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1.
Cereb Cortex ; 31(8): 3856-3871, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-33825852

RESUMO

Cognitive performance in children is predictive of academic and social outcomes; therefore, understanding neurobiological mechanisms underlying individual differences in cognition during development may be important for improving quality of life. The belief that a single, psychological construct underlies many cognitive processes is pervasive throughout society. However, it is unclear if there is a consistent neural substrate underlying many cognitive processes. Here, we show that a distributed configuration of cortical surface area and apparent thickness, when controlling for global imaging measures, is differentially associated with cognitive performance on different types of tasks in a large sample (N = 10 145) of 9-11-year-old children from the Adolescent Brain and Cognitive DevelopmentSM (ABCD) study. The minimal overlap in these regionalization patterns of association has implications for competing theories about developing intellectual functions. Surprisingly, not controlling for sociodemographic factors increased the similarity between these regionalization patterns. This highlights the importance of understanding the shared variance between sociodemographic factors, cognition and brain structure, particularly with a population-based sample such as ABCD.


Assuntos
Córtex Cerebral/anatomia & histologia , Córtex Cerebral/fisiologia , Cognição/fisiologia , Adolescente , Desenvolvimento do Adolescente , Criança , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Desempenho Psicomotor/fisiologia , Sensibilidade e Especificidade , Fatores Sociodemográficos
2.
Mol Psychiatry ; 22(6): 792-801, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28348379

RESUMO

The most recent genome-wide association studies (GWAS) of schizophrenia (SCZ) identified hundreds of risk variants potentially implicated in the disease. Further, novel statistical methodology designed for polygenic architecture revealed more potential risk variants. This can provide a link between individual genetic factors and the mechanistic underpinnings of SCZ. Intriguingly, a large number of genes coding for ionotropic and metabotropic receptors for various neurotransmitters-glutamate, γ-aminobutyric acid (GABA), dopamine, serotonin, acetylcholine and opioids-and numerous ion channels were associated with SCZ. Here, we review these findings from the standpoint of classical neurobiological knowledge of neuronal synaptic transmission and regulation of electrical excitability. We show that a substantial proportion of the identified genes are involved in intracellular cascades known to integrate 'slow' (G-protein-coupled receptors) and 'fast' (ionotropic receptors) neurotransmission converging on the protein DARPP-32. Inspection of the Human Brain Transcriptome Project database confirms that that these genes are indeed expressed in the brain, with the expression profile following specific developmental trajectories, underscoring their relevance to brain organization and function. These findings extend the existing pathophysiology hypothesis by suggesting a unifying role of dysregulation in neuronal excitability and synaptic integration in SCZ. This emergent model supports the concept of SCZ as an 'associative' disorder-a breakdown in the communication across different slow and fast neurotransmitter systems through intracellular signaling pathways-and may unify a number of currently competing hypotheses of SCZ pathophysiology.


Assuntos
Receptores Ionotrópicos de Glutamato/genética , Receptores de Glutamato Metabotrópico/genética , Esquizofrenia/genética , Encéfalo/metabolismo , Dopamina/metabolismo , Fosfoproteína 32 Regulada por cAMP e Dopamina/metabolismo , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores Ionotrópicos de Glutamato/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Fatores de Risco , Transdução de Sinais/genética , Transmissão Sináptica/genética , Ácido gama-Aminobutírico/metabolismo
3.
J Nanosci Nanotechnol ; 18(6): 4217-4221, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29442765

RESUMO

The flicker noise of source follower transistors is the dominant noise source in image sensors. This paper reports a systematic study of the shallow trench isolation effect in transistors with different sizes under high temperature conditions that correspond to the quantity of empty defect sites. The effects of shallow trench isolation sidewall defects on flicker noise characteristics are investigated. In addition, the low-frequency noise and subthreshold swing degrade simultaneously in accordance to the device gate width scaling. Both serious subthreshold leakage and considerable noise can be attributed to the high trap density near the STI edge. Consequently, we propose a coincidental relationship between the noise level and the subthreshold characteristic; its trend is identical to the experiments and simulation results.

