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The parathyroid glands of adult Mongolian gerbils were studied under an operation microscope, as well as with the aid of conventional light microscopy, and transmission and scanning electron microscopy. The mean serum level of calcium was 5.1 mEq/1 and that of phosphorus was 4.8 mg/100 ml. The animals possessed two small parathyroid glands, usually situated anteriorly and slightly laterally to the superior thyroid poles. The glands had a rich vascular supply and were composed of sheets of chief cells, which varied in electron density and content of organelles. No water-clear, oxyphil, or intraglandular fat cells were found. Some mitochondria exhibited electron lucent areas, and separation and bulbous projections of the membranes. The cell membranes were straight or tortuous and possessed microvilli, occasionally with central filamentous structures. The intercellular spaces were usually narrow. It is supposed that the variants of chief cells are interchangeable and that the differences in their morphological appearance are related to differences in functional state.

An electron microscopical study of parathyroid glands from 13-day old chick embryos cultured for 2 days on media with different concentrations of calcium was conducted. The same as in non-cultured embryonic glands, the cells in all cultures contained a moderate amount of rough endoplasmic reticulum and a large Golgi complex with many cisternae, vacuoles, vesicles, coated vesicles and small prosecretory granules. In addition, large secretory granules, which are very rare in the non-cultured controls appeared frequently in the cultures and were especially numerous in the glands cultured on high-calcium medium. The fact that the amount of secretory granules varied according to the concentration of calcium in the medium is interpreted as indicating that the rate of parathyroid hormone secretion in the embryo is already responsive to variations in the concentration of calcium. To the extent that in vitro results may be accepted as representative of what happens in vivo these results support the idea that the embryonic gland may be controlled by variations in the calcemia as the adult gland does.

An acinic cell carcinoma of the laryngotracheal junction developed in a 54-year-old woman 46 years after administration of radiation to her thyroid gland. Although salivary gland neoplasia has been associated with a history of radiation therapy during childhood, acinic cell carcinoma in such a setting is rare. In addition, she had parathyroid hyperplasia and multiple thyroid adenomas, lesions that have been associated with prior administration of radiation. A history of exposure to radiation should be sought in patients with salivary gland neoplasms of the larynx or trachea.

A case of nonfunctioning parathyroid carcinoma in a 69-year-old female has been studied by light and electron microscopy. The tumor, located on the left side of the anterior neck, was well encapsulated by connective tissue but showed invasion to the capsule and to the thyroid. The tumor cells exhibited a trabecular arrangement surrounded by capillary networks but focally showed several ductal structures. They were polygonal in shape, had a large nucleus showing frequent mitosis and poor cytoplasm containing glycogen. Some tumor cells had clear and abundant cytoplasm, and resembled water-clear cells of the parathyroid. Immunohistochemically, no thyroglobulin was demonstrated in the tumor tissue. Electronmicroscopically, the tumor cells with high N/C ratio contained poorly developed cell organelles and abundant glycogen particles. They were poor in secretory granules and had no conglomeration of lipid. Desmosomes and tonofibrils were observed. The ratio of the reported number of nonfunctioning parathyroid carcinoma to that of functioning one in Japan was compared with that in western countries. No difference of the ratio was found between these two, when identical criteria were employed.

The parenchyma of parathyroid (PT) glands of neonatal, growing and adult dogs consisted of dark and light chief cells. In growing and adult dogs, dark chief cells had an electron-dense cytoplasm, prominent rough endoplasmic reticulum (rER) and Golgi apparatus. Based on the secretion cycle proposed by Roth and Capen [1974], they were referred to as active cells. Light chief cells had an electronlucent cytoplasm, inconspicuous rER and Golgi apparatus. They were referred to as inactive cells in resting stages or in stages of transition between active and inactive forms or vice versa. In neonatal dogs, dark chief cells were similar to those in growing and adult dogs and light chief cells had the features of the cells referred to as cells in transitional stages. There were no cells in resting stages. The morphological findings suggest that PT activity in growing dogs was similar to that in adult dogs, whereas in neonatal dogs it was different; this may be related to the animal's developmental status or to changes in serum calcium concentration after birth.

