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Biomedical subjects

E Gould

Publications and source records attributed to E Gould.

At least 91 records · Page 5Linked to original sources

Exposure to excess glucocorticoids alters dendritic morphology of adult hippocampal pyramidal neurons.

We have used Golgi-impregnated tissue to demonstrate that exposure to excess glucocorticoids alters dendritic morphology in a specific population of neurons in the adult rat hippocampus. Daily injection of 10 mg of corticosterone for 21 days resulted in decreased numbers of apical dendritic branch points and decreased total apical dendritic length measured in a 100-microns-thick section in CA3 pyramidal cells compared to sham-injected and non-injected controls. In contrast, no changes were observed in CA3 pyramidal cell basal dendritic morphology. Furthermore, no changes were observed in the dendritic morphology of CA1 pyramidal cells or granule cells of the dentate gyrus. Cross-sectional cell body area of any of the 3 cell types examined in this study was unaffected by corticosterone treatment. Finally, qualitative analysis of Nissl-stained tissue from the same brains revealed increased numbers of darkly staining, apparently shrunken CA3 pyramidal cells in corticosterone treated compared to control brains. The changes in dendritic morphology we have observed may be indicative of neurons in the early stages of degeneration, as prolonged exposure to high levels of corticosterone has been shown by others to result in a loss of CA3 pyramidal cells. Additionally, these results suggest possible structural alterations which may occur under physiological conditions in which corticosterone levels are chronically elevated such as in aged animals.

Animals↗

Pseudosarcomatous myofibroblastic proliferations in the urinary bladder of children.

Ten examples of a pseudosarcomatous myofibroblastic proliferation occurring in the urinary bladder of children (aged 2 to 16 years) are reported. The lesions appeared as polypoid nodular masses of variable size with myxoid and hemorrhagic areas. They consisted of compact fascicles of elongated spindle cells with minimal atypia. Myxoid areas of variable extension and scattered inflammatory cells were constant features, whereas diffuse collagen deposition was not common. Despite the striking cellularity of some of the lesions, most showed minimal mitotic activity. Ultrastructurally, the predominant cells had features of myofibroblasts. Six cases studied by immunocytochemical methods expressed vimentin and muscle-specific actin. In addition, two of these cases expressed desmin and two others cytokeratin. Infiltration into the muscularis propria of the urinary bladder was demonstrated in six cases and into the perivesical soft tissues in two. However, none of the eight patients for whom follow-up information is available has had local recurrence or metastasis develop 18 months to 6 years after surgical excision.

Actins↗

Dendritic spine density of adult hippocampal pyramidal cells is sensitive to thyroid hormone.

In order to determine whether pyramidal cells of the adult hippocampus are morphologically sensitive to thyroid hormone, we performed single-section Golgi impregnation analyses on brains from hyperthyroid and control rats. Quantitative analyses of Golgi-impregnated pyramidal cells from the CA1 region showed a significant decrease in the density of apical dendritic spines with hyperthyroidism. In contrast, no changes were observed in spine density of basal dendrites or in cross-sectional cell body area of CA1 pyramidal cells. No changes in any of these morphological variables were detected in pyramidal cells of the CA3 region with hyperthyroidism. These results suggest that spine density of the apical dendrites of CA1 pyramidal cells is specifically affected by thyroid hormone in adulthood. Since dendritic spines are thought to represent postsynaptic sites it is likely that this morphological change results in altered hippocampal function.

Animals↗

Developing forebrain astrocytes are sensitive to thyroid hormone.

Previous studies have shown that developing neurons of the basal forebrain and hippocampus are sensitive to thyroid hormone (Gould and Butcher: J. Neurosci., 9:3347-3358, 1989; Rami et al: Neuroscience, 19:1217-1226, 1986). In order to determine whether or not thyroid hormone influences the development of astrocytes in brain regions where neurons are affected, we performed vimentin and glial fibrillary acidic protein (GFAP) immunocytochemical and single-section Golgi-impregnation analyses on the basal forebrain and hippocampus of control and neonatally thyroid hormone treated rats. For purposes of comparison, glial cells of the pontomesencephalotegmental (PMT) region, a region where developing neurons are not morphologically affected by thyroid hormone imbalances (Gould and Butcher, op. cit.), were also examined. Neonatal thyroid hormone treatment resulted in a premature disappearance of vimentin-immunoreactive radial glia in the basal forebrain and hippocampus. In addition, a premature appearance of GFAP-immunoreactive astrocytes with mature morphological characteristics was observed in the basal forebrain and hippocampus of thyroid hormone treated animals. Quantitative analyses revealed significant increases in the density of GFAP-immunostained astrocytes and in the cross-sectional cell body area and the number of primary processes in Golgi-impregnated astrocytes of the basal forebrain and hippocampus of animals treated neonatally with thyroid hormone. In contrast, no changes in any of these parameters were observed in glial cells of the PMT region with neonatal thyroid hormone treatment.

