RT technology. Substantiality of an education system for radiation oncologist, RT technologist, and medical physicists is our current most important issue. J. Med. Invest. 57: 1-11, February, 2010

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The renin-angiotensin system (RAS) has been demonstrated to play a critical role in the initiation and progression of atherosclerosis, thereby contributing to development of cardiovascular diseases. Angiotensin II (Ang II), a major substrate in RAS, stimulates atherosclerosis through various deleterious effects such as endothelial dysfunction, cellular proliferation and inflammation. Recently, local RAS in vasculature is reported to play an important role. Many of these atherogenic actions of Ang II are mediated by reactive oxygen species (ROS). Investigation of the role of ROS and inflammation induced by RAS may provide a clue to understanding the pathophysiology of atherosclerotic diseases, and may lead to a new therapeutic strategy. J. Med. Invest. 57: 12-25, February, 2010

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Severe influenza is characterized clinicopathologically by multiple organ failure, although the relationship amongst virus and host factors that influence this morbid outcome and the underlying mechanisms of action remain unclear. The present study identified marked upregulation of matrix metalloproteinase (MMP)-9 and pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) in various organs after intranasal infection of influenza A WSN virus. MMP-9 and TNF-α were upregulated in the lung, the site of initial infection, as well as in the brain and heart. The infection-induced MMP-9 upregulation was inhibited by anti-TNF-α antibodies and by anti-oxidative reagents pyrrolidine dithiocarbamate and N-acetyl-L-cysteine, which inhibit activation of nuclear factor kappa B (NF-κB), as well as by nordihydroguaiaretic acid, which inhibits activation of activator protein 1 (AP-1). In addition, MMP-9 upregulation via TNF-α was also suppressed by inhibitors of mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinase 1/2 and p38, and partly by a c-Jun N-terminal kinase inhibitor. These results indicated that the influenza-induced MMP-9 upregulation in various organs is mediated through MAPK-NF-κB- and/or AP-1-dependent mechanisms. Strategies that neutralize TNF-α as well as inhibitors of MAPK-NF-κ B- and/or AP-1-dependent pathways may be useful for suppressing the MMP-9 effect and thus preventing multiple organ failure in severe influenza. J. Med. Invest. 57: 26-34, February, 2010

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Purpose. In this investigation, we studied differences in chemical metabolites in certain brain regions between autistic patients and normal control subjects. Methods. Proton magnetic resonance spectroscopy (¹H-MRS) was used to evaluate functional activity in these regions. Specific regions studied were right and left dorsolateral prefrontal cortex(DLPFC) and the anterior cingulated cortex(ACC). Results. In the ACC, the N-acetylaspartate(NAA)/creatine/phosphocreatine(Cr) ratio in autistic patients (n=31) was significantly lower than that in control subjects (n=28). The decrease in the NAA/Cr ratio for the ACC was much greater in the group with worst social ability. NAA/Cr for the left DLPFC and social ability of autistic patients also correlated well. Furthermore, NAA/Cr for the left DLPFC in the group with intelligence quotient (IQ) below 50 was significantly less than in controls. NAA/Cr for the right DLPFC in autistic patients was not decreased compared to controls, and did not correlate with IQ or social ability. Conclusions. These findings suggest neuronal dysfunction in the ACC and left DLPFC in autism, and also a relationship between social disability and metabolic dysfunction in these regions. Dysfunction in the ACC and the left DLPFC may contribute to the pathogenesis of autism. J. Med. Invest. 57: 35-44, February, 2010

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Objective: To assess the prevalence of undernutrition, incidence of infectious diseases and the situation of feeding practices to determine the risk factors for undernutrition among children aged 6 to 18 months in rural Vietnam. Design: A cross-sectional study was conducted among one hundred eighty-eight mother-child pairs in Bac Giang, Vietnam. Weight and height of the children were measured and referred to data from the WHO/CDC/NCHS. Incidence of infectious diseases was diagnosed based on the WHO Recommended Surveillance Standards. Data on socio-demographic variables and feeding practices were obtained through a structured questionnaire. Result: The prevalence of underweight, stunting and wasting was 19.7%, 23.4% and 5.3%, respectively. The incidence of diarrhea and acute respiratory infections (ARIs) during the last 14 days of the interview was 12.2% and 20.2%, respectively. Although 99% of the children were breastfed, the prevalence of exclusive breastfeeding in the first 4 mo was 21.3%. Non-exclusive breastfeeding in the first 4 month (OR 3.95, p=0.025) and low birth weight (OR 4.38, p=0.009) were associated with underweight in the children, while incidence of infectious disease was not (OR 1.16, p=0.734). Conclusion: Undernutrition is highly prevalent in the study site and non-exclusive breast feeding is one of the risk factors. J. Med. Invest. 57: 45-53, February, 2010