Staining of frozen sections of small parathyroid biopsies from patients with primary hyperparathyroidism with Sudan II or IV revealed the almost uniform presence of numerous prominent intracellular sudanophilic bodies in the chief cells of suppressed "normal" parathyroid glands. These sudanophilic bodies were generally absent from the abnormal chief cells of parathyroid adenomas and chief cell hyperplasias. This difference in intracellular lipid provides a rapid, reliable, and easy method for distinguishing at the time of parathyroid exploration between an adenoma which is always accompanied by "normal" parathyroid glands and a chief cell hyperplasia in which all of the glands are abnormal.

On the basis of the results of histological, histochemical, and electron microscopic studies of pathologically altered parathyroid glands (PTG) in primary and secondary (chronic renal insufficiency) hyperparathyrosis a classification of tumors of this organ is suggested. It takes into account the fact that PTG tumors have a complex histological structure and heterogeneous cellular composition: chief dark, chief clear, transitional oxiphilic, exiphilic, small (round), spindle cells, and C-cells with different structural and functional orientation. Staining with Sudan-III of frozen sections of PTG tissue in primary hyperparathyrosis may be recommended as an additional test for differential diagnosis between adenoma and hyperplasia taking into account that the cytoplasm of chief cells of adenoma contains Sudanophilic bodies, while the cytoplasm of small cells of adenoma and chief (dark and clear) cells of hyperplasid PTG does not. The appearance of C-cells in the thymus, thyroid glands and adenomatous PTG in primary hyperparathyrosis may be considered to be a compensatory-adaptative response to hypercalciemia. Formation of C-cell adenomatosis in a normal PTG combined with PTG adenoma indicates the activity of these glands.

Electron microscopic examination of chief cells of rat parathyroid glands incubated with the antibiotic ionophore X537A showed selective alterations of the Golgi complex. The changes were dependent on the duration of X537A exposure. After 50 minutes of incubation, the cisternae and vesicles of the Golgi complex appeared highly swollen and disorganized. Because of its selective action, X537A might be a useful tool in the investigation of the role of Golgi apparatus in parathormone secretion.

Isolated parathyroid glands from normal adult Mongolian gerbils were incubated for 15 minutes to 3 1/2 hours either at high or low concentrations of Ca2+ and Mg2+ after which they were studied ultrastructurally, using the pyroantimonate technique and x-ray analysis for identification and son concentrations were mainly composed of suppressed chief cells with moderate or high cytoplasmic density, sparsely developed endoplasmic reticulum, often large Golgi complex, occassional cytoplasmic accumulations of secretory granules, lipoid bodies, glycogen-like particles, and numerous often large mitochondria. Ca2+-containing precipitates were found mainly in mitochondria. Autophagic vacuoles contained Ca2+-loaded degenerating mitochondria. Glands exposed to low concentrations of Ca2+ and Mg2+ were mainly composed of stimulated and active chief cells; characteristic features were a moderate or low cytoplasmic density, prominent endoplasmic reticulum, small Golgi complex, medium-sized, or small mitochondria, and smooth electron lucent vacuoles with or without an association of mitochondria. Ca2+-containing precipitates were found mainly in smooth vacuoles and cytosol, but also in mitochondria and routh vacuoles. Myelin-like figures and crystalloid bodies occurred in some mitochondria, and normal or degenerating mitochondria withoug Ca2+-loading were seen in autophagic vacuoles. In addition, some stimulated chief cells exhibited double membrane-limited sequestered areas of cytoplasm with a rich content of free ribosomes and glycogen-like particles. The chief cell mitochondria seem to possess capacity for rapid accumulation of Ca2+, associated with an increase in volume at functional suppression. At stimulation of parathyroid function the endoplasmic reticulum is prominent in the active cells, and there seems to be a decrease in the volume and Ca2+-content of the mitochondria occasionally associated with degenerative changes, and a decrease also in the number of free ribosomes and glycogen-like particles in the stimulated cells.

