Solitary thyroid nodules in 71 children and adolescents.

Seventy-one children and adolescents with a solitary nodule of the thyroid gland were seen over a 27-year period and all had their nodules removed surgically. All of the patients had preoperative thyroid scintiscans, 55 of which showed a cold nodule. The most common cause of solitary thyroid nodules was follicular adenoma. Fourteen of the 55 cold nodules were malignant (25.5%) while no malignancies were present in warm or hot nodules. Available diagnostic methods for attempting differentiation of benign from malignant solitary nodules are reviewed and recommendations to their clinical management as derived from our experience are presented.

Pediatric renal artery dysplasia: a morphologic study.

Renal arteries from 12 pediatric patients who had stenosis due to renal artery dysplasia (9 surgical resections and 3 autopsy cases) were examined by light microscopy. The patients ranged in age from 15 months to 14 years; the male/female ratio was one. Bilateral renal artery disease was clinically diagnosed in 8 of the 12 patients; 6 of the 8 also had aortic anomalies. All of the lesions were designated as forms of dysplasia, a departure from previous reports in which dysplasia was subclassified as fibroplasia and hyperplasia. The most common lesion was medial fibrous dysplasia (6), followed by perimedial elastic dysplasia (4); intimal fibrous dysplasia (1) and medial muscular dysplasia (1) were the least common. Medial fibrous dysplasia was present as often with bilateral as with unilateral renal artery stenosis, while perimedial elastic dysplasia was seen exclusively in patients with bilateral renal artery disease. Three patients who came to autopsy had extrarenal vascular involvement by a similar dysplastic lesion. The three patients who had neurofibromatosis showed no distinctive histologic type of renal artery dysplasia.

Influence of testosterone and dihydrotestosterone on bone-matrix induced endochondral bone formation.

A bone matrix-induced endochondral bone development model has been used to study the effects of androgens on different stages of bone development in castrated young adult rats. Androgen treatment, especially with dihydrotestosterone (DHT) for 7 days, inhibited 35SO4 incorporation by the developing cartilage in the induced plaques. Castrated control animals maintained for 11 days after implantation of bone matrix showed significantly lower calcium levels in the induced implant than was observed earlier in the unoperated controls. DHT treatment for 11 days caused dramatic increases in levels of calcium in the implants. Testosterone had little effect. When androgen treatment was continued for 21 days, while levels of alkaline phosphatase in the implants were unaffected, levels of calcium in the implants were significantly higher than on day 11 for both castrated control and androgen-treated animals. Peak alkaline phosphatase activity (day 10) is known to precede peak calcium mineralizing activity (day 12) in this model and it is also known that calcium levels remain high thereafter. Evaluation of calcium and alkaline phosphatase levels in the proximal tibial metaphyses of castrated control and androgen-treated groups of animals showed no changes after 11 days treatment. Prolonged treatment (21 days) elevated the levels of alkaline phosphatase whereas no change was observed in calcium levels in the tibial metaphyses. These findings demonstrate that androgens stimulate mineralization and that DHT is more active when used for short periods of time and in early stages of bone development in matrix-induced implants.

Chondrogenic potential of mesenchymal cells elicited by bone matrix in vitro.

Demineralized bone matrix (DBM) induces development of bone in vivo via the endochondral mode of development. Early events in this inductive process involve the appearance of mesenchymal cells (day 3) followed by chondrogenic differentiation (day 7) after subcutaneous implantation of DBM. In this investigation the chondrogenic potential in vitro of day 3 and day 4 mesenchymal cells from a DBM-induced implant has been explored. Immunofluorescent examination of day 3 cell cultures maintained for 4 days revealed the presence of type II collagen and cartilage-specific proteoglycans only in spherical or polyhedral cells. Micromass cultures and agarose suspension cultures showed toluidine-blue metachromasia in only a small population of cells. Biochemical estimation of 35SO4-labeled proteoglycans from suspension cultures of day 3 and day 4 cells maintained for 3 days indicated the presence of 29% and 38% large cartilage-specific proteoglycans, respectively. Addition of bone-inductive guanidine extract of DBM to the cultures did not significantly increase the percentage of large proteoglycans. These observations suggest that day 3 and day 4 cells can undergo chondrogenic differentiation in vitro without the continued presence of the bone-inductive guanidine extract. The presence of guanidine extract in cultures did not enhance chondrogenic expression or promote the recruitment of mesenchymal cells and their transformation to the chondrogenic phenotype.

