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Biomedical subjects

C C Capen

Publications and source records attributed to C C Capen.

At least 127 records · Page 7Linked to original sources
PubMed1981

Ultrastructural and biochemical evaluation of adrenal medullary hyperplasia and pheochromocytoma in aged bulls.

Pheochromocytomas and adrenal medullary hyperplasia were investigated ultrastructurally and by assaying catecholamines in tissue and urine. Three of seven bulls had concomitant thyroid C-cell neoplasms and normal parathyroid glands. Pheochromocytomas were either bilateral or unilateral, and were composed of large chromaffin cells predominantly in the storage phase of the secretory cycle. Two pheochromocytomas were composed of cells with ultrastructural characteristics of the epinephrine-secreting type and contained round secretory granules of low electron density. The norepinephrine-secreting type of chromaffin cell predominated in one pheochromocytoma and had storage granules with an electron-dense, eccentric core and a wide submembranous space. Two pheochromocytomas were composed of a mixture of epinephrine- and norepinephrine-secreting cells. Adrenal medullary hyperplasia in four bulls consisted of multinodular or diffuse areas of hyperchromatic chromaffin cells that were non-encapsulated, and compressed adjacent cortical tissue. Tissue and urinary concentrations of norepinephrine were increased in bulls with adrenal medullary hyperplasia or pheochromocytoma, but urinary vanillylmandelic acid and unconjugated epinephrine levels were not different from those of control bulls with a normal adrenal medulla.

Adrenal Gland Neoplasms↗
PubMed1981

Hypercalcemia associated with an adenocarcinoma derived from the apocrine glands of the anal sac.

Clinical, gross, and light microscopic findings are described for 36 dogs, 33 females and three males, with adenocarcinomas arising from the apocrine glands of the anal sac. All tumors had light microscopic features of malignancy and 22 of 23 metastasized to iliac and lumbar lymph nodes. Nine dogs had disseminated metastases, but bone metastases were found in only one dog. Differentiated neoplasms formed secretory acini and tubules lined by tall columnar or cuboidal epithelium. Most neoplasms were histologically bimorphic, with glandular areas and solid nests. Parathyroid glands were atrophic. Hypercalcemia (mean = 16.1 mg/dl) was present in 20 of 22 dogs (90%) and hypophosphatemia (mean = 3.2 mg/dl) in 12 of 17 (71%). Remission of hypercalcemia by tumor ablation and recurrence of hypercalcemia with tumor regrowth suggested that the tumor produced a substance that caused hypercalcemia. This unique clinicopathologic syndrome is characterized by hypercalcemia in old, predominantly female, dogs with an adenocarcinoma arising from the apocrine glands of the anal sac.

Adenocarcinoma↗
PubMed1981

Thyrotoxicosis and a thyrotropin-secreting pituitary tumor causing unilateral exophthalmos.

Hyperthyroidism due to a TSH-secreting pituitary tumor has been noted by a number of investigators. We describe a unique case in which a 17-yr-old female presented with clinical hyperthyroidism, a goiter, and unilateral exophthalmos. Serum T4, free T4, and T3 (RIA) were consistently elevated along with elevated TSH levels (range, 10-100 microunits/ml). Skull x-rays and computed tomography scan revealed a tumor invading the right orbit. Other pituitary function studies were normal and LATs was undetectable. Surgery performed resulted in 70% removal of the pituitary tumor and confirmed the presence of tumor infiltration into the right orbit. TRH tests done pre- and postoperatively (patient still clinically hyperthyroid with elevated T4 and TSH levels) showed TSH and PRL responsiveness. Electron microscopy of the tumor demonstrated features typical of pituitary thyrotrophs. Monolayer cultures of pituitary cells released TSH over time into the media but did not respond to TRH stimulation. Pituitary adenoma tissue content of immunoreactive TSH was 65 microunits/g wet tissue and demonstrated immunosimilarity with human standard. We conclude that the patient had a TSH-secreting pituitary tumor responsive to TRH stimulation.

Adenoma, Chromophobe↗
PubMed1981

Histomorphometric evaluation of the effects of intermittent 1,25-dihydroxycholecalciferol administration on cortical bone remodeling in adult dogs.