Female baboons maintained under laboratory conditions were subjected to a series of 10 weekly injections (4 mg/kg body weight) of the synthetic glucocorticoid, triamcinolone hexacetonide. In response to the treatment, serum immunoreactive parathyroid hormone (PTH) levels were raised, though blood calcium levels remained within normal physiological limits. Light and electron-microscopic studies were made on the parathyroid glands at the end of the experimental period. The baboon parathyroid glands were composed of 'light' and 'dark' forms of the chief cells in varying ratios from gland to gland even within a single animal. Glucocorticoid-induced parathyroid hyperactivity as measured by circulating PTH levels was not accompanied by cellular hypertrophy, though there was an increase in the relative number of 'light' cells. At the ultrastructural level, after treatment, many of the 'light' cells were found to contain more free ribosomes, larger profiles of granular endoplasmic reticulum and had better developed mitochondria. Interdigitations between adjacent chief cells were more complex in treated glands. Apart from these features, chief cells of treated glands were basically similar to those of untreated controls. Our study showed that functional parathyroid hyperactivity in baboons is not necessarily accompanied by significant ultrastructural changes in chief cells.

Ultrastructural changes in the parathyroid glands of dexamethasone-treated mice were examined. Many chief cells of the treated mice contained a decreased number of prosecretory granules, secretory granules and storage granules, and an increased number of lipid droplets, compared with the control mice. In addition, myelin-like structures associated with cisternae of the granular endoplasmic reticulum were observed in the parathyroid glands of the treated mice. These findings suggest that cellular activity of the parathyroid gland may be suppressed by dexamethasone.

The endocrine response of porcine parathyroid gland tissue slices in vitro to aluminum was studied by electron microscopy and radioimmunoassay of PTH. Medium aluminum concentrations were 20 to 500 ng/ml covering the range corresponding to concentrations reported in the plasma of aluminum-intoxicated hemodialyzed patients. Aluminum inhibited iPTH-release and caused severe cell alterations. This inhibition was incomplete and there was an aluminum-insensitive iPTH-release capacity. This phenomenon seemed to be due to heterogeneous parathyroid cell population as regards aluminum sensitivity, perhaps linked to the spontaneous asynchronous cyclic parathyroid cell changes. Sensitivity to aluminum was modulated by the extra-cellular calcium concentration. Sensitivity to extra-cellular calcium concentration variations persisted in aluminum intoxicated tissues. The severity of the observed cell lesions induced by high concentrations of aluminum suggested that the recovery of an iPTH-release capacity when parathyroid tissue was withdrawn from a toxic environment and switched to aluminum-free media is more likely to be due to activation of a "less-sensitive to aluminum" cell pool than to a true reversibility of the toxic effect.

An in vitro model for studies of parathyroid physiology is described using single cell suspensions and adherent monolayer cultures of human parathyroid tissue. The isolated cells were viable and maintained functional properties tested by calcium and magnesium sensitivity. Parathyroid hormone (PTH) secretion could be suppressed by rising calcium and magnesium concentrations. The secretory behaviour of the cells was not altered by cultivation or cryopreservation. The morphological integrity of the individual cells after mechanical and enzymatic preparation was confirmed by light and electron microscopy.

Fine structural and enzyme histochemical observations on ultimobranchial body and parathyroid gland of the caecilian Chthonerpeton are presented. The cell clusters and follicles of the ultimobranchial body consist mainly of granulated cells which are termed C-cells and obviously belong to the APUD cell series. In the larger follicles additional possibly exhausted degranulated cells and replacement cells occur. A rich supply of nerve fibres has been found in this gland. Frequently nerve terminals were observed to come into synaptic contact with the C-cells. Two categories of nerve fibres occur: a) fibres containing large polymorphic electron dense granules (probably purinergic fibres), b) fibres containing small electron transparent vesicles and a few electron dense granules (probably cholinergic fibres). The parathyroid gland consists of elongated cells (one cell type) poor in organelles and often containing fields of glycogen and lipid droplets. The cells are further characterized by fair amounts of lysosomal enzymes; they are interconnected by maculae adhaerentes and occludentes. No nerves and blood vessels have been found in the parathyroid gland of Chthonerpeton.

The secretory mechanism of the parathyroid glands of fluoride-treated rats is evaluated ultrastructurally and compared to that of control rats. The principal difference between the two groups of rats concerns the rate of activity of the chief cells of the gland. In the control animals, these cells are predominantly inactive. In the fluoride-treated rats, they exhibit a more active stage of the secretory cycle. The active chief cells in rats treated with fluoride contain increased numbers of secretory granules. These granules are released into the perivascular spaces within cytoplasmic projections suggesting an apocrine-like mechanism for the secretion of parathyroid hormone. Secretory granules are observed free in the perivascular spaces and within the cytoplasm of capillary endothelial cells in the parathyroid glands.

