RESUMEN
A recent study identified a variant of the NUDT15 gene (rs116855232 C>T) associated with intolerance to thiopurine in Korean patients with Crohn's disease. This study prompted us to substantiate the finding in a Taiwanese population. Four hundred and four children with acute lymphoblastic leukemia (ALL), and 100 adults with chronic immune thrombocytopenic purpura or localized lymphoma having normal bone marrow were examined. Two candidate gene approaches, pyrosequencing for NUDT15 and TaqMan assay for thiopurine methyltransferase (TPMT) genotyping (rs1142345 A>G), were performed. We showed a risk allele frequency of NUDT15 of 11.6% in children with ALL and 15.5% in adults. By contrast, the risk allele frequency of TPMT was only 1.6% in children with ALL and 0.5% in adults. The high frequency of risk variant for NUDT15, but not the very low frequency of risk variant for TPMT, was closely associated with the intolerance to mercaptopurine in children with ALL in Taiwan, contrast to that of European descent. In regard to NUDT15 polymorphism, the maximal tolerable daily doses of mercaptopurine in homozygotes, heterozygotes and wild-type groups were 9.4 mg m-2, 30.7 mg m-2 and 44.1 mg m-2, respectively. The outcomes did not differ significantly among the different genotypes.
Asunto(s)
Antimetabolitos Antineoplásicos/efectos adversos , Mercaptopurina/efectos adversos , Variantes Farmacogenómicas , Polimorfismo Genético , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Pirofosfatasas/genética , Factores de Edad , Antimetabolitos Antineoplásicos/administración & dosificación , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Heterocigoto , Homocigoto , Humanos , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Masculino , Dosis Máxima Tolerada , Mercaptopurina/administración & dosificación , Farmacogenética , Pruebas de Farmacogenómica/métodos , Fenotipo , Reacción en Cadena de la Polimerasa , Medicina de Precisión , Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimología , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Valor Predictivo de las Pruebas , Pirofosfatasas/metabolismo , Factores de Riesgo , Taiwán , Factores de Tiempo , Resultado del TratamientoRESUMEN
Postdental procedure bacteremia is common and troublesome. The comparative efficacy of multiple prophylactic interventions is unclear. We compared the efficacy of interventions for the prevention of postdental procedure bacteremia. We conducted a review of ClinicalKey, Cochrane CENTRAL, Embase, ProQuest, PubMed, ScienceDirect, Web of Science, and ClinicalTrials.gov from inception to December 4, 2018. Randomized controlled trials that evaluated prophylactic interventions for the prevention of postdental procedure bacteremia were eligible. The primary outcome was the incidence of postdental procedure bacteremia. A total of 24 trials were included with 2,147 participants. Our network meta-analysis demonstrated that intravenous administration of 1,000/200 mg of amoxicillin/clavulanate provided the least incidence of postdental procedure bacteremia among all the prophylactic interventions (odds ratio = 0.03, 95% CI = 0.00 to 0.63) as compared with the placebo/controls. Oral 3 g of amoxicillin had the least incidence of postdental procedure bacteremia among all oral or topical forms of prophylactic interventions (odds ratio = 0.10, 95% CI = 0.02 to 0.44) as compared with the placebo/controls. No serious adverse events, such as anaphylactic shock, mortality, and the development of antibiotic-resistant bacteria, were reported. None of the included subjects were of high risk of infectious endocarditis. Our network meta-analysis demonstrates that intravenous amoxicillin/clavulanate and oral amoxicillin might be the best prophylactic interventions in preventing postdental procedure bacteremia among all the oral/topical forms of interventions for the overall populations.
