Dry eye signs and symptoms in aromatase inhibitor treatment and the relationship with pain

PurposeAromatase inhibitors (AIs) limit the synthesis of oestrogen in peripheral tissues thus lowering levels of oestrogen. The primary aim was to evaluate whether women treated with AIs have altered dry eye symptoms and signs. A sub-aim was to investigate whether symptoms of dry eye in postmenopausal women were associated with symptoms of non-eye pain, ocular pain and self-rated pain perception.MethodsThis cross-sectional, observational, single visit study recruited 56 postmenopausal women (mean age 64.1 + 7.9 years) and 52 undergoing AI treatment (mean age 66.6 + 9.0). Ocular symptoms (OSDI, MGD14) and pain questionnaires (PSQ, OPAS) were administered and signs of dry eye and meibomian gland dysfunction were evaluated.ResultsAlmost half of each group reported dry eye symptoms, defined as OSDI>12 (48% control, 46% AI). The PSQ score was significantly higher in the AI group (p = 0.04). Neither frequency or severity of dry eye (or MGD) symptoms scores were significantly different between groups. In the AI group, meibomian gland expressibility score was worse (p = 0.003); there were no differences in any other signs. Higher OSDI scores were associated with higher OPAS eye-pain scores (r = 0.49, p < 0.001), but not OPAS non-eye pain (r = 0.09, p = 0.35). Pain perception (PSQ) showed a moderate positive association with OPAS eye-pain (r = 0.30, p = 0.003).ConclusionsIn this study elevated ocular symptoms were observed in both the AI treated and the untreated groups, with no difference between the groups. Women undergoing AI treatment for early stage breast cancer had worse meibum expressibility score and increased pain perception compared to an untreated group of women.     

DNA双链断裂残留损伤与癌细胞辐射敏感性研究

目的 了解不同组织来源癌细胞株和人体肿瘤组织原代细胞的DNA双链断裂损伤修复的个体差异性,探寻预测癌细胞辐射敏感性的生物指标。方法 ⁶⁰Co γ射线照射诱发DNA损伤,脉冲电场凝胶电泳检测DNA双链断裂损伤修复,细胞克隆形成能力法检测细胞辐射敏感性。结果 8个不同组织来源癌细胞株的辐射敏感性有较大的差异(D₀为0.65~2.15 Gy),不同细胞株20 Gy γ射线照射诱发产生的DNA双链断裂原初损伤有一定的差别,但与细胞辐射抗性无相关性。辐射敏感细胞SX-10的DNA双链断裂修复缺陷发生在早期快速修复相,而A2780细胞的修复缺陷是发生在晚期慢速修复相。20 Gy照射修复2 h后DNA双链断裂残留量与细胞辐射敏感性指标D₀或SF₂值有显著的相关性。不同个体患者脑肿瘤组织原代细胞之间,辐射诱发DNA双链断裂的修复反应存在明显差异,修复2 h后残留损伤的个体差异性分布类似于癌细胞株。结论 DNA双链断裂残留损伤与癌细胞辐射抗性有显著相关性,可作生物指标预测肿瘤组织细胞对放射治疗的反应性。     

The possible role of stromal cell stimulation in worsening the prognosis of a subset of patients with breast cancer

This review examines the evidence that a subset of patients with breast cancer have tumors that are stimulated to grow by host cells in the tumor stroma. The search for such a minority group was prompted by the following observations. Adjuvant chemotherapy which is immunosuppressive improves disease-free interval and survival, whereas non-specific immunostimulation worsens the prognosis. Intrinsic immune reactivity is associated with a poor prognosis. A subset of tumors with a bad prognosis has anaplastic cells, dermal lymphatic invasion and a moderate to intense lymphoplasmacytic stromal infiltrate. Evidence is reviewed that adjuvant chemotherapy may be beneficial by virtue of its immunosuppressive effects in addition to tumor kill of minimal residual disease.     

