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1.
J Dairy Sci ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38762114

RESUMO

The manufacturing method of String cheese is similar to Mozzarella, but the hot curd is extruded through narrow tubes or pipes, which align the protein fibers that provides the characteristic ability for consumers to pull strings from this cheese. Firmness is another important performance attribute for consumers who just bite into the String cheese without peeling off strings. There have only been a few studies on String cheese, but it is known that stringiness and firmness decrease during prolonged storage, which is a particular challenge for exporting String cheese. We explored 2 treatments to try to retain the stringiness and firmness of String cheese for longer storage periods. The techniques used were high pressure processing (HPP; 600 MPa for 3 min) and reduced storage temperature (0°C). In other cheese varieties, these techniques have helped extend the performance shelf-life. We tested these techniques using the 2 main types of commercial String cheese: direct acid (DASC) and cultured String cheese (CSC), that were obtained from 2 different manufacturing facilities. The DASC had higher fat (∼2.2%) and higher pH values (∼0.2 units) compared with the CSC. The CSC had higher protein content (∼3.4%), higher insoluble calcium content (∼8 mg insoluble Ca/g protein) and higher hardness values (∼4 N) compared with the DASC. Due to the compositional differences, the 2 varieties were statistically analyzed separately for all other attributes. In both cheese types, HPP caused an immediate reduction in stringiness, some solubilization of insoluble calcium, and a slight increase in the cheese pH values. HPP also caused a slight increase in the TPA hardness of the CSC samples until 14 d (possibly due to a slight increase in cheese pH). The use of the 0°C storage temperature reduced proteolysis and helped retain firmness during storage. Low temperature storage could help extend the performance shelf-life of String cheese by a couple of months, but HPP was not suitable as the process caused an immediate reduction in stringiness due to the disruption of the matrix induced by the HPP treatment.

2.
Inn Med (Heidelb) ; 64(1): 88-92, 2023 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-36418500

RESUMO

A 26-year-old woman with type 2 diabetes mellitus and discontinued intensive conventional insulin therapy was admitted to the authors' hospital with acute upper abdominal pain. Severe hypertriglyceridemia and acute pancreatitis were diagnosed. Treatment included insulin administration and plasmapheresis. On day 3, the patient developed sudden haemodynamic instability and in-hospital cardiopulmonary arrest. Focused echocardiography showed pericardial effusion with right ventricular collapse. Pericardiocentesis was performed, leading to a return of spontaneous circulation.


Assuntos
Tamponamento Cardíaco , Diabetes Mellitus Tipo 2 , Insulinas , Pancreatite , Feminino , Humanos , Adulto , Tamponamento Cardíaco/diagnóstico , Doença Aguda , Diabetes Mellitus Tipo 2/complicações , Pancreatite/complicações , Dor Abdominal
3.
J Chem Phys ; 156(7): 074502, 2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35183081

RESUMO

We apply field-cycling (FC) 31P nuclear magnetic resonance (NMR) to access the reorientational susceptibility of two glass formers, m-tricresyl phosphate (m-TCP) and tri-butyl phosphate (TBP). Although FC 31P studies are still instrumentally demanding, together with FC 1H data, they provide site-resolved information. A crossover from dipolar relaxation at low frequencies to relaxation determined by chemical shift anisotropy at high frequencies and probed by conventional NMR is identified. A comparison is made between dielectric (DS) and depolarized light scattering (DLS) relaxation spectra demonstrating similar behavior close to Tg, including an excess wing contribution for m-TCP. The time constants of 31P NMR and DLS, probing the molecular core, agree. The 1H data monitoring the dynamics of the phenyl groups yield slightly shorter correlation times. At high temperatures, the DS relaxation spectra show a bimodal character: a fast component in agreement with 1H data, and a slow component much slower than 31P NMR and DLS suggest. We discuss the possible origins of the slow component. All time constants tend to merge toward Tg. Hence, we propose that site-specific dynamics disappear and a common α-relaxation establishes near Tg. In addition, we compare the diffusion coefficient D(T) determined by FC and static field gradient 1H NMR. Concerning TBP, we present FC 31P data of both α- and ß-processes. Regarding the latter, we compare the DS and NMR susceptibility on absolute scale, yielding a significantly stronger ß-relaxation in the 31P NMR spectra.