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Profilaxis Antibiótica , Bacteriemia/prevención & control , Odontología , Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Antibacterianos/uso terapéutico , Humanos , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
We have developed and characterized a line of Madin-Darby canine kidney (MDCK) cells overexpressing the human insulin receptor. The expressed receptor was found to be processed normally, and its intrinsic tyrosine kinase was determined to be functional from both in vitro and in vivo phosphorylation studies. The expressed receptor was able to mediate an insulin-stimulated increase in both anti-phosphotyrosine-precipitable and anti-insulin receptor substrate 1-precipitable phosphatidylinositol 3-kinase activity. Moreover, insulin-induced glycogen synthase activity was greater and more sensitive to insulin in the transfected cells than in the parental cells. Interestingly, insulin promoted tubule-like growth in cells overexpressing the insulin receptor but not in the parental cells. Another advantage of this cell system lies in its ability to polarize into distinct basolateral and apical membrane compartments. With the use of biotinylation and Western analysis, the expressed insulin receptor was found to be preferentially expressed in the basolateral membrane (fivefold greater) in comparison with the apical membrane. Therefore, MDCK cells overexpressing the insulin receptor represent a novel system to study not only the pathway of insulin signaling, but also this pathway in the context of cell polarity.
Asunto(s)
Riñón/metabolismo , Receptor de Insulina/fisiología , Transducción de Señal/fisiología , Animales , Línea Celular , Perros , Humanos , Riñón/citología , Riñón/enzimología , Proteínas Tirosina Quinasas/metabolismo , Receptor de Insulina/biosíntesis , Proteínas Recombinantes/biosíntesis , TransfecciónRESUMEN
Experiments were conducted to evaluate the impact of groundwater chemistry and travel distance on the transport and fate behavior of PRD-1, a bacteriophage employed as a surrogate tracer for pathogenic enteric viruses. The experiments were conducted in the unconfined aquifer at the United States Geological Survey Cape Cod Toxic-Substances Hydrology Research Site in Falmouth, Massachusetts. The transport behavior of bromide (Br(-)) and PRD-1 were evaluated in a sewage-effluent contaminated zone and a shallower uncontaminated zone at this site. Several multilevel sampling devices located along a 13-m transect were used to collect vertically discrete samples to examine longitudinal and vertical variability of PRD-1 retardation and attenuation. The concentration of viable bacteriophage in the aqueous phase decreased greatly during the first few meters of transport. This decrease is attributed to a combination of colloid filtration (attachment) and inactivation. The removal was greater (10(-12) relative recovery) and occurred within the first meter for the uncontaminated zone, whereas it was lesser (10(-9) relative recovery) and occurred over 4m in the contaminated zone. The lesser removal observed for the contaminated zone is attributed to the influence of sorbed and dissolved organic matter, phosphate, and other anions, which are present in higher concentrations in the contaminated zone, on PRD-1 attachment. After the initial decrease, the aqueous PRD-1 concentrations remained essentially constant in both zones for the remainder of the tests (total travel distances of 13 m), irrespective of variations in geochemical properties within and between the two zones. The viable, mobile PRD-1 particles traveled at nearly the rate of bromide, which was used as a non-reactive tracer. The results of this study indicate that a small fraction of viable virus particles may persist in the aqueous phase and travel significant distances in the subsurface environment.
Asunto(s)
Bacteriófago PRD1 , Inactivación de Virus , Agua/química , Bromuros , Conductividad Eléctrica , Concentración de Iones de Hidrógeno , Aguas del Alcantarillado , Suelo , Temperatura , Contaminantes del AguaRESUMEN
BACKGROUND: Primary dysmenorrhoea (PDM) is inexorably common. PDM women suffer from cramping pain in the lower abdomen that starts with menstruation and lasts for 24-72 h. Up to 90% of adolescent girls and more than 50% of menstruating women worldwide report suffering from it. Ten to 20% of PDM women describe their suffering as severe and distressing. However, nothing is known regarding the association of PDM with possible brain anomalies or abnormalities. METHODS: High-resolution T1-weighted anatomical brain magnetic resonance images (MRI) were acquired for each subject and inspected for incidental findings (normal variants and abnormalities) as a routine procedure in our PDM-related multimodal neuroimaging studies. Altogether, 330 right-handed young women [otherwise healthy PDMs = 163; non-PDM healthy controls (HCs) = 167] were enrolled during the period of 2006-2014. Binomial proportion test was performed for between-group comparisons. RESULTS: PDMs demonstrated significantly higher prevalence of overall incidental brain MRI findings (PDMs: n = 18, 11.0%; HCs: n = 6, 3.6%; p = 0.005) that should be ascribed to a preponderance of normal variants (PDMs: n = 16, 9.8%; HCs: n = 3, 1.8%; p = 0.001), especially cavum septum pellucidum. No significant between-group difference of abnormal findings was found (PDMs: n = 2, 1.2%; HCs: n = 3, 1.8%; p = 0.336). CONCLUSIONS: We report here that otherwise healthy PDMs are associated with high prevalence of normal variants but not brain abnormalities. Our observations invite further epidemiological and neuroscientific studies.
