RESUMO
The glycan loop of Zika virus (ZIKV) envelope protein (E) contains the glycosylation site and has been well documented to be important for viral pathogenesis and transmission. In the present study, we report that deletions in the E glycan loop, which were recorded in African ZIKV strains previously, have re-emerged in their contemporary Asian lineages. Here, we generated recombinant ZIKV containing specific deletions in the E glycan loop by reverse genetics. Extensive in vitro and in vivo characterization of these deletion mutants demonstrated an attenuated phenotype in an adult A129 mouse model and reduced oral infections in mosquitoes. Surprisingly, these glycan loop deletion mutants exhibited an enhanced neurovirulence phenotype, and resulted in a more severe microcephalic brain in neonatal mouse models. Crystal structures of the ZIKV E protein and a deletion mutant at 2.5 and 2.6 Å, respectively, revealed that deletion of the glycan loop induces encephalitic flavivirus-like conformational alterations, including the appearance of perforations on the surface and a clear change in the topology of the loops. Overall, our results demonstrate that the E glycan loop deletions represent neonatal mouse neurovirulence markers of ZIKV. IMPORTANCE Zika virus (ZIKV) has been identified as a cause of microcephaly and acquired evolutionary mutations since its discovery. Previously deletions in the E glycan loop were recorded in African ZIKV strains, which have re-emerged in the contemporary Asian lineages recently. The glycan loop deletion mutants are not glycosylated, which are attenuated in adult A129 mouse model and reduced oral infections in mosquitoes. More importantly, the glycan loop deletion mutants induce an encephalitic flavivirus-like conformational alteration in the E homodimer, resulting in a significant enhancement of neonatal mouse neurovirulence. This study underscores the critical role of glycan loop deletion mutants in ZIKV pathogenesis, highlighting a need for global virological surveillance for such ZIKV variants.
Assuntos
Proteínas do Envelope Viral , Infecção por Zika virus , Zika virus , Animais , Camundongos , Modelos Animais de Doenças , Polissacarídeos/química , Proteínas do Envelope Viral/genética , Virulência , Replicação Viral/genética , Zika virus/genética , Zika virus/patogenicidade , Infecção por Zika virus/virologiaRESUMO
Testicular invasion and persistence are features of Zika virus (ZIKV), but their mechanisms are still unknown. Here, we showed that S100A4+ macrophages, a myeloid macrophage subpopulation with susceptibility to ZIKV infection, facilitated ZIKV invasion and persistence in the seminiferous tubules. In ZIKV-infected mice, S100A4+ macrophages were specifically recruited into the interstitial space of testes and differentiated into interferon-γ-expressing M1 macrophages. With interferon-γ mediation, S100A4+ macrophages down-regulated Claudin-1 expression and induced its redistribution from the cytosol to nucleus, thus increasing the permeability of the blood-testis barrier which facilitated S100A4+ macrophages invasion into the seminiferous tubules. Intraluminal S100A4+ macrophages were segregated from CD8+ T cells and consequently helped ZIKV evade cellular immunity. As a result, ZIKV continued to replicate in intraluminal S100A4+ macrophages even when the spermatogenic cells disappeared. Deficiencies in S100A4 or interferon-γ signaling both reduced ZIKV infection in the seminiferous tubules. These results demonstrated crucial roles of S100A4+ macrophages in ZIKV infection in testes.
