Response of V79 cells to low doses of X-rays and negative pi-mesons: clonogenic survival and DNA strand breaks

Mammalian cells are hypersensitive to very low doses of X-rays (< 0.2 Gy), a response which is followed by increased radioresistance up to 1 Gy. Increased radioresistance is postulated to be a response to DNA damage, possibly single-strand breaks, and it appears to be a characteristic of low linear energy transfer (LET) radiation. Here we demonstrate a correspondence between the extent of the increased radioresistance and linear energy transfer of 250 kVp X-rays and plateau and Bragg peak negative pi-mesons. The results support our hypothesis since the size of the increased radioresistant response appears to correspond to the number of radiation induced single-strand breaks. Furthermore, since survival prior to the increased radioresistant response (< 0.2 Gy) was LET-independent, these data support the notion that the increased radioresistant response may dictate the overall survival response to higher doses. However, while these data provide further circumstantial evidence for the involvement of DNA strand breaks in the triggering of increased radioresistance, more direct conclusions cannot be made. The data are not accurate enough to detect structure in the single-strand break profiles, the production of single-strand breaks being apparently linear with dose.     

The ratio of initial/residual DNA damage predicts intrinsic radiosensitivity in seven cervix carcinoma cell lines

The single-cell gel electrophoresis (comet) assay was used to measure radiation-produced DNA double-strand breaks (dsbs) in a series of seven cervical tumour cell lines (ME180, HT3, C33A, C41, SiHa, MS751 and CaSki). The proportion of DNA dsbs was measured immediately after radiation treatment (initial damage) and 16 h later after incubation at 37 degrees C (residual damage). Linear dose-response curves were seen for initial (slopes 0.23-0.66) and residual (slopes 0.16-0.87) DNA dsbs. Neither of the slopes of the linear regression analysis on the initial and on the residual DNA dsbs dose-response curves (range 0-80 Gy) correlated with SF2 (surviving fraction at 2 Gy) measured after high- (HDR) or low-dose-rate (LDR) irradiation. An association was evident between SF2 after HDR and LDR irradiation and the ratio of the absolute level of initial and residual damage after a single dose of 60 Gy. However, a significant correlation was found between HDR (r= -0.78, P = 0.04) and LDR (r = -0.86, P = 0.03) SF2 values and the ratio of the slopes of the initial and residual DNA dsbs dose-response curves (range 0.47-0.99), representing the fraction of DNA damage remaining. These results indicate that the neutral comet assay can be used to predict radiosensitivity of cervical tumour cell lines by assessing the ratio of initial and residual DNA dsbs.     

灵活而经济生产热轧板带的奥钢联炉卷轧机技术

描述了炉卷轧机技术的多种方案,介绍了奥钢联在此领域取得的新成果,展示了这些技术方案是如何满足市场的广泛需要的。     

Pathophysiology of aquaporin-2 in water balance disorders

The binaural interaction component (BIC) of the 500-Hz human frequency-following response (FFR) was evaluated as a function of interaural intensity difference (IID) using a lateralization paradigm. The robust FFR interaction component (FFR-BIC) was shown to decrease systematically with increasing IID with no discernible FFR-BIC for IID values larger than about 20 dB. These findings are similar to that observed for the high-frequency auditory brainstem response interaction component (ABR-BIC). Thus, like the ABR-BIC, the FFR-BIC may be correlated with binaural fusion and the perceived location of the fused image of the sound. These results taken together suggest that the binaural neurons in the brainstem are able to utilize IID cues presented in both low-frequency and high-frequency sounds.     

Renal aquaporins

Aquaporins (AQPs) are a newly recognized family of transmembrane proteins that function as molecular water channels. At least four aquaporins are expressed in the kidney where they mediate rapid water transport across water-permeable epithelia and play critical roles in urinary concentrating and diluting processes. AQP1 is constitutively expressed at extremely high levels in the proximal tubule and descending limb of Henle's loop. AQP2, -3 and -4 are expressed predominantly in the collecting duct system. AQP2 is the predominant water channel in the apical plasma membrane and AQP3 and -4 are found in the basolateral plasma membrane. Short-term regulation of collecting duct water permeability by vasopressin is largely a consequence of regulated trafficking of AQP2-containing vesicles to and from the apical plasma membrane.     

Oesophageal reflex responses: abnormalities of the enteric nervous system in patients with oesophageal symptoms

An intraluminal balloon was used to study the peristaltic reflex, which is mediated by the intrinsic nerves of the oesophagus. Serial balloon distension was performed in nine asymptomatic volunteers and 133 patients with oesophageal symptoms. Eight of the volunteers had a normal response with proximal stimulation and distal inhibition of motility. Only 42 patients (31.6 per cent) had a normal response. The commonest abnormal response (39.1 per cent) was some form of failure of the distal inhibitory reflex. Other patterns of abnormality were an unresponsive oesophagus (15.8 per cent) with no motility change during balloon inflation, or spasm (13.5 per cent) proximal to the balloon. These alterations of secondary peristaltic activity suggest that there are abnormalities of the intrinsic (enteric) nerves of the oesophagus. Different abnormalities were found in patients with similar symptoms. Awareness of this difference might allow a more rational approach to treatment. This hypothesis was tested in a small pilot study treating functional dysphagia with cisapride. Three of nine patients had marked symptomatic improvement within 4 weeks and all three had an unresponsive oesophagus. The remaining six patients, who had failure of distal inhibition or a normal response, did not improve.     

Decreased aquaporin-2 expression and apical plasma membrane delivery in kidney collecting ducts of polyuric hypercalcemic rats

Hypercalcemia is frequently associated with a urinary concentrating defect and overt polyuria. The molecular mechanisms underlying this defect are poorly understood. Dysregulation of aquaporin-2 (AQP2), the predominant vasopressin-regulated water channel, is known to be associated with a range of congenital and acquired water balance disorders including nephrogenic diabetes insipidus and states of water retention. This study examines the effect of hypercalcemia on the expression of AQP2 in rat kidney. Rats were treated orally for 7 d with dihydrotachysterol, which produced significant hypercalcemia with a 15 +/- 2% increase in plasma calcium concentration. Immunoblotting and densitometry of membrane fractions revealed a significant decrease in AQP2 expression in kidney inner medulla of hypercalcemic rats to 45.7 +/- 6.8% (n = 11) of control levels (100 +/- 12%, n = 9). A similar reduction in AQP2 expression was seen in cortex (36.9 +/- 4.2% of control levels, n = 6). Urine production increased in parallel, from 11.3 +/- 1.4 to a maximum of 25.3 +/- 1.9 ml/d (P < 0.01), whereas urine osmolality decreased from 2007 +/- 186 mosmol/kg x H2O to 925 +/- 103 mosmol/kg x H2O (P < 0.01). Immunocytochemistry confirmed a decrease in total AQP2 labeling of collecting duct principal cells from kidneys of hypercalcemic rats, and reduced apical labeling. Immunoelectron microscopy demonstrated a significant reduction in AQP2 labeling of the apical plasma membrane, consistent with the development of polyuria. In summary, the results strongly suggest that AQP2 downregulation and reduced apical plasma membrane delivery of AQP2 play important roles in the development of polyuria in association with hypercalcemia.