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1.
Nature ; 554(7692): 337-340, 2018 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-29446380

RESUMO

Auroral substorms, dynamic phenomena that occur in the upper atmosphere at night, are caused by global reconfiguration of the magnetosphere, which releases stored solar wind energy. These storms are characterized by auroral brightening from dusk to midnight, followed by violent motions of distinct auroral arcs that suddenly break up, and the subsequent emergence of diffuse, pulsating auroral patches at dawn. Pulsating aurorae, which are quasiperiodic, blinking patches of light tens to hundreds of kilometres across, appear at altitudes of about 100 kilometres in the high-latitude regions of both hemispheres, and multiple patches often cover the entire sky. This auroral pulsation, with periods of several to tens of seconds, is generated by the intermittent precipitation of energetic electrons (several to tens of kiloelectronvolts) arriving from the magnetosphere and colliding with the atoms and molecules of the upper atmosphere. A possible cause of this precipitation is the interaction between magnetospheric electrons and electromagnetic waves called whistler-mode chorus waves. However, no direct observational evidence of this interaction has been obtained so far. Here we report that energetic electrons are scattered by chorus waves, resulting in their precipitation. Our observations were made in March 2017 with a magnetospheric spacecraft equipped with a high-angular-resolution electron sensor and electromagnetic field instruments. The measured quasiperiodic precipitating electron flux was sufficiently intense to generate a pulsating aurora, which was indeed simultaneously observed by a ground auroral imager.

2.
Earth Planets Space ; 72(1): 111, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32831576

RESUMO

We investigate the longitudinal structure of the oxygen torus in the inner magnetosphere for a specific event found on 12 September 2017, using simultaneous observations from the Van Allen Probe B and Arase satellites. It is found that Probe B observed a clear enhancement in the average plasma mass (M) up to 3-4 amu at L = 3.3-3.6 and magnetic local time (MLT) = 9.0 h. In the afternoon sector at MLT ~ 16.0 h, both Probe B and Arase found no clear enhancements in M. This result suggests that the oxygen torus does not extend over all MLT but is skewed toward the dawn. Since a similar result has been reported for another event of the oxygen torus in a previous study, a crescent-shaped torus or a pinched torus centered around dawn may be a general feature of the O+ density enhancement in the inner magnetosphere. We newly find that an electromagnetic ion cyclotron (EMIC) wave in the H+ band appeared coincidently with the oxygen torus. From the lower cutoff frequency of the EMIC wave, the ion composition of the oxygen torus is estimated to be 80.6% H+, 3.4% He+, and 16.0% O+. According to the linearized dispersion relation for EMIC waves, both He+ and O+ ions inhibit EMIC wave growth and the stabilizing effect is stronger for He+ than O+. Therefore, when the H+ fraction or M is constant, the denser O+ ions are naturally accompanied by the more tenuous He+ ions, resulting in a weaker stabilizing effect (i.e., larger growth rate). From the Probe B observations, we find that the growth rate becomes larger in the oxygen torus than in the adjacent regions in the plasma trough and the plasmasphere.

