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AIM: To investigate the proliferation and mineralization of a human cementoblast cell line under alkaline conditions. METHODOLOGY: A human cementoblast cell line was cultured in alkaline media with several pHs (pH 7.6, 8.0 and 8.4) without CO2 . Cell numbers, phospho-p44/42 expression, alkaline phosphatase (ALP) activity and mineralization were evaluated. The significance of differences between groups was assessed using two-way analysis of variance 15 (ANOVA) followed by Bonferroni's multiple comparison test (α = 0.01). RESULTS: Cell numbers increased in a time-dependent manner in the high pH medium groups. Western blot analysis revealed the upregulated expression of phospho-p44/42 under alkaline conditions. ALP activity was also increased at pH 8.0 and 8.4. Alizarin red staining revealed increased mineralization in the high pH medium groups. The incorporation of the transient receptor potential ankyrin subfamily member 1 (TRPA1) antagonist HC030031 markedly negated the effect on proliferation and mineralization. CONCLUSIONS: Extracellular alkaline conditions promoted the proliferation and mineralization of human cementoblasts in vitro via TRPA1.
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Fosfatase Alcalina , Cemento Dentário , Calcificação Fisiológica , Contagem de Células , Diferenciação Celular , Linhagem Celular , Proliferação de Células , Células Cultivadas , HumanosRESUMO
OBJECTIVES: To compare the effect of femoral bone tunnel configuration on tendon-bone healing in an anterior cruciate ligament (ACL) reconstruction animal model. METHODS: Anterior cruciate ligament reconstruction using the plantaris tendon as graft material was performed on both knees of 24 rabbits (48 knees) to mimic ACL reconstruction by two different suspensory fixation devices for graft fixation. For the adjustable fixation device model (Socket group; group S), a 5 mm deep socket was created in the lateral femoral condyle (LFC) of the right knee. For the fixed-loop model (Tunnel group; group T), a femoral tunnel penetrating the LFC was created in the left knee. Animals were sacrificed at four and eight weeks after surgery for histological evaluation and biomechanical testing. RESULTS: Histologically, both groups showed a mixture of direct and indirect healing patterns at four weeks, whereas only indirect healing patterns were observed in both groups at eight weeks. No significant histological differences were seen between the two groups at four and eight weeks in the roof zone (four weeks, S: mean 4.8 sd 1.7, T: mean 4.5 sd 0.5, p = 0.14; eight weeks, S: mean 5.8 sd 0.8, T: mean 4.8 sd 1.8, p = 0.88, Mann-Whitney U test) or side zone (four weeks, S: mean 5.0 sd 1.2, T: mean 4.8 sd 0.4, p = 0.43; eight weeks, S: mean 5.3 sd 0.8,T: mean 5.5 sd 0.8, p = 0.61, Mann-Whitney U test) . Similarly, no significant difference was seen in the maximum failure load between group S and group T at four (15.6 sd 9.0N and 13.1 sd 5.6N) or eight weeks (12.6 sd 3.6N and 17.1 sd 6.4N, respectively). CONCLUSION: Regardless of bone tunnel configuration, tendon-bone healing after ACL reconstruction primarily occurred through indirect healing. No significant histological or mechanical differences were observed between adjustable and fixed-loop femoral cortical suspension methods.Cite this article: Y. Sato, R. Akagi, Y. Akatsu, Y. Matsuura, S. Takahashi, S. Yamaguchi, T. Enomoto, R. Nakagawa, H. Hoshi, T. Sasaki, S. Kimura, Y. Ogawa, A. Sadamasu, S. Ohtori, T. Sasho. The effect of femoral bone tunnel configuration on tendon-bone healing in an anterior cruciate ligament reconstruction: An animal study. Bone Joint Res 2018;7:327-335. DOI: 10.1302/2046-3758.75.BJR-2017-0238.R2.
