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Biomedical subjects

C C Capen

Publications and source records attributed to C C Capen.

At least 109 records · Page 6Linked to original sources
PubMed1986

Effects of mithramycin on transplantable canine perianal gland carcinoma (CAC-9) in nude mice: biochemical, histomorphometric, and ultrastructural investigations.

A serially transplantable perianal gland carcinoma (CAC-9) was developed in nude mice from a hypercalcemic dog that has been maintained through passage 20. Tumor doubling rate of CAC-9 was 3.1 +/- 0.4 days. Mithramycin (MMC) injected intraperitoneally (8 mg/kg) into nude mice bearing CAC-9 markedly decreased the tumor volume 2 weeks post-injection. MMC returned the elevated serum and urine calcium levels in mice with CAC-9 back to similar values as controls. The few remaining viable tumor cells after MMC were large and had numerous aggregations of intermediate filaments that displaced cytoplasmic organelles. Histomorphometric evaluation of lumbar vertebrae reveled no significant differences in bone resorption of nude mice bearing CAC-9 compared to saline-treated controls. This rapidly growing tumor line in nude mice associated with mild hypercalcemia will be a useful animal model to evaluate combinations of chemotherapy for cancer-associated hypercalcemia.

Anal Gland Neoplasms↗
PubMed1986

Humoral hypercalcemia of malignancy in nude mouse model of a canine adenocarcinoma derived from apocrine glands of the anal sac. Biochemical, histomorphometric, and ultrastructural studies.

A serially transplantable tumor line, designated CAC-8, has been developed in nude mice from a spontaneously occurring adenocarcinoma of the anal sac from a hypercalcemic dog. Nude mice with transplanted CAC-8 developed hypercalcemia (mean 16.3 +/- 0.6 mg/dl) and moderate hypophosphatemia without bone metastasis. Urinary excretion of calcium and hydroxyproline were increased 6- and 2.3-fold, respectively. Urinary excretion of cAMP was moderately increased but phosphorus excretion was not significantly altered. Serum 1,25-dihydroxycholecalciferol was increased significantly in tumor-bearing nude mice in proportion to the magnitude of tumor-induced hypercalcemia. Histomorphometric evaluation of lumbar vertebrae from nude mice with CAC-8 revealed decreased total and cortical bone volume, a 3.3-fold increase in bone resorption rate and a 2.5-fold increase in bone formation rate at the tissue level. The transplanted CAC-8 has maintained the histologic pattern of the original carcinoma up to the present sixth passage. Ultrastructural evaluation of transplanted tumor cells revealed 150-250-nm secretory-like granules. The granules did not stain by using an ultrastructural cytochemical (uranaffin) stain specific for neuroendocrine secretory granules. Ultrastructurally, the parathyroid glands of nude mice with CAC-8 appeared inactive with large intracytoplasmic whorl of agranular membranes. These data suggest the transplanted carcinoma secreted a humoral factor which resulted in hypercalcemia. The tumor line (CAC-8) propagated in nude mice represents an animal model of humoral hypercalcemia of malignancy that shares many features with the syndrome described in human patients. Unique features of this transplanted carcinoma associated with hypercalcemia include increased serum dihydroxycholecalciferol, increased rate of bone formation as well as bone resorption, an absence of bone metastases, and evidence of parathyroid gland suppression.

Adenocarcinoma↗
PubMed1985

Structural and functional properties of adult rat heart myocytes lysed with digitonin.

Low concentrations of digitonin disrupt the sarcolemma of adult rat heart myocytes selectively and completely. When the digitonin lysis is carried out in the presence of 10 mM Mg-ATP, the permeabilized cells retain the rod-cell morphology typical of heart cells in situ and show spontaneous phasic contractions. The rate of contraction is a function of the free Ca2+ concentration from a pCa of 7.2 to 5.2. Higher levels of free Ca2+ result in hypercontracture of the myocytes into round cells with characteristically distorted morphology. The sarcoplasmic reticulum of digitonin-lysed myocytes takes up Ca2+ in an ATP-dependent reaction that is inhibited and reversed by caffeine and strongly enhanced by procaine or ruthenium red. The Ca2+ accumulation has a Km of 0.6 microM Ca2+, depends on Pi (Km of 13 mM), and is strongly inhibited by bicarbonate ion. The hypercontracture of digitonin-lysed myocytes is a function of both the pCa and the Mg-ATP concentration of the suspending medium. Hypercontracture requires ATP. Hypercontracture due to Ca2+ overload occurs at lower Ca2+ concentrations when Mg-ATP is decreased from 10 to 1 mM. However, at low concentrations of Mg-ATP (in the range from 1 to 10 microM), hypercontracture also occurs and is essentially Ca2+-independent. Since hypercontracture of heart myocytes appears analogous to the formation of contraction bands in situ, these observations may be relevant to the phenomena of oxygen paradox and of Ca2+ paradox in intact myocardial tissue.

