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The spectrum of trace elements was determined in 19 cases of colon carcinoma with analytical electron microscope. Besides, the quantities of trace elements in the cancerous tissue and the mucosa beyond the site of cancer were measured in 31 cases by flameless atomic absorption spectrophotometry. A reprocessing technique was applied to convert the paraffin sections directly to resin sections in order to recover the assessment of elements in these tissues. Fe, Al and macro elements Ca, S were recovered in 100% of the cases in both the cancer tissue and the mucosa taken beyond the site of cancer. The recovery rates of Ni and macro elements including K, Mg, P, Cl were 50%. The recovery rates of Si in poorly-differentiated adenocarcinoma were higher than that in the mucosa far from the cancer site. The levels of Cu, Zn and Ni in the cancerous tissue were lower than those detected in the mucosa (P < 0.01). No significant difference was noticed between the cancerous tissue and the mucosa beyond the site of cancer on Fe, Mn, Pb, Co and Cr contents.

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Light (LM) and electron (EM) microscope comparisons of the cytochemistry and immunocytochemistry of neuritic plaques and neurofibrillary tangles, the main histopathological changes in the brains of Alzheimer's disease sufferers, have been almost impossible because of the disparity between the two technologies. By embedding unosmicated brain tissue in the acrylic resin LR White, direct comparisons can be made between techniques applied at the LM level with those at the EM level. After partial dehydration in 70% ethanol, the tissue is embedded by rapid infiltration and polymerization at 0 degrees C, which has been shown to maximally preserve tissue immunoreactivity. Semithin sections are then receptive to routine LM stains, silver stains e.g. Gomori's methenamine silver, and immunocytochemistry with immunoperoxidase or immunocolloidal gold. Serial thin sections are stable in the EM and can be immunolabelled and directly compared with their LM counterparts. Results from the use of a mouse monoclonal antibody against beta-amyloid and a rabbit polyclonal antibody against ubiquitin are presented. LR White resin includes no elements other than carbon, oxygen and nitrogen, of which it is composed, so that sections of it are valuable for sensitive X-ray energy dispersive microanalysis.

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The presence of microparticles of clay is demonstrated in the dermis of the foot in a patient with endemic elephantiasis. The particles are seen to be in the phagosomes of macrophages or in the cytoplasm of other cells. The conducting lymphatic in the subdermal tissue is found to be impermeable to Patent Blue Violet dye and to be fibrosed. The failure to conduct lymph to the node produces a permanent deposit of silica in the dermal tissues; a parallel is drawn with similar deposits in the lung in pneumoconiosis.

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Previous studies have shown that estrogen therapy in postmenopausal women results in an increase in serum immunoreactive parathyroid hormone (iPTH) levels. It has been assumed that this effect of estrogen on PTH secretion is indirect, being mediated via mild hypocalcemia resulting from an inhibition of bone resorption. We evaluated the direct effect of 17 beta-estradiol (E2) and of progesterone (Prog) on secretion of PTH from bovine parathyroid tissue in vitro. Both E2 and Prog caused a significant stimulation of PTH secretion within one hour, which was progressive for the three-hour observation period. The responses were dose-related from 10(-7) to 5 X 10(-10) mol/L. There was no PTH response to 10(-7) mol/L alpha-E2, 3-methoxy estriol, estrone, testosterone, or 20-alpha-hydroxy progesterone, indicating specificity of the responses to E2 and Prog. There was a minimal PTH secretory response to 10(-6) mol/L cortisol and 10(-6) mol/L estrone. The E2 receptor antagonist tamoxifen did not inhibit the E2 effect on PTH secretion. This observation plus the rapid PTH response suggests that this hormonal effect may not be via the conventional intracellular E2 receptor. Therefore, E2 and Prog can stimulate PTH secretion by rapid, direct, and specific effects on parathyroid cells. These gonadal hormones may, therefore, be important in calcium homeostasis via their direct stimulatory effect on PTH secretion.

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Incubation of thyroparathyroid gland from 8-day-old rats with estradiol (10(-7) and 10(-9) M) and progesterone (10(-9) and 3 X 10(-10) M) resulted in stimulation of CT secretion. The effect of the gonadal steroids on CT secretion occurred at near physiological concentrations and persisted for at least 73 h. The studies demonstrate that exposure to gonadal steroids results in direct and prolonged stimulation of CT secretion. Therefore the decrease in bone resorption observed after the administration of gonadal steroids in vivo may at least in part be mediated via stimulation of CT secretion.

