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1.
Soft Matter ; 19(36): 6871-6874, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37682026

RESUMO

Pure cyclic diamino acids (CdAA) gel differently than combinations of CdAAs, altering the gelation behavior to highly-branched colloidal protein crystal networks reminiscent of traditional fat crystal networks in canola oil, making it an exciting structuring agent for unsaturated oils.

2.
Lett Appl Microbiol ; 65(4): 292-297, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28727890

RESUMO

The effect of surfactant type and concentration on a bland soap formulation's ability to remove bacteria from hands remains largely unstudied. Several combinations of surfactants and water were combined to test bacterial removal efficacy using a hand-washing device (two pieces of pig skin and a mechanical motor) to simulate a hand wash. A nalidixic acid-resistant, nonpathogenic strain of Escherichia coli (ATCC 11229) was used. Two anionic surfactants, sodium lauryl sulphate and sodium stearoyl lactylate, and two nonionic surfactants, poloxamer 407 and sorbitan monostearate, each in concentrations of 2, 5 and 10% were studied. A slight positive (r2  = 0·17) but significant (P = 0·03) correlation was observed between hydrophile-lipophile balance value and mean log reduction. No correlation was observed between pH of the treatment solution and the mean log reduction (r2  = 0·05, P = 0·25). A 10% sodium lauryl sulphate mixture showed the highest log reduction (x¯ = 1·1 log CFU reduction, SD = 0·54), and was the only treatment significantly different from washing with water (P = 0·0005). There was a correlation between increasing surfactant concentrations above the critical micelle concentration, and mean microbial reduction (r2  = 0·62, P = 0·001). SIGNIFICANCE AND IMPACT OF THE STUDY: This study characterizes the role of surfactants in removing microbes during a hand wash. Numerous studies address how surfactants support antimicrobial effect in soap, or cause irritation of skin, but no published studies show which surfactants are best for removing microbes. We used pig skin as a model for human skin and a lathering device to simulate a hand wash. A 10% sodium lauryl sulphate mixture was the only treatment significantly different from a water wash. There was a strong correlation between increasing surfactant concentrations above the critical micelle concentration and mean microbial reduction.


Assuntos
Desinfecção/métodos , Escherichia coli/efeitos dos fármacos , Desinfecção das Mãos/métodos , Sabões/farmacologia , Tensoativos/farmacologia , Animais , Contagem de Colônia Microbiana , Mãos/microbiologia , Hexoses/farmacologia , Humanos , Poloxâmero/farmacologia , Pele/microbiologia , Dodecilsulfato de Sódio/farmacologia , Estearatos/farmacologia , Sus scrofa , Suínos , Água/química
3.
Vox Sang ; 110(3): 266-77, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26689441

RESUMO

BACKGROUND AND OBJECTIVES: The recent establishment of the National Healthcare Safety Network Hemovigilance Module in the United States affords an opportunity to compare results with those of other developed nations. MATERIALS AND METHODS: Using data from national haemovigilance systems, reactions associated with red blood cell (RBC) transfusion and residual risks of transfusion-transmitted infectious diseases were assembled from 17 nations. Country-specific rates of adverse events were pooled using random-effects Poisson regression. RESULTS: Febrile non-haemolytic and delayed serologic transfusion reactions were the most frequent adverse events reported after RBC transfusion, occurring in 26 patients per 100 000 RBC units and 25 patients per 100 000 RBC units administered, respectively. Rates of allergic, febrile non-haemolytic and delayed haemolytic transfusion reactions in the United States were significantly greater than the pooled rates from other countries. Frequencies of adverse events generated from the national haemovigilance programme in the United States were considerably lower than when obtained through active surveillance. CONCLUSION: Haemovigilance reports of adverse events in the United States are comparable to, or greater than, reports from other developed countries. Rates generated from haemovigilance programmes are lower than those obtained through active surveillance. The lack of universal leucoreduction of RBC units may be a contributing factor to the higher rate of some adverse events in the United States.


