金地鼠颊囊癌前病变的细胞增殖动力学研究

目的研究口腔上皮组织癌和癌前病变的细胞动力学变化特征。方法采用Ｓａｌｅｙ的ＤＭＢＡ涂布诱导法，建立金地鼠颊囊癌前病变模型，并用溴脱氧尿苷流式细胞动力学检测方法，对３０只叙利亚种金地鼠进行分组对照研究。结果涂药组光镜下的细胞病变程度随涂药时间延长而逐渐加重，而空白对照组无变化；ＦＣＭ检测显示涂药组与对照组在Ｓ期阳性细胞检出率存在显著差异。即使在光镜下表现为轻度不典型增生时，ＦＣＭ检测结果也有显著差别。结论金地鼠颊囊癌前病变具有细胞异常增殖的细胞动力学特征     

金地鼠颊囊癌模型PCNA,BrdU及光镜观察结果的相关分析

癌变的早期诊断对提高疗效具有特殊意义，为了寻求简捷，高效，超前，可靠的诊断方法，实验以ＤＭＢＡ（二甲基苯并蒽）诱导的金地鼠颊囊致癌模型为对象，以ＰＣＮＡ（增殖细胞核抗原）ＢｒｄＶ（溴脱氧尿嘧啶）等免疫组化技术为手段；以光镜观察诊断为对照，对三种观察结果进行相关分析，发现三者间有高度显著的相关性，证实了免疫组化方法在癌变诊断中有一定的参考价值，实验还发现ＰＣＮＡ和ＢｒｄＵ检测结果比较每天敏感，简捷，     

Diagnosis of cypress pollen allergy: in vivo and in vitro standardization of a Juniperus ashei pollen extract

BACKGROUND: Cypress pollen allergy is a major cause of rhinoconjunctivitis and asthma in the Mediterranean area. The nonstandardized cypress allergen extracts currently available for the diagnosis of cypress allergy have a low level of activity. The search for an active material has led to the selection of Juniperus ashei (Ja) pollen because of its very high cross-reactivity with cypress extracts and its superior allergenic activity. The aim of this study was to characterize in vitro and calibrate in vivo an in-house reference extract (IHRS) of J. ashei pollen and determine the specificity and sensitivity of a standardized Ja extract for the prick test diagnosis of cypress allergy. METHODS: Juniperus ashei pollen extract was analysed by 2-D electrophoresis. The IHRS Ja extract was calibrated by skin prick testing in 28 cypress-allergic patients. The sensitivity and specificity of cypress allergy diagnosis using a standardized Ja extract was studied by skin prick test in 42 cypress-allergic patients and 53 nonallergic patients. Jun a 1 content of the IHRS was determined by a monoclonal antibody-based electrophoretic technique. RESULTS: The Jun a 1 content of the 100 IR/ml Ja IHRS extract was 180 microg/ml. For in vivo diagnosis of cypress allergy, Ja pollen extract demonstrated a sensitivity of 95%, a specificity of 100%, a negative predictive value of 96%, and a positive predictive value of 100%. CONCLUSION: Standardized Ja pollen extract is therefore a very appropriate tool for the in vivo diagnosis of cypress pollen allergy and good candidate for specific immunotherapy.     

Androgenic control of porphyrin in the harderian glands of the male syrian hamster is modulated by the photoperiod,which suggests that the sexual differences in porphyrin concentrations in this gland are important functionally

Background: The porphyrin concentrations of the Harderian glands of Syrian hamsters show marked sexual differences, with male levels being much lower than those of females. Porphyrinogenesis is inhibited by androgens, so orchidectomy leads to elevated male porphyrin concentrations; however, a number of other procedures (some of which also lower androgen levels) prevent this. We studied the effects of short-day photoperiods and melatonin on Harderian porphyrin concentrations. Methods: Intact, castrated, or pinealectomized hamsters of both sexes were exposed to long-day or short-day photoperiods. Intact or castrated hamsters were given melatonin injections in the morning or the afternoon, or were given beeswax pellets containing melatonin. After a variable period, Harderian glands were dissected and porphyrins were measured. Results: Prolonged short-day exposure (13 weeks) led to increased Harderian porphyrin concentrations and this rise was prevented by pinealectomy. The rise in Harderian porphyrins following short-day exposure was small, compared with that following castration. Short-day photoperiods also prevented the rise in porphyrin levels associated with castration and this effect was prevented by removal of the pineal. Melatonin injections, whether given in the morning or in the afternoon, had no effect on Harderian porphyrin concentration of castrated male hamsters. Continuous release melatonin pellets reduced the postcastrational rise in porphyrin levels in one experiment, while having no effect in another. In female hamster, neither short photoperiods nor melatonin pellets influenced Harderian porphyrin concentrations. Conclusions: These results suggested that a factor from the pineal gland helps maintain the low levels of porphyrin which are characteristic of male Harderian glands, despite the decrease in androgen levels which typically results from exposure to short days. Morning and afternoon injections of melatonin and continuous release melatonin pellets failed to resolve the question of whether this pineal factor is melatonin. Our results demonstrated that low male and high female porphyrin levels are maintained in Syrian hamsters, despite seasonal variations in the hormonal milieu, suggesting that these sexual differences are important for the (still unestablished) function of the Harderian glands in this species. © 1994 Wiley-Liss, Inc.     