Assuntos
Macrófagos/metabolismo , Proteína A4 de Ligação a Cálcio da Família S100/imunologia , Infecção por Zika virus/imunologia , Animais , Claudina-1/genética , Claudina-1/metabolismo , Interferon gama/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Viral , Proteína A4 de Ligação a Cálcio da Família S100/metabolismo , Túbulos Seminíferos/virologia , Testículo/imunologia , Testículo/virologia , Replicação Viral/imunologia , Replicação Viral/fisiologia , Zika virus/imunologia , Infecção por Zika virus/virologiaRESUMO
Atmospheric precipitation samples were collected in 2018, 2019, and 2021 in Beijing to study the concentrations and changes of the main metal elements and water-soluble ionsï¼ the wet deposition fluxes of heavy metals, water-soluble ions, dissolved inorganic nitrogen, and sulfur in the atmospheric precipitation and their impacts on the ecological environmentï¼ and the scavenging mechanisms of the typical precipitation to atmospheric pollutants during the study period. The results showed that the precipitation in Beijing during the study period was mostly neutral or alkaline, and the frequency of acid rain occurrence was very low, only accounting for 3.06%. The total concentrations of major metal elements in 2018, 2019, and 2021 were ï¼4 787.46 ±4 704.31ï¼, ï¼7 663.07 ±8 395.05ï¼, and ï¼2 629.13 ±2 369.51ï¼ µg·L-1, respectively. The total equivalent concentrations of ions in 2018, 2019, and 2021 were ï¼851.68 ±649.16ï¼, ï¼973.98 ±850.94ï¼, and ï¼644.31 ±531.16ï¼ µeq·L-1, respectively. The interannual changes in major metal elements and ions followed the order of 2019 > 2018 > 2021. The seasonal average total concentrations of major metal elements in spring, summer, autumn, and winter were ï¼9 624.25 ±7 327.92ï¼, ï¼4 088.67 ±5 710.14ï¼, ï¼3 357.68 ±3 995.64ï¼, and ï¼6 203.19 ±3 857.43ï¼ µg·L-1, respectively, and the seasonal average total equivalent concentrations of ions in spring, summer, autumn, and winter were ï¼1 014.71 ±512.21ï¼, ï¼729.83 ±589.90ï¼, ï¼724.35 ±681.40ï¼, and ï¼1 014.03 ±359.67ï¼ µeq·L-1, respectively, all presenting the order of spring > winter > summer > autumn. NO3- and SO42- were the main acid-causing ions in precipitation, whereas NH4+ and Ca2+ were the main acid-neutralizing ions. The wet deposition fluxes of the heavy metal Cd were very low [ï¼0.05 ±0.01ï¼ mg·ï¼m2·aï¼-1], only accounting for ï¼0.13 ±0.04ï¼% of the total wet deposition fluxes of main metal elementsï¼ however, its soil safety years were 291 years, significantly lower than those of other heavy metals, displaying that its ecological risk was relatively the highest. The total wet precipitation flux of water-soluble ions NH4+, Ca2+, NO3-, and SO42- accounted for ï¼85.72 ±2.18ï¼% of the wet precipitation flux of total ions, suggesting that their comprehensive impact on the ecological environment might have been higher. DIN wet deposition flux was mainly characterized by NH4+-N, which had a positive impact on the ecological environment in summer. SO42--S wet deposition flux was higher in summer, so its positive impact on the ecological environment was also greater. The scavenging effects of atmospheric precipitations to pollutants from the air were impacted by various factors, and the synergism effects of these factors could directly influence the scavenging mechanisms of precipitation to pollutants.
RESUMO
Zika virus (ZIKV; Flaviviridae) is a devastating virus transmitted to humans by the mosquito Aedes aegypti. The interaction of the virus with the mosquito vector is poorly known. The double-stranded RNA (dsRNA)-mediated interruption or activation of immunity-related genes in the Toll, IMD, JAK-STAT, and short interfering RNA (siRNA) pathways did not affect ZIKV infection in A. aegypti. Transcriptome-based analysis indicated that most immunity-related genes were upregulated in response to ZIKV infection, including leucine-rich immune protein (LRIM) genes. Further, there was a significant increment in the ZIKV load in LRIM9-, LRIM10A-, and LIRM10B-silenced A. aegypti, suggesting their function in modulating viral infection. Further, gene function enrichment analysis revealed that viral infection increased global ribosomal activity. Silencing of RpL23 and RpL27, two ribosomal large subunit genes, increased mosquito resistance to ZIKV infection. In vitro fat body culture assay revealed that the expression of RpL23 and RpL27 was responsive to the Juvenile hormone (JH) signaling pathway. These two genes were transcriptionally regulated by JH and its receptor methoprene-tolerant (Met) complex. Silencing of Met also inhibited ZIKV infection in A. aegypti. This suggests that ZIKV enhances ribosomal activity through JH regulation to promote infection in mosquitoes. Together, these data reveal A. aegypti immune responses to ZIKV and suggest a control strategy that reduces ZIKV transmission by modulating host factors. IMPORTANCE Most flaviviruses are transmitted between hosts by arthropod vectors such as mosquitoes. Since therapeutics or vaccines are lacking for most mosquito-borne diseases, reducing the mosquito vector competence is an effective way to decrease disease burden. We used high-throughput sequencing technology to study the interaction between mosquito Aedes aegypti and ZIKV. Leucine-rich immune protein (LRIM) genes were involved in the defense in response to viral infection. In addition, RNA interference (RNAi) silencing of RpL23 and RpL27, two JH-regulated ribosomal large subunit genes, suppressed ZIKV infection in A. aegypti. These results suggest a novel control strategy that could block the transmission of ZIKV.
