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An 80-year-old woman was referred to our hospital due to the presence of a mass that was identified on a chest X-ray. A further investigation demonstrated advanced adenoid cystic carcinoma of the lungs. Anti-cancer chemotherapy with docetaxel was carried out and the lesion remained as stable disease. Subsequently, pleural effusion was detected, and an investigation of the pleural effusion revealed the existence of malignant cells with an epidermal growth factor (EGFR) mutation. Gefitinib was administered and the pleural effusion resolved. This is the first case of a positive EGFR mutation of adenoid cystic carcinoma of the lung with a favorable response to an EGFR-tyrosine kinase inhibitor.

An 80-year-old woman was referred to our hospital due to the presence of a mass that was identified on a chest X-ray. A further investigation demonstrated advanced adenoid cystic carcinoma of the lungs. Anti-cancer chemotherapy with docetaxel was carried out and the lesion remained as stable disease. Subsequently, pleural effusion was detected, and an investigation of the pleural effusion revealed the existence of malignant cells with an epidermal growth factor (EGFR) mutation. Gefitinib was administered and the pleural effusion resolved. This is the first case of a positive EGFR mutation of adenoid cystic carcinoma of the lung with a favorable response to an EGFR-tyrosine kinase inhibitor.

Background We are occasionally presented with patients with unclassifiable interstitial pneumonia of unknown etiology. Idiopathic pulmonary upper lobe fibrosis (IPUF) does not fit any of the currently defined subsets of idiopathic interstitial pneumonias (IIPs). This study was performed to examine clinical, functional, and pathological characteristics of IPUF. Methods We present 9 cases of histologically confirmed IPUF. The clinical and histological characteristics of the 9 patients were evaluated. The baseline respiratory function of all patients was measured. There were 7 patients whose forced vital capacity (FVC) had been monitored for at least a year who were selected to quantify the yearly decline in FVC. Results All patients were slender, with a body mass index of 16.0–19.8kg/m 2 . Seven patients had a history of pneumothorax. Six patients died 1.8 to 5.7 years after the onset of the first symptoms. Fundamental histological features were intraalveolar collagen deposition and densely packed elastic fibers in the subpleural areas. These findings are the same as those seen in pleuroparenchymal fibroelastosis. However, the visceral pleura was thickened with dense collagen in only 2 patients, and pleural thickening was localized, if present, in the remaining 7 patients. Ventilatory impairment was also a characteristic. The time course decline of FVC was rapid and almost linear. The median yearly decline in FVC was −20.3% (range, −7.7% to −26.5%), which was more rapid than that reported for chronic fibrosing interstitial pneumonias such as idiopathic pulmonary fibrosis. Conclusions IPUF is a unique pulmonary fibrosis that results in rapid deterioration of ventilatory function and poor prognosis.

BackgroundEldecalcitol is an analog of 1,25-dihydroxyvitamin D3 that improves bone mineral density; however, the effect of eldecalcitol on the risk of fractures is unclear. The objective of this study is to examine whether eldecalcitol is superior to alfacalcidol in preventing osteoporotic fractures. This trial is registered with ClinicalTrials.gov, number NCT00144456.Methods and resultsThis 3year randomized, double-blind, active comparator, superiority trial tested the efficacy of daily oral 0.75μg eldecalcitol versus 1.0μg alfacalcidol for prevention of osteoporotic fractures. 1054 osteoporotic patients 46 to 92years old were randomly assigned 1:1 to receive eldecalcitol (n=528) or alfacalcidol (n=526). Patients were stratified by study site and serum 25-hydroxyvitamin D level. Patients with low serum 25-hydroxyvitamin D levels (