Animals↗

Mixed medullary-papillary carcinoma of the thyroid: a previously unrecognized variant of thyroid carcinoma.

Two unusual medullary carcinomas of the thyroid gland and their metastases contained a population of cells (20% to 25%) with the characteristic clear nuclei of papillary carcinoma. The predominant component of the tumors exhibited the typical growth pattern and cytologic features of medullary carcinoma with abundant amyloid deposits. The cells with clear nuclei lined follicle-like or tubular structures. In both the primary and the metastatic lesions, immunoreactive thyroglobulin was demonstrated only in the cells with clear nuclei, while calcitonin, carcinoembryonic antigen, and neuron-specific enolase were present only in cells of the predominant medullary carcinomatous component. Moreover, intense and diffuse staining for cytokeratin was seen only in the cells with clear nuclei, but not in those of the major medullary carcinomatous component. These findings suggest the existence of a distinctive variant of mixed medullary-papillary carcinoma that can be recognized with routine stains.

Adult↗

Short-term glucocorticoid manipulations affect neuronal morphology and survival in the adult dentate gyrus.

In order to determine whether short-term glucocorticoid manipulations influence the morphology and survival of neurons in the adult mammalian hippocampal formation, we performed quantitative analyses of Golgi-impregnated and Nissl-stained tissue from the brains of sham operated male rats, adrenalectomized male rats and adrenalectomized male rats which received corticosterone replacement. Three days after adrenalectomy, massive cell death, as detected by a dramatic increase in number of pyknotic cells, was observed in the granule cell layer of the dentate gyrus. By seven days following adrenalectomy, the numbers of pyknotic cells were even greater. Moreover, significant decreases in cross-sectional cell body area and numbers of dendritic branch points of Golgi-impregnated dentate gyrus granule cells were detected at seven days after adrenalectomy. Replacement of corticosterone to adrenalectomized rats prevented the appearance of large numbers of pyknotic cells as well as the decrease in granule cell cross-sectional cell body area and the numbers of dendritic branch points. In contrast, no obvious signs of degeneration were detected in the pyramidal cell layers of the CA1 and CA3 regions of the hippocampus at either three or seven days following adrenalectomy. In addition, no significant changes in morphological characteristics were observed in CA1 or CA3 pyramidal cells with adrenalectomy. These results show that dentate gyrus granule cells require glucocorticoids for their survival and for the maintenance of normal morphology and suggest that granule cell morphology and/or survival may undergo constant fluctuation in response to diurnal rhythms or stress-induced changes in glucocorticoid levels.

Adrenalectomy↗

Gonadal steroids modify dendritic spine density in ventromedial hypothalamic neurons: a Golgi study in the adult rat.

Neurons in the adult rat ventromedial hypothalamic nucleus (VMN, 4-6 neurons per brain; 3-7 brains per group) were studied under various hormonal conditions using the single-section Golgi impregnation technique. Intact rats of both sexes and ovariectomized females treated with oil, estrogen or estrogen and progesterone were used. Golgi-impregnated neurons in the VMN were analyzed to determine possible differences in cell body size, number of primary dendrites, number of dendritic branch-points and spine density. The only significant differences found were in spine density. In the VMN of ovariectomized rats given oil, there were significantly fewer spines on primary dendrites than in either estrogen-treated, estrogen plus progesterone-treated or intact female rats. There were no differences between intact male and female rats observed in any parameter. In addition, when spine density of VMN neurons was assessed throughout the estrous cycle, it was determined that spine density was significantly lower at diestrus than proestrus.

Animals↗

Naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons.

We have used Golgi-impregnated tissue to demonstrate that apical dendritic spine density in CA1 hippocampal pyramidal cells undergoes a cyclic fluctuation as estradiol and progesterone levels vary across the estrous cycle in the adult female rat. We observed a 30% decrease in apical dendritic spine density over the 24-hr period between the late proestrus and the late estrus phases of the cycle. Spine density then appears to cycle back to proestrus values over a period of several days. In contrast, no significant changes in dendritic spine density across the estrous cycle occur in CA3 pyramidal cells or dentate gyrus granule cells. These results demonstrate rapid and ongoing dendritic plasticity in a specific population of hippocampal neurons in experimentally unmanipulated animals.

Animals↗

Sex differences and thyroid hormone sensitivity of hippocampal pyramidal cells.