4.
Eur Rev Med Pharmacol Sci ; 28(1): 278-287, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38235879

RESUMO

OBJECTIVE: To investigate the effects of parecoxib on postoperative cognitive dysfunction, and serum levels of neuron-specific enolase (NSE) and S100ß protein (S100ß) in elderly patients undergoing surgery. PATIENTS AND METHODS: The retrospective cohort study method was used to collect the clinical data of 94 elderly patients who underwent elective orthopedic and general anesthesia surgery in our hospital from September 2020 to February 2022. 94 patients were divided into the control group (47 cases) and the study group (47 cases), according to different intervention methods. In the study group, 40 mg of parecoxib was injected intravenously into patients 30 min before the induction of anesthesia, and the patients in the control group were given the same dose of normal saline intravenously before the operation. The basic clinical data of the patients were collected. The levels of the indexes before operation and 6 hours after operation were compared between the two groups, including the Montreal Cognitive Scale (MoCA) score, inflammatory factor indicators [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), interleukin-10 (IL-10), interleukin-1ß (IL-1ß), monocyte chemokine-1 (MCP-1), and inducible nitric oxide synthase (iNOS)], serum cortisol (CORT), beta-amyloid (ß-AP), adiponectin (ADP), NSE, and S100ß. RESULTS: No significant differences in the preoperative MoCA score, TNF-α, IL-6, CRP, IL-10, IL-1ß, MCP-1, iNOS, CORT, ß-AP, ADP, NSE, and S100ß levels were observed between the two groups (p>0.05). The postoperative MoCA score in the study group was significantly higher than that in the control group (p<0.05). The postoperative levels of TNF-α, IL-6, CRP and IL-1ß in the study group were significantly lower than those in the control group (p<0.05), and the postoperative levels of IL-10, MCP-1 and iNOS in the study group were significantly higher than those in the control group (p<0.05). CONCLUSIONS: Parecoxib can notably inhibit the levels of postoperative inflammatory cytokines, improve neurological dysfunction, and reduce the occurrence of postoperative cognitive dysfunction in patients. The contents of serum NSE and S100ß have potential value in the diagnosis of postoperative cognitive dysfunction in elderly patients.


Assuntos
Disfunção Cognitiva , Isoxazóis , Complicações Cognitivas Pós-Operatórias , Humanos , Idoso , Interleucina-10 , Fator de Necrose Tumoral alfa , Interleucina-6 , Estudos Retrospectivos , Proteína C-Reativa , Fosfopiruvato Hidratase
5.
Nat Commun ; 15(1): 2655, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38531894

RESUMO

Genetic pleiotropy is abundant across spatially distributed brain characteristics derived from one neuroimaging modality (e.g. structural, functional or diffusion magnetic resonance imaging [MRI]). A better understanding of pleiotropy across modalities could inform us on the integration of brain function, micro- and macrostructure. Here we show extensive genetic overlap across neuroimaging modalities at a locus and gene level in the UK Biobank (N = 34,029) and ABCD Study (N = 8607). When jointly analysing phenotypes derived from structural, functional and diffusion MRI in a genome-wide association study (GWAS) with the Multivariate Omnibus Statistical Test (MOSTest), we boost the discovery of loci and genes beyond previously identified effects for each modality individually. Cross-modality genes are involved in fundamental biological processes and predominantly expressed during prenatal brain development. We additionally boost prediction of psychiatric disorders by conditioning independent GWAS on our multimodal multivariate GWAS. These findings shed light on the shared genetic mechanisms underlying variation in brain morphology, functional connectivity, and tissue composition.


Assuntos
Estudo de Associação Genômica Ampla , Neuroimagem , Humanos , Estudo de Associação Genômica Ampla/métodos , Fenótipo , Pleiotropia Genética , Encéfalo/anatomia & histologia , Polimorfismo de Nucleotídeo Único , Predisposição Genética para Doença
6.
J Natl Cancer Inst ; 66(1): 121-4, 1981 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-6935452

