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Objective: To investigate the correlation between the first tarsometatarsal joint (TMT1) sagittal mobility and hallux valgus (HV) combined with transfer metatarsalgia (TM). Methods: The weight-bearing CT (WBCT) imaging data of 111 HV patients (167 feet) who were treated at the Foot and Ankle Surgery Center, Beijing Tongren Hospital Affiliated to Capital Medical University from January 2018 to January 2020 were retrospectively analyzed. The patients underwent PedCAT WBCT scans of both feet, and the hallux valgus angle (HVA), intermetatarsal angle (IMA), plantar distance (PD), medial cuneiform-first metatarsal angle (CMA) and metatarsal protrusion distance (MPD) were measured using CubeVue software. PD and CMA were signs of TMT1 instability. Visual analogue scale (VAS) and foot and ankle ability measures (FAAM) scores were obtained. The patients were divided into TM group and non-TM group according to the presence of metatarsalgia. The TM group and the non-TM group were compared in terms of HVA, IMA, PD, CMA, MPD, VAS and FAAM. Correlations between PD, CMA and HVA, IMA, VAS, FAAM were analyzed using Spearman correlation. Results: Total of 111 cases were included in this study, there were 35 males and 76 females with a mean age of (57.7±14.1) years. The average values of HVA (37.9°±8.6°), IMA (17.9°±2.6°), CMA (2.1°±0.3°) and PD [(1.8±0.4) mm] in TM group were all significantly higher than those in the non-TM group [HVA (32.5°±9.1°), IMA (15.1°±3.4°), CMA (1.7°±0.3°) and PD (1.6±0.2) mm] (All P<0.001). There was no significant difference in MPD between the two groups (P=0.580). The TM group demonstrated a higher VAS score when compared with the non-TM group (P<0.001). The FAAM score of the TM group (54.1±11.8) was significantly lower than that in the non-TM group (66.2±11.4) (P<0.001). The results of Spearman correlation analysis showed that there was no correlation between PD and HVA, IMA and VAS score. There was a negative correlation between PD, CMA and FAAM score, and the difference was statistically significant (rs=-0.637, -0.254, both P<0.001); CMA was positively correlated with HVA, IMA, and VAS score (rs=0.603, 0.971, 0.269, all P<0.001). Conclusions: WBCT is helpful for the diagnosis of TMT1 sagittal instability. The severity of TMT1 sagittal instability is positively correlated with hallux valgus and TM. The TMT1 instability may play an important role in the pathogenesis of hallux valgus.
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Hallux Valgus , Huesos Metatarsianos , Metatarsalgia , Masculino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Hallux Valgus/diagnóstico por imagen , Hallux Valgus/cirugía , Estudios Retrospectivos , Radiografía , Osteotomía/métodos , Huesos Metatarsianos/cirugía , Resultado del TratamientoRESUMEN
Recent advances in MRI and increasing knowledge on the characterization and anatomical variability of medial temporal lobe (MTL) anatomy have paved the way for more specific subdivisions of the MTL in humans. In addition, recent studies suggest that early changes in many neurodegenerative and neuropsychiatric diseases are better detected in smaller subregions of the MTL rather than with whole structure analyses. Here, we developed a new protocol using 7 Tesla (T) MRI incorporating novel anatomical findings for the manual segmentation of entorhinal cortex (ErC), perirhinal cortex (PrC; divided into area 35 and 36), parahippocampal cortex (PhC), and hippocampus; which includes the subfields subiculum (Sub), CA1, CA2, as well as CA3 and dentate gyrus (DG) which are separated by the endfolial pathway covering most of the long axis of the hippocampus. We provide detailed instructions alongside slice-by-slice segmentations to ease learning for the untrained but also more experienced raters. Twenty-two subjects were scanned (19-32 yrs, mean age = 26 years, 12 females) with a turbo spin echo (TSE) T2-weighted MRI sequence with high-resolution oblique coronal slices oriented orthogonal to the long axis of the hippocampus (in-plane resolution 0.44 × 0.44 mm2) and 1.0 mm slice thickness. The scans were manually delineated by two experienced raters, to assess intra- and inter-rater reliability. The Dice Similarity Index (DSI) was above 0.78 for all regions and the Intraclass Correlation Coefficients (ICC) were between 0.76 to 0.99 both for intra- and inter-rater reliability. In conclusion, this study presents a fine-grained and comprehensive segmentation protocol for MTL structures at 7 T MRI that closely follows recent knowledge from anatomical studies. More specific subdivisions (e.g. area 35 and 36 in PrC, and the separation of DG and CA3) may pave the way for more precise delineations thereby enabling the detection of early volumetric changes in dementia and neuropsychiatric diseases.