The effects of intermittent low doses (1.25 mug daily, administered intravenously for 6 days and withdrawn for 14 days for 3 complete cycles) of 1,25-dihydroxycholecalciferol (1,25-[OH](2)D(3)) on cortical bone were determined and compared in ribs with steady state and regionally accelerated remodeling in adult intact female dogs. The bone changes were analyzed by dynamic bone histomorphometric methods, using tetracycline and DCAF (2,4 BIS) N, N' di (carboxymethyl) (amino methyl fluorescein) in vivo double labeling of bones before treatment and after 60 days of intermittent 1,25-(OH)(2)D(3) administration. Serum calcium and phosphorus levels increased during 1,25-(OH)(2)D(3) administration. Urinary hydroxyproline excretion increased during the first interval of 1,25-(OH)(2)D(3) administration but was not changed significantly during the last two intervals. In normal cortical bone (11th rib) following the administration of 1,25-(OH)(2)D(3) there was a marked decrease in the activation frequency, bone formation rate, osteoid seam thickness, seam circumference, and mean appositional rate. Although recruitment of new remodeling sites was decreased after 1,25-(OH)(2)D(3), previously existing remodeling units continued to completion. These effects resulted in a preponderance of mature osteons in normal cortical bone. The morphometric changes in cortical bone (9th rib) exposed to both 1,25-(OH)(2)D(3) and periosteal elevation were characterized by a marked increase in both the activation frequency and bone formation rate and associated with a decrease in the osteon formation time. Other morphometric parameters that were increased included radial closure rate, numbers of osteoid seams and resorption cavities, ratio of bone resorbing to forming sites, percentage labeled and circumference of osteoid seams, and total and cortical bone areas. The combined effect of periosteal elevation and 1,25-(OH)(2)D(3) were markedly different from those observed with 1,25-(OH)(2)D(3) alone. These findings suggest that the rapid bone turnover induced by tissue injury will mask or alter the effects of hormones on bone remodeling when studied over a relatively short period of time.

Animals↗
PubMed1981

The effects of 1,25-dihydroxycholecalciferol, parathyroid hormone, and thyroxine on trabecular bone remodeling in adult dogs. A histomorphometric study.

The effects of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3), parathyroid hormone (PTH), and L-thyroxine (T4) on trabecular bone remodeling were evaluated by histomorphometric methods in adult female beagle dogs. Intravenous 1,25-(OH)2D3 (1.25 micrograms/day in equally divided doses) was administered intermittently for 6 days and withdrawn 14 days for three complete cycles. PTH was administered intravenously (2.5 U/kg/day) in divided doses 6 hours apart for 60 days. Thyroxine was given orally (1.0 mg/kg/day) in divided doses for a similar interval. Static and dynamic changes were evaluated using tetracycline and DCAF (2,4 BIS) N, N', Di (carboxymethyl) (amino methyl fluorescein) in vivo double labeling of bone from the iliac crest taken before treatment and after 60 days. The intermittent administration of 1,25-(OH)2D3 stimulated the bone resorption rate and depressed the formation rate. 1,25-(OH)2D3 increased trabecular resorption surfaces; osteoid surface, volume, and thickness; mineralization lag time; and osteoblast number but decreased the bone volume. Multiple small daily doses of PTH resulted in an overall negative balance in trabecular bone. This was associated with an increased trabecular surface-to-volume ratio, bone resorption and formation rates, active forming surfaces, osteoid volume and surface, life span of bone forming and resorbing sites, and the number of osteoclast nuclei. Thyroxine appeared to increase bone mass by enhancing the switch-over from the resorptive to the formative phase of remodeling. Coupling between osteoid apposition and mineralization was increased by recruiting more forming sites and prolonging their life span. Thyroxine increased bone resorption and formation rates, trabecular bone volume and balance, number of osteoclast nuclei, and life span of bone forming sites. The osteoid seam thickness and mineralization lag time were decreased. The present study demonstrated that 1,25-(OH)2D3, PTH, and thyroxine at the dose and schedule used, markedly altered stimulators of remodeling in trabecular bone of adult dogs.

Animals↗
PubMed1981

Induced lymphocytic thyroiditis in dogs: effect of intrathyroidal injection of thyroid autoantibodies.