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A number of recent publications have reported an increased frequency prevalence of glucose intolerance with hyperinsulinemia in liver cirrhosis. The aim of this work was to detect, in CCl₄-induced liver cirrhosis rat, the presence and starting point of muscle and liver insulin resistance. Eighteen rats received intraperitoneal injection of 2 ml of soybean oil containing of CCl₄ twice a week for 20 weeks. We executed standard oral glucose tolerance and clamp study to evaluate systemic insulin resistance. Hepatic glucose uptake was much lower in CCl₄ group than that in control group, but peripheral glucose uptake was not decreased in this study. In contrast, early-phase insulin secretion was enhanced in CCl₄ rat using oral glucose load during clamp methods. These data suggested that increased early insulin secretion compensate adequately for hepatic insulin resistance in rats. However there was a report that peripheral glucose uptake was decreased in the case of human liver cirrhosis, which was formed in the course of time. In a chronic condition, this may be associated with reduced insulin content and developed systemic insulin resistance in liver cirrhosis. Then a long term observation study will be required to examine the presence of muscle insulin resistance in liver cirrhosis. J. Med. Invest. 57: 54-61, February, 2010

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Childhood obesity is one of the most serious public health problems in Japan, especially in Tokushima compared with other prefectures. This study was designed to clarify the life habits which predispose to development of obesity and can be modified through an appropriate intervention program to combat childhood obesity and its lifestyle-related diseases. A total of 216 school children from Itano Town, a municipality of Tokushima Prefecture, Japan, who are attending the fourth grade (9-10 years) of elementary schools, participated in the study from 2004 to 2007. The study included child’s life habits questionnaire, investigating physical activity by recording the daily steps using a pedometer, anthropometric measurements, hematological examination and hemodynamometry in a cross-sectional survey during a two-month period from June to July every year. We conclude that there are considerable gender-related differences for developing obesity and other lifestyle-related diseases; and all intervention strategies against obesity must consider such gender differences. For example, restriction of television watching hours must be intervened for controlling obesity in boys, however for girls, promotion of exercise practice or making more steps per day with adequate sleeping periods should be intervened as the proper approaches for preventing and controlling obesity and other lifestyle-related diseases. J. Med. Invest. 57: 62-68, February, 2010

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Prolonged life expectancy must be recognized as an excellent achievement of modern medicine, but not all the elderly people are satisfied with their lives. Life satisfaction is a multi-dimensional issue that depends on many objective and subjective characteristics. In this study, we aimed at investigating the factors affecting life satisfaction of 314 elderly Japanese women attending in 28 elderly-care and welfare facilities at Tokushima Prefecture, Japan. Our results indicated that elderly subjects with depression tendencies always show significantly lower degrees of life satisfaction than others who are not depressed (p<0.001) regardless of their cognitive status. Furthermore, elderly women who shared decision for their living place and whose opinions were considered for daily life decisions reported significantly more life satisfaction levels than others. We conclude that elderly life satisfaction is affected by various determinants however, with different influencing weight. Life satisfaction of elderly people, with or without dementia, is greatly affected by their mood status and share in decision making. Avoiding elderly people depressive mood, sharing them in various daily decisions, considering their opinions, and allowing them to decide their elderly-care facility placement are crucial determinants for their life satisfaction and essential for their coping, adaptation, well-being and successful aging. J. Med. Invest. 57: 69-80, February, 2010

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The Barthel Index (BI) cannot be used to measure initial stroke severity or by extension, to stratify patients by severity in acute stroke trials because most patients are bedbound in the first few hours after stroke, either by their deficit or by medical directive. Our objectives were to clarify the threshold of acute BI for use in the prediction of subsequent independence in activities of daily living (ADL) and to assist in the definition of acute stroke rehabilitation goals. Subjects comprised 78 patients out of 191 inpatients admitted with acute stroke at our hospital during 2006-2007. The BI ADL score was divided into 2 ranges (BI>=60 and <=40), in a process similar to previous studies. During the acute period (from onset to approximately 3 weeks), all patients with a BI>=40 could improve their ADL in 6 months. Patients with a BI<=40 exhibited two ADL recovery outcomes (improved and no change) at 6 months. We also found that the skill level of basic activities related to standing was significant indicator of BI improvement (P<0.001). BI scores determined at approximately 3 weeks were reliable predictors of ADL disabilities at 6 months. J. Med. Invest. 57: 81-88, February, 2010