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OBJECTIVE: The aim of this report was to evaluate the impact of hormone replacement therapy (HRT) on lymphocytic infiltration of the endometrium in postmenopausal women. METHOD: This study included 58 Japanese patients who had undergone hysterectomy at the University Hospital of Occupational and Environmental Health, Japan. Before surgery, nine patients had received 17ß-estradiol (E2), 0.72 mg transdermally for 2-8 weeks (E2 group); 16 patients had received an Estra-1,3,5(10)-triene-3,16α, 17ß-triol (E3) vaginal tablet 0.5 mg per month five times (E3 group); and 19 patients had received 17ß-estradiol, 0.62 mg, and norethindrone acetate (P), 2.70 mg for 3-16 weeks (E2 + P group). Fourteen patients received no HRT (control group). We examined uterine tissue specimens immunohistochemically for CD45+, CD3+, CD4+, CD8+, CD20+, CD56+, and Ki67 antigen-positive cells. RESULTS: The numbers of CD56 + cells were significantly increased in the E2 group compared with all other groups (E2 vs. E3: 7.0 vs. 0.75, p = 0.017; E2 vs. E2 + P: 7.0 vs. 0.58, p = 0.009; E2 vs. CONTROL: 7.0 vs. 0.43, p = 0.010). The numbers of CD3+ cells were significantly increased in the E2 group compared with the control group (149.3 vs. 42.6, p = 0.008). CONCLUSION: 17ß-Estradiol induced the proliferation of endometrial uterine natural killer cells (CD56+) in postmenopausal women.
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Endométrio/efeitos dos fármacos , Estradiol/farmacologia , Terapia de Reposição de Estrogênios , Células Matadoras Naturais/efeitos dos fármacos , Pós-Menopausa , Administração Cutânea , Proliferação de Células/efeitos dos fármacos , Endométrio/citologia , Estradiol/administração & dosagem , Feminino , Humanos , Células Matadoras Naturais/citologia , Pessoa de Meia-IdadeRESUMO
Utilizing a graphite-disk probe attached with a thin aluminum disk, we have developed a friction-free viscosity measurement system. The probe is levitated above a NdFeB magnet because of diamagnetic effect and rotated by an electromagnetically induced torque. The probe is absolutely free form mechanical friction, and therefore, the accurate measurements of the viscosity of gases can be achieved. To demonstrate the accuracy and sensitivity of our method, we measured the viscosity of 8 kinds of gases and its temperature change from 278 K to 318 K, and we confirmed a good agreement between the obtained values and literature values. This paper demonstrates that our method has the ability to measure the fluid viscosity in the order of µPa â s.
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STUDY DESIGN: Vertebral fracture load and stiffness from a metastatic vertebral defect model were predicted using nonlinear finite element models (FEM) and validated experimentally. OBJECTIVE: The study objective was to develop and validate an FEM-based tool for predicting polymer-augmented lytic vertebral fracture load and stiffness and the influence of metastatic filling materials. SUMMARY OF BACKGROUND DATA: Percutaneous vertebroplasty has the potential to reduce vertebral fracture risk affected with lytic metastases by providing mechanical stabilization. However, it has been shown that the mismatch in mechanical properties between poly(methyl-methacrylate) (PMMA) and bone induces secondary fractures and intervertebral disc degeneration. A biodegradable copolymer, poly(propylene fumarate-co-caprolactone) (P(PF-co-CL)), has been shown to possess the appropriate mechanical properties for bone defect repair. METHODS: Simulated metastatic lytic defects were created in 40 cadaveric vertebral bodies, which were randomized into 4 groups: intact vertebral body (intact), simulated defect without treatment (negative), defect treated with P(PF-co-CL) (copolymer), and defect treated with PMMA (PMMA). Spines were imaged with quantitative computed tomography (QCT), and QCT/FEM-subject-specific, nonlinear models were created. Predicted fracture loads and stiffness were identified and compared with experimentally measured values using Pearson correlation analysis and paired t test. RESULTS: There was no significant difference between the measured and predicted fracture loads and stiffness for each group. Predicted fracture loads were larger for PMMA augmentation (3960 N [1371 N]) than that for the copolymer, negative and intact groups (3484 N [1497 N], 3237 N [1744 N], and 1747 N [702 N]). A similar trend was observed in the predicted stiffness. Moreover, predicted and experimental fracture loads were strongly correlated (R=0.78), whereas stiffness showed moderate correlation (R=0.39). CONCLUSION: QCT/FEM was successful for predicting fracture loads of metastatic, polymer-augmented vertebral bodies. Overall, we have demonstrated that QCT/FEM may be a useful tool for predicting in situ vertebral fracture load resulting from vertebroplasty. LEVEL OF EVIDENCE: N/A.