Asunto(s)
Encéfalo/patología , Dismenorrea/complicaciones , Hallazgos Incidentales , Adolescente , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Neuroimagen , Prevalencia , Tabique Pelúcido/patología , Adulto JovenRESUMEN
A forced-gradient tracer test was conducted at the Georgetown site to study the transport of natural organic matter (NOM) in groundwater. In particular, the goal of this experiment was to investigate the interactions between NOM and the aquifer matrix. A detailed three-dimensional characterization of the hydrologic conductivity heterogeneity of the site was obtained using slug tests. The transport of a conservative tracer (chloride) was successfully reproduced using these conductivity data. Despite the good simulation of the flow field, NOM breakthrough curves could not be reproduced using a two-site sorption model with spatially constant parameters. Preliminary results suggest that different mechanisms for the adsorption/desorption processes, as well as their spatial variability, may significantly affect the transport and fate of NOM.
Asunto(s)
Carbono , Simulación por Computador , Agua Dulce , Modelos Teóricos , Movimientos del Agua , Contaminantes Químicos del Agua/análisis , Adsorción , Estudios de Evaluación como Asunto , Estrés MecánicoRESUMEN
fMRI was used to investigate brain organization for reading in Chinese. Subjects were shown two-character Chinese words. A control task was used to eliminate the non-linguistic visual and motor confounds. Results show that naming of Chinese logographs is characterized by left-lateralized neuronal networks for the processing of orthographic, phonological, and semantic attributes. The orchestration of the middle frontal cortex, superior temporal cortex, superior parietal cortex, basal temporal area and extrastriate cortices of the left hemisphere may manifest the particularity of the central representation of simple word naming in Chinese.
Asunto(s)
Corteza Cerebral/fisiología , Lateralidad Funcional/fisiología , Imagen por Resonancia Magnética , Lectura , Adulto , Femenino , Lóbulo Frontal/fisiología , Humanos , Masculino , Lóbulo Parietal/fisiología , Percepción Espacial/fisiología , Lóbulo Temporal/fisiologíaRESUMEN
Visceral hypersensitivity in gastric fundus is a possible pathogenesis for functional dyspepsia. The cortical representation of gastric fundus is still unclear. Growing evidence shows that the insula, but not the primary or secondary somatosensory region (SI or SII), may be the cortical target for visceral pain. Animal studies have also demonstrated that amygdala plays an important role in processing visceral pain. We used fMRI to study central projection of stomach pain from fundus balloon distension. We also tested the hypothesis that there will be neither S1 nor S2 activation, but amygdala activation with the fundus distension. A 3T-fMRI was performed on 10 healthy subjects during baseline, fullness (12.7 +/- 0.6 mmHg) and moderate gastric pain (17.0 +/- 0.8 mmHg). fMRI signal was modelled by convolving the predetermined psychophysical response. Statistical comparisons were performed between conditions on a group level. Gastric pain activated a wide range of cortical and subcortical structures, including thalamus and insula, anterior and posterior cingulate cortices, basal ganglia, caudate nuclei, amygdala, brain stem, cerebellum and prefrontal cortex (P < 0.001). A subset of these neuronal substrates was engaged in the central processing of fullness sensation. SI and SII were not activated during the fundus stimulation. In conclusion, the constellation of neuronal structures activated by fundus distension overlaps the pain matrices induced musculocutaneous pain, with the exception of the absence of SI or SII activation. This may account for the vague nature of visceral sensation/pain. Our data also confirms that the insula and amygdala may act as the central role in visceral sensation/pain, as well as in the proposed sensory-limbic model of learning and memory of pain.
