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BACKGROUND: Of the Rh blood type, Del is a rare variant that elicits the weakest anti-D reactivity. In this study, we revisit the genetic changes of Del allele and characterise the RHD splicing transcripts to realise the molecular basis of Del formation in the Taiwanese population. STUDY DESIGN AND METHODS: The RHD exons from Del and D-positive individuals were amplified by polymerase chain reaction (PCR) using different primer pairs followed by sequencing analyses. In addition, full-length RHD transcripts were reversed transcribed and amplified by nested-PCR. The type and frequency of the RHD splicing transcripts were analysed after sequencing the PCR products that were subcloned into a cloning vector. RESULTS: All Del individuals had a characteristic 1227G>A mutation. No deletion of the exon sequences was found. At least nine types of RHD splicing transcripts including exons 7/8/9 deletion, 7/9 deletion, 8/9 deletion, 9 deletion, 2/3/7/9 deletion, 2/3/7/8/9 deletion, exons 7/8/9 deletion with replacement of exon 3 with RHCE exon 3, exon 9 deletion with cryptic insertion of 170 bp of intron 7 and exons 7/8/9 deletion with cryptic insertion of 117 bp of intron 3 were identified in the Del -RBC. These aberrant splicing transcripts led to production of frame shift or truncated D antigen. Notably, no full-length RHD transcript was identified in the Del -RBC. CONCLUSION: The RHD 1227G>A mutation contributes to the molecular basis of Del phenotype in the Taiwanese population. The point mutation results in aberrant frame shift or exon deletion transcripts and generates D protein with weak antigen presenting function.
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Éxons , Mutação INDEL , Mutação Puntual , Splicing de RNA , Sistema do Grupo Sanguíneo Rh-Hr/genética , Feminino , Humanos , Masculino , Sistema do Grupo Sanguíneo Rh-Hr/imunologia , TaiwanRESUMO
BACKGROUND AND OBJECTIVES: Ael is a rare blood type that is characterized by weak agglutination of RBCs when reacts with anti-A antibody in adsorption-elution test. Although IVS6 + 5GâA mutation is known to associate with the Ael blood type, genetic and mechanistic evaluation for the weak agglutination of Ael with IVS6 + 5GâA mutation has not yet been completely addressed. MATERIALS AND METHODS: In this study, five cases of confirmed Ael individuals were analysed. The cDNAs for the A(el) alleles were obtained by cloning method for sequence analyses. The erythroleukemia K562 cells were used as the cell study model and were transfected with the A(el) expression construct. Flow cytometry analysis was then performed to determine the levels of surface antigen expression. RESULTS: The results indicated that IVS6 + 5GâA attributes to all cases of Ael . RT-PCR analyses revealed the presence of at least 10 types of aberrant A(el) splicing transcripts. Most of the transcripts caused early termination and produced non-functional protein during translation. Nevertheless, the transcript without exons 5-6 was predicted to generate functional Ael glycosyltransferase lacking 57 amino acids at the N-terminal segment. When the exons 5-6 deletion transcript was stably expressed in the K562 cells, weak agglutination of the cells can be induced by adding anti-A antibody followed by adsorption-elution test. CONCLUSION: This study demonstrates that aberrant splicing of A transcripts contributes to weak A expression and the weak agglutination of Ael -RBCs, adding to the complexity for the regulatory mechanisms of ABO gene expression.