3.
Allergy ; 72(11): 1728-1736, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28439905

RESUMO

BACKGROUND: Dermatophagoides farinae is a source of airborne house dust mite (HDM) allergens. We elucidated IgE-reactive allergens from D. farinae by two-dimensional immunoblotting-based allergenome analysis, and identified one new allergen, named Der f 35, that possesses IgE-binding capacity comparable to that of Der f 2. The aim of this study was to clarify the allergenic capacity of new HDM allergen Der f 35. METHODS: We cloned der f 35 from D. farinae mRNA and produced recombinant Der f 35 in Escherichia coli. The IgE-binding capacity of Der f 35 and its cross-reactivity with group 2 allergens from D. farinae and Psoroptes ovis were determined by enzyme-linked immunosorbent assay (ELISA) and ELISA inhibition assays, respectively. RESULTS: The deduced amino acid sequence for der f 35, which possesses the MD-2-related lipid-recognition domain, showed higher identity with group 2 allergens from P. ovis (61.5%) and Blomia tropicalis (50.7%) than with Der f 2 (40.8%). Der f 35 showed IgE-binding frequencies of 77.5% (31/40) for the native form upon allergenome analysis and 51.4% (18/35) for recombinant structure by ELISA. Der f 35 showed cross-reactivity with Der f 2 and Pso o 2 in reaction with HDM-allergic patients' IgE by ELISA inhibition assay. CONCLUSION: Der f 35 is a candidate major allergen from D. farinae, which is more similar to group 2 allergens from sheep scab mite and storage mites. Der f 35 could be responsible for the cross-reactivity among group 2 mite allergens.


Assuntos
Alérgenos/imunologia , Antígenos de Dermatophagoides/imunologia , Reações Cruzadas/imunologia , Ácaros/imunologia , Animais , Proteínas de Artrópodes/imunologia , Dermatophagoides farinae/imunologia , Imunoglobulina E/metabolismo , Psoroptidae/imunologia , Análise de Sequência de Proteína , Ovinos
4.
J Endocrinol Invest ; 36(8): 564-7, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23385627

RESUMO

BACKGROUND: Recently, it has been reported that the incidence of primary aldosteronism (PA) among patients with hypertension is much more frequent than previously reported. AIM: In the present study, we investigated the frequency and features of PA associated with subclinical Cushing syndrome (SCS). MATERIAL AND METHODS: Subjects included consecutive patients (no.=39) who were diagnosed as PA and performed adrenal venous sampling between 2003 and 2011 in our institute. RESULTS: In 39 subjects who were diagnosed as PA, 29 patients were operated and 5 cases (12.8%) showed no suppression in low-dose dexamethasone suppression test. Four cases of them were demonstrated to be associated with SCS, and one was associated with overt Cushing syndrome (CS). Post-operatively, 3 cases received replacement therapy of hydrocortisone, while others did not. Pathological findings indicated the diagnosis of aldosterone-producing adenoma in 4 cases associated with SCS, and of idiopathic hyperaldosteronismin in one case associated with overt CS. In all 5 cases, immunohistochemical analysis demonstrated the immunoreactivities of both 3ßHSD and P450c17 in the adrenocortical tumors, the marked cortical atrophy in the zona fasciculata and reticularis, the decreased dehydroepiandrosterone sulfotransferase expression, and suppression of hypothalamo- pituitary-adrenal axis indicating the autonomous secretion of cortisol from the tumor. CONCLUSIONS: The present study suggests that PA is frequently associated with SCS with prevalence of more than 10%, justifying the routine examinations for SCS in PA cases.


Assuntos
Neoplasias do Córtex Suprarrenal/complicações , Síndrome de Cushing/complicações , Hiperaldosteronismo/etiologia , Adenoma/diagnóstico , Neoplasias das Glândulas Suprarrenais/diagnóstico , Adulto , Dexametasona , Feminino , Humanos , Hidrocortisona/metabolismo , Masculino , Pessoa de Meia-Idade
5.
Space Sci Rev ; 218(5): 38, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35757012

RESUMO

This paper presents the highlights of joint observations of the inner magnetosphere by the Arase spacecraft, the Van Allen Probes spacecraft, and ground-based experiments integrated into spacecraft programs. The concurrent operation of the two missions in 2017-2019 facilitated the separation of the spatial and temporal structures of dynamic phenomena occurring in the inner magnetosphere. Because the orbital inclination angle of Arase is larger than that of Van Allen Probes, Arase collected observations at higher L -shells up to L ∼ 10 . After March 2017, similar variations in plasma and waves were detected by Van Allen Probes and Arase. We describe plasma wave observations at longitudinally separated locations in space and geomagnetically-conjugate locations in space and on the ground. The results of instrument intercalibrations between the two missions are also presented. Arase continued its normal operation after the scientific operation of Van Allen Probes completed in October 2019. The combined Van Allen Probes (2012-2019) and Arase (2017-present) observations will cover a full solar cycle. This will be the first comprehensive long-term observation of the inner magnetosphere and radiation belts.

