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1.
Clin Exp Immunol ; 200(3): 302-309, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32155293

RESUMEN

Stroke can be a cause of death, while in non-fatal cases it is a common cause of various disabilities resulting from associated brain damage. However, whether a specific periodontal pathogen is associated with increased risk of unfavorable outcome after stroke remains unknown. We examined risk factors for unfavorable outcome following stroke occurrence, including serum antibody titers to periodontal pathogens. The enrolled cohort included 534 patients who had experienced an acute stroke, who were divided into favorable (n = 337) and unfavorable (n = 197) outcome groups according to modified ranking scale (mRS) score determined at 3 months after onset (favorable = score 0 or 1; unfavorable = score 2-6). The associations of risk factors with unfavorable outcome, including serum titers of IgG antibodies to 16 periodontal pathogens, were examined. Logistic regression analysis showed that the initial National Institutes of Health stroke scale score [odds ratio (OR) = 1·24, 95% confidence interval (CI) = 1·18-1·31, P < 0·001] and C-reactive protein (OR = 1·29, 95% CI = 1·10-1·51, P = 0·002) were independently associated with unfavorable outcome after stroke. Following adjustment with those, detection of the antibody for Fusobacterium nucleatum ATCC 10953 in serum remained an independent predictor of unfavorable outcome (OR = 3·12, 95% CI = 1·55-6·29, P = 0·002). Determination of the antibody titer to F. nucleatum ATCC 10953 in serum may be useful as a predictor of unfavorable outcome after stroke.


Asunto(s)
Anticuerpos Antibacterianos/sangre , Fusobacterium nucleatum/metabolismo , Inmunoglobulina G/sangre , Accidente Cerebrovascular/sangre , Anciano , Anciano de 80 o más Años , Anticuerpos Antibacterianos/inmunología , Femenino , Fusobacterium nucleatum/inmunología , Humanos , Inmunoglobulina G/inmunología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Factores de Riesgo , Accidente Cerebrovascular/inmunología
2.
AIDS Care ; 32(7): 829-834, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-31426660

RESUMEN

The aim of the study was to evaluate the oral environment and the taste function of Japanese HIV-infected patients treated with antiretroviral therapy. Their median age of 73 patients taking anti-HIV drugs was 46 years. The median period of taking anti-HIV drugs was 30 months. The oral condition was evaluated by measurement of oral moisture, amount of saliva secretion, the number of oral bacteria, presence of oral candida, a taste test, and the number of missing teeth. The levels of oral moisture and secreted saliva were significantly lower in the HIV-infected group than in the healthy volunteer (control) group. The HIV-infected group showed a more robust decrease in taste sensation than the control group. The number of missing teeth was significantly higher in the HIV-infected group than in the control group. Furthermore, all of the evaluated oral conditions were worse in the HIV-infected patients whose CD4+ T lymphocyte counts were less than 500/mm3 than in the control group. It became clear that the patients taking anti-HIV drugs, especially the CD4+ count < 500/mm3 group, had a deteriorated oral environment and dysgeusia, suggesting that the management of oral hygiene is necessary to maintain oral health, which leads to systemic health.


Asunto(s)
Infecciones por VIH , Gusto , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Infecciones por VIH/tratamiento farmacológico , Humanos , Japón/epidemiología , Persona de Mediana Edad
3.
Oral Dis ; 21(5): 626-33, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25703825

RESUMEN

OBJECTIVE: A large number of individuals have halitosis. The total amount of volatile sulfur compounds, which are the main cause of halitosis, has been correlated with periodontitis following bacterial infection. In this study, Porphyromonas gingivalis (Pg), a major periodontopathogenic bacterium, was isolated from patients with halitosis by the amplification of 16S rRNA, and the ability of isolated Pg to produce methyl mercaptan (CH3 SH) was determined to clarify the relationship between halitosis and Pg infection. MATERIALS AND METHODS: CH3 SH concentrations were measured in patients using Oral Chroma. The production of CH3 SH by Pg standard and clinical strains was also measured in vitro. Real-time PCR was performed to compare the expression of mgl mRNA (which encoded l-methionine-a-deamino-g-mercaptomethane-lyase) among the Pg strains. The production of CH3 SH and the expression of mgl mRNA were also determined to assess the effects of oriental medicine. RESULTS: The production of CH3 SH and the expression of mgl mRNA strongly correlated with each other in the presence of l-methionine. The expression of mgl mRNA by Pg W83 was strongly inhibited by magnoliaceae. CONCLUSION: The production of CH3 SH was correlated with the expression of mgl. Furthermore, the oriental medicine, magnoliaceae, may represent a potential treatment for halitosis.


