PubMed Health⌕ Search

Biomedical subjects

J M Strum

Publications and source records attributed to J M Strum.

At least 37 records · Page 2Linked to original sources

Angiogenic responses elicited from chorioallantoic membrane vessels by neoplastic, preneoplastic, and normal mammary tissues from GR mice.

Neoplastic tumors are able to elicit the ingrowth of new capillaries, a process known as angiogenesis. The chorioallantoic membrane (CAM) of chicken embryos was used in an assay for this response, and normal mammary glands and various mammary growths from GR mice, including plaques, hyperplasic alveolar nodules, and hormone-dependent and hormone-independent tumors were tested. Fifteen percent of the male mammary glands tested were positive, as were 28% of the resting female mammary glands. Fifty percent of the plaques and 63% of the hyperplastic alveolar nodules tested induced neovascularization. Eighty percent of the hormone-dependent tumors and 97% of the hormone-independent tumors tested elicited angiogenesis. A fine-structural study revealed that capillaries invaded to within less than 0.5 microns of the tumor cells, but no penetration of tumor cells through the basal lamina was observed. Positive responses were directly correlated with the neoplastic potential of the tissues tested, indicating that angiogenesis can predict mammary gland growths most likely to become malignant.

Allantois↗

Autoradiographic evidence of a loss of iodination within hormone-dependent GR mouse mammary tumors as they progress to independence.

The purpose of this study was to determine by use of light- and electron-microscope autoradiography whether or not iodination occurred in mammary tumors of female GR mice. Of the sixty tumors studied it was found that pregnancy-dependent and hormone-induced tumors possessed iodinating ability. Although mammary glands from nonpregnant GR mice lacked the ability to iodinate, by the 16th day of pregnancy in response to hormonal stimulation the glands readily iodinated casein, and some epithelial cells contained ultrastructural cytochemical evidence of mammary peroxidase. Preneoplastic mammary gland lesions known as hyperplastic alveolar nodules were also able to iodinate, as were plaques, the disc-shaped lesions which give rise to the hormone-responsive mammary tumors in this strain. Plaques also contained epithelial cells with mammary peroxidase activity. When hormone-induced mammary tumors were transplanted into syngeneic mice they retained the ability to iodinate for several generations. However, as the tumors progressed to hormone independence, the ability to iodinate was gradually lost. Hormone-independent mammary tumors from GR mice lacked both iodinating ability and cytochemical evidence of mammary peroxidase. These findings suggest that iodination depends upon hormone-responsive cells within the mammary tumors and that as these cells become hormone unresponsive, the ability to iodinate is lost.

Animals↗

Harderian glands in mice: fluorescence, peroxidase activity and fine structure.

The Harderian glands of albino mice are composed of tubulo-alveoli which contain two secretory cell types. The most common cell (type A) displayed a natural red fluorescence due to the presence of porphyrins. Lipid droplets in this cell and along its apical border were often intensely fluorescent. The less common cell (type B) did not fluoresce. The type B cell contained unusual lipid droplets surrounded by concentric layers of membranes, and sometimes displayed cylindrical organelles believed to be associated with the formation of pigment. A dense red-brown pigment was observed in the lumens of a few tubulo-alveoli and it did not fluoresce, but areas where pigment formation was taking place fluoresced brightly. Myoepithelial cells, containing thick and thin filaments, were found underlying both secretory cell types. Fenestrated capillaries and adrenergic and cholinergic nerve endings were abundant in the adjacent connective tissue. Endogenous peroxidase activity was identified in both secretory cell types and was found localized only within tubules and vesicles of the smooth endoplasmic reticulum.

Animals↗

Constant light exposure induces damage and squamous metaplasia in Harderian glands of albino mice.

Harderian glands from control albino mice kept in a cyclical light/dark environment had tubulo-alveoli comprised of lipid-filled glandular epithelial cells. The porphyrin content of the gland measured 122 microgram/100 mg gland. Constant light exposure for 24 hr caused exopthalmos grossly. Histologically most of the secretory cells were swollen and the lumens of many tubulo-alveoli were obliterated; a few areas of the gland showed damage. The porphyrin content had decreased to 116 microgram/100 mg gland. After 3 days of constant light exposure the tubulo-alveoli were markedly altered. Lipid and cellular debris filled the lumens, and lining cells were highly irregular, ranging in shape from columnar to squamous. The porphyrin content had decreased to 72 micro/100 mg gland and leukocytes and macrophages were abundant. Despite this extensive damage a number of tubulo-alveolar epithelial cells were observed under-going mitosis. After 7 days of constant exposure to light, some tubulo-alveolar epithelial cells had undergone squamous metaplasia, and the porphyrin content had dropped markedly to 50 microgram/100 gland. These pronounced cellular changes are believed to result from a direct effect of light on the gland.