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Mapeo Encefálico/métodos , Hipocampo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Lóbulo Temporal/diagnóstico por imagen , Adulto , Mapeo Encefálico/normas , Giro Dentado/diagnóstico por imagen , Giro Dentado/fisiología , Femenino , Hipocampo/fisiología , Humanos , Imagen por Resonancia Magnética/normas , Masculino , Lóbulo Temporal/fisiología , Adulto JovenRESUMEN
Erythropoietin (EPO) is a glycoprotein hormone conventionally thought to be responsible only in producing red blood cells in our body. However, with the discovery of the presence of EPO and EPO receptors in the retinal layers, the EPO seems to have physiological roles in the eye. In this review, we revisit the role of EPO in the eye. We look into the biological role of EPO in the development of the eye and the physiologic roles that it has. Apart from that, we seek to understand the mechanisms and pathways of EPO that contributes to the therapeutic and pathological conditions of the various ocular disorders such as diabetic retinopathy, retinopathy of prematurity, glaucoma, age-related macular degeneration, optic neuritis, and retinal detachment. With these understandings, we discuss the clinical applications of EPO for treatment of ocular disorders, modes of administration, EPO formulations, current clinical trials, and its future directions.
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Eritropoyetina/uso terapéutico , Oftalmopatías/tratamiento farmacológico , Eritropoyetina/fisiología , Oftalmopatías/etiología , Oftalmopatías/fisiopatología , Oftalmopatías/prevención & control , HumanosRESUMEN
Cardiomyocyte death is an important reason for the cardiac syndromes, such as heart failure (HF) and myocardial infarction (MI). In the heart diseases, necrosis is one of the main forms of cell death. MicroRNAs (miRNAs) are a class of small non-coding RNAs that mediate post-transcriptional gene silencing. Hitherto, it is not yet clear whether miRNA can regulate necrosis in cardiomyocyte. In this work, we performed a microarray to detect miRNAs in response to H2O2 treatment, and the results showed that miR-874 was substantially increased. We further studied the function of miR-874, and observed that knockdown of miR-874 attenuated necrosis in the cellular model and also MI in the animal model. We searched for the downstream mediator of miR-874 and identified that caspase-8 was a target of miR-874. Caspase-8 was able to antagonize necrosis. When suppressed by miR-874, caspase-8 lost the ability to repress necrotic program. In exploring the molecular mechanism by which miR-874 expression is regulated, we identified that Foxo3a could transcriptionally repress miR-874 expression. Foxo3a transgenic or knockout mice exhibited a low or high expression level of miR-874, and a reduced or enhanced necrosis and MI. Our present study reveals a novel myocardial necrotic regulating model, which is composed of Foxo3a, miR-874 and caspase-8. Modulation of their levels may provide a new approach for tackling myocardial necrosis.
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Caspasa 8/genética , MicroARNs/genética , Miocardio/patología , Miocitos Cardíacos/fisiología , Regiones no Traducidas 3' , Animales , Apoptosis , Secuencia de Bases , Sitios de Unión , Caspasa 8/metabolismo , Células Cultivadas , Represión Enzimática , Proteína Forkhead Box O3 , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Peróxido de Hidrógeno/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Necrosis , Oxidantes/farmacología , Regiones Promotoras Genéticas , Interferencia de ARNRESUMEN
Since the summer of 2006, bacterial boll rot of cotton has been observed on fruits of 'Xinluzao 31' (Xinluzao 6 × Acala) in Xinjiang Province. It resulted in as much as 20% yield loss in several fields. Symptoms do not appear on the outer carpel. In the infected cotton bolls, fibers do not mature completely and seed tissue exhibits brown necrotic coloration. Lint and seeds from 24 surface-disinfested cotton bolls were triturated and plated onto King's medium B (KB). Plates were incubated at 28°C for 48 h. Forty eight strains with yellow pigmentation on KB were characterized. All were nonfluorescent on KB, gram negative, facultatively anaerobic, unable to produce indole from tryptophan, able to reduce nitrate to nitrite, and produce acid from glucose, cellobiose, lactose, melibiose, and melonate. In addition, 16S rDNA in seven strains was amplified with universal primers (1). The PCR products were cloned into pGEM-T easy vector and sequenced. A BLAST search of the seven sequences against the GenBank nucleotide library indicated 100% identity with the 16S rDNA sequence of Enterobacter agglomerans strain A80. Then an additional primer pair, pagF and pagR (3), was used for more specific amplification of Pantoea agglomerans 16S rDNA, which resulted in single highly specific fragments of approximately 1 kb. On the basis of morphological, physiological, biochemical characteristics, and 16S rRNA gene sequence analysis, we identified the bacterium to be P. agglomerans. To confirm pathogenicity, cell suspensions (1 × 108 CFU/ml) of eight representative strains were used to inoculate cotton at peak bolling stage in the field. Cell suspensions, or water as the control, were applied to stigma scars, wall sutures, and scratch wounds on bracts, calyxes, and bolls. Alternatively, a needle was used to puncture through a drop of suspension placed on the boll wall suture and bracts. At least 20 bolls or flowers were inoculated with each bacterial strain per inoculation method. Infection occurred only when bacterial injections breached the endocarp of the boll either through the carpel wall or a suture between carpel sections. Disease symptoms developed 1 week postinoculation. The inoculated organism was reisolated from the diseased tissues. P. agglomerans is generally regarded to be a soil saprophyte or leaf epiphyte, but strains can opportunistically infect plants triggering gall formations or human wounds causing septic arthritis. The disease symptoms and pathogen characteristics observed in this study are identical to those reported in the United States (2). To our knowledge, this is the first report of P. agglomerans causing boll rot of cotton in China. References: (1) S. Manulisi and I. Barash. Mol. Plant Pathol. 4:307, 2003. (2) E. G. Medrano et al. J. Appl. Microbiol. 103:436, 2007. (3) S. Vorwerk et al. Agric. For. Entomol. 9:57, 2007.