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Sistema ABO de Grupos Sanguíneos/genética , Mutação , Fenótipo , Alelos , Tipagem e Reações Cruzadas Sanguíneas , Linhagem Celular Tumoral , Éxons , HumanosRESUMO
HLA-A*31:01 was reported to be associated with carbamazepine (CBZ)-induced severe cutaneous adverse reactions (SCAR), including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We conducted an international study using consensus diagnosis criteria to enroll a total of 93 patients with CBZ-SCAR from Europe or Asia. We found that HLA-A*31:01 showed a significant association with CBZ-DRESS in Europeans (P<0.001; odds ratio (OR) (95% confidence interval (CI))=57.6 (11.0-340)), and the strong association was also found in Chinese (P<0.001; OR (95% CI)=23.0 (4.2-125)). However, HLA-A*31:01 had no association with CBZ-SJS/TEN in neither Chinese nor Europeans. By comparison, HLA-B*15:02 showed a strong association with CBZ-SJS/TEN in Chinese (P<0.001, OR (95% CI)=58.1 (17.6-192)). A meta-analysis of this and other published studies confirmed that in all populations, HLA-A*31:01 had an extremely strong association with CBZ-DRESS (P<0.001, a pooled OR (95% CI)=13.2 (8.4-20.8)), but a much weaker association with CBZ-SJS/TEN (P=0.01, OR (95% CI)=3.94 (1.4-11.5)). Our data revealed that HLA-A*31:01 is a specific predictor for CBZ-DRESS but not for CBZ-SJS/TEN. More studies are needed to investigate the genetic determinant of CBZ-SJS/TEN in Europeans. Considering the potential clinical utility, the cost-effectiveness of the combined HLA-A*31:01 and HLA-B*15:02 genetic test to prevent CBZ-SCAR in Chinese needs further investigation.
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Carbamazepina/uso terapêutico , Antígenos HLA-A/genética , Pele/efeitos dos fármacos , Carbamazepina/efeitos adversos , Estudos de Coortes , HumanosRESUMO
Objective: To comparatively evaluate the accuracy and the scan time of three full-arch scan strategies on the head-simulator, to explore a full-arch scan strategy with better clinical operability and high accuracy. Methods: A cross-controlled study design was used. A model with melamine-formaldehyde resin teeth and silica gel gingiva of an upper dental arch which can be fixed on a head simulator was scanned with an optical scanner (ATOS Core) in order to obtain the standard tessellation language (STL) dataset as reference. Intraoral scans were performed on the model fixed on the head simulator with four intraoral scanners (IOS) [A (TRIOS 3), B (CS 3600), C (CEREC Omnicam), D (iTero)]. The STL datasets were obtained from each of the four different IOS systems by using three scan strategies (scan strategies 1, 2 and 3 were composed of 10, 5 and 7 paths respectively) all by one attending doctor with 3 years of intraoral scanning experience. For each scanner and each scan strategy, nine scans were acquired. And the scan time was recorded for each scan. Following the scan strategy, the scan path was completed to obtain a full-arch digital model, and the scan time was recorded as full-arch scan time. Complementary scans were performed to fill the missing image, and this scan time was recorded as complementary scan time. The total scan time was obtained by adding full-arch scan time and complementary scan time. Through the Geomagic Wrap software, the three-dimensional (3D) models were overlaid by best fit alignment function and compared to obtain the root mean square values of the discrepancies by 3D compare function. The intraoral scanning datasets were compared with the reference for trueness. The nine intraoral scanning datasets were cross compared with same scan strategy and same intraoral scanner for precision. Results: There were no significant differences among the three scan strategies for trueness (P>0.05), while the differences among the three scan strategies for precision were affected by difference IOSs (P<0.05), and only scan strategy 3 showed the highest precision with all the four IOS. The full-arch scan time of scan strategies 1, 2 and 3 were (130±24), (72±17) and (90±19) s respectively (P<0.05). For complementary scan time, scan strategy 2 [(50±24) s] took longer time than scan strategy 1 [(26±18) s] and scan strategy [(25±21) s] (P<0.05), while no significant differences between the latter two (P>0.05). For total scan time, scan strategy 1 [(156±31) s] took longer time than scan strategy 2 [(122±30) s ] and scan strategy 3 [(115±29) s ] (P<0.05), while no significant differences between the latter two (P>0.05). Conclusions: Full-arch scanning on the head-simulator with scan strategy 3 which can obtain scanning datasets with high accuracy, was more convenient to operate and took shorter scan time, and is generally suitable for intraoral scanners commonly used in clinic.