4.
J Phys Chem B ; 125(49): 13519-13532, 2021 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-34860530

RESUMO

Spin-lattice relaxation rates R1(ω,T), probed via high-field and field-cycling nuclear magnetic resonance (NMR), are used to test the validity of frequency-temperature superposition (FTS) for the reorientation dynamics in viscous liquids. For several liquids, FTS is found to apply so that master curves can be generated. The susceptibility spectra are highly similar to those obtained from depolarized light scattering (DLS) and reveal an excess wing. Where FTS works, two approaches are suggested to access the susceptibility: (i) a plot of deuteron R1(T) vs the spin-spin relaxation rate R2(T) and (ii) a plot of R1(T) vs an independently measured reference time τref(T). Using single-frequency scans, (i) allows one to extract the relaxation stretching as well as the NMR coupling constant. Surveying 26 data sets, we find Kohlrausch functions with exponents 0.39 < ßK ≤ 0.67. Plots of the spin-spin relaxation rate R2─rescaled by the NMR coupling constant─as a function of temperature allow one to test how well site-specific NMR relaxations couple to a given reference process. Upon cooling of flexible molecule liquids, the site-specific dynamics is found to merge, suggesting that near Tg the molecules reorient essentially as a rigid entity. This presents a possible resolution for the much lower stretching parameters reported here at high temperatures that contrast with the ones that were reported to be universal in a recent DLS study close to Tg. Our analysis underlines that deuteron relaxation is a uniquely powerful tool to probe single-particle reorientation.


Assuntos
Temperatura Alta , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Temperatura , Viscosidade
5.
J Chem Phys ; 154(12): 124503, 2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33810699

RESUMO

We combine field-cycling (FC) relaxometry and molecular dynamics (MD) simulations to study the rotational and translational dynamics associated with the glassy slowdown of glycerol. The 1H NMR spin-lattice relaxation rates R1(ω) probed in the FC measurements for different isotope-labelled compounds are computed from the MD trajectories for broad frequency and temperature ranges. We find high correspondence between experiment and simulation. Concerning the rotational motion, we observe that the aliphatic and hydroxyl groups show similar correlation times but different stretching parameters, while the overall reorientation associated with the structural relaxation remains largely isotropic. Additional analysis of the simulation results reveals that transitions between different molecular configurations are slow on the time scale of the structural relaxation at least at sufficiently high temperatures, indicating that glycerol rotates at a rigid entity, but the reorientation is slower for elongated than for compact conformers. The translational contribution to R1(ω) is well described by the force-free hard sphere model. At sufficiently low frequencies, universal square-root laws provide access to the molecular diffusion coefficients. In both experiment and simulation, the time scales of the rotational and translational motions show an unusually large separation, which is at variance with the Stokes-Einstein-Debye relation. To further explore this effect, we investigate the structure and dynamics on various length scales in the simulations. We observe that a prepeak in the static structure factor S(q), which is related to a local segregation of aliphatic and hydroxyl groups, is accompanied by a peak in the correlation times τ(q) from coherent scattering functions.

6.
J Magn Reson ; 277: 79-85, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28258024

RESUMO

Field-Cycling (FC) NMR experiments were carried out at 1H Larmor frequencies down to about 3Hz. This could be achieved by fast switching a high polarizing magnetic field down to a low evolution field which is tilted with respect to the polarization field. Then, the low frequency Larmor precession of the nuclear spin magnetization about this evolution field is registered by means of FIDs in a high detection field. The crucial technical point of the experiment is the stabilization of the evolution field, which is achieved by compensating for temporal magnetic field fluctuations of all three spatial components. The paper reports on some other basic low field experiments such as the simultaneous measurement of the Larmor frequency and the spin-lattice relaxation time in such small fields as well as the irradiation of oscillating transversal magnetic field pulses at very low frequencies as a novel method for field calibration in low field FC NMR. The potential of low field FC is exemplified by the 1H relaxation dispersion of water at frequencies below about 2kHz stemming from the slow proton exchange process.