Albinism↗

A method demonstrating motor endplates for light and electron microscopy.

The cytochemical localization of acetylcholinesterase activity at motor endplates is commonly employed prior to electron microscopic examination. Methods which involve the use of thiocholine esters often lead to a loss of resolution due to the spread to surrounding tissues of an extremely dense reaction product. A method is presented in which esterase positive sites are revealed by incubation with hexazotized pararosaniline and indoxyl acetate. The osmiophilic property of the reaction product which remains localized to the synaptic cleft allows speedy identification and detailed examination of the endplate at the ultrastructural level. An application of the procedure is also described.

Animals↗

Human breast epithelium in organ culture: effect of hormones on growth and morphology.

Normal breast tissue from a 17-year-old girl was grown in organ culture for 3 weeks. A comparison was made between the effects on the epithelium of a defined culture medium containing various combinations of hormones and serum-supplemented medium that has been used to successfully maintain other human tissues for 4 months routinely, and in some cases for up to 1 year. After culture for 3 weeks the explants were exposed to [3H]thymidine and autoradiographs were prepared and evaluated in order to determine labeling indexes. The only serum-free defined medium that permitted any significant survival or labeling of the cells contained insulin + hydroxycortisone + prolactin. However, serum-supplemented medium along gave an even higher labeling index, and this was elevated more in media containing either progesterone or other combinations of hormones. Our study indicates that normal human breast (removed at the early postovulatory stage of the menstrual cycle) can be maintained in a differentiated state for 12 days in serum-supplemented media. By 2 weeks the cells had begun to migrate onto the surface of the explant. They then began to accumulate tonofilaments so that after 3 weeks in culture nearly all of the cells contained tonofilaments. The one exception was found in breast tissue cultured in the presence of human chorionic gonadotropin, where the cells maintained differentiated characteristics, despite the fact that they contained many lysosomes.

Adolescent↗

Pale cell carcinoma: ultrastructure of a hormone-dependent mammary tumor in GR mice.

Pale cell carcinoma, a hormone-dependent mammary tumor in GR mice, consists mostly of islands of pale cells and dark cells, interrupted by a few areas containing keratinized cells. In this study the pale cells (electron-lucent), were arranged in bands adjacent to vascular spaces, while the dark cells, which produced mammary tumor virus, were clustered around lumens. A morphometric analysis revealed that pale cells were larger than dark cells and had other differences that indicated they were swollen. The areas having keratinized cells (or cells displaying squamous cell differentiation) resulted from a transformation of certain pale cells, perhaps in response to injury. The cells developed large desmosomes, accumulated tonofilaments, and sometimes displayed keratohyalin granules; and although most pale cells did not fully keratinize, a few did. Moreover, they remained within pale cell carcinomas that had regressed.

Animals↗

Structural alterations within N-nitrosomethylurea-induced mammary tumors after in vivo treatment with cis-hydroxyproline.

N-Nitrosomethylurea-induced mammary tumors in Buffalo rats were examined ultrastructurally and compared with tumors from rats treated in vivo for 9 days with cis-hydroxyproline (CHP). The tumors from untreated animals were heterogeneous histologically but often had their cells arranged in clusters called pseudolobules. At the periphery of the pseudolobules in control tumors, a few myoepithelial cells showed evidence of basal lamina secretion. Outlining the pseudolobules were many mast cells. Treatment with CHP inhibited the growth of the tumors. It increased the extent of atrophy and regression and also induced cyst-like areas to form within the pseudolobules. These "pseudocysts" were actually part of the stromal compartment and they sometimes contained multilayered basal lamina and mast cells. The extensive multilayering of the basal lamina observed after CHP-treatment was thought to arise from extensive infoldings as the pseudolobules "shrank" due to atrophy and loss of cells. The multilayering and cell debris disappeared from the pseudocysts, leaving many spaces bounded by myoepithelial cells. The remaining myoepithelial cells appeared atrophied, but often had an expanded rough endoplasmic reticulum. We did not observe evidence of basal lamina secretion by cells in treated tumors, which correlates with CHP's ability to block type IV collagen production.

Animals↗

N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder cancer in C57BL/6 X DBA/2 F1 mice as a useful model for study of chemoprevention of cancer with retinoids.