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Técnica de Moldagem Odontológica , Modelos Dentários , Desenho Assistido por Computador , Arco Dental , Imageamento TridimensionalRESUMO
INTRODUCTION: B lymphocyte chemoattractant (BLC/CXCL13), a CXC chemokine, is involved in B1 and B2 cell trafficking for the activation of autoreactive T helper (Th) cells and autoantibody production in target organs during the development of lupus. CXCL13 can induce the trafficking of CXCR5+ T lymphocyte subset designated as follicular helper T lymphocytes (T(FH)) which are specifically involved in autoantibody production. MATERIALS AND METHODS: We herein measured the plasma concentrations of CXCL13, B-cell-activating factor of the TNF family (BAFF), and T(FH)-cells-related cytokine IL-21 and cell surface expression of T(FH)-related receptor CXCR5 and IL-21R on CD4+Th and CD19+B cells in 35 systemic lupus erythematosus (SLE) patients and 23 sex- and age-matched control subjects (NC) using enzyme-linked immunosorbent assay and flow cytometry, respectively. RESULTS AND DISCUSSION: Plasma CXCL13, BAFF, and IL-21 concentrations were significantly higher in SLE patients than NC group (all p < 0.0001). Increase in CXCL13 concentration correlated positively and significantly with SLEDAI score in SLE patients (r = 0.399, p = 0.032). Cell surface expression of CXCR5 on Th and B cells and IL-21R on B cells was however significantly lower in SLE patients than controls (both p < 0.01). It may indicate that most differentiated T(FH) cells migrate out from circulation into lymphoid organ upon activation during the disease development of SLE. CONCLUSIONS: The above results suggest that the elevated production of CXCL13, BAFF, and IL-21 may be associated with the function of T(FH) for the immunopathogenesis in SLE, and CXCL13 may serve as a potential disease marker of SLE.
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Linfócitos B/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Quimiocina CXCL13/biossíntese , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Adulto , Antígenos CD/biossíntese , Fator Ativador de Células B/biossíntese , Fator Ativador de Células B/sangue , Fator Ativador de Células B/genética , Linfócitos B/imunologia , Linfócitos B/patologia , Biomarcadores/sangue , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Movimento Celular/imunologia , Células Cultivadas , Quimiocina CXCL13/sangue , Quimiocina CXCL13/genética , Progressão da Doença , Feminino , Humanos , Interleucinas/biossíntese , Interleucinas/sangue , Interleucinas/genética , Lúpus Eritematoso Sistêmico/sangue , Masculino , Pessoa de Meia-Idade , Receptores CXCR5/genética , Receptores CXCR5/metabolismo , Receptores de Interleucina-21/genética , Receptores de Interleucina-21/metabolismoRESUMO
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease associated with aberrant activation of T and B lymphocytes for the production of inflammatory cytokines and autoreactive antibodies. Animal studies of SLE have indicated that Toll-like receptors (TLR) are important in the pathogenesis of murine lupus. In the present clinical study, differential protein expressions of TLR-1-9 of monocytes and different lymphocyte subsets from patients with SLE and normal control subjects were determined by flow cytometry. Results showed that the expression of intracellular TLRs (TLR-3, -8, -9) and extracellular TLRs (TLR-1, -2, -4, -5, -6) were elevated in monocytes, CD4(+) T lymphocytes, CD8(+) T lymphocytes and B lymphocytes of SLE patients compared to control subjects (all P < 0.001). Moreover, cell surface expression of TLR-4 on CD4(+) T lymphocytes and CD8(+) T lymphocytes, and TLR-6 on B lymphocytes, were correlated positively with SLE disease activity index (SLEDAI) (TLR-4 on CD4(+) T lymphocytes and CD8(+) T lymphocytes: r = 0.536, P = 0.04; r = 0.713, P = 0.003; TLR-6 in B lymphocytes: r = 0.572, P = 0.026). In concordance with the above results, there is an observable increased relative induction (%) of inflammatory cytokine interleukin (IL)-1beta, IL-6, IL-10 and IL-12, chemokines CCL2, CXCL8, CCL5 and CXCL10 from peripheral blood mononuclear cells (PBMC) upon differential stimulation by PolyIC (TLR-3 ligand), lipopolysaccharide (TLR-4 ligand), peptidoglycan (TLR-2 ligand), flagellin (TLR-5 ligand), R837 (TLR-7 ligand) and CpG DNA (TLR-9 ligand) in SLE patients compared to controls. These results suggest that the innate immune response for extracellular pathogens and self-originated DNA plays immunopathological roles via TLR activation in SLE.
