Circulating 1,25-Dihydroxycholecalciferol After Intravenous Injections of l{alpha}-Hydroxycholecalciferol in Patients on Regular Haemodialysis

The formation of 1.25-dihydroxycholecalciferol (1.25-(OH)₂D₃after single intravenous injections of 1-hydroxycholecalciferol(1-OHD₃) was examined in four patients with chronic renal failureon regular haemodialysis. Following 1–3µg 1-OHD₃administered at weekly intervals, 1.25-(OH)₂D₃ appeared in thecirculation within 1 h, and peak concentrations were reachedbetween 2 h and 5 h. By 8 h serum 1.25-(OH)₂D₃ concentrationshad started declining and by 44 h they had returned to baselineafter 1µg 1-OHD₃ but they were still above basal after2 and 3 µg by an average of 30 pmol/l. One week afterinjections, concentrations were back to basal in all patientsstudied. The serum 1,25-(OH)₂D₃ dose response to injected la-OHDwas linear, indicating ample capacity of the liver 25-hydroxylaseto further hydroxylate 1-OHD. However, examination of the individualresponses revealed lower increments in serum 1.25-(OH)₃ concentrationsin the patients with the highest basal serum 25-hydroxyvitaminD concen trations. Intravenous 1-OHD₃ may be useful in the furtherstudy of the interactions between 1.25-(OH)₂₃ calcium and PTHin chronic renal failure, as well as of the hepatic metabolismof vitamin D.     

Chloride current activated by cyclic AMP and parathyroid hormone in rat osteoblasts

In primary cultures of rat osteoblasts, studied with the whole-cell configuration of the patch-clamp technique, 8-bromo-cyclic AMP (8BrcAMP) forskolin (FS) and 1–34 parathyroid hormone (PTH) were shown to activate a Cl conductance. This conductance shows a pronounced outward rectification, even with symmetrical Cl concentrations. It is blocked partially and reversibly by 4,4-diisothiocyanatostilbene 2,2-disulfonic acid (DIDS) or diphenylcarboxylate (DPC). The blockade induced by DIDS is time-and voltage-dependent. The Cl responses to FS and PTH develop slowly, after a delay of several seconds and are very slowly reversible. These responses were observed only in a fraction of the cells tested and their detection was favoured by cell dialysis. This Cl current should be taken into account for studying possible modulations of the voltage-gated Ca currents of osteoblasts. It is suggested that its physiological role may be related to the well-known morphological changes induced by PTH in osteoblasts. The cyclic AMP-sensitivity, the outward rectification and the sensitivity to dialysis of this Cl current are reminiscent of the properties of the cystic fibrosis-sensitive Cl channels of epithelial cells.     

Thymus Ontogeny in Frogs: T-Cell Renewal at Metamorphosis

Metamorphosis in amphibians presents a unique problem for the developing immune system. Because tadpoles are free-living, they need an immune system to protect against potential pathogens. However, at metamorphosis, they acquire a variety of new adultspecific molecules to which the tadpole immune system must become tolerant. We hypothesized that Xenopus laevis tadpoles may avoid potentially destructive antiself responses by largely discarding the larval immune system at metamorphosis and acquiring a new one. By implanting triploid (3N) thymuses into diploid (2N) hosts, we examined the influx and expansion of host T-cell precursors in the donor thymus of normally metamorphosing and metamorphosis-inhibited frogs. We observed that donor thymocytes are replaced by host-derived cells during metamorphosis, but inhibition of metamorphosis does not prevent this exchange of cells. The implanted thymuses export T cells to the spleen. This donor-derived pool of cells declines after metamorphosis in normally developing frogs but is retained to a greater extent if metamorphosis is inhibited. These studies confirm previous observations of a metamorphosis-associated wave of expansion of T cells and demonstrate that it is not dependent on the relatively high concentrations of thyroid hormones required for metamorphosis. Although some larval T cells persist through metamorphosis, others may be destroyed or the larval population is significantly diluted by the expanding adult population.     

Lifelong food restriction prevents senile osteopenia and hyperparathyroidism in F344 rats

Studies were carried out on male F344 rats to examine the influence of aging and life-prolonging food restriction on bone and circulating parathyroid hormone levels. In ad libitum fed animals, the weight, density and calcium content of the femur increased with age and achieved their peak levels by 12 months of age. These levels remained stable until about 24 months and by 27 months of age the ad libitum fed animals had lost appreciable amounts of bone. The maturation of the femurs of the animals maintained on 60% of the ad libitum food intake was delayed and their bones were lighter, less dense and contained less calcium than bones from ad libitum fed rats of corresponding ages. But at 6, 12 and 24 months of age, the femur strength to body weight ratios were very highly significantly greater (P < 0.0001) for the restricted animals compared to the ad libitum fed controls. Circulating immunoreactive parathyroid hormone increased progressively with aging in the animals fed ad libitum and the animals that experienced bone loss at advanced age also had the highest level of the hormone. In contrast, in the food restricted animals aging was not associated with a marked increase in serum parathyroid hormone or with senile bone loss. The data are discussed in relation to the mechanism of the observed changes.     

重症SIRS患者的正常甲状腺病态综合征

目的：探索全身炎症反应综合征（SIRS）患者的正常甲状腺病态综合征（ESS）的发生规律。 方法： 测定50例SIRS病人的总三碘甲状腺原氨酸（TT3）、总四碘甲状腺原氨酸（TT4）、游离三碘甲状腺原氨酸（FT3）、游离四碘甲状腺原氨酸（FT4）、促甲状腺素（TSH），并根据是否多脏器功能障碍综合征（MODS）分组。计算急性生理和慢性健康评估Ⅱ（APACHEⅡ）评分，记录病人转归以及从发病到检测的时间（患病时间）。 结果： TT3或FT3降低的45例。TT3与APACHEⅡ评分呈对数负相关（r＝－0.330，P<0.05）,TT3/TT4与患病时间呈对数负相关（r=－0.316, P<0.05）。MODS组的TT3、TT4、FT3水平显著低于无MODS组（P<0.05）。 结论： SIRS和MODS病人发生低T3、低T4可能性大，反映炎症反应对甲状腺轴的影响，随着病情加重、患病时间延长，影响进一步深化。     

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.     

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.     

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.