Highly invasive carcinomas of the urinary bladder were induced in male C57BL/6 X DBA/2 F1 (hereafter called B6D2F1) mice by gastric intubation of N-butyl-(4-hydroxybutyl)nitrosamine (OH-BBN) using a quantitative dosing schedule. Animals received either 5 or 10 mg OH-BBN per intubation, two times each week, for 9 weeks for a total dose of either 90 or 180 mg, and they were killed 6 months after the first carcinogen intubation. Seven days after the final intubation of OH-BBN, animals were fed either a placebo diet or diet supplemented with either 150 or 200 mg 13-cis-retinoic acid per kg of diet. A 41 and 43% incidence of urinary bladder cancer was observed in mice given the low and high dose of carcinogen, respectively, and fed a placebo diet. Sixty-seven % of the carcinomas induced in these animals invaded either into or through the urinary bladder wall. Varying degrees of transitional and either squamous or glandular or both squamous and glandular differentiation were observed in the carcinomas. Feeding of diet supplemented with 13-cis-retinoic acid reduced cancer incidence; the degree of reduction was proportional to the dose of retinoid administered. The highly invasive nature of the carcinomas induced by quantitative administration of OH-BBN in B6D2F1, mice provides a useful animal model of the highly invasive variant of human transitional cell urinary bladder cancer in which to study chemoprevention by retinoids as well as other compounds.

Animals↗

Effect of iodide-deficiency on rat mammary gland.

When rats are kept iodide-deficient, atrophy and necrosis takes place in the mammary gland and areas of dysplasia and atypia are seen. Administration of estradiol to iodide-deficient rats stimulates cell division in the gland and leads to the formation of alveoli. Continued stimulation by estradiol produces changes in the newly-formed alveolar cells. Their nucleoli are altered and show a separation of components. Ribosomes and lipid droplets increase and the cells synthesize large vacuoles containing protein. The secretion of great quantities of this material into areas of the tissue where regressive changes have occurred undoubtedly contributes to the formation of cysts within the gland. The present findings indicate that iodide-deficiency alters the structure and function of mammary gland alveolar cells and makes them highly sensitive to stimulation by estradiol.

Animals↗

Alterations within the rat thyroid gland during vitamin A deficiency.

Thyroid glands from female rats kept vitamin A deficient for one, two, and three months were examined by electron microscopy. After one month on the diet, no consistent alterations were noted. After two months, the colloid in some follicles displayed a peripheral zone of decreased density. In addition, ultimobranchial follicles within the gland had become keratinized. After two to three months on the diet, cells were seen entering the colloid. Many of these cells were identified as follicular cells since they often occurred in groups and occasionally exhibited remnants of desmosomes. Often the cells within the colloid appeared vacuolated, and by light microscopy were thought to contain lipid. However, electron microscopy revealed that these cells contained many digestive vacuoles rather than lipid droplets. Quantitative and autoradiographic studies indicated that thyroids of vitamin A deficient rats took up less radioiodide than thyroids of control rats. The keratinization of ultimorbranchial follicles in vitamin-A deficiency has been suggested as preliminary in the histogenesis of squamous cell carcinoma. However, an effect of vitamin A deficiency on thyroid follicular cells has not heretofore been reported. It's possible that the presence of follicular cells in the colloid reflects an accelerated turnover of these cells and could indicate an early pathological sign.

Acid Phosphatase↗

Analysis of mammary tumors for cytochemical evidence of endogenous mammary peroxidase.

The purpose of this study was to determine whether or not endogenous mammary peroxidase can serve as a cytochemical marker to distinguish ovarian hormone-dependent from ovarian hormone independent mammary tumors. Spontaneous mammary tumors arising in virgin C3H and GR mice (hormone independent tumors) and hormone-dependent mammary tumors arising during pregnancy in GR mice were examined. None of these tumors contained mammary peroxidase. Mammary tumors induced in Sprague-Dawley rats with methylnitrousourea (MNU) and dimethylbenzanthracene (DMBA) were also examined. These tumors included hormone-dependent and hormone independent ones. Several of the DMBA-induced hormone-dependent tumors contained a few peroxidase-positive cells, but the hormone independent tumors were negative. All of the MNU-induced tumors examined were negative for mammary peroxidase. Twenty human breast tumors (malignant and non-malignant) removed from women at surgery, were also negative for mammary peroxidase. Our results indicate that endogenous mammary peroxidase cannot be used to distinguish hormone-dependent from hormone independent mammary tumors.