In an effort to determine if sex differences exist in the morphologic characteristics of pyramidal cells and granule cells of the hippocampal formation and whether sex plays a role in determining thyroid hormone sensitivity of these neuronal populations, we used single-section Golgi impregnation to examine the effects of neonatal thyroid hormone administration on hippocampal cells from the brains of adult rats of both sexes. Quantitative analyses of control brains revealed sex differences in the number of primary dendrites and the number of spines on the apical dendritic shaft of CA3 pyramidal cells. These differences showed opposite trends; females possessed more primary dendrites, whereas males showed more apical excrescences. Neonatal treatment with thyroid hormone resulted in long-lasting and dramatic changes of the entire CA3 pyramidal cell. CA3 pyramidal cells from thyroid hormone-treated animals showed significantly larger cell body areas, greater numbers of dendritic branchpoints, and longer dendrites. In addition, CA3 pyramidal cells from thyroid hormone-treated animals showed changes in the morphological characteristics which were shown to be sexually dimorphic; treatment resulted in significantly greater numbers of both primary dendrites and apical excrescences. These treatment differences occurred in both sexes and were of equal magnitude, regardless of sex. On the other hand, no sex differences in the morphologic parameters examined were detected for pyramidal cells in the CA1 region. Moreover, neonatal thyroid hormone treatment did not affect the cell body area, dendritic branch points, or the length of dendrites of these cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood.

Gonadal steroids are known to influence hippocampal physiology in adulthood. It is presently unknown whether gonadal steroids influence the morphology of hippocampal neurons in the adult intact rat brain. In order to determine whether female sex hormones influence hippocampal morphology in the intact adult, we performed Golgi impregnation on brains from ovariectomized rats and ovariectomized rats which received estradiol or estradiol and progesterone replacement. Removal of circulating gonadal steroids by ovariectomy of adult female rats resulted in a profound decrease in dendritic spine density in CA1 pyramidal cells of the hippocampus. Estradiol replacement prevented the observed decrease in dendritic spine density; progesterone augmented the effect of estradiol within a short time period (5 hr). Ovariectomy or gonadal steroid replacement did not affect spine density of CA3 pyramidal cells or granule cells of the dentate gyrus. These results demonstrate that gonadal steroids are necessary for the maintenance of normal adult CA1 hippocampal pyramidal cell structure. The short time course required to observe these effects (3 d for the estradiol effect and 5 hr for the progesterone effect) implies that CA1 pyramidal cell dendritic spine density may fluctuate during the normal (4-5 d) rat estrous cycle.

Animals↗

Basal forebrain neurons undergo somatal and dendritic remodeling during postnatal development: a single-section Golgi and choline acetyltransferase analysis.

In attempt to determine whether or not morphologic changes occur in the cholinergic basal forebrain during postnatal development. Golgi-impregnated and choline acetyltransferase-positive cells were examined in adult and postnatal day (P) 10, 14, 18, and 27 rats. Light microscopic analyses revealed progressive increases in in cross-sectional cell body area, number of primary dendrites, number of dendritic branch points, and length of the longest dendrite that peaked at P18 and thereafter decreased to smaller adult values with the exception of dendritic length which monotonically increased until adulthood. These findings suggest that extensive remodeling of cholinergic neurons in the basal complex occurs even at relatively late postnatal periods.

Animals↗

Oxyphil and squamous variants of medullary thyroid carcinoma.

Two unusual morphologic variants of medullary thyroid carcinoma not previously described are reported. The first tumor was composed predominantly of large eosinophilic cells indistinguishable at the light microscopic level from Hürthle cells. Focal areas of conventional medullary carcinoma were also present. Electron microscopic study showed mitochondrion-rich cells containing round neurosecretory granules. Immunoreactive calcitonin and carcinoembryonic antigen (CEA) were demonstrated within most tumor cells. The second tumor had areas of typical medullary carcinoma but exhibited extensive squamous differentiation. The tumor was positive for CEA, neuron-specific enolase, and chromogranin but negative for calcitonin. Oxyphil and squamous cells must be added to the long list of cell types that have been described in medullary thyroid carcinoma.

Adult↗

Cholinergic projections to the substantia nigra from the pedunculopontine and laterodorsal tegmental nuclei.