6.
Sci Rep ; 11(1): 13724, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34257336

RESUMO

Pulsating aurorae (PsA) are caused by the intermittent precipitations of magnetospheric electrons (energies of a few keV to a few tens of keV) through wave-particle interactions, thereby depositing most of their energy at altitudes ~ 100 km. However, the maximum energy of precipitated electrons and its impacts on the atmosphere are unknown. Herein, we report unique observations by the European Incoherent Scatter (EISCAT) radar showing electron precipitations ranging from a few hundred keV to a few MeV during a PsA associated with a weak geomagnetic storm. Simultaneously, the Arase spacecraft has observed intense whistler-mode chorus waves at the conjugate location along magnetic field lines. A computer simulation based on the EISCAT observations shows immediate catalytic ozone depletion at the mesospheric altitudes. Since PsA occurs frequently, often in daily basis, and extends its impact over large MLT areas, we anticipate that the PsA possesses a significant forcing to the mesospheric ozone chemistry in high latitudes through high energy electron precipitations. Therefore, the generation of PsA results in the depletion of mesospheric ozone through high-energy electron precipitations caused by whistler-mode chorus waves, which are similar to the well-known effect due to solar energetic protons triggered by solar flares.

7.
Space Sci Rev ; 215(1): 9, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30880847

RESUMO

With the advent of the Heliophysics/Geospace System Observatory (H/GSO), a complement of multi-spacecraft missions and ground-based observatories to study the space environment, data retrieval, analysis, and visualization of space physics data can be daunting. The Space Physics Environment Data Analysis System (SPEDAS), a grass-roots software development platform (www.spedas.org), is now officially supported by NASA Heliophysics as part of its data environment infrastructure. It serves more than a dozen space missions and ground observatories and can integrate the full complement of past and upcoming space physics missions with minimal resources, following clear, simple, and well-proven guidelines. Free, modular and configurable to the needs of individual missions, it works in both command-line (ideal for experienced users) and Graphical User Interface (GUI) mode (reducing the learning curve for first-time users). Both options have "crib-sheets," user-command sequences in ASCII format that can facilitate record-and-repeat actions, especially for complex operations and plotting. Crib-sheets enhance scientific interactions, as users can move rapidly and accurately from exchanges of technical information on data processing to efficient discussions regarding data interpretation and science. SPEDAS can readily query and ingest all International Solar Terrestrial Physics (ISTP)-compatible products from the Space Physics Data Facility (SPDF), enabling access to a vast collection of historic and current mission data. The planned incorporation of Heliophysics Application Programmer's Interface (HAPI) standards will facilitate data ingestion from distributed datasets that adhere to these standards. Although SPEDAS is currently Interactive Data Language (IDL)-based (and interfaces to Java-based tools such as Autoplot), efforts are under-way to expand it further to work with python (first as an interface tool and potentially even receiving an under-the-hood replacement). We review the SPEDAS development history, goals, and current implementation. We explain its "modes of use" with examples geared for users and outline its technical implementation and requirements with software developers in mind. We also describe SPEDAS personnel and software management, interfaces with other organizations, resources and support structure available to the community, and future development plans. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11214-018-0576-4) contains supplementary material, which is available to authorized users.