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Estrogen therapy has been used to inhibit bone resorption and prevent osteoporosis in postmenopausal women. Previous studies have disagreed as to whether the mechanism of estrogen action involves stimulation of calcitonin (CT) secretion. We evaluated the direct effects of 17 beta-estradiol (E2) and progesterone (Prog) on CT secretion from the thyroid C cells of 8-day-old rats in vitro. Both E2 and Prog caused a significant stimulation of CT secretion within 1 h, which was progressive for the 3-h observation period. The responses were dose related from 10(-7) to 5 X 10(-10) M. There was no CT response to 10(-7) M alpha-estradiol, estriol, 3-methoxyestriol, estrone, testosterone, or 20 alpha-hydroxyprogesterone, indicating specificity of the responses to E2 and Prog. There was a minimal CT secretory response to 10(-6) M cortisol. The E2 receptor antagonist tamoxifen did not inhibit the E2 effect on CT secretion. This observation plus the rapid CT response suggest that this hormonal effect may not be via the conventional intracellular E2 receptor. Therefore, E2 and Prog can stimulate CT secretion by rapid, direct, and specific effects on the thyroid C cell. The gonadal hormones may, therefore, be important in inhibiting bone resorption via their direct stimulatory effect on CT secretion.

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Granulomatous lymphadenopathy, associated with the presence of needle-like refractile particles, was recognised in two dogs. The material was detected in macrophages, either free within the cytoplasm or in membrane-bound lysosomes. By mineral analysis under direct vision in an electron microscope microanalyser (EMMA 4) the particles were found to contain aluminosilicate.

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This study evaluated the effect of parasympathetic agonists and antagonists on immunoreactive (i) PTH secretion in vitro and on serum iPTH in vivo in rats. In in vitro studies pilocarpine or bethanechol significantly inhibited PTH secretion. This inhibition was blocked by the simultaneous addition of atropine to the incubation medium. In in vivo studies, the cholinergic agonists pilocarpine and bethanechol and the cholinergic antagonist atropine were administered to rats by IV infusion. Blood was obtained before and again after two hours of infusion for analysis of iPTH. Pilocarpine or bethanechol significantly decreased serum iPTH. This inhibition by either agent was blocked by the simultaneous administration of atropine. Administration of atropine alone significantly increased serum iPTH above baseline. This stimulation of basal serum iPTH by parasympathetic blockade suggests that even basal PTH secretion may be influenced by endogenous parasympathetic tone. Therefore, the following conclusions were reached: (1) parasympathetic influences inhibit PTH secretion, and (2) endogenous parasympathetic tone may be an inhibitory modulator of basal secretion of PTH.

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Exposure of rat ovaries to talc was accomplished by intrabursal injection. As early as 1 and up to 18 months after treatment, the ovaries and associated tissue were cystic in appearance; these changes were the result of bursal distention. Histologically the ovarian tissue was decreased in amount and spread as a remnant on the inner wall of the bursa. In four to 10 treated animals but in no controls, focal areas of papillary change were noted in the surface epithelium of the ovary. Polarized light and electron microscope microanalysis confirmed the presence of talc in the surface epithelium, ovarian cortex, and connective tissue matrix of the bursa. Although the changes in the ovarian surface may be related to direct effects of talc exposure, it is postulated that these changes might also be related to constant exposure to the high concentrations of steroid hormones which have undoubtedly accumulated in the intrabursal space.

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Purified secretin infused in an estimated physiological dose caused an increase in serum immunoreactive PTH (iPTH) and calcitonin (iCT) in man. Ingestion of a gastric acid-stimulating test meal, a procedure known to increase endogenous secretin, caused increases in serum iPTH and plasma iCT in normal subjects. Ingestion of antacid with the test meal blunted the increase in both iPTH and iCT. Ingestion of the test meal by pernicious anemia patients with achlorhydria caused no stimulation of either serum iPTH or plasma iCT. Therefore, based on the observations that 1) exogenous secretin stimulated iPTH and iCT, 2) an acid-stimulating test meal is known to stimulate endogenous secretin release (4), 3) the test meal increased both serum iPTH and iCT in normal man, an effect nullified by simultaneous antacid ingestion, and 4) the test meal caused no increase in either iPTH or iCT in achlorhydric patients, we conclude that endogenous secretin possibly mediates this effect of test meal and, therefore, may play a physiological role in modulating the secretion of PTH and CT.