Benign hepatocellular tumors in the young. A clinicopathologic spectrum.

Hepatic tumors unassociated with cirrhosis were encountered in seven patients aged 10 to 19 years. Four patients had received androgens for aplastic anemia. Two patients had transfusional hemosiderosis. One patient had had a renal transplant 2 1/2 years ago. Two patients are alive at 2 3/4 and 2 1/2 years after surgical resections. Nodules were found at autopsy in the others. The tumors were well differentiated and, in the androgen-related cases, differed from the others in the following features: canalicular bile retention, mild nuclear atypia, and acinar formation. No mitoses, vascular invasion, or metastatic tumor were evident. The clinical setting was variable; different factors, including iron overload and androgen therapy, played a role in the development of tumor. Although the androgen-related cases showed mild cellular atypia, biologic evidence of malignancy was lacking as in most previous reports.

A study of two enteroendocrine cells in the duodenum of the gerbil-Meriones unguiculatus.

Gastrin-secreting G cells and enterochromaffin cells have been examined in the duodenum of the gerbil-Meriones unguiculatus. G cells examined by immunoperoxidase and immunofluorescence methods were seen primarily located in the mucosa lining the villi and rarely in the glands of Lieberkühn. They were flask-shaped cells that extended from the basal lamina to the mucosal surface. Immunoreactive gastrin was localized all over in the cytoplasm but was especially concentrated in the juxtanuclear and subnuclear regions. Enterochromaffin cells were identified by a serotonin-specific formaldehyde-induced fluorescence method. These cells were also primarily located in the duodenal villi, were flask-shaped and revealed an intense yellow fluorescence that was especially concentrated in the subnuclear cytoplasm. At the ultrastructural level the enterochromaffin cells showed numerous pleomorphic electron-dense secretory granules especially located in the subnuclear cytoplasm. Microfilament bundles were often observed, especially in the perinuclear region.

An ultrastructural and cytochemical study of enteroendocrine cells of the pyloric antrum in the gerbil, Meriones unguiculatus.

Enteroendocrine cells of the gastric antrum have been examined in the gerbil, Meriones unguiculatus. Gastrin-secreting G cells were identified by immunocytochemical methods and by transmission electron microscopy. They were present in the lower and middle third of the pyloric antral glands. G cells were polyhedral in shape and often extended to the gland lumen where they presented a microvillous and pinocytotic surface. These cells were characterized by numerous electron-dense and immunoreactive secretory granules. Enterochromaffin cells were identified by a serotonin-specific formaldehyde-induced fluorescence method, and by electron microscopy which revealed pleomorphic secretory granules of varying electron densities. These cells also had luminal projections and had a shape and distribution essentially similar to those of the G cells. A third endocrine cell type was identified as Dl cell in the pyloric glands. This cell type was recognized by the presence of numerous secretory granules having an electron-dense core and a clear peripheral space, as also by the presence of microfilament bundles, especially in the perinuclear region. The functional correlates of these morphological observations are discussed with reference to their secretory product and the manner of its release, especially by the G cells.

Effect of concanavalin A dose, unbound concanavalin A, temperature, Ca2+ and Mg2+, and vinblastine on capping of concanavalin A receptors of human peripheral blood lymphocytes.