8.
Hum Reprod ; 23(2): 285-9, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18037605

RESUMO

BACKGROUND: Changes in blood flow impedance of the uterine artery (UA) and uterine radial artery (RA) which is in the lower-extremity of the UA were examined during early pregnancy. METHODS: Blood flow impedance was assessed by transvaginal color-pulsed-Doppler-ultrasonography in 72 women from weeks 4-16 of pregnancy and expressed as a resistance index (RI). RESULTS: RA-RI remained at the late-luteal phase level until the 5th week of pregnancy, decreased until the 7th week, and remained low until the 10th week. UA-RI remained at the late-luteal phase level until the 10th week, and then gradually decreased until the 16th week. In nine women with spontaneous abortion, five out of six women with impaired growth of the gestational sac showed high RA-RI at the 6th week of pregnancy, whereas all three women with loss of fetal heart beat at the 8th week showed normal changes in RA-RI. CONCLUSIONS: Our results show different changes in blood flow impedance between the UA and RA during early pregnancy. A significant decrease of RA-RI after the 5th week may reflect vascular remodeling in the maternal-fetal interface at placentation, whereas a significant decrease of UA-RI after the 10th week may reflect changes of the whole uterine blood flow associated with uterine growth.


Assuntos
Gravidez , Útero/irrigação sanguínea , Resistência Vascular , Aborto Espontâneo/fisiopatologia , Adulto , Artérias/diagnóstico por imagem , Feminino , Morte Fetal , Humanos , Fase Luteal , Complicações na Gravidez/fisiopatologia , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Fluxo Sanguíneo Regional , Ultrassonografia Doppler em Cores , Ultrassonografia Doppler de Pulso
9.
Food Chem Toxicol ; 46(3): 1125-30, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18155340

RESUMO

Resveratrol, a polyphenolic phytoalexin, has free-radical scavenging activity and we found that it induces chromosomal aberrations, micronuclei, and sister chromatid exchanges in vitro. We synthesized its analogue 4-hydroxy-trans-stilbene (4-OH) and found that it has the same in vitro clastogenic activities as resveratrol, suggesting that the 4' hydroxy group of resveratrol is responsible for the effect. We fed resveratrol and 4-OH to young adult ICR mice at 0, 0.2, 2, or 20 ppm in their standard powder diet for 6 months and investigated the antioxidative effects. Half of each group was given 3000 ppm potassium bromate (KBrO(3)) in water for the last week to cause oxidative damage. Body weight gain tended to increase in males at 0.2 ppm resveratrol or 4-OH, and in females at 2 ppm 4-OH. Micronucleus (MN) analysis in bone marrow erythrocytes showed that the KBrO(3) tendency to induce MN was not prevented by the dietary resveratrol or 4-OH, which themselves did not induce MN under the present conditions. In this pilot study, resveratrol and 4-OH showed no obvious effect, either beneficial or adverse, at doses that are feasible in daily life for humans.


Assuntos
Antioxidantes/farmacologia , Dieta , Estilbenos/farmacologia , Animais , Antioxidantes/administração & dosagem , Peso Corporal/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Feminino , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Testes para Micronúcleos , Projetos Piloto , Resveratrol , Estilbenos/administração & dosagem
10.
Kyobu Geka ; 61(13): 1126-9, 2008 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-19068700

RESUMO

Submuscular Nuss procedure using mammary areola incision was performed on adult pectus excavatum. The skin was incised approximately 3 cm (almost half the entire areolar circumference). The subcutaneous tissue and pectoralis major muscle were incised to reach the 4th rib. The pectoralis major muscle and serratus anterior muscle were separated from the costae and intercostal muscle. A part of the 3rd intercostal muscle was removed. The sternum and cartilages were robust; therefore the anterior chest wall was elevated with a jack allowing Nuss procedure. After fixing a bar, a drainage tubes were placed beneath the bilateral pleural cavity and muscular layer. Then, the pectoralis major muscle was sutured and the subcutaneous tissue was closed with 2 layers of suturing. The skin was closed with 6-0 nylon sutures, leaving no obvious scar. The mammary areola incision which is used for breast cancer can also successfully applied to Nuss procedure. The Nuss procedure using mammary areola incision is recommended for pectus excavatum with upper chest depression.