Asunto(s)
Dolor Abdominal/fisiopatología , Mapeo Encefálico , Encéfalo/fisiología , Fundus Gástrico/inervación , Fundus Gástrico/fisiopatología , Adulto , Amígdala del Cerebelo/fisiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Neuronas/fisiología , PresiónRESUMEN
We performed a positron emission tomography study, using regional cerebral blood flow as the index of brain activity, to address the specificity of brain activation pattern by acupuncture stimulation of short duration at the classical analgesic point. Needling manipulation at 2 Hz was performed at a classical point of prominent analgesic efficacy (Li 4, Heku) and a near-by non-classical/non-analgesic point, respectively, in normal subjects. Regions activated by acupuncture stimulation at Li 4 included the hypothalamus with an extension to midbrain, the insula, the anterior cingulate cortex, and the cerebellum. Of note, it was only the stimulation at Li 4 that activated the hypothalamus under the similar psychophysical ratings of acupuncture sensation (deqi) as elicited by the stimulation at the two points, respectively. The data suggested that the hypothalamus might characterize the central expression of acupuncture stimulation at the classical analgesic point and serve as one key element in mediating analgesic efficacy of acupuncture stimulation.
Asunto(s)
Analgesia por Acupuntura/métodos , Encéfalo/fisiopatología , Circulación Cerebrovascular/fisiología , Hipotálamo/diagnóstico por imagen , Hipotálamo/fisiopatología , Dolor/fisiopatología , Adulto , Vías Aferentes/diagnóstico por imagen , Vías Aferentes/fisiopatología , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Femenino , Humanos , Masculino , Tomografía Computarizada de EmisiónRESUMEN
We studied, using standard microelectrode technique, the effects of caffeine alone and in conjunction with epinephrine in ventricular myocardial fibers obtained from the failing hearts of 12 recipients of heart transplant. Results revealed that caffeine (1-3 mM) prolonged slightly the duration of fast response action potential near final repolarization and the twitch curve but slightly increased, or even decreased, the twitch force. Epinephrine (3 microM) induced a submaximal positive inotropic effect in myocardial fibers obtained from the failing hearts. Caffeine at 1 mM significantly potentiated the force of contraction and accelerated the rate of twitch relaxation increased by epinephrine. Increasing concentration of caffeine to 3 mM in the presence of epinephrine did not enhance further the twitch force but rather induced the delayed after-depolarization in two of eight experiments. In a preparation from one patient with dilated cardiomyopathy, the combination of caffeine and epinephrine induced repetitive triggered rhythms. The present findings suggest that, in human ventricular myocardium obtained from certain patients transplanted for congestive heart failure, caffeine could induce positive inotropy and triggered automaticity through a potentiation of the actions of catecholamines.
