121 research outputs found
Biochemical study of testosterone in skin: in vivo and in vitro metabolism of testosterone in rat skin
In vitro and in vivo testosterone metabolism was studied
using rat skin. The in vitro stoichiometric studies strongly suggested
the existence in the skin of 5a-reductase and other enzymes involved
in testosterone metabolism. The predominant metabolites were 5adihydrotestosterone,
androstandiol and 6.4-androstenedione. The rate
of testosterone metabolism in vitro was higher in preputial skin than in
dorsal skin. The main metabolites were androstandiol and 6 4-androstenedione
in vivo whereas dihydrotestosterone and androstandiol were
predominant in vitro. .6.4-Pathway is considered to be more active in
vivo in adults than in newborns. The difference in the in vivo uptake
increase of testosterone-3H after castration suggests the possible existence
in the organs and skin areas of androgen pools of different sizes.
The in vivo uptake and metabolism of testosterone were examined in
the nuclei of newborn rats. Dihydrotestosterone and androstandiol
detected in the nuclei of preputial skin, dorsal skin and liver were
42.8%, 24.3% and 27.8%, of total radioactivity incorporated into the
respective organs. The liver incorporated only a small amount of
radioactivity compared with the skin.</p
Bilateral segmental lung transplantation for children: Transplantation using split adult living-donor lower lobe
[Figure: see text
Renal ADAM10 and 17: Their Physiological and Medical Meanings
A disintegrin and metalloproteinases (ADAMs) are a Zn2+-dependent transmembrane and secreted metalloprotease superfamily, so-called “molecular scissors,” and they consist of an N-terminal signal sequence, a prodomain, zinc-binding metalloprotease domain, disintegrin domain, cysteine-rich domain, transmembrane domain and cytoplasmic tail. ADAMs perform proteolytic processing of the ectodomains of diverse transmembrane molecules into bioactive mediators. This review summarizes on their most well-known members, ADAM10 and 17, focusing on the kidneys. ADAM10 is expressed in renal tubular cells and affects the expression of specific brush border genes, and its activation is involved in some renal diseases. ADAM17 is weakly expressed in normal kidneys, but its expression is markedly induced in the tubules, capillaries, glomeruli, and mesangium, and it is involved in interstitial fibrosis and tubular atrophy. So far, the various substrates have been identified in the kidneys. Shedding fragments become released ligands, such as Notch and EGFR ligands, and act as the chemoattractant factors including CXCL16. Their ectodomain shedding is closely correlated with pathological factors, which include inflammation, interstitial fibrosis, and renal injury. Also, the substrates of both ADAMs contain the molecules that play important roles at the plasma membrane, such as meaprin, E-cadherin, Klotho, and CADM1. By being released into urine, the shedding products could be useful for biomarkers of renal diseases, but ADAM10 and 17 per se are also notable as biomarkers. Furthermore, ADAM10 and/or 17 inhibitions based on various strategies such as small molecules, antibodies, and their recombinant prodomains are valuable, because they potentially protect renal tissues and promote renal regeneration. Although temporal and spatial regulations of inhibitors are problems to be solved, their inhibitors could be useful for renal diseases
The effects of a Jewish primary school education in England on the religious observance and practice of less or non-observant parents of the pupils
The main aim of this research is to determine whether or not there has been any noticeable change in the level of religious observance and practice of less or non-observant parents which directly or indirectly can be attributed to the influence of their children and the Jewish primary school they attend. There is a frequently voiced assumption amongst those involved in Jewish education that parents, whose children attend a Jewish primary school, have increased their level of observance due to the influence of their children and the school. However, no previous research has been carried out in the United Kingdom in order to examine the basis of this premise. The purpose ofmy own research is to test this assumption in a thorough and rigorous manner by means of both questionnaires and in-depth interviews with parents of pupils attending three Jewish primary schools in England.
In addition, there are two further specific areas that will be investigated as supplementary parts ofthe main research:
[i] To compare the extent of similarities and differences of any such changes in religious observance between those Jewish families in England who formed part ofmy study, and those in the USA whose children attend Jewish day schools, who have also been the subject of separate research in the USA.
[ii] To determine whether within the data of this research study, there is any correlation with previous research in the field of social psychology regarding causes and effects of social conformity and deviation. The data from this specific area of research will be used to focus on the effects of a crucial inter-connection between parents, children and the school.
