The role of the central nervous system in the pathogenesis of polycystic ovary syndrome.

This article reviews the master gland concept and the hypothalamic-pituitary-ovarian axis with respect to embryological development and maturation through normal puberty. Intrinsic function and extrinsic modulation of the pulse generator are discussed. The neuroendocrine disturbances evident in polycystic ovary syndrome (PCOS) are reviewed and put into the context of the recent consensus definition of the syndrome. Modern theories are presented addressing a significant role for neuroendocrine dysfunction during pubertal maturation in the aetiology of PCOS.

Modulation of retinoblastoma cell characteristics by hexamethylene bis-acetamide and other differentiating agents in culture.

The undifferentiated Y-79 retinoblastoma cell line can be induced by specific agents to express characteristics of mature retinal cells. In the present study, attached Y-79 cell cultures were treated with hexamethylene bis-acetamide (HMBA) and other differentiating agents and examined for "neuronal" and other properties. Immunocytochemical staining was performed with antibodies against neuron- and retina-specific antigens, [synaptophysin, interphotoreceptor retinoid-binding protein (IRBP), neural cell adhesion molecule (N-CAM), and rod- and cone-specific transducin (TR alpha and TC alpha)] and microtubule-associated protein (MAP-1) and tubulin. Enhanced expression of tubulin was observed with cAMP treatment in FBS media. Expression of N-CAM was observed in all groups. Morphological differentiation was pronounced with HMBA and butyrate treatment, with HMBA inducing increased tubulin expression after 2 weeks of treatment. Expression of TR alpha was minimal under all culture conditions, whereas TC alpha was ubiquitously expressed. This supports the concept that Y-79 retinoblastoma is predominantly of cone neuronal origin and that, surprisingly, immunocytochemical differentiation is not correlated with the marked morphological changes induced by the major differentiating agents used.

Differential regulation of arylamine and arylalkylamine N-acetyltransferases in human retinoblastoma (Y-79) cells.

For the first time, arylamine and arylalkylamine N-acetyltransferase (NAT) activities are shown to be differentially regulated. In a human retinoblastoma (Y-79) cell line, arylalkylamine NAT activity, but not arylamine NAT activity increased (3-5-fold) rapidly (1-3 h) in response to treatment with dibutyryl cAMP. In contrast, treatment with butyrate showed a delayed (3-5 days) increase (3-5-fold) in arylamine NAT activity but not in arylalkylamine NAT activity. The differential response to these agents in Y-79 cells provides a model system for future studies on the regulatory relationship between the two enzyme activities.

Human retinoblastoma cells express alpha B-crystallin in vivo and in vitro.

alpha B-crystallin is a major lens protein that is a member of the heat-shock family of proteins. Using immunohistochemical and northern blot techniques, we now demonstrate its presence in freshly-fixed retinoblastoma tissue. The protein is also abundantly expressed in cultured human retinoblastoma cells (Y-79 NEI, WERI Rb-1) as well as two subcultured Y-79 lines (ATCC and GM01232C). High expression of alpha B-crystallin may be involved in tumor growth and/or be a marker for general oncogenic "stress" in the tumor tissue.

Cytolysis of corneal epithelial cells by hydrogen peroxide.

Superoxide radicals or products generated by these radicals in a xanthine/xanthine oxidase system lyse cultured rat and human corneal epithelial cells as measured in a chromium-51 release assay. Partial protection from this lysis is afforded by superoxide dismutase and complete protection is obtained with catalase. Hydrogen peroxide, a product of the dismutation of superoxide radicals, lyses these cells directly and is implicated as the toxic agent in the xanthine/xanthine oxidase reaction. Hydrogen peroxide also decreases cell proliferation and decreases the intact DNA. Therefore, hydrogen peroxide appears to be toxic to corneal epithelial cells. The implications of these data on the safety of hydrogen peroxide as a contact lens disinfectant are discussed.

Corneal oxygen scavenging systems: lysis of corneal epithelial cells by superoxide anions.