Adenosine Triphosphate↗
PubMed1985

Mitochondrial enzyme retention by irreversibly damaged rectangular isolated adult rat heart myocytes.

A one hour hypoxic incubation causes the release of a small but significant amount of cytosolic lactic dehydrogenase from glucose-deprived isolated adult rat heart myocytes. However, enzymes associated with the mitochondria are not liberated, and there is no increase in the number of hypercontracted cells. These observations led Piper et al. (Life Sciences 35, 127-134 [1984]) to conclude that reversibly injured myocytes can release cytosolic proteins. This conclusion was based on the supposition that irreversibly hypoxic injury must cause mitochondrial enzyme efflux and hypercontracture. The present study establishes that this supposition is invalid.

Adenosine Triphosphate↗
PubMed1985

Testicular (Sertoli's cell)-like tumors of the ovary induced by N-ethyl-N-nitrosourea (ENU) in rats.

N-ethyl-N-nitrosourea (ENU) administered intraperitoneally or transplacentally to Sprague-Dawley (CD) and BD-IV (Berlin Druckrey IV) rats increased the incidence (26.6%) of an uncommon ovarian tumor with testicular characteristics compared either to controls (3.0%) or rats administered diethylnitrosamine (3.3%). The induced tumors were composed of tubular structures that resembled seminiferous tubules lined by Sertoli's-like cells. The abundant electron-lucent cytoplasm of the tumor cells contained polyribosomes, lipid bodies, and mitochondria but few additional organelles. Sertoli's cell-like tumors appeared to develop from the ovarian stroma in the hilar region of the ovary. They usually were benign and resulted in unilateral enlargement of the ovary. The mean serum concentrations of testosterone, estrone, and estradiol in selected rats with ovarian tumors were elevated above mean serum values in controls. There was not a consistent direct correlation between tumor diameter and circulating hormone level. Ethyl nitrosourea-induced ovarian tumors composed of testicular (Sertoli's-like) cells will provide a reproducible animal model to investigate the histogenesis and hormone secreting properties of this unique gonadal neoplasm.

Animals↗
PubMed1984

The effect of nerve growth factor and antibodies to nerve growth factor on ethylnitrosourea-induced neoplastic proliferation in rat trigeminal nerves.

Sprague-Dawley (CD) rats were injected intravenously with ethylnitrosourea at a dose of 20 mg/kg on day 20 of gestation. This exposure resulted in early neoplastic proliferation or development of a neurinoma of the trigeminal nerve in 58% of the offspring at 90 days of age. Implantation of osmotic microinfusion pumps containing 2.5S nerve growth factor prior to ethylnitrosourea administration significantly reduced the incidence of early neoplastic proliferation. Postnatal implantation of microinfusion pumps containing 2.5S nerve growth factor also resulted in a significant but less pronounced reduction of early neoplastic proliferation. Immunoglobulin G directed against nerve growth factor (anti-nerve growth factor) did not influence the incidence of early neoplastic proliferation when administered via microinfusion pumps implanted on day 15 postnatally. These findings suggest that nerve growth factor has a protective effect on the developing nervous system against ethylnitrosourea-induced carcinogenesis.

Animals↗
PubMed1984

Syncytial cells in canine parathyroid glands.

Multinucleated syncytial cells consisting of clusters of closely apposed, darkly staining nuclei and densely eosinophilic cytoplasm were present in parathyroid glands from 25 of 36 dogs (69%). They were most often located either peripherally in the parathyroid gland or adjacent to blood vessels. The numbers of nuclei per syncytial cell ranged from two to greater than 30. Syncytial cells had degenerative changes as suggested by vacuolated mitochondria, dilated rough endoplasmic reticulum, irregular nuclear outlines, and condensed nuclear chromatin. These ultrastructural changes contrasted sharply with adjacent chief cells that had well-preserved organelles. The presence of desmosomes and fragments of cell membranes between nuclei suggested that syncytial cells were derived from fusion of adjacent chief cells rather than nuclear division without cytokinesis. Syncytial cells were present in normal, hyperplastic, and inactive parathyroid glands from dogs. There were no significant correlations between the presence of multinucleated cells and age of dog, parathyroid histology, and changes in the concentrations of serum calcium, phosphorus, creatinine, or plasma parathyroid hormone. Syncytial cells occurred frequently in canine parathyroid glands regardless of the state of activity of the gland or the concentration of plasma parathyroid hormone or serum calcium.