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The role of the DNA double-strand-break (DSB) checkpoint/repair genes, ATM, BRCA1 and TP53, in sporadic breast cancer requires clarification, since ATM and BRCA1 mutations are rare in sporadic tumours. In an attempt to explain this phenomenon, we postulated that (i) in addition to genetic deletion, abnormal expression of DSB checkpoint/repair proteins might abolish the function of these genes and (ii) there might be a combined effect of individual defective genes during breast cancer pathogenesis. Using a largely homogenous group of 74 specimens of early-onset (< or =35 years of age) infiltrating ductal carcinomas, we examined associations between pathological grade and genetic deletion and/or abnormal protein expression of ATM, BRCA1 and TP53. The results showed that high-grade tumours displayed a high frequency of loss of heterozygosity (LOH) at, and/or abnormal expression of, ATM, BRCA1 and TP53. Multigenetic analysis showed abnormalities in BRCA1 to be independently associated with high-grade tumours. ATM and TP53 appeared to play an assistant role, abnormalities in these genes significantly increasing the possibility of poor differentiation in tumours with abnormalities in BRCA1. Furthermore, a higher number of abnormalities (LOH or abnormal expression) in these three genes correlated with poor tumour differentiation. Thus, this study suggests that combined changes in several DSB checkpoint/repair genes belonging to a common functional pathway are associated with breast cancer pathogenesis.
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Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patología , Transformación Celular Neoplásica , Daño del ADN , Reparación del ADN , Regulación Neoplásica de la Expresión Génica , Genes BRCA1 , Genes p53 , Estadificación de Neoplasias , Proteínas Serina-Treonina Quinasas/genética , Adulto , Edad de Inicio , Proteínas de la Ataxia Telangiectasia Mutada , Proteínas de Ciclo Celular , Diferenciación Celular , Análisis Mutacional de ADN , Proteínas de Unión al ADN , Femenino , Eliminación de Gen , Humanos , Inmunohistoquímica , Pérdida de Heterocigocidad , Reacción en Cadena de la Polimerasa , Proteínas Supresoras de TumorRESUMEN
There have been previous reports of somatostatin- and acetylcholinesterase (AChE)-positive patches in the superficial layers of the presubiculum in monkeys. In this study, we show additional instances of patches in the presubiculum, as demonstrated by cytochrome oxidase (CO), by myelin and Nissl stains, and by the calcium-binding proteins calbindin (CB), calretinin (CR), and parvalbumin (PV). Markers are differentially expressed along the lateral and longitudinal axes. Comparisons of adjacent sections reacted for different markers suggest that the CB+ and CR+ patches, and CO+ and AChE+ patches generally correspond, but not the CB+ and CO+ patches. In cross section, patches are about 100-300 microm in width. Sections cut tangentially through the superficial layers indicate that the pattern of CO and AChE labeling is in fact patchlike in layer I, but that the apparent patches in layer II (CB and CR) form a reticular or lattice-like network. As patches are restricted to the presubiculum, these labeling patterns provide a convenient marker for the boundary between the presubiculum and the adjoining posteroventral retrosplenial cortex. More work is necessary to determine how this modularity may relate to the functional organization of the presubiculum.
