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Biomedical subjects

E Flynn

Publications and source records attributed to E Flynn.

At least 55 records · Page 3Linked to original sources

Directed lysis of experimental cancer by beta-carotene in liposomes.

The purpose of this study was to extend the knowledge of the antitumor activity of liposomes and to identify, for the first time, the antitumor effect of liposomes with the antioxidant beta-carotene. The administration of the carotenoid encapsulated in in liposomes has the advantages of quantitation, facilitation, and most importantly an increased therapeutic response, resulting in the accentuation of regression of carcinoma in the hamster pouch. Tumors induced after the application of the carcinogen 7,12-dimethylbenz[alpha]anthracene (0.5%) were injected with liposomes composed of phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine in a ratio of 1:1:1 (large unilamellar vesicles). Tumor-bearing animals were divided into four groups, each containing 10 hamsters. The group treated with the liposomes of beta-carotene exhibited a significantly lower tumor burden (approx 5,000-fold difference) than the control tumor group. Electron- and light-micrographic analyses were used to substantiate the gross observations of tumor regression. It was noted that the carcinoma cells endocytozed liposomes in increased numbers compared with normal mucosa treated with liposomes. In addition, non-tumor-bearing hamsters injected with beta-carotene liposomes or liposomes alone did not exhibit any pathological change to the normal mucosa. An inflammatory infiltrate consisting of mononuclear cells, mast cells, and some polymorphonuclear leukocytes was noted, and degranulating polymorphonuclear leukocytes and mast cells and eosinophils predominated in the tumor controls (7,12-dimethylbenz[alpha]anthracene treated only). Notably, not all areas of degenerating dysplasia or early carcinoma exhibited a dense inflammatory response adjacent to the mucosa after the injection of beta-carotene liposomes. The results demonstrate a selective nontoxic therapy to regress experimental oral cancer.

Animals↗

The administration of beta carotene to prevent and regress oral carcinoma in the hamster cheek pouch and the associated enhancement of the immune response.

In the past four years this laboratory has utilized the hamster cheek pouch tumor model to investigate the anticancer activities of antioxidants, such as beta carotene. These molecules, which have exhibited no evidence of toxicity, have been administered systemically (oral ingestion), and locally to the tumor site in the hamster cheek pouch. The results have been either the inhibition of tumor growth, or the regression of tumor. Adjacent to the degenerating tumors a dense inflammatory infiltrate was observed. Specifically, the cytokines, tumor necrosis factor alpha, and beta, have been immunohistochemically localized to the site of regressed oral carcinoma. Recently, liposomes composed of phosphaditylcholine, phosphaditylserine, and phosphodityelanolamine were combined with beta carotene and injected locally to oral squamous cell carcinoma of the hamster. The results indicated that tumor cells accumulated the liposomes and were lysed while normal mucosal cells did not demonstrate this effect. Therefore antioxidants such as beta carotene can be localized to a tumor site, without a toxic response. Future studies on the anticancer activity of the antioxidants need to focus on the cellular and molecular changes produced in the immune effectors and in the mucosal cells following administration of the antioxidants.

9,10-Dimethyl-1,2-benzanthracene↗

Growth characteristics of human epidermal melanocytes in pure culture with special reference to genetic differences.

Human melanocyte cultures were established using disaggregated epidermal cell suspensions derived from foreskins and plated onto culture dishes in medium containing 2% fetal bovine serum, growth factors, hormones, and melanocyte growth factor (MGF) extracted from bovine hypothalamus (Wilkins et al., J.Cell. Physiol., 122:350, 1985). After 2 days in culture the cells were transferred to serum-free medium to eliminate keratinocyte and fibroblast growth. Melanocytes grew preferentially and pure melanocyte populations could be harvested after 12-16 days in vitro. Melanocytes were later subcultured in the presence of 1% FBS. Pure melanocyte cultures were characterized by light and electron microscopic criteria, as well as by cytochemical demonstration of the melanocyte-specific enzyme, tyrosinase. At the ultrastructural level, cultured melanocytes derived from black (negroid) neonatal skin (B-M) had numerous mature rod-shaped stage IV melanosomes, while white (caucasoid) skin-derived melanocytes (W-M) in culture contained no mature melanosomes. Growth rate, cell yield, and in vitro lifespan for B-M were more than twice that for W-M in pure melanocyte cultures in the presence of MGF. Our results suggest that MGF-dependent growth of B-M differs from that of W-M.

Black People↗

A local pathophysiologic mechanism of the resorption of residual ridges: prostaglandin as a mediator of bone resorption.

The role of PG as a bone resorption mediator in RRR was investigated in the rat model and the following may be concluded from the data. 1. PG is suggested to be a mediator of the RRR. 2. The continuous and localized bone resorption in RRR may be caused by continuous synthesis of local PG. 3. PG producing cells and specific stimuli responsible for RRR are still unknown.

Alveolar Process↗

Characteristics of cultivated adult human nevocellular nevus cells.

Nevus cells are of biologic interest because of their uncertain relationship to epidermal melanocytes and of clinical interest because of their statistical association with melanoma. We report a technique that allows reliable cultivation of nevus cells from small acquired and congenital nevi and permits in vitro characterization of this cell type. Morphologically, cultured nevus cells were found to closely resemble epidermal melanocytes from the same or comparably aged donors, manifesting marked dendricity and specific ultrastructural features characteristic of melanocytes; but could be distinguished by the presence of occasional large binucleate or trinucleate cells and by the frequent finding of grouped melanosomes in nevus cell cytoplasm. Growth kinetics were also similar for nevus cells and epidermal melanocytes, with population doubling times of 1-2 weeks in hormone-supplemented serum-free medium, and substantial growth enhancement by fetal bovine serum. As previously noted for epidermal melanocytes, nevus cells in serum-free culture demonstrated striking substrate responsiveness, with far greater attachment rates and degree of cytoplasmic spreading on fibronectin or type I/III collagen than on laminin, type IV collagen, or uncoated plastic. These strong similarities in vitro suggest that morphologic and behavioral differences observed between epidermal melanocytes and nevus cells in the skin may result from local environmental influences rather than from intrinsic cellular differences. The availability of a satisfactory culture system for nevus cells may facilitate future investigations into their malignant potential and other biologic features.

