Interaction of rat liver glucocorticoid receptor with histones

The activated glucocorticoid-receptor complexes (GRC) from rat liver bind tightly to histone (from calf thymus)-agarose and cannot be eluted with 3 M KCl or 50% ethylene glycol, but can be eluted with 20 mM pyridoxal 5'-phosphate (PALP). Purified activated GRC were found to have much higher affinity for histones H3 and H4 (arginine-rich histones) than for histones H2A and H2B (slightly lysine-rich histones) and to have negligible affinity for histone H1 (lysine-rich histone). The GRC bound to immobilized histones could be eluted with PALP, but not with its related compounds, such as pyridoxamine, pyridoxamine 5'-phosphate, pyridoxal, and pyridoxine, suggesting a specific effect of PALP. Not only activated GRC but also unactivated GRC were found to bind to immobilized histones. However, from their profiles of elution from a histone-agarose column by 20 mM PALP, the activated GRC seemed to have higher affinity than unactivated GRC for histone. Our results suggest that the binding of GRC to histones could be associated with a mechanism for alteration of the chromosome structure by the hormonal signals, before the binding of the GRC to a specific sequence of DNA in regulatory elements of glucocorticoid-responsible genes.     

A national surveillance study of the current status of reirradiation using brachytherapy in Japan

PurposeThis study aimed to explore the current status and pattern of practice for reirradiation using brachytherapy (ReRT-BT) through a survey in Japan.Materials and MethodsWe distributed an e-mail-based questionnaire to 153 institutions equipped with high-dose-rate brachytherapy facilities.ResultsWe received responses from 76 institutions (49.7%). Forty-three of these institutions performed ReRT-BT and 42 institutions (55%) performed ReRT-BT during 2009–2018. However, 29 of the 42 institutions (69%) reported difficulty in obtaining ReRT-BT case information from their respective databases. Almost all the institutions encountered insufficient database system to extract details about the ReRT-BT cases. Responses from 33 institutions included the number of ReRT-BT cases; this increased from 90 in the period 2009–2013 (institution median = 0.5; 0–16) to 172 in the period 2014–2018 (institution median = 2; 0–26). Nine institutions had to perform ReRT-BT for more than one case per year. The major location for cancer treatment was the pelvis (94%), followed by the head and neck (5%) and others (1%). In six site-specific scenarios, barring uterine corpus cancer recurrence, more than 90% of radiation oncologists agreed to perform ReRT-BT, whereas other areas (head and neck, prostate, and rectal cancer) gained 16–37% agreement.ConclusionsThis decade saw an increase in the number of ReRT-BT cases in Japan and radiation oncologists’ interest in ReRT-BT as a viable therapeutic option. However, scarce availability, immature education system, and insufficient database system are barriers to further consensus building.     

Domestic hygiene behaviour of mothers with children aged 0-5 years old in Tayabo village,Nueva Ecija,the Philippines

A cross-sectional survey was carried out in a rural village in Nueva Ecija province in the Philippines to identify the association between mothers' hygiene behaviour and their socioeconomic status and household environment. A total of 206 mothers with children aged 0-5 years old participated in this study. Household visits with face-to-face interviews using a structured questionnaire and observation of household environments were conducted. Logistic regression analysis revealed that the frequency of water boiling in mothers was significantly associated with children aged under two years old and the availability of domestic electricity. Availability of domestic electricity, mother's educational level, possession of a private lavatory and of a private well were significant predictors of whether hand-washing with soap was practiced after defecation. For hand-washing with soap before feeding children, child's age under one year old and the volume of the water supply were statistically significant. The volume of the water supply was identified as a significant predictor. Although health educational programme participation rates were very high (83.2%), no significant association with hygiene behaviour was observed. This study indicates that improvements in water availability, household environment and health education may contribute to more frequent hand-washing.     

Properties of an adenosine triphosphate-stimulated factor that enhances the nuclear binding of activated glucocorticoid-receptor complex: binding to histone-agarose

Recently we have purified and characterized a factor in rat liver cytosol that enhances nuclear binding of the activated glucocorticoid-receptor complex in the presence of ATP [an ATP-stimulated translocation promoter (ASTP)]. It has a mol wt of 93,000, S value of 6.5, and pI of 4.5. Here we report studies on the binding of ASTP to histones from calf thymus. Higher salt concentrations were required to disrupt the binding of ASTP to histone-agarose than to disrupt its binding to the anion exchanger diethylaminoethyl-cellulose (half-maximal concentration for inhibition: 200 mM vs. 60 mM KCl). ATP decreased the binding of ASTP to histone-agarose in a dose-dependent fashion, but ADP and AMP had no appreciable effect on the binding. Pyridoxal 5'-phosphate (10 mM) inhibited the binding of ASTP to histone-agarose, whereas 10 mM pyridoxal, pyridoxamine 5'-phosphate, pyridoxamine, and pyridoxine were not inhibitory. ASTP did not bind to histone-agarose that had been pretreated with pyridoxal 5'-phosphate and then reduced with sodium borohydride. In contrast, ASTP pretreated in the same way could bind to histone-agarose. Therefore, modification of lysine residues of histones by pyridoxal 5'-phosphate (Schiff base) presumably inhibited the binding of ASTP to the immobilized histone. Competition experiments with various histones (H1, H2A, H2B, H3, and H4) indicated that ASTP bound to the arginine-rich histones H3 and H4, with preference for H4. These observations together suggest that lysine residues in H4 and H3 are essential for the binding of ASTP to histone. The implications of this interaction are discussed.     