Assuntos
Mama/cirurgia , Tórax em Funil/cirurgia , Adulto , Humanos , Masculino , Procedimentos Cirúrgicos Torácicos/métodos
11.
Cancer Res ; 54(7): 1672-7, 1994 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-8137280

RESUMO

New sublines of Chinese hamster CHL cells stably expressing human NAT1 or NAT2 N-acetyltransferases or O-acetyltransferase of Salmonella typhimurium were established, and their sensitivities to carcinogenic nitroarenes and aromatic amines were compared using the in vitro micronucleus test. The subline expressing human NAT2 N-acetyltransferase exhibited the highest sensitivity to the clastogenicities of 1,8-dinitropyrene and 2-nitrofluorene. These results raise the possibility that human NAT2 N-acetyltransferase is involved in the metabolic activation of 1,8-dinitro-pyrene and 2-nitrofluorene. Since human NAT2 N-acetyltransferase exhibits a marked genetic polymorphism, the polymorphic status of human N-acetyltransferase could be a genetic predisposing factor to cancers caused by the nitroarenes. In contrast, the subline expressing O-acetyltransferase of S. typhimurium exhibited the highest sensitivity to the clastogenicity of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) when the microsomes prepared from rat liver were present. This suggests that O-acetyltransferase of S. typhimurium has a higher ability to activate IQ than do the human acetyltransferases. Acetyltransferase enzymes of human enteric bacteria might contribute to the metabolic activation of IQ. The sublines could provide a new tool for investigation of the mechanism of metabolic activation and for assessment of cancer risk of nitroarenes and aromatic amines to humans.


Assuntos
Acetiltransferases , Aciltransferases/biossíntese , Arilamina N-Acetiltransferase/biossíntese , Fluorenos/toxicidade , Testes para Micronúcleos , Mutagênicos/toxicidade , Pirenos/toxicidade , Quinolinas/toxicidade , Salmonella typhimurium/enzimologia , Animais , Sequência de Bases , Biotransformação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cricetinae , Cricetulus , Fluorenos/metabolismo , Expressão Gênica , Genes Bacterianos , Humanos , Cinética , Dados de Sequência Molecular , Mutagênicos/metabolismo , Oligodesoxirribonucleotídeos , Plasmídeos , Pirenos/metabolismo , Quinolinas/metabolismo , Transfecção
12.
Biochim Biophys Acta ; 1118(2): 123-9, 1992 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-1730027

RESUMO

When compared with sperm whale MbO2 as a reference Aplysia MbO2 is extremely susceptible to autoxidation, and its pH dependence for the reaction is also unusual. Kinetic and thermodynamic analyses have shown that two types of carboxyl group with pKa = 4.3 and 6.1 at 25 degrees C are involved in the stability property of Aplysia MbO2, the protonation of these groups being responsible for an increase in its autoxidation rate in the acidic pH range. Since protoheme has two carboxyl groups of the propionic acid side-chains, we have prepared Aplysia myoglobin containing the dimethylester of protohemin. The autoxidation of this derivative was found to be described by the involvement of only one type of carboxyl group with pKa = 4.4. A possible candidate for the protein residue was therefore discussed on the basis of the known amino acid sequences of three Aplysia myoglobins: it is suggested that Glu-94, next to the proximal His-95, is the most likely candidate.


Assuntos
Aplysia/metabolismo , Ésteres/metabolismo , Heme/análogos & derivados , Mioglobina/metabolismo , Sequência de Aminoácidos , Animais , Heme/metabolismo , Concentração de Íons de Hidrogênio , Dados de Sequência Molecular , Oxirredução , Especificidade da Espécie , Análise Espectral
13.
Biochim Biophys Acta ; 956(2): 127-32, 1988 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-3167065