The parathyroid glands of young male rats given 150 ppm fluoride in their drinking water for 10 weeks were examined by transmission electron microscopy. As a result of fluoride ingestion, the parathyroid chief cells of the experimental animals accumulated glycogen in excess of that seen in control animals given distilled drinking water for the same time period. In the majority of active chief cells, glycogen granules were diffusely spread throughout the cytoplasm as single granules or in small deposits. Large aggregations of glycogen granules were also seen within intercellular spaces. Accompanying the increase in glycogen was a rise in the number and development of the organelles associated with protein synthesis and secretion. The accumulation of glycogen is similar to that in hyperparathyroidism caused by chronic stimulation and prolonged secretory activity of the parathyroid gland. The results of this study suggest that increased amounts of glycogen occur in hyperactive chief cells of the parathyroid in response to the ingestion of large doses of fluoride.

The histochemical localization of alkaline phosphatase in sheep parathyroid gland was investigated using light and electron microscopy. The reaction products of enzyme activity were observed by light microscopy in pericytes. By electron microscopy they were limited to the intercellular spaces between the gland cells, being exclusively confined to the external surface of plasma membrane.

A retrospective study was done to correlate serum calcium concentrations and parathyroid gland ultrastructure to clinical, immunologic, and pathologic changes experimentally induced in gnotobiotic dogs by canine distemper virus (CDV). Dogs infected with CDV had significantly reduced serum calcium concentrations associated with ultrastructural evidence of parathyroid gland inactivity, degeneration, and viral inclusions. Although CDV-infected dogs exhibited neurologic signs, minimal lesions were present in the central nervous system. It is suggested that viral-induced parathyroid dysfunction may contribute to neutrologic disturbance of CDV infection.

Histologic, ultrastructural, and immunofluorescent changes in the parathyroid glands of rabbits have been studied after 48 hours of ozone inhalation at a dosage of 0.75 ppm. The frequent changes observed included hyperplastic parathyroiditis followed by capillary proliferation and leukocytic infiltration. The progressive cytologic events consisted of the presence of eosinophilic leukocytes, reticuloendothelial and lymphocytic infiltration, disaggregation of the parenchyma, and interstitial edema. The ultrastructural changes consisted of degeneration of nuclei, atrophy of the mitochondria, dilatation and atrophy of the endoplasmic reticulum of the chief cells of the parathyroid gland, proliferation of the venous limb of the capillary network, and the prominent interstitial elements. The immunofluorescent techniques revealed positive immunologic response. These data suggest that ozone inhalation perhaps triggers an immune reaction which causes inflammatory injury to the parathyroid gland. The possibility that the modified functional chemical groups of the parathyroid gland act as autoantigen is discussed.

A fine-structure study of the parathyroid proper and adjacent tissues has been performed in the gerbils. The chief cells were observed in three phases of the secretory cycle. The resting chief cells contained prominent lipid droplets, mitochondria and an atrophied Golgi apparatus in a finely granular cytoplasm. The intermediate-phase chief cells were also rich in lipid but showed an organelle assembly which is much less developed than in the actively secreting cells. The active chief cells possessed a noncisternal rough endoplasmic reticulum, located often in close proximity of the mitochondria. A prominent Golgi apparatus, numerous pro-secretory granules and lysosomes are characteristic of the active cells. The significance of these morphological variations is discussed. Large mitochondria-rich cells, akin to oxyphil cells were observed in the tissue adjacent to the parathyroid proper.

