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1.
J Neurosurg Case Lessons ; 7(10)2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38437676

RESUMEN

BACKGROUND: Bifocal germ cell tumors, with primarily identical tissue composition, occur concurrently in the neurohypophyseal and pineal regions. OBSERVATIONS: A 16-year-old male patient exhibited increased intracranial pressure symptoms, with concurrent tumors in the pineal and neurohypophyseal regions, causing obstructive hydrocephalus. His serum human chorionic gonadotropin level was elevated, measuring 506.6 mIU/mL. Upon gross endoscopic examination, the pineal tumor appeared white, whereas the neurohypophyseal tumor appeared red and hemorrhagic. Because of the limited sample size of the latter, a frozen section biopsy was feasible only for the pineal lesion, which indicated the presence of a germinoma. Subsequently, carboplatin and etoposide were administered, resulting in the reduction of the pineal tumor, but no effect was observed in the neurohypophyseal tumor. Histopathological analysis confirmed the pineal lesion as a germinoma, whereas the neurohypophyseal lesion was an embryonal carcinoma. Thus, the treatment was altered to ifosfamide, carboplatin, and etoposide (ICE), leading to a response in both tumors. The patient underwent three additional cycles of ICE therapy and high-dose chemotherapy, followed by whole craniospinal irradiation, achieving complete remission. LESSONS: Although most bifocal germ cell tumors share the same histological tissue, occasional differences may arise, necessitating separate biopsies for accurate assessment.

2.
Comp Immunol Microbiol Infect Dis ; 73: 101540, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32911379

RESUMEN

Rhodococcus equi causes suppurative pneumonia in foals aged 1-3 months; moreover, it has emerged as a pathogenic cause of zoonotic diseases. After the initial report of the ruminant-pathogenic factor VapN encoded by the novel virulence plasmid pVAPN, several reports have described ruminant infections caused by vapN-harboring R. equi. Herein, we conducted a serological epidemiological surveillance in goats at a breeding farm (Farm A) and characterized the vapN-harboring R. equi isolates from this farm. First, we established a simple screening enzyme-linked immunosorbent assay (ELISA) using recombinant glutathione S-transferase-tagged VapN as an immobilized antigen. This method revealed that the VapN antibody titers were elevated in 12 of 42 goats. Subsequently, we attempted to isolate R. equi from the goat feces and soil of Farm A. choE+/vapN+R. equi was isolated from the feces of Goat No. 27 and a soil sample near the shed. The pulsed-field gel electrophoresis (PFGE) patterns of five vapN-harboring R. equi strains isolated from Farm A in 2013 and 2019 were investigated and found to be the same except for the strain (OKI2019F1). However, no difference was observed in VapN expression and growth in macrophages among these vapN-harboring R. equi isolates. Our results revealed that some goats had histories of vapN-harboring R. equi infections, and two genomic types of vapN-harboring R. equi were found in isolates from Farm A. Ruminant-specific (pVAPN-carrying) R. equi might be an unrecognized pathogen in Japan and further studies are required to determine its prevalence and distribution.


Asunto(s)
Infecciones por Actinomycetales/veterinaria , Enfermedades de las Cabras/epidemiología , Rhodococcus equi/inmunología , Rhodococcus/inmunología , Infecciones por Actinomycetales/epidemiología , Animales , Anticuerpos Antibacterianos/sangre , Bovinos , Enfermedades de los Bovinos/microbiología , Femenino , Enfermedades de las Cabras/microbiología , Cabras , Japón , Rhodococcus equi/genética
3.
Arch Virol ; 154(5): 775-81, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19343474

RESUMEN

Feline infectious peritonitis (FIP) is a feline coronavirus (FCoV)-induced fatal disease of domestic and wild cats. The infiltration of neutrophils into granulomatous lesions is unusual for a viral disease, but it is a typical finding of FIP. This study aimed to investigate the reason for the lesions containing neutrophils in cats with FIP. Neutrophils of cats with FIP were cultured, and changes in the cell survival rate were assessed. In addition, the presence or absence of neutrophil survival factors was investigated in specimens collected from cats with FIP. Furthermore, it was investigated whether macrophages, one of the target cells of FIPV infection, produce neutrophil survival factors (TNF-alpha, GM-CSF, and G-CSF). We showed that virus-infected macrophages overproduce neutrophil survival factors, and these factors act on neutrophils and up-regulate their survival. These observations suggest that sustained production of neutrophil survival factors by macrophages during FCoV infection is sufficient for neutrophil survival and contributes to development of granulomatous lesions.