Assuntos
Segurança do Sangue/estatística & dados numéricos , Transfusão de Eritrócitos/efeitos adversos , Reação Transfusional/etiologia , América , Ásia , Australásia , Doenças Transmissíveis/transmissão , Europa (Continente) , Humanos , Risco , Viroses/transmissão
4.
Chem Soc Rev ; 44(17): 6035-58, 2015 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-25941907

RESUMO

Rational design of small molecular gelators is an elusive and herculean task, despite the rapidly growing body of literature devoted to such gels over the past decade. The process of self-assembly, in molecular gels, is intricate and must balance parameters influencing solubility and those contrasting forces that govern epitaxial growth into axially symmetric elongated aggregates. Although the gelator-gelator interactions are of paramount importance in understanding gelation, the solvent-gelator specific (i.e., H-bonding) and nonspecific (dipole-dipole, dipole-induced and instantaneous dipole induced forces) intermolecular interactions are equally important. Solvent properties mediate the self-assembly of molecular gelators into their self-assembled fibrillar networks. Herein, solubility parameters of solvents, ranging from partition coefficients (log P), to Henry's law constants (HLC), to solvatochromic parameters (ET(30)), and Kamlet-Taft parameters (ß, α and π), and to Hansen solubility parameters (δp, δd, δh), are correlated with the gelation ability of numerous classes of molecular gelators. Advanced solvent clustering techniques have led to the development of a priori tools that can identify the solvents that will be gelled and not gelled by molecular gelators. These tools will greatly aid in the development of novel gelators without solely relying on serendipitous discoveries. These tools illustrate that the quest for the universal gelator should be left in the hands of Don Quixote and as researchers we must focus on identifying gelators capable of gelling classes of solvents as there is likely no one gelator capable of gelling all solvents.


Assuntos
Géis/química , Solventes/química , Modelos Químicos , Solubilidade , Termodinâmica
5.
Soft Matter ; 10(43): 8652-8, 2014 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-25252108

RESUMO

Molecular rotors may be utilized as non-invasive, non-disruptive and highly sensitive alternatives to conventional measures of bulk viscosity when the oil is entrained in a colloidal fat crystal network. Oil viscosity changes based on the molecular confinement of the oil, which is dependent on its molecular volume. Changes in micro-viscosity were not dependent on the solids content, but instead were strongly dependent on the box-counting fractal dimension in high-space filling colloidal fat crystal networks (i.e., D > 1.89). A bulk oil viscosity is often an overestimation of the actual viscosity of the entrained oil and may not be appropriate when predicting diffusion in multi-phase materials.

6.
Nat Genet ; 16(4): 372-4, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9241275

RESUMO

Pathogenic mutations in a large number of human epithelial keratins have been well characterized. However, analogous mutations in the hard alpha-keratins of hair and nail have not yet been described. Monilethrix is a rare autosomal dominant hair defect with variable expression. Hairs from affected individuals show a beaded structure of alternating elliptical nodes and constrictions (internodes). These internodes exhibit a high prospensity to weathering and fracture. Strong evidence that trichocyte keratin defects might underlie this hair disorder was provided by genetic linkage analyses that mapped this disease to the type-II keratin gene cluster on 12q13. All affected individuals from a four-generation British family with monilethrix, previously linked to the type-II keratin gene cluster, as well as three unrelated single monilethrix patients, exhibited a heterozygous point mutation in the gene for type-II hair cortex keratin hHb6, leading to lysine substitution of a highly conserved glutamic acid residue in the helix termination motif (Glu 410 Lys). In a three-generation French family with monilethrix of a milder and variable phenotype, we detected another heterozygous point mutation in the same glutamic acid codon of hHb6, which resulted in a conservative aspartic acid substitution (Glu 410 Asp). These mutations provide the first direct evidence for involvement of hair keratins in hair disease.