The ultrastructure of the parathyroid glands was studied in chick embryos developing normally in ovo or in shell-less culture (after removal of the eggshell). Shell-less chick embryos are significantly hypocalcemic relative to their in ovo counterparts. At 12 days of incubation, the parathyroid glands of shell-less embryos contain more lipid and show evidence of increased protein synthetic activity relative to those grown in ovo (more rough endoplasmic reticulum, presence of some dense secretory granules). The glands from in ovo embryos do not contain secretory granules at this age. At 15 days of incubation, the in ovo glands have developed signs of protein synthetic activity similar to those of the 12-day shell-less embryos. However, the parathyroids of the 15-day shell-less embryos appear strikingly more active than at 12 days, containing stacks of concentric RER membranes and increased numbers of secretory granules. By 18 days of incubation, the ultrastructure of the glands of the two groups is indistinguishable, both appearing to be more active than the 15-day shell-less group. Thus, protein synthetic activity of the parathyroid glands, as detected by ultrastructural alterations of the chief cells, normally appears to be initiated during the latter part of embryogenesis (by approximately 15 days incubation) and its onset can be stimulated at least 3 days prematurely by hypocalcemia.

Parathyroid glands of cattle, dogs, cats, mice and rats were immersed in glutaraldehyde or mixtures consisting of glutaraldehyde, formaldehyde and acrolein in either Na-phosphate, Na/K-phosphate or Na-cacodylate buffer, and postfixed with OsO4 in the same buffers or, alternatively, in s-collidine. Excellent preservation of bovine, feline and murine parathyroid glands was achieved with fixation mixtures containing 1% glutaraldehyde, 1.5-2% formaldehyde and 2.5-5% acrolein in 0.1 M Na-cacodylate with or without Ca2+ and Mg2+, Na-phosphate or Na/K-phosphate at 4 degrees C followed by postfixation with 1% OsO4 in the same buffers or in s-collidine containing sucrose, Ca2+ and Mg2+. This procedure largely abolished the occurrence of parathyroid cell variants. Bovine parathyroid glands were also satisfactorily preserved with 1% glutaraldehyde and 2% formaldehyde whereas 1% glutaraldehyde and 2.5 or 5% acrolein, lower or higher buffer osmolarity, or immersion at room temperature led to vacuolization of RER and to breakdown of membranes. In contrast, all fixation protocols led to the formation of dark and light cell variants and to multinucleated syncytial cells in dog and rat parathyroids. The results thus show that parathyroid cell variants arise during immersion fixation and that aldehydes, buffers and temperature are important factors for provoking parathyroid cell variants.

Distributions of parathyroid hormone (PTH), proparathyroid hormone (ProPTH), preproparathyroid hormone (PreProPTH), and parathyroid secretory protein (PSP) were analyzed in subcellular fractions prepared from homogenates of bovine parathyroid glands. Slices of bovine parathyroid glands were incubated with radiolabeled amino acids for 3--30 min to selectively label newly synthesized proteins. Subcellular fractions were prepared from homogenates of the gland slices by differential centrifugation. Newly synthesized labeled hormonal polypeptides in the fractions were analyzed by electrophoresis on polyacrylamide gels, and total amounts of PTH and ProPTH (previously formed and newly synthesized) were determined by immunoassay. Ninety percent of total immunoreactive, 70--80% of newly synthesized PTH, ProPTH, and PreProPTH, and 50% of PSP were found in sedimentable particulate fractions. The low speed (800 X g) pellet, which consisted predominantly of cell debris and nuclei with adherent remnants of cytoplasm, contained 30--50% of the ProPTH and PTH. The intermediate speed (10,000 X g) pellet, which contained granules, was relatively enriched in PTH. Most particulate-associated hormone could be solubilized by treatment with deoxycholate (DOC) 98% and 97% of radiolabeled and 93% and 83% of immunoreactive ProPTH and PTH, respectively, in particulates sedimenting at 10,000 and 105,000 X g were rendered DOC-soluble. Approximately 50% of the PTH and ProPTH in the particulates resisted digestion by combined trypsin and chymotrypsin, whereas PreProPTH was completely susceptible to proteolysis. Up to 50% of the radiolabeled PTH and ProPTH added exogenously to parathyroid gland slices before homogenization became associated with the particulate fractions, and 70--80% or radiolabeled PreProPTH added to the subcellular fractions readily associated with the sedimentable material. The results indicate that in homogenates of parathyroid glands, PTH, ProPTH, PreProPTH, and PSP are associated with particulate structures. Furthermore, up to 50% of the association of ProPTH, PTH, and PSP with particulate fractions seems to be nonsepcific and occurs during the disruption of the tissues. The remaining 50% or more of hormonal protein is presumably sequestered within membrane-limited structures, such as microsomal vesicles. The complete susceptibility in particulate fractions of newly synthesized PreProPTH, but not of ProPTH, to limited proteolysis indicates that the two precursors are located in different subcellular compartments and suggests that PreProPTH is converted to ProPTH before its entry into the intracisternal space of the endoplasmic reticulum. Alternatively, the PreProPTH identified in parathyroid gland slices may represent polypeptide chains synthesized in the cell sol on polyribosomes that are not attached to endoplasmic reticulum but are adsorbed nonspecifically to the particulate fraction of the cell during the process of tissue homogenization.

