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Plasma concentrations of insulin-like growth factor-I (IGF-I) have been shown to be controlled by growth hormone, insulin and nutritional status of animals.1–3 In previous papers, the present authors demonstrated that quantity and nutritional quality of dietary proteins significantly affect the plasma concentration of IGF-I.4 The concentration correlated well with the growth rate or the rate of whole body protein synthesis.5 We also showed that liver content of IGF-I mRNA was also strongly affected by the status of protein nutrition.6 7 It decreased greatly under protein deprivation and it was highly correlated with the plasma IGF-I concentration. The content of the mRNA species of larger molecular weight was most severely affected. These results strongly suggest that the rate of body protein synthesis or growth rate is regulated by the plasma concentration of IGF-I through liver IGF-I mRNA content (or the rate of synthesis and secretion of IGF-I by liver).

Dry etching of 4H-silicon carbide (SiC) is studied using chlorine trifluoride gas at 673-973K and atmospheric pressure in a horizontal reactor. The etch rate of C-face and Si-face of 4H-SiC can be greater than 10 um/min at substrate temperatures higher than 723 K. The etch rate of Si-face is lower than that of C-face. The etch rate increases with the chlorine trifluoride gas flow rate. The etched surface of Si-face shows many pits having a hexagonal edge shape and tends to be rough. However, the C-face maintains a very smooth surface after the etching. The average roughness of the etched surface tends to be low at the higher temperatures. The etch rate behavior is discussed from the view points of the transport phenomena in the reactor and the chemical process at the substrate surface; their rate constants are obtained.

A new cDNA clone for rat IGF-I mRNA was obtained. The cDNA contained a new base sequence as cDNA in the 3' region. The sequence coincided with a part of the sequence reported earlier by Shimatsu and Rotwein5) in exon 5 of the rat IGF-I gene. The presence of this cDNA proved the previous suggestion to be true that the size heterogeneity of IGF-I mRNA is primarily due to the heterogeneity of the 3'-untranslated region.

1. We have characterized the insulin receptor in primary cultured quail oviduct cells and examined the hormonal regulation of its level. 2. We have also shown the recycling pathway of insulin receptors in the cultured cells using specific inhibitors (tunicamycin, chloroquine, monensin, and brefeldin A). 3. Our data suggest that glucocorticoids play important physiological roles in egg-white protein synthesis through increasing the number of insulin receptors and insulin through enhancing the transport of amino acids.

Corrigendum: Frequent somatic mutations of the transcription factor ATBF1 in human prostate cancer

3-N-Alkylcyanoacetamidoquinoline 1-oxides (3a and 3c) react with Ac 2 O at room temperature in chloroform to afford 1-alkyl-3-cyano-4H-pyrrolo [3,2-b]quinolin-2-ones (4a and 4c). The cyclization of 3-N- alkylethoxycarbonylacetamidoquinoline 1-oxides (3b and 3d) occurs upon heating with Ac 2 O at 60°C. 3-(3,3-Dicyanopropoxy)quinoline 1-oxide (5) also cyclizes to the pyranoquinoline (6) when treated with Ac 2 O at room temperature in chloroform-DMF

3-Bromo-4-nitroquinoline 1-oxide (1) reacted with 2-methylaminoethanol, 1-amino-2-propanol and ethylenediamine to give the corresponding 3-amino-4-nitroquinoline 1-oxides (2, 4 and 7), which readily underwent the intramolecular cyclization, upon heating with Ac 2 O in DMF, to afford the morpholino[2,3-b]quinolines (3 and 6) and the piperazino[2,3-b]quinoline (8). The reaction of 1 with N,N'-dimethylethylenediamine afforded directly the piperazinoquinoline (10), and that with 2-aminoethanethiol gave the thiomorpholino[2,3-b]quinoline (11) and its 10-oxide (12)

Treatment of 3-dialkylamino-4-aminopyridines (1) with nitric and sulfuric acids affords imidazo-[4,5-c] pyridine derivatives (2, 3 and 4) and 1,2,3- triazolo [4,5-c] pyridine 2-oxides (5) by cyclization reaction of the corresponding 4-nitroaminopyridines