Animals↗
PubMed1984

Histological and ultrastructural evaluation of cardiac lesions in idiopathic cardiomyopathy in dogs.

Described are pathological studies of eight dogs which died in congestive heart failure, with a clinical diagnosis of congestive cardiomyopathy. Examination revealed marked dilatation and enlargement of all four chambers of the heart. The ventricular walls were thin with small atrophic papillary muscles. Histological studies on the myocardium revealed scattered areas of myocardial necrosis, especially around the papillary muscles of the left ventricle and random scattered areas of fibrosis. Electron microscopic studies revealed fewer and disoriented myofibrils, myocytolysis, increased numbers of mitochondria with swelling and inclusions, increased glycogen granules and increased numbers of lysosomes, lipofuscin granules and lipid droplets. Mild Z-band abnormalities were found throughout the myofibers.

Animals↗
PubMed1983

Immunocytochemical demonstration of insulin in spontaneous pancreatic islet cell tumors of Fischer rats.

Nineteen spontaneous pancreatic islet cell tumors were studied in 26-month-old control Fischer 344 rats. Seventeen of 19 (89%) tumors demonstrated insulin reactivity using peroxidase-antiperoxidase immunocytochemistry. None of ten tumors had positive glucagon immunoreactivity. Immunocytochemical and ultrastructural observations suggested that spontaneous occurring islet cell tumors of F344 rats were composed exclusively of beta cells.

Adenoma, Islet Cell↗
PubMed1983

Hypercalcemia in dogs with adenocarcinoma derived from apocrine glands of the anal sac. Biochemical and histomorphometric investigations.

Hypercalcemia, hypercalciuria, and hyperphosphaturia were present in female dogs with adenocarcinomas derived from apocrine glands of the anal sac (CA). Remission of hypercalcemia accompanied tumor excision in all six dogs undergoing surgery, whereas tumor recurrence or growth of metastases was associated with a return of hypercalcemia. Preoperatively, the plasma concentrations of immunoreactive parathyroid hormone in all dogs were undetectable or in the low normal range. Plasma concentrations of 13,14-dihydro-15-keto-prostaglandin E2 (PGE2M) and serum 1,25-dihydroxyvitamin D were not significantly different from control dogs. Urinary cyclic AMP and hydroxyproline were increased in dogs with CA. No immunoreactive parathyroid hormone was detected in extracts from tumor tissue, and parathyroid glands from dogs with CA had ultrastructural characteristics of secretory inactivity. Lumbar vertebrae from hypercalcemic dogs had decreased trabecular bone volume and increased osteoclastic bone resorption compared with age-matched control dogs. After tumor excision, serum total calcium returned to the normal range, whereas immunoreactive parathyroid hormone increased 2- to 20-fold and 1,25-dihydroxyvitamin D decreased 2- to 8-fold. Postoperative hypocalcemia was not observed. These results indicate that CA produces a hypercalcemic factor other than immunoreactive parathyroid hormone or prostaglandin E2 that increases osteoclastic osteolysis distant from the tumor and results in hypercalcemia, hypercalciuria, and hyperphosphaturia.

Adenocarcinoma↗
PubMed1983

Hypercalcemia in dogs with lymphosarcoma. Biochemical, ultrastructural, and histomorphometric investigations.

Dogs with lymphosarcoma and hypercalcemia had decreased trabecular bone volume and increased osteoclastic osteolysis, whereas dogs with lymphosarcoma that were normocalcemic did not have increased bone resorption. Increased osteoclastic resorption was present only in bone from hypercalcemic dogs that contained neoplastic tissue but not in bone free of tumors, suggesting that the factor(s) responsible for stimulating bone resorption were elaborated locally by the tumor tissue. Hypercalcemic dogs with lymphosarcoma had decreased concentrations of plasma immunoreactive parathyroid hormone and serum 1,25-(OH)2D compared with normocalcemic dogs with lymphosarcoma and control dogs with and without other neoplasms. Immunoreactive parathyroid hormone was not detected in lymphosarcoma tissue. The plasma concentration of 13,14-dihydro-15-keto-prostaglandin E2 (PGE2M) was increased approximately 2-fold in hypercalcemic dogs with lymphosarcoma as compared with other groups. Urine excretion of calcium, phosphorus, and hydroxyproline were increased in hypercalcemic dogs with lymphosarcoma. Ultrastructurally, lymphosarcomas were composed of tumor cells with large nuclei and a paucity of cytoplasmic organelles. Light and electron microscopic examination of parathyroid glands revealed inactive or atrophic chief cells in dogs with lymphosarcoma and hypercalcemia. The increased osteoclastic bone resorption in hypercalcemic dogs with lymphosarcoma was not mediated by increased circulating levels of immunoreactive parathyroid hormone and 1,25-(OH)2D but was dependent upon infiltration of bone marrow by neoplastic cells and, presumably, the local production of a bone resorption-stimulating factor.