Ultrastructural changes of the parathyroid glands of vagotomized rabbits were examined. Many chief cells at 6, 12, 18 and 24 h after vagotomy are rich in free ribosomes compared to control rabbits. The main changes in the parathyroid glands of rabbits at 12, 18 and 24 h after vagotomy as compared with the control animals are a proliferation of the Golgi complexes, an increased number of secretory granules in the peripheral cytoplasm, and a frequent occurrence of enlarged intercellular spaces containing finely particulate substance. Large secretory granules, heterogeneously dense bodies, multivesicular bodies and lipid droplets apparently decrease in number in many chief cells at 12, 18 and 24 h after the operation. These alterations suggest that synthesis and release of parathyroid hormone are stimulated in many chief cells of the vagotomized rabbits. In addition, correlations of the occurrence of large secretory granules and various bodies are discussed.

The long term (70 days) effects of administering ethane-1-hydroxy-1,1-diphosphonate (EHDP) (4 mg. per kg. per day) on parathyroid function was investigated in pregnant cows fed a low calcium diet. Serum calcium and phosphorus were significantly lower at parturition and postpartum in EHDP-treated cows compared to pregnant control cows fed the low calcium diet. Plasma immunoreactive parathyroid hormone levels were similar prepartum, at parturition, and postpartum in cows administered EHDP and control cows. Immediately available calcium reserves were greater preparation in control cows than in cows receiving EHDP as indicated by a more rapid rate of return of serum calcium toward normal levels following ethylenediaminetetraacetic acid (EDTA)-induced hypocalcemia approximately 10 days prepartum. EHDP-treated cows responded to the hypocalcemic challenge with similar changes in plasma immunoreactive parathyroid hormone levels as in control cows; however, urinary hydroxyproline excretion increased at certain intervals only in control cows. Ultrastructurally, chief cells in parathyroid glands of both groups of cows were in an active stage of the secretory cycle with well developed organelles concerned with hormonela synthesis. Chief cells in cows administered EHDP were degranulated and contained fewer secretory granules in response to the hypocalcemia than those in control cows. Chief cells in EHDP-treated cows often had prominent perinuclear accumulations of microfilaments, scattered vacuolated mitochondria, and lysosomal bodies in the cytoplasm. Thyroid C-cells were densely granulated and thyroid calcitonin content was similar in both groups of cows. The principal defect in calcium homeostasis of EHDP-treated cows appeared to be an impairment both in bone calcium mobilization and bone matrix catabolism in response to the secretion of parathyroid hormone. In vitro uptake of 45Ca by duodenal mucosa and urinary excretion of cyclic adenosine monophosphate were similar in both groups of cows. The ability of the parathyroid glands to synthesize and secrete parathyroid hormone in response to hypocalcemia induced either by EDTA or associated with parturition was not impaired by the administration of EHDP.

Morphological studies of the parathyroid glands from adult Mongolian gerbils in which hypercalcaemia had been induced by thyroidectomy and calcium injections for 2-19 days were carried out. The potassium pyro-antimonate technique and subsequent X-ray analysis of the precipitates were used for ultrastructural localization of cations. Ultrastructurally, most (suppressed) chief cells exhibited a dense cytoplasm, medium-sized or large mitochondria, glycogen particles, inconspicuous endoplasmic reticulum and Golgi complex, calcium-containing precipitates mainly in mitochondria and nuclei, and sometimes also lysosomal bodies and accumulations of secretory granules which occasionally seemed to be discharged into cytoplasmic vacuoles. A few parenchymal cells showed a low cytoplasmic density, few organelles, and structurally altered mitochondria, occasionally with associated smooth-surfaced vacuoles. These cells possessed calcium-containing precipitates in mitochondria, smooth-surfaced vacuoles, and also diffusely in the cytosol. It is concluded, that, in the main part of the parenchymal cells, the hypercalcaemia had resulted in a suppression primarily of the synthetic and later also of the secretory activity, and that the calcium-containing precipitation is different in the chief cell variants.