Relationship between muscle fatigue and oxygen uptake during cycle ergometer exercise with different ramp slope increments

Summary The surface electromyogram (EMG) from active muscle and oxygen uptake ( ) were studied simultaneously to examine changes of motor unit (MU) activity during exercise tests with different ramp increments. Six male subjects performed four exhausting cycle exercises with different ramp slopes of 10, 20, 30 and 40 W · min^–1 on different days. The EMG signals taken from the vastus lateralis muscle were stored on a digital data recorder and converted to obtain the integrated EMG (iEMG). The was measured, with 20-s intervals, by the mixing chamber method. A non-linear increase in iEMG against work load was observed for each exercise in all subjects. The break point of the linear relationship of iEMG was determined by the crossing point of the two regression lines (iEMG_bp). Significant differences were obtained in the exercise intensities corresponding to maximal oxygen uptake ( ) and the iEMG_bp between 10 and 30, and 10 and 40 W · min –1 ramp exercises (P < 0.05). However, no significant differences were obtained in and corresponding to the iEMG_bp during the four ramp exercises. With respect to the relationship between and exercise intensity during the ramp increments, the -exercise intensity slope showed significant differences only for the upper half (i.e. above iEMG_bp). These results demonstrated that the and at which a nonlinear increase in iEMG was observed were not varied by the change of ramp slopes but by the exercise intensity corresponding to and the iEMG_bp was varied by the change of ramp slopes. In addition, the significant differences in the exercise intensity slopes for the upper half of the tests would suggest that the recruitment patterns of MU and/or muscle metabolic state might be considerably altered depending upon the ramp slope increments.     

Homologous recombination in the fission yeast Schizosaccharomyces pombe: different requirements for the rhp51+, rhp54+ and rad22+ genes

The Schizosaccharomyces pombe rhp51 ⁺ , rad22 ⁺ and rhp54 ⁺ genes are homologous to RAD51, RAD52 and RAD54 respectively, which are indispensable in the recombinational repair of double-strand breaks (DSBs) in Saccharomyces cerevisiae. The rhp51Δ and rhp54Δ strains are extremely sensitive to ionizing radiation; the rad22Δ mutant turned out to be much less sensitive. Homologous recombination in these mutants was studied by targeted integration at the leu1-32 locus. These experiments revealed that rhp51Δ and rhp54Δ are equally impaired in the integration of plasmid molecules (15-fold reduction), while integration in the rad22Δ mutant is only reduced by a factor of two. Blot-analysis demonstrated that the majority of the leu⁺ transformants of the wild-type and rad22Δ strains have integrated one or more copies of the vector. Gene conversion events were observed in less than 10% of the transformants. Interestingly, the relative contribution of gene conversion events is much higher in a rhp51Δ and a rhp54Δ background. Meiotic recombination is hardly affected in the rad22Δ mutant. The rhp51Δ and rhp54Δ strains also show minor deficiencies in this type of recombination. The viability of spores is 46% in the rad22Δ strain and 27% in the rhp54Δ strain, as compared with wild-type cells. However, in the rhp51Δ mutant the spore viability is only 1.7%, suggesting an essential role for Rhp51 in meiosis. The function of Rhp51 and Rhp54 in damage repair and recombination resembles the role of Rad51 and Rad54 in S. cerevisiae. Compared with Rad52 from S. cerevisiae, Rad22 has a much less prominent role in the recombinational repair pathway in S. pombe. Received: 20 July 1996     

The use of a double-marker shuttle vector to study DNA double-strand break repair in wild-type and radiation-sensitive mutants of the yeast Saccharomyces cerevisiae

An episomal DNA vector (YpJA18), encoding two selectable recombinant yeast genes (TRP1, URA3), was constructed to assess the fidelity of DNA repair in haploid repair-competent (RAD) wild-type yeast and several radiation-sensitive mutants. Either a DNA double-strand break (DSB) or a double-strand gap of 169 bp (DSG) was introduced by restriction enzymes in-vitro within the coding sequence of the URA3 gene of this vector. To eliminate transfer artefacts, selection was first applied for the undamaged TRP1 gene followed by counter selection for URA3 gene activity, which indicated correct repair of the DSB and DSG. Correct repair of the damaged URA3 gene was found to be about 90% in RAD cells (normalized for the expression of undamaged URA3 in TRP ⁺ transformants). Plasmids isolated from the transformants (URA ⁺ TRP ⁺) carry both unique sites (ApaI and NcoI) within the URA3 gene indicating the precise restitution of the 169-bp gap. An excision-repair-defective rad4-4 mutant repaired these lesions as correctly as RAD cells, whereas the mutants rad50-1, rad51-1 and rad54-1, proven to be defective in DSB repair and mitotic recombination, showed less than 5% correct repair of such lesions. In contrast, a representative of the RAD6 epistasis group of genes, the rev2-1 mutant which is sensitive towards UV and ionizing radiation, had a significantly reduced ability (about 20%) for the correct repair of both DSBs and DSGs.     