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We examined a series of site-directed point mutants of human immunodeficiency virus type 1 (HIV-1) Vif for their interaction with cellular anti-viral factors APOBEC3G/APOBEC3F. Mutant viruses that display growth-defect in H9 cells did not counteract effectively APOBEC3G and/or APOBEC3F without exception, as monitored by single-cycle infectivity assays. While growth-defective mutants of Vif C-terminal region were unable to suppress APOBEC3G/APOBEC3F, some N-terminal region mutants did neutralize one of APOBEC3G/APOBEC3F. These data have suggested that members of APOBEC3 family other than APOBEC3G/APOBEC3F are not important for anti-HIV-1 activity. Furthermore, APOPEC3G/APOBEC3F were found to differently associate with Vif in virions as analyzed by equilibrium density centrifugation. Taken together, these results indicated that interaction of HIV-1 Vif and APOBEC3G is distinct from that between Vif and APOBEC3F. J. Med. Invest. 57: 89-94, February, 2010

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Phosphaturia has been documented following cadmium (Cd) exposure in both humans and experimental animals. The fibroblast growth factor 23 (FGF23)/klotho axis serves as an essential phosphate homeostasis pathway in the bone-kidney axis. In the present study, we investigated the effects of Cd on phosphate (Pi) homeostasis in mice. Following Cd injection into WT mice, plasma FGF23 concentration was significantly increased. Urinary Pi excretion levels were significantly higher in Cd-injected WT mice than in control group. Plasma Pi concentration decreased only slightly compared with control group. No change was observed in plasma parathyroid hormone and 1,25-dihydroxy vitamin D₃ in both group of mice. We observed a decrease in phosphate transport activity and also decrease in expression of renal phosphate transporter SLC34A3 [NaPi-IIc/NPT2c], but not SLC34A1 [NaPi-IIa/NPT2a]. Furthermore, we examined the effect of Cd on Npt2c in Npt2a-knockout (KO) mice which expresses Npt2c as a major NaPi co-transporter. Injecting Cd to Npt2aKO mice induced significant increase in plasma FGF23 concentration and urinary Pi excretion levels. Furthermore, we observed a decrease in phosphate transport activity and renal Npt2c expression in Cd-injected Npt2a KO mice. The present study suggests that hypophosphatemia induced by Cd may be closely associated with the FGF23/klotho axis. J. Med. Invest. 57: 95-108, February, 2010

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In order to investigate the transcallosal effects of repetitive transcranial magnetic stimulation (rTMS), we studied median somatosensory evoked potentials (SEPs) before and after applying monophasic very low-frequency (0.2 Hz) subthreshold rTMS over the right motor cortex. For SEPs, median nerve was stimulated on each side. Sham rTMS served as the control. Twelve healthy subjects participated in this study. After rTMS over the right hemisphere, the amplitude of N34 component in right median SEPs recorded from the left parietal scalp (C3’) increased significantly. Other components of right or left median SEPs or those after sham stimulation showed no changes. Monophasic 0.2 Hz subthreshold rTMS over the motor cortex predominantly affected the contralateral SEPs, probably through the transcallosal pathway. J. Med. Invest. 57: 109-113, February, 2010

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Childhood overweight/obesity is growing steeply, globally. It is usually regarded as a risk factor for severe obesity over life-time course. Here, we investigated temporal course of overweight/obesity development in Japanese school children. A six-year longitudinal study was performed on 16,245 Japanese primary school children (8,427 boys and 7,818 girls) comprising three cohorts of 1^st∼3^rd grade. A baseline survey was conducted at 2001, followed by annual baseline studies from 2002∼2007 to determine the prevalence and track overweight/obesity. Our results showed that the prevalence of overweight was 15∼23% in boys and 15∼18% in girls, however, for obesity it ranged between 4∼7% in boys; and 2∼4% in girls. As regards for tracking status, 60∼80% of overweight and 35∼70% of obese Japanese primary school boys track into overweight or obese junior high school adolescents. However, these percentages are lower among primary school girls, where only 50∼70% overweight and 30∼60% obese primary school girls track into overweight and obese adolescents, respectively. We conclude that Japanese boys are fatter than girls; and ∼80% of overweight/obese Japanese primary school children track into junior high school overweight/obese adolescents. J. Med. Invest. 57: 114-123, February, 2010

