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Biomedical subjects

B A Flaxman

Publications and source records attributed to B A Flaxman.

At least 19 recordsLinked to original sources
PubMed1983

Granulomatous mycosis fungoides. A 14-year follow-up of a case.

This is a 14-year follow-up of a patient with granulomatous mycosis fungoides. The patient has had nodular lesions of mycosis fungoides for more than 30 years, an unusually long survival for the nodular form of the disease that is often quickly fatal. The role of the granulomatous inflammatory response in his survival is speculated upon.

Follow-Up Studies↗
PubMed1981

Relative resistance to methotrexate by proliferating normal rabbit epidermal cells in vitro.

Primary cell cultures of normal rabbit epidermal cells (keratinocytes) were established without the use of enzymatic techniques. Six experiments were carried out on cells from six different rabbits. When these cells were exposed to methotrexate (MTX) for 24 h at 1 micrograms/ml, proliferation, as measured by cells entering mitosis, was significantly inhibited (P less than 0.05) in only one experiment. When the dose of MTX was elevated to 100 micrograms/ml, only two experiments showed significant inhibition of mitosis. This minimal inhibition of mitosis by MTX was contrasted by the dramatic inhibitory effect of this antimetabolite on DNA synthesis. At 1 micrograms/ml MTX for 24 h, DNA synthesis, as measured by [3H]deoxyuridine uptake, was inhibited greater than 95%. We can conclude that under certain conditions, the rabbit keratinocyte may represent a normal cell type that is inherently resistant to the anti-proliferative effects of methotrexate.

Animals↗
PubMed1981

Pruritus: identifying and treating the causes.

The physician's ability to successfully treat and at least control, if not cure, the skin diseases resulting in pruritus has come through better understanding of skin physiology and the fortuitous discovery of a number of pharmacologic agents that significantly influence the pathologic processes causing itching. While the therapeutic armamentarium is far from perfect, the experienced practitioner can use it to considerable clinical benefit for the pruritus patient.

Dermatitis, Atopic↗
PubMed1977

Effects of methotrexate on proliferation of human keratinocytes in vitro.

Normal human keratinocytes, propagated as epithelial outgrowths in vitro, were exposed to different concentrations of methotrexate (MTX) for different periods of time. After a 1-hr exposure, DNA synthesis was inhibited in a reversible manner. No change in the mitotic index was observed. After a 6-hr exposure, both DNA synthesis and mitosis were inhibited, again in a reversible fashion. Prolonged exposure (24 hr) resulted in irreversible mitotic inhibition even when followed by recovery periods of 168 hr. The effective concentrations of MTX in vitro were similar to those described previously in vivo.

Culture Techniques↗
PubMed1976

Effect of prolactin on maintenance of prelactating human mammary gland in vitro.

Human mammary tissue from a female at the end of the second trimester of pregnancy was studied in organ culture in a chemically defined medium. Sampling was carried out at 1, 2 and 3 weeks. Without hormones, there was nearly total lobuloalveolar degeneration in all specimens at all times. Addition of insulin, hydrocortisone and ovine prolactin, in combination at a concentration of 5 mug per ml each, did not affect the extent of degeneration. Raising the concentration of prolactin to 50 mug per ml resulted in greatly improved lobulo-alveolar maintenance in all specimens and continued epithelial cell DNA synthesis for up to 3 weeks in vitro.

Breast↗
PubMed1976

Growth and differentiation of skin.

During the past 25 years, attention has turned from the morphologic aspects of skin development which are well known, to the mechanisms that control this development. Although our knowledge of these mechanisms is still limited, some avenues of investigation appear promising, e.g., epithelial-mesenchymal interactions, cell communication and other cell surface phenomena, and certain aspects of the proliferative process. In the analysis of what controls growth and differentiation, skin, as the experimental system, has played a major role.

Animals↗
PubMed1976

Rabbit corneal epithelial cells grown in vitro without serum.

Primary outgrowth cultures of normal rabbit corneal epithelium can be initiated and propagated in vitro up to 6 days in serum-free medium. By the eighth day the majority of cells have ceased to divide. Epithelial cells grown without serum show DNA synthetic activity at a level comparable to control cultures grown with added serum.

Animals↗
PubMed1975

Effect of pharmacological agents on human keratinocyte mitosis in vitro. II. Inhibition by catecholamines.

Catecholamines produce mitotic inhibition in primary cell cultures of human keratinocytes probably via a block in the G2 part of the cell cycle. Epinephrine produced significant mitotic inhibition (49%) at a concentration as low as 4.5 X 10(-10) M, while its analog, isoproterenol, produced 47% inhibition at 1 X 10(-10) M. Norepinephrine elicited a 49% inhibitory response at 1 X 10(-8) M. One other catecholamine, dopamine, caused a 53% decrease in mitosis at 1 X 10(-6) M. Other structurally related amines to exhibit mitotic inhibition were phenylephrine, 58% at 1 X 10(-7) M; octopamine, 47% at 1 X 10(-5) M; and tyramine, 52% at 1 X 10(-4) M. Serotonin showed no mitotic inhibition at 1 X 10(-4) M. Various alpha and beta adrenergic blocking agents were added to the cell system. The alpha blocking agent, phentolamine, had no effect on mitosis. When added in conjunction with epinephrine or norepinephrine, no reduction of the catecholamine-induced mitotic inhibition was observed. The beta blocking agent, propranolol, by itself showed slight mitotic inhibition at 1 X 10(-6) M. When added along with epinephrine or noreinephrine, propranolol reduced the catecholamine-induced mitotic inhibition approximately 65%. In addition, propranolol blocked mitotic inhibition caused by phenylephrine, an alpha adrenergic agent. However, another beta blocking agent, dichloroisoproterenol, showed strong mitotic inhibition (53%) when added to the cultures at a concentration of 1 X 10(-8) M. The effect was reduced to zero in the presence of propranolol. These data suggest that while beta receptors may be involved in the catecholamine-induced mitotic inhibition of human keratinocytes in vitro, the nature of the receptor-molecule interaction may be complex.