Reactions of 3-fluoro- (1a), 3-bromo- (1b), 3-methyl- (1c), 3-methoxy- (1d) and 3-acetamidoquinoline 1-oxides (1e) with acylating agents (POCl 3 , Ac 2 O, TsCl and PhCOCl) were examined (table). While only 2-substituted quinolines were obtained from 1a and 1b, fair amounts of 4-substituted products were formed in reactions of 1d, the sole formation of the 4-acetoxyquinoline (6) with Ac 2 O being the most significant result. 2-Chloroquinoline, 4-chloroquinolines and 2-tosyloxyquinolines were formed (and sometimes predominate) in addition to 2-quinolinones in reactions with TsCl

Reinvestigation of the reaction of 3-bromo-4-nitroquinoline 1-oxide (2) with 1-morpholinocyclohexene (3) has revealed that the reaction proceeds by a multistep ionic process involving the initial formation of 3-morpholino-4-nitro-2-(2-oxocyclohexyl)quinoline (6) and the subsequent transformation of 6 into 10-nitro-1,2,3,4-tetrahydrobenzofuro[3,2-b]quinoline (5). Not only 2 reacts with various enamines in the same way, but also 3-bromo-4-nitropyridine N-oxide (7) undergoes the same type of reaction.

Skiing is a typical winter activity units included in the Physical Education curriculum in Hokkaido which located in northern Japan. Upon examination of the present skiing unit, many problems are evident. It seems that these problems have resulted from the present unit planning which has been constructed and modeled after the alpine skiing unit.The purpose of this study is to inquire into the possibility of improving the skiing classes by introduce a cross-country skiing unit.The procedure included (1) the planning of a cross-country skiing unit, (2) instruction based on the planed unit, and (3) comparison between the alpine skiing type unit and the cross-country skiing type unit.The subjects of this unit were 259 students from Asahikawa Junior High School, and the instructional period was from Feb. to March, 1987.The results were as follows:1. In reviewing the present skiing units which prevailed in Physical Education classes, many practical problems were found. These problems included class size, financial expenditures, facilities and equipment, and a biased view of nature of physical education teachers.2. We found that a cross-country skiing type unit had a positive possibility for problem-solving after the instruction of the designated unit.In conclusion, it is suggested that the cross-country skiing type unit should be introduced in many schools because it has the potential to be more effective than the alpine skiing type unit.

The reaction of ketene with Schiff bases was investigated. Heating of ketene with Schiff bases (1a-l) without solvent gave α-unsubstituted β-lactams (2a-l). The reaction of ketene with ethyl N-furfurylideneglycinate (1k) to give the β-lactam 2k was carried out at various temperatures, and it was found that the yield of 2k was not much influenced by the reaction temperature. β-Lactams (2d, f, k, l) were treated with 10% aqueous sodium hydroxide in dioxane to give the corresponding carboxylic acids (4d, f, k, l) in good yields. Compounds 4d, f, l reacted with various amines in the presence of dicyclohexylcarbodiimide (DCC) to give the corresponding amides (5a-c, 8a-d).

A simple method for the quantification of antithrombin activity was demonstrated by means of fibrinogen agarose plate. The principle of the method is the growth of fibrin rings by residual thrombin on fibrinogen agarose plate after the reaction with antithrombin. The mixtures of defibrinated plasma or serum, and thrombin were incubated for about 30min at 37°C, and then poured into the wells in the fibrinogen agarose plate with micropipettes. After the incubation of the plate for about one hr at 37°C, the diameters of fibrin rings were measured. As a control, saline was used in place of samples. The antithrombin activity index was indicated by the square of the control diameter which was divided by that of the sample diameter. The reproducibility of the method was 4.8% in coefficient of variation in plasma and 5.4% in serum, and normal values were estimated as 1.5-2.5 in plasma and 1.4-2.0 in serum. There was a significant correlation between the values obtained with this method and with the biological one by Biggs et al. With this method we tested about 70 samples from patients. In cases of liver cirrhosis and disseminated intravascular coagulation (DIC), antithrombin activity index decreased.