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Childhood overweight is an important worldwide problem of public health concern, with metabolic, physical and psychosocial complications. More and more evidence is accumulating that children who gain weight rapidly earlier in life are at higher risk of becoming overweight later in adulthood life. Therefore, in a seven-year longitudinal study, we studied mid-childhood and early adolescence weight and height growth velocities among 5,024 Japanese 2^nd grade primary school boys and girls along with its effect on the likelihood of being overweight adolescents by the age of 14 y. Our findings showed that weight growth velocity of both sexes was associated with being overweight at the end of longitudinal study. Boys’ risk of accelerated weight growth velocity and becoming overweight adolescents was almost doubled during ages 7∼11 y and become reduced afterward. Otherwise, odds ratios of girls’ weight growth velocity peaks were found only at ages from 9∼10 and 10∼11 y. Thus, we suggest a critical window of mid-childhood period associated with adolescence risk of overweight, and we recommend that studying weight growth determinants during 7∼11 y of boys and 9∼11 y of girls may help in developing and applying proper programs for prevention and intervention of overweight problem. J. Med. Invest. 57: 124-132, February, 2010

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We studied the lumbar spines of 117 adults (39 women and 78 men) with spondylolysis unrelated to low back pain using multidetector computed tomography (CT). Of the 117 subjects with spondylolysis, including five with multiple-level spondylolysis, there were 124 vertebrae with spondylolysis. In adult lumbar spines with unilateral spondylolysis, there was no significant difference between the incidence of spondylolisthesis in female and male subjects. However, in those with bilateral spondylolysis, there was a significantly higher incidence of spondylolisthesis in female subjects (90.9%) than in males (66.2%). Furthermore, females with bilateral spondylolysis had significant more slippage than males. Lumbar index and lumbar lordosis were not significantly different between male and female subjects, and did not significantly correlate with slippage. In conclusion, to treat acute spondylolysis in adolescents, it is important to obtain bony union at least unilaterally, especially in female subjects, to prevent further slippage. J. Med. Invest. 57: 133-137, February, 2010

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The “in vivo cryotechnique” (IVCT) is a new method of morphological analysis which has the advantage of freezing tissues in living animals without stopping their blood circulation. The purpose of this study was to investigate the effect of parathyroid hormone (PTH) on renal type II Na-Pi transporters (NaPi-IIa and NaPi-IIc) and ”cryobiopsy” (CB) using special cryoforceps as a simple method of the IVCT. The kidney tissues were biopsied at various time points after PTH administration by CB using liquid nitrogen as the cryogen. By hematoxylin-eosin (HE) staining the kidney tissues, well-frozen areas without visible ice crystals were obtained in the tissue surface areas, and the brush border membrane (BBM) of proximal tubules was well preserved at a light microscopic level. Immunohistochemical evaluation showed that PTH downregulated NaPi-IIa and NaPi-IIc at the BBM, being controlled by a different mechanism. In this method, the PTH-induced internalization of NaPi-IIc from microvilli to subapical compartments was not observed in the tissue preparations. NaPi-IIc protein appears to be degraded in microvilli of the proximal tubular cells after the injection of PTH. We suggest that CB using liquid nitrogen is useful to investigate renal type II Na-Pi transporters at the light microscopic level. J. Med. Invest. 57: 138-145, February, 2010

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This study aimed to clarify the therapeutic effects of postoperative ambulation after total knee arthroplasty (TKA) on deep venous thrombosis (DVT) in patients with osteoarthritis (OA) and rheumatoid arthritis (RA) after TKA. Subjects of this study were thirty-seven inpatients (21 inpatients: OA, 16 inpatients: RA) undergoing TKA (32 female and 5 male). Subjects were divided into two groups, deep venous thrombosis (DVT) group (n=25) and non-DVT group (N group, n=12). The cutoff value was 10.0 µg/ml plasma D-dimer level measured on 7^th postoperative day. The N group was below the cutoff value. Another cutoff value divided into two groups, ambulatory group (n=26) and non-ambulatory group (n=11). Ambulatory group was the date of ambulation beginning below 7^th day. Statistical analysis confirmed that all subjects showed a significant correlation to the date of ambulation. Postoperative ambulation beginning had strong association with the level of D-dimer (r=0.71). Group comparison showed that the non-ambulatory group had significant higher values of D-dimer than ambulatory group (P=0.022). Typical case supported these results. Postoperative early ambulation within a week after TKA kept patients with OA and RA after TKA lower level of D-dimer. J. Med. Invest. 57: 146-151, February, 2010