RESUMO
This study analyzed the seasonal variation, sources, and source-specific health risks of PM2.5-bound metals in Xinxiang city, Henan province. A total of 112 daily PM2.5 samples were collected over four consecutive seasons during 2019-2020. In total, 19 elements were identified using inductively coupled plasma atomic emission spectroscopy (ICP-AES). The annual concentrations of PM2.5 and 11 heavy metals were calculated to be (66.25±35.73) µg·m-3 and (1.32±0.84) µg·m-3, respectively. Strong seasonal variations were observed in PM2.5 concentrations and the concentrations of associated metal elements, with the lowest concentrations all occurring in summer. The highest concentrations of dust-related elements (e.g., Al, Ca, Fe, Mg,and Ti) were recorded in spring, differing significantly from other elements, which all exhibited the highest mass concentrations in winter. The results apportioned from positive matrix factorization (PMF) and potential source contribution function (PSCF) models showed that the major sources of PM2.5-bound elements were Ni-and Co-related emissions (5.8%), motor vehicles (13.7%), Cd-related emissions(5.1%), combustion emissions (18.2%), and dust (57.3%). Health risk models showed that there were no obvious non-carcinogenic risks associated with these metals, because their hazard quotient (HQ) values were all below 1. Lifetime carcinogenic risks of the five apportioned sources were all higher than the acceptable level (1×10-6). Of these five sources, combustion emissions were the largest contributors to cancer risk (8.74×10-6, 36.9%) and non-cancer risk (0.60, 25.6%). This study suggests that control strategies to mitigate exposure risk in Xinxiang should emphasize reducing the sources of combustion emissions.
Assuntos
Metais Pesados , Material Particulado , Clima , Monitoramento Ambiental , Humanos , Metais Pesados/análise , Material Particulado/efeitos adversos , Material Particulado/análise , Estações do AnoRESUMO
In the title compound, C(18)H(23)N(5)O(2), the triazolopyrimidine ring system is essentially planar, with a maximum displacement of 0.032â (2)â Å, and forms a dihedral angle of 87.59â (15)° with the phenyl ring. In the crystal, mol-ecules are linked by inter-molecular C-Hâ¯O hydrogen bonds and C-Hâ¯π inter-actions into chains parallel to the c axis.
RESUMO
The title compound, C(19)H(21)N(3)O(3)S, was synthesized via the aza-Wittig reaction of functionalized imino-phospho-rane with phenyl isocyanate under mild conditions. In the mol-ecule, the fused thienopyrimidine ring system is essentially planar, with a maximum deviation of 0.072â (2)â Å, and makes a dihedral angle of 60.11â (9)° with the phenyl ring. An intra-molecular C-Hâ¯O hydrogen bond is present. The crystal packing is stabilized by inter-molecular N-Hâ¯O and C-Hâ¯O hydrogen bonds.
RESUMO
The title compound, C(19)H(21)N(3)O(3)S, was synthesized via an aza-Wittig reaction of a functionalized imino-phospho-rane with phenyl isocyanate under mild conditions. In the mol-ecule, the fused thienopyrimidine ring system makes a dihedral angle of 66.30â (11)° with the phenyl ring. An intra-molecular C-Hâ¯O hydrogen bond occurs. The terminal -OCH(2)CH(3) group is disordered over two sites with refined occupancies of 0.537â (13) and 0.463â (13). The crystal packing is stabilized by inter-molecular C-Hâ¯O and N-Hâ¯O hydrogen bonds.