7.
Ecol Modell ; 340: 126-133, 2016 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-27890965

RESUMO

Social bees are central place foragers collecting floral resources from the surrounding landscape, but little is known about the probability of a scouting bee finding a particular flower patch. We therefore developed a software tool, BEESCOUT, to theoretically examine how bees might explore a landscape and distribute their scouting activities over time and space. An image file can be imported, which is interpreted by the model as a "forage map" with certain colours representing certain crops or habitat types as specified by the user. BEESCOUT calculates the size and location of these potential food sources in that landscape relative to a bee colony. An individual-based model then determines the detection probabilities of the food patches by bees, based on parameter values gathered from the flight patterns of radar-tracked honeybees and bumblebees. Various "search modes" describe hypothetical search strategies for the long-range exploration of scouting bees. The resulting detection probabilities of forage patches can be used as input for the recently developed honeybee model BEEHAVE, to explore realistic scenarios of colony growth and death in response to different stressors. In example simulations, we find that detection probabilities for food sources close to the colony fit empirical data reasonably well. However, for food sources further away no empirical data are available to validate model output. The simulated detection probabilities depend largely on the bees' search mode, and whether they exchange information about food source locations. Nevertheless, we show that landscape structure and connectivity of food sources can have a strong impact on the results. We believe that BEESCOUT is a valuable tool to better understand how landscape configurations and searching behaviour of bees affect detection probabilities of food sources. It can also guide the collection of relevant data and the design of experiments to close knowledge gaps, and provides a useful extension to the BEEHAVE honeybee model, enabling future users to explore how landscape structure and food availability affect the foraging decisions and patch visitation rates of the bees and, in consequence, to predict colony development and survival.

8.
J Phys Chem B ; 120(31): 7754-66, 2016 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-27420118

RESUMO

Due to the single-particle character of the quadrupolar interaction in molecular systems, (2)H NMR poses a unique method for probing reorientational dynamics. Spin-lattice relaxation gives access to the spectral density, and its frequency dependency can be monitored by field-cycling (FC) techniques. However, most FC NMR studies employ (1)H; the use of (2)H is still rare. We report on the application of (2)H FC NMR for investigating the dynamics in molecular liquids and polymers. Commercial as well as home-built relaxometers are employed accessing a frequency range from 30 Hz to 6 MHz. Due to low gyromagnetic ratio, high coupling constants, and finite FC switching times, current (2)H FC NMR does not reach the dispersion region in liquids (toluene and glycerol), yet good agreement with the results from conventional high-field (HF) relaxation studies is demonstrated. The pronounced difference at low frequencies between (2)H and (1)H FC NMR data shows the relevance of intermolecular relaxation in the case of (1)H NMR. In the case of the polymers polybutadiene and poly(ethylene-alt-propylene), very similar relaxation dispersion is observed and attributed to Rouse and entanglement dynamics. Combination with HF (2)H relaxation data via applying frequency-temperature superposition allows the reconstruction of the full spectral density reflecting both polymer as well as glassy dynamics. Transformation into the time domain yields the reorientational correlation function C2(t) extending over nine decades in time with a long-time power law, C2(t) ∝ t(-0.45±0.05), which does not conform to the prediction of the tube-reptation model, for which ∝ t(-0.25) is expected. Entanglement sets in below C2(t = τe) ≅ S(2) = 0.001, where τe is the entanglement time and S the corresponding order parameter. Finally, we discuss the future prospects of the (2)H FC NMR technique.

