Neonatal imprinting of alveolar macrophages via neutrophil-derived 12-HETE.

Resident-tissue macrophages (RTMs) arise from embryonic precursors, yet the developmental signals that shape their longevity remain largely unknown. Here we demonstrate in mice genetically deficient in 12-lipoxygenase and 15-lipoxygenase (Alox15 mice) that neonatal neutrophil-derived 12-HETE is required for self-renewal and maintenance of alveolar macrophages (AMs) during lung development. Although the seeding and differentiation of AM progenitors remained intact, the absence of 12-HETE led to a significant reduction in AMs in adult lungs and enhanced senescence owing to increased prostaglandin E production.

From infection to repair: Understanding the workings of our innate immune cells.

In a world filled with microbes, some posing a threat to our body, our immune system is key to living a healthy life. The innate immune system is made of various cell types that act to guard our bodies. Unlike the adaptive immune system that has a specific response, our innate immune system encompasses cells that elicit unspecific immune responses, triggered whenever the right signals are detected.

A Custom Genotyping Array Reveals Population-Level Heterogeneity for the Genetic Risks of Prostate Cancer and Other Cancers in Africa.

Although prostate cancer is the leading cause of cancer mortality for African men, the vast majority of known disease associations have been detected in European study cohorts. Furthermore, most genome-wide association studies have used genotyping arrays that are hindered by SNP ascertainment bias. To overcome these disparities in genomic medicine, the Men of African Descent and Carcinoma of the Prostate (MADCaP) Network has developed a genotyping array that is optimized for African populations.

CTCF-Induced Circular DNA Complexes Observed by Atomic Force Microscopy.

The CTCF protein has emerged as a key architectural protein involved in genome organization. Although hypothesized to initiate DNA looping, direct evidence of CTCF-induced DNA loop formation is still missing. Several studies have shown that the 11 zinc finger (11 ZF) domain of CTCF is actively involved in DNA binding.

The oral education clinic: A pharmacist- and nurse-led clinic to support patients starting oral systemic anti-cancer treatments.

With the increased number of oral systemic anti-cancer treatments available, patients need to be managed safely and effectively in line with national guidance. In response to guidance in 2011, Oxford University Hospitals NHS Foundation Trust implemented an 'Oral Education Clinic'. This nurse- and pharmacist-led clinic facilitates the delivery of patient education, highlighting key safety aspects of drug administration and management, and ensures follow-up is arranged as per protocol.

Elucidation of insulin assembly at acidic and neutral pH: Characterization of low molecular weight oligomers.

Deficiency in insulin secretion and function that characterize type 2 diabetes often requires administration of extraneous insulin, leading to injection-site amyloidosis. Insulin aggregation at neutral pH is not well understood. Although oligomer formation is believed to play an important role, insulin oligomers have not been fully characterized yet.

Physiology, pathology and pharmacology of the male reproductive system.

The male reproductive system consists of the testes, a ductal system and sex accessory organs. Production of sperm by the testes combined with fluids formed by the sex accessory organs (e.g.

Endocrinology of sex steroid hormones and cell dynamics in the periodontium.

Numerous scientific studies assert the existence of hormone-sensitive periodontal tissues. Tissue specificity of hormone localization, identification of hormone receptors and the metabolism of hormones are evidence that periodontal tissues are targets for sex steroid hormones. Although the etiologies of periodontal endocrinopathies are diverse, periodontal pathologies are primarily the consequence of the actions and interactions of sex steroid hormones on specific cells found in the periodontium.

Current treatment options for the management of esophageal cancer.

In recent years, esophageal cancer characteristics and management options have evolved significantly. There has been a sharp increase in the frequency of esophageal adenocarcinoma and a decline in the frequency of squamous cell carcinoma. A more comprehensive understanding of prognostic factors influencing outcome has also been developed.

Down-regulation of neutral sphingomyelinase in androgen-dependent smooth muscle.

Background: During puberty, proliferation of guinea pig seminal vesicle smooth muscle (SVM) is mediated by androgen-induced basal release of norepinephrine (NE), signaling through the post-junctional alpha1-adrenoceptor. In the adult, the SVM is terminally differentiated, such that cell number is androgen resistant. Sphingomyelinase activation generates second messenger ceramides, which in vascular smooth muscle have been reported to counter the alpha1-adrenoceptor-mediated contractile response and activate apoptosis.

Candida albicans: the estrogen target for vaginal colonization.

Background: Estradiol (E(2)) stimulates colonization of the vagina by Candida albicans. Although this yeast expresses an estrogen-binding protein (EBP), the cellular target for estrogenic modulation of this infection is unresolved. Findings support direct E(2)-induced C.

Androgen-induced norepinephrine release mediating guinea pig seminal vesicle smooth muscle proliferation: potential role of pre-synaptic alpha2-adrenoceptors.

Background: Recent studies from our laboratory have demonstrated that androgen-induced basal norepinephrine (NE) release is responsible for the onset of proliferation in seminal vesicle smooth muscle (SVM) cells during early puberty. With subsequent sexual maturation, SVM was irreversibly differentiated to an androgen-resistant-amitotic state in which basal NE release remained elevated and resistant to androgen withdrawal or repletion. Based on these findings, we hypothesized that this irreversible elevation of basal NE release during pubertal development is caused, at least in part, by the down-regulation of pre-synaptic NE feedback inhibition, secondary to irreversible reduction in the expression of neuronal (pre-synaptic) alpha(2)-adrenoceptors.

Daily transdermal administration of selegiline to guinea-pigs preferentially inhibits monoamine oxidase activity in brain when compared with intestinal and hepatic tissues.