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Cimentos Ósseos/uso terapêutico , Poliésteres/uso terapêutico , Fraturas da Coluna Vertebral/etiologia , Neoplasias da Coluna Vertebral/cirurgia , Coluna Vertebral/diagnóstico por imagem , Vertebroplastia/efeitos adversos , Vertebroplastia/métodos , Implantes Absorvíveis , Idoso , Idoso de 80 Anos ou mais , Materiais Biocompatíveis/uso terapêutico , Fenômenos Biomecânicos , Cadáver , Módulo de Elasticidade , Análise de Elementos Finitos , Previsões , Humanos , Pessoa de Meia-Idade , Modelos Teóricos , Dinâmica não Linear , Polimetil Metacrilato/uso terapêutico , Fatores de Risco , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/prevenção & controle , Neoplasias da Coluna Vertebral/secundário , Coluna Vertebral/cirurgia , Tomografia Computadorizada por Raios X/métodosRESUMO
PURPOSE: To review the treatment of primary retroperitoneal mucinous cystadenocarcinoma (PRMC). CASE REPORT: A 30-year-old woman had a large retroperitoneal mucinous adenocarcinoma treated with conservative laparoscopic surgery. Two years later, she was found to have bilateral ovarian cysts at the time of cesarean section. Since cystectomies revealed mucinous adenocarcinoma, she underwent complete surgical staging and adjuvant chemotherapy at this time. CONCLUSION: A rare case of similar cancer in the ovary following treatment for PRMC was described. It is unclear whether the prognosis is improved by oophorectomy. Further cases and long-term follow-up are necessary.
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Adenocarcinoma Mucinoso/cirurgia , Cistadenocarcinoma Mucinoso/cirurgia , Segunda Neoplasia Primária/cirurgia , Neoplasias Ovarianas/cirurgia , Neoplasias Retroperitoneais/cirurgia , Adenocarcinoma Mucinoso/patologia , Adulto , Cistadenocarcinoma Mucinoso/patologia , Feminino , Humanos , Segunda Neoplasia Primária/patologia , Neoplasias Ovarianas/patologia , Ovariectomia , Neoplasias Retroperitoneais/patologiaRESUMO
We experimentally study the spectral broadening of intense, â¼ 100 femtosecond laser pulses at 785 nm coupled into different kinds of hollow core capillary fibers, all filled with air at ambient pressure. Differently from observations in other gases, the spectra are broadened with a strong red-shift due to highly efficient intrapulse Raman scattering. Numerical simulations show that such spectra can be explained only by increasing the Raman fraction of the third order nonlinearity close to 100%. Experimentally, these broadened and red-shifted pulses do not generally allow for straightforward compression using, for example, standard chirped mirrors. However, using special hollow fibers that are internally coated with silver and polymer we obtain pulse durations in the sub-20 fs regime with energies up to 300 µJ.
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To investigate the topographical distribution and patterns of deposition of immunolabelled abnormal prion protein (PrP(Sc)), interspecies transmission of atypical L-type bovine spongiform encephalopathy (BSE) to Cheviot ewes (ARQ/ARQ genotype) was performed. L-type BSE was successfully transmitted via the intracerebral route to a ewe, with an incubation period of 1,562 days. Minimal vacuolar change was detected in the basal ganglia, thalamus and brainstem, and PrP(Sc) accumulated throughout the brain. The L-type BSE-affected sheep was characterized by conspicuous fine particulate deposits in the neuropil, particulate and/or granular intraneuronal and intraglial deposits, and the absence of PrP(Sc) plaques or stellate deposits. In addition, immunohistochemical and western blot analyses revealed that PrP(Sc) accumulation was present in peripheral nervous tissues (including the trigeminal ganglia and dorsal root ganglion) and adrenal glands, but was absent in lymphoid tissues. These results suggest that L-type BSE has distinct and distinguishable characteristics as well as PrP(Sc) tissue tropism in sheep.