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Leucócitos Mononucleares/metabolismo , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Receptores Toll-Like/metabolismo , Adulto , Aminoquinolinas/farmacologia , Linfócitos B/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Quimiocinas/metabolismo , Fosfatos de Dinucleosídeos/farmacologia , Feminino , Flagelina/farmacologia , Humanos , Imiquimode , Imunidade Inata/imunologia , Indutores de Interferon/farmacologia , Interleucinas/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Lipopolissacarídeos/farmacologia , Lúpus Eritematoso Sistêmico/diagnóstico , Pessoa de Meia-Idade , Monócitos/metabolismo , Peptidoglicano/farmacologia , Poli I-C/farmacologia , RNA/farmacologia , Índice de Gravidade de Doença , Receptores Toll-Like/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Adulto JovemRESUMO
The fundamental building block of the copper oxide superconductors is a Cu4O4 square plaquette. The plaquettes in most of these materials are slightly distorted to form a rectangular lattice, for which an influential theory predicts that high-transition-temperature (high-T(c)) superconductivity is nucleated in 'stripes' aligned along one of the axes. This theory received strong support from experiments that indicated a one-dimensional character for the magnetic excitations in the high-T(c) material YBa2Cu3O6.6 (ref. 4). Here we report neutron scattering data on 'untwinned' YBa2Cu3O6+x crystals, in which the orientation of the rectangular lattice is maintained throughout the entire volume. Contrary to the earlier claim, we demonstrate that the geometry of the magnetic fluctuations is two-dimensional. Rigid stripe arrays therefore appear to be ruled out over a wide range of doping levels in YBa2Cu3O6+x, but the data may be consistent with liquid-crystalline stripe order. The debate about stripes has therefore been reopened.
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Objective: To observe the status of the sinus membrane using fiber optic endoscope during the lateral window approach sinus floor elevation to provide a reference for clinicians when evelvating the sinus mucoperiosteum. Methods: Sixty-six patients (72 sides) who underwent maxillary sinus floor elevation in Beijing Ruicheng Stomatology Hospital from September 2016 to December 2019 were selected, including 40 males and 26 females, aged 26-80 years old [(56.2±11.5) years]. And fiber optic endoscopy was used to observe the maxillary mucoperiosteum during the operation. Results: The status of maxillary sinus mucoperiosteal during lateral window approach sinus floor elevation can be divided into four categories: â Class â , complete periosteal, no damage to mucoperiosteum; â¡Class â ¡, periosteal injury, unexposed laminae propria; â¢Class â ¢, periosteal Rupture, exposed lamina propria; ⣠Class â £, mucoperiosteum perforation, rupture of periosteum, lamina propria and epithelial layer. A total of 72 operations were performed, including 18 cases of class I, 28 cases of class â ¡, 4 cases of class â ¢, and 22 cases of class â £. Conclusions: The status of maxillary sinus mucoperiosteal during lateral window approach sinus floor elevation can be divided into four categories. Fiberoptic endoscopy as a clinical auxiliary examination method can improve the operator's control of the status of the maxillary sinus membrane and assist the peeling of the mucosa.
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Seio Maxilar , Levantamento do Assoalho do Seio Maxilar , Adulto , Idoso , Idoso de 80 Anos ou mais , Endoscópios , Feminino , Humanos , Masculino , Maxila , Seio Maxilar/cirurgia , Pessoa de Meia-Idade , Mucosa NasalRESUMO
INTRODUCTION: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease associated with aberrant activation of T and B lymphocytes. Abnormal activation of intracellular signaling molecules in lymphocytes by inflammatory cytokines can instigate the inflammation in SLE. MATERIALS AND METHODS: The activation of extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) in inflammatory cytokine IL-18-activated monocytes, CD4+ T helper (Th) lymphocytes, CD8+ T lymphocytes, and CD19+ B lymphocytes in 22 SLE patients and 20 sex- and age-matched control subjects were measured by flow cytometry. RESULTS AND DISCUSSION: The basal expressions of phospho-p38 MAPK in CD4+ T lymphocytes, CD8+ T lymphocytes, and B lymphocytes were significantly higher in SLE patients than controls (all p<0.05). The expression of phospho-p38 MAPK in CD4+ T lymphocytes, CD8+ T lymphocytes and B lymphocytes, and phospho-JNK in CD8+ T lymphocytes and B lymphocytes was also significantly elevated in SLE patients upon the activation by IL-18, exhibiting significant correlation with the plasma concentrations of Th1 chemokine CXCL10 (all p<0.05). The expression of phospho-JNK in IL-18 activated CD8+ T lymphocytes and the relative % fold increase of the expression of phospho-JNK upon IL-18 activation in B lymphocytes were significantly correlated with SLE disease activity index (both p<0.05). CONCLUSION: The inflammation-mediated activation of JNK and p38 MAPK signaling pathways in T and B lymphocytes can be the underlying intracellular mechanisms causing lymphocyte hyperactivity in SLE.