RESUMO

Unlike mammalian oxymyoglobins, Aplysia MbO2 is extremely susceptible to autoxidation, and its pH dependence is also unusual. Kinetic formulation has revealed that two kinds of dissociable group with pK1 = 4.3 and pK2 = 6.1, respectively, at 25 degrees C are involved in the stability property of Aplysia MbO2. In order to characterize thermodynamically these dissociation processes involved, the effect of temperature on K1 and K2 was studied by analyzing the pH dependence for the autoxidation rate of Aplysia MbO2 in 0.1 M buffer over the pH range of 4-11, and at 15, 25 and 35 degrees C. The resulting thermodynamic parameters for each group were both those to be expected for the ionization of a carboxyl group; the delta H degrees value being numerically much less than 1 kcal.mol-1, or zero in practice, but being associated with a large negative value of delta S degrees of the order of -20 cal.mol-1.K-1. Taking into account the fact that Aplysia myoglobin contains only a single histidine residue corresponding to the heme-binding proximal one, we can unequivocally conclude that the two kinds of the dissociable group involved in the unusual stability of Aplysia MbO2 must both be carboxyl groups, the protonation of these groups being responsible for an increase in its autoxidation rate in the acidic pH range.


Assuntos
Mioglobina , Animais , Aplysia , Bovinos , Concentração de Íons de Hidrogênio , Cinética , Matemática , Termodinâmica
14.
Biochim Biophys Acta ; 1543(1): 131-45, 2000 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-11087949

RESUMO

A myoglobin-like protein isolated from Tetrahymena pyriformis is composed of 121 amino acid residues. This is much smaller than sperm whale myoglobin by 32 residues, suggesting a distinct origin from the common globin gene. We have therefore examined this unique protein for its structural, spectral and stability properties. As a result, the rate of autoxidation of Tetrahymena oxymyoglobin (MbO(2)) was found to be almost comparable to that of sperm whale MbO(2) over a wide range of pH 4-12 in 0.1 M buffer at 25 degrees C. Moreover, both pH profiles exhibited the remarkable proton-assisted process, which can be performed in sperm whale myoglobin by the distal (E7) histidine as its catalytic residue. These kinetic observations are also in full accord with spectral examinations for the presence of a distal histidine in ciliated protozoa myoglobin. At the same time, we have isolated the globin genes both from T. pyriformis and Tetrahymena thermophila, and found that there is no intron in their genomic structures. This is in sharp contrast to previous reports on the homologous globin genes from Paramecium caudatum and Chlamydomonas eugametos. Rather, the Tetrahymena genes seemed to be related to the cyanobacterial globin gene from Nostoc commune. These contracted or truncated globins thus have a marked diversity in the cDNA, protein, and genomic structures.


Assuntos
Mioglobina/isolamento & purificação , Proteínas de Protozoários/isolamento & purificação , Tetrahymena pyriformis/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Espectroscopia de Ressonância de Spin Eletrônica , Evolução Molecular , Genoma de Protozoário , Histidina/análise , Cinética , Dados de Sequência Molecular , Mioglobina/química , Mioglobina/genética , Oxirredução , Conformação Proteica , Alinhamento de Sequência , Espectrofotometria
15.
Biochim Biophys Acta ; 1038(1): 23-8, 1990 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-2317515

RESUMO

Native oxymyoglobin (MbO2) was isolated directly from the skeletal muscle of bigeye tuna (Thunnus obesus) with complete separation from metmyoglobin (metMb) on a CM-cellulose column. It was examined for its stability properties over a wide range of pH values (pH 5-12) in 0.1 M buffer at 25 degrees C. When compared with sperm whale MbO2 as a reference, the tuna MbO2 was found to be much more susceptible to autoxidation. Kinetic analysis has revealed that the rate constant for a nucleophilic displacement of O2- from MbO2 by an entering water molecule is 10-times higher than the corresponding value for sperm whale MbO2. The magnitude of the circular dichroism of bigeye tuna myoglobin at 222 nm was comparable to that of sperm whale myoglobin, but its hydropathy profile revealed the region corresponding to the distal side of the heme iron to be apparently less hydrophobic. The kinetic simulation also demonstrated that accessibility of the solvent water molecule to the heme pocket is clearly a key factor in the stability properties of the bound dioxygen.