Assuntos
Doenças do Cabelo/genética , Queratinas/genética , Mutação , Adolescente , Criança , Feminino , Ácido Glutâmico , Doenças do Cabelo/patologia , Heterozigoto , Humanos , Lisina , Masculino , Pessoa de Meia-Idade , Linhagem
7.
Nanoscale ; 15(42): 16933-16946, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37850382

RESUMO

Substituting the sole primary hydroxyl group of the low molecular weight organogelator (LMOG), 1,3:2,4-dibenzylidene-D-sorbitol (DBS), with a halogen atom (Cl, Br, or I; i.e., 6-Cl-DBS, 6-Br-DBS, or 6-I-DBS) drastically alters the supramolecular self-assembled fibrillar network (SAFiN) that forms when the molecules aggregate. The SAFiN varies depending on the solvent properties, impacting the role of non-covalent hydrogen- and halogen-bonding interactions along and between fibers. The halogenated DBS derivatives have more coherent crystalline fibers than DBS, with larger length-to-width aspect ratios. High-resolution synchrotron powder X-ray diffraction of each wet-state gel in toluene and DFT optimization obtained complete structures for the three halogenated DBS derivatives in their SAFiNs. The presence of a halogen atom reduces the reliance on hydrogen bonding by enabling new halogen bonding interactions that impact the self-assembly behavior, especially in solvents of higher polarity. For 6-I-DBS and 6-Br-DBS, the primary forces driving molecular self-assembly are C-H⋯π and intermolecular halogen-to-halogen interactions, and there is one unique molecule in each unit cell. However, the Cl atoms of 6-Cl-DBS are not close, and its SAFiN structures rely more on hydrogen bonding. As a result, the enhanced hydrogen bonding, electronic differences among the halogens, and spatial factors allow its unit cell to include two independent molecules of 6-Cl-DBS.

8.
Food Chem ; 382: 132326, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35152026

RESUMO

10 wt% oil-in-water emulsions with varied palm olein and stearin PO:PS ratios stabilized with 0.8 wt% Tween80 and tempered to obtain partially crystalline (CR) droplets (cooled from 80 to 4 °C and held overnight to induce nucleation/crystallization) or undercooled liquid (UC) droplets (cooled from 80 °C to 37 °C) produced emulsions with constant droplet size and polymorphism. However, zeta-potential decreased in undercooled emulsions due to crystallization/orientation of interfacial Tween, increasing alignment and ultimately a greater dipole moment. Significant differences in overall bioaccessibility between PO and PS present for the CR (PO bioaccessible fraction was 91%, whereas PS was 60%) and UC emulsions (PO and PS bioaccessibility were 96% and 77%).When only the solid fat content differs, and all other physical attributes remain constant, lipid digestibility decreases with increasing solid fat content; these findings, along with others, can be employed during food formulation and design more healthful foods.


Assuntos
Polissorbatos , Água , Cristalização , Digestão , Emulsões/química , Tamanho da Partícula , Polissorbatos/química , Água/química
9.
J Agric Food Chem ; 69(30): 8394-8402, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34313430

RESUMO

Changes in the physical states, induced with different sous vide cooking temperatures, significantly (P < 0.05) altered lipid bioaccessibility measured in the TNO-simulated gastrointestinal tract model-1 of AAA boneless beef striploin, containing the longissimus lumborum muscle. The denaturation of actin significantly correlates with the total cumulative free fatty acid (FFA) bioaccessibility, whereby the striploin cooked to 60 °C presents the maximum lipid bioaccessibility (15.8 ± 1.0%), rate constant (ka) for FFA hydrolysis (0.087 ± 0.003 min-1), and greatest actin denaturation enthalpy (-0.57 ± 0.06 ΔH). Thus, thermal treatments above 60 °C significantly decrease the kinetics of lipolysis (70 °C = 0.042 ± 0.002 min-1 and 80 °C = 0.047 ± 0.002 min-1) and the resultant total lipid bioaccessibility (70 °C = 8.6 ± 0.7 and 80 °C = 8.3 ± 0.5%). This research highlights the potential to manipulate the physical food structure to alter digestion kinetics, supporting the need to understand supramolecular structures in food and their nutritional outcomes.