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Lúpus Eritematoso Sistêmico/imunologia , Linfócitos/imunologia , Proteínas Quinases Ativadas por Mitógeno/imunologia , Adulto , Idoso , Linfócitos B , Linfócitos T CD8-Positivos , Estudos de Casos e Controles , Feminino , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Pessoa de Meia-Idade , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Monócitos , Linfócitos T Auxiliares-Indutores , Adulto Jovem , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
CD26, a T cell co-stimulatory molecule and dipeptidyl peptidase IV for the degradation of interferon-gamma-induced chemokine, participates in multiple immunopathological roles in leukocyte homing and inflammation. Decreased circulating concentration of soluble (s)CD26 in patients with systemic lupus erythematosus (SLE), rheumatoid arthritis and murine model of arthritis and encephalomyelitis have been reported. In the present study, the plasma concentration of sCD26 and chemokines, and cell surface expression of CD26 on monocytes, CD4+T lymphocytes, CD8+T lymphocytes, CD19+B lymphocytes and invariant natural killer T (iNKT) lymphocytes were analyzed using ELISA and flow cytometry, respectively, in 23 SLE patients and 14 sex- and age-matched control subjects. Although there was no significant difference between plasma concentrations of soluble CD26 in SLE patients with controls (p > 0.05), there was significant elevated Th1 chemokines CXCL10 and CXCL9 but not Th2 chemokine CCL2, and down-regulation in iNKT lymphocytes number and cell surface expression of CD26 on CD4+T and iNKT lymphocytes of SLE patients compared with controls (all p < 0.05). Decreased circulating number of iNKT cells and CD26 on iNKT cells can be important for the immunopathogenesis by exacerbating Th1-related inflammation in SLE.
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Dipeptidil Peptidase 4/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Células T Matadoras Naturais/imunologia , Células Th1/imunologia , Adulto , Quimiocina CCL2/biossíntese , Quimiocina CXCL10/biossíntese , Quimiocina CXCL9/biossíntese , Dipeptidil Peptidase 4/biossíntese , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Lúpus Eritematoso Sistêmico/metabolismo , Células T Matadoras Naturais/metabolismo , Células Th1/metabolismoRESUMO
Objective:To investigate the effect of vestibular rehabilitation exercise combined with manual reduction in the treatment of benign paroxysmal positional vertigoï¼BPPVï¼. Method:A total of 186 patients with benign paroxysmal positional vertigo were selected and randomly divided into experimental group and control group . The control group was treated with manual reduction, while the experimental group was treated with manual reduction combined with vestibular rehabilitation exercises. Patients with posterior semicircular canal BPPV carried out Brandt-Daroff exercises, while patients with horizontal semicircular canal BPPV carried out Cawthorne-Cooksey exercises and position restriction. To analyze the clinical curative effect, DHI score, residual dizziness and recurrence of the two groups. Result:There was no significant difference in total efficiency rate and DHI score between the two groups at the first diagnosisï¼P>0.05ï¼. After 1 week, 2 weeks and 1 month of follow-up, the total efficiency rate of the experimental group were 90.3%, 91.4% and 93.5% respectively, which were significantly higher than those of the control groupï¼P<0.05ï¼. Synchronously, the scores of DHI in experimental group were respectively 14.33±5.71, 12.25±4.98 and 9.45±3.70, which were significantly lower than the control groupï¼P<0.05ï¼. For the experimental group, in the first diagnosis, 1 week, 2 weeks and 1 month after follow-up, residual dizziness patients were 29 cases, 13 cases, 8 cases and 0 cases. The mean duration of residual dizziness was ï¼5.86±4.71ï¼ days, which was significantly lower than that in the control groupï¼P<0.05ï¼. One month after follow-up, the recurrence of patients in the experimental group were 5 cases, while the control group were 11 cases, significant difference between the two groupsï¼χ²=4.704, P=0.030ï¼. Conclusion:Manual reduction combined with vestibular rehabilitation exercise can significantly improve the therapeutic effect of BPPV, ameliorate the residual dizziness symptoms and reduce the recurrence rate, meanwhile improve the balance function and quality life of patients.