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Hipocampo/anatomía & histología , Hipocampo/química , Acetilcolinesterasa/análisis , Animales , Proteínas de Unión al Calcio/análisis , Corteza Cerebral/anatomía & histología , Corteza Cerebral/química , Complejo IV de Transporte de Electrones/análisis , Histocitoquímica , Macaca , Vaina de Mielina/químicaRESUMEN
The distribution and morphology of developing corpus callosum (CC) axons in rat visual cortex was studied by unilateral application of the in vivo anterograde tracer biotinylated dextran amine (BDA) to the visual or auditory cortex of newborns through adults. Changes in the distribution and morphology of CC axons during development were observed. Following BDA placement only in visual cortex, nearly all CC projections were to visual cortex (homotopic CC projections). At postnatal day (PND) 5-8, labeled CC axons were found throughout the contralateral visual cortex, including area 17; these CC axons could be followed from the white matter to layer I. By PND 13, few CC axons were found in medial area 17, indicating the existence of transitory CC axons in area 17 at younger ages. Morphological changes were investigated at the area 17/18a border and showed that CC axon collaterals were not formed until PND 8, and terminal arbors were not visible until PND 13; by PND 17, the adult CC-axon terminal pattern was present. At all ages, only a few heterotopic CC projections from visual to auditory cortex were found in the gray matter, although many labeled CC axons extended laterally into the white matter underlying the auditory cortex. Following BDA placement only in auditory cortex, CC projections to both auditory (homotopic CC projections) and visual (heterotopic CC projections) cortex were observed. At all ages, the homotopic CC projections were present throughout the auditory cortex, but were not distributed homogeneously; densely labeled CC axons showed a distinct columnar organization. The heterotopic CC projections were present in all visual cortical areas, including medial area 17, in significant numbers until PND 24, but were mostly eliminated by PND 28, at which time a labeling pattern similar to the adult was found. Thus, most of the heterotopic CC projections were transitory. The present study confirms the existence of transitory CC axons projecting through all layers of the visual cortex, as revealed by DiI, and extends the DiI results by showing that these transitory CC axons arise from both homotopic and heterotopic origins. Furthermore, different sources of transitory CC axons have different timetables for elimination.
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Axones/ultraestructura , Biotina/análogos & derivados , Cuerpo Calloso/citología , Cuerpo Calloso/crecimiento & desarrollo , Vías Nerviosas/citología , Vías Nerviosas/crecimiento & desarrollo , Corteza Visual/citología , Corteza Visual/crecimiento & desarrollo , Factores de Edad , Animales , Animales Recién Nacidos , Corteza Auditiva/citología , Corteza Auditiva/crecimiento & desarrollo , Dextranos , Colorantes Fluorescentes , Lateralidad Funcional/fisiología , Ratas , Ratas Sprague-DawleyRESUMEN
Corpus callosum (CC) projections in adult mammals were generally thought to be excitatory and to use excitatory amino acids as their transmitters. Little information has been available about the electrical properties and neurochemical status of developing CC connections. The present study investigated the chemical status of rat CC axons during postnatal development by using antibodies to neuropeptide Y (NPY) and to somatostatin (SOM). Both NPY-immunoreactive (ir) and SOM-ir axons were found in the CC of the rat from newborn through adult; however, the number of SOM-ir CC axons is less than that of NPY-ir CC axons at corresponding ages. The density of both NPY-ir and SOM-ir CC axons initially increased, then peaked, and finally decreased to the mature level. In the adult, only a few NPY-ir and SOM-ir CC axons were found in the CC. These results indicate that many NPY-ir and SOM-ir CC axons are transitory during early postnatal development. The results also suggest that the functions of CC connections in adult mammals may be different from that of developing ones. The present results as well as the previous results demonstrate that both developing and mature CC connections are chemically heterogeneous.
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Envejecimiento/metabolismo , Animales Recién Nacidos/metabolismo , Axones/metabolismo , Cuerpo Calloso/metabolismo , Neuropéptido Y/metabolismo , Somatostatina/metabolismo , Animales , Animales Recién Nacidos/crecimiento & desarrollo , Femenino , Inmunohistoquímica , Masculino , RatasRESUMEN
The entorhinal and perirhinal cortices have long been accorded a special role in the communications between neocortical areas and the hippocampal formation. Less attention has been paid to the presubiculum, which, however, is also a component of the parahippocampal gyrus, receives dense inputs from several cortical areas, and itself is a major source of connections to the entorhinal cortex (EC). In part of a closer investigation of corticohippocampal systems, the authors applied single-axon analysis to the connections from the inferior parietal lobule (IPL) to the presubiculum. One major result from this approach was the finding that many of these axons (at least 10 of 14) branch beyond the presubiculum. For 4 axons, branches were followed to area TF and to the border between the perirhinal and entorhinal cortices, raising the suggestion that these areas, which sometimes are viewed as serial stages, are tightly interconnected. In addition, the current data identify several features of presubicular organization that may be relevant to its functional role in visuospatial or memory processes: 1) Terminations from the IPL, as previously reported for prefrontal connections (Goldman-Rakic et al. [1984] Neuroscience 12:719-743), form two to four patches in the superficial layers. These align in stripes, but only for short distances ( approximately 1.5 mm). This pattern suggests a strong compartmentalization in layers I and II that is also indicated by cytochrome oxidase and other markers. 2) Connections tend to be bistratified, terminating in layers I-II and deeper in layer III. 3) Single axons terminate in layer I alone or in different combinations of layers. This may imply some heterogeneity of subtypes. 4) Individual axons, both ipsilateral projecting (n = 14 axons) and contralateral projecting (n = 6 axons), tend to have large arbors (0.3-0.8 mm across). Finally, the authors observe that projections from the IPL, except for its anteriormost portion, converge at the perirhinal-entorhinal border around the posterior tip of the rhinal sulcus. These projections partially overlap with projections from ventromedial areas TE and TF, and this convergence may contribute to the severe deficits in visual recognition memory resulting from ablations of rhinal cortex.