Effects of aging on luteinizing hormone release in different physiological states of the female golden hamster

Effects of aging on estrous cycles and LH release in response to luteinizing hormone releasing hormone (LHRH), castration, and estradiol benzoate were studied in the female golden hamster (Mesocricetus auratus). About 80% to 90% of female golden hamsters still cycled regularly when reaching 19–22 months of age. However, some animals showed age-induced irregularity of the estrous cycle which included an interruption of complete absence of estrous vaginal discharge. Young female hamsters (3–5 months) had significantly (p<0.01) higher basal LH concentration than old animals (19–22 months) in the morning of each stage of estrous cycle. LHRH elicited about 20–30 fold increase in serum LH concentrations in both young and old hamsters. No significant difference in LH release was observed between young and old hamsters in response to LHRH. In acyclic hamsters, the peak of LH release in response to LHRH was delayed. LHRH-induced LH release was greater in the morning of proestrus than during diestrus in both young and old hamsters. LH increase was significantly greater in the young than in old hamsters on the 13th and 15th day after castration. However, positive feedback stimulation of LH release by estradiol benzoate was the same in both young and old hamsters. These results indicate that in the female hamster, LH response to acute stimuli such as LHRH and estrogens is the same in the young as in the old animal and that circulating basal LH concentration may decrease or its degradation or clearance may increase during the aging process in female golden hamsters. Irregularity of estrous cycles in aging hamsters may be related to delayed responsiveness of pituitary LH to LHRH stimulation.     

Sinus CT scans and mediator release in nasal secretions after nasal challenge with cypress pollens

BACKGROUND: Involvement of paranasal sinuses has been suggested in allergic rhinitis but not clearly demonstrated. AIMS: To investigate the relationship between intermittent allergic rhinitis and computerized tomography (CT). METHODS: Twenty patients with intermittent rhinitis and sensitized to cypress pollens underwent unilateral nasal provocation tests (NPTs) using increasing concentrations of cypress pollens out of the pollen season. Sinus CT-scans were carried out just before a NPT and 24 h later. Nasal lavage was carried out just before a NPT, 30 min after a positive challenge and again 24 h later. Leucotriene C4/D4, intracellular adhesion molecule-1 and eosinophil cationic protein were measured in nasal secretions. RESULTS: Thirteen patients (65%) showed an alteration in their CT-scans after allergen challenge. Ten of them showed sinus changes controlateral to their allergenic provocation. Radiological changes mainly affected the osteomeatal complex and the ethmoid sinuses. Pre-existing abnormalities (13 of 20 cases) mainly concerned the maxillary sinuses. There was no correlation between CT-scan abnormalities and levels of mediators released in nasal secretions. CONCLUSIONS: We have shown that nasal allergen challenge can produce radiological changes in the paranasal sinuses. This mainly concerned the ethmoid sinuses.     

环境物理因子的最佳条件的选择

目的：利用黄金数比例规律找出环境物理因子对人体的最佳条件：方法：人体的相当一部分内容与黄金数有着密切的联系，为此把复杂的人体可以简化为比例加破缺的比例实体；环境物理因子：如环境温度、湿度、环境光波和声波以及环境气压和氧分压，当它们处在黄金数比例附近时，会在人体产生和谐合柏作用。结果：环境物理因子选择在黄金数比例附近时，在心理上产生美和舒适感。已经发现，当精神愉快时，人脑电波频率下限(8Hz)和上限(12．9Hz)之比恰为黄金数。结论：环境物理因子的最佳条件是可以选择的。     

PULMONARY ADENOMA AND ENDOCRINE CELL HYPERPLASIA IN SYRIAN GOLDEN HAMSTER TREATED WITH 4-NITROQUINOLINE 1-OXIDE

Chronic effects of 4-nitroquinoline 1-oxide (4 NQO) on the lungs of Syrian golden hamsters were studied. 4 NQO was subcutaneously injected weekly for 3 weeks at a dose of 20 mg/kg body weight. The animals were sacrificed at the 65th and 80th experimental weeks. Two cases of pulmonary adenomas were demonstrated in the 10 4 NQO-treated animals at the 80th week, and the tumor cells contained cytoplasmic lamellar inclusion bodies. In a previous study, we reported 4 NQO- induced pulmonary endocrine cell hyperplasias in the 4 NQO-treated hamster after the 20th experimental week (Jpn. J. Cancer Res., 77,1986). In the present study, 12 pulmonary endocrine cell hyperplasias were recognized in serial sections of the 24 treated animals. The hyperplastic lesions showed positive immunoreactivity to calcitonin. The hyperplastic lesion did not develop to pulmonary endocrine cell neoplasm. ACTA PATHOL JPN 38 : 1097∼1104, 1988.     

Lost in Translation (LiT)

Translational medicine is a roller coaster with occasional brilliant successes and a large majority of failures. Lost in Translation 1 (‘LiT1’), beginning in the 1950s, was a golden era built upon earlier advances in experimental physiology, biochemistry and pharmacology, with a dash of serendipity, that led to the discovery of many new drugs for serious illnesses. LiT2 saw the large-scale industrialization of drug discovery using high-throughput screens and assays based on affinity for the target molecule. The links between drug development and university sciences and medicine weakened, but there were still some brilliant successes. In LiT3, the coverage of translational medicine expanded from molecular biology to drug budgets, with much greater emphasis on safety and official regulation. Compared with R&D expenditure, the number of breakthrough discoveries in LiT3 was disappointing, but monoclonal antibodies for immunity and inflammation brought in a new golden era and kinase inhibitors such as imatinib were breakthroughs in cancer. The pharmaceutical industry is trying to revive the LiT1 approach by using phenotypic assays and closer links with academia. LiT4 faces a data explosion generated by the genome project, GWAS, ENCODE and the ‘omics’ that is in danger of leaving LiT4 in a computerized cloud. Industrial laboratories are filled with masses of automated machinery while the scientists sit in a separate room viewing the results on their computers. Big Data will need Big Thinking in LiT4 but with so many unmet medical needs and so many new opportunities being revealed there are high hopes that the roller coaster will ride high again.