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Encefalopatia Espongiforme Bovina/metabolismo , Proteínas PrPSc/análise , Proteínas PrPSc/metabolismo , Animais , Western Blotting , Bovinos , Encefalopatia Espongiforme Bovina/patologia , Encefalopatia Espongiforme Bovina/transmissão , Imuno-Histoquímica , Ovinos , Doenças dos Ovinos/metabolismo , Doenças dos Ovinos/patologiaRESUMO
This study was conducted to elucidate the prognostic significance of BAF57 in patients with endometrial carcinoma. We investigated the relationship between the immunohistochemical expression of BAF57 and various clinicopathological variables in 111 endometrial carcinomas. Both univariate and multivariate regression analyses were performed. The correlations between the BAF57 expression and the other variables including estrogen receptor (ER) and p53 were examined. The high nuclear BAF57 expression was detected in 42 (37.8%) endometrial carcinomas, and 69 (62.2%) endometrial carcinomas were defined as having low nuclear BAF57 expression. The BAF57 expression was significantly associated with the surgical stage, grade of the tumor, myometrial invasion, lympho-vascular space invasion (LVSI) and lymph node metastasis. The 10-year overall survival rates of patients with low and high BAF57 expression were 96.9% and 58.2%, respectively (p<0.001). A multivariate analysis identified BAF57 expression as an independent prognostic factor. The BAF57 expression was significantly correlated with p53 expression (r=0.312, P=0.001), but was not correlated with ER expression (r= -0.141, P=0.14). The high BAF57 expression is an independent marker of poor prognosis of the patients in endometrial carcinomas. The inhibition of BAF57 activity may be one of the candidates for endometrial cancer therapy, especially therapy for aggressive tumors showing overexpression of p53.
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Proteínas Cromossômicas não Histona/metabolismo , Proteínas de Ligação a DNA/metabolismo , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/metabolismo , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/secundário , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Prognóstico , Receptores de Estrogênio/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
Equilibrium function in the cerebellum (vestibulo-cerebellar system) can deteriorate under the influence of alcohol. In the Romberg posture, the center of gravity, which was measured every 50 ms by stabilometry, appeared to shift with alcohol ingestion. In the previous study, a locus in the center of gravity (stabilogram) was converted to values of statistical indices such as area of sway, total locus length, and locus length per unit area, although these indices could not always distinguish between the statokinesigrams sampled from seven healthy young males in sober and intoxicated states. This measurement was made with an AMTI force plate. In this study, "translation error" was estimated in a d-dimensional embedding space in order to compare statokinesigrams recorded before and after the ingestion of doubly diluted brandy in 30 s (1 ≤ d ≤ 10). We succeeded in validating a stochastic differential equation as a mathematical model of the body sway. The randomness in the model was preserved after alcohol intake and significantly increased in the medial/lateral direction. Visual information referred by the postural control system when standing might be interfered by the effects of intoxication, which was regarded as disturbance. This method is considered to be useful to diagnose the disorders of the vestibulocerebellar system.