Assuntos
Culinária , Lipídeos , Animais , Bovinos , Músculos , Temperatura
11.
Br J Dermatol ; 160(3): 527-33, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19067701

RESUMO

BACKGROUND: Pili annulati is an autosomal dominant hair shaft disorder characterized by alternating light and dark bands in hairs of affected individuals. Recently, a locus for pili annulati was mapped to chromosome 12q24.32-24.33 and recombination events defined a critical region of 9.2 cM (3.9 Mb). OBJECTIVES: The aim of the current study was to narrow the size of the candidate region and to identify the pathogenic mutation for pili annulati by analysing the candidate genes. METHODS: In three families with 90 individuals, including 40 affected subjects, linkage analysis was performed with 13 microsatellite markers in the candidate region on chromosome 12. Candidate genes were analysed for their expression in hair follicles and other tissues by reverse transcriptase-polymerase chain reaction (RT-PCR) and mutation analysis. RESULTS: Multipoint LOD score analysis for all three families confirmed the locus on the long arm of chromosome 12 with a maximum LOD score of 12.26 at marker D12S357. In two families, recombinations were identified which narrowed the region to 2.9 Mb containing 36 genes. We analysed the candidate genes in this region by RT-PCR and found that 24 were expressed in human hair follicles. Based on the result of the expression analysis, DNA sequencing of the coding region of the candidate genes was performed; this did not result in the discovery of a causal mutation. CONCLUSION: We reduced the critical interval of pili annulati to 2.9 Mb and excluded mutations in the coding region of all 36 possible candidate genes by sequence analysis.


Assuntos
Cromossomos Humanos Par 12/genética , Cabelo/anormalidades , Mutação , Mapeamento Cromossômico/métodos , Análise Mutacional de DNA/métodos , Feminino , Folículo Piloso/metabolismo , Humanos , Escore Lod , Masculino , Repetições de Microssatélites , Linhagem , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos
12.
Science ; 184(4139): 857-65, 1974 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-17782370

RESUMO

The probable range of seepage into the marine environment is 0.2 x 10(6) to 6.0 x 10(6) metric tons per year. Within this range the best estimate for the present marine seepage worldwide is on the order of 0.6 x 10(6) metric tons per year. This estimate is based on the presumption that only a few other areas around the world are as seepage-prone as southern California. Measurements of seeps and seepage rates are too few to allow an accurate estimation by observation and measurement techniques alone. Seepage potential can, however, be related to geologic criteria, and these provide sound bases for marine seepage assessment. On the basis of this estimate, areas of high seepage potential contribute about 45 percent of the worldwide seepage, areas of moderate seepage about 55 percent, and areas of low seepage less than 1 percent. The situation varies somewhat from ocean to ocean. In the Pacific Ocean, areas of high seep potential are by far the major contributors. In the Atlantic, Indian, Arctic, and Southern oceans, areas of moderate seep potential are most significant because areas of high seep potential are relatively rare in these realnis. The circum-Pacific area is the area of greatest seepage; it contributes about 40 percent of the world's total.

13.
Adv Food Nutr Res ; 88: 1-45, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31151722

RESUMO

Nanotechnology is a rapidly developing toolbox that provides solutions to numerous challenges in the food industry and meet public demands for healthier and safer food products. The diversity of nanostructures and their vast, tunable functionality drives their inclusion in food products and packaging materials to improve their nutritional quality through bioactive fortification and probiotics encapsulation, enhance their safety due to their antimicrobial and sensing capabilities and confer novel sensorial properties. In this food nanotechnology state-of-the-art communication, matrix materials with particular focus on food-grade components, existing and novel production techniques, and current and potential applications in the fields of food quality, safety and preservation, nutrient bioaccessibility and digestibility will be detailed. Additionally, a thorough analysis of potential strategies to assess the safety of these novel nanostructures is presented.