RESUMO
In the title compound, C(20)H(18)N(2)O(4), all non-H atoms of the three fused rings of the benzofuro[3,2-d]pyrimidine system are almost coplanar (r.m.s. deviation 0.021â Å). The dihedral angle between the fused ring system and the benzene ring is 1.47â (12)°. Intra-molecular and inter-molecular C-Hâ¯O hydrogen bonds together with weak C-Hâ¯π inter-actions stabilize the structure.
RESUMO
Mosquitoes act as vectors of numerous pathogens that cause human diseases. Dengue virus (DENV) transmitted by mosquito, Aedes aegypti, is responsible for dengue fever epidemics worldwide with a serious impact on human health. Currently, disease control mainly relies on vector targeted intervention strategies. Therefore, it is imperative to understand the molecular mechanisms underlying the innate immune response of mosquitoes against pathogens. In the present study, the expression profiles of immunity-related genes in the midgut responding to DENV infection by feeding were analyzed by transcriptome and quantitative real-time PCR. The level of Antimicrobial peptides (AMPs) increased seven days post-infection (d.p.i.), which could be induced by the Toll immune pathway. The expression of reactive oxygen species (ROS) genes, including antioxidant genes, such as HPX7, HPX8A, HPX8B, HPX8C were induced at one d.p.i. and peaked again at ten d.p.i. in the midgut. Interestingly, down-regulation of the antioxidant gene HPX8C by RNA interference led to reduction in the virus titer in the mosquito, probably due to the elevated levels of ROS. Application of a ROS inhibitor and scavenger molecules further established the role of oxygen free radicals in the modulation of the immune response to DENV infection. Overall, our comparative transcriptome analyses provide valuable information about the regulation of immunity related genes in the transmission vector in response to DENV infection. It further allows us to identify novel molecular mechanisms underlying the host-virus interaction, which might aid in the development of novel strategies to control mosquito-borne diseases.
Assuntos
Aedes/genética , Aedes/imunologia , Imunidade Inata , Peroxidase/genética , Aedes/virologia , Animais , Peptídeos Catiônicos Antimicrobianos/genética , Dengue/imunologia , Vírus da Dengue , Sistema Digestório/imunologia , Sistema Digestório/virologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Heme/genética , Heme/imunologia , Interações entre Hospedeiro e Microrganismos , Camundongos , Peroxidase/imunologia , Interferência de RNA , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais , Organismos Livres de Patógenos Específicos , Receptores Toll-Like/genéticaRESUMO
In the title compound, C(10)H(11)ClN(4)O(2)S, the triazole ring carries methyl and ethoxy-carbonyl groups and is bound via a methyl-ene bridge to a chloro-thia-zole unit. There is also evidence for significant electron delocalization in the triazolyl system. Intra- and inter-molecular C-Hâ¯O hydrogen bonds together with strong π-π stacking inter-actions [centroid-centroid distance 3.620â (1)â Å] stabilize the structure.
RESUMO
In the title compound, C(14)H(16)ClN(5)O(3), there is evidence for significant electron delocalization in the triazolyl system. Intra-molecular C-Hâ¯O and inter-molecular C-Hâ¯O and C-Hâ¯N hydrogen bonds stabilize the structure.
RESUMO
The aza-Wittig reactions of iminophosphorane 3 with aromatic isocyanates generated carbodiimides 4, which were reacted with alkylamines under mild conditions to give a series of 2-(alkylamino)-5,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-ones 6 and 8 in satisfactory yield. Their structures were confirmed by (1)H NMR, EI-MS, IR and elementary analysis, and compound 8c was further analyzed by single-crystal X-ray diffraction. The preliminary bioassays indicated that these compounds showed excellent fungicidal activities against six kinds of fungi.