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Hipocampo/fisiología , Macaca mulatta/fisiología , Lóbulo Parietal/fisiología , Transmisión Sináptica/fisiología , Lóbulo Temporal/fisiología , Animales , Axones/fisiología , Axones/ultraestructura , Dendritas/fisiología , Dendritas/ultraestructura , Femenino , Masculino , Vías Olfatorias/fisiología , Terminales Presinápticos/ultraestructuraRESUMEN
Neurons of layer I play an important role in the development of the basic structural and functional organization of the mammalian cerebral cortex. Basic data, however, concerning the spatial and temporal distribution of the neuron populations in layer I are still limited, especially for human material. The present study investigates the distribution of Cajal-Retzius (CR) and non Cajal-Retzius (NCR) neurons in thirteen cortical areas in the newborn human in terms of their relative density and possible subtypes. Neuronal populations were identified by immunohistochemistry for parvalbumin. Three main results are reported. First, parvalbumin-immunoreactive (Parv-ir) CR cells were observed in all of the neocortical areas examined. These areas also had a Parv-ir horizontal fiber plexus in deep layer I, confirming to the horizontal plexus classically associated with CR neurons. Second, many Parv-ir CR cells showed clear signs of degeneration. Third, in addition to the large CR cells, smaller Parv-ir NCR neurons occurred in many of the neocortical areas examined. These were morphologically heterogeneous and may represent several subtypes. By sampling across several areas, we were able to establish that these NCR cells occurred at higher density in primary sensory areas 3, 1, 17, and 41. Because of this variability in density of Parv-ir NCR cells, the ratio of Parv-ir CR to Parv-ir NCR cells is selectively lower in primary sensory areas. Recent investigations in somatosensory cortex of early postnatal rat report complex spatiotemporal patterns of correlated spontaneous activity among neurons in layer I (Schwartz et al. 1998). An interesting possibility is that regional variability in this activity may play a major role in the organization of cortical circuitry in different areas.
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Corteza Cerebral/citología , Corteza Cerebral/metabolismo , Neuronas/citología , Neuronas/metabolismo , Parvalbúminas/metabolismo , Axones/metabolismo , Axones/ultraestructura , Recuento de Células , Tamaño de la Célula , Corteza Cerebral/crecimiento & desarrollo , Humanos , Inmunohistoquímica , Recién NacidoRESUMEN
Data from both animal and clinical studies suggest that anti-idiotype antibodies deposited in glomeruli may be involved in the pathogenesis of glomerulonephritis. This study was conducted to examine the role of a hybridoma-AB1-2-derived IgG anti-T15 idiotype (IgG anti-T15) in the immunopathogenesis of a short-term experimental IgA nephropathy. BALB/c mice (12/group) were administered intravenously with: (1) an equal mass (1 mg) of T15-hybridoma-derived IgA antiphosphorylcholine (PC) and PC-conjugated bovine serum albumin (BSA-PC) antigen; (2) 1 mg of IgA anti-PC, 1 mg of BSA-PC antigen, and 3 mg of IgG anti-T15, or (3) 1 mg of BSA-PC antigen alone. The mice were sacrificed 6 h after the injection. A 6-hour clearance study was performed. The initial phase of elimination of BSA-PC antigen in mice receiving IgA anti-PC/BSA-PC/IgG anti-T15 or those receiving the antigen alone was significantly faster than that in those receiving IgA anti-PC/BSA-PC (p < 0.001). There was no significant difference in the elimination rate of BSA-PC antigen between mice receiving IgA anti-PC/BSA-PC/IgG anti-T15 and those receiving BSA-PC antigen alone. The late phases of elimination of the BSA-PC antigen in mice receiving IgA anti-PC/BSA-PC/IgG anti-T15 showed somewhat similar to those of BSA-PC antigen in mice receiving IgA anti-PC/BSA-PC. Moreover, mice injected with IgA anti-PC/BSA-PC/IgG anti-T15 showed a significantly less glomerular BSA-PC antigen deposition than those injected with IgA anti-PC/BSA-PC (positive control), as demonstrated by light microscopy, autoradiography, and immunohistochemistry (each p < 0.001). It is inferred that the injected IgG anti-T15 could react with the IgA anti-PC in vivo, directly interfering with immune complex formation by the IgA anti-PC and BSA-PC antigen, thereby resulting in diminished glomerular deposition of the BSA-PC antigen. These findings suggest that an anti-idiotype antibody may be protective in the immunopathogenesis of IgA nephropathy, because of its inhibitory effect on glomerular trapping of an antigen.