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Vertigem Posicional Paroxística Benigna , Tontura , Terapia por Exercício , Humanos , Recidiva , Canais SemicircularesRESUMO
OBJECTIVE: L-3-n-butylphthalide (L-NBP) is a type of anti-ischemic cranial nerve protective drug that may act on vascular dementia (VD). Phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT/PKB) signaling pathway can up-regulate B-cell lymphoma 2 (Bcl-2) expression, reduce reactive oxygen species (ROS) production, and alleviate cell apoptosis. This study aimed at investigating the role of L-NBP on neurological function and cell apoptosis in VD mouse through regulating PI3K/AKT signaling pathway. MATERIALS AND METHODS: The mice were divided into four groups, including Sham, VD, VD + solvent, and VD + L-NBP. HT22 cells were cultured in vitro and treated by ischemia/reperfusion (I/R). HT22 cells were divided into four groups, including I/R, VD + solvent, VD + L-NBP, and VD + L-NBP + LY294002 groups. Phosphorylated AKT (p-AKT) and Bcl-2 expressions were tested. ROS content in hippocampus tissue was detected by flow cytometry. Cell apoptosis was evaluated by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay. RESULTS: ROS content and cell apoptosis increased, while p-AKT and Bcl-2 expressions reduced in hippocampus tissue from VD group compared with sham group. L-NBP significantly up-regulated p-AKT and Bcl-2 expressions and decreased ROS content and cell apoptosis in hippocampus tissue. I/R treatment markedly induced HT22 cell apoptosis and ROS production, and reduced p-AKT and Bcl-2 expressions. L-NBP treatment markedly up-regulated p-AKT and Bcl-2 levels, restrained cell apoptosis, and reduced ROS content in TH22 cells intervened by I/R. LY294002 apparently attenuated the protective effect of L-NBP on HT22 cells. CONCLUSIONS: L-NBP protects VD by up-regulating PI3K/AKT signaling pathway, elevating Bcl-2 expression, reducing nerve cell apoptosis, and restraining ROS production.
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Apoptose/efeitos dos fármacos , Benzofuranos/farmacologia , Demência Vascular/tratamento farmacológico , Animais , Demência Vascular/metabolismo , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinase/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
A magnetic skyrmion lattice is a microstructure consisting of hexagonally aligned skyrmions. While a skyrmion as a topologically protected carrier of information promises a number of applications, an easily accessible probe of the skyrmion and skyrmion lattice at mesoscopic scale is of significance. It is known that neutron scattering, Lorentz transmission electron microscopy, and spin-resolved STM as effective probes of skyrmions have been established. In this work, we propose that the spatial contour of dielectric permittivity in a skyrmion lattice with ferromagnetic interaction and in-plane (xy) Dzyaloshinskii-Moriya (DM) interaction can be used to characterize the skyrmion lattice. The phase field and Monte Carlo simulations are employed to develop the one-to-one correspondence between the magnetic skyrmion lattice and dielectric dipole lattice, both exhibiting the hexagonal symmetry. Under excitation of in-plane electric field in the microwave range, the dielectric permittivity shows the dumbbell-like pattern with the axis perpendicular to the electric field, while it is circle-like for the electric field along the z-axis. The dependences of the spatial contour of dielectric permittivity on external magnetic field along the z-axis and dielectric frequency dispersion are discussed.