RESUMO
Yellow fever mosquito Aedes aegypti transmits many devastating arthropod-borne viruses (arboviruses), such as dengue virus, yellow fever virus, Chikungunya virus, and Zika virus, which cause great concern to human health. Mosquito control is an effective method to block the spread of infectious diseases. Ae. aegypti uses its innate immune system to fight against arboviruses, parasites, and fungi. In this review, we briefly summarize the recent findings in the immune response of Ae. aegypti against arboviral and entomopathogenic infections. This review enriches our understanding of the mosquito immune system and provides evidence to support the development of novel mosquito control strategies.
Assuntos
Aedes/imunologia , Arbovírus/fisiologia , Micoses/imunologia , Viroses/imunologia , Animais , Humanos , Imunidade Inata , Controle de Infecções , Proteínas de Insetos/metabolismo , Mosquitos Vetores , Transdução de Sinais , Receptores Toll-Like/metabolismoRESUMO
OBJECTIVE: To study the genetic aberrations and their pathologic significance in follicular lymphoma (FL). METHODS: Paraffin-embedded tissue samples of 55 cases of FL, 28 cases of other small B-cell lymphomas and 10 cases of reactive follicular hyperplasia were retrieved. Nested polymerase chain reaction (PCR) was used to detect clonal rearrangement of immunoglobulin heavy chain gene (IgH) in FL and other small B-cell lymphomas. The translocation t (14; 18) was studied by PCR and dual-color fluorescence in-situ hybridization (FISH) in FL. Cases of reactive follicular hyperplasia were used as controls. RESULTS: Amongst the 55 cases studied, 49 cases were nodal and 6 cases were extranodal. There were 33 males and 22 females. The male-to-female ratio was 1.5:1. The median age of the patients was 57 years. Twenty-five cases belonged to histologic grade 1, while 19 cases were grade 2 and 11 cases were grade 3. Beta-actin DNA was detected in 50 cases of FL. Amongst those 50 cases, clonal IgH rearrangement was present in 34 (68%). Twenty-four cases (48%) and 25 cases (50%) were positive for FR3A and FR2 respectively. Fifteen cases (30%) showed dual positivity for both FR3A and FR2. Thirty-four cases (68%) demonstrated clonal IgH rearrangement. As for other small B-cell lymphomas, 25 cases were positive for beta-actin. FR3A and FR2 were detected in 18 and 17 cases respectively. Clonal IgH rearrangement was demonstrated in 24 cases. In contrast, none of the 4 cases of reactive follicular hyperplasia showed the clonal rearrangement pattern. Amongst the 44 cases of nodal FL analyzed, t (14; 18) was detected in 15 cases (with 14 cases in MBR and 1 case in mcr). In general, FISH was superior to PCR in detecting t (14; 18) using paraffin-embedded tissue samples. CONCLUSIONS: The detection rate of clonal IgH rearrangement in FL is lower than that in other small B-cell lymphomas. Demonstration of t (14; 18) in paraffin-embedded tissue samples by FISH helps in diagnosis of FL. FISH is superior to PCR, as the technique is more sensitive and less labor intensive.
Assuntos
Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 18/genética , Rearranjo Gênico de Cadeia Pesada de Linfócito B/genética , Linfoma Folicular/genética , Translocação Genética , Actinas/metabolismo , Adulto , Idoso , Feminino , Humanos , Hibridização in Situ Fluorescente/métodos , Linfoma de Células B/genética , Linfoma de Células B/metabolismo , Linfoma Folicular/metabolismo , Masculino , Pessoa de Meia-Idade , Inclusão em Parafina , Reação em Cadeia da Polimerase/métodosRESUMO
In 2014, Guangzhou City, South China, suffered from its worst outbreak of dengue fever in decades. Larval mosquito habitat surveillance was carried out by using android mobile devices in four study sites in May 2015. The habitats with larval mosquitoes were recorded as photo waypoints in OruxMaps or in videos. The total number of potential mosquito habitats was 342, of which 166 (49%) were found to have mosquito larvae or pupae. Small containers were the most abundant potential habitats, accounting for 26% of the total number. More mosquito larvae and pupae, were found in small containers than in other objects holding water, for example, potted or hydroponic plants (p < 0.05). Mosquito larvae were collected from all plastic road barriers, used tires, and underground water. Aedes albopictus larvae were found from small and large containers, stumps, among others. The overall route index (RI) was 11.3, which was 14.2 times higher than the grade C criteria of the National Patriotic Health Campaign Committee (NPHCC), China. The higher RIs were found from the bird and flower markets, schools, and underground parking lots. The results indicated that Android mobile devices are a convenient and useful tool for surveillance of mosquito habitats, and the enhancement of source reduction may benefit the prevention and control of dengue vector mosquitoes.
