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Biomedical subjects

H Rothstein

Publications and source records attributed to H Rothstein.

At least 37 records · Page 2Linked to original sources

Studies on corneal endothelial growth and repair. III. Effects of DNA and RNA synthesis inhibitors upon restoration of transparency following injury.

The effects of inhibition of DNA and RNA synthesis on the repair of corneal endothelial wounds has been studied. Hydroxyurea which stops DNA synthesis and mitosis in the endothelium does not prevent restoration of transparency. However, the endothelial cell density of healed wounds in animals receiving the drug is decreased. Actinomycin D, which blocks DNA-primed RNA synthesis, not only prevents mitosis but stops migration of cells into the wound focus as well. In this case the wound does not heal and the cornea does not regain transparency.

Animals↗

Hypophysectomy exerts a radioprotective effect on frog lens.

Exposure to X-rays usually causes cataracts in frogs. These cataracts are always preceded by misalignment of the structures called meridional rows (MR). When cell division is completely halted by hypophysectomy, however, irradiation no longer disturbs the orientation of the MR. Since the MR are the structures formed as lens epithelial cells differentiate into lens fibres it is reasonable to propose that radiocataractogenesis depends upon a mitosis-driven formation of pathological fibres from epithelial cells that have been rendered abnormal by exposure to X-rays.

Animals↗

Studies on corneal endothelial growth and repair. II. increased transcription as detected by incorporation of 3H-uridine and 3H-actinomycin D.

Endothelial cells from injured frog corneas undergo increased 3H-uridine and 3H-actinomycin D (3H-AMD) incorporation as judged by autoradiography. The increase in 3H-AMD binding occurs when living endothelium is labeled in vitro or when fixed preparations are exposed to the drug. The changes in 3H-AMD incorporation detected by the two methods are comparable (55 and 62% for living and pre-fixed tissue respectively). However, when fixed endothelium is also de-histonized with 2 N HCl, differential binding of 3H-AMD is eliminated. This result suggests that the enhanced incorporation of 3H-AMD into nuclei is at least partly due to a modification in the association of chromosomal proteins with DNA and not entirely to cell permeability changes that may accompany wound repair. This contrasts with observations of cells that are killed outright by the injury. Such cells bind very large amounts of 3H-AMD compared with their living neighbors. Here the difference in incorporation is eliminated by prefixation. Thus, in the dead cells increased binding may be due to a reduction of cell surface permeability barriers which accompanies cell morbidity.

Animals↗

Complete elimination of mitosis and DNA synthesis in the lens of the hypophysectomized frog: effects on cell migration and fiber growth.

Three weeks after hypophysectomy mitosis and DNA synthesis are absent in the lens of the leopard frog (Rana iiens). By labeling germinative zone cells in their last DNA synthetic period we were able to follow them in the absence of further proliferation. By this means it has been demonstrated that migration of epithelial cells to the equator of the lens is stopped. Based on indirect measurements it seems that lens fiber formation also ceases. A correlation coefficient of 0.86 was computed between average labeling index and average distance migrated. In hypophysectomized animals the correlation coefficient between time and migration was 0.02 while in intact animals it is 0.87.

Animals↗

Total disappearance of cell proliferation in the lens of a hypophysectomized animal: in vivo and in vitro maintenance of inhibition with reversal by pituitary factors.

Cell cycle kinetics of lens epithelium were studied in frogs following hypophysectomy, and subsequent replacement therapy with bovine growth hormone (bGH). Hypophysectomy led to a complete absence of cells in DNA synthesis and mitosis within 4 weeks. A small number of G2 nuclei was present in all preparations, but the number was much reduced with time after surgery. Occasional preparations with a significant G2 population were encountered. The major block to cycle traverse appeared to be in the G0-G1 segment. Mechanical injury to the lenses of hypophysectomized animals caused the cells to move closer to S without, however, reaching it. The in vivo block to cycle traverse persisted in organ-cultured lenses maintained in medium containing serum of hypophysectomized animals. The block to cycle traverse was reversed when the lenses were cultured in medium containing the serum of hypophysectomized animals that received replacement therapy with bGH. The serum became effective between 1 and 2 days after the star of replacement therapy. The lens epithelial cells from hypophysectomized frogs incur a deficit such that a protracted prereplicative phase is detected when favourable growth conditions are restored.

Animals↗

Mitotic variations in the lens epithelium of the frog IV. Studies with isolated anuran pituitary factors.

Proteins corresponding to growth hormone and prolactin have been electrophoretically separated from the pituitary gland of the frog (Rana pipiens berlandieri and Rana catesbeiana). These substances can independently stimulate mitosis in the lenses of animals where it had previously been inhibited by means of hypophysectomy. DNA synthesis is greatly augmented six days after the start of hormone administration to intact animals. Nine days are required before this occurs in hypophysectomized ones. No other anterior pituitary hormone has been found to achieve the effect described. Initial attempts at amino acid analysis, though incomplete, indicate that the two frog hormones are different from each other as well as from their bovine counterparts. Pituitary factors do not affect mitotic activity in either corneal epi or endothelium of the frog.

Amino Acid Sequence↗

Seasonal variations in mitosis in the frog: a field study.

Field studies have shown that there is a seasonal variation in mitosis of lens and corneal epithelium (high in May and June, low during the rest of the year). This phenomenon can be reproduced in the laboratory by temperature manipulation. The response in the lens depends on the presence of the pituitary gland while the corneal one seems to be independent of it.

Animals↗

Congenital cataracts associated with disorganized meridional rows in a new laboratory animal: the degu (Octodon degus).

A new laboratory animal, Octodon degus, a hystricomorph rodent, was found to display a naturally occurring congenital cataract. Histological examination of the lens epithelium revealed that a marked disorganization of the meridional rows is associated with the opacity. Studies of offspring of cataractous parents indicates that the disorganization precedes cataract appearance. These findings are discussed in reference to a general theory of meridional row involvement in a number of types of cataracts.

Animals↗