Vitamin D insufficiency is a risk for both skeletal and nonskeletal health. However, some ambiguity remains about threshold serum 25(OH)D for vitamin D insufficiency. To determine the threshold serum 25(OH)D to maintain normal calcium availability without elevation in serum parathyroid hormone (PTH) among Japanese subjects with various calcium intakes, we conducted a multicenter prospective open-labeled study. We recruited 107 ambulatory subjects without disorders affecting vitamin D metabolism to whom oral vitamin D3 800 IU/day for 4 weeks or 1,200 IU/day for 8 weeks was given. Serum 25(OH)D, PTH, calcium, phosphate, and magnesium were measured before and after vitamin D3 supplementation. Calcium intake was assessed by questionnaires. When all the data were combined, serum 25(OH)D was negatively correlated with PTH. The cubic spline curve between serum 25(OH)D and PTH indicated PTH reached its plateau between 35 and 40 pg/ml at 25(OH)D between 25 and 30 ng/ml. Vitamin D3 supplementation increased serum 25(OH)D and decreased PTH. Change in PTH correlated positively with baseline serum 25(OH)D. From the regression analyses, baseline serum 25(OH)D above 28 ng/ml corresponded to the threshold level without reduction in PTH after vitamin D3 supplementation. In multivariate regression analyses, age but not calcium intake was a significant determinant of PTH. We concluded that a serum 25(OH)D level of 28 ng/ml was identified as a threshold for vitamin D insufficiency necessary to stabilize PTH to optimal levels.

背景．肺原発の印環細胞癌は稀な腫瘍であり，予後がよくない．抗癌剤の効果についてもまとまった臨床研究はない．症例．38歳，男性．検診で右肺の異常陰影を指摘され，受診した．右上葉の無気肺があり入院となった．気管支鏡下洗浄液の細胞診で腺癌と診断された．右中葉・下葉には癌性リンパ管症を示唆する陰影に加え，小脳虫部に転移結節があり，全身化学療法を行った．ドセタキセル+シスプラチン，イリノテカン+シスプラチンはいずれも無効で，S-1を次に選択した．S-1開始後，後腹膜の左腸腰筋外側や右副腎の転移結節が一時的ではあるが，著明に縮小した．死後剖検が行われ，印環細胞成分を有する肺原発腺癌であった．結論．胃癌に有効性が確認されているS-1の治療効果を肺原発印環細胞癌で検討する意義がある．

Background The histological pattern of pleuroparenchymal fibroelastosis (PPFE) is well defined, but its clinical features remain unclear. Methods We retrospectively examined the predominantly involved lung-fields (based on abnormal opacities on computed tomography [CT] images), and the initial value and annual decline of respiratory function in patients with pulmonary fibrosis presenting with histologically confirmed PPFE. Results Thirteen female and nine male subjects were included. Eleven interpreters independently analyzed 231 CT image series. One-third of the CT series (78/231) was interpreted as demonstrating equal involvement of the upper and lower lung fields, i.e., six out of 21 patients had equal involvement of the upper and lower lung fields, based on a majority decision of the interpreters. The residual volume/total lung capacity (RV/TLC) was increased and correlated inversely with forced vital capacity (FVC) at the initial measurement. FVC followed two patterns of decline over time: a gradual decline over a follow-up period of more than 6 years (−55mL/year, R 2 =0.799), and a relatively rapid decline over a shorter period (−364mL/year, R 2 =0.855) as determined by mixed-effect linear regression. Conclusions The predominantly involved sites seen on CT images of PPFE were not limited to the upper lobes. In some cases, upper lung fields were predominantly involved, but in other cases, both upper and lower lung fields were equally involved. Two patterns of FVC decline exists: a rapid decline over a short period and a slow decline over a longer period, suggesting that the disease follows a heterogeneous clinical course.

Calcium intake was negatively associated with bone resorption marker such as DPD, NTX, and P1NP in Japanese postmenopausal osteoporotic patients. Not only to suppress bone resorption but also to keep higher hip bone mineral density were observed in the patients with higher intake of calcium than 800mg/day and higher vitamin D condition (more than 50nmol/L of serum 25 (OH) D). Higher calcium intake than 800mg/day from dairy and Tofu products, higher intake of vitamin D than 10μg/day from fish, and higher intake of vitamin K from vegetables should be recommended in Japanese postmenopausal osteoporotic patients. We should also pay attention to their losing weight and excess intake of these nutrients from supplements.