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Anticuerpos Antiidiotipos/farmacología , Complejo Antígeno-Anticuerpo/metabolismo , Mesangio Glomerular/metabolismo , Inmunoglobulina A/metabolismo , Animales , Anticuerpos Antiidiotipos/inmunología , Antígenos/inmunología , Antígenos/metabolismo , Femenino , Mesangio Glomerular/efectos de los fármacos , Mesangio Glomerular/patología , Glomerulonefritis por IGA/etiología , Glomerulonefritis por IGA/inmunología , Glomerulonefritis por IGA/metabolismo , Riñón/efectos de los fármacos , Riñón/patología , Riñón/fisiología , Ratones , Ratones Endogámicos BALB C , Fosforilcolina/inmunología , Albúmina Sérica Bovina/inmunologíaAsunto(s)
Lesión Renal Aguda/inducido químicamente , Antibacterianos/efectos adversos , Eritromicina/efectos adversos , Nefritis Intersticial/inducido químicamente , Enfermedad Aguda , Antihipertensivos/uso terapéutico , Enalapril/uso terapéutico , Glomerulonefritis por IGA/complicaciones , Humanos , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Masculino , Persona de Mediana EdadRESUMEN
Polymeric (p) IgA constitutes 13% of total serum IgA, whereas monomeric (m) IgA represents the other 87%. pIgA tends to form complexes in the circulation that eventually localize in the glomerulus. mIgA is a nonprecipitable antibody. When complexed with an antigen in vivo, the circulating mIgA immune complex (IC) thus formed does not deposit in the glomerulus. The purpose of the present study was to evaluate the influence of mIgA on the formation of pIgA-lC and subsequent glomerular deposition of the IC in an experimental model of IgA nephropathy. The influence of mIgA anti-dinitrophenyl (DNP) on pIgA anti-DNP/DNP-conjugated BSA (BSA-DNP) IC formation was assessed by double diffusion test and competition PAGE in combination with autoradiography. Only the BSA-DNP, a model antigen of relatively low molecular mass, was radiolabeled and monitored throughout the latter experiment. An analysis of clearance kinetics (1 and 6 hours) of the antigen using 4-week-old female BALB/c mice, and a series of renal studies were performed after intravenous injection with a single dose of combined pIgA anti-DNP, BSA-DNP, and mIgA anti-DNP. As demonstrated by the double diffusion test, addition of mIgA anti-DNP resulted in suppression of the precipitating reaction of pIgA anti-DNP and BSA-DNP. This effect was confirmed by PAGE for size determination of the BSA-DNP which had been complexed with either pIgA anti-DNP or a mixture of pIgA anti-DNP and mIgA anti-DNP. The clearance kinetics studies showed that the elimination of BSA-DNP injected with pIgA anti-DNP was prolonged in the presence of mIgA anti-DNP in a partially dose-dependent manner. The experimental mice receiving pIgA anti-DNP, BSA-DNP, and mIgA anti-DNP showed less hematuria (p < 0.005) than mice receiving pIgA anti-DNP and BSA-DNP (positive control) when examined 1 hour after injection. Immunofluorescence study of the renal tissue of mice receiving pIgA anti-DNP, BSA-DNP, and mIgA anti-DNP showed a suppressed glomerular localization of IgA and third component of complement, as compared with those injected with pIgA anti-DNP and BSA-DNP alone. Similarly, a significant decrease of glomerular BSA-DNP deposits was observed in mice receiving pIgA anti-DNP, BSA-DNP, and mIgA anti-DNP compared with those receiving pIgA anti-DNP and BSA-DNP alone, as demonstrated by light microscopic autoradiography. These findings indicate that a high dose of specific mIgA was capable of modulating glomerular deposition of the pIgA-IC in this animal model of IgAN.
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Complejo Antígeno-Anticuerpo/metabolismo , Glomerulonefritis por IGA/prevención & control , Inmunoglobulina A/metabolismo , Inmunoglobulina A/uso terapéutico , Glomérulos Renales/inmunología , Animales , Femenino , Glomerulonefritis por IGA/inmunología , Glomerulonefritis por IGA/patología , Glomérulos Renales/patología , Ratones , Ratones Endogámicos BALB CRESUMEN
Biotinylated dextran amine (BDA) has proven to be an excellent anterograde tracer in adult mammalian brains, having some advantages over other anterograde tracers such as Phaseolus vulgaris-leucoagglutinin (PHA-L) and biocytin. However, results are inferior when BDA is used in neonatal mammals. To improve the sensitivity and quality of BDA labeling in neonatal mammalian brains, the tetramethylbenzidine-sodium tungstate (TMB-ST) method for horseradish peroxidase (HRP) histochemistry was modified and used in BDA histochemistry. After BDA application to the visual cortex of neonatal rat and cat, contralateral and ipsilateral cortical and subcortical regions were examined for BDA-labeled exons and terminals. The modified BDA histochemistry produced corpus callosum (CC) axons in neonatal rat and cat that were heavily and continuously labeled. The distribution, trajectories, branching and termination of individual CC axons, and even possible axon-axon contracts, were clearly identified in exquisite detail, even at low magnification. The quality of BDA labeling in the ipsilateral lateral geniculate nucleus and superior colliculus was similar to that of the CC axonal labeling. These results indicate that the modified BDA histochemistry provides a very sensitive and reliable approach to revealing the detailed distribution and morphology of projecting axons and terminals in the developing mammalian nervous system.