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Intoxicação Alcoólica/diagnóstico , Intoxicação Alcoólica/fisiopatologia , Algoritmos , Diagnóstico por Computador/métodos , Equilíbrio Postural , Postura , Humanos , Dinâmica não Linear , Adulto JovemRESUMO
The origin and transmission routes of atypical bovine spongiform encephalopathy (BSE) remain unclear. To assess whether the biological and biochemical characteristics of atypical L-type BSE detected in Japanese cattle (BSE/JP24) are conserved during serial passages within a single host, 3 calves were inoculated intracerebrally with a brain homogenate prepared from first-passaged BSE/JP24-affected cattle. Detailed immunohistochemical and neuropathologic analysis of the brains of second-passaged animals, which had developed the disease and survived for an average of 16 months after inoculation, revealed distribution of spongiform changes and disease-associated prion protein (PrP(Sc)) throughout the brain. Although immunolabeled PrP(Sc) obtained from brain tissue was characterized by the presence of PrP plaques and diffuse synaptic granular accumulations, no stellate-type deposits were detected. Western blot analysis suggested no obvious differences in PrP(Sc) molecular mass or glycoform pattern in the brains of first- and second-passaged cattle. These findings suggest failures to identify differences in mean incubation period and biochemical and neuropathologic properties of the BSE/JP24 prion between the first and second passages in cattle.
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Encéfalo/patologia , Encefalopatia Espongiforme Bovina/transmissão , Proteínas PrPSc/metabolismo , Animais , Western Blotting/veterinária , Encéfalo/metabolismo , Bovinos , Encefalopatia Espongiforme Bovina/metabolismo , Encefalopatia Espongiforme Bovina/patologia , Feminino , Glicosilação , Imuno-Histoquímica/veterinária , Proteínas PrPSc/análise , Conformação Proteica , Estabilidade Proteica , Inoculações SeriadasRESUMO
The atomic alignment effect has been studied for the dissociative energy transfer reaction of metal carbonyls (Fe(CO)(5), Ni(CO)(4)) with the oriented Ar ((3)P(2), M(J) = 2). The emission intensity from the excited metal products (Fe*, Ni*) has been measured as a function of the atomic alignment in the collision frame. The selectivity of the atomic orbital alignment of Ar ((3)P(2), M(J) = 2) (rank 2 moment, a(2)) is found to be opposite for the two reaction systems; the Fe(CO)(5) reaction is favorable at the Π configuration (positive a(2)), while the Ni(CO)(4) reaction is favorable at the Σ configuration (negative a(2)). Moreover, a significant spin alignment effect (rank 4 moment, a(4)) is recognized only in the Ni(CO)(4) reaction. The atomic alignment effect turns out to be essentially different between the two reaction systems; the Fe(CO)(5) reaction is controlled by the configuration of the half-filled 3p atomic orbital of Ar ((3)P(2)) in the collision frame (L dependence), whereas the Ni(CO)(4) reaction is controlled by the configuration of the total angular moment J (including spin) of Ar ((3)P(2)) in the collision frame (J dependence). As the origin of J dependence observed only in the Ni(CO)(4) reaction, the correlation (and/or the interference) between two electron exchange processes via the electron rearrangements is proposed.
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Argônio/química , Compostos Carbonílicos de Ferro/química , Níquel/química , Transferência de EnergiaRESUMO
The oriented CO (a (3)Π, v' = 0, Ω = 1 and 2) beam has been prepared by using an electric hexapole and applied to the energy transfer reaction of CO (a (3)Π, v' = 0, Ω = 1 and 2) + NO (X (2)Π) â NO (A (2)Σ(+), B (2)Π) + CO (X (1)Σ(+)). The emission spectra of NO (A (2)Σ(+), B(2)Π) have been measured at three orientation configurations (C-end, O-end, random). The shape of the emission spectra (and/or the internal excitation of products) turns out to be insensitive to the molecular orientation. The vibrational distributions of NO (A (2)Σ(+), v' = 0-2) and NO (B (2)Π, v' = 0-2) are determined to be N(v'=0):N(v'=1):N(v'=2) = 1:0.40 ± 0.05:0.10 ± 0.05 and N(v'=0):N(v'=1):N(v'= 2) = 1:0.6 ± 0.1:0.7 ± 0.1, respectively, and the branching ratio γ/ß [=NO (A (2)Σ(+))/NO (B (2)Π)] is estimated to be γ/ß â¼ 0.3 ± 0.1 by means of spectral simulation. These vibrational distributions of NO (A, B) can be essentially attributed to the product-pair correlations between CO (X, vâ³) and NO (A (2)Σ(+), v' = 0-2), NO (B (2)Π, v' = 0-2) due to energetic restriction under the vibrational distribution of CO (X, vâ³) produced from the vertical transition of CO (a (3)Π, v' = 0) â CO (X, vâ³) in the course of energy transfer. The steric opacity function has been determined at two wavelength regions: 220 < λ < 290 nm [NO (A â X) is dominant]; 320 < λ < 400 nm [NO (B â X) is dominant]. For both channels NO (A (2)Σ(+), B(2)Π), a significant CO (a (3)Π) alignment effect is recognized; the largest reactivity at the sideways direction with the small reactivity at the molecular axis direction is observed. These CO (a (3)Π) alignment effects can be essentially attributed to the steric asymmetry on two sets of molecular orbital overlap, [CO (2π) + NO (6σ (2π))] and [CO (5σ) + NO (1π (2π))]. All experimental observations support the electron exchange mechanism that is operative through the formation of a weakly bound complex OCNO.