Calcium supplementation could accelerate bone mineral accrual, but the effect of other dietary factors in children is unclear. The aim of this study was to determine associations of changes in diet with bone accrual in Japanese children. All female (n=262) and male (n=286) school children aged 10-15 years living in a small town were recruited. We measured bone status at the os calcis using quantitative ultrasound (QUS) and assessed diet and other lifestyle factors using questionnaires annually for 5 years. The greatest increase in QUS values was observed between ages 11-13 years in boys and girls and peak bone status was attained typically by age 14-15 years (approximately 2 years since menarche) in girls and 1-2 years later in boys. Initial bone status adjusted by height and weight in 10-year-old or 11-year-old children was associated positively with intake of small fish and dairy products, and negatively with age of menarche in girls, and negatively with preference for meat in boys. Annual increase in QUS bone status in girls age 10 years or 11 years was associated positively with increased intake of fish, fruit, vegetables, soybeans, and intake of milk products and negatively with preference for meat. Annual increase in QUS bone status in boys was associated positively with increased height and weight, increased intake of small fish and vegetables, intake of dairy products, and awareness of bone measurement. Thus, a dietary change incorporating an increased intake of fish, fruit, vegetables, and soy products could lead to higher bone QUS values in children.

To the Editor: Idiopathic pleuroparenchymal fibroelastosis is a peculiar pulmonary fibrosis proposed by Frankel et al . [1] in 2003 and is almost the same concept as idiopathic pulmonary upper lobe fibrosis proposed by Amitani et al. [2]. There are no known causes for fibrosis in idiopathic pleuroparenchymal fibroelastosis. Sometimes, pleuroparenchymal fibroelastosis (PPFE) has underlying diseases or conditions, such as collagen vascular diseases, anti-cancer chemotherapy, irradiation, asbestos exposure and bone-marrow transplantation [3]. Herein, we report the case of a female who received living-donor lung transplantation and died of pulmonary fibrosis, which was pathologically compatible with PPFE in addition to constrictive bronchiolitis, which is a manifestation of chronic lung allograft dysfunction (CLAD) [4]. A 30-yr-old female suffering from idiopathic pulmonary arterial hypertension underwent living-donor lung transplantation surgery and received a right lower lobe from her younger sister and a left lower lobe from her mother in December 2003. 20 months after the lung transplantation she had dyspnoea and a chest radiograph disclosed bilateral ground-glass shadows. 1 month later, right open lung biopsy was performed and a diagnosis of interstitial pneumonia was obtained. Pulse therapy with methylprednisolone slightly improved her condition and prednisolone was administered after the pulse therapy. However, bilateral interstitial opacities gradually deteriorated (fig. 1) with increased dyspnoea. 49 months after the lung transplantation, her daily life had worsened to almost whole-day bed rest. 18 days prior to her death she …

The peak bone mass is acquired at around the age of 16 years in young Japanese women according to the results of a cross-sectional study. We measured the bone mineral content of os calcis once a year for 5 years in girls aged 10 to 17 years and in boys aged 10 to 15 years, and provided medical information about osteoporosis and nutritional guidance to prevent osteoporosis during this period. We found that the peak in bone minerals was reached by the age of 14 years or 2 years post-menarche in girls and was older than 15 years in boys. The increase in bone minerals was associated with an increased intake of fish, soybean, fruit, and vegetables in girls, and with an increased intake of small fish and vegetables and consciousness of bone requirements in boys. We suggest from these results that bone measurement and medical and nutritional education are important for acquiring adequate peak bone mass in adolescence which will be one of the most effective ways to prevent osteoporosis in later life.

Aims To investigate the histological evolution in the development of pleuroparenchymal fibroelastosis (PPFE). Methods and results We examined four patients who had undergone surgical lung biopsy twice, or who had undergone surgical lung biopsy and had been autopsied, and in whom the histological diagnosis of the first biopsy was not PPFE, but the diagnosis of the second biopsy or of the autopsy was PPFE. The histological patterns of the first biopsy were cellular and fibrotic interstitial pneumonia, cellular interstitial pneumonia (CIP) with organizing pneumonia, CIP with granulomas and acute lung injury in cases 1, 2, 3, and 4, respectively. Septal elastosis was already present in the non-specific interstitial pneumonia-like histology of case 1, but a few additional years were necessary to reach consolidated subpleural fibroelastosis. In case 3, subpleural fibroelastosis was already present in the first biopsy, but only to a small extent. Twelve years later, it was replaced by a long band of fibroelastosis. The septal inflammation and fibrosis and airspace organization observed in the first biopsies were replaced by less cellular subpleural fibroelastosis within 3–12 years. Conclusions Interstitial inflammation or acute lung injury may be an initial step in the development of PPFE.