Animals↗
PubMed1983

Characterization of N-ethyl-N-nitrosourea--induced mammary tumors in the rat.

A single intraperitoneal inoculation of 180 mg/kg N-ethyl-N-nitrosourea (ENU) into 30-day-old outbred Sprague-Dawley (CD) rats resulted in an 90% incidence of mammary tumors (MTs) after an average latent period of 93 days, with an 85% rate of malignancy. The incidence, induction period, number of tumors per rats, and the rate of malignancy were reduced in rats ovariectomized prior to or shortly after (5 days) ENU exposure. Over 70% of the ENU-induced MTs regressed following ovarioectomy. The malignant MTs developed from nodules located in the terminal end buds (TEB), which are believed to contain the most susceptible cell population for chemical carcinogens. The serum calcium was elevated above control values in 92% of intact rats evaluated with MTs in the absence of bone metastases. No correlation was demonstrated between the volume of MTs or total number of MTs and the serum calcium level. The ENU-induced MT is a reproducible animal model that can be used in the investigation of the early changes in mammary cells (especially TEB) and the interrelationships between the carcinogen and ovarian hormones associated with neoplastic transformation.

Adenofibroma↗
PubMed1982

Relationship of serum total calcium to albumin and total protein in dogs.

A positive linear relationship was found between total calcium and albumin and between total calcium and total protein in the serum of 209 dogs. Total calcium concentration correlated with the concentration of albumin (r = 0.575; P less than 0.001) and with the concentration of total protein (r = 0.411; P less than 0.001). A correction formula for calcium was derived on the basis of the concentration of albumin: adjusted calcium (mg/dl) = calcium (mg/dl) - albumin (g/dl) + 3.5. The correction formula for calcium, based on the concentration of serum total protein was: adjusted calcium (mg/dl) = calcium (mg/dl) - 0.4 [total serum protein (g/dl)] + 3.3. Hypocalcemia (less than or equal to 8.7 mg/dl) was detected in 32 of the dogs. After adjustment of the measured total calcium for albumin and serum total protein, 29 (91%) of the dogs had calcium concentrations within the normal range. Hypercalcemia was not associated with hyperalbuminemia or hyperproteinemia. In 91% of dogs with disorders of calcium metabolism and in 86% of dogs less than 6 months old, calcium concentrations were outside the 95% confidence intervals for albumin and total protein calculated from the 209 dogs. It was concluded that adjustment of serum total calcium for protein concentration is essential for correct interpretation of calcium values and detection of abnormalities in calcium metabolism.

Animals↗
PubMed1982

Autoimmune lymphocytic thyroiditis in dogs.

Primary diseases of the thyroid gland, especially lymphocytic thyroiditis and idiopathic follicular atrophy, were the most common lesions associated with clinical hypothyroidism in pet dogs. Lymphocytic thyroiditis resembled naturally occurring lymphocytic thyroiditis in the Obese-strain of White Leghorn chickens and Hashimoto's thyroiditis in man. The morphology of the thyroid lesion and frequent occurrence of circulating thyroglobulin autoantibodies suggested that lymphocytic thyroiditis was immune-mediated in pet dogs. Thyroid lesions similar to naturally occurring autoimmune thyroiditis in experimental dogs were induced by a local thyroidal graft-versus-host reaction. The lesions observed in the thyroid lobe which was not injected with immunocompetent cells appeared to develop from the formation of thyroid antibodies in the gland by migrating host lymphocytes. Autoimmune lymphocytic thyroiditis occurred secondary to an unrelated immune response occurring in target tissue.

Animals↗
PubMed1982

Multiparametric evaluation of the toxic responses of normal human cells treated in vitro with different classes of environmental toxicants.