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Monóxido de Carbono/química , Físico-Química , Transferência de Energia , Óxido Nítrico/química , Elétrons , Isomerismo , Termodinâmica , VibraçãoRESUMO
IL28B genetic polymorphism is related to interferon-sensitivity in chronic hepatitis C, but the significance of grafts carrying different genotypes from recipients is still unclear in liver transplantation. A 51-year-old Japanese male carrying a minor genotype underwent dual liver transplantation for liver cirrhosis due to hepatitis C virus (HCV). The left lobe graft carried a major genotype, and the right a minor genotype. He achieved virological response during the course of pegylated-interferon and ribavirin therapy against recurrent hepatitis C for 2 years, but HCV relapsed immediately at the end of the therapy. Two years after antiviral therapy, liver biopsy was performed from each graft. The specimens showed A1F0 in the left lobe graft and A2F2 in the right. Moreover, quantitative polymerase chain reaction was performed using RNA extracted from each specimen to see there was no HCV RNA in the left lobe whereas there was in the right. This case provides clear evidence that IL28B genetic variants determine interferon sensitivity in recurrent hepatitis C following liver transplantation, which could result in new strategies for donor selection or for posttransplant antiviral therapy to HCV positive recipients.
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Variação Genética , Hepatite C/genética , Interleucinas/genética , Transplante de Fígado/efeitos adversos , Sequência de Bases , Primers do DNA , Humanos , Interferons , Masculino , Pessoa de Meia-Idade , Recidiva , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
We have studied how the KrF* formation in the NF3 þ Kr*(3P2) reaction depends on the mutual configuration between the orientation of the NF3 molecule and the alignment of the Kr*(3P2, M(J) = 2) atom in the collision frame. The molecular steric opacity function has been determined as a function of the atomic orbital alignment (M'(L)) in the collision frame. The molecular steric opacity function turns out to depend remarkably on M'(L) ; the |M'(L)| = 1 alignment is favorable at the molecular axis direction, whereas the M'(L) = 0 alignment is favorable at the sideways direction with a very poor reactivity at the molecular axis direction. The influence of deformation of the NF3 geometry on the electron affinity has been evaluated by ab initio calculation, and the M'(L) dependent intermolecular potential has been estimated from the interaction potential for the bromine-rare gas system. We propose the "collision-induced harpooning mechanism" as a novel process for the harpooning in which collisional deformation of the NF3 geometry with C(s) symmetry plays an important role as an initiating factor on electron transfer for the formation of NF3(-) due to increasing the electron affinity of NF3 and due to localizing the negative charge on the closest F-atom of NF3(-) anion. All experimental observations can support the collision-induced harpooning mechanism.