9,10-Dimethyl-1,2-benzanthracene↗

A mammary gland whole mount technique that preserves cell fine structure for electron miscroscopy.

A mammary gland whole mount technique has been developed that preserves cell fine structure and makes it possible to also examine the preparations by electron microscopy. The glands are placed on glass microscope slides, fixed in a paraformaldehyde-glutaraldehyde mixture, defatted in acetone, stained with 0.5% methylene blue (or trypan blue) in saline, and dehydrated in ethanol. They are evaluated and photographed in 100% ethanol. Then specific areas (i.e. containing small growths, tumors, or other lesions) are selected, excised and prepared for electroscopy. The ultrastructural preservation is good, organelles are evident and there is no observable dye precipitate. The only unusual finding is that cell membranes display a "negative" image.

Animals↗

Estrogen-induced alterations in the myoepithelial cells of the rat mammary gland.

Estradiol benzoate was injected into virgin rats, at a concentration of 50 microgram/day, for 7 days. The animals were fixed by perfusion and the mammary glands prepared for electron microscopy. Many myoepithelial cells in the mammary glands were altered as a result of the estradiol treatment. The affected cells had a markedly reduced number of myofilaments that were restricted to a specific region of the cytoplasm. Large foot-like projections with many vesicles extended from the myoepithelial cells into the surrounding connective tissue. The altered cells also had more organelles, suggesting that their metabolic activity was increased. Nuclei in the altered cells had deep infoldings that may reflect an increase in nuclear/cytoplasmic exchanges. The results of this study indicate that estradiol causes specific morphological alterations in myoepithelial cells of the mammary gland.

Animals↗

Site of iodination in rat mammary gland.

The ability of the mammary gland to take up and organically bind radioiodide was studied in non-pregnant, pregnant, and lactating rats. Autoradiography was used to determine whether duct cells or alveolar cells are responsible for iodination in the rat mammary gland. Iodination was not detected in mammary glands from non-pregnant rats, but occurred late in the twelfth day of gestation and continued throughout pregnancy and lactation. Protein-containing vacuoles in alveolar cells and casein-like proteins in milk were the major sites where iodination occurred within the gland. Milk proteins in the lumens of ductules adjacent to alveoli were also iodinated. In contrast, ducts, myoepithelial cells, fat cells, blood vessels and other histological components of the gland did not show iodinating capability. Cytochemistry was also used to identify endogenous mammary peroxidase activity in the same glands, and it was found that the presence and location of this enzyme was correlated with the ability to iodinate.

Animals↗

Hormonal activation of mammary gland peroxidase.

Ultrastructural cytochemistry was used to detect an endogenous peroxidase in the rat mammary gland. The enzyme was identified only during the latter half of pregnancy and during lactation, indicating its possible dependence upon hormones. To test this hypothesis, specific hormones associated with the development and differentiation of the mammary gland were used both in vivo and in vitro in an effort to induce, or unmask, the activity of the enzyme. Estrogen injected into nonpregnant rats induced some peroxidase activity in the mammary glands of a few animals. Two hormone combinations tested in organ cultures of mouse mammary gland were able to activate the enzyme: (1) dexamethasone + insulin and (2) dexamethasone + insulin + prolactin.

Animals↗

3H-fucose incorporation into glycoproteins of toad bladder epithelial cells.

Electron microscope autoradiography was used to detect the incorporation of 3H-fucose into glycoproteins of toad bladder epithelial cells. After short exposure to 3H-fucose, without a chase period, the Golgi regions of all four cell types were labeled. When exposure to 3H-fucose was followed by chase periods (1,3,4 and 6 hours) the apical and basal-lateral plasma membranes of granular cells were heavily labeled. Apical granules and the cytoplasm of granular cells were also labeled, suggesting that they both provide the means for glycoprotein transfer from the Golgi to the plasma membranes. The heaviest labeling in mitochondria-rich cells, after the 1- and 3-hour chase periods, was over the apical tubules, although the apical and basal-lateral plasma membranes were also heavily labeled. After 4- and 6-hour chases, the labeling of the apical tubules decreased, whereas the labeling of the plasma membranes increased, strongly suggesting that in these cells apical tubules play a major role in the transfer of glycoproteins from the Golgi to the plasma membrane. Our results demonstrate that the route of 3H-fucose incorporation into plasma membrane glycoproteins and the rate of glycoprotein synthesis and breakdown are not the same in the two major epithelial cell types in toad bladder.

Animals↗