Use of serum-free hormonally defined media to evaluate the effects of growth factors and inhibitors on proliferation of estrogen-responsive mammary and pituitary tumor cells in culture

Summary Serum-free defined media have been developed for assay of the mitogenic effects of growth factors on human MCF-7, human T-47D, and mouse COMMA-D mammary cells as well as for identification of mitogens and inhibitors of GH₄C₁ rat pituitary tumor cell growth. These lines were shown to grow in vivo in response to a variety of hormones including estrogens and thyroid hormones. With mammary cells, complete hormonally and nutritionally defined media were established that supported continuous passage at 50 to 90% of the serum stimulated rate. The strategy used to measure mitogens for mammary cells was to identify nutritional conditions where the growth rate was reduced greatly without impairing the response to picomolar to nanomolar concentration of growth factors. The effects of polypeptide growth factors and tissue extracts were estimated by their addition to basal medium and measuring cell number increases or labeled thymidine incorporation into DNA. In a variation of this methodology, the MTW9/PL2 rat mammary cells were used to identify secreted autocrine growth factors; nutritionally defined conditions were sought for growth of these rat cells in the complete absence of exogenous growth factors. The factors secreted into the medium were detected by bioassays with COMMA-D or MCF-7 mammary cell lines. The effects of growth factors-inhibitors on pituitary cells were measured by a related method; the GH₄C₁ cells were grown at less than optimal rates in a defined medium designated TRM-1. Addition of mitogens to TRM-1 stimulated pituitary cell growth whereas addition of inhibitors caused reduced levels of growth. The methods described in this report offer new means of assaying growth factors-inhibitors for a range of mammary and pituitary tumor cells.     

Possible pathways of circulation of human endogenous retrovirus similar to mouse mammary tumor virus

It is shown that polypeptides which are immunologically related to gp52 mammary tumor virus are found in T and B peripheral blood lymphocytes in all breast cancer patients, in children with B-cell lymphosarcomas, and in B lymphocytes of some healthy donors. These proteins are not found in patients with tumors of other sites. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 11, pp.554–556, November, 1995 Presented by Yu. N. Solov'ev, Member of the Russian Academy of Medical Sciences     

Differential effects of sex hormones on autoantibody production and proteinuria in chronic graft-versus-host disease-induced experimental lupus nephritis

In patients with systemic lupus erythematosus, the female-to-male ratio is as high as 10:1. Sex hormones are thought to play a role in this difference in susceptibility. In a previous study, we demonstrated a high susceptibility of female mice to the development of glomerulonephritis after induction of chronic graft-versus-host disease (GVHD), compared with male mice. In order to unravel further this gender-related difference (C57Bl/10*DBA/2)F¹ hybrid mice were either castrated or ovariectomized and treated with 17β-ethinyloestradiol or testosterone-decanoate preceding the induction of chronic GVHD. Testosterone-decanoate reduced significantly the development of albuminuria in females. In contrast, proteinuria of 17β-ethinyloestradiol-treated female mice was in the same range as that of sham-operated mice. Autoantibody levels against glomerular basement membrane, renal tubular epithelium, dsDNA and ssDNA, as determined by ELISA, were higher in 17β-ethinyloestradiol-treated female mice than in all other groups. Immunofluorescence studies showed the presence of immunoglobulin and complement deposits in glomeruli of all animals, without significant differences between the experimental groups. Our findings confirm earlier observations, in that testosterone-decanoate is shown to be an inhibitory compound, whereas 17β-ethinyloestradiol has stimulating properties in autoimmunity. Moreover, our results show for the first time differential hormonal effects on autoantibody levels and proteinuria in experimental lupus nephritis.     

性腺激素在绝经和继发性闭经中水平的对比研究

目的:探讨性腺激素在绝经与继发性闭经中的不同变化特点,评价卵巢功能,为二者的鉴别诊断和临床治疗提供依据.方法:采用放射免疫分析对40例正常月经者(1组)、40例绝经者(2组)及40例继发性闭经者(3组)的血清性腺激素进行测定,并相互对比各组检测结果.结果:2组FSH和LH值高于1组和3组,其中3组高于1组,E2反之;1组和2组PRL值水平接近,但二者明显低于3组;2组P值低于1组和3组,1组和3组水平接近;1组和3组t值相近,二者均高于2组.结论:绝经期卵巢萎缩伴卵巢功能衰竭,继发性闭经多为HPOU(下丘脑-垂体-卵巢-子宫)轴、肾上腺轴和甲状腺轴功能失调所致,卵巢功能尚存.     

Effect of potassium iodide and perchlorate on the secretion of thyroid hormones

The effect of potassium iodide and perchlorate was studied on parameters characterizing the secretion of thyroid hormones: the cyclic AMP level in the thyroid gland tissue and the number of intracellular colloid drops during stimulation with thyroid hormones. Excess of iodide was shown to depress these indices whereas perchlorate prevented the inhibitory effect of iodide. The results support the view that the adenylate-cyclase system of the thyroid gland is sensitive to the organic iodine concentration. Excess of iodide evidently reduces the ability of perchlorate to affect its concentration in the gland, so that the process of organification of iodine and the secretion of thyroid hormones are maintained at the optimal level.Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 12, pp. 653–655, December, 1978.     