Febrile neutropenia frequently develops after chemotherapy, and the prompt administration of antimicrobial agents is required for treatment. In the present study, we searched for predictive factors for the failure of the initial antimicrobial agents used for febrile neutropenia (FN) in patients with lung cancer. Sixty FN patients treated in our ward from June 2005 to May 2011 were retrospectively analyzed. The definition of FN and the response to antimicrobial agents were determined by the Japanese guidelines. We divided the FN patients into two groups by their response to the initial antimicrobial agents. Next, the characteristics of the two groups were compared. The Multinational Association of Supportive Care in Cancer (MASCC) score did not differ between the two groups. The non-responder group demonstrated significant elevation of serum C-reactive protein (CRP) level. A multivariate analysis demonstrated that a CRP level higher than 10 mg/dl is an independent risk factor for the failure of initial antimicrobial agents for FN with lung cancer (OR 11.0, 95 % CI 1.635–74.5). When the CRP score was added to the MASCC score, the scoring system could more precisely predict the failure of initial antimicrobial agents in patients with lung cancer who developed febrile neutropenia.

The greatest increase in bone density was observed around ages 10-14 years in girls and thereafter peak bone mass was attained. Maximizing peak bone mass during adolescence is one of the most important strategies to decrease osteoporotic fractures later in life. Initial bone mass adjusted by height and weight in 10-year-old girl was associated positively with intakes of dairy products and small fish. Annual increase in bone mass from age 10 years to 11 years was associated positively with increased intake of fish, fruit, vegetables, and soybeans. Thus, not only calcium but also adequate dietary patterns such as increased intake of fish, fruit, vegetables, and soy products lead to higher peak bone mass in adolescent and will decrease the risk of bone fracture in postmenopausal age.

Dieting methods for preventing age-related diseases such as cardiovascular disease, hypertension and diabetes, as well as osteoporosis are proposed here. Losing weight to prevent and ameliorate metabolic syndrome can lead to loss of bone and muscle mass. However, when subjects had milk before dinner while dieting, their fat mass was efficiently decreased and their muscle mass increased without any change of bone mass. Increased intake of vitamin D enhanced these effects. Therefore we suggest that people with high risk of metabolic disorders should take more low fat dairy products and fish, together with fruits, vegetables, and soy in order to increase their intake of calcium, vitamin D, n-3 polyunsaturated fatty acids, protein, antioxidants, various vitamins and minerals, and fiber to protect them from the deterioration of arteries and bones.

An inadequate calcium intake among Japanese youth has been commonly observed and it has been asso­ciated with lower bone mineral density (BMD).1,2 Moreover, the increasing prevalence of unhealthy dieting practices is seen among young women in most industrialized countries. In fact, more frequent dieting has been associated with lower BMD in Japanese young women.1 The increasing prevalence of unhealthful dieting practices may also adversely affect dairy food consumption.

The relationship between bone mineral content (BMC) divided by bone width (BW) and diet and lifestyle in early adulthood were investigated from the view point of preventing osteoporosis at a young age in Asian women. BMC/BW of 161 healthy Asian women aged 19-25 y were measured by single-photon absorptiometry. Current and past dietary habits and physical activity were also studied. BMC/BW varied from 0.21 to 0.48 g/cm2. Bone density correlated well with dietary habit from infancy to the present especially with calcium and past physical activity. These two factors showed additive effects on BMC/BW. In multiple-regression analysis, liking sports, body mass index, no milk intake in childhood, protein intake, frequency of dieting, and skipping meals were contributors to bone density and predictive of 23% of the variability in BMC/BW in the total group. The multiple-regression coefficient was 0.518. Smoking, drinking, and duration of sunbathing might have no effect on BMC/BW in early adulthood.

