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Biomedical subjects

H M Jensen

Publications and source records attributed to H M Jensen.

32 records · Page 2Linked to original sources

Lack of toxicity of methylene blue chloride to supravitally stained human mammary tissues.

Methylene blue chloride (MBC) has been used previously as a supravital stain to facilitate the excision and subsequent transplantation of mammary epithelial structures by delineating them from surrounding connective tissue and fat, which stain less intensely. This study was undertaken to determine why MBC selectively stains epithelium and if it has any long-term toxicity to epithelial cells. Light microscopy indicated that MBC was taken up into cell cytoplasm, but neither thin-section nor scanning electron microscopy indicated the mechanism of uptake or cytoplasmic localization. Spectrophotometry indicated that relative MBC uptake was greatest by macrophage and mammary epithelial cell lines and least by endothelial and fibroblast cell lines, offering an explanation for the more intense staining of epithelium. Toxicity of MBC to the cell lines was dose dependent and corresponded roughly to the MBC uptake capacity of the cell lines. Low concentrations were stimulatory to growth of some cell lines in serum-free medium. Comparisons of primary epithelial cultures from 28 pairs of MBC-treated and untreated human breast tissues indicated no significant effect of MBC on the growth of cells of any classification (normal, nonmalignant atypical, and malignant). These results confirm that supravital MBC staining of mammary tissues may be used with confidence that it will not bias the outcome of subsequent experiments requiring healthy, proliferating mammary epithelium.

Biological Transport↗

Angiogenesis induced by "normal" human breast tissue: a probable marker for precancer.

Normal human breast lobules, freshly isolated by precision microdissection of tissue stained with methylene blue chloride, were assayed for their ability to induce neovascularization (angiogenesis) in rabbit irises. Histologically, normal lobules from cancerous breast induced angiogenesis twice as often as lobules from noncancerous breasts, suggesting that preneoplastic transformation is diffuse.

Age Factors↗

Persistent and atypical lobules in the human breast may be precancerous.

Persistent human mammary lobules (PL) remaining after the menopause, and certain atypical lobules (ALA) are morphologically similar to the common preneoplastic hyperplastic alveolar nodule (HAN) of mice of strains having a high incidence of mammary carcinoma. This and other evidence suggest that like the HAN of mice human PL and ALA are precancerous.

Animals↗

Preneoplastic lesions in the human breast.

A subgross sampling technique with histological confirmation was used to study the pathology of 119 whole human breasts, either cancer-associated (that is, containing cancer or contralateral to a cancer) or taken from random routine autopsies. Atypical lobules were observed much more frequently in the cancer-associated group than in the group of routine autopsy breasts. Atypical lobules showed varying degrees of anaplasia that formed a continuum between normal epithelium and carcinoma in situ, usually of the common ductal type. As apprarent markers for increased cancer risk, atypical lobules in the human breast may be homologous to hyperplastic alveolar nodules that are abundant in high mammary cancer strains of mice. This indirect evidence supports the hypothesis that atypical lesions are common preneoplastic lesions in the human mammary gland.

Breast Neoplasms↗

Preneoplastic lesions of the human mammary gland transplanted into the nude athymic mouse.

Morphologically normal lobules and atypical lobules postulated precancerous to ductal carcinoma were transplanted to test their biological behavior. Supravital staining disclosed the 1 to 4-mm microorgans. "Cleared" mammary fat pads of nude mice were optimal transplantation sites. Of the total of 217 transplants from 19 cancer-associated and 13 non-cancer-associated breast, 151 survived after 2 to 27 weeks. Of 61 surviving normal-appearing lobules from cancer-associated breasts transplanted without prior in vitro maintenance, 20 (30%) dedifferentiated, and of 48 surviving lobules from noncancerous breasts, 11 (20%) dedifferentiated. Fifteen of 28 histologically normal-appearing lobules (60%) obtained from cancer-associated breasts after age 50 dedifferentiated. Thirty of 36 atypical lobules isolated from the breast tissue were obtained from cancer-associated breasts and the 5 of those that dedifferentiated came from cancer-associated breasts. Twenty of 22 (90%) dedifferentiating transplants from cancer-associated breasts showed a vascularization response, whereas 3 of 7 (43%) from noncancer-associated breasts did so. If dedifferentiation in this experimental setting is indicative of a precancerous potential, the data on normal-appearing lobules obtained from cancer-associated breasts from women over age 50 suggest that these lobules carry the greatest precancerous potential. Such lobules probably belong to a type persisting after menopause and they may be hormonally autonomous. Such lobules might undergo further atypia in vivo and, eventually, cancerous transformation.

Adult↗

An atlas of subgross pathology of the human breast with special reference to possible precancerous lesions.

One hundred ninety-six whole human breasts were examined by a subgross sampling technique with histologic confirmation. The method permitted the enumeration and identification of essentially all the focal dysplastic, metaplastic, hyperplastic, anaplastic, and neoplastic lesions. Of the 196, 119 were suitable for complete quantitative morphologic analysis of the focal lesions by type. They consisted of 67 breasts obtained by autopsy, 29 cancerous breasts obtained by mastectomy, and 23 contralateral to those with cancer. All lesions, photographed subgrossly, were subsequently confirmed and correlated histologically. Morphologic evidence supported the hypothesis that most lesions traditionally grouped as mammary dysplasia or fibrocystic disease, including apocrine cysts, sclerosing adenosis, fibroadenomas, various forms of lobules (sclerotic, dilated, hypersecretory, hyperplastic, atypical, or anaplastic), ductal carcinoma in situ (DCIS), and lobular carcinoma in situ (LCIS), arose in terminal ductal-lobular units (TDLU) or in the lobules themselves. A probable exception was papilloma of ducts larger than terminal ones. Isolated foci of DCIS within the TDLU were seen in 40% of cancerous breasts, which indicated that the disease often was multifocal. Of the contralateral breasts, the 60% with clinical cancer contained such lesions, and data were in accord with the clinically known fact that women with previous breast cancer have a high rate of the disease in the remaining one. An atypical lobule (AL) of type A (ALA) had the following characteristics: a) It was more common in cancerous breasts or in those contralateral to cancer than in breasts not so identified; b) it had lobular morphology and was a terminal structure on the mammary tree; c) it tended to persist after the menopause, whereas normal lobules usually atrophied; d) it variable degrees of anaplasia forming an arbitrary continuum from normal lobules to ductal carcinoma in situ; and e) as ALA progressed to DCIS, the unfolded lobule resembled a duct which gave the false impression that DCIS was a ductal lesion. The morphologic evidence supported that hypothesis that the lesions herein called AL were derived from TDLU and were precancerous.

Adenocarcinoma, Scirrhous↗

Hemolytic disease of the newborn following maternal self-injection of blood.

A teenage primigravida with no prior history of transfusion presented with anti-D, anti-C, and anti-E in her serum and subsequently developed anti-Fya. The infant had hemolytic disease of the newborn. The antibodies were provoked by the girl's self-injection of her partner's blood for emotional gratification. Clinicians and transfusion services should be aware that hemolytic disease of the newborn in a first pregnancy can be caused by self-inflicted maternal immunization. Close communication between clinicians and transfusion service is emphasized.

Adolescent↗