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Alpha-thalassemia has been estimated to account for over 60% of hydrops fetalis cases in Taiwan. The most common genotypic lesion found in alpha-thalassemia-1 cases in Taiwan is deletion of a large segment of the alpha-globin gene cluster, termed the Southeast Asian-type deletion (-SEA/; further referred to as SEA-type deletion). Seven chorionic villus samples (CVS) from pregnancies of couples both heterozygous for SEA-type deletion were studied. Non-radioactive Southern-blot hybridization using the dig-alkaline phosphatase detection system was developed to fulfill this purpose. The results were compared with corresponding polymerase chain reaction (PCR) data to elucidate the effectiveness of these two protocols in the diagnosis of the SEA-type deletion. The data showed that of the seven CVS, three demonstrated a distinctive band pattern, indicating their homozygous status of SEA-type deletion, whereas two showed heterozygous patterns, and the other two were free of the deletion. Homozygosity of the deletion was confirmed by Southern-blot hybridization performed on DNA samples extracted from the abortus tissue. However, two of the three cases with SEA-type deletion showed heterozygous PCR results. Maternal cell contamination could be responsible for the artifacts in the PCR results, but the influence due to the contamination is minimal in non-radioactive Southern-blot hybridization. We concluded that PCR is suitable for screening of carrier adults with SEA-type deletion, and non-radioactive Southern hybridization is ideal for early prenatal diagnosis of the SEA-type deletion.
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Southern Blotting/métodos , Deleção de Genes , Complicações Hematológicas na Gravidez/diagnóstico , Talassemia alfa/diagnóstico , Talassemia alfa/genética , Sudeste Asiático , Amostra da Vilosidade Coriônica , Digoxigenina , Feminino , Triagem de Portadores Genéticos , Testes Genéticos , Humanos , Masculino , Reação em Cadeia da Polimerase , Gravidez , Complicações Hematológicas na Gravidez/epidemiologia , Taiwan , Talassemia alfa/epidemiologiaRESUMO
We describe a novel and relatively inexpensive spectrofluorescence system that supplies rapidly alternating wavelengths to either a standard cuvette or an isolated perfused heart. Its use is illustrated by determining changes in cytosolic intracellular Ca2+ concentration ([Ca2+]i) by using the Ca(2+)-sensitive fluorescent dye fura 2 in a rabbit heart preparation. The system uses two precision electromechanical shutters (capable of gating with respect to the electrocardiographic R wave for signal averaging) allowing alternate fura 2 excitation wavelengths (340 and 380 nm) without moving optical components and uses a fiber optic for conducting excitation and collecting epifluorescence. Sample recordings tracing the [Ca2+]i transient in an entire cardiac cycle and in capturing specific isolated regions (diastole and systole) of the cycle are presented. Limitations of this low-cost but easily implemented system are discussed.
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Cálcio/análise , Fura-2/análise , Miocárdio/química , Animais , Citosol/química , Diástole , Eletrocardiografia , Tecnologia de Fibra Óptica , Fura-2/química , Técnicas In Vitro , Masculino , Fibras Ópticas , Coelhos , Software , Espectrometria de Fluorescência , SístoleRESUMO
PURPOSE OF INVESTIGATION: This study was designed to examine the therapeutic effectiveness and mechanism of action of Tripterygium Wilfordii polyglycoside (TWP) in the treatment of endometriosis. METHODS: An experimental endometriosis model was developed using New Zealand White rabbits where endometrial tissue was autotransplanted into the peritoneum. Six weeks after transplantation, a total of 22 rabbits were randomly placed into two groups: Group I (n=17) was treated with TWP (10 mg/kg/day) and Group 2 (n=5) served as the water-fed control for three successive months. The volume of endometrial implants was measured before and after administration of TWP and water. Immune and endocrine systems were investigated in the normal phase, six weeks after induction of endometriosis, and three months after TWP treatment and water administration. RESULTS: After treatment with TWP, the average volume of endometrial implants significantly decreased (p < 0.0001), and the antiendometrial antibody (EmAb) level decreased (p < 0.05) to near normal levels, but it did not decrease in the untreated controls. Serum FSH and LH levels also decreased after TWP treatment. Furthermore, electron microscopic examination of the pituitary ultrastructure revealed morphological changes in gonadotropic cells (G-cell) after treatment with TWP, and changes gradually disappeared four weeks after withdrawal of TWP. CONCLUSION: This study indicates that TWP has both hormonal and immune system action that is effective as a medical treatment for experimental endometriosis by modulating both reproductive endocrine functions and immunosuppression that results in remission of the disease.
