-During pregnancy, lymphocytes infiltrating the rabbit lacrimal gland disperse to the interacinar space from their normal focal concentrations, basal fluid secretion decreases, pilocarpine-induced fluid secretion increases, and stimulated fluid protein concentration decreases. Ductal epithelial cell prolactin (PRL) content increases and redistributes from the apical to the basal-lateral cytoplasm. A replication-incompetent adenovirus vector for rabbit PRL (AdPRL) was used to test the hypothesis that increased intracrine/autocrine PRL signaling alters secretory protein traffic in an ex vivo lacrimal acinar cell model. AdPRL had no discernable influence on microtubules or actin microfilaments or their responses to carbachol (CCh). Endogenous and transduced PRLs exhibited similar, nonpolarized, punctate distributions. Cells secreted PRL consititutively and at increased rates in response to CCh. In contrast, constitutive secretion of ␤-hexosaminidase was negligible, suggesting that the constitutive pathway for PRL is relatively inaccessible to typical secretory proteins. AdPRL had no significant effect on total secretion of ␤-hexosaminidase or syncollingreen fluorescent protein (GFP), a chimeric secretory protein construct. However, it reversed the polarized distributions of vesicles containing rab3D and syncollin-GFP. Live-cell imaging indicated that AdPRL redirected CCh-dependent syncollin-GFP exocytosis from the apical plasma membrane to the basal-lateral membrane. Elevated concentrations of exogenous rabbit PRL in the ambient medium elicited similar changes. These observations suggest that elevated PRL, as occurs in the physiological hyperprolactinemia of pregnancy, induces lacrimal epithelial cells to express a mixed exocrine/endocrine phenotype that secretes fluid to the acinus-duct lumen but secretes proteins to the underlying tissue space. This phenotype may contribute to the pregnancy-associated immunoarchitecture. ocular surface; mucosal immunity; pregnancy; Sjögren's syndrome THE OCULAR SURFACE SYSTEM maintains a thin fluid film that comprises an external milieu necessary for optimal homeostasis of its mucosal tissues and of the cornea. Disruptions of ocular surface homeostasis frequently elicit sensations of dryness, itching, or burning. These symptoms may be associated with immune system diseases, such as Sjögren's syndrome and graft vs. host disease, but most cases occur without the typical signs of autoimmune disease. They occur more frequently in women than men and are often associated with altered states of the systemic hormonal milieu: perimenopause, postmenopause, pregnancy, lactation, oral contraceptive use (39), and estrogen or estrogen-progesterone replacement therapy (35,36). Among men, the frequency increases with age (8).Aging in men is accompanied by gradual decreases in gonadal and adrenal production of androgens. The physiological states associated with altered ocular surface system homeostasis in women share one well-known common denominator, a decrease in the amount of testosterone that...

The rabbit lacrimal gland undergoes an immunophysiological transformation during pregnancy, reminiscent of that of the mammary gland as it prepares to deliver secretory IgA into the nascent fluid product. The contents of TGF-beta and prolactin (PRL) within ductal epithelial cells increase, and their primary localizations shift from the apical to the basal cytoplasm, suggesting a transformation from exocrine to paracrine secretion. Studies with ex vivo acinar cell models demonstrated that elevated PRL suppresses traffic of secretory proteins into the regulated exocrine apparatus and directs them into a novel, induced, regulated paracrine apparatus [Wang, Y., Chiu, C.T., Nakamura, T., Walker, A.M., Petridou, B., Trousdale M.D., Hamm-Alvarez S.F., Schechter J.E., Mircheff A.K., 2007. Elevated prolactin redirects secretory vesicle traffic in rabbit lacrimal acinar cells. Am. J. Physiol. Endocrinol. Metab. 292, E1122-E1134]. However, it was not clear whether PRL itself entered the induced paracrine apparatus. In the present study, confocal immunofluorescence microscopy revealed that natively expressed PRL and over-expressed PRL co-localized with PRL receptors (PRLR); rab11, a marker for the recycling endosome; gamma-adaptin, a marker for the Golgi complex and trans-Golgi network; and rab7, a marker for the autophagic lysosomal apparatus. Natively expressed, over-expressed, and endocytosed PRL also co-localized with rab4 and rab5A, markers for the early endosome, and with rab3D, a marker for regulated exocrine secretory vesicles. Endocytosed PRL was stored in intact form and released in response to stimulation with carbachol. Subcellular fractionation analysis detected relative excesses of PRL over PRLR in fractions that contained fragments of the recycling endosome and fractions that contained both secretory vesicle fragments and prelysosomal and autolysosomal fragments. EM-gold microscopy demonstrated PRL within small vesicles, consistent with endosomes or secondary lysosomes, and in large vesicles, consistent with regulated secretory vesicles. The secretory vesicles were preponderantly localized in the apical cytoplasm of control cells, and in the basal cytoplasm of PRL over-expressing cells. These results indicate that when lacrimal epithelial cells synthesize PRL, and when they endocytose it from their ambient medium, they traffic it both into the endosomes that constitute the constitutive transcytotic paracrine apparatus and also into regulated secretory vesicles, which are associated with the exocrine apparatus at low PRL levels and with the induced paracrine apparatus at high PRL levels.

Objectives: This report presents, for the first time, findings on the vox populis as to who constitutes the “vulnerables in biomedical research.” Methods: The 3‐City Tuskegee Legacy Project (TLP) study used the TLP questionnaire as administered via random‐digit‐dial telephone interviews to 1,162 adult Black people, non‐Hispanic White people, and two Puerto Rican (PR) Hispanic groups: Mainland United States and San Juan (SJ) in three cities. The classification schema was based upon respondents' answers to an open‐ended question asking which groups of people were the most vulnerable when participating in biomedical research. Results: Subjects provided 749 valid open‐ended responses, which were grouped into 29 direct response categories, leading to a four‐tier classification schema for vulnerability traits. Tier 1, the summary tier, had five vulnerability categories: 1) Race/ethnicity; 2) Age; 3) SES; 4) Health; and, 5) Gender. Black people and Mainland United States PR Hispanics most frequently identified Race/Ethnicity as a vulnerability trait (42.1 percent of Black people and 42.6 percent of Mainland United States. PR Hispanics versus 15.4 percent of White people and 16.7 percent of SJ R Hispanics) (P < 0.007), while White people and SJ PR Hispanics most frequently identified Age (48.3 percent and 29.2 percent) as a vulnerability trait. Conclusions: The response patterns on “who was vulnerable” were similar for the two minority groups (Black people and Mainland US PR Hispanics), and notably different from the response patterns of the two majority groups (White people and SJ PR Hispanics). Further, the vox populis definition of vulnerables differed from the current official definitions as used by the US federal government.

Metacrobeles amblyurus n. sp. (Cephalobina, Cephaloboidea) is described from sand dunes of Death Valley, California, USA. It shares with other Metacrobeles species a far posterior vulva as well as five lateral lines but is distinguished from previously known species in having a blunt (vs more tapering) conical tail. Probolae of M. amblyurus n. sp. are low conical-rounded, adjacent lips are fused into three pairs, and guard processes are lacking. The very narrow vulva in M. amblyurus n. sp. appears to be plugged in adult females, and juveniles apparently hatch exclusively within the body of the dead mother. Type localities of the two previously known species of Metacrobeles are in western Africa and this is the first confirmed report of Metacrobeles from another continent.

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