9.
Mol Biol Rep ; 40(11): 6205-12, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24065537

RESUMO

Beta-thalassemia is the most frequent hereditary blood disorder in Tunisia because of its geographic localization and history. This pathology is characterized by a complex multisystem process with genetic and biochemical interactions. The aim of this work was to establish phenotype/genotype association through studying the distribution and the relationship between ß-thalassemia and α-thalassemia mutations and three polymorphic markers: the C → T polymorphism at -158 of the Gγ gene, the RFLP haplotype and the repeated sequence (AT)xTy in the ß globin silencer, in two groups of ß-thalassemia major and ß-thalassemia intermedia (TI) patients. Statistical analysis has shown that moderate expression seen in TI patients was significantly associated to ß(+) -87 (C → G), -30 (T → A) and IVSI-6 (T → C) mutations, haplotypes VIII, IX and Nb and to XmnI polymorphism. The regression analysis of combined genotypes (mutation/XmnI/RFLP haplotype) revealed that they contribute to justify 17.1 % of clinical expression diversity (p < 0.05). Among the studied genotypes the XmnI polymorphism seems to be the most determinant modulating factor, followed by the ß-thalassemia mutation and RFLP haplotype. Our findings highlight the heterogeneity of molecular background of ß-thalassemia that would be responsible of clinical variability.


Assuntos
Estudos de Associação Genética , Heterogeneidade Genética , Globinas beta/genética , Talassemia beta/diagnóstico , Talassemia beta/genética , Adolescente , Adulto , Criança , Pré-Escolar , Ordem dos Genes , Haplótipos , Hemoglobinas/genética , Hemoglobinas/metabolismo , Humanos , Pessoa de Meia-Idade , Mutação , Motivos de Nucleotídeos , Fenótipo , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Regiões Promotoras Genéticas , Tunísia , Adulto Jovem , Talassemia alfa/genética , Talassemia alfa/metabolismo , Talassemia beta/sangue , gama-Globinas/genética
10.
Herz ; 35(5): 342-51, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20842474

RESUMO

Throughout life, damage to the vascular endothelium is pivotal in the development of cardiovascular disease. Therefore, a detailed understanding of the underlying mechanisms involved in endothelial cell restoration is of fundamental importance for preventive and therapeutic concepts in cardiovascular disease. The goal of regenerative medicine is the use of tissue-specific progenitor cells for a more effective repair process with reduction of fibrocellular remodelling, fibrosis and loss of functional properties.According to the hitherto assumed primary model of endothelial regeneration only adjacent and intact mature endothelial cells replace damaged endothelium. Since Asahara and colleagues first described that a peripheral blood mononuclear cell population was able to differentiate into endothelial cells in vitro and incorporate into ischemic tissue at sites of angiogenesis in vivo, the model of endothelial regeneration has been extended. The majority of clinical trials on human cell therapy for ischemic vascular disease are based on cell surface antigen expression of CD34 or VEGFR2 to identify endothelial progenitor cells.A precise characterization of the angiogenic properties of different subsets of endothelial regenerating cells and their course of action to gain sufficient long-term regeneration of the injured vessel is a necessary precondition before clinical trials of human cell therapy become a routine reality.


Assuntos
Transplante de Células , Endotélio Vascular/fisiopatologia , Regeneração Tecidual Guiada/métodos , Isquemia/fisiopatologia , Isquemia/terapia , Neovascularização Fisiológica/fisiologia , Células-Tronco/fisiologia , Animais , Antígenos CD34/metabolismo , Transplante de Medula Óssea , Células Endoteliais/transplante , Hemangioblastos/transplante , Humanos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
11.
Oncogene ; 26(39): 5752-61, 2007 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-17353902

RESUMO

The hedgehog (Hh) signaling pathway regulates progenitor cells during embryogenesis and tumorigenesis in multiple organ systems. We have investigated the activity of this pathway in adult gliomas, and demonstrate that the Hh pathway is operational and activated within grade II and III gliomas, but not grade IV de novo glioblastoma multiforme. Furthermore, our studies reveal that pathway activity and responsiveness is confined to progenitor cells within these tumors. Additionally, we demonstrate that Hh signaling in glioma progenitor cells is ligand-dependent and provide evidence documenting the in vivo source of Sonic hedgehog protein. These findings suggest a regulatory role for the Hh pathway in progenitor cells within grade II and III gliomas, and the potential clinical utility of monitoring and targeting this pathway in these primary brain tumors.