A 46-year-old man developed respiratory distress with air leak syndrome (ALS), including pneumothorax, pneumomediastinum, and subcutaneous emphysema. Open lung biopsy was performed and revealed the histopathologic evidence of bronchiolitis obliterans organizing pneumonia (BOOP), which responded well to steroid treatment. As far as we know, this appears to be the first case of BOOP presenting with ALS as one of its major complications.

Vitamin D insufficiency is a risk for both skeletal and nonskeletal health. However, some ambiguity remains about threshold serum 25(OH)D for vitamin D insufficiency. To determine the threshold serum 25(OH)D to maintain normal calcium availability without elevation in serum parathyroid hormone (PTH) among Japanese subjects with various calcium intakes, we conducted a multicenter prospective open-labeled study. We recruited 107 ambulatory subjects without disorders affecting vitamin D metabolism to whom oral vitamin D₃ 800 IU/day for 4 weeks or 1,200 IU/day for 8 weeks was given. Serum 25(OH)D, PTH, calcium, phosphate, and magnesium were measured before and after vitamin D₃ supplementation. Calcium intake was assessed by questionnaires. When all the data were combined, serum 25(OH)D was negatively correlated with PTH. The cubic spline curve between serum 25(OH)D and PTH indicated PTH reached its plateau between 35 and 40 pg/ml at 25(OH)D between 25 and 30 ng/ml. Vitamin D₃ supplementation increased serum 25(OH)D and decreased PTH. Change in PTH correlated positively with baseline serum 25(OH)D. From the regression analyses, baseline serum 25(OH)D above 28 ng/ml corresponded to the threshold level without reduction in PTH after vitamin D₃ supplementation. In multivariate regression analyses, age but not calcium intake was a significant determinant of PTH. We concluded that a serum 25(OH)D level of 28 ng/ml was identified as a threshold for vitamin D insufficiency necessary to stabilize PTH to optimal levels.

Bone fractures are affected by bone mineral density, bone turnover, and risk of falls. Nutritional status could influence all these factors. The preventive effect of higher intake of calcium (1200 - 1500 mg/day) and vitamin D (10 - 20 microg/day) on osteoporotic fractures is well established and these are strongly recommended for the prevention of fractures in European and North American countries. Comparing to Western people, Japanese calcium intake (529+/-285 mg/day, n = 8,964) is much lower. We discuss recent data of other nutrients and factors which may be associated with fractures risk, such as vitamin K, C, B(12), potassium, magnesium, soy isoflavon, and homocysteine, and suggest several recipes and proper food intake to decrease fracture risk in Japanese elderly people as follows. Japanese elderly is recommended to add milk to traditional dish such as Miso soup for enhancement of calcium intake. They should take fish at least every other day to take more vitamin D and protein. Also, reinforcements of soy, fruit, and vegetable intake to increase vitamin K, vitamin C, potassium, magnesium, soy isoflavon and to decrease in homocysteine formation are recommended.

Bone disorders clearly related to nutrition are osteomalacia and osteoporosis. Osteomalacia is caused by a deficiency of vitamin D or a disturbance of its metabolism. Dietary deficiency of phosphate or excess of aluminum or cadmium will also cause osteomalacia. Osteoporosis is associated with low intake of calcium and other nutrients. Dietary copper deficiency might stimulate bone metabolism and increase in hip fractures. Excess vitamin A intake was also associated with lower bone mineral density and higher risk of hip fractures. Excess vitamin D sometimes causes mental simplicity, congenital heart disease and calcification of soft tissue. Therefore not only diet but also drugs and supplements of nutrients should be carefully observed in older women.

Recent development of pharmacological treatments with proven efficacy will increase demand for the more effective management of patients with osteoporosis. Osteoporosis is a chronic disease concerned many risk factors such as diet and nutrition, and pharmacological efficacy could much depend on such nutritional conditions in patients as calcium, vitamin D, and protein, etc. Especially Japanese elderly usually took extremely low calcium and protein intake as well as low vitamin D, however, physicians usually give just pharmacological prescription. Therefore firstly we had better assess the nutritional conditions in each patient by body weight, serum albumin, and dietary questionnaires and give them selected pharmacological prescription together with dietary and nutritional guidance for their effective treatment of drugs. Thus we can manage each patient with not only pharmacological but also nutritional treatments that will be effective in cost-performance and good compliance for chronic disease as osteoporosis. Moreover combined nutritional treatments could work more effective in the patients of osteoporosis with inflammatory disease and high nutritional metabolic rate.