RESUMO

A difference in the mechanism of transmembrane transport was demonstrated for methotrexate (MTX) and MTX bound to the high molecular weight carrier bovine serum albumin (MTX-BSA) when the drug dose needed to reduce growth of cells to 50% of that of untreated cells (ID50) was compared in the sensitive L1210 leukemia and 3 L1210 sublines resistant to MTX by virtue of either deficient MTX transport or high levels of dihydrofolate dehydrogenase (DHFD). The loss of transport increased the ID50 for inhibition of growth rate by free MTX tenfold to twentyfold, whereas the elevation of DHFD levels increased the ID50 by tenfold. In contrast, deficiency of transport resulted in only a twofold increase in the ID50 for MTX-BSA, and elevation of DHFD caused a tenfold increase similar to that for free MTX. This difference was confirmed in studies of inhibition of DHFD activity by free and BSA-bound MTX. MTX-BSA but not MTX had antitumor activity against the transport-deficient L1210 line in (C57BL/6 x DBA/2)F1. These studies confirm a separate mode of cell entry for MTX-BSA and suggest a role for these complexes in overcoming resistance.


Assuntos
Leucemia L1210/metabolismo , Metotrexato/metabolismo , Soroalbumina Bovina/metabolismo , Tetra-Hidrofolato Desidrogenase/metabolismo , Animais , Transporte Biológico , Linhagem Celular , Química Farmacêutica , Resistência a Medicamentos , Feminino , Antagonistas do Ácido Fólico , Leucemia L1210/tratamento farmacológico , Leucemia L1210/enzimologia , Camundongos
7.
Sci Rep ; 6: 30309, 2016 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-27457516

RESUMO

Perovskite SrIrO3 has long been proposed as an exotic semimetal induced by the interplay between the spin-orbit coupling and electron correlations. However, its low-lying electronic structure is still lacking. We synthesize high-quality perovskite SrIrO3 (100) films by means of oxide molecular beam epitaxy, and then systemically investigate their low energy electronic structure using in-situ angle-resolved photoemission spectroscopy. We find that the hole-like bands around R and the electron-like bands around U(T) intersect the Fermi level simultaneously, providing the direct evidence of the semimetallic ground state in this compound. Comparing with the density functional theory, we discover that the bandwidth of states near Fermi level is extremely small, and there exists a pronounced mixing between the Jeff = 1/2 and Jeff = 3/2 states. Moreover, our data reveal that the predicted Dirac degeneracy protected by the mirror-symmetry, which was theoretically suggested to be the key to realize the non-trivial topological properties, is actually lifted in perovskite SrIrO3 thin films. Our findings pose strong constraints on the current theoretical models for the 5d iridates.

8.
Arch Pathol Lab Med ; 118(10): 1023-5, 1994 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7944886

RESUMO

We report a rare case of cardiac tamponade caused by hemopericardium secondary to erosion and rupture of a coronary artery by an adjacent solitary myocardial abscess. The resulting tamponade led to the sudden death of this 46-year-old man. Antemortem blood culture and the postmortem microscopic examination of the myocardial abscess revealed the causative agent to be Staphylococcus aureus. Hemopericardium due to ventricular wall rupture secondary to a myocardial abscess has been infrequently reported, but, to our knowledge, only one other report of hemopericardium due to coronary artery rupture related to myocardial abscess has been published.


Assuntos
Abscesso/complicações , Cardiomiopatias/complicações , Doença das Coronárias/etiologia , Derrame Pericárdico/etiologia , Infecções Estafilocócicas/complicações , Abscesso/patologia , Cardiomiopatias/patologia , Doença das Coronárias/patologia , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pericárdico/patologia , Ruptura Espontânea/etiologia , Ruptura Espontânea/patologia , Infecções Estafilocócicas/patologia
9.
Forensic Sci Int ; 73(1): 35-40, 1995 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-7750880

RESUMO

Diastereomeric dipeptides were derived from the amino acid enantiomers in dentin by O-phthalaldehyde-N-acetyl-L-cysteine. The products were separated using high performance liquid chromatography (HPLC) and detected by fluorescence detector. A short analysis time (total analysis time was 15 min, including retention time, sample derivatization time and column regeneration time) was used. The sensitivity of detection was 1 pmol and high resolution (Rs = 1.5) was reached. We determined the D/L ratio of aspartic acid in dentin of 28 first premolars. The correlation value between the D/L ratio of aspartic acid and actual age was 0.9887; errors of +/- 1 year accounted for 46.4%, and no error exceeded 5 years.