Catecholamines↗
PubMed1975

Organ culture of human skin in chemically defined medium.

Explants of adult human skin were grown in vitro in a chemically defined medium without serum. Under these conditions the epidermis was well maintained for up to 7 days, during which time new stratum corneum formation was observed. Most often the stratum corneum was orthokeratotic and associated with a prominent granular layer. Parakeratotic regions were also evident and these were not associated with a granular layer. During the first 5 days in culture there was a signficant increase in DNA synthesis (as measured radioautographically) and mitosis.

Culture Media↗
PubMed1975

DNA repair in tumor cells from the variant form of xeroderma pigmentosum.

Cells from most patients with xeroderma pigmentosum (XP) can be shown to be defective in repairing ultraviolet (UV) light-induced damage to their DNA, for they have a reduced rate of UV-induced thymidine incorporation. XP variants, however, have clinical manifestations of XP, but all their tissues tested to date have a normal rate of UV-induced 3H-thymidine incorporation. We have now tested tumor cells from an XP variant and from a typical XP patient. The variant's tumor cells, in contrast to those of the typical patient, had no detectable defect in their UV-induced thymidine corporation. We conclude, therefore, that the cells that formed tumors in this XP variant resemble his other cells in DNA repair capacity, and do not represent a minor cell population with the kind of DNA repair defect that is reflected in reduced UV-induced thymidine incorporation.

Autoradiography↗
PubMed1975

The effect of vitamin A on growth and differentiation of human keratinocytes in vitro.

Epithelial outgrowths (keratinocytes) from normal human skin in vitro were exposed daily for 30 min to vitamin A alcohol for periods up to 5 weeks. There was a markedly decreased number of keratohyaline granules in treated cultures, indicating an effect on the differentiation process, but there was no evidence for mucous metaplasia. The area of vitamin A-treated outgrowths was greater than that of controls at all times. In addition, there was a higher mitotic index, higher labeling index, and larger growth fraction in treated cultures. The combination of altered differentiation and enhanced proliferation of keratinocytes would appear to account for the larger outgrowth area found in vitamin A-treated cultures.

Autoradiography↗
PubMed1975

In vitro analysis of the control of keratinocyte proliferation in human epidermis by physiologic and pharmacologic agents.

Human keratinocytes grown in vitro as epithelial outgrowths or as organ cultures maintain many of their normal functions such as proliferation and keratinization. These in vitro systems have been used to analyze the effect of various agents on proliferation. All adenine nucleotides, including dibutyryl cyclic AMP, blocked mitosis in the G2 part of the cell cycle at concentrations of 1 times 10(-4) M. Some nonadenine nucleotides also showed this effect, but only at higher concentrations, an indication that the effect was specific for adenine nucleotides. Dibutyryl cyclic AMP and theophylline both depressed the incorporation of [3H]thymidine into DNA. Catecholamines such as isoproterenol, epinephrine, and norepinephrine were also potent inhibitors of mitosis (G2 block) at concentrations of 1 times 10(-8) to 1 times 10(-10) M. The fact that the effect could be blocked by the beta-blocking agent, propranolol, suggests the existence of specific membrane receptor sites. However, dichloroisoproterenol, another beta blocker, had distinct inhibitory properties in itself and thus indicated that the mechanism of action of catecholamines in human keratinocytes is complex and may involve more than binding to specific receptor sites. Histamine at a concentration of 2 times 10(-6) M was also a strong mitotic inhibitor. This finding is directly opposed to that in rat skin where mitosis is stimulated. Imidazole acetate, a histamine breakdown product, was found to be a striking mitotic stimulator in organ culture. A water-extractable protein (chalone) from human skin also caused a block in G2. Most of the substances tested occur naturally in the cell or organism and their ability to stimulate or depress proliferation in vitro suggests that they play a regulatory role in vivo.

Adenine Nucleotides↗
PubMed1975

Effect of pharmacologic agents on human keratinocyte mitosis in vitro. III. Inhibition by histamine and methylated analogs.

Keratinocytes from normal human skin were propagated in vitro. Histamine at 2 times 10(-6) M inhibited mitosis 68%. The side-chain methylated analogs, n-methylhistamine and n,n-dimethylhistamine, produced an inhibitory response of 53 and 60%, respectively, at 1 times 10(-6) M. The side-chain acetylated analog, n-acetylhistamine, did not elicit an inhibitory response in concentrations as high as 1 times 10(-4) M. The ring-methylated analogs, 1-methylhistamine and 4-methylhistamine, produced some degree of mitotic inhibition at 1 times 10(-4) M. When the H1-blocking agent, pyrilamine, or the H2-blocking agent, metiamide, was added in conjunction with histamine, the histamine-induced mitotic inhibition was abolished. These data indicate that human keratinocytes may possess receptors for histamine which could play a role in the regulation of human keratinocyte proliferation in vivo.

Histamine↗