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1.
J Mammary Gland Biol Neoplasia ; 24(1): 99-108, 2019 03.
Article in English | MEDLINE | ID: mdl-30099649

ABSTRACT

Androgens influence mammary gland development but the specific role of the androgen receptor (AR) in mammary function is largely unknown. We identified cell subsets that express AR in vivo and determined the effect of AR activation and transgenic AR inhibition on sub-populations of the normal mouse mammary epithelium by flow cytometry and immunohistochemistry. Immunolocalisation of AR with markers of lineage identity was also performed in human breast tissues. AR activation in vivo significantly decreased the proportion of basal cells, and caused an accumulation of cells that expressed a basal cell marker but exhibited morphological features of luminal identity. Conversely, in AR null mice the proportion of basal mammary epithelial cells was significantly increased. Inhibition of AR increased basal but not luminal progenitor cell activity in vitro. A small population of AR-positive cells in a basal-to-luminal phenotype transition was also evident in human breast lobules. Collectively, these data support a role for AR in promoting a luminal phenotype in mammary epithelial cells.


Subject(s)
Epithelial Cells/metabolism , Mammary Glands, Animal/physiology , Mammary Glands, Human/physiology , Receptors, Androgen/metabolism , Animals , Cell Differentiation , Cell Proliferation , Cells, Cultured , Estrogen Receptor alpha/metabolism , Estrus/metabolism , Female , Humans , Mammary Glands, Animal/cytology , Mammary Glands, Human/cytology , Mice , Mice, Knockout , Premenopause/metabolism , Primary Cell Culture , Receptors, Androgen/genetics , Receptors, Progesterone/metabolism , Signal Transduction/physiology
2.
Psychol Med ; 44(2): 361-70, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23480876

ABSTRACT

BACKGROUND: Despite its high prevalence and associated levels of impairment, the latent structure of social anxiety disorder (SAD) is not well understood, with published studies reporting inconsistent results. Furthermore, it is unknown whether the latent structure of social fears in individuals with and without SAD is the same. METHOD: Exploratory factor analysis (EFA) and confirmatory factor analysis followed by multiple indicators multiple causes (MIMIC) analysis were conducted on 13 commonly feared social situations assessed in a nationally representative sample including individuals with SAD and those with social fears but who did not meet DSM-IV criteria for SAD. RESULTS: An EFA conducted in the full sample, including individuals with no social fears (88% of the sample), yielded only one factor. When the sample was restricted to those with at least one social fear, the EFA yielded three factors, in both the subsample with at least one social fear but no SAD and the subsample with SAD. The three factors represented feared situations related to public performance, close scrutiny and social interaction. The MIMIC analyses further indicated that the three-factor structure was able to explain differences in prevalence of social fears across a broad range of sociodemographic covariates. CONCLUSIONS: Among individuals with at least one social fear and those with DSM-IV SAD the latent structure of social fears appears to be best described by three factors, although this may partially depend on how the sample is specified. These results may help reconcile the findings of different numbers of factors identified in previous studies.


Subject(s)
Factor Analysis, Statistical , Phobic Disorders/physiopathology , Adolescent , Adult , Female , Humans , Male , Middle Aged , Phobic Disorders/classification , Phobic Disorders/epidemiology , Prevalence , Reaction Time/physiology , Socioeconomic Factors , United States/epidemiology , Young Adult
3.
Trans R Soc Trop Med Hyg ; 100(7): 642-9, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16274713

ABSTRACT

Controlled heat delivered as radio waves has been used successfully in the treatment of cutaneous leishmaniasis (CL). Here we investigated whether local heat therapy has systemic effects, as measured by the modulation of cytokine production following heat therapy of CL lesions compared with antimonial (Glucantime) treatment. Patients with CL were randomly assigned into this study. Heat (50 degrees C for 30s) was applied once. The control group received Glucantime therapy for 20 d. Cytokine production by peripheral blood mononuclear cells was assayed on days 0, 14 and 28 after onset of treatment. At the end of 28 d, 75% of lesions were healing or healed in the heat therapy group and 90% in the control group (P=0.1261). There was a decrease in IFN-gamma, IL-5 and TNF-alpha levels comparing day 0 with day 28 in both groups, but no difference between the two therapy groups. In patients with only one of several lesions treated with heat therapy, the untreated lesions also healed. Local heat therapy in CL lesions leads to systemic cytokine responses similar to that induced by systemic Glucantime therapy.


Subject(s)
Antiprotozoal Agents/therapeutic use , Cytokines/metabolism , Hot Temperature/therapeutic use , Leishmaniasis, Cutaneous/therapy , Meglumine/therapeutic use , Organometallic Compounds/therapeutic use , Adolescent , Adult , Aged , Female , Humans , Interferon-gamma/metabolism , Interleukin-10/metabolism , Interleukin-5/metabolism , Leishmaniasis, Cutaneous/drug therapy , Leishmaniasis, Cutaneous/immunology , Leukocytes, Mononuclear/immunology , Male , Meglumine Antimoniate , Middle Aged , Treatment Outcome , Tumor Necrosis Factor-alpha/metabolism
4.
J Control Release ; 52(1-2): 41-51, 1998 Mar 02.
Article in English | MEDLINE | ID: mdl-9685934

ABSTRACT

Thermosensitive polymer networks were synthesized from poly(ethylene glycol), hexamethylene diisocyanate and 1,2,6-hexanetriol in stoichiometric proportions. By varying the amount of 1,2,6-hexanetriol and the molar mass of the poly(ethylene glycol), a wide range of networks with different crosslinking densities was prepared. The networks obtained were characterized by the temperature dependence of their degree of equilibrium swelling in water and by their Young's moduli. For each network, the molecular weight between crosslinks was estimated. The structure of the hydrogels was analysed with respect to scaling laws, and it was found that the results obtained with PEG 1500 and PEG 6000 hydrogels are in agreement with theoretical predictions, whereas those obtained with PEG 400 hydrogels are in disagreement. The release properties of PEG hydrogels were studied by the determination of the diffusion coefficient for acebutolol chlorhydrate and by an analysis of the effect of temperature on these coefficients. Finally, these release properties were correlated with the swelling and structural properties of the hydrogels.


Subject(s)
Polyethylene Glycols/chemistry , Acebutolol/administration & dosage , Diffusion , Hydrogel, Polyethylene Glycol Dimethacrylate , Molecular Weight , Polyethylene Glycols/administration & dosage , Temperature
5.
Arq. bras. med ; 66(1): 67-71, jan.-fev. 1992. tab
Article in Portuguese | LILACS | ID: lil-228170

ABSTRACT

Aztreonam é um composto de uma nova classe de agentes Beta-lactâmicos monocíclicos sintéticos com atividade contra a grande maioria das bactérias Gram-negativas, mas nao contra as bactérias Gram-positivas ou anaeróbias. Aztreonam foi usado para tratar 23 pacientes com importantes infeccçoes por germes Gram-negativos. Neste estudo dos 17 homens e seis mulheres, haviam 11 casos de infecçoes urinárias, três de pneumonia, três de meningite e seis com outros locais de infecçao. Noventa por cento das infecçoes foram curadas tanto por critérios clínicos como microbiológicos sem significantes reaçoes adversas ou toxicidade pela droga.


Subject(s)
Humans , Male , Female , Aztreonam/therapeutic use , Gram-Negative Bacterial Infections/drug therapy , Monobactams/therapeutic use , Prospective Studies , Treatment Outcome
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