Assuntos
Determinação da Idade pelos Dentes/métodos , Ácido Aspártico/análise , Cromatografia Líquida de Alta Pressão/métodos , Dentina/química , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estereoisomerismo
10.
Environ Pollut ; 119(2): 163-75, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12152824

RESUMO

In highly polluted sites, stomatal behavior is sluggish with respect to light, vapor pressure deficit, and internal CO2 concentration (Ci) and poorly described by existing models. Statistical models were developed to estimate stomatal conductance (gs) of 40-year-old ponderosa pine at three sites differing in pollutant exposure for the purpose of calculating O3 uptake. Gs was estimated using julian day, hour of day, pre-dawn xylem potential and photosynthetic photon flux density (PPFD). The median difference between estimated and observed field gs did not exceed 10 mmol H2O m(-2) s(-1), and estimated gs within 95% confidence intervals. 03 uptake was calculated from hourly estimated gs, hourly O3 concentration, and a constant to correct for the difference in diffusivity between water vapor and 03. The simulation model TREGRO was also used to calculate the cumulative 03 uptake at all three sites. 03 uptake estimated by the statistical model was higher than that simulated by TREGRO because gas exchange rates were proportionally higher. O3 exposure and uptake were significantly correlated (r2>0.92), because O3 exposure and gs were highly correlated in both statistical and simulation models.


Assuntos
Poluentes Atmosféricos/metabolismo , Modelos Biológicos , Ozônio/metabolismo , Pinus/metabolismo , California , Ritmo Circadiano , Clima , Monitoramento Ambiental/métodos , Poluição Ambiental , Modelos Estatísticos , Ozônio/administração & dosagem , Fotossíntese/fisiologia , Folhas de Planta/metabolismo , Estações do Ano
11.
Jpn J Ophthalmol ; 33(1): 120-4, 1989.
Artigo em Inglês | MEDLINE | ID: mdl-2543856

RESUMO

The patient, a 56-year-old man, presented with dendritic keratitis in the right eye and geographic keratitis in the left, with decreased corneal sensation in both eyes. The virus isolated from both eyes was identified as herpes simplex virus (HSV-1) by the indirect immunofluorescent method using anti-HSV-1 monoclonal antibody. Antibody tests of paired sera suggested that the epithelial lesions were not primary but recurrent. No significant difference was observed in DNA cleavage patterns between the virus isolates obtained bilaterally.


Assuntos
Ceratite Dendrítica/diagnóstico , Divisão Celular , DNA Viral , Imunofluorescência , Humanos , Ceratite Dendrítica/patologia , Masculino , Pessoa de Meia-Idade , Recidiva , Simplexvirus/efeitos dos fármacos , Simplexvirus/genética , Simplexvirus/isolamento & purificação
12.
Int Migr Rev ; 33(4): 954-87, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-12349707

RESUMO

The peculiar features of China's socialist transitional economy, including the coexistence of "plan" and "nonplan" mechanisms, the hukou institution, uneven spatial development, and gendered constraints and opportunities, have brought about a high degree of heterogeneity among population movements. Using the 1990 Census data on reasons for migration, and an empirical analysis of both national patterns and migration in Guangdong, the author documents the socioeconomic characteristics and spatial patterns of major types of migration, focusing on migration for employment in industry and business, male migration due to job transfer, and female marriage migration. The author argues that the multitude of migration types, and the contrasts among them, are products of the combination of state-planning and market mechanisms. The findings highlight institutional explanations for migration, and show that the "plan"/"nonplan" dichotomy is more meaningful that the economic-social dichotomy for understanding population movements in China.