Asunto(s)
Potenciales de Acción/efectos de los fármacos , Cafeína/farmacología , Cardiotónicos/farmacología , Epinefrina/farmacología , Ventrículos Cardíacos/efectos de los fármacos , Contracción Miocárdica/efectos de los fármacos , Agonistas Adrenérgicos , Adulto , Calcio/metabolismo , Gasto Cardíaco Bajo/fisiopatología , Interacciones Farmacológicas , Femenino , Humanos , MasculinoRESUMEN
The eradication of the 2 mosquito-borne parasitic diseases, malaria and lymphatic filariasis, is one of the greatest achievements of the parasite control campaigns in Taiwan. Most of the soil-transmitted nematode infections, with the exception of pinworm infection, are currently well controlled and limited to some aboriginal areas. Food-borne parasitic zoonosis such as infections with Angiostrongylus cantonensis, Clonorchis sinensis, and Taenia saginata asiatica are not rare, but the former is seasonal and the latter 2 are ethnically and geographically associated. Intestinal protozoal infections with Giardia lamblia and Cryptosporidium parvum are at low levels but may be widely distributed. Opportunistic protozoal infections among patients with acquired immunodeficiency syndrome, which included amebic colitis, Pneumocystis carinii pneumonia, and cerebral toxoplasmosis, are becoming increasingly important. The rapid increase in international travel and the introduction of large numbers of foreign workers from other countries in Southeast Asia may change the epidemiological patterns of parasitic infections in Taiwan.
Asunto(s)
Enfermedades Parasitarias/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Animales , Humanos , Taiwán/epidemiologíaRESUMEN
OBJECTIVE: To investigate the effects of acupuncture on neural activity detected by use of manganese-enhanced functional magnetic resonance imaging (fMRI) and elucidate the relationship between somatic acupoint stimulation and brain activation. ANIMALS: 40 New Zealand White rabbits. PROCEDURE: Manganese-enhanced fMRI was performed in anesthetized rabbits manipulated with electroacupuncture (EA) on Zusanli (ST-36) and Yanglingquan (GB-34) acupoints. Image acquisition was performed on a 1.5T superconductive clinical scanner with a circular polarized extremity coil. T1-weighted images were acquired sequentially as follows: baseline, after mannitol injection, after manganese infusion, and 5 and 20 minutes after initiation of EA. RESULTS: Changes in focal neural activity were detected by use of manganese-enhanced fMRI. Stimulation on Zusanli (ST-36) for 5 minutes resulted in activation of the hippocampus, whereas stimulation on Yanglingquan (GB-34) resulted in activation of the hypothalamus, insula, and motor cortex. Activation became less specific after 20 minutes of EA. Furthermore, stimulation on ipsilateral acupoints led to bilateral brain activation. CONCLUSIONS AND CLINICAL RELEVANCE: Each acupoint has a corresponding cerebral linkage, and stimulation on these points resulted in time-dependent neural activation. Understanding the linkage between peripheral acupoint stimulation and central neural pathways may provide a useful guide for clinical applications of acupuncture.
Asunto(s)
Encéfalo/fisiología , Electroacupuntura/veterinaria , Imagen por Resonancia Magnética/veterinaria , Manitol/administración & dosificación , Conejos/fisiología , Animales , Encéfalo/anatomía & histología , Femenino , Imagen por Resonancia Magnética/métodos , Masculino , ManganesoRESUMEN
Role of endocardial endothelium in the electromechanical activity of human heart was studied in isolated human atrial and ventricular muscle fibers obtained at cardiac surgery. The endocardial endothelium was damaged by brief exposure to a bolus of the detergent Triton X-100 (0.25-1 vol%). Triton at concentrations of up to 1 vol% reduced twitch force by one-fifth and one-fourth in guinea-pig sinoatrial and ventricular tissues, respectively, but did not change the action potential configuration. In human atrial tissues, however, a brief exposure to 20 microliters of Triton (0.25-1 vol%) depressed the excitability of both fast and slow response action potentials and reduced markedly the twitch force. The effects of Triton were less potent in human ventricular tissues but Triton still decreased significantly the twitch force (-37 +/- 6.4%) at a concentration of 0.25 vol%. Also, the positive inotropic response to phenylephrine (10-100 microM) was shifted to the higher concentrations by Triton treatment. The present findings indicate that the diseased human atrial and ventricular tissues were more sensitive to the effects of endocardial damage induced by Triton exposure than the healthy animal cardiac tissues were. In addition, the electromechanical responses to the adrenergic agonist phenylephrine were decreased in human cardiac tissues with defective endocardial endothelium.