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Twenty-eight calves were exposed to 5 g of homogenized brainstems confirmed as bovine spongiform encephalopathy (BSE) agents. Two to five animals were sequentially killed for post-mortem analyses 20 months post-inoculation (MPI) at intervals of 6 or 12 months. Samples from animals challenged orally with BSE agents were examined by Western blot and immunohistochemical analyses. Immunolabelled, disease-associated prion protein (PrPsc) was detected in a small portion of follicles in the continuous Peyer's patch from the posterior portion of the small intestine involving the entire ileum and the posterior jejunum but not in the discrete Peyer's patches in the remaining jejunum in preclinical animals at 20, 36, and 48 MPI. The PrPsc-positive cells corresponded to tingible body macrophages on double immunofluorescence labelling. In addition, PrPsc accumulated in 7 of 14 animals in the central nervous system (CNS) after 34 MPI, and five of them developed clinical signs and were killed at 34, 46, 58, and 66 MPI. Two preclinical animals killed at 36 and 48 MPI presented the earliest detectable and smallest deposition of immunolabelled PrPsc in the dorsal motor nucleus of the vagus nerve, the spinal trigeminal nucleus of the medulla oblongata at the obex region, and/or the intermediolateral nucleus of the 13th thoracic segment of the spinal cord. Based on serial killing, no PrPsc was detectable in the CNS, including the medulla oblongata at the obex level, before 30 MPI, by Western blot and immunohistochemical analyses. These results are important for understanding the pathogenesis of BSE.
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Encefalopatia Espongiforme Bovina/transmissão , Nódulos Linfáticos Agregados/patologia , Príons/isolamento & purificação , Animais , Bovinos , Feminino , Intestino Delgado/patologia , Masculino , CamundongosRESUMO
To characterize the biological and biochemical properties of H-type bovine spongiform encephalopathy (BSE), a transmission study with a Canadian H-type isolate was performed with bovinized transgenic mice (TgBoPrP), which were inoculated intracerebrally with brain homogenate from cattle with H-type BSE. All mice exhibited characteristic neurologic signs, and the subsequent passage showed a shortened incubation period. The distribution of disease-associated prion protein (PrP(Sc)) was determined by immunohistochemistry, Western blot, and paraffin-embedded tissue (PET) blot. Biochemical properties and higher molecular weight of the glycoform pattern were well conserved within mice. Immunolabeled granular PrP(Sc), aggregates, and/or plaque-like deposits were mainly detected in the following brain locations: septal nuclei, subcallosal regions, hypothalamus, paraventricular nucleus of the thalamus, interstitial nucleus of the stria terminalis, and the reticular formation of the midbrain. Weak reactivity was detected by immunohistochemistry and PET blot in the cerebral cortex, most thalamic nuclei, the hippocampus, medulla oblongata, and cerebellum. These findings indicate that the H-type BSE prion has biological and biochemical properties distinct from those of C-type and L-type BSE in TgBoPrP mice, which suggests that TgBoPrP mice constitute a useful animal model to distinguish isolates from BSE-infected cattle.
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Encefalopatia Espongiforme Bovina/transmissão , Proteínas PrPSc/metabolismo , Animais , Western Blotting/veterinária , Canadá , Bovinos , Encefalopatia Espongiforme Bovina/metabolismo , Encefalopatia Espongiforme Bovina/patologia , Feminino , Imuno-Histoquímica/veterinária , Camundongos , Camundongos Transgênicos , Modelos Animais , Peso Molecular , Inclusão em Parafina/veterinária , Proteínas PrPSc/análiseRESUMO
BACKGROUND: High plasma levels of C-reactive protein (CRP) constitute a powerful predictive marker of cardiovascular events. Several lines of evidence suggest that CRP has prothrombogenic effects. However, whether CRP directly participates in the pathogenesis of thrombosis in vivo has not been fully clarified. OBJECTIVE: To test whether human CRP (hCRP) affects arterial thrombus formation after balloon injury of smooth muscle cell (SMC)-rich or macrophage-rich neointima. METHODS: We compared the susceptibility of transgenic (Tg) rabbits expressing hCRP (46.21 ± 13.85 mg L(-1), n = 22) and non-Tg rabbits to arterial thrombus formation after balloon injury of SMC-rich or macrophage-rich neointima. RESULTS: Thrombus size on SMC-rich or macrophage-rich neointima was significantly increased, and was accompanied by an increase in fibrin content in hCRP-Tg rabbits, as compared with non-Tg rabbits. Thrombus size did not significantly differ between SMC-rich and macrophage-rich neointima in hCRP-Tg rabbits. Tissue factor (TF) mRNA expression and activity in these neointimal lesions were significantly increased in hCRP-Tg rabbits as compared with non-Tg rabbits. The degree of CRP deposition correlated with the elevated TF expression and thrombus size on injured neointima. In addition, hCRP isolated from hCRP-Tg rabbit plasma induced TF mRNA expression and activity in rabbit cultured vascular SMCs. CONCLUSIONS: These results suggest that elevated plasma hCRP levels promote thrombus formation on injured SMC-rich neointima by enhancing TF expression, but have no additive effects in macrophage-rich neointima.
