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1.
Cureus ; 16(6): e61571, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38962623

RESUMEN

A woman in her 60s with a past medical history of recurrent Helicobacter pylori (H. pylori) presented for surgical consultation after a colonoscopy revealed a mass in the rectum. Preoperative biopsy revealed mucosal excrescence with no dysplasia or malignant changes. The final pathology showed a solid, submucosal rectal mass that was positive for SOX10 and S100 on immunohistochemistry, supporting our diagnosis of Schwannoma. This case emphasizes the importance of considering schwannomas in the differential diagnosis of patients presenting with a rectal mass no matter how rare it may be.

2.
J Mol Biol ; 436(18): 168706, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39002715

RESUMEN

Copper nitrite reductases (CuNiRs) exhibit a strong pH dependence of their catalytic activity. Structural movies can be obtained by serially recording multiple structures (frames) from the same spot of a crystal using the MSOX serial crystallography approach. This method has been combined with on-line single crystal optical spectroscopy to capture the pH-dependent structural changes that accompany during turnover of CuNiRs from two Rhizobia species. The structural movies, initiated by the redox activation of a type-1 copper site (T1Cu) via X-ray generated photoelectrons, have been obtained for the substrate-free and substrate-bound states at low (high enzymatic activity) and high (low enzymatic activity) pH. At low pH, formation of the product nitric oxide (NO) is complete at the catalytic type-2 copper site (T2Cu) after a dose of 3 MGy (frame 5) with full bleaching of the T1Cu ligand-to-metal charge transfer (LMCT) 455 nm band (S(σ)Cys â†’ T1Cu2+) which in itself indicates the electronic route of proton-coupled electron transfer (PCET) from T1Cu to T2Cu. In contrast at high pH, the changes in optical spectra are relatively small and the formation of NO is only observed in later frames (frame 15 in Br2DNiR, 10 MGy), consistent with the loss of PCET required for catalysis. This is accompanied by decarboxylation of the catalytic AspCAT residue, with CO2 trapped in the catalytic pocket.


Asunto(s)
Cobre , Nitrito Reductasas , Nitrito Reductasas/química , Nitrito Reductasas/metabolismo , Concentración de Iones de Hidrógeno , Cobre/metabolismo , Cobre/química , Oxidación-Reducción , Cristalografía por Rayos X , Óxido Nítrico/metabolismo , Óxido Nítrico/química , Modelos Moleculares , Dominio Catalítico , Análisis Espectral/métodos , Conformación Proteica
3.
Cureus ; 16(4): e58342, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38756315

RESUMEN

A 72-year-old woman with a prior sigmoid resection for colon cancer underwent a right hemicolectomy after a colonoscopy revealed a mass in the hepatic flexure. A preoperative biopsy at colonoscopy showed tubulovillous dysplasia with high-grade neoplasm. The final specimen pathology revealed benign mucosal elements with mucin pools consistent with colitis cystica profunda (CCP). CCP is a benign lesion; no further treatment was necessary after resection. To our knowledge, this is the first reported case of CCP in the right colon, presenting atypically in the hepatic flexure. This case report brings to light the difficulty and importance of making an accurate diagnosis of CCP.

4.
Cureus ; 16(3): e56931, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38665716

RESUMEN

A woman in her 20s with a past medical history of surgical debulking of a right neck mass presented to the hospital for persistent and worsening right shoulder pain. The shoulder pain was associated with trismus and back and neck pain. A CT scan of the neck with contrast revealed post-surgical changes with increased heterotopic ossification throughout the surgical site extending to the supraclavicular soft tissues and the left sternocleidomastoid muscle, suggesting muscle ossification. A biopsy was performed, and the patient was diagnosed with myositis ossificans (MO). Initial treatment began with the administration of steroids and analgesics. She was scheduled for a follow-up with orthopedics, rheumatology, and genetics, but she was lost for follow-up. MO is a very rare medical condition usually associated with trauma, and in our patient, the symptoms started after a chiropractic adjustment.

5.
Cureus ; 16(2): e55077, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38550497

RESUMEN

Ewing sarcoma is one of the most common primary bone tumors arising from neuroectodermal cells mainly presenting in the younger population. Instances of this highly malignant tumor manifesting outside of the bone and outside of the typical age range create an unfamiliar clinical scenario. In this report, we present a rare extraskeletal Ewing sarcoma in a 42-year-old woman with a subcutaneous soft tissue mass in the posterior chest displaying a positive EWSR1 gene rearrangement via fluorescence in situ hybridization. The patient is currently on a chemotherapy regimen showing favorable response to the tumor size despite additional complications. This overall presentation of Ewing sarcoma allows further understanding of the malignancy and fosters better care for future cases.