Adriamycin-induced DNA strand breaks in HeLa and in P388 leukaemia cells detected using in situ nick translation

DNA strand breaks produced by adriamycin (ADR) were measured in HeLa cells and ADR-sensitive and -resistant P388 leukaemia cells, using the in situ nick translation method. The break sites in the DNA were translated artificially in the presence of Escherichia coli DNA polymerase I and 3H-labelled dTTP, and were visualized by autoradiographic observation of the grains. The DNA strand breaks in the HeLa cells increased in a dose-dependent manner, compared with findings in the untreated control cells, i.e., 15.2 fold at 20 micrograms/ml of ADR for 1 h. This level correlated with DNA single-strand breaks detected by the alkaline elution method. DNA breaks were also noted in the ADR-sensitive P388 cells, but in the ADR-resistant cells the level of DNA strand breaks was low. The enhanced cytotoxicity is apparently the consequence of the enhanced potential of ADR to cause breaks in the DNA strands. Our findings show that the survival response of the cells decreases and the level of DNA strand breaks increases following exposure to ADR. ADR resistance may be mediated by a reduction in the level of DNA strand breaks.     

In situ dormancy of B lymphocytes programmed for an IgE antibody response and their sudden release from unresponsiveness under in vitro conditions

Priming of CBA/J mice with different doses of antigen has aprofound effect on the ratio of IgE versus IgG antibodies appearingupon Immunization. Repeated injections of minute doses induceIgG and high titers of IgE antibodies. Large doses elicit ahigh IgG but a very low IgE antibody titer. In order to studythe modalities for activation and inactivation of IgE-producingB cells, an in vitro culture system was established in whichspleen cells from animals primed with keyhole limpet hemocyaninwere re-stliulated with antigen. In contrast to the expectationfrom the in vivo situation, spleen cells from animals Immunizedwith large doses of antigen and virtually lacking IgE antibodiesproduce high amounts of IgE antibodies upon re-stimulation invitro. The titers in spleen cell cultures from mice primed withminute doses remain proportional to the response measured asserum antibodies. In accordance with the induction of high amountsof IgE antibodies in spleen cell cultures from mice primed withlarge doses, the frequency of IgE antibody-secreting cells wasraised drastically, 1000-fold. The in vitro response is a trueanamnestic response. The sudden appearance in high frequencyof IgE antibody-forming cells among spleen cells isolated fromprimed mice which have high IgG but virtually no IgE antibodytiters is as yet unexplained and the origin of the B memorycells has not yet been traced. The answer might be crucial forour understanding of the down-regulation of the IgE Immune responses.     

浙贝母种子两种低温解除休眠过程中酯酶同工酶的电泳分析

为了探讨浙贝母种子低温解除休眠的生理机制,用电泳手段分析了浙贝母种子在8～10℃和3～5℃两种低温下解除休眠过程中酯酶同工酶的电泳图谱。结果表明两种低温条件下酯酶同工酶的变化规律相似。随着低温处理,一些原有谱带的颜色加深,并有新谱带的出现。这些结果说明两种低温下解除休眠的过程可能存在着相似的代谢机制。     

浙贝母低温解除休眠过程中淀粉酶和还原糖的研究

研究了浙贝母低温解除休眠过程中淀粉酶的活性和还原糖的含量变化。结果表明,芽和鳞片的内在代谢均发生了变化,鳞片近轴面表皮的淀粉酶活性和还原糖含量比鳞片的内部贮备组织高,但和芽的该两项指标接近。