The thesis includes an examination of previous allied research and its implications relating to the nature of religious identity and changes in parental behaviour attributed to the influence of their children's Jewish education.
It also contains chapters outlining the historical and social background which led to a weakening ofJewish religious observance in the UK during the zo" century and a study of the changing role of the traditional Jewish family and its effect on the levels of religious observance in Anglo-Jewry. The data from questionnaires and interviews are analysed in a thorough manner. The results and conclusions of this thesis should be of benefit to those planning and administering Jewish primary schools in the UK
Optimal regimens of sulfamethoxazole-trimethoprim for chemoprophylaxis of Pneumocystis pneumonia in patients with systemic rheumatic diseases: results from a non-blinded, randomized controlled trial
Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons
The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions
Somatic mutations of CADM1 in aldosterone-producing adenomas and gap junction-dependent regulation of aldosterone production
Aldosterone-producing adenomas (APAs) are the commonest curable cause of hypertension. Most have gain-of-function somatic mutations of ion channels or transporters. Herein we report the discovery, replication and phenotype of mutations in the neuronal cell adhesion gene CADM1. Independent whole exome sequencing of 40 and 81 APAs found intramembranous p.Val380Asp or p.Gly379Asp variants in two patients whose hypertension and periodic primary aldosteronism were cured by adrenalectomy. Replication identified two more APAs with each variant (total, n = 6). The most upregulated gene (10- to 25-fold) in human adrenocortical H295R cells transduced with the mutations (compared to wildtype) was CYP11B2 (aldosterone synthase), and biological rhythms were the most differentially expressed process. CADM1 knockdown or mutation inhibited gap junction (GJ)-permeable dye transfer. GJ blockade by Gap27 increased CYP11B2 similarly to CADM1 mutation. Human adrenal zona glomerulosa (ZG) expression of GJA1 (the main GJ protein) was patchy, and annular GJs (sequelae of GJ communication) were less prominent in CYP11B2-positive micronodules than adjacent ZG. Somatic mutations of CADM1 cause reversible hypertension and reveal a role for GJ communication in suppressing physiological aldosterone production
Activated brain mast cells contribute to postoperative cognitive dysfunction by evoking microglia activation and neuronal apoptosis
Secretion of mast cell inflammatory mediators is enhanced by CADM1-dependent adhesion to sensory neurons
Neuroimmune interactions are important in the pathophysiology of many chronic inflammatory diseases, particularly those associated with alterations in sensory processing and pain. Mast cells and sensory neuron nerve endings are found in areas of the body exposed to the external environment; both are specialized to sense potential damage by injury or pathogens and signal to the immune system and nervous system respectively, to elicit protective responses. Cell adhesion molecule 1 (CADM1), also known as SynCAM1, has previously been identified as an adhesion molecule which may couple mast cells to sensory neurons however, whether this molecule exerts a functional as well as structural role in neuroimmune cross-talk is unknown. Here we show, using a newly developed in vitro co-culture system consisting of murine bone marrow derived mast cells (BMMC) and adult sensory neurons isolated from dorsal root ganglions (DRG), that CADM1 is expressed in mast cells and adult sensory neurons and mediates strong adhesion between the two cell types. Non-neuronal cells in the DRG cultures did not express CADM1, and mast cells did not adhere to them. The interaction of BMMCs with sensory neurons was found to induce mast cell degranulation and IL-6 secretion and to enhance responses to antigen stimulation and activation of FcεRI receptors. Secretion of TNFα in contrast was not affected, nor was secretion evoked by compound 48/80. Co-cultures of BMMCs with HEK 293 cells, which also express CADM1, while also leading to adhesion did not replicate the effects of sensory neurons on mast cells, indicative of a neuron-specific interaction. Application of a CADM1 blocking peptide or knockdown of CADM1 in BMMCs significantly decreased BMMC attachment to sensory neurites and abolished the enhanced secretory responses of mast cells. In conclusion, CADM1 is necessary and sufficient to drive mast cell-sensory neuron adhesion and promote the development of a microenvironment in which neurons enhance mast cell responsiveness to antigen; this interaction could explain why the incidence of painful neuroinflammatory disorders such as irritable bowel syndrome (IBS) are increased in atopic patients
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