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Proteína C-Reativa/metabolismo , Artéria Femoral/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Trombose/genética , Túnica Íntima/metabolismo , Lesões do Sistema Vascular/metabolismo , Animais , Animais Geneticamente Modificados , Proteína C-Reativa/genética , Cateterismo , Proliferação de Células , Células Cultivadas , Modelos Animais de Doenças , Artéria Femoral/lesões , Artéria Femoral/patologia , Humanos , Hiperlipidemias/genética , Hiperlipidemias/metabolismo , Macrófagos/metabolismo , Masculino , Músculo Liso Vascular/lesões , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , RNA Mensageiro/metabolismo , Coelhos , Tromboplastina/genética , Trombose/sangue , Trombose/metabolismo , Trombose/patologia , Fatores de Tempo , Túnica Íntima/lesões , Túnica Íntima/patologia , Regulação para Cima , Lesões do Sistema Vascular/sangue , Lesões do Sistema Vascular/genética , Lesões do Sistema Vascular/patologiaRESUMO
Small cell lung cancer with interstitial lung disease (ILD-SCLC) is difficult to treat because of the risk of fatal pneumonitis. Our study aims to evaluate the validity of topotecan (TOP) as chemotherapy for patients with relapsed ILD-SCLC. Overall survival was compared between TOP and other drugs as second-line treatments for ILD-SCLC patients. Forty-seven patients began chemotherapy and second-line treatment was administered in 48.5% of relapsed cases. The response rate of TOP for second-line therapy was 16.7%. Hematologic toxicities were grade 4 anemia, grade 3 neutropenia and grade 3 thrombocytopenia. Mild pulmonary toxicity was observed in 1 case. Patients receiving TOP as second-line treatment showed no significant difference in survival when compared to patients who underwent other regimens (median survival time 179 vs. 76 days; p =0.76). TOP is a well tolerated drug and is a viable candidate for second-line treatment of ILD-SCLC patients.
Assuntos
Antineoplásicos/uso terapêutico , Doenças Pulmonares Intersticiais/complicações , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/complicações , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Topotecan/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Topotecan/efeitos adversosRESUMO
We report a case who had undergone operation of very early malignant pleural mesothelioma (MPM). A 58-year-old woman admitted to first visited hospital because of pleural effusion of the right side. She received a diagnosis of epithelial type MPM which had been confirmed from a pleural biopsy spacemen obtained by thoracoscopy under local anesthesia. An abnormal change of the pleura could not be detected on chest X-ray and thoracic computed tomography (CT) scan after chest drainage. She was referred to our hospital for surgery, and was undergone an extrapleural pneumonectomy followed by postoperative treatment with cisplatin puls gemcitabine. Pathologically, the disease was diagnosed as stage IA based on the classification of International Mesothelioma Interest Group (IMIG). There is a no evidence of the relapse 9 months after the operation. An early diagnosis of the MPM is very difficult. The thoracoscope with local anesthesia was very effective for early diagnose of a MPM.