Asunto(s)
Coronavirus Felino/inmunología , Peritonitis Infecciosa Felina/inmunología , Macrófagos/inmunología , Neutrófilos/inmunología , Animales , Gatos , Células Cultivadas , Coronavirus Felino/patogenicidad , Expresión Génica , Factor Estimulante de Colonias de Granulocitos/inmunología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Granuloma/inmunología , Granuloma/virología , Macrófagos/metabolismo , Macrófagos/virología , Neutrófilos/virología , ARN Mensajero/metabolismo , Factor de Necrosis Tumoral alfa/inmunología
4.
Bioorg Med Chem Lett ; 18(17): 4849-52, 2008 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-18701284

RESUMEN

We describe herein the synthesis and biological evaluation of a series of novel cephalosporins with potent activity against Pseudomonas aeruginosa. Introduction of various amino groups to the 4-position of a 3-amino-2-methylpyrazole cephalosporin 3-side chain resulted in enhanced MIC values against multiple Pseudomonas aeruginosa strains and ultimately led to the discovery of FR264205 (15) with excellent anti-bacterial activity and weak convulsion effect by direct intracerebroventricular injection assay.


Asunto(s)
Antibacterianos/síntesis química , Antibacterianos/farmacología , Cefalosporinas/síntesis química , Cefalosporinas/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Animales , Antibacterianos/efectos adversos , Antibacterianos/química , Ceftazidima/farmacología , Cefalosporinas/efectos adversos , Cefalosporinas/química , Diseño de Fármacos , Evaluación Preclínica de Medicamentos , Ratones , Pseudomonas aeruginosa/crecimiento & desarrollo , Convulsiones/inducido químicamente , Relación Estructura-Actividad
5.
Bioorg Med Chem ; 16(5): 2261-75, 2008 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-18082409

RESUMEN

AmpC beta-lactamase is one of the leading causes of Pseudomonas aeruginosa (P. aeruginosa) resistance to cephalosporins. FR259647 is a cephalosporin having a novel pyrazolium substituent at the 3-position and exhibits excellent activity (MIC=1 microg/mL) against the AmpC beta-lactamase overproducing P. aeruginosa FP1380 strain in comparison with the third-generation cephalosporins FK518 [Abstracts of Papers, 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, Atlanta, GA, October 21-24, 1990, Abs. 454; Abstracts of Papers, 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, Atlanta, GA, October 21-24, 1990, Abs. 455; Abstracts of Papers, 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, Atlanta, GA, October 21-24, 1990, Abs. 456; Abstracts of Papers, 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, Atlanta, GA, October 21-24, 1990, Abs. 457] (MIC=16 microg/mL) and ceftazidime (CAZ) (MIC=128 microg/mL). The stability of FR259647 and FK518 to AmpC beta-lactamase was evaluated using MIC assays against both the P. aeruginosa PAO1 strain and a PAO1 mutant strain overproducing AmpC beta-lactamase as a differential assay, which indicates that the main difference derives from their stability to AmpC beta-lactamase. A structural analysis using computer simulations indicated that the difference in stability may be due to steric hindrance of the 3-position substituents causing differential affinity. This steric hindrance may disturb entry of the cephalosporins into the binding pocket. We predicted the possibility of inhibition of entry as a potential means of enhancing stability by conformational analysis. In order to validate this speculation, novel FR259647 derivatives 4-9 were designed, calculated, synthesized, and evaluated. As a result, we demonstrated that their probability of entry correlated with the MIC ratio of the mutant strain to the parent strain and supports the validity of our model.