Asunto(s)
Endocardio/fisiopatología , Cardiopatías/fisiopatología , Corazón/fisiopatología , Animales , Electrofisiología , Endocardio/patología , Cobayas , Corazón/efectos de los fármacos , Atrios Cardíacos , Cardiopatías/patología , Ventrículos Cardíacos , Humanos , Contracción Miocárdica/efectos de los fármacos , Octoxinol/farmacología , Fenilefrina/farmacologíaRESUMEN
The long-term outcome of 1390 children with acute lymphoblastic leukemia (ALL), treated in two successive clinical trials (Taiwan Pediatric Oncology Group (TPOG)-ALL-97 and TPOG-ALL-2002) between 1997 and 2007, is reported. The event-free survival improved significantly (P=0.0004) over this period, 69.3+/-1.9% in 1997-2001 to 77.4+/-1.7% in 2002-2007. A randomized trial in TPOG-97 testing L-asparaginase versus epidoxorubicin in combination with vincristine and prednisolone for remission induction in standard-risk (SR; low-risk) patients yielded similar outcomes. Another randomized trial, in TPOG-2002, showed that for SR patients, two reinduction courses did not improve long-term outcome over one course. Decreasing use of prophylactic cranial irradiation in the period 1997-2008 was not associated with increased rates of CNS relapse, prompting complete omission of prophylactic cranial irradiation from TPOG protocols, beginning in 2009. Decreased use of etoposide and cranial irradiation likely contributed to the low incidence of second cancers. High-risk B-lineage ALL, T-cell, CD10 negativity, t(9;22), infant, and higher leukocyte count were consistently adverse factors, whereas hyperdiploidy >50 was a consistently favorable factor. Higher leukocyte count and t(9;22) retained prognostic significance in both TPOG-97 and TPOG-2002 by multivariate analysis. Although long-term outcome in TPOG clinical trials is comparable with results being reported worldwide, the persistent strength of certain prognostic variables and the lower frequencies of favorable outcome predictors, such as ETV6-RUNX1 and hyperdiploidy >50, in Taiwanese children warrant renewed effort to cure a higher proportion of patients while preserving their quality of life.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/terapia , Neoplasias Primarias Secundarias/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Niño , Preescolar , Aberraciones Cromosómicas , Terapia Combinada , Irradiación Craneana , Femenino , Estudios de Seguimiento , Humanos , Inmunofenotipificación , Lactante , Masculino , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Neoplasia Residual , Neoplasias Primarias Secundarias/genética , Neoplasias Primarias Secundarias/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Pronóstico , Inducción de Remisión , Factores de Riesgo , Tasa de Supervivencia , Taiwán , Factores de Tiempo , Resultado del TratamientoRESUMEN
c-KIT mutations have been described in core-binding factor (CBF) acute myeloid leukemia (AML) at diagnosis. The role of c-KIT mutations in the relapse of CBF-AML is not clear. The role of CSF1R mutation in the pathogenesis of AML remains to be determined. We analyzed receptor tyrosine kinases (RTKs) and Ras mutations on 154 children with AML. Also, we examined the paired diagnosis and relapse samples in CBF-AML. CBF-AML accounted for 27% (41/154). c-KIT mutations were detected in 41.5% of CBF-AML at diagnosis (6 in exon 8, 10 in exon 17 and 1 in both exons 8 and 17) , FLT3-TKD 2.7%, N-Ras mutations 7.3% and K-Ras mutations 4.9%. FLT3-LM and CSF1R mutations were not found in CBF-AML. The mutations of RTKs and Ras were mutually exclusive except for one patient who had both c-KIT and N-Ras mutations. Eight of the 41 CBF-AML patients relapsed; four patients retained the identical c-KIT mutation patterns as those at diagnosis, the remaining four without c-KIT mutations at diagnosis did not acquire c-KIT mutations at relapse. Our study showed that 54% of childhood CBF-AML had RTKs and/or Ras mutations; c-KIT but not CSF1R mutations play a role in the leukemogenesis of childhood CBF-AML.