Assuntos
Peixes/fisiologia , Mioglobina , Atum/fisiologia , Animais , Dicroísmo Circular , Heme , Concentração de Íons de Hidrogênio , Cinética , Músculos/análise , Mioglobina/isolamento & purificação , Oxirredução , Solubilidade , Relação Estrutura-Atividade , Água
16.
Biochim Biophys Acta ; 1208(2): 306-9, 1994 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-7947962

RESUMO

Hemoglobin VII (TaVII) is a major component in the larval hemolymph of Tokunagayusurika akamusi, a common midge (Diptera) found in Japan. This protein contains 150 amino-acid residues including the usual distal histidine at position 64. When the aquomet-form was placed in acidic pH range, its Soret peak was considerably blue-shifted and accompanied by a marked decrease in intensity, indicative of the protein being converted into a structure quite similar to that of Aplysia myoglobin lacking the distal histidine residue. The pH-dependent magnetic circular dichroism spectra in the Soret region have also revealed that TaVII hemoglobin is in an equilibrium between a hexacoordinate and a pentacoordinate structure for its ferric heme iron. We attribute this to a transition from an iron-ligated water molecule that is hydrogen-bonded to the distal histidine, to a water-free iron with the histidine swung-out of the heme pocket. Furthermore, this process was described by the involvement of a single dissociable group with pKa = 6.3 in 0.1 M KCl at 25 degrees C.


Assuntos
Dípteros/química , Hemolinfa/química , Animais , Dicroísmo Circular , Hemoglobinas/isolamento & purificação , Histidina/química , Concentração de Íons de Hidrogênio , Larva/química , Estrutura Molecular
17.
Biochim Biophys Acta ; 1385(1): 89-100, 1998 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-9630537

RESUMO

One of the components of hemoglobin from the larval hemolyph of Tokunagayusurika akamusi possesses naturally occurring substitution at the E7 helical position (Leu E7) [M. Fukuda, T. Takagi, K. Shikama, Biochim. Biophys. Acta 1157 (1993) 185-191]. Its oxygen affinity is almost comparable to those of mammalian myoglobins and it exhibits Bohr effect. Both acidic and alkaline forms of the ferric hemoglobin have been investigated using 1H NMR in order to gain insight into molecular mechanisms for relatively high oxygen affinity and Bohr effect of this protein. The NMR data indicated that the acidic form of the protein possesses pentacoordinated heme, and that the alkaline form possessing OH- appears with increasing the pH value. pH titration yielded a pK value of 7.2 for the acid-alkaline transition, and this value is the lowest among the values reported so far for various myoglobins and hemoglobins. The kinetic measurements of the transition revealed that the activation energy for the dissociation of the Fe-bound OH-, as well as the dissociation and association rates, decrease with increasing the pH value. These pH dependence properties are likely to be related to the Bohr effect of this protein.


Assuntos
Dípteros/química , Larva/química , Metemoglobina/química , Animais , Heme/química , Concentração de Íons de Hidrogênio , Ressonância Magnética Nuclear Biomolecular , Termodinâmica , Água/química
18.
Biochim Biophys Acta ; 1387(1-2): 165-76, 1998 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-9748556