Assuntos
Demografia , Características da População , Dinâmica Populacional , Fatores Socioeconômicos , Migrantes , Ásia , China , Países em Desenvolvimento , Economia , Emigração e Imigração , Ásia Oriental , Geografia , População
13.
Cell Death Dis ; 4: e681, 2013 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-23788038

RESUMO

Lon protease is a multifunction protein and operates in protein quality control and stress response pathways in mitochondria. Human Lon is upregulated under oxidative and hypoxic stresses that represent the stress phenotypes of cancer. However, little literature undertakes comprehensive and detailed investigations on the tumorigenic role of Lon. Overexpression of Lon promotes cell proliferation, apoptotic resistance to stresses, and transformation. Furthermore, Lon overexpression induces the production of mitochondrial reactive oxygen species (ROS) that result from Lon-mediated upregulation of NDUFS8, a mitochondrial Fe-S protein in complex I of electron transport chain. Increased level of mitochondrial ROS promotes cell proliferation, cell survival, cell migration, and epithelial-mesenchymal transition through mitogen-activated protein kinase (MAPK) and Ras-ERK activation. Overall, the present report for the first time demonstrates the role of Lon overexpression in tumorigenesis. Lon overexpression gives an apoptotic resistance to stresses and induces mitochondrial ROS production through Complex I as signaling molecules to activate Ras and MAPK signaling, giving the survival advantages and adaptation to cancer cells. Finally, in silico and immunohistochemistry analysis showed that Lon is overexpressed specifically in various types of cancer tissue including oral cancer.


Assuntos
Carcinogênese/metabolismo , Mitocôndrias/enzimologia , NADH Desidrogenase/metabolismo , Protease La/metabolismo , Superóxidos/metabolismo , Carcinoma de Células Escamosas/enzimologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Estabilidade Enzimática , Transição Epitelial-Mesenquimal , Expressão Gênica , Células HEK293 , Humanos , Sistema de Sinalização das MAP Quinases , Neoplasias Bucais/enzimologia , Fenótipo , Protease La/genética , Regulação para Cima
15.
Theor Appl Genet ; 110(8): 1445-52, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15841361

RESUMO

Amylose content (AC), gel consistency (GC) and gelatinazation temperature (GT) are three important traits that influence the cooking and eating quality of rice. The objective of this study was to characterize the genetic components, including main-effect quantitative trait loci (QTLs), epistatic QTLs and QTL-by-environment interactions (QEs), that are involved in the control of these three traits. A population of doubled haploid (DH) lines derived from a cross between two indica varieties Zhenshan 97 and H94 was used, and data were collected from a field experiment conducted in two different environments. A genetic linkage map consisting of 218 simple sequence repeat (SSR) loci was constructed, and QTL analysis performed using QTLMAPPER 1.6: resolved the genetic components into main-effect QTLs, epistatic QTLs and QEs. The analysis detected a total of 12 main-effect QTLs for the three traits, with a QTL corresponding to the Wx locus showing a major effect on AC and GC, and a QTL corresponding to the Alk locus having a major effect on GT. Ten digenic interactions involving 19 loci were detected for the three traits, and six main-effect QTLs and two pairs of epistatic QTLs were involved in QEs. While the main-effect QTLs, especially the ones corresponding to known major loci, apparently played predominant roles in the genetic basis of the traits, under certain conditions epistatic effects and QEs also played important roles in controlling the traits. The implications of the findings for rice quality improvement are discussed.


Assuntos
Meio Ambiente , Epistasia Genética , Alimentos , Temperatura Alta , Oryza/genética , Fenótipo , Locos de Características Quantitativas , Amilose/metabolismo , Mapeamento Cromossômico , Cruzamentos Genéticos , Repetições Minissatélites/genética , Oryza/metabolismo
16.
Reg Stud ; 28(3): 241-58, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-12318666

RESUMO

"This paper focuses on spatial variation of growth within a state. Using Ohio as a case study, two hypotheses are extracted from the literature. First, the theories of polarization and polarization reversal suggest that in the old industrial core the leading sector role of manufacturing has diminished in old manufacturing poles, and that income growth trends differ substantially between these old poles and new centres of development. Second, the theories of suburbanization and migration reversals suggest that population growth is contingent upon level of urbanization, and that the relationship has changed drastically between the pre-1970s, 1970s, and post-1970s periods." (SUMMARY IN FRE AND GER)


Assuntos
Demografia , Economia , Renda , Dinâmica Populacional , Crescimento Demográfico , Urbanização , América , Países Desenvolvidos , Emigração e Imigração , Geografia , América do Norte , Ohio , População , Pesquisa , Fatores Socioeconômicos , Estados Unidos , População Urbana
17.
Kroc Found Ser ; 17: 13-26, 1984.
Artigo em Inglês | MEDLINE | ID: mdl-6595345