Asunto(s)
Factores de Unión al Sitio Principal , Genes ras/genética , Leucemia Mieloide Aguda/genética , Mutación , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Tirosina Quinasas Receptoras/genética , Receptor de Factor Estimulante de Colonias de Macrófagos/genética , Adolescente , Médula Ósea/patología , Niño , Preescolar , Análisis Mutacional de ADN , Humanos , Leucemia Mieloide Aguda/etiología , Recurrencia , Factores de TiempoRESUMEN
In the early 1990s, the search for protein kinases led to the discovery of a novel family of non-receptor tyrosine kinases, the Janus kinases or JAKs. These proteins were unusual because they contained two kinase homology domains and no other known signaling modules. It soon became clear that these were not 'just another' type of kinase. Their ability to complement mutant cells insensitive to interferons and to be activated by a variety of cytokines demonstrated their central signaling function. Now, as we approach the end of the decade, it is evident from biochemical studies to knockout mice that JAKs play non-redundant functions in development, differentiation, and host defense mechanisms. Here, recent progress is reviewed, with particular emphasis on structure-function studies aimed at revealing how this family of tyrosine kinases is regulated.
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Proteínas Tirosina Quinasas/fisiología , Transducción de Señal , Animales , Citocinas/fisiología , Humanos , Interferones/fisiología , Ratones , Ratones NoqueadosRESUMEN
Mice have two lysozyme c genes that are the products of a gene duplication. The rat genome also possesses two lysozyme genes, which implies that the duplication of the lysozyme gene preceded the mouse-rat divergence. Concerted evolution has homogenized the 3' half (middle of exon 2 through 3' flanking) of the genes in each species. A mosaic pattern of concerted evolution is found for the 5' half of the gene, with both the 5' and 3' ends, but not the middle, of exon 1 evolving in a concerted fashion. Differences exist in the homogenization pattern in the rat and mouse, suggesting the existence of species-specific patterns of concerted evolution. Exon 1 contains most of the amino acid substitutions that distinguish mouse M from mouse P lysozyme or rat 1 from rat 2 lysozyme. Some of the amino acid differences found between mouse lysozyme genes are found also in the rat, and they suggest that rat 1 and 2 are homologous to mouse M and P, respectively. Nuclease S1 mapping indicated that only the rat 1 gene is expressed at detectable levels, and, specifically, that this gene is expressed by cells in the lung, small intestine, and spleen. The mouse expresses different lysozyme genes in the intestinal (P) and macrophage (M) cells, while the rat expresses only one gene in both of these tissues. The absence of detectable expression and the accumulation of a large number of amino acid substitutions in the parts of exons 1 and 2 of the rat 2 gene not participating in concerted evolution suggest that the rat 2 gene is a pseudogene.
Asunto(s)
Isoenzimas/genética , Muramidasa/genética , Filogenia , Ratas/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Inducción Enzimática , Exones , Genes , Isoenzimas/biosíntesis , Ratones/genética , Modelos Genéticos , Datos de Secuencia Molecular , Familia de Multigenes , Muramidasa/biosíntesis , Especificidad de Órganos , Seudogenes , Secuencias Repetitivas de Ácidos Nucleicos , Roedores/genética , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Especificidad de la EspecieRESUMEN
We would like to present a patient, who was a 60 years old man, 160 cm tall, weighing 55 kg, which received debridement for his pressure sores under epidural anesthesia. While inserting the Touhy needle, there was obvious loss of resistance at the level of 9 cm below the skin. When the test dose was injected, the compliance was good. Later, the anesthesia behaved as unilateral block. After the operation, the computerized tomography revealed the epidural catheter was between the facia of right psoas major muscle. Form this case, there were some lesions: (1) The distance from the skin to the lumbar dura mater is seldom longer than 7 cm. (2) The obvious loss-of-resistance and good compliance of test dose are not the guarantee of epidural anesthesia. (3) The psoas block may be another cause of unilateral block of lumbar epidural anesthesia.