RESUMO

Elephant myoglobins both from Asian and African species have a glutamine in place of the usual distal (E7) histidine at position 64. We have isolated native oxymyoglobin directly from the skeletal muscle of African elephant (Loxodonta africana), and examined the autoxidation rate of oxymyoglobin (MbO2) to metmyoglobin (metMb) as a function of pH in 0.1 M buffer at 25 degreesC. As a result, African elephant MbO2 was found to be equally resistant to autoxidation as sperm whale myoglobin. However, the elephant myoglobin exhibited a distinct rate saturation below pH 6. Kinetic analysis of the pH profiles for the autoxidation rate has disclosed that African elephant MbO2 does not show any proton-catalyzed process, such as the one that can play a dominant role in the autoxidation reaction of sperm whale myoglobin by involving the distal histidine as its catalytic residue. Such a greater stability of African elephant MbO2 at low pH could be explained almost completely by the single H64Q mutation of sperm whale myoglobin. In African elephant aqua-metmyoglobin the Soret band was considerably broadened so as to produce another peak in the pentacoordinate 395 nm region. This unique spectral feature was therefore analyzed to show that the myoglobin is in equilibrium between two species, depending upon the presence or absence of a water molecule at the sixth coordinate position.


Assuntos
Elefantes , Mioglobina/química , Baleias , África , Animais , Concentração de Íons de Hidrogênio , Cinética , Metamioglobina/química , Músculo Esquelético/metabolismo , Mioglobina/genética , Oxirredução , Espectrofotometria
19.
J Clin Oncol ; 14(1): 204-13, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8558199

RESUMO

PURPOSE: We analyzed complete remission (CR), disease-free survival (DFS), and event-free survival (EFS) rates in two groups of patients treated with either N4-behenoyl-1-beta-D-arabinosylcytosine (BHAC) or cytarabine, and analyzed DFS with or without ubenimex, a biologic response modifier. PATIENTS AND METHODS: Newly diagnosed patients with acute myeloid leukemia (AML) were randomized to receive either BHAC or cytarabine as remission-induction combination chemotherapy and two courses of consolidation therapy. After maintenance/intensification therapy, patients in CR were randomized to receive either ubenimex and no drug. RESULTS: Of 341 patients registered, 326 were assessable. The age of assessable patients ranged from 15 to 82 years (median, 48). The overall CR rate was 77%: 72% in the BHAC group and 81% in the cytarabine group, and there was a significant difference between the two groups (P = .035, chi 2 test). The predicted 55-month EFS rate of all patients was 30%: 23% in the BHAC group and 35% in the cytarabine group, with a significant difference between groups (P = .0253). The predicted 55-month DFS rate of all CR patients was 38% and that of CR patients less than 50 years of age was 47%. There was no significant difference in DFS between the ubenimex group and the group that did not receive ubenimex. CONCLUSION: Analyses of our clinical trial showed that the use of BHAC in remission-induction therapy and in consolidation therapy resulted in poorer CR and EFS rates in adult AML patients compared with the use of cytarabine at the doses and schedules tested. Immunotherapy with ubenimex after the end of all chemotherapy did not improve DFS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide/tratamento farmacológico , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Distribuição de Qui-Quadrado , Citarabina/administração & dosagem , Citarabina/análogos & derivados , Daunorrubicina/administração & dosagem , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Leucina/administração & dosagem , Leucina/análogos & derivados , Leucemia Mieloide/mortalidade , Modelos Logísticos , Masculino , Mercaptopurina/administração & dosagem , Pessoa de Meia-Idade , Análise Multivariada , Prednisolona/administração & dosagem , Estudos Prospectivos , Indução de Remissão , Taxa de Sobrevida , Resultado do Tratamento
20.
J Mol Biol ; 209(3): 489-91, 1989 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-2585497

RESUMO

Myoglobins can be divided into two groups. One group contains the usual myoglobins that have histidine at the distal (E7) position, and the other contains a few, but interesting myoglobins that lack the usual distal histidine residue. Spectroscopic examinations have shown that there is a remarkable difference in the Soret band between the two types of myoglobin, and an absorbance ratio of the Soret peak of the acidic met-form to that of the oxy-form seems to be very useful as a simple criterion for predicting whether or not a myoglobin has the usual distal histidine residue.


Assuntos
Histidina , Mioglobina , Animais , Aplysia , Metamioglobina , Análise Espectral
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