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Overexpression of galectin-3 in a variety of cancer cell lines has been shown to correlate with tumor progression and metastasis. In this study, we investigated the expression of galectin-3 in clear cell renal cell carcinoma (CC-RCC) and evaluated the relationship between galectin-3 expression levels and the clinicopathological features of CC-RCC. Expression of galectin-3 in the kidney cancer cell lines Caki-1, Caki-2, A704, ACHN and KPK-1 were evaluated using western blot analysis, while galectin-3 expression in CC-RCC tissues and normal parenchyma were measured by real-time PCR and immunohistochemistry. We found that galectin-3 was overexpressed in the Caki-1, Caki-2, A704, ACHN and KPK-1 cell lines and that the expression level in CC-RCC was also significantly higher than that in renal parenchyma obtained from the same patient samples (p=0.039). Galectin-3 expression in CC-RCC with distant metastasis was also significantly higher than that in CC-RCC without distant metastasis (p=0.045). In conclusion, we revealed that galectin-3 is highly expressed in CC-RCC, especially in CC-RCC with distant metastasis, suggesting that galectin-3 may serve as a novel target molecule for predicting CC-RCC metastasis. J. Med. Invest. 57: 152-157, February, 2010

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Ovarian smooth muscle tumors are a very rare type of ovarian tumor. In this paper, we report the case of a 62-year-old woman who had a huge smooth muscle tumor of the right ovary. The values of all the serum tumor markers were within normal limit. The tumor measured 25 cm in diameter and weighed 6,200 g. Histological examination revealed that coagulative cellular atypia was modetare to severe, necrosis was not present and mitotic index was low. According to the criteria for the evaluation of the uterine smooth muscle tumors, this huge tumor was diagnosed as atypical leiomyoma. However, we finally made a diagnosis of this tumor as a smooth muscle tumor of uncertain malignant potential (STUMP) because of its huge size. Further information is required regarding the characteristics of ovarian smooth muscle tumor and the propriety to introduce uterine tumor histological criteria to ovarian tumors. J. Med. Invest. 57: 158-162, February, 2010

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Platinum-based chemotherapy is the standard regimen for the treatment of gynecologic cancers; however, hypersensitivity reactions (HR) to platinum often lead to discontinuation of this effective treatment. Here we performed a desensitization protocol for platinum infusion in 3 patients who required platinum re-administration after developing HR. Two patients (Case 1 and 2) were treated with the desensitization protocol successfully without developing HR during the subsequent 3 courses. Case 3 tolerated desensitization well for 2 courses, but in the 3^rd course, she developed severe HR immediately after the initiation of cisplatin infusion because the desensitization protocol was unintentionally omitted. These cases show the usefulness and effectiveness of the desensitization protocol for the continuation of platinum treatment in patients who have undergone an extended number of treatments. J. Med. Invest. 57: 163-167, February, 2010

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Objective. There is evidence that multiple sclerosis (MS) is not only characterized by immune mediated inflammatory reactions but also by neurodegenerative processes. Neutralization of oxidative stress and excitotoxicity, might represent a therapeutic approach to provide neuroprotection in MS. The purpose of this study was to compare changes in total antioxidative status and activities of chosen antioxidative enzymes, such as: SOD, CAT in erythrocytes of patients with MS before and after using WBCT with control group. Materials and methods. 32 patients with multiple sclerosis (ICD10-G35) and 20 healthy subjects were recruited for the study. The examined MS group (n=16) was treated with a series of 10 daily exposures in a cryogenic chamber (2-3 min, from -120°C to -110°C) and program of exercises. The control MS group (n=16) had only exercises. Plasma TAS as well as SOD and CAT activities in erythrocytes were measured. Results. The level of TAS in MS patients was distinctly reduced compared to healthy subjects. After two weeks of WBCT treatment an increase of TAS in the whole examined group (p>0,01) were observed in relation to control MS group. There was not increase of CuZnSOD and CAT activities. Conclusion. Our results suggest positive antioxidant effects of WBCT as a short-term adjuvant treatment for patients suffered due to MS. J. Med. Invest. 57: 168-173, February, 2010

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Solitary adrenal metastasis from endometrial adenocarcinoma is extremely rare. We report herein the case of a laparoscopically resected solitary adrenal metastasis originating from endometrial adenocarcinoma. The patient was a 55-year-old woman who had undergone total abdominal hysterectomy for stage IIIc endometrial carcinoma, followed by 7 courses of adjuvant chemotherapy comprising carboplatin and paclitaxel. However, the patient developed an isolated right adrenal metastasis 15 months postoperatively. The solitary adrenal metastasis (diameter, 5.7 cm) was removed laparoscopically. The patient has now been in good health without recurrence for 5 years and 7 months after laparoscopic surgery. To the best of our knowledge, this is the first case of solitary adrenal metastasis originating from endometrial adenocarcinoma that is controlled for the long term by successful laparoscopic resection. J. Med. Invest. 57: 174-177, February, 2010

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