Selegiline has been formulated in an acrylic polymer adhesive mixture to be employed as a constant release topical patch for daily transdermal administration. Application of this selegiline transdermal system (STS) to guinea-pigs resulted in an average delivery of 1.185 mg selegiline/cm(2) patch/24 h.

Androgen induced norepinephrine release from postganglionic neurons mediates accessory sex organ smooth muscle proliferation.

Purpose: Guinea pig seminal vesicle smooth muscle displays an initial androgen dependent, proliferative response during early puberty, followed by progression to an androgen resistant, amitotic state in adults. We determined the role of norepinephrine in androgen dependent pubertal proliferation and in the subsequent terminal differentiation of adult seminal vesicle smooth muscle.

Materials And Methods: Guinea pig seminal vesicle provided a suitable model since its unique anatomy allowed clean harvest of smooth muscle without epithelium.

Protein kinase C mediated anti-proliferative glucocorticoid-sphinganine synergism in cultured Pollard III prostate tumor cells.

Purpose: Experimental effort focused on the growth inhibition of an androgen-resistant prostatic carcinoma, using pharmacological inhibition of protein kinase C (PKC) as the therapeutic target.

Materials And Methods: Studies were performed in cell culture using the Pollard (PA) III androgen-insensitive spontaneous rat prostate tumor cells, and the human prostate tumor lines, PC-3 and LnCaP. Pharmacological agents included steroid hormones and PKC modulators; measured parameters of tumor growth/function included cell number, PKC activity and sphingolipid metabolism.

m-Calpain activation/depletion is associated with androgen-induced reduction of protein kinase C and proliferation of male accessory sex organ smooth muscle cells.

Purpose: In the guinea pig seminal vesicle smooth muscle (SVM), androgen-dependent proliferation and terminal differentiation appear to be coupled to protein kinase C (PKC). This is based on the observations that both the soluble (cytosolic) enzyme and the Triton X-100 solubilizable form of the particulate enzyme were reduced during proliferation but were androgen-resistant in the amitotic state of adults. The purpose of the present investigation was to determine if the reduction in PKC activity was linked to the translocation of the activated enzyme to acceptor sites in the Triton X-100 insoluble fraction of the cell or reflected enzyme depletion due to proteolysis by androgen-dependent activation of the u- and/or m-calpains.

Protein kinases and the androgen-induced proliferation of accessory sex organ smooth muscle.

The possible role of second messenger systems in androgen-dependent smooth muscle proliferation was investigated. Focusing on the hormone-sensitive guinea pig seminal vesicle, we analyzed changes in protein kinase C (PKC) and cAMP-dependent type I and II protein kinases during the androgen-dependent smooth muscle proliferation of puberty, as well as in the transition to the nonproliferative state of the adult. The androgenic sensitivity of the cAMP-dependent type I and II protein kinases and the cAMP-dependent phosphorylations of soluble muscle proteins did not correlate with the qualitative change in the androgenic sensitivity of the prepubertal vs.

Operative stretchers. Use in ophthalmologic procedures.

Operative stretchers have been used at Holy Spirit Hospital for more than 500 ophthalmologic procedures. Most of those procedures have been extracapsular cataract extraction with intraocular lens implants performed as ambulatory surgery procedures. We also have used these stretchers for the inpatient procedures such as scleral buckling.

Actions and interactions of estradiol and retinoic acid in mouse anterior prostate gland.

Experiments were designed to define the ability of retinoic acid to block the estrogen-induced metaplasia in the mouse anterior prostate gland (coagulating gland), and to elucidate some of the biochemical correlates of the actions and interactions of these two compounds. In castrated mice, the estrogen-induced metaplasia of epithelial cells consisted of multi-layered, nonpolarized cells, which accumulated to fill the lumen of the acini. Retinoic acid had no discernable effect on epithelial morphology of castrates, but significantly reduced the estrogen-induced metaplasia.

Etiological considerations for the growth of stroma in benign prostatic hyperplasia.

The finding that human benign prostatic hyperplasia (BPH) consisted primarily of fibromuscular tissue has led to basic research into the hormonal control of the growth of male accessory sex organ smooth muscle. By using the separated epithelium and muscle layers of the guinea pig seminal vesicle, it was determined that the epithelium exhibited only reversible androgen-induced growths, whereas the muscle proved to be a target tissue for both androgen and estrogen, and exhibited irreversible growth responses. It was of particular interest that the normal androgen-dependent pubertal development of the muscle involved an approximate twofold increase in DNA, followed by the development of a complete and relatively selective androgenic insensitivity in this parameter.

Characterization and androgenic regulation of soluble protein kinases and protein phosphorylation in rat ventral prostate gland.

The soluble protein kinase activities for protamine and casein, the histone kinases modulated by cAMP or Ca2+ and phospholipid, as well as the phosphorylation patterns of endogenous proteins were measured in rat ventral prostates from normal adults, castrates, and dihydrotestosterone-treated castrates. In normal prostate, the ratio of cAMP-dependent type I and II kinases was approximately 1:5. After a 3-week period of castration-induced regression, the concentrations of both enzymes were increased, but on a total organ basis, type I was decreased to 56%, while type II was reduced to 20% of normal levels.

Androgen and estrogen effect on guinea pig seminal vesicle muscle: a combined stereological and biochemical study.

A combined electron microscopic stereological and biochemical study of the smooth muscle cells of guinea pig seminal vesicles was performed in intact, castrated, castrated and dihydrotestosterone- or estradiol-treated adult animals. Castration led to cell atrophy as determined stereologically by a decreased single cell volume and biochemically by no change in DNA content coupled with an increase in the DNA concentration. Treatment of castrates with dihydrotestosterone restored both the stereological and biochemical parameters of the cell size to slightly supranormal levels.