Multifocal infiltrations of lymphocytes and macrophages were present in the thyroid glands of dogs 1 month after an intrathyroidal injection (0.5 ml) of canine serum containing thyroglobulin autoantibodies. The development of thyroiditis was associated with a gradual increase in the incorporation of tritiated thymidine by the peripheral blood mononuclear cells. There was no alteration in circulating thyroid hormone values or thyroglobulin autoantibody titer for 1 month. Control dogs given a similar volume of canine serum without thyroglobulin antibodies did not have an inflammatory reaction in the thyroid gland, and the phytomitogen responses of lymphocytes did not change, compared with base-line values. An intrathyroidal injection of canine thyroglobulin autoantibodies induced lesions similar to naturally occurring lymphocytic thyroiditis in dogs, indicating that thyroid autoantibodies have an important role in the pathogenesis of immune-mediated thyroiditis.

Animals↗
PubMed1981

Effects of thyroxine on cortical bone remodeling in adult dogs: a histomorphometric study.

The effects of thyroxine on cortical bone remodeling were studied under conditions of normal and accelerated remodeling induced by surgical elevation of the periosteum. Six adult female beagle dogs were administered orally 1.0 mg of L-thyroxine per kg body weight daily for 60 days. Static and dynamic changes were evaluated using tetracycline and DCAF (2,4-bis-N,N'-dicarboxymethyl aminomethyl fluorescein) in vivo double labeling of rib specimens taken before treatment and after 60 days. Thyroxine administered in moderate pharmacologic doses increased the activation frequency, number of bone-forming and -resorbing sites, and the osteoid seam circumference in unaltered bone. Thyroxine, by activating skeletal remodeling, increased bone turnover and both formation and resorption at the tissue level. In ribs with periosteal elevation and accelerated remodeling, thyroxine increased the activation frequency, number of bone resorption and formation sites, and ratio of bone resorptive-to-formative surfaces. In addition, thyroxine under these conditions resulted in an increase in the osteoid seam circumference, radial closure rate, and bone formation rate at the tissue level but decreased the osteon formation time. Under conditions of accelerated remodeling, thyroxine increased osteoblastic and resorptive activity to a greater degree than in unaltered bone and resulted in bone changes similar to that described in human beings with thyrotoxicosis. The increased serum calcium and phosphorus levels and urinary hydroxyproline excretion at several intervals during thyroxine administration were consistent with the morphometric evidence of increased bone turnover and resorption. These findings suggest that thyroxine is a potent activator of skeletal remodeling under conditions of both normal and accelerated remodeling.

Animals↗
PubMed1981

Histomorphometric evaluation of the effects of low dose parathyroid hormone administration on cortical bone remodeling in adult dogs.

The effects of low dose levels of parathyroid hormone (PTH) on cortical bone remodeling of adult dogs were evaluated under conditions of normal turnover and accelerated remodeling produced by periosteal elevation. Six female dogs were administered PTH (2.5 units per kg. per day) intravenously in equally divided doses 6 hours apart for 60 days. The level and dose schedule of PTH used in this study resulted in a significant elevation in blood calcium above baseline values only at experimental day 5, no change in serum phosphorus and magnesium, and a transient increase in urinary hydroxyproline excretion on day 10. Accelerated cortical bone remodeling was induced by surgical elevation of periosteum of the 9th rib prior to PTH administration. Static and dynamic bone changes were analyzed using histomorphometric methods following tetracycline and DCAF ((2,4 bis) N, N'-di-(Carboxymethyl) aminomethyl fluorescein) in vivo double labeling. The results of this study suggested that the response of cortical bone to PTH was dependent upon the existing remodeling rate. PTH increased the radial closure rate and decreased the osteon formation time in unaltered cortical bone. These findings suggested that the initial anabolic effect of PTH may be due to increased bone formation at the osteoblastic level in existing Haversian units. In ribs with periosteal elevation, PTH decreased the circumference and thickness of osteoid seams, and there was a trend toward prolonged osteon formation time. The number of bone resorption sites was greater than the number of formation sites. PTH administration did not significantly change activation frequency or remodeling in cortical bone of adult dogs under conditions of normal turnover or accelerated remodeling. The accelerated remodeling produced by periosteal elevation appeared to mask certain responses to cortical bone to low dose levels of PTH.

Age Factors↗
PubMed1981

Lymphocytic thyroiditis in dogs; induction with a local graft-versus-host reaction.