Plasma concentration of pigment epithelium-derived factor in patients with diabetic retinopathy

CONTEXT: Pigment epithelium-derived factor (PEDF) is a strong inhibitor of angiogenesis. Eyes with diabetic retinopathy have low levels of ocular PEDF; however, the PEDF levels in the blood of diabetics have still not been determined. OBJECTIVES: Our objective was to determine the plasma levels of PEDF in diabetic patients and to determine the relationship with the stage of the diabetic retinopathy. DESIGN AND SETTING: This study was designed as a cross-sectional, institutional study. PATIENTS OR OTHER PARTICIPANTS: A total of 145 Japanese were studied; 112 had type 2 diabetes mellitus, and 33 were healthy controls. INTERVENTION: There was no intervention. MAIN OUTCOME MEASURES: The plasma level of PEDF was measured by ELISA, and the stage of diabetic retinopathy was determined by ophthalmic examinations. Clinical systemic status of diabetic patients was also examined. RESULTS: The plasma PEDF level in diabetic patients (6.68 +/- 0.54 microg/ml; mean +/- sem) was significantly higher than that in controls (4.38 +/- 0.59 microg/ml, P = 0.03), and the level was especially high in patients with proliferative diabetic retinopathy (7.78 +/- 0.98 microg/ml; n = 45; P = 0.005). The gender (P = 0.03), blood urea nitrogen (P = 0.005), and triglycerides (P = 0.04) were significant and independent determinants of plasma PEDF levels in diabetic patients. CONCLUSIONS: The PEDF level in the plasma was significantly elevated in diabetic patients, especially those with proliferative diabetic retinopathy. High levels of PEDF in the plasma may be related to the progression of diabetic retinopathy.     

Alteration in the inducibility by dexamethasone of the activity of tyrosine aminotransferase and tryptophan oxygenase in regenerating rat liver after partial hepatectomy

In adrenalectomized rats, the activity of tryptophan oxygenase in liver cytosol was increased 4 h after dexamethasone injection, with a peak on day 2. It then gradually decreased to the value obtained in normal animals treated with dexamethasone. In adrenalectomized, 70% hepatectomized rats, tryptophan oxygenase activity decreased significantly during the period of DNA synthesis after partial hepatectomy; it then increased to above the level existing before hepatectomy, reaching a maximum on day 5, and subsequently returned to the level before hepatectomy. These changes were well correlated with those of dexamethasone receptors at all times after adrenalectomy and partial hepatectomy. In adrenalectomized rats, tyrosine aminotransferase activity was increased 4 h after dexamethasone injection, reached a maximum on day 2, and then remained elevated. The level was increased by subsequent 70% hepatectomy, reached a maximum on day 5, and then began to decrease, but activity was still high on day 10 after hepatectomy when the receptor level had returned to the value existing before hepatectomy. When actinomycin D or cycloheximide was injected with dexamethasone, the induction of the two enzymes was completely inhibited. The activities of the two enzymes in regenerating liver of rats without adrenals and without glucocorticoid treatment were as low as those in adrenalectomized rats without glucocorticoid treatment. Thus, there was a good correlation between the dexamethasone receptor level and the induction of tryptophan oxygenase, but there was a dissociation between the receptor level and the induction of tyrosine aminotransferase after adrenalectomy and partial hepatectomy. The mechanism of this dissociation is unknown.     

Negative brain potentials reflect the subjective distance between standard and deviant tones

The purpose of this study was to examine the effects on event-related brain potentials (ERPs) of occasionally presented deviants in a sequence of tones. The sequence consisted of a series of frequent standard C5 tones from the diatonic musical scale, in which three deviants (F #5, C6, and F #6) and a target (C4) were occasionally embedded. Twenty subjects were asked to detect the target. The deviants elicited frontal N2. The amplitude of the N2 was smaller for C6 than for the other two deviants, whereas peak latencies increased as a function of the frequency distance between the deviant and the standard. The smaller N2 to C6 than that to the other deviants was considered to reflect closer subjective distance due to the octave relationship between C6 and the standard C5.