The cholinergic innervation of the compact and reticular parts of the substantia nigra in the rat was investigated by use of highly sensitive retrograde and anterograde tract-tracing methods in combination with choline acetyltransferase immunohistochemistry. The fluorescent tracers True Blue, propidium iodide, or fluorogold were infused preferentially into either nigral subnucleus. Cells positive for choline acetyltransferase and retrograde tracer were found in both the pedunculopontine and laterodorsal tegmental nuclei, although considerably more double-labeled somata were observed in the former than in the latter component of the pontomesencephalotegmental cholinergic complex. Approximately 2-3 times more cholinergic cells were labeled in the peduculopontine and laterodorsal tegmental nuclei when tracer injections were centered in the compact nigral subdivision than when infusions of about the same size were confined totally to the reticular part. Infusions of the anterogradely transported tracer Phaseolus vulgaris leucoagglutinin into the pontomesencephalotegmental cholinergic complex resulted in uptake and transport of that label to both nigral subnuclei, and some of the Phaseolus vulgaris leucoagglutinin-accumulating somata and proximal processes also demonstrated choline acetyltransferase-like immunoreactivity. The Phaseolus vulgaris agglutinin-labeled entities in the substantia nigra exhibited terminal-like profiles that were reminiscent of the pattern of nigral choline acetyltransferase-positive puncta demonstrated immunohistochemically by use of nickel ammonium sulfate enhancement of the final reaction product in the avidin-biotin procedure. These observations strongly support the contention that the pontomesencephalotegmental cholinergic complex is the major source of cholinergic projections to both the compact and reticular portions of the rat substantia nigra.

Animals↗

Nerve growth factor receptor is associated with cholinergic neurons of the basal forebrain but not the pontomesencephalon.

Sequential immunohistochemical demonstration of nerve growth factor receptor and cholinergic acetyltransferase on the same tissue section in the rat revealed that approximately 92% of all cholinergic neurons in the basal forebrain possessed that receptor. Only 0.9% of the neurons demonstrating nerve growth factor receptor in the basal nuclear complex lacked the cholinergic synthetic enzyme, and a similarly small percentage of cholinergic cells, 7.1%, were choline acetyltransferase-positive but nerve growth factor receptor-negative. Affiliation of nerve growth factor receptor with structural entities morphologically indistinguishable from those demonstrating choline acetyltransferase on separate but corresponding tissue sections was also observed in the telencephalic fiber tracts and terminal fields of basal forebrain cholinergic neurons, including cholinergic puncta in the reticular nucleus of the thalamus. Nerve growth factor receptor was not found in association with choline acetyltransferase-positive somata of the pedunculopontine and laterodorsal tegmental nuclei, however, nor were fibers immunoreactive for nerve growth factor receptor observed originating from those cell bodies. These results suggest that nerve growth factor receptor, which is probably synthesized in cholinergic basal forebrain somata and transported throughout their dendritic and axonal arbors, has a physiologic role in those cells in the adult nervous system. This does not appear to be the case for phenotypically similar neurons of the pontomesencephalotegmental cholinergic complex.

Animals↗

Signet ring cell sinus histiocytosis. A previously unrecognized histologic condition mimicking metastatic adenocarcinoma in lymph nodes.

The axillary lymph nodes in a radical mastectomy specimen from a 70-year-old insulin-dependent diabetic patient contained significantly vacuolated sinus histiocytes. The histologic picture closely resembled metastatic signet ring cell adenocarcinoma. The signet ring histiocytes did not stain with the mucicarmine or periodic acid-schiff stains or any of the immunohistochemical epithelial markers. The differential diagnosis and the possible origin of these vacuolated histiocytes are discussed.

Adenocarcinoma, Mucinous↗

Malignant giant cell tumor of soft parts presenting as a skin tumor.

Malignant giant cell tumor of soft parts is a rare neoplasm that histologically resembles a giant cell tumor of bone. It has a distinctive multinodular growth pattern and is composed of numerous osteoclast-like giant cells, histiocytes, and fibroblasts. Although this tumor is usually found in deep soft tissues, a superficial form has been described in the subcutaneous tissue and fascia. The authors report two patients, aged 75 and 78, with malignant giant cell tumors presenting as ulcerating skin nodules of the arm and foot. The tumors were relatively small, measuring less than 3.5 cm in greatest dimension, and involved the entire dermis and subcutaneous tissue. The clinical differential diagnoses included Kaposi's sarcoma, melanoma, and hematoma. Dermatopathologists and dermatologists should be aware of this entity to avoid confusion with other benign and malignant neoplasms that may contain multinucleated giant cells. The distinguishing histologic and immunohistochemical features of this tumor are discussed.

Aged↗

Scleromyxedema and severe myositis.

A case of scleromyxedema with associated rhabdomyolysis is reported. This appears to be a well-documented, although rare complication of scleromyxedema. This case is unique in that mucin was demonstrated in the muscle as well as the skin, and spontaneous resolution of the rhabdomyolysis occurred with the implementation of IV fluids and bed rest.

Adult↗