The ultrastructure of long-term parathyroid autografts and their donor glands has been studied in nine patients with chronic renal failure. Autografts showed ultrastructural features of functional activity. Unusual findings included the presence of 'spironolactone-like' concentric membranous bodies derived from the endoplasmic reticulum in one hyperplastic autograft and prominent intracellular intermediate filaments (tonofilaments) in the donor parathyroid gland and recurrent autograft growths in another patient.

Histological preparations of thyroid, parathyroid and thymus glands of Herpestes edwardsi were examined for calcitonin cells. They reveal that (1) the thyroid calcitonin cells are oval, rounded and rarely elongated in shape; these cells and their nuclei are distinctly larger than those of the follicular cells and their nuclei; (2) calcitonin cells are unevenly distributed in the thyroid, with the result that certain portions of the thyroid are completely devoid of these cells; (3) on an average, calcitonin cells are in a ratio of 10-15 cells/100 follicular cells; (4) the parathyroid and thymus glands do not display calcitonin cells, and (5) the thyroid gland displays unusual follicles of two categories, (a) follicles with ciliated epithelial cells and (b) follicles with squamous epithelium.

In dogs and aged 6 days or 5 months, the parathyroid (PT) glands exhibited differences of both the distribution and ultrastructure of dark and light cells. Morphometric estimates of cytoplasm, nucleus, mitochondria, rough endoplasmic reticulum (rER), Golgi apparatus, secretory granules, lysosomes and plasma membranes of both dark and light cells were obtained by point counting volumetry from PT glands of dogs of the two age groups and calculated per one hypothetical average PT cell. It was evident that in the PT glands of 6-day-old puppies the volume of the average PT cell was significantly smaller than in the PT glands of the 5-month-old dogs, but the cell surface was not significantly different. The volume of mitochondria, rER and lysosomes was higher in the average PT cell of the 5-month-old dogs, whereas the surface of Golgi apparatus and rER did not differ. Though the difference of the cellular and mitochondrial volume is probably related to the age difference between the two groups, the findings on Golgi apparatus, plasma membranes and lysosomes suggest that the secretory activity or at least the potency for the secretion of parathyroid hormone was higher in PT glands of the 6-day-old dogs than in the 5-month-old dogs.

Blood vascular beds of the rat parathyroid glands were reproduced with a methacrylate casting medium and observed with a scanning electron microscope. The rat possesses only a single pair (one left and the other right) of parathyroid glands. Each gland was found to contain a rich capillary network which was completely isolated from the capillary plexus of the thyroid gland. Each parathyroid gland received some small afferent arteries from the superior thyroid artery and emitted a thick efferent vein continuous with the superior thyroid vein. The capillary network of the parathyroid gland consisted of freely anastomosing capillaries. The afferent arteries were divided in the superficial and deep layers of the gland. The thick efferent vein arose in the deep layer of the gland. Some small or accessory efferent veins arose in the superficial layers of the gland. These also drained into the superior thyroid vein.

The frequency of lipid droplets in the parathyroid glands of young, adult and senile golden hamsters after starvation was investigated. In the parathyroid glands of the young and senile golden hamsters, the number of lipid droplets increased to reach a peak by 2 days, then decreased slowly by 5 days after starvation, and decreased rapidly after refeeding. In the glands of adult animals it increased to reach a peak by 5 days after starvation and decreased rapidly after refeeding. These findings suggest that in the fasting condition there is a relationship between the number of lipid droplets and aging.