The cornea has inherent protection from superoxide radicals from the presence of superoxide dismutase. However, the dismutation of these radicals results in the generation of hydrogen peroxide. The corneal scavenging systems for hydrogen peroxide is minimal as there are only low levels of catalase and glutathione peroxidase present. We have demonstrated the cytolytic capabilities of oxygen radicals in the cornea and reversed this lysis with catalase. These data indicate that hydrogen peroxide is the primary damaging agent in this system.

Cell-mediated lysis of murine target cells by nonimmune salmonid lymphoid preparations.

Lymphoid preparations from nonimmune rainbow and brook trout were found to lyse murine tumor cells (EL-4 & P815Y) in vitro in an 18 hr 51Cr-release assay conducted at 16-18 degrees C. Lysis was proportional to the effector: target cell ratio, required direct cell to cell contact, and was not depleted by the removal of nylon wool adherent cells. Lymphoid populations from peripheral blood, the thymus, and the anterior kidney, but not the spleen, were active in the cytotoxicity assay. Individual fish varied considerably in their ability to lyse one or both target cells. These data and the results of unlabelled target cell inhibition studies suggest that the reaction is selective if not specific. The addition of PHA to the reaction mixture resulted in markedly enhanced cytotoxic reactivity. In the presence of PHA lysis was readily detectable at 4 hr. The data demonstrate that nonimmune Salmonids possess a cytolytic effector cell population which has considerable cytotoxic potential and may represent a heterogeneous "natural killer cell" population.

Investigation into an outbreak of food poisoning.

During an outbreak of food poisoning at a church camp, 16 of the 25 people attending were affected. Despite a thorough search for a bacterial pathogen none was identified. An examination of the Escherichia coli serotypes present suggest that E. coli O159. H9 may have been the organism causing the outbreak.

Antibody-mediated basophil accumulations in cutaneous hypersensitivity reactions of guinea pigs.

Cutaneous basophil hypersensitivity (CBH) was studied in guinea pigs by using simplified histologic techniques. Animals immunized with oxazolone or picryl conjugates of keyhole limpet hemocyanin (KLH) emulsified with complete (CFA) or incomplete Freund's adjunvant (IFA) were found to have hapten-specific cutaneous basophil reactions when skin tested at 1 week with oxazolone or picryl chloride contant painting or intradermal injection of oxazolone or picryl-conjugated human serum albumin, respectively. Thus, hapten-specific cutaneous basophil reactions were present in guinea pigs immunized with CFA for classical delayed hypersensitivity, and in animals immunized with IFA for Jones-Mote reactions. Hapten-specific 24-hr cutaneous basophil reactions were passively transferred with immune serum from donors sensitized with conjugates of oxazolone or picryl-KLH in CFA or IFA, and with serum from oxazolone contact-sensitized animals as well. As little as 0.5 ml sera obtained from donors 1 week after immunization could systemically transfer cutaneous basophil reactions. It is likely that hapten-specific cutaneous basophil reactions are mediated by small quantities of serum antibodies. We conclude that antibody-mediated cutaneous basophil reactions may be distinctive hypersensitivity responses that can be distinguished from classical anaphylactic, Arthus, and delayed hypersensitivities. It is suggested that CBH reactions are heterogeneous and that antibody products of B lymphocytes, and factors probably derived from T lymphocytes, play a role in basophil accumulations at cutaneous hypersensitivity reactions.

Augmentation of delayed-type hypersensitivity by doses of cyclophosphamide which do not affect antibody responses.

Mice immunized with more SRBC than are required to produce optimal delayed-type hypersensitivity reactions, developed good antibody responses and poor delayed foot pad reactions. Cyclophosphamide treatment in low doses (20 mg/kg) before immunization, augmented the delayed-type hypersensitivity without affecting antibody responses. Cyclophosphamide did not augment delayed responses to optimal doses of SRBC (0.01%), but did augment the delayed hypersensitivity response of mice immunized with a suboptimal antigen dose (0.001%); which produced no detectable antibody response with or without cyclophosphamide pretreatment. These results suggest that antibody feedback is not the sole regulator of delayed reactions; the possibility that suppressor T cells may also be involved is discussed.