Physician's guidelines for osteoporosis based on evidence from randomized, controlled clinical trials were available in many countries. Most of these guidelines include not only pharmacological therapies but also non-pharmacological treatments. Non-pharmacological treatments include nutrition as high intake of calcium and vitamin D. The calcium intakes are 1,200-1,500 mg/day in WHO, North America, and Europe, while that in Japan is as low as 800 mg/day. The vitamin D intakes are 10-20 microg/day in all other countries except Japan, in which the intake is about 5 microg/day. Other dietary guidelines in most of the countries including having optimal body weight, maintaining adequate protein intake, balanced diet, and avoiding excess sodium and caffeine are similar to Japanese guidelines. However, enough intakes of vitamin K and other vitamins and minerals are not included in these guidelines except Japan because of weak evidences so far.

We encountered a case in which the symptoms of hypoxia and hemoptysis improved after performing repeated pulmonary artery embolizations and bronchial artery embolization. A 22-year-old man was hospitalized in our institution with high fever, headache and unconsciousness in May of 2001. Subendocranial abscess was diagnosed, so we performed antibiotic therapy and drainage, but at that time he showed symptoms of hypoxia. We diagnosed Osler-Weber-Rendu syndrome because of multiple small nodular shadows in his chest CT, multiple arteriovenous fistulae in both lungs on pulmonary arteriography, and telangiectasis. We performed pulmonary artery embolization 6 times, and his hypoxia and right to left shunts improved. In the course of our therapy, hemoptysis appeared and dilatation of vessels was detected in the left bronchial arteriography, so we performed embolization of the left bronchial artery and the symptom improved. We concluded that we should take care to detect not only pulmonary arterial lesions but also bronchial arterial leisions in the diagnosis and therapy of respiratory symptoms of Osler-Weber-Rendu syndrome.

Subclinical vitamins deficiency is common in the elderly, especially in osteoporotic patients. However, most physicians in this area are just focused on drugs for the treatment of osteoporosis. It is already established that several vitamins influence bone turnover, bone mineral density, or even the risk of hip fractures. Improving these vitamins status may help to treat and prevent osteoporosis in elderly people. Recently higher vitamin D intake is recognized to be needed to keep not only bone health but also muscle strength. More sun exposure might be needed for improved bone health in the elderly. Deficiency of Vitamin K, C, or B(12) may be also important modifiable risk factors for osteoporosis and bone fracture. Excessive retinal supplementation may become associated with higher bone loss. Thus such diet rich in fruit and vegetables together with fish and meat could fulfill a balance among these vitamins and should be recommended for prevention or treatment of osteoporosis.

Increased mechanical loading of the skeleton results in bone gain, whereas unloading the skeleton leads to bone loss. Regular exercise, especially resistance and high-impact activities, contributes to development of high peak bone mass and the greatest effects on bone mass appear to occur in early adolescence. Therefore, it seems reasonable to turn our attention to intervening in the younger population to establish lifelong exercise habit that maximize peak bone mass. Adequate calcium intake together with exercise is crucial to develop optimal peak bone mass and to preserve bone mass throughout life. This lifelong exercise may prevent osteoporosis and reduce fracture risk by attenuating age-related bone loss and lowering the incidence of falls. Moreover such lifestyle as sitting on Tatami mat could also stimulate bone accumulation in early adolescent girls. Sports participation may offset the negative effect of smoking on bone mass.

Japanese recommended dietary allowance of vitamin D is quite low and about half to one third of the West, however, 1alpha-OH-D as a drug is popular usage for osteoporosis patients in Japan. The different way of thinking of vitamin D may come from quite low calcium intake in Japanese and more biosynthesized vitamin D owing to a location lower in latitude of Japan. Still, recommended dietary allowance of vitamin D in the West will be raised much higher level in near future owing to many evidences demonstrating the shortages of vitamin D for optimal bone health in Western elderly. More researches will be needed to decide adequate intake of vitamin D for Japanese.