6.
Curr Pharm Des ; 2023 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-37218201

RESUMEN

Scintigraphic imaging was satisfactory in animal experiments, i.e., in the radioimmunodetection with 125J anti-tissue polypeptide antigen monoclonal antibodies and implanted HELA cell carcinomas. Unlabeled anti-mouse antibodies (AMAB), in a surplus of 40:1, 200:1 and 4000:1 compared to the radioactive antibody, were administered five days after administering the 125I anti-TPA antibody (RAAB). In immunoscintigraphies, radioactivity accumulated in the liver immediately after administering the secondary antibody, and the tumor's imaging worsened. It can be expected that imunoscintigraphic imaging might improve when radioimmunodetection is re-performed after the formation of human anti-mouse antibodies (AMAB) and when the ratio of the primary to the secondary antibody is nearly equivalent because, in this ratio, the formation of immune complexes might be accelerated. It is possible to measure the quantity of formed anti-mouse antibodies (AMAB) with immunography measurements. A second administration of diagnostic or therapeutic monoclonal antibodies might lead to the formation of immune complexes if the quantities of the monoclonal antibodies and the anti-mouse antibodies have an equivalent ratio. A second performance of the radioimmunodetection four to eight weeks after the first radioimmunodetection can achieve better tumor imaging because human anti-mouse antibodies (AMAB) can be formed. Immune complexes of the radioactive antibody and the human anti-mouse antibody (AMAB) can be formed to concentrate radioactivity in the tumor.

9.
Protein Sci ; 30(11): 2310-2323, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34562300

RESUMEN

We report the crystal structure of the copper-containing nitrite reductase (NirK) from the Gram-negative bacterium Sinorhizobium meliloti 2011 (Sm), together with complex structural alignment and docking studies with both non-cognate and the physiologically related pseudoazurins, SmPaz1 and SmPaz2, respectively. S. meliloti is a rhizobacterium used for the formulation of Medicago sativa bionoculants, and SmNirK plays a key role in this symbiosis through the denitrification pathway. The structure of SmNirK, solved at a resolution of 2.5 Å, showed a striking resemblance with the overall structure of the well-known Class I NirKs composed of two Greek key ß-barrel domains. The activity of SmNirK is ~12% of the activity reported for classical NirKs, which could be attributed to several factors such as subtle structural differences in the secondary proton channel, solvent accessibility of the substrate channel, and that the denitrifying activity has to be finely regulated within the endosymbiont. In vitro kinetics performed in homogenous and heterogeneous media showed that both SmPaz1 and SmPaz2, which are coded in different regions of the genome, donate electrons to SmNirK with similar performance. Even though the energetics of the interprotein electron transfer (ET) process is not favorable with either electron donors, adduct formation mediated by conserved residues allows minimizing the distance between the copper centers involved in the interprotein ET process.


Asunto(s)
Azurina/química , Proteínas Bacterianas/química , Nitrito Reductasas/química , Sinorhizobium meliloti/enzimología , Cristalografía por Rayos X , Dominios Proteicos
10.
Curr Pharm Des ; 27(30): 3281-3292, 2021 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-33588721

RESUMEN

BACKGROUND: Schizophrenia is a chronic mental illness that in 80% of cases has a genetic etiology. In the last years, 260 risk genes with a predisposition to schizophrenia have been discovered and correlations between risk genes and the therapeutic efficacy of an antipsychotic treatment/pharmacotherapy resistance have been reported. OBJECTIVE: The objective of this review is to update the main risk genes involved in schizophrenia and to establish an association between the single nucleotide polymorphisms (SNPs) of these genes and pharmacotherapy resistance/efficacy of a determined antipsychotic treatment. Besides, neural networks in the brain centers involved in schizophrenia will be updated to point out the altered functions of classical neurotransmitters and neuropeptides due to risk genes. METHODS: In schizophrenia, important risk genes, such as catechol-O-methyl transferase (COMT), monoamine oxidase (MAO A/B), glutamic acid decarboxylase 67 (GAD 67), dysbindin-1 and neuregulin-1 will be mentioned. To describe the function of these risk genes, neural networks in the ventral tegmental area, hippocampus and prefrontal cortex will also be developed. RESULTS: An association between the SNPs of some risk genes and the efficacy of an antipsychotic treatment is reported: SNPs such as rs165599 (COMT gene), rs1801028 (D2 receptor gene) and rsSer9Gly (D3 receptor gene) are associated with a better antipsychotic treatment efficacy (e.g., treatment of negative schizophrenic symptoms with risperidone). The rs4680 SNP (COMT and D2 receptor genes) is associated with antipsychoticinduced dopamine hypersensitivity and pharmacotherapy resistance. The function of risk genes is described: COMT and MAO A/B genes, with reduced activity in the corresponding enzymes, are associated with a decrease in dopamine degradation and hence dopamine hyperactivity occurred via D2 receptors. The GAD 67 risk gene is linked with GABAergic dysfunction and consequently GABAergic neurons weakly presynaptically inhibit D2 dopaminergic neurons. The D-amino acid oxidase activator (DAOA) risk gene is connected with glutamatergic dysfunction via NMDA receptors. Glutamatergic neurons might exert a weak presynaptic inhibition upon 5- HT2A serotonergic neurons located in the ventral tegmental area and hippocampus. Neural networks in the latter two regions and in the prefrontal cortex are updated. CONCLUSION: It is important to examine the SNPs of the risk genes involved in schizophrenia to establish a correlation between these SNPs and the efficacy of a determined antipsychotic drug. In the future, after examining these SNPs, it might be possible to choose the most appropriate antipsychotic drug. Thus, schizophrenic patients with a good response to a determined antipsychotic treatment and patients with resistance to this treatment could be well differentiated.


Asunto(s)
Antipsicóticos , Esquizofrenia , Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Catecol O-Metiltransferasa/genética , Catecol O-Metiltransferasa/uso terapéutico , Genotipo , Humanos , Péptidos y Proteínas de Señalización Intracelular/uso terapéutico , Polimorfismo de Nucleótido Simple , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/genética
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