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OBJECTIVE: To investigate bcl-6 protein expression and gene rearrangement patterns in diffuse large B-cell lymphoma (DLBCL) and their clinicopathologic significance. METHODS: Immunohistochemical studies for bcl-6 and CD10 proteins were performed on 51 cases of DLBCL paraffin-embedded tissues (including 22 nodal samples and 29 extranodal samples) and 10 cases of reactive lymphoid hyperplasia (RLH) paraffin-embedded tissues. Interphase fluorescence in-situ hybridization (FISH) with dual color breakapart probe was also used to identify rearrangement of bcl-6 gene in 32 cases of nodal DLBCL tissues (including 22 paraffin-embedded samples and 10 fresh samples) and 5 cases of RLH paraffin-embedded tissues. RESULTS: (1) The rates of bcl-6 protein expression in nodal DLBCL, extranodal DLBCL and RLH were 72.7% (16/22), 75.9% (22/29) and 100.0% (10/10) respectively. The rates of CD10 expression were 40.9% (9/22), 41.4% (12/29) and 100.0% (10/10) respectively. All lymphoma samples which expressed CD10 also showed co-expression of bcl-6 protein. (2) The co-expression of bcl-6 and CD10 was observed in 40.9% (9/22) nodal DLBCL and 41.4% (12/29) extranodal DLBCL. Low clinical stage (stage I and II) was more frequently observed in cases with co-expression of bcl-6 and CD10 (P < 0.05). (3) The rates of bcl-6 gene rearrangement in nodal DLBCL was 28.1% (9/32), with 27.3% (6/22) in paraffin-embedded tissues and 30.0% (3/10) in fresh tissues. There was no statistically significant difference found between the two groups (P > 0.05). Bcl-6 gene rearrangement was not found in all the 5 cases of RLH, and there was a significant difference between RLH and DLBCL (P < 0.05). CONCLUSIONS: The rate of bcl-6 protein expression is high in DLBCL cases, and the detection of bcl-6 and CD10 protein co-expression may help in the diagnosis and differential diagnosis of DLBCL. Those DLBCL cases with co-expression of bcl-6 and CD10 may also have a better prognostic implication. On the other hand, bcl-6 gene rearrangement can be identified by interphase FISH with dual color breakapart probe in both paraffin-embedded and fresh lymphoma tissues.
Assuntos
Rearranjo Gênico , Linfoma de Células B/genética , Linfoma Difuso de Grandes Células B/genética , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Hibridização in Situ Fluorescente , Linfoma de Células B/metabolismo , Linfoma de Células B/patologia , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neprilisina/metabolismo , Proteínas Proto-Oncogênicas c-bcl-6/genética , Pseudolinfoma/genéticaRESUMO
AIM: To investigate the significance of c-kit gene mutation in gastrointestinal stromal tumors (GIST). METHODS: Fifty two cases of GIST and 28 cases of other tumors were examined. DNA samples were extracted from paraffin sections and fresh blocks. Exons 11, 9 and 13 of the c-kit gene were amplified by PCR and sequenced. RESULTS: Mutations of exon 11 were found in 14 of 25 malignant GISTs (56%), mutations of exon 11 of the c-kit gene were revealed in 2 of 19 borderline GISTs (10.5%), and no mutation was found in benign tumors. The mutation rate showed significant difference (chi2=14.39, P<0.01) between malignant and benign GISTs. Most of mutations consisted of the in-frame deletion or replication from 3 to 48 bp in heterozygous and homozygous fashions, None of the mutations disrupted the downstream reading frame of the gene. Point mutations and frame deletions were most frequently observed at codons 550-560, but duplications were most concentrated at codons 570-585. No mutations of exons 9 and 13 were revealed in GISTs, Neither c-kit gene expression nor gene mutations were found in 3 leiomyomas, 8 leiomyosarcomas, 2 schwannomas, 2 malignant peripheral nerve sheath tumors, 2 intra-abdominal fibromatoses, 2 malignant fibrous histiocytomas and 9 adenocarcinomas. CONCLUSION: C-kit gene mutations occur preferentially in malignant GISTs and might be a clinically useful adjunct marker in the evaluation of GISTs and can help to differentiate GISTs from other mesenchymal tumors of gastrointestinal tract, such as smooth muscle tumors, schwannomas, etc.