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Encéfalo/crecimiento & desarrollo , Animales , Animales Recién Nacidos , Axones/ultraestructura , Bencidinas , Biotina/análogos & derivados , Encéfalo/anatomía & histología , Química Encefálica/fisiología , Gatos , Corteza Cerebral/citología , Corteza Cerebral/crecimiento & desarrollo , Corteza Cerebral/metabolismo , Compuestos Cromogénicos , Dextranos , Colorantes Fluorescentes , Histocitoquímica , Peroxidasa de Rábano Silvestre , Terminaciones Nerviosas/ultraestructura , Ratas , Compuestos de TungstenoRESUMEN
To establish models of proteinuria in the mouse, BALB/c mice were injected with puromycin aminonucleoside (PAN, 1.5 or 4.5 mg/10 g body weight), adriamycin (AD, 0.2 mg/10 g body weight) intravenously or bovine serum albumin (BSA, 100 mg/10 g body weight) intraperitoneally. Proteinuria was measured as the ratio of urinary albumin (micrograms/ml) to creatinine (mg/dl) and further characterized by isotyping the immunoglobulin. Although not obtained with PAN (followed for 4 weeks), proteinuria was readily attained in the mouse after treatment with AD or BSA. Most AD-treated mice (5/7) developed an abrupt increase of proteinuria at day 2 after injection, with the ratio of urinary albumin to creatinine in the range 0.28-0.45. The degree of proteinuria increased with time and all mice tested (7/7) showed overt proteinuria at day 4. These mice became anuric at day 5 and died at days 6 and 7. For BSA, 4 h after administration, four of seven mice showed enhanced proteinuria, lasting 8 h with urinary albumin and creatinine in a ratio < 0.05. Isotyping of urine samples collected at the time of heavy proteinuria (ratio of urinary albumin to creatinine: > 0.40 for AD-treated mice, > 0.15 for BSA-treated mice) showed that all of the mice (7/7) with AD-induced proteinuria (ADp) and three of four mice with BSA-induced proteinuria (BSAp) revealed urinary IgG2b and IgA, while only one of seven control mice showed IgG2b alone in urine. The mice were sacrificed at the time they presented with heavy proteinura for pathologic and anionic studies on renal tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
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Doxorrubicina/toxicidad , Proteinuria/inducido químicamente , Albúmina Sérica Bovina/toxicidad , Animales , Creatinina/sangre , Modelos Animales de Enfermedad , Femenino , Mesangio Glomerular/efectos de los fármacos , Mesangio Glomerular/patología , Mesangio Glomerular/ultraestructura , Inyecciones Intravenosas , Riñón/citología , Riñón/efectos de los fármacos , Riñón/fisiopatología , Ratones , Ratones Endogámicos BALB C , Microscopía , Proteinuria/patología , Puromicina Aminonucleósido/toxicidadRESUMEN
Corpus callosum (CC) axons in visual cortex were labeled anterogradely by in vivo biotinylated dextran amine (BDA) in neonatal cat at postnatal day (PND) 6, 10 and 15. Labeled CC axons were distributed throughout the visual cortex including medial area 17. The number of CC axons in medial area 17 increased from PND 6 to PND 10, and then decreased from PND 10 to PND 15. At PND 15, few CC axons could be followed into the grey matter in medial area 17. Thus, BDA labels transitory CC axons that extend through all cortical layers in medial area 17, confirming the results revealed by in vitro DiI labeling.
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Axones , Biotina/análogos & derivados , Cuerpo Calloso/ultraestructura , Dextranos , Corteza Visual/ultraestructura , Animales , Animales Recién Nacidos , Animales Lactantes , Transporte Axonal , Carbocianinas , Gatos , Cuerpo Calloso/crecimiento & desarrollo , Corteza Visual/crecimiento & desarrolloRESUMEN
Many immunocytochemical studies have identified different types of neurotransmitters localized in the corpus callosum (CC) axons in the adult mammal. Few studies have looked at the development of different neurochemically identified CC systems. Previous studies on the development of cat CC axons have indicated that a large number of transitory CC axons project to the cortex during early postnatal development. The present study focuses on the development of one neurochemically identified group of CC axons in the cat, labeled with an antibody against neuropeptide Y (NPY), to determine if this group participates in transitory CC axonal growth. Cats at specified ages from birth to adulthood were studied with a routine method of immunocytochemistry for antiserum to NPY. NPY-immunoreactive (ir) CC axons were detected at all stages examined, from newborn to adult; the peak density occurred during postnatal weeks (PNW) 3-4. During PNW 1-2, the density of NPY-ir CC axons increased gradually; some NPY-ir axons at this age had growth cones located within the CC bundle between the cerebral hemispheres. The density of the NPY-ir CC axons decreased gradually during PNW 5-7, and from PNW 8 to maturity only a few NPY-ir CC axons were observed. These results indicate that at least two types of NPY-ir CC axons (i.e., transitory and permanent) exist during development, and that most of these axons are eliminated or only express NPY-ir for a short period during development. The results also indicate that neurochemical subsets of CC axons participate in the extensive transitory growth observed by means of the membrane tracer DiI but they may follow unique developmental timetables.