Assuntos
Indústria Alimentícia/tendências , Alimentos/normas , Nanoestruturas/classificação , Nanotecnologia/métodos , Biopolímeros , Indústria Alimentícia/normas , Conservação de Alimentos/métodos , Inocuidade dos Alimentos/métodos , Marketing/tendências , Nanopartículas
14.
Br J Dermatol ; 159(3): 725-9, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18647308

RESUMO

BACKGROUND: Human hair follicle keratin-associated proteins (KAPs) comprise a large multigene family of proteins thought to be responsible for the bundling of keratin intermediate filaments. Recently, four new KAP family members KAP24.1, KAP25.1, KAP26.1 and KAP27.1 were identified from the genome, but the expression of only one, KAP24.1, was investigated and shown in hair follicles. OBJECTIVES: In the current study, the expression of the remaining members of the family were analysed. METHODS: Reverse transcriptase-polymerase chain reaction analysis of samples from numerous human organs was used. RESULTS: Only KAP26.1 showed expression, which was limited to the hair follicle. By in situ hybridization and immunohistochemistry using a specific antiserum, KAP26.1 was localized to the differentiated portion of the hair cuticle. CONCLUSIONS: As well as KAP24.1 in hair follicles, expression of KAP26.1 was shown and is found in the differentiated part of the hair cuticle.


Assuntos
Folículo Piloso/química , Proteínas de Filamentos Intermediários/genética , Sequência de Aminoácidos , Sequência de Bases , Técnica Indireta de Fluorescência para Anticorpo/métodos , Expressão Gênica , Humanos , Hibridização In Situ/métodos , Proteínas de Filamentos Intermediários/análise , Dados de Sequência Molecular , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos
15.
Food Funct ; 9(3): 1809-1815, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29513342

RESUMO

In vivo studies measuring true fractional calcium (Ca) absorption have shown that dietary fat is a significant predictor of absorption and is influenced by luminal pH levels. However, whether changes in Ca bioaccessibility (CaB) can explain the effects on absorption has not been examined. In the current study, we examined two high fat diets enriched in either monounsaturated fatty acids or saturated fatty acids (SFA), and a low-fat diet (LFD), each with 50 mg Ca, and measured CaB at different intestinal regions during normal acidic or higher (pH = 7) gastrointestinal conditions using an in vitro gastrointestinal model. During normal pH conditions in the jejunum, there was an interaction between diet and time for CaB (P < 0.02), and CaB during the SFA diet was higher than LFD (P = 0.05). CaB was reduced by 90 ± 3% during higher compared with normal pH under all dietary conditions (P < 0.001). These findings indicate that fat intake, especially SFA enriched, is associated with a greater CaB in the jejunum, and may explain the higher Ca absorption in previous studies. In addition, the marked reduction in CaB under higher pH conditions could have implications in persons taking medications to reduce gastric acid.


Assuntos
Cálcio da Dieta/metabolismo , Gorduras na Dieta/metabolismo , Mucosa Intestinal/metabolismo , Ácidos Graxos/metabolismo , Ácidos Graxos Monoinsaturados/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Modelos Biológicos
16.
Food Res Int ; 97: 307-317, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28578056

RESUMO

Trans and saturated fat replacers/substitutes have been a tremendously active area of research for the food industry. Unlike polymers used for hydrogels, oleogels utilize small, amphiphilic molecules that self-assemble via highly specific, non-covalent interactions entrapping liquid oil via capillary forces. Edible applications of oleogels have replaced the need for trans unsaturated and saturated fatty acids to structure processed foods. These innovations mitigate the use of hardstock fats that are associated with deleterious health risks and negative consumer perception. Over the past decade, oleogels have made significant strides towards emulating desired sensory traits while maintaining healthy nutritional profile of the oil. Due to the rapid advancements in the past decade, the most promising technologies will be reviewed.


Assuntos
Substitutos da Gordura , Tecnologia de Alimentos , Tecnologia de Alimentos/métodos , Tecnologia de Alimentos/tendências , Compostos Orgânicos
17.
J Thromb Haemost ; 15(10): 1951-1962, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28796444