The capping of Concanavalin A (Con A) receptors induced by Con A was studied using human peripheral blood lymphocytes. The effects of Con A dose (5--100 micrograms/ml), pretreatment at 4 degrees C, unbound Con A, extracellular Ca2+ and Mg2+ and vinblastine were evaluated using Con A-horseradish peroxidase and electron microscopy. Lymphocytes incubated with Con A at 4 degrees C and fixed with glutaraldehyde exhibited Con A-horseradish peroxidase around the entire cell periphery. After raising the temperature to 37 degrees C, the Con A-horseradish peroxidase moved to form a cap at one pole of the cell and subsequently underwent endocytosis. Capping of Con A receptors induced by Con A at 37 degrees C was observed only at low Con A concentrations in the presence of unbound Con A and extracellular Ca2+ and Mg2+. Increased capping was found after pretreatment of cells with Con A at 4 degrees C, removing unbound Con A and/or removing extracellular Ca2+ and Mg2+, and by treatment with vinblastine. Following removal of both unbound Con A and extracellular Ca2+ and Mg2+, the percentage of capped cells at 37 degrees C was the same as on pretreatment at 4 degrees C under the same conditions. While pretreatment at 4 degrees C caused the breakdown of microtubules, removal of unbound Con A and/or extracellular Ca2+ and Mg2+ had no morphological effect on microtubules or microfilaments. Following exposure of lymphocytes to vinblastine and removal of unbound Con A, capping of Con A receptors by Con A was observed in over 90% of cells at all Con A dosages. However, when cells were exposed to vinblastine in the presence of unbound Con A the formation of Con A caps was either partially or completely inhibited.

Estrogen and tracheal secretion: the effect of estrogen on the epithelial secretory cells of the rat trachea.

Epithelial secretory cells of the tracheal mucosa obtained from ovariectomized control and ovariectomized estrogen-treated rats were studied morphologically by scanning and transmission electron microscopy and by the combined periodic acid Schiff (PAS) and alcian blue (AB) staining method. A significant decrease was observed in the number of large PAS-reactive secretory cells following estrogen treatment. Concomitantly the number of the Mixed+ cells containing both weakly acid and neutral glycoproteins was found to increase significantly. A majority of the observed secretory cells exhibited either an apical protrusion loaded with secretory granules, extending to a maximum distance of 7.9 micrometer into the tracheal lumen or an apical indentation devoid of mature secretory granules, descending to 5.6 micrometer below the luminal surface. The frequency of cells exhibiting an apical indentation was significantly greater in estrogen-treated animals than in controls. The present findings indicate that estrogen treatment of ovariectomized rats results in: 1) an increase in the synthesis of weakly acid glycoprotein within tracheal secretory cells; 2) a concomitant decrease in the frequency of secretory cells containing neutral glycoprotein; and 3) a general increase in the secretion by the tracheal cells.

Sharpey fiber bone development in surgically implanted dog mandible. A scanning electron-microscopic study.

Ticonium metal implant placed surgically in the previously edentulatized adult dog mandible induced the formation of an extensive Sharpey fiber system. Sharpey's fibers extended from the peri-implant area, deep into alveolar bone. The frequency of Sharpey's fibers and the degree of their mineralization varied from scattered location and unmineralized state to heavy clustering and full mineralization. This study suggests that the formation of Sharpey's fibers and the degree of their mineralization are determined by biophysical forces of pressure received at a given site.

Histochemical and ultrastructural study of the parafollicular (C) cells in the thyroid of the gerbil, Meriones unguiculatus.

A histochemical and electron-microscopic study has been done on the parafollicular (C) cells of the thyroid in the gerbil. Histochemical tests revealed the characteristic presence of alpha-glycerophosphoric dehydrogenase and the presence of phenolic groups and indoleamines. Acid phosphatase levels were similar to those observed in the apical cytoplasm of the follicular cells. Electron microscopy revealed characteristic presence of noncisternal rough endoplasmic reticulum, well-developed Golgi apparatus, numerous prosecretory granules and a few electrondense mature secretory granules. Most characteristic of these cells was the presence of numerous, large, electron-lucent vesicles which often were packed in the cytoplasmic processes that were located subjacent to the follicular cells and close to the blood capillaries. Significance of these histochemical and ultrastructural findings is emphasized particularly in regard to the presence of monoamines and their possible role in the release of calcitonin and thyroxin.

Fine-structure study of the parathyroid in the gerbil, Meriones unguiculatus.

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.