It is widely accepted that development of a higher peak bone mass during adolescent years protects against postmenopausal osteoporosis. It is wise to instill in children good eating habits before adolescence. However, low intake of calcium, frequent intake of fast food, convenience food and oily snack as well as cyclical dieting often observed in recent Japanese children. Educating children about osteoporosis at school could accelerate higher bone mass accumulation by improvement of their diet and other lifestyle factors. Significantly higher bone accruals was observed in Japanese children who had increased intake of vegetable, fruit, fish and small fish along with consciousness of bone measurement.

Strategies for the prevention of osteoporosis in young and middle aged adults include: a balanced diet which provides a calcium intake of at least 800 mg/day; encouragement of a physically active lifestyle; avoidance of smoking and of high alcohol and caffeine intakes; minimization of glucocorticoid use; promotion of intake of vitamin D, protein, vitamin K, vitamin C and potassium.

A procedure for fractional determination of soybean sterols is presented. Sterols in lipid extracts were fractionated into four classes, fatty acid esters, the free form, acylated glucosides and non-acylated glucosides, by Florisil column chromatography. Sterol contents in the four classes were determined colorimetrically with ferric chloride-perchloric acid reagent. Before the colorimetry, the fatty acid ester fraction was hydrolyzed with ethanolic KOH, and the sterol was isolated as tomatinide. The free sterol fraction was directly treated with tomatine solution. The tomatinides were dissociated with dimethyl sulfoxide. To avoid the contamination of pigments from the acylated glucoside fraction, the second Florisil column was rinsed with diethyl ether between the elution with the first solvent (0 to 50% diethyl ether in n-heхane) and that with the second solvent (0 to 30% methanol in diethyl ether).

When rats were subjected to the stress of burns, tumors, or partial hepatectomy, a notable new peak of glucocorticoid binding protein appeared on DEAE-cellulose chromatography. This peak accompanied the original peak, which was the only dominant peak in intact rats. The appearance of the new binding protein was concomitant with a high rise in serum corticosterone levels. The new peak was eluted with 0.12-0.14 M NaCl and another, small new peak with 0.02-0.03 M NaCl, while the original peak of intact rats was eluted with 0.05-0.08 M NaCl. In rats adrenalectomized prior to the stress, the new peaks did not appear. To mimic these stressful conditions which provoked a burst of endogenous glucocorticoid, rats were administered with an exogenous high dose of dexamethasone (100 micrograms/100 g B.W.) in vivo. The new peak eluted with 0.12-0.14 M NaCl was again observed and was more dominant in the hormone-treated rats than the stressed rats. These three peaks eluted with 0.02-0.03 M, 0.05-0.08 M, and 0.12-0.14 M NaCl are called here Peak A, B, and C, respectively. This is the first demonstration of the effect of physiological changes in serum levels of glucocorticoid hormone on the nature of glucocorticoid binding protein by DEAE-cellulose chromatography.

A new glucocorticoid-binding protein (Peak C) eluted with 0.14 M NaCl on DEAE-cellulose chromatography was identified previously in the rats subjected to stress or treated with glucocorticoid (100 micrograms/100 g body wt.), while the 'classic' glucocorticoid receptor (Peak B) eluted with 0.07 M NaCl was found predominantly in untreated rats. The new glucocorticoid-binding protein, Peak C, was characterized by Scatchard analysis and competition with other steroids as a glucocorticoid receptor. The saturation curve of Peak C for dexamethasone was sigmoidal, whereas that of Peak B was hyperbolic. The Hill coefficient was 1.0 for Peak B and 3.1 for Peak C. These results show that Peak C has multiple binding sites. Peak C bound specifically to only natural or synthetic glucocorticoids, whereas Peak B bound not only to glucocorticoids but also to progesterone and aldosterone. Peak C was far more labile than Peak B, its binding activity decreasing 80% when it was incubated for 30 min at 25 degrees C. The molecular sizes of these two peaks (B and C) were similar, being about 90 000-100 000 as determined by Sepharose 6B column chromatography at high ionic strength (0.34 M KCl). The hormone-receptor complex of Peak C bound to rat liver chromatin specifically, but did not bind to calf thymus DNA. The complex of Peak B bound to not only the chromatin but also calf thymus DNA. Peak B reacted well with antiserum to the 'classic' glucocorticoid receptor, but Peak C did not react with this antiserum. These results indicate that Peak C is a different glucocorticoid receptor protein from Peak B, or classic glucocorticoid receptor, and plays physiologically important roles as a glucocorticoid receptor mediating the action of the hormone at a high level.