RESUMO

Essentials How best to quantify thrombosis risk with peripherally inserted central catheters (PICC) is unknown. Data from a registry were used to develop the Michigan Risk Score (MRS) for PICC thrombosis. Five risk factors were associated with PICC thrombosis and used to develop a risk score. MRS was predictive of the risk of PICC thrombosis and can be useful in clinical practice. SUMMARY: Background Peripherally inserted central catheters (PICCs) are associated with upper extremity deep vein thrombosis (DVT). We developed a score to predict risk of PICC-related thrombosis. Methods Using data from the Michigan Hospital Medicine Safety Consortium, image-confirmed upper-extremity DVT cases were identified. A logistic, mixed-effects model with hospital-specific random intercepts was used to identify factors associated with PICC-DVT. Points were assigned to each predictor, stratifying patients into four classes of risk. Internal validation was performed by bootstrapping with assessment of calibration and discrimination of the model. Results Of 23 010 patients who received PICCs, 475 (2.1%) developed symptomatic PICC-DVT. Risk factors associated with PICC-DVT included: history of DVT; multi-lumen PICC; active cancer; presence of another CVC when the PICC was placed; and white blood cell count greater than 12 000. Four risk classes were created based on thrombosis risk. Thrombosis rates were 0.9% for class I, 1.6% for class II, 2.7% for class III and 4.7% for class IV, with marginal predicted probabilities of 0.9% (0.7, 1.2), 1.5% (1.2, 1.9), 2.6% (2.2, 3.0) and 4.5% (3.7, 5.4) for classes I, II, III, and IV, respectively. The risk classification rule was strongly associated with PICC-DVT, with odds ratios of 1.68 (95% CI, 1.19, 2.37), 2.90 (95% CI, 2.09, 4.01) and 5.20 (95% CI, 3.65, 7.42) for risk classes II, III and IV vs. risk class I, respectively. Conclusion The Michigan PICC-DVT Risk Score offers a novel way to estimate risk of DVT associated with PICCs and can help inform appropriateness of PICC insertion.


Assuntos
Obstrução do Cateter/etiologia , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/instrumentação , Cateterismo Periférico/efeitos adversos , Cateterismo Periférico/instrumentação , Cateteres de Demora , Cateteres Venosos Centrais , Técnicas de Apoio para a Decisão , Trombose Venosa Profunda de Membros Superiores/etiologia , Idoso , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Sistema de Registros , Medição de Risco , Fatores de Risco
18.
J Natl Cancer Inst ; 90(1): 37-42, 1998 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-9428781

RESUMO

BACKGROUND: Estrogen exposure is a major risk factor for breast cancer. Increased estrogen responsiveness of breast epithelium may enhance this effect. We examined the relationship between breast cancer diagnosis and 1) the presence and absence of estrogen receptor expression in benign breast epithelium, 2) the level of expression and 3) its variation during the menstrual cycle, and 4) other established risk factors. e.g., age, age at menarche, parity, and family history. METHODS: We measured estrogen receptor expression (as % of positive cells) by immunohistochemistry in normal breast epithelium from 376 women undergoing diagnostic or therapeutic breast surgery. Data on established risk factors were collected prior to surgery and those on menstrual cycle dates at the time of surgery. Logistic regression was used to assess risks (odds ratios [ORs]). RESULTS: The crude OR for breast cancer in women with estrogen receptor-positive breast epithelium versus those without was 3.16 (95% confidence interval [CI] = 1.89-5.28), with an OR of 2.49 (95% CI = 1.25-4.96) for premenopausal and an OR of 3.32 (95% CI = 1.43-7.68) for postmenopausal women. The ORs remained high and statistically significant after controlling for age and other breast cancer risk factors. The level of estrogen receptor expression was higher in patients with breast cancer than in control subjects and it was related to breast cancer risk in postmenopausal women (P trend <.005). Expression declined as expected in premenopausal control subjects as the menstrual cycle progressed but rose in breast cancer patients (P trend <.015). CONCLUSIONS: The overexpression of estrogen receptors in normal breast epithelium may augment estrogen sensitivity and hence the risk of breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Mama/metabolismo , Receptores de Estrogênio/metabolismo , Adulto , Neoplasias da Mama/etiologia , Neoplasias da Mama/fisiopatologia , Estudos de Casos e Controles , Epitélio/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Ciclo Menstrual , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Risco , Fatores de Risco
19.
Cancer Res ; 54(4): 993-7, 1994 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-8313390