Assuntos
Neoplasias Encefálicas/genética , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Proteínas Hedgehog/genética , Células-Tronco Neoplásicas/fisiologia , Transdução de Sinais , Animais , Western Blotting , Neoplasias Encefálicas/classificação , Glioma/classificação , Humanos , Ligantes , Camundongos , Estadiamento de Neoplasias , Receptores Patched , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Receptores de Superfície Celular/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição/fisiologia , Células Tumorais Cultivadas , Proteína GLI1 em Dedos de Zinco
12.
J Nanosci Nanotechnol ; 3(1-2): 3-17, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12908227

RESUMO

The article gives a comprehensive overview of hydrogen storage in carbon nanostructures, including experimental results and theoretical calculations. Soon after the discovery of carbon nanotubes in 1991, different research groups succeeded in filling carbon nanotubes with some elements, and, therefore, the question arose of filling carbon nanotubes with hydrogen by possibly using new effects such as nano-capillarity. Subsequently, very promising experiments claiming high hydrogen storage capacities in different carbon nanostructures initiated enormous research activity. Hydrogen storage capacities have been reported that exceed the benchmark for automotive application of 6.5 wt% set by the U.S. Department of Energy. However, the experimental data obtained with different methods for various carbon nanostructures show an extreme scatter. Classical calculations based on physisorption of hydrogen molecules could not explain the high storage capacities measured at ambient temperature, and, assuming chemisorption of hydrogen atoms, hydrogen release requires temperatures too high for technical applications. Up to now, only a few calculations and experiments indicate the possibility of an intermediate binding energy. Recently, serious doubt has arisen in relation to several key experiments, causing considerable controversy. Furthermore, high hydrogen storage capacities measured for carbon nanofibers did not survive cross-checking in different laboratories. Therefore, in light of today's knowledge, it is becoming less likely that at moderate pressures around room temperature carbon nanostructures can store the amount of hydrogen required for automotive applications.


Assuntos
Hidrogênio/química , Modelos Moleculares , Nanotecnologia/métodos , Nanotubos de Carbono/química , Adsorção , Simulação por Computador , Fontes de Energia Elétrica , Eletroquímica/métodos , Hidrogênio/isolamento & purificação , Ligação de Hidrogênio , Substâncias Macromoleculares , Modelos Químicos , Conformação Molecular , Nanotubos de Carbono/isolamento & purificação
13.
JAMA ; 286(19): 2437-40, 2001 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-11712939

RESUMO

CONTEXT: Oculopharyngeal muscular dystrophy (OPMD) is a rare myopathy caused by polyalanine triplet repeat expansion in the gene for poly(A) binding protein 2 (PABP2) and is found in isolated cohorts throughout the world. We have observed numerous cases of OPMD in New Mexico. OBJECTIVE: To characterize the clinical, genetic, and demographic features of the OPMD population in New Mexico. DESIGN, SETTING, AND PARTICIPANTS: Cohort study with analysis of outpatient clinic medical records from 1965 to 2001 at the University of New Mexico Hospital and the New Mexico VA Health Care System in Albuquerque, which serve the entire state. MAIN OUTCOME MEASURES: Clinical phenotype, supplemented with genetic confirmation (n = 10 patients) and in-depth clinical evaluations (n = 49 patients). RESULTS: We identified 216 cases of OPMD (99 women and 117 men) from 39 kindreds of New Mexicans spanning up to 4 generations. All patients were Hispanic, and the majority of probands came from northern New Mexico. In patients who had both ocular and pharyngeal muscle weakness, ptosis was just as likely to occur before or concurrent with dysphagia. Proximal limb muscle weakness and gait abnormalities were common and occurred later than ocular or pharyngeal weakness. The clinical expression of OPMD caused marked debility, although life-table analysis showed no decrease in life expectancy compared with unaffected family members (P =.81). Ten individuals from different kindreds were found to have an identical polyalanine triplet repeat expansion ([GCG](9)) in the PABP2 gene. CONCLUSIONS: Individuals in this cohort had clinical and genetic characteristics of classic OPMD. Longevity was not affected, but patients experienced considerable morbidity. The origin of the PABP2 mutation in New Mexican OPMD patients is unclear, although the geographic and genetic isolation of northern New Mexicans with a long ancestry in this region may have contributed to the development of this cohort. This disease cohort represents a large and previously unrecognized health care issue in the state of New Mexico and should serve to raise the awareness of this disorder among clinicians who treat Hispanics in the Southwest and throughout the United States.