Asunto(s)
Proteínas Bacterianas/antagonistas & inhibidores , Proteínas Bacterianas/metabolismo , Cefalosporinas/química , Cefalosporinas/farmacología , Inhibidores de beta-Lactamasas , beta-Lactamasas/metabolismo , Proteínas Bacterianas/química , Estabilidad de Enzimas/efectos de los fármacos , Imagenología Tridimensional , Modelos Moleculares , Estructura Molecular , Unión Proteica , Pseudomonas aeruginosa/efectos de los fármacos , Resistencia betalactámica/efectos de los fármacos , beta-Lactamasas/química
6.
Virology ; 364(1): 64-72, 2007 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-17382365

RESUMEN

The pathogenicity of feline infectious peritonitis virus (FIPV) is known to depend on macrophage tropism, and this macrophage infection is enhanced by mediation via anti-S antibody (antibody-dependent enhancement, ADE). In this study, we found that TNF-alpha production was increased with viral replication in macrophages inoculated with a mixture of FIPV and anti-S antibody, and demonstrated that this culture supernatant had feline PBMC apoptosis-inducing activity. We also demonstrated that the expression level of the FIPV virus receptor, feline aminopeptidase N (fAPN), was increased in macrophages of FIP cats. For upregulation of TNF-alpha and fAPN in macrophages, viral replication in macrophages is necessary, and their expressions were increased by ADE of FIPV infection. It was demonstrated that a heat-resistant fAPN-inducing factor was present in the culture supernatant of FIPV-infected macrophages, and this factor was TNF-alpha: fAPN expression was upregulated in recombinant feline TNF-alpha-treated macrophages, and FIPV infectivity was increased in these macrophages. These findings suggested that FIPV replication in macrophages increases TNF-alpha production in macrophages, and the produced TNF-alpha acts and upregulates fAPN expression, increasing FIPV sensitivity.


Asunto(s)
Antígenos CD13/metabolismo , Coronavirus Felino/patogenicidad , Macrófagos/inmunología , Macrófagos/virología , Receptores Virales/metabolismo , Factor de Necrosis Tumoral alfa/biosíntesis , Animales , Apoptosis , Secuencia de Bases , Gatos , Células Cultivadas , Coronavirus Felino/genética , Coronavirus Felino/fisiología , Medios de Cultivo Condicionados , Cartilla de ADN/genética , Peritonitis Infecciosa Felina/genética , Peritonitis Infecciosa Felina/inmunología , Peritonitis Infecciosa Felina/metabolismo , Peritonitis Infecciosa Felina/virología , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/patología , Macrófagos/efectos de los fármacos , Macrófagos/enzimología , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Viral/genética , ARN Viral/metabolismo , Receptores Virales/genética , Proteínas Recombinantes/farmacología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/farmacología , Regulación hacia Arriba , Replicación Viral/efectos de los fármacos
7.
J Org Chem ; 67(4): 1359-67, 2002 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-11846687

RESUMEN

A general and efficient synthesis of allenes using a palladium(0)/diethylzinc system is described. Treatment of mesylates or trichloroacetates of (E)- or (Z)-2-bromoalk-2-en-1-ols with diethylzinc in the presence of a catalytic amount of palladium(0) affords allenes bearing an aminoalkyl, alkyl, or aryl substituent(s) in good to high yields. No transfer of chirality from the stereogenic center carrying the mesyloxy group to the allene was observed.

9.
J Org Chem ; 63(20): 7053-7061, 1998 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-11672331

RESUMEN

Although reactions of 2,3-trans-N-arylsulfonyl-3-alkyl-2-alkenylaziridines with organocopper reagents give a mixture of two or three products, the corresponding 2,3-cis-isomers provide a highly efficient route to synthetically important nonracemic (E)-allylamines. It is also found that the reaction proceeds via the well-known anti-S(N)2' pathway.

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