RESUMO

We conducted a case-control study of estrogen receptor (ER) and progesterone receptor (PgR) expression in benign breast epithelium from 120 women (51 breast cancer cases and 69 benign disease controls) who underwent breast operations at University Hospital, Syracuse, New York. Benign samples were obtained and processed immunohistochemically for ER and PgR (Abbott, Chicago, IL). Receptor positivity was defined as any nuclear immunostaining. Proportionately more cases than controls were ER positive (84% versus 57%); PgR positivity was similar in cases and controls (86%). Logistic regression yielded an adjusted odds ratio of 6.5 for breast cancer among ER-positive women (95% confidence interval of 1.5 and 27.4); odds ratio of PgR positivity was 0.3 (95% confidence interval of 0.1 and 1.9). Adjustment for known risk factors for breast cancer did not change the odds ratio. ER-positive breast epithelium needs evaluation as a possible risk marker for breast cancer.


Assuntos
Neoplasias da Mama/química , Mama/química , Receptores de Estrogênio/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Divisão Celular , Epitélio/química , Feminino , Humanos , Mastectomia , Ciclo Menstrual , Pessoa de Meia-Idade , Receptores de Progesterona/análise
20.
Cancer Res ; 55(21): 4844-9, 1995 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-7585518

RESUMO

1-O-Octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) is a synthetic diether phospholipid that is competitive with phosphatidylserine binding to the regulatory domain of protein kinase C (PKC). Our previous studies indicate that the selective inhibition of tumor cell growth by ET-18-OCH3 may be due to altered signal transduction mechanisms, including the inhibition of PKC. To further define the mechanism of action of ET-18-OCH3, we have used it to study the role of PKC in regulation of the transcription factor NF-kappa B, which is activated by diverse stimuli. In the 293.27.2 human kidney cell line, as in hematopoietic cells of all lineages, NF-kappa B is stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 alpha (IL-1 alpha). The response to either TNF-alpha or IL-1 alpha is synergistically enhanced by TPA. However, the regulatory mechanisms and signal transduction systems responsible for NF-kappa B activation in response to these different stimuli have not been determined in detail. We have used ET-18-OCH3 and auranofin, which inhibit PKC by different mechanisms, to assess the role of PKC in NF-kappa B activation. ET-18-OCH3 markedly inhibits TPA-induced NF-kappa B activation, as measured by HIV long terminal repeat-directed expression of beta-galactosidase. The IC50 for inhibition by ET-18-OCH3 is approximately 2 microM, a noncytotoxic concentration. Inhibition of TPA-induced NF-kappa B activation was dependent upon preincubation with ET-18-OCH3, and the drug was active at approximately 2 mol% of total cellular phospholipid. ET-18-OCH3 did not inhibit NF-kappa B activation by either TNF-alpha or IL-1 alpha, indicating that there are multiple distinct signal transduction pathways leading to activation of NF-kappa B. We have confirmed these results using auranofin, an antirheumatic drug that is a specific PKC inhibitor interacting with the catalytic domain. Like ET-18-OCH3, auranofin blocked NF-kappa B activation by TPA but not by TNF-alpha or IL-1 alpha. Also like the ether lipid, auranofin only partially blocked the synergy exhibited by TPA and TNF-alpha. To confirm the role of NF-kappa B in this response, we measured NF-kappa B by electrophoretic mobility shift assay. Both ET-18-OCH3 and auranofin inhibited cellular induction of the active NF-kappa B complex in response to TPA but not in response to TNF-alpha.(ABSTRACT TRUNCATED AT 400 WORDS)


Assuntos
Antineoplásicos/farmacologia , Carcinógenos/antagonistas & inibidores , Carcinógenos/farmacologia , Interleucina-1/farmacologia , NF-kappa B/antagonistas & inibidores , NF-kappa B/efeitos dos fármacos , Éteres Fosfolipídicos/farmacologia , Acetato de Tetradecanoilforbol/antagonistas & inibidores , Acetato de Tetradecanoilforbol/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Auranofina/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Interações Medicamentosas , Inibidores Enzimáticos/farmacologia , Expressão Gênica/efeitos dos fármacos , HIV/genética , Humanos , Rim/citologia , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/fisiologia , Sequências Repetitivas de Ácido Nucleico , Estimulação Química , Transfecção
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