Fifty million allogeneic canine lymphocytes were injected in the left lobe of the thyroid gland of 10 dogs. The left lobe of the gland was surgically removed at 1 and 4 weeks after injection. The intrathyroidal injection of immunocompetent cells resulted in local graft vs host reaction within the thyroid gland. Multifocal infiltration of lymphocytes, plasma cells, and macrophages associated with scattered, isolated, or small groups of degenerated follicular cells were present in the follicular wall and colloid on day 7. Thyroidal lesions at 1 month after injection were characterized by extensive destruction of follicular cells, disseminated foci of mononuclear cell infiltration, and electrondense deposits between follicular cells and the basement membrane. The contralateral (noninjected) lobe of the thyroid gland at 4 weeks after injection was infiltrated by lymphocytes, macrophages, and many plasma cells. The inflammatory lesions were associated with multifocal areas of degeneration of follicular cells and focal electron-dense thickenings of the basement membrane. The noninjected lobe, following hemithyroidectomy at 1 week after injection of the thyroid gland undergoing graft-vs-host reaction, either had a focal infiltration of polymorphonuclear leukocytes, lymphocytes, macrophages, and mast cells or had no significant lesions.

Animals↗
PubMed1980

Chemically induced (streptozotocin-alloxan) diabetes mellitus in the dog. Biochemical and ultrastructural studies.

Adult beagle dogs were infused intravenously with alloxan (50 mg/kg) and streptozotocin (30 mg/kg) in order to investigate sequential changes in plasma glucose, insulin, glucagon, and cortisol. These biochemical findings were correlated with ultrastructural alterations in pancreatic islets. Following infusion, the dogs became hyperglycemic by 2 hours, severely hypoglycemic by 6 to 14 hours, and permanently hyperglycemic by 24 hours. Plasma immunoreactive insulin increased sharply from 6 to 10 hours, then declined to nearly undetectable levels by 24 hours. Ultrastructurally, beta cells at 2 hours had clumped nuclear chromatin, vacuolated mitochondria, and dilated individual profiles of endoplasmic reticulum. Secretory granules appeared swollen but retained their internal cores. Degeneration of beta cells was severe after 10 hours, and plasma membranes of beta cells were disrupted by 24 hours. The cytoplasmic area of adjacent beta cells coalesced and had accumulations of membranous debris, lipofuscin, and autophagic vacuoles. Alpha and delta cells appeared to be unaffected. Plasma glucagon levels decreased markedly at 10 hours and were related reciprocally to changes in plasma insulin. Pancreatic islets in dogs with chronic (16 months) diabetes were small and composed primarily of granulated alpha and delta cells. Poorly granulated beta cells with degenerative changes were present in an occasional islet. The results of this investigation demonstrated that the combined administration of a single dose of alloxan and streptozotocin selectively destroyed the beta cells, while alpha and delta cells of the islets of Langerhans remained unaltered. Pathologic evidence of toxicity was not present in other organs. Chemically induced diabetes mellitus in dogs is a reproducible animal model that should prove useful in studies requiring repeated experimental manipulations or sampling of biologic fluids in order to evaluate the long-term effects of different routes of delivery or preparations of insulin to control the persistent hyperglycemia.

Alloxan↗
PubMed1980

Fine structural lesions and hormonal alterations in thyroid glands of perinatal rats exposed in utero and by the milk to polychlorinated biphenyls.

Polychlorinated biphenyls (PCB) produced ultrastructural lesions of thyroid follicular cells and a reduction in serum levels of thyroid hormones in neonatal (0, 7, 14, and 21 days of age) Osborne-Mendel rats exposed to 50 or 500 ppm PCB in utero and by the milk. Litter size was decreased significantly in rats fed 500 ppm PCB. Body weights at 21 days of age were reduced in rats exposed to 50 and 500 ppm PCB. The ultrastructural lesions in follicular cells were dose- and age-dependent but were less extensive than in adult rats of the same strain. At all ages the lesions in thyroid follicular cells were characterized by increased development of rough endoplasmic reticulum and vacuolization of mitochondria. There was an increase of colloid droplets and lysosomes in the older age groups (14 and 21 days) but little evidence for colloid droplet-lysosome interaction necessary for the secretion of thyroid hormones. Shortening of microvilli, with the formation of club-shaped or branching forms, was observed only in 21-day-old rat pups. These ultrastructural alterations in follicular cells exposed to PCB were associated with a significant reduction in serum thyroxine in the rats at birth and at 7, 14, and 21 days of age. Serum triiodothyronine was reduced significantly in 7- and 14-day-old rat pups. The ultrastructural alterations in follicular cells appeared to contribute to the significant lowering of serum thyroid hormone levels in 14- and 21-day-old rats exposed to PCB. These findings suggest that alterations in thyroid structure and function may be important in the pathogenesis of certain metabolic disorders associated with PCB intoxication.