Hypocalcemia was induced in adult Mongolian gerbils by a combination of a calcium deficient diet and repeated injections of ethylene-diamine-tetra-acetate (EDTA). This treatment caused tetany and death in some of the animals. Laboratory analyses on the eight experimental day disclosed significantly decreased concentrations of serum calcium and significantly increased concentrations of serum phosphate. Stereological methods and semi-automatic image analysis were used for ultrastructural study of the parathyroid glands with the aim of disclosing if any quantitative alterations occur in prolonged hypocalcemia. Compared with normocalcemic animals no significant change was observed in the hypocalcemic gerbils with regard to the nuclear profile area, the volume densities of nucleus, mitochondria, endoplasmic reticulum, Golgi complex, lysosomes, secretory granules and storage granules, or the surface density of the cell membrane. The only significant change in the hypocalcemic animals was a slight increase in the volume density of lipoid bodies and a similarly slight decrease in the surface density of the endoplasmic reticulum, changes which at present are difficult to explain. The data demonstrate that hypocalcemic stimulation in vivo does not give rise to quantitative morphological changes in parathyroid chief cells, and thus do not support the idea of a functional adaptation of the chief cells to variations in the ambient calcium concentration.

Ultrastructural morphometry was performed on human parathyroid tissue from adenomas in chronic and acute (pernicious) hyperparathyroidism (HPT) including contralateral atrophic glands with the aim to compare the observed alterations with the corresponding clinico-functional findings. Quantitative assessment of various cell organelles, nucleus and cell perimeter revealed that significant correlations between ultrastructural features and laboratory parameters were only calculable by regarding extreme ranges of functional stages, i.e. adenomas of acute HPT (hyperparathyroid crisis) and contralateral atrophic glands. In chief cells of chronic HPT there was an inhomogeneity of measurements due to the disparate composition of the adenomatous tissue. Our results show that large complex lipid bodies and extensive accumulations of glycogen are valuable indicators of a functionally suppressed chief cell in atrophic parathyroid glands. An increased number of coated pits and vesicles is amongst other features (increase in size or number of Golgi apparatus, rough endoplasmic reticulum, mitochondria, nucleus and nucleolus as well as extension of the plasma membrane) characteristic of an endocrine stimulation.

Parathyroid cells exhibit ultrastructural heterogeneity. This has been interpreted as an indication that the cells are undergoing secretory cycles, varying in synthetic activity. By electron microscopy we examined step sections at 1 and 2 micron intervals and serial sections of parathyroids from normocalcemic rats of three different age groups. The secretory cells in all three age groups exhibit structural polarity: nuclei and secondary lysosomes are generally located towards the interstitial tissue, whereas the Golgi is confined mainly to regions in the interior of the cell sheets. Cell surfaces facing the interstitial tissue are smooth, whereas plasma membranes in the interior of the cell sheets form tortuous areas. Consequently, an individual cell profile may show quite different appearance depending on section level. Our results do not support the concept that the observed heterogeneity is necessarily due to differences in organelle contents between the cells. The present investigation thus offers an alternative explanation to the ultrastructural variability among secretory parathyroid cells in the rat.

The parathyroid gland of healthy senile dogs aged 8.5 to 15 years was compared with that of mature control dogs by examination with the electron microscope. Preparations fixed by perfusion with glutaraldehyde showed the cytoplasmic matrix of most parenchymal cells to be uniformly dense. None of the cells were of the extremely light type and dark cells were much less frequently noted than in preparations fixed by immersion in glutaraldehyde or osmium tetroxide. Syncytial cells and so-called coloid follicles were more frequent in senile dogs than in control dogs. It was suggested that the content of the latter structures is not colloid but necrotic substance hiving origin from the parenchymal cells and that perhaps the occasional cells containing large, membrane-bound inclusions may be degenerating cells which ultimately produce this necrotic substance. Oxyphil cells and mitochondria-rich cells of another type were found in all senile dogs, but not in the controls. These cells, especially the mitochondria-rich cells, frequently contained bizarre mitochondria that were modified in shape, size and arrangement. The most striking feature of these mitochondria was the concentric arrangement of elongated mitochondria which seemed to consist of densely layered cup-shaped mitochondria. Such mitochondria were noted in all senile dogs aged ten years and over. The significance of mitochondrial ple-morphism in the parathyroid gland of senile dogs was discussed.

Small electron dense plaques (EDP) were found in the plasma membrane of pancreatic islet A-, B- and D-cells and parathyroid chief cells of mice and gerbils. The identification of the EDP was facilitated by the use of special fixation techniques. The EDP may represent sites of calcium binding in the cell membranes.