RESUMO

In recent years it has become apparent that at least part of the transcellular movements of Na and Cl are linked by a process or processes which couple the entry of Na to Cl across the apical cell membrane of the intestinal cell. In some tissues, eg, gallbladder and renal tubule, this coupled transport of Na and Cl may be the predominant electrolyte-transporting mechanism. Studies in rabbit ileal brush-border membrane vesicles present evidence for a coupled NaCl process that has the same ionic specificities and similar kinetics as the processes demonstrated by influx techniques across the apical membrane of the intact epithelium. However, the vesicles also exhibit Na:H and Cl:HCO3 exchange processes and the inhibitors thought to be specific for either the NaCl cotransport system (loop diuretics), for the Na:H exchange (high-dose amiloride), or for the Cl:HCO3 exchange (disulfonic stilbenes such as SITS or DIDS), do not prove to be so. It is possible that all three processes could be present in intestinal brush-border membranes. Furthermore, the techniques of isolating vesicles could uncouple or otherwise inhibit the coupled NaCl process. Nonetheless, the preponderance of evidence at this time indicates that parallel ion exchangers of Na:H and Cl:HCO3, as initially suggested by Turnberg et al [4], account for coupled NaCl transport in rabbit ileum. Additional studies will be necessary to determine if this is the only mechanism in the intestinal apical membrane and whether this conclusion applies to other tissues such as gallbladder and renal tubule.


Assuntos
Cloreto de Sódio/metabolismo , Animais , Bicarbonatos/metabolismo , Transporte Biológico , Cloretos/metabolismo , Epitélio/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Troca Iônica , Microvilosidades/metabolismo , Sódio/metabolismo
18.
J Mol Cell Cardiol ; 20(9): 789-99, 1988 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2852723

RESUMO

The beta-adrenergic agonist 1-isoproterenol induced an early (less than 1 min) stimulation of endocytosis, amino acid transport and hexose transport, monitored by the temperature-sensitive uptake of horseradish peroxidase, alpha-aminoisobutyrate and 2-deoxyglucose, respectively, in rat ventricle cubes. This stimulation was time- and concentration-dependent and was maximum at 10(-8) M isoproterenol. The beta-adrenergic antagonist propranolol blocked isoproterenol stimulation of membrane transport, thereby confirming beta-adrenoceptor mediation; 2.5 mM EGTA, 1 mM LaCl2 and 100 microM verapamil blocked the hormonal response without affecting basal transport. The calcium ionophore A23187 caused an acute stimulation of endocytosis, hexose and amino acid transport. Isoproterenol rapidly (less than 30 s) stimulated 45Ca2+ influx. These data suggest that stimulus-response (stimulus-"transport") coupling is mediated by a rise in cytosolic Ca2+ concentration. A rapid (less than 30 to 60 s) increase in ornithine decarboxylase (ODC) activity, followed by an early (less than 1 to 2 min), sustained increase in putrescine, spermidine and spermine concentrations was evoked by 10(-7) M isoproterenol. The ODC inhibitor alpha-difluoromethylornithine (DFMO, 5 mM) suppressed the isoproterenol-induced increase in ODC and polyamine levels and the stimulation of 45Ca influx, endocytosis, hexose transport, and amino acid transport. Putrescine (0.5 mM) negated DFMO inhibition and restored the increase in polyamines, 45Ca influx, endocytosis, and transport of hexose and amino acid. These data suggest that polyamine synthesis is involved in isoproterenol stimulation of Ca2+ influx and membrane transport functions in ventricular myocardium. These findings are consistent with a model for signal transduction and stimulus-response coupling in which polyamines function as intracellular messengers to generate cytosolic Ca2+ signals by stimulating Ca2+ influx.