Ultracentrifugal separation and analysis of chylomicron, very low, low and high density lipoproteins in the sera from patients with liver metastasis of cancer were carried out. Studies were made on the relationship between lipoprotein and alkaline phosphatase (Al-P) on cellogel electrophoresis. 1) On cellogel electrophoresis, the serum Al-P isozyme of a patient with liver metastasis was divided into Bands I and II. Band I which corresponds to macromolecular Al-P is characteristic of liver metastasis. 2) Band I was found only in high density lipoprotein (HDL) fraction. This result indicates that the density of Band I is very close to that of HDL. 3) The electrophoretic mobility of macromolecular Al-P was the same with that of HDL. 4) No relationship was found between Band II which corresponds to Al-P with a small molecular weight and lipoprotein. 5) By treatment with receptor destroying enzyme of the serum, the electrophoretic mobility of the lipoproteins remained unchanged. Band I, however, was detached from HDL and moved toward the origin. These results suggest that Al-P bands contain a large quantity of sialic acid.

A facile synthetic method for pyrimidine acyclonucleosides is described. Bis (trimethylsilyl) ethers of uracils (1-3) react with 2-substituted 1, 3-dioxolanes (4) in the presence of a Lewis acid to form 1-[α-(2-hydroxyethoxy) alkyl] uracil derivatives. Treatment of these reaction mixtures with methanol containing sodium hydrogen carbonate or aqueous sodium hydroxide gives pyrimidine acyclonucleosides (5a-g).

Insulin-like growth factor I (IGF-I, or somatomedin C) is a hormone, which has been shown to be important in the anabolism of dietary proteins into body proteins (Spencer, 1983). Plasma IGF-I level is affected by many nutritional factors including energy intake (Isley et al., 1983), dietary protein level (Prewitt et al., 1982) and nutritional quality of dietary proteins (Bolze et al., 1985; Takahashi et al., 1988). IGF-I probably works in coordination with insulin but in a different manner in the anabolism of dietary proteins, because, different from insulin, plasma immunoreactive IGF-I level does not increase significantly after a meal and is primarily affected by the dietary composition of the nutrients. Another evidence of the difference in the response of insulin and IGF-I is the manner of response of these two hormones to streptozotocin administration. Imraunoreactive insulin level decreases very quickly after streptozotocin administration whereas IGF-I level is affected gradually, presumably as a secondary effect of insulin deficiency (Takahashi et al., 1988).

A facile synthetic method for pyrimidine acyclonucleosides is described. Bis (trimethylsilyl) ethers of uracils (1-3) react with 2-substituted 1, 3-dioxolanes (4) in the presence of a Lewis acid to form 1-[α-(2-hydroxyethoxy) alkyl] uracil derivatives. Treatment of these reaction mixtures with methanol containing sodium hydrogen carbonate or aqueous sodium hydroxide gives pyrimidine acyclonucleosides (5a-g).

Background Pathological stage and grade have limited ability to predict the outcomes of superficial urothelial bladder carcinoma at initial transurethral resection (TUR). AT-motif binding factor 1 (ATBF1) is a tumor suppressive transcription factor that is normally localized to the nucleus but has been detected in the cytoplasm in several cancers. Here, we examined the diagnostic value of the intracellular localization of ATBF1 as a marker for the identification of high risk urothelial bladder carcinoma. Methods Seven anti-ATBF1 antibodies were generated to cover the entire ATBF1 sequence. Four human influenza hemagglutinin-derived amino acid sequence-tagged expression vectors with truncated ATBF1 cDNA were constructed to map the functional domains of nuclear localization signals (NLSs) with the consensus sequence KR[X10-12]K. A total of 117 samples from initial TUR of human bladder carcinomas were analyzed. None of the patients had received chemotherapy or radiotherapy before pathological evaluation. Results ATBF1 nuclear localization was regulated synergistically by three NLSs on ATBF1. The cytoplasmic fragments of ATBF1 lacked NLSs. Patients were divided into two groups according to positive nuclear staining of ATBF1, and significant differences in overall survival (P = 0.021) and intravesical recurrence-free survival (P = 0.013) were detected between ATBF1+ (n = 110) and ATBF1− (n = 7) cases. Multivariate analysis revealed that ATBF1 staining was an independent prognostic factor for intravesical recurrence-free survival after adjusting for cellular grading and pathological staging (P = 0.008). Conclusions Cleavage of ATBF1 leads to the cytoplasmic localization of ATBF1 fragments and downregulates nuclear ATBF1. Alterations in the subcellular localization of ATBF1 due to fragmentation of the protein are related to the malignant character of urothelial carcinoma. Pathological evaluation using anti-ATBF1 antibodies enabled the identification of highly malignant cases that had been overlooked at initial TUR. Nuclear localization of ATBF1 indicates better prognosis of urothelial carcinoma. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2845-5) contains supplementary material, which is available to authorized users.