Assuntos
Hispânico ou Latino/genética , Distrofias Musculares/etnologia , Adulto , Idoso , Proteínas de Ligação a DNA/genética , Feminino , Hispânico ou Latino/estatística & dados numéricos , Humanos , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Distrofias Musculares/diagnóstico , Distrofias Musculares/epidemiologia , Distrofias Musculares/genética , New Mexico/epidemiologia , Fenótipo , Proteína II de Ligação a Poli(A) , Expansão das Repetições de Trinucleotídeos
14.
J Forensic Sci ; 46(2): 392-5, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11305449

RESUMO

Tumors of the central nervous system are an unusual cause of sudden death. This report describes the sudden death of a presumed healthy 28-year-old woman from primary diffuse leptomeningeal gliomatosis. She presented to an emergency room with headache and vomiting, subsequently became unresponsive and was pronounced dead 14 h later. Autopsy revealed a diffuse extensive infiltrate of well-differentiated astrocytoma in the leptomeninges of the brain and spinal cord without an underlying parenchymal tumor. Primary diffuse leptomeningeal gliomatosis is a rare tumor that arises within the leptomeninges from small neuroglial heterotopic rests that undergo neoplastic transformation. Grossly. this tumor can mimic leptomeningeal carcinomatosis, pachymeningitis, tuberculosis, sarcoidosis, and fungal infections. However, the histologic features of primary diffuse leptomeningeal gliomatosis should allow it to be readily distinguished from grossly similar conditions. The mechanism of death in this case is most likely tumor obstruction of cerebrospinal fluid outflow resulting in the usual complications seen with increased intracranial pressure. Although this tumor is aggressive and is associated with a rapidly progressive fatal course, it has not been previously associated with sudden death.


Assuntos
Astrocitoma/patologia , Morte Súbita/etiologia , Neoplasias Meníngeas/patologia , Adulto , Autopsia , Causas de Morte , Líquido Cefalorraquidiano , Feminino , Humanos , Pressão Intracraniana
15.
Ann Neurol ; 48(5): 812-5, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11079550

RESUMO

Intranuclear inclusions are one of the ultrastructural hallmarks of oculopharyngeal muscular dystrophy (OPMD), a disorder caused by small polyalanine (GCG) expansions in the gene that codes for a ubiquitous nuclear protein called poly(A) binding protein 2 (PABP2). We studied OPMD skeletal muscle and found that 1.0 to 10.0% of myocyte nuclei contained discreet PABP2 immunoreactive intranuclear inclusions, providing the first direct evidence of the relation between the proposed gene for OPMD and the pathology of OPMD.


Assuntos
Corpos de Inclusão/patologia , Músculos/patologia , Distrofias Musculares/genética , Distrofias Musculares/patologia , Proteínas de Ligação a RNA/análise , Humanos , Imuno-Histoquímica , Proteínas de Ligação a Poli(A)
16.
Proc Natl Acad Sci U S A ; 96(13): 7388-93, 1999 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-10377424