Adult↗

Selective cultivation of human melanocytes from newborn and adult epidermis.

Development of adequate culture systems for the human epidermal melanocyte is critical to further advances in pigment cell biology. We now report selective growth and long-term maintenance of melanocytes derived from both newborn and adult skin specimens. Disaggregated epidermal cell suspensions were plated in a hormone-supplemented medium containing cholera toxin and a hypothalamic extract treated to remove keratinocyte growth-promoting activity. After 3-4 weeks, pure melanocyte populations could be harvested and serially passaged up to 6 times over several months for a total of 10 or more cumulative population doublings in vitro. Electron microscopic studies revealed metabolically active cells with abundant melanosomes in various stages of melanization throughout the culture lifespan. Differences in size and number of melanosomes attributable to race of the tissue donor were readily apparent, and pigment content of melanocytes from both black and Caucasian donors appeared to increase with time in culture. Newborn melanocytes proliferated more rapidly and survived longer than did adult melanocytes, but there were no consistent morphologic differences as a function of donor age. Comparison of growth potential for the 3 major skin-derived cell types in this hormone-supplemented medium revealed striking specificity for melanocytes, with total elimination of keratinocytes over 1-2 weeks, and no fibroblast proliferation whatever in the absence of serum supplementation. This system promises to facilitate in vitro investigation of epidermal melanocytes in normal and diseased human skin.

Adult↗

Factors affecting plasma benzo[a]pyrene levels in environmental studies.

Benzo[a]pyrene (BaP) is a useful indicator of exposure to polycyclic aromatic hydrocarbons (PAHs), airborne carcinogenic compounds. Radioimmunoassay was used to test for plasma BaP differences in 61 subjects divided into three groups based on geographic-demographic locale: urban-industrial, urban-residential, and outer suburban. The results showed that the urban-industrial area participants had a significantly higher mean plasma BaP level than did the outer suburban subjects. The urban-residential subjects did not have a significantly different mean plasma benzo[a]pyrene level from either of the other two groups. Obesity, as measured by Quetelet's index, was found to have a significant correlation with BaP levels. These results indicate that radioimmunoassay of plasma for BaP may be used successfully to judge environmental exposure to PAHs, provided physiological considerations such as obesity are taken into account.

Adult↗

Chronologic and actinically induced aging in human facial skin.

Clinical and histologic stigmata of aging are much more prominent in habitually sun-exposed skin than in sun-protected skin, but other possible manifestations of actinically induced aging are almost unexplored. We have examined the interrelation of chronologic and actinic aging using paired preauricular (sun-exposed) and postauricular (sun-protected) skin specimens. Keratinocyte cultures derived from sun-exposed skin consistently had a shorter in vitro lifespan but increased plating efficiency compared with cultures derived from adjacent sun-protected skin of the same individual, confirming a previous study of different paired body sites. Electron microscopic histologic sections revealed focal abnormalities of keratinocyte proliferation and alignment in vitro especially in those cultures derived from sun-exposed skin and decreased intercellular contact in stratified colonies at late passage, regardless of donor site. One-micron histologic sections of the original biopsy specimens revealed no striking site-related keratinocyte alterations, but sun-exposed specimens had fewer epidermal Langerhans cells (p less than 0.001), averaging approximately 50 percent the number in sun-protected skin, a possible exaggeration of the previously reported age-associated decrease in this cell population. These data suggest that sun exposure indeed accelerates aging by several criteria and that, regardless of mechanism, environmental factors may adversely affect the appearance and function of aging skin in ways amenable to experimental quantitation.

Age Factors↗

Retinoid inhibition of experimental lingual carcinogenesis: ultrastructural observations.

Sixty-four male and female Syrian golden hamsters (Mesocricetus auratus) were divided into 4 equal groups. Group 1 animals had the posterior lateral borders of their tongues painted three times weekly with a 0.5% solution of 7,12-dimethylbenz[a]anthracene (DMBA) in acetone. Group 2 animals were painted with DMBA and also received 10 mg of 13-cis-retinoic acid in peanut oil administered orally by pipette twice weekly. Group 3 animals received only retinoid, and group 4 animals were untreated controls. Four animals in each group were killed at 12, 14, 16, and 18 weeks. In the DMBA-painted animals receiving 13-cis-retinoic acid, the leukoplakia and epidermoid carcinomas developed more slowly and were better differentiated microscopically. The better degree of differentiation was demonstrated by ultrastructural studies. Less cellular separation and fewer microvilli-like structures were evident. No tubular mitochondria were observed. Less dispersion of heterochromatin occurred throughout nuclei, and the basal lamina tended to be regular and continuous.

9,10-Dimethyl-1,2-benzanthracene↗

A collaborative assessment of workload and patient care needs in four rehabilitation facilities.

This article describes the process used by nurse executives at four freestanding rehabilitation facilities to implement and validate an interactive patient classification system. The research process involved defining critical indicators, measuring workloads by level of staff, and validating the number of care hours for the levels of patient classification. The database enabled the four consortium members to share their knowledge, resources, and costs of implementing a patient classification system, and it provides a benchmark of rehabilitation services. The study data are being used in making staffing decisions, preparing and defending budgets, and identifying the cost of care by disability classification.

Attitude of Health Personnel↗