Background Recently, several lines of evidence have shown the aberrant expression of cell-cycle-related proteins and tumor suppressor proteins in vulnerable neurons of the Alzheimer's disease (AD) brain and transgenic mouse models of AD; these proteins are associated with various paradigms of neuronal death. It has been reported that ATBF1 induces cell cycle arrest associated with neuronal differentiation in the developing rat brain, and that gene is one of the candidate tumor suppressor genes for prostate and breast cancers in whose cells overexpressed ATBF1 induces cell cycle arrest. However, the involvement of ATBF1 in AD pathogenesis is as yet unknown. Results We found that ATBF1 was up-regulated in the brains of 17-month-old Tg2576 mice compared with those of age-matched wild-type mice. Moreover, our in vitro studies showed that Aβ1-42 and DNA-damaging drugs, namely, etoposide and homocysteine, increased the expression ATBF1 level in primary rat cortical neurons, whereas the knockdown of ATBF1 in these neurons protected against neuronal death induced by Aβ1-42, etoposide, and homocysteine, indicating that ATBF1 mediates neuronal death in response to these substances. In addition, we found that ATBF1-mediated neuronal death is dependent on ataxia-telangiectasia mutated (ATM) because the blockage of ATM activity by treatment with ATM inhibitors, caffeine and KU55933, abolished ATBF1 function in neuronal death. Furthermore, Aβ1-42 phosphorylates ATM, and ATBF1 interacts with phosphorylated ATM. Conclusions To the best of our knowledge, this is the first report that Aβ1-42 and DNA-damaging drugs increased the ATBF1 expression level in primary rat cortical neurons; this increase, in turn, may activate ATM signaling responsible for neuronal death through the binding of ATBF1 to phosphorylated ATM. ATBF1 may therefore be a suitable target for therapeutic intervention of AD.

Background Residual alcohol effects on physiological and psychological symptoms are commonly experienced the morning after alcohol consumption. The purpose of this study was to assess the effects of L-ornithine on subjective feelings and salivary stress markers the morning after alcohol consumption and to investigate whether L-ornithine acutely accelerates ethanol metabolism. Methods This study had a randomized, placebo-controlled, double-masked crossover design. Subjects were all healthy Japanese adults with the ‘flusher’ phenotype for alcohol tolerance. In experiment 1, 11 subjects drank 0.4 g/kg body weight alcohol 1.5 h before their usual bedtime. Half an hour after drinking, they ingested either a placebo or 400 mg ornithine. The next morning on awakening, subjects completed a questionnaire containing a visual analog scale (VAS), the Oguri-Shirakawa-Azumi sleep inventory MA version (OSA-MA), and a profile of mood states (POMS) and collected a saliva sample for measurement of salivary stress markers (cortisol, secretory immunoglobulin A, and α-amylase). In experiment 2, placebo or 400 mg ornithine were administrated to 16 subjects both before and after drinking, and the feeling of drunkenness, breath ethanol concentration and one-leg standing time were repeatedly investigated until 180 min after alcohol consumption. Results There were significant decreases in “awareness”, “feeling of fatigue” and “lassitude” VAS scores and in “anger-hostility” and “confusion” POMS scores and a significant increase in “sleep length” in the OSA-MA test. Salivary cortisol concentrations on awakening were reduced after ornithine supplementation. There were no differences between ornithine and placebo in any of the subjective or physiological parameters of acute alcohol metabolism. Conclusions Taking 400 mg ornithine after alcohol consumption improved various negative feelings and decreased the salivary stress marker cortisol the next morning. These effects were not caused by an increase in acute alcohol metabolism.