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Two patient receiving minocycline developed blue-black pigmentation on the legs. Biopsies from the pigmented areas demonstrated granules containing iron, a pigment with staining properties similar to melanin, and a third pigment which may be a degradation product of minocycline. Electron microscopy showed that some, but not all the granules were membrane-bound and they were situated mainly within macrophages. Analytical electron microscopy showed that the granules contained iron, sulphur, chlorine and, in one case, calcium.

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Evidence for an association of endemic non-filarial elephantiasis of the lower legs with areas of red clay soils around volcanoes has been noted in several countries bordering the Rift Valley in East Africa. It was of interest to observe whether the association is also present in an area of endemic prevalence of the disease in West Africa. Such an area occurs in the Cameroon highlands where it has been suggested that onchocerciasis might be an etiological factor. The present study describes the results of a survey in this area. There was no statistical evidence of a relationship with onchocerciasis and the content of mineral microparticles in lymphatic tissues of the lower legs was again established. Climatic, geological and soil characteristics were similar to those in East Africa. It is considered that the disease in the two widely separated non-bancrofti areas is of similar etiology and it is proposed that it may be interpreted as silicosis of peripheral lymphatics of the lower legs.

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The effect of histamine and histamine H2 receptors on secretion off parathyroid hormone (PTH) was evaluated by 1) adding histamine phosphate (with or without the histamine H2 receptor antagonist, cimetidine) to the medium in in vitro incubation studies with bovine parathyroid tissue, 2) infusing histamine into rats, and 3) infusing the histamine H1 receptor antagonist, diphenhydramine, or cimetidine into normal men and patients with primary hyperparathyroidism. In vitro, histamine (10(-5)-10(-7) M) caused a dose-related significant stimulation of immunoreactive PTH (iPTH) secretion; this was blocked by the simultaneous addition of cimetidine (10(-5) M). Intravenous infusion of histamine significantly increased serum iPTH in rats. In normal man, infusion of diphenhydramine had no effect, but cimetidine (300 or 450 mg) significantly decreased serum iPTH. However, cimetidine had no effect on serum iTh in primary hyperparathyroid patients. The in vitro observations indicate that histamine can stimulate iPTH secretion by a direct effect on the parathyroid cell and that this is probably a specific effect via histamine H2 receptors because the effect was blocked by the H2 receptor antagonist, cimetidine. The observed inhibition of basal PTH concentration by cimetidine induced histamine H2 receptor blockade (but not by H1 blockade) in normal human subjects suggests that endogenous histamine with H2 receptor activation stimulates even basal PTH secretion and may serve as a modulator of PTH secretion in normal man. Loss of this modulating effect of H2 receptors on PTH secretion is a characteristic of primary hyperparathyroidism.

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Our previous in vitro and in vivo studies demonstrated that exogenous somatostatin inhibited secretion of both parathyroid hormone (PTH) and calcitonin (CT). This study evaluates the possible role of endogenous somatostatin in PTH and CT secretion. Rats receiving somatostatin antiserum i.v. had significantly greater circulating levels of serum immunoreactive PTH (iPTH) and CT (iCT) than rats receiving normal rabbit serum. In in vitro studies with bovine parathyroid tissue, the addition of somatostatin antiserum to the medium significantly increased PTH secretion from basal, low calcium-stimulated and high calcium-suppressed parathyroid tissue. These combined observations strongly suggest that endogenous somatostatin must have a suppressive effect on PTH and CT secretion. The in vitro observations with isolated parathyroid tissue suggest that somatostatin is synthesized by cells within this tissue. These data strongly suggest that somatostatin is a locally-synthesized hormone that has a role in modulation of both PTH and CT secretion.

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A case of mepacrine pigmentation occurring in a patient with systemic lupus erythematosus has been investigated by fluorescent light microscopy, gas--liquid chromatography and analytical electron microscopy. There is strong evidence for the presence of mepacrine itself within the typical granules, which have been shown by electron microscopy to be membrane bound and intracellular. Analytical electron microscopy also showed that the granules contain large quantities of iron and smaller quantities of sulphur.

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