Assuntos
Neoplasias Gastrointestinais/genética , Mutação , Proteínas Proto-Oncogênicas c-kit/genética , Células Estromais/fisiologia , Sequência de Aminoácidos , Análise Mutacional de DNA , Éxons , Humanos , Dados de Sequência Molecular , Proteínas Proto-Oncogênicas c-kit/metabolismoRESUMO
OBJECTIVE: To explore the clinicopathological, immunohistochemical and molecular genetic features of intra-abdomen extra-gastrointestinal stromal tumors (EGISTs) and their differential diagnosis. METHODS: Nine cases of EGISTs from the abdominal cavity or retroperitoneum which were previously diagnosed as leiomyoma, leiomyoblastoma, or leiomyosarcoma etc. by a panel of antibodies such as CD117, CD34, alpha-SMA, MSA, desmin, S-100, and PGP9.5 from which five cases were detected for c-kit gene mutation. RESULTS: The tumors occurred in 5 men and 4 women, the age ranged from 38 to 72 years (mean 61.7 years). Four cases arose from the mesentery, two from omentum, two from retroperitoneum and one located at the hilus of the spleen. The size of tumors ranged from 5 cm to 23 cm (mean 12.9 cm) in diameter and the tumor cell components varied: mainly spindle cells (seven cases), epithelioid cells (one case), mixed cells (one case). Tumors expressed CD117 (8/9), CD34 (5/9), alpha-SMA (3/9), MSA (4/9), desmin (0), S-100 protein (1/9) and PGP9.5 (1/9). Of the five cases examined for heterozygous deletion mutation of 11 exon of the c-kit gene two were found positive. Two borderline cases showed long-term survival of 8 years and 11 years, respectively. In seven malignant cases, two showed adverse outcome, one survived 4 years without recurrence, two were lost in follow up and two new cases were still being in followed. CONCLUSIONS: GIST-type stromal tumors can also occur in the abdomen, most cases were borderline or malignant, tumor coagulative necrosis, mitoses >or= 5 per 50 high-power fields and obvious nuclear atypia indicating malignancy. Differential diagnosis of EGIST including benign or malignant smooth muscle tumors, benign or malignant nerve sheath tumors etc.
Assuntos
Neoplasias Peritoneais/patologia , Neoplasias Retroperitoneais/patologia , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Leiomioma/patologia , Leiomiossarcoma/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/química , Neoplasias Peritoneais/genética , Proteínas Proto-Oncogênicas c-kit/genética , Neoplasias Retroperitoneais/química , Neoplasias Retroperitoneais/genéticaRESUMO
A simple, sensitive and convenient ion chromatography(IC) method was established for the simultaneous determination of twelve water-soluble inorganic anions(F- , Cl- , NO2(-), NO3(-), SO3(2-), SO4(2-) , PO4(3-)), and fifteen water-soluble organic ions(formate, acetate, MSA, oxalate, malonate, succinate, phthalates, etc.) in atmospheric aerosols. The linear concentrations ranged from 0.005 microg/m3 to 500 microg/m3 ( r = 0.999-0.9999). The relative standard deviation (RSD) were 0.43%-2.00% and the detection limits were from 2.7 ng/m3 to 88 ng/m3. The proposed method was successfully applied to the simultaneous determination of those inorganic ions and organic ions in PM2.5 of Beijing.