Carcinoid Tumor of the Middle Ear Containing Serotonin and Multiple Peptide Hormones A Case Report and Review of the Pathology Literature

A 69-year old man complaining of longstanding hearing loss and mild otorrhea was found to have a mass obliterating the external auditory canal and polypous tympanic mucosa with accompanying absence of the tympanic membrane and ossicular chain. Tumors excised from the external auditory canal and tympanum showed histologic features essentially characteristic of a carcinoid tumor: a ribbon or festoon arrangement of tumor cells, formation of anastomosing cords and glandular spaces, presence of numerous argyrophilic as well as argentaffin secretory granules within many of the tumor cells, and ultrastructur-al evidence of neurosecretory granules in the tumor cell cytoplasm. Immunohistochemically, the tumor was found to contain not only neuronal marker substances such as neuron-specific enolase, S 100 protein and chromogranin A, but also serotonin and multiple peptide hormones such as pancreatic polypeptide, glucagon, cholecystokinin and leucine-enkephalin. A review of the pathology of 17 previous cases of carcinoid of the middle ear suggested that this type of carcinoid may have a variegated hormone profile among carcinoids of foregut origin, and hormonally may resemble ileal carcinoid arising from the midgut, although their histogenetic origins may differ, because of frequent production of serotonin. Acta Pathol Jpn 42: 614–620, 1992.     

Nocturnal hormonal responses to resistance exercise

The effects of resistance exercise on the nocturnal responses of cortisol (CO), testosterone (TEST), human growth hormone (hGH), and thyroid hormones (T₃, T₄) were examined in eight trained weight lifters. Each subject completed two trials using a counterbalanced design: a control, no exercise trial (CON) and a heavy resistance exercise session of three sets of six exercises to exhaustion (RE). The exercise session took place between 1900 and 2000 hours. Blood was sampled prior to and at 20-min intervals after RE. For both trials blood was sampled at hourly intervals from 2100 hours until 0700 hours. The hGH and CO concentrations were increased up to 40-min post-exercise (P < 0.05), but returned to resting levels 1 h post-exercise. Nocturnal hGH concentration was not affected by RE (P > 0.26) and peaked at 0200 hours and declined until 0700 hours. Similarly, the CO responses were similar between the trails (P > 0.14). This CO concentrations declined from 2200 hours until 0100 hours, then increased steadily until 0700 hours. The TEST concentrations during both trials rose steadily from 2200 hours until 0700 hours; however, the rise in TEST from 0500–0700 hours during RE was greater than during the CON trails (P = 0.059). The T₃ concentrations were unchanged by exercise and were similar at all times between trails. The T₄ concentrations were elevated for 20 min after RE; however nocturnal T₄ concentrations were lower after RE than during CON. These results would suggest that bGH and CO may have limited nocturnal reactivity to resistance exercise. However, the nocturnal alterations of TEST and T4 after resistance exercise, although small, may have implications for muscle anabolism.     

异种移植免疫学及其潜在风险的研究进展

同种器官移植成功率的提高导致了供体器官的严重短缺.采用解剖学上与人类相近的动物,比如猪的器官可以解决这种危机.但从猪到人的器官移植需要克服很多障碍,包括免疫学,生理学及其伦理道德问题.超急性排斥反应是猪到人异种器官移植的首要免疫学障碍,目前主要通过敲除半乳糖α1,3半乳糖(galactose-α1,3-galactose,Gal)抗原来克服超急性排斥反应.除此之外,仍有其它的非-Gal抗原可能引起猪到人的移植物的失功,例如N-羟乙酰神经氨酸等.除了免疫学障碍,猪器官携带的病毒及可能引起的异种移植的潜在风险也不容忽视.虽然现在还没有明显的实验数据显示猪到人的病原体的感染,但当猪到人的免疫学障碍被克服后,感染将成为又一研究热点.     

Evaluation of sympathoadrenal activity adrenocortical function and androgenic status in five men during a Himalayan mountaineering expedition (ascent of Mt Pabil, 7,102 m, 23,294 ft)

Summary Sympathoadrenal activity, adrenocortical function and androgenic status were studied in five well-trained mountaineers during the different phases of a mountaineering expedition during the ascent of Mt Pabil (7,102 m) in the Ganesh Himal massif. Sympathoadrenal activity was evaluated by measuring urinary excretion of adrenaline, noradrenaline, metanephrines, and vanillinmandelic acid. Adrenocortical function was assessed by measuring urinary excretion of free cortisol, 17 OHCS (17-hydroxycorticosteroids) and androgenic status by measuring testosterone glucuronide, Adiol (5-androstane-3, 17 diol) and 17KS (17-ketosteroids).Reference values were obtained at Chamonix at 1,037 m during rest. During trekking noradrenaline increased significantly while Adiol and 17-KS decreased. The fall in the urinary androgenic pool persisted during the next phases of the expedition. At base camp (4,800 m) noradrenaline, its metabolites and free cortisol increased mainly during physical activity. Above 6,000 m, adrenaline, noradrenaline, their metabolites, free cortisol and 17-OHCS reached a maximum value. During the return to sea level, the urinary level of these parameters was still high.The drop in the urinary androgenic pool observed during trekking and exposure to high altitude confirms results obtained in other studies on prolonged efforts. This hypoandrogenicity may play an important role in the metabolic adaptations as well as in the mental state of the climbers. The increase of sympathoadrenal activity and of adrenocortical function may be considered as a regulatory element in the adaptative response to hypoxia and other stressors proper to high altitude.This work was supported in part by a grant from the Direction des Recherches, Etudes et Techniques des Armées (Contract 80.1114)