Eight compounds representing three classes of chemicals were evaluated for their toxic effects on normal neonatal human foreskin fibroblasts in vitro. A battery of toxicity assays was employed to measure the effects of the chemicals on cell viability, DNA synthesis, protein synthesis, DNA repair synthesis, cell ultrastructure, membrane-bound and soluble cytoplasmic proteins, and the activities of six enzymes: beta-glucuronidase, acid phosphatase, gamma-glutamyl transpeptidase, alkaline phosphatase, 5'mononucleotidase, and calcium-magnesium activated (Na+,K+)-dependent ATPase. The compounds evaluated included two antibiotics, each with a metabolic derivative-sulfamethazine (SMZ) and acetylsulfamethazine (ASZ), and carbadox (CBX) and desoxycarbadox (DCX); two anthelmintics-haloxon (HAL) and sansalid (SAN); and a steroid with a metabolic derivative, 17 alpha-estradiol (17-AE) and 17 alpha-estradiol-17-beta-D-glucoside (AE-G). Compounds with similar biological functions often elicited different patterns of response in the normal fibroblasts. For example, the two anthelmintics, HAL and SAN, were similar to each other in that they induced 50% relative cloning efficiencies (EC50) at approximately the same concentrations (HAL = 52 microgram/ml, SAN = 58 microgram/ml), and neither inhibited protein synthesis. They differed, however, in their effects of DNA synthesis. SAN did not inhibit DAN synthesis, while HAL was a profound inhibitor of DNA synthesis (98% inhibition after 4 h at 100 microgram/ml). Because the various toxicants elicited such a variety of response patterns as measured by a multiplicity of parameters, we conclude that similarities in survival responses of cells to closely related toxicants may arise frequently through toxic action at different sites within the cells.

Anthelmintics↗
PubMed1982

Ultrastructural evaluation of adenocarcinomas derived from apocrine glands of the anal sac associated with hypercalcemia in dogs.

Adenocarcinomas derived from apocrine glands of the anal sac and associated with persistent hypercalcemia in dogs were composed of tumor cells with numerous profiles of rough endoplasmic reticulum, clusters of free ribosomes, and a prominent Golgi apparatus. Neoplastic cells contained microtubules, microfilaments, tonofibrils, and had two types of electron-dense granules. Large lysosomelike dense bodies ranged from 0.6 to 2.2 microns in diameter and had a poorly delineated limiting membrane. Small granules (150-400 nm in diameter) had a sharply delineated limiting membrane with a narrow submembranous space and a homogeneous dense core. These smaller granules usually were located near the apexes of neoplastic cells, whereas the larger granules were situated near the base of cells. Apocrine cells in glands of the anal sac from control dogs that were in the secretory phase were columnar and had large dilated profiles of rough endoplasmic reticulum. Membranes of the endoplasmic reticulum fused with the plasmalemma and appeared to secrete their product directly into the lumens of acini, characteristic of merocrine secretion. Apical blebs of electron-lucent cytoplasm pinched off from nonneoplastic aprocine cells and were released into glandular lumens. Similar electron-lucent cytoplasmic blebs were present at the apexes of tumor cells. Myoepithelial cells were present between the epithelial cells and basement membrane in normal apocrine glands and were absent in neoplasms derived from these glands. Identification of the contents of the secretory-like granules in tumor cells and characterization of the hypercalcemic factor in the plasma or tumor tissue from dogs with this syndrome will help explain the pathogenesis of hypercalcemia associated with malignancy in animals and man.

Adenocarcinoma↗
PubMed1981

Histologic and ultrastructural evaluation of thyroid lesions associated with hypothyroidism in dogs.

Thyroid lesions in 16 pet dogs with hypothyroidism were evaluated by light and electron microscopy. Lymphocytic thyroiditis, found in seven dogs, was characterized by diffuse infiltration of the thyroid gland by lymphocytes, plasma cells and macrophages with formation of some lymphoid nodules and destruction of follicles, progressing to replacement of most of the thyroid by fibrous connective tissue. The basement membrane around follicles was thick and had electron-dense deposits. The morphology of the thyroid lesions and the presence of circulating thyroglobulin autoantibodies suggested that lymphocytic thyroiditis was immune-mediated. Idiopathic follicular atrophy, found in nine dogs, was characterized by loss of thyroid parenchyma and replacement by adipose connective tissue. Degeneration of individual follicular cells was present in the early stage, with exfoliation into the colloid and interfollicular area. Most of the thyroid gland consisted of adipose connective tissue with either interspersed small follicles or individual follicular cells that had dilated rough endoplasmic reticulum, large Golgi apparatus, and intracytoplasmic microfollicles in the advanced stage. Follicular atrophy was a degenerative lesion of follicular cells of unknown cause, not associated with inflammatory destruction in the thyroid gland.

Animals↗