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Axones/química , Cuerpo Calloso/química , Crecimiento/fisiología , Neuropéptido Y/análisis , Animales , Axones/ultraestructura , Gatos , Cuerpo Calloso/anatomía & histología , Inmunohistoquímica , Neuropéptido Y/inmunologíaRESUMEN
BACKGROUND: Pedestrian-vehicle collision is a serious public health problem today in Taiwan, but this issue of pedestrian safety has received relatively little attention. The purpose of this study was to evaluate the characteristics of pedestrian injury after involvement in a collision. METHODS: An epidemiologic study on 845 traffic accident consecutive victims, managed at Tri-Service General Hospital in 1990, was performed. They were interviewed with a brief questionnaire about demographic data and types of accident including injured site, Injury Severity Score (ISS) and outcome; the latter was obtained by review of medical records and by a telephone survey performed four months after discharge. RESULTS: Results showed a common distribution of injuries for all age groups. Of the 845 patients, 487 were male and 358 were female (sex ratio = 1.4:1). The majority of injuries (84.8%) occurred for pedestrians who were walking on the side of, or crossing, the road. Four hundred and ninety-six victims (58.7%) were treated in the Emergency Department only, while 342 patients (40.5%) were further admitted as inpatients; the remaining 34 patients (4.0%) died in the Emergency Department (0.8%), or as inpatients (3.2%). The study showed fatality rates according to age as follows: 0.5% age 1 to 19, 1.8% age 20 to 39, 4.6% age 40 to 59, 7.5% age 60 or older, with the elderly having the highest pedestrian death rate. Elder pedestrians who were struck by motor vehicles also had the highest fatality rate of all pedestrian injury victims. The percentage of pedestrian injuries is fairly constant from month to month. For time of day, 12 noon and 3 to 5 pm were associated with the most injuries for age 0-19 youths; 4 pm and 10 pm for age 20-59 adults; 8 am and 7 pm for age 60 or older. There was a significant difference of mean ISS between the nonsurvivors (27.8) and the survivors (4.6) (p < 0.01). When nonsurvivors were compared with survivors, among the aged (> 60), high Abbreviated Injury Scale (AIS) of head, and high ISS were most common among nonsurvivors (p < 0.01). CONCLUSIONS: That pedestrians are the least protected participants in traffic. Situations is reflected by a considerable fatality rate among pedestrians. Data from this study should be useful for designing, implementing, and evaluating a targeted pedestrian safety program in Taiwan.
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Accidentes de Tránsito/estadística & datos numéricos , Adolescente , Adulto , Factores de Edad , Anciano , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Factores Sexuales , Taiwán/epidemiologíaRESUMEN
BACKGROUND: IgA nephropathy is induced by the IgA-immune complex (IC). IgA nephropathy associated with heavy proteinuria is considered a more progressive form of the disease. To elucidate the mechanism by which the latter condition occurs, we investigated the effect of proteinuria on the glomerular deposition of IgA-IC. EXPERIMENTAL DESIGN: BALB/c female mice that had been made proteinuric by adriamycin or bovine serum albumin (BSA) were injected with TEPC-15 hybridoma-derived IgA anti-phosphorylcholine (PC) and individual specific antigens. The 6-hour clearance kinetics of IgA were measured, and the accumulation of IgA deposits and the third complement component (C3) in the glomerulus were analyzed. RESULTS: The clearance kinetics of 125I-IgA injected together with a specific antigen, PC-conjugated BSA (BSA-PC), showed only a minimal distinction between the experimental (proteinuric) and the control (nonproteinuric) groups of mice. However, analysis of renal tissue by immunofluorescence and light microscopic autoradiography revealed markedly enhanced mesangial IgA-IC deposition in the proteinuric mice receiving IgA and one of three specific antigens, BSA-PC, PC-conjugated cytochrome-c, and a pneumococcal C-polysaccharide. Immunofluorescence also showed augmented mesangial C3 deposition in proteinuric mice that received IgA/PC-conjugated cytochrome-c or IgA/pneumococcal C-polysaccharide. In addition, adriamycin or BSA per se did not influence glomerular IgA-IC localization. CONCLUSIONS: Glomerular localization of nephritogenic IgA-IC was comparably enhanced in mice with proteinuria induced by various methods. Thus, a vicious cycle for the progression of IgA nephropathy might ensue in proteinuric states.