Assuntos
Canais de Cálcio/efeitos dos fármacos , Cálcio/farmacocinética , Isoproterenol/farmacocinética , Miocárdio/metabolismo , Poliaminas/farmacocinética , Ácidos Aminoisobutíricos/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Desoxiglucose/metabolismo , Relação Dose-Resposta a Droga , Eflornitina/farmacologia , Feminino , Peroxidase do Rábano Silvestre/metabolismo , Ornitina Descarboxilase/metabolismo , Ratos , Ratos Endogâmicos , Receptores Adrenérgicos beta/efeitos dos fármacos
19.
Mol Cell Biochem ; 34(1): 35-41, 1981 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-6164913

RESUMO

Hormone stimulated lipolysis of mouse and rabbit adipocytes as measured by both free fatty acid and glycerol release, is proportionally elevated with increase in the adipocyte cAMP level up to 1 nmol/g. The correlation coefficients are 0.94 and 0.97 for FFA/cAMP and glycerol/cAMP respectively. Increments in cAMP greater than 1 nmol/g show no correlation with increase in lipolysis. The release of lipolytic products, glycerol and free fatty acids, from white adipocytes in response to ACTH, epinephrine or norepinephrine was measured using radiochemical assays in short term incubation systems, with cAMP levels measured at the same time and from the same cell sample. Under the conditions studied, epinephrine is a more effective lipolytic hormone than ACTh in mouse adipocyte, and ACTH is more effective than epinephrine in rabbit adipocyte. The effect of catecholamines on the rabbit adipocyte is not modified by phentolamine (10 microM), but it is potentiated by 1-methyl-3-isobutyl xanthine (0.1 mM). The results suggest that cAMP mediates the action of these lipolytic hormones in white adipocytes of mouse and rabbit.


Assuntos
Tecido Adiposo/metabolismo , Hormônio Adrenocorticotrópico/farmacologia , Catecolaminas/farmacologia , AMP Cíclico/metabolismo , Metabolismo dos Lipídeos , 1-Metil-3-Isobutilxantina/farmacologia , Tecido Adiposo/citologia , Animais , Epinefrina/farmacologia , Masculino , Camundongos , Norepinefrina/farmacologia , Fentolamina/farmacologia , Propranolol/farmacologia , Coelhos , Especificidade da Espécie
20.
Mol Cell Biochem ; 34(1): 43-50, 1981 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-6262626

RESUMO

The isolated intact white adipocyte of the Swiss mouse responds to both ACTH and catecholamines by an elevation of cAMP levels and an increase in lipolysis. However, in the isolated plasma membrane of the mouse adipocyte, adenylate cyclase loses its responsiveness to ACTH but retains its ability to respond to catecholamines. This lack of responsiveness to ACTH by adenylate cyclase of mouse adipocyte plasma membrane can be overcome, at least partially, by addition of GPP (NH)p, an analog of GTP, to the assay medium. The data on mouse adipocyte membrane suggests that the coupling of ACTH receptor to adenylate cyclase is dependent on GTP and that catecholamine-activation of adenylate cyclase is less dependent on this nucleotide. The isolated intact white adipocyte of adult New Zealand rabbit responds to ACTH, but does not (or only weakly) respond to catecholamines. In contrast to the mouse plasma membrane preparation, adenylate cyclase of adipocyte membrane of the rabbit responds to ACTH. And the addition of GPP(NH)P is not required to demonstrate the CTH: sensitive adenylate cyclase activity. The difference between mouse and rabbit adipocyte membrane in the requirement for GPP(NH)P in ACTH action is not readily explained. The lack of catecholamine sensitivity of rabbit membrane enzyme cannot be reversed by addition of GPP(NH)P or adenosine deaminase. These two adenylate cyclase model systems using mouse and rabbit adipocyte plasma membrane may be useful tools for the study of the specificity and mechanism of action of lipolytic hormones such as ACTH and catecholamines.


Assuntos
Adenilil Ciclases/metabolismo , Tecido Adiposo/enzimologia , Hormônio Adrenocorticotrópico/farmacologia , Catecolaminas/farmacologia , Tecido Adiposo/citologia , Animais , Membrana Celular/enzimologia , Estabilidade de Medicamentos , Epinefrina/farmacologia , Guanilil Imidodifosfato/farmacologia , Metabolismo dos Lipídeos , Camundongos , Coelhos , Receptores de Superfície Celular/metabolismo , Receptores da Corticotropina , Especificidade da Espécie
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