Assuntos
Endometriose/tratamento farmacológico , Glicosídeos/farmacologia , Fitoterapia/métodos , Extratos Vegetais/farmacologia , Tripterygium , Animais , Modelos Animais de Doenças , Endométrio/efeitos dos fármacos , Endométrio/patologia , Feminino , Hormônio Foliculoestimulante/análise , Hormônio Luteinizante/análise , Medicina Tradicional Chinesa , Extratos Vegetais/uso terapêutico , Probabilidade , Coelhos , Radioimunoensaio , Distribuição Aleatória , Valores de Referência , Estatísticas não Paramétricas , Resultado do TratamentoRESUMO
Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM) can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca(2+) dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic ß receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic ß receptors, and a nitric oxide associated relaxing mechanism.
Assuntos
Jejuno/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Miosinas/metabolismo , Taurina/farmacologia , Antagonistas Adrenérgicos alfa/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Atropina/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Cimetidina/farmacologia , Difenidramina/farmacologia , Sistema Nervoso Entérico/efeitos dos fármacos , Antagonistas dos Receptores Histamínicos H1/farmacologia , Antagonistas dos Receptores H2 da Histamina/farmacologia , Jejuno/fisiologia , Masculino , Antagonistas Muscarínicos/farmacologia , Quinase de Cadeia Leve de Miosina/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/antagonistas & inibidores , Fentolamina/farmacologia , Fosforilação , Propranolol/farmacologia , Ratos Sprague-Dawley , Taurina/antagonistas & inibidores , Tetrodotoxina/farmacologia , Verapamil/farmacologiaRESUMO
The dielectric and ferroelectric behaviors of a ferroelectric are substantially determined by its domain structure and domain wall dynamics at mesoscopic level. A relationship between the domain walls and high frequency mesoscopic dielectric response is highly appreciated for high frequency applications of ferroelectrics. In this work we investigate the low electric field driven motion of 90°-domain walls and the frequency-domain spectrum of dielectric permittivity in normally strained ferroelectric lattice using the phase-field simulations. It is revealed that, the high-frequency dielectric permittivity is spatially inhomogeneous and reaches the highest value on the 90°-domain walls. A tensile strain favors the parallel domains but suppresses the kinetics of the 90° domain wall motion driven by electric field, while the compressive strain results in the opposite behaviors. The physics underlying the wall motions and thus the dielectric response is associated with the long-range elastic energy. The major contribution to the dielectric response is from the polarization fluctuations on the 90°-domain walls, which are more mobile than those inside the domains. The relevance of the simulated results wth recent experiments is discussed.
RESUMO
Certain gene polymorphisms are associated with human aging. This study investigated polymorphisms of a metabolism-related gene, Klotho, and an inflammatory gene, IL6, for association with the aging process in a healthy Han Chinese population. A total of 482 healthy subjects were recruited and divided into aging and young groups according to chronological age and biological age. Snapshots were used to detect a Klotho gene tag SNP (rs571118) and the F-SNPs rs9536314 (F352V) and rs9527025 (C370S), and an interleukin 6 (IL-6) gene tag SNP (rs1524107) and the F-SNPs rs1800795 (-174G/C) and rs1800796 (-572G/C). Klotho F352V and IL-6-174G/C was G homozygous, C370S was T homozygous while IL-6-572G/C MAF less than 5%. There was a statistically significant difference in the Klotho rs571118 SNP between chronological age groups, but not biological age groups. However, other SNPs, including IL-6 gene SNPs, didn't correlate with age in the Han Chinese population. Human aging is a complex process that includes chronological and biological aging. Our current data showed that Klotho gene rs571118 SNP was associated with chronological aging, but not biological aging, in a Han Chinese population. Further study will investigate genetic build up for the difference between chronological and biological aging.