RESUMO

The protein huntingtin (htt), aggregated in neuronal nuclear inclusions, is pathognomonic of Huntington's disease (HD). Constructs, translated in vitro from the N terminus of htt, containing either polyQ23 from a normal individual, or polyQ41 or polyQ67 from an HD patient, were all soluble. Transglutaminase (TGase) crosslinked these proteins, and the aggregations did not have the staining properties of amyloid. More TGase-catalyzed aggregates formed when the polyglutamine domain of htt exceeded the pathologic threshold of polyQ36. Furthermore, shorter htt constructs, containing 135 aa or fewer, formed more aggregates than did larger htt constructs. TGase activity in the HD brain was increased compared with the control, with notable increases in cell nuclei. The increased TGase activity was brain specific. In lymphoblastoid cells from HD patients, TGase activity was decreased. TGase-mediated crosslinking of htt may be involved in the formation of the nonamyloidogenic nuclear inclusions found in the HD brain. The staining properties of nuclear inclusions in the HD brain revealed that they were not amyloid.


Assuntos
Encéfalo/metabolismo , Doença de Huntington/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas Nucleares/metabolismo , Transglutaminases/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/ultraestrutura , Núcleo Celular/metabolismo , Reagentes de Ligações Cruzadas , Dimerização , Ativação Enzimática , Humanos , Proteína Huntingtina , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/metabolismo
17.
Hum Pathol ; 30(5): 577-81, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10333230

RESUMO

Kearns-Sayre syndrome (KSS) and Pearson's marrow-pancreas syndrome (PMPS) are rare disorders caused by the same molecular defect, one of several deletion mutations in mitochondrial DNA (mtDNA). KSS is an encephalomyopathy with ophthalmoplegia, retinal degeneration, ataxia, and endocrine abnormalities. PMPS is a disorder of childhood characterized by refractory anemia, vacuolization of bone marrow cells, and exocrine pancreas dysfunction. Children with PMPS that have a mild phenotype, or are supported through bone marrow failure, often develop the encephalomyopathic features of KSS. The subject of numerous reports in the neuromuscular, genetic, and pediatric literature in recent years, very few cases of either disorder have ever been studied at autopsy. We report the results of our studies of a patient with clinically documented KSS who presented with renal dysfunction and was found to have a novel mtDNA deletion and degenerative changes in the central nervous system, retina, skeletal muscle, and pancreas.


Assuntos
Doenças da Medula Óssea/patologia , DNA Mitocondrial/genética , Síndrome de Kearns-Sayre/genética , Síndrome de Kearns-Sayre/patologia , Pancreatopatias/patologia , Adolescente , Sequência de Bases , Encéfalo/patologia , Evolução Fatal , Humanos , Masculino , Deleção de Sequência , Síndrome
18.
Hum Mol Genet ; 8(3): 397-407, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9949199

RESUMO

Huntington's disease (HD) is an inherited, neurodegenerative disorder caused by the expansion of a glutamine repeat in the N-terminus of the huntingtin protein. To gain insight into the pathogenesis of HD, we generated transgenic mice that express a cDNA encoding an N-terminal fragment (171 amino acids) of huntingtin with 82, 44 or 18 glutamines. Mice expressing relatively low steady-state levels of N171 huntingtin with 82 glutamine repeats (N171-82Q) develop behavioral abnormalities, including loss of coordination, tremors, hypokinesis and abnormal gait, before dying prematurely. In mice exhibiting these abnormalities, diffuse nuclear labeling, intranuclear inclusions and neuritic aggregates, all immunoreactive with an antibody to the N-terminus (amino acids 1-17) of huntingtin (AP194), were found in multiple populations of neurons. None of these behavioral or pathological phenotypes were seen in mice expressing N171-18Q. These findings are consistent with the idea that N-terminal fragments of huntingtin with a repeat expansion are toxic to neurons, and that N-terminal fragments are prone to form both intranuclear inclusions and neuritic aggregates.


Assuntos
Doença de Huntington/genética , Doença de Huntington/patologia , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/genética , Fragmentos de Peptídeos/genética , Animais , Sequência de Bases , Núcleo Celular/patologia , Primers do DNA/genética , Modelos Animais de Doenças , Humanos , Proteína Huntingtina , Doença de Huntington/fisiopatologia , Corpos de Inclusão/patologia , Camundongos , Camundongos Transgênicos , Neuritos/patologia , Fenótipo
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