Age Factors↗
PubMed1980

Biochemical and immunological investigations on hypothyroidism in dogs.

Circulating antibody titers (1:20 to 1:2560) against thyroglobulin were demonstrated in 48% of pet dogs with hypothyroidism by the chromic chloride passive hemagglutination test. Four of six dogs with acanthosis nigricans (1:20) and one of six male dogs with hyperestrogenism (1:40) had low titers of antibody against thyroglobulin whereas clinically normal pet dogs and dogs with other selected endocrinopathies (hypoadrenocorticism, cortisol-excess, diabetes mellitus) or obesity were consistently negative. Circulating immune complexes evaluated by the mastocytoma cell-assay were present in the sera of 20% of pet dogs with hypothyroidism but were absent in clinically normal dogs. Although variations in dose significantly altered the quantitative response of the thyroid gland to thyrotropin the qualitative pattern of response was similar for T3 but not T4 in clinically normal laboratory beagles. The peak increases for serum triiodothyronine and thyroxine were observed either at eight (0.1 and 0.2 I.U bTSH/5 lbs) or 12 (1.0 I.U. bTYSH/5 lbs) hours postthyrotropin. Dogs with naturally occurring hypothyroidism had a decreased serum T3 and T4 at baseline and eight hours postthyrotropin (1.0 I.U. bTSH/5 lbs) compared to clinically normal pet dogs, laboratory beagles and dogs with other clinical endocrinopathies. The consistent lack of a significant increase of serum T3 and T4 in response to thyrotropin was necessary for the separation of certain hypothyroid from euthyroid pet dogs in which the baseline level of thyroid hormones were equivocal.

Animals↗
PubMed1979

Morphometric analysis of skeletal response to vitamin D in uremic rats fed a low calcium diet.

The response of tibial metaphyses to pharmacologic levels of vitamin D in uremic rats fed a low calcium diet was evaluated morphometrically. Uremic (5/6 nephrectomized) rats given vitamin D had increased percent metaphyseal hard tissue, trabecular surface perimeter and percent trabecular osteoid surface and reduced numbers of osteoblasts and osteoclasts per millimeter of trabecular perimeter compared to either uremic rats given placebo or sham-operated rats given vitamin D. It was concluded that the resistance of metaphyseal trabeculae in uremic rats to vitamin D was due in part to the increase in osteoid-covered surfaces which inhibited osteoclasis and subsequent remodeling. The pathogenesis of worsening osteomalacia as a consequence of vitamin D administration to uremic rats on a low calcium diet remains unclear.

Animals↗
PubMed1979

Morphologic variations and aging in the atrioventricular conduction system of large breed dogs.

The microscopic anatomy of the atrioventricular node, bundle of His, both bundle branches and surrounding fibrous cardiac skeleton was studied in 40 large breed dogs of various ages. In the AV conduction system of all dogs over five years of age there was an increase of fibrous connective tissue, an infiltration of adipose tissue, loss of conduction fibers and focal fibrosis extending from the central fibrous body. Fibrosis was seen in the summit of the interventricular septum posterior to the AV node in dogs of all ages. Chondroid metaplasia was consistently observed in the central fibrous body and the root of the aorta in large breed dogs, including ten Doberman Pinschers of all ages. This metaplasia varied from a few chondroblasts and chondrocytes to mature chondrocytes with mineralization. Bone formation was seen in eight dogs. These changes appeared in close approximation to the cardiac conduction system above the bundle of His. No degenerative changes were seen in the AV bundle. Approximately one-half of the large breed dogs five years of age and older had thickened medial and intima proliferation in the small coronary arterioles supplying the AV node. The results of this study suggest that the presence of cartilage and bone in the central fibrous body is a normal occurrence in large breed dogs at all ages.

Aging↗