Riboflavin(RF)-productivity of reseoflavin(RoF)-resistant strains of Staphylococcus aureus, Bacillus pumilus and Bacillus subtilis was studied. Two of three types of resistant strains of S. aureus were shown to produce more RF than the parent strains. Resistant strains of B. pumilus were also RF-producing, and one type (fp) of the resistant strains from B. subtilis HW produced a large amount of RF in the culture medium. The hereditary stability of RF-producing properties of the fp type was also shown.

When rats were treated with a high dose (greater than or equal to 20 micrograms/100 g BW) of dexamethasone, their liver cytosol showed a predominant peak of specific binding protein of glucocorticoid eluting with 0.13-0.14 M NaCl on diethylaminoethyl cellulose chromatography. On the other hand, when rats were treated with a low dose (approximately 2 micrograms/100 g BW) of dexamethasone, the cytosol showed only the same peak as that of untreated rats, which is widely thought to be that of the typical glucocorticoid receptor. The appearance of the new binding peak depended both on the dose of hormone and the time (from 30 min to 20 h) after dexamethasone treatment; it disappeared 40 h after treatment. A peak similar to that in the cytosol also appeared in the nuclear fraction after treatment with a high dose of hormone. The glucocorticoid-inducible enzymes, tryptophan dioxygenase [(TO) EC 1.13.11.11] and tyrosine aminotransferase (EC 2.6.1.5) were assayed as physiological markers of receptor function. TO induction correlated well with the appearance of the new binding peak in terms of dose- and time dependence on glucocorticoid, whereas tyrosine aminotransferase induction did not. The new peak of glucocorticoid-binding protein detected in the cytosol and nuclear fractions may thus represent the glucocorticoid receptor species involved in TO induction, physiological changes under stress, and pharmacological changes after therapy with high doses of glucocorticoid hormones.

When young rats (less than 14 days old) were treated once a day for 2 days with 100 micrograms/100 g body weight of dexamethasone, their liver cytosol showed a sharp new peak of glucocorticoid binding protein (peak C) eluted with 0.14 M NaCl on DEAE-cellulose chromatography. When the young rats were given a single injection of the hormone, the chromatogram showed a dominant peak of binding protein (peak B), eluted with 0.07 M NaCl, which was similar to that in untreated rats. The appearance of peak C on two treatments of young rats with hormone was confirmed by both in vivo and in vitro labeling and also studies on the nuclear fraction. Peaks B and C were specific hormone-binding proteins as shown with excess unlabeled hormone. The appearance of peak C was concomitant with the precocious induction of tryptophan dioxygenase in the liver of the young rats, and pretreatment with two injections of dexamethasone were necessary for maximal enzyme induction. On the other hand, in adult rats a single injection of dexamethasone (of 20 micrograms/100 g body weight or more) was enough to cause the appearance of peak C and induce tryptophan dioxygenase activity maximally; an additional injection of the hormone did not change the chromatographic pattern of the specific binding or the enzyme activity. For this effect in young rats, dexamethasone could not be replaced by other hormones such as glucagon, growth hormone, thyroid hormones, insulin, sex steroids or short-acting glucocorticoid.

Tryptophan 2, 3-dioxygenase activity follows a characteristic pattern of change during development of suckling rats; namely, it is appears 2 weeks after birth and then increases to the adult level by day 22. Glucocorticoids, potent inducers of the enzyme in adult rats, can induce its precocious appearance on day 8 or 10 after birth (1) or even on day 4 (2). The induced level is not more than the adult basal level. We investigated the conditions controlling the response to glucocorticoid before day 14 in suckling rats without using tryptophan. Pretreatment with dexamethasone for 2 days increased the induction by glucocorticoid, resulting in 2 to 3 times higher activity than the adult basal level. Actinomycin D and cycloheximide inhibited this enzyme induction.