Asunto(s)
Halitosis/microbiología , Porphyromonas gingivalis/genética , Porphyromonas gingivalis/metabolismo , ARN Mensajero/biosíntesis , Compuestos de Sulfhidrilo/metabolismo , Adulto , Anciano , Antiinfecciosos/farmacología , Proteínas Bacterianas/efectos de los fármacos , Infecciones por Bacteroidaceae/metabolismo , Infecciones por Bacteroidaceae/microbiología , Medicamentos Herbarios Chinos/farmacología , Femenino , Humanos , Magnoliaceae , Masculino , Metionina/metabolismo , Metionina/farmacología , Persona de Mediana Edad , Periodontitis/metabolismo , Periodontitis/microbiología , Porphyromonas gingivalis/aislamiento & purificación , ARN Mensajero/efectos de los fármacos , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Adulto Joven
4.
Clin Genet ; 82(5): 425-32, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22575033

RESUMEN

Auditory neuropathy is a hearing disorder characterized by normal outer hair cell function and abnormal neural conduction of the auditory pathway. Aetiology and clinical presentation of congenital or early-onset auditory neuropathy are heterogeneous, and their correlations are not well understood. Genetic backgrounds and associated phenotypes of congenital or early-onset auditory neuropathy were investigated by systematically screening a cohort of 23 patients from unrelated Japanese families. Of the 23 patients, 13 (56.5%) had biallelic mutations in OTOF, whereas little or no association was detected with GJB2 or PJVK, respectively. Nine different mutations of OTOF were detected, and seven of them were novel. p.R1939Q, which was previously reported in one family in the United States, was found in 13 of the 23 patients (56.5%), and a founder effect was determined for this mutation. p.R1939Q homozygotes and compound heterozygotes of p.R1939Q and truncating mutations or a putative splice site mutation presented with stable, and severe-to-profound hearing loss with a flat or gently sloping audiogram, whereas patients who had non-truncating mutations except for p.R1939Q presented with moderate hearing loss with a steeply sloping, gently sloping or flat audiogram, or temperature-sensitive auditory neuropathy. These results support the clinical significance of comprehensive mutation screening for auditory neuropathy.


Asunto(s)
Efecto Fundador , Estudios de Asociación Genética/métodos , Pérdida Auditiva Central/epidemiología , Pérdida Auditiva Central/genética , Proteínas de la Membrana/genética , Adulto , Secuencia de Aminoácidos , Pueblo Asiatico/genética , Niño , Preescolar , Conexina 26 , Conexinas/genética , Conexinas/metabolismo , Femenino , Pruebas Genéticas , Genotipo , Heterocigoto , Homocigoto , Humanos , Lactante , Masculino , Datos de Secuencia Molecular , Mutación , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Fenotipo , Prevalencia , Conformación Proteica , Análisis de Secuencia de ADN
5.
Transpl Infect Dis ; 14(4): E1-6, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22487245

RESUMEN

Linezolid (LZD) is the first oxazolidinone antibiotic that is effective against drug-resistant gram-positive organisms. Hematological toxicities such as thrombocytopenia, anemia, and leukocytopenia are common in LZD therapy. However, LZD-induced pure red cell aplasia (PRCA) is very rare. A 56-year-old man with myelodysplastic syndrome underwent allogeneic bone marrow transplantation from a human leukocyte antigen-matched and ABO blood type-matched unrelated male donor. He had bacteremia caused by Staphylococcus epidermidis after engraftment of neutrophils and red blood cells. We first administered vancomycin, but then changed to intravenous LZD because of kidney damage. Two weeks after LZD therapy, the patient's hemoglobin and reticulocyte levels were 6.8 g/dL and 0.3%, respectively. Bone marrow examination revealed red blood cell aplasia (myeloid/erythroid ratio was 402). The patient showed rapid recovery of normal erythropoiesis within 2 weeks of LZD cessation. It is important to be aware of the hematological effects associated with LZD in the setting of stem cell transplantation,particularly for those with pre-existing myelosuppression, renal insufficiency, and those receiving concomitant drugs that produce bone marrow suppression. We advocate that a reticulocyte count be performed periodically for detecting bone marrow suppression, including PRCA, during LZD therapy.


Asunto(s)
Acetamidas/efectos adversos , Antiinfecciosos/efectos adversos , Bacteriemia/tratamiento farmacológico , Oxazolidinonas/efectos adversos , Aplasia Pura de Células Rojas/inducido químicamente , Staphylococcus epidermidis/efectos de los fármacos , Trasplante de Células Madre/efectos adversos , Trasplante Homólogo/efectos adversos , Acetamidas/uso terapéutico , Bacteriemia/microbiología , Humanos , Linezolid , Masculino , Persona de Mediana Edad , Oxazolidinonas/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología
6.
Kyobu Geka ; 64(7): 561-5, 2011 Jul.
Artículo en Japonés | MEDLINE | ID: mdl-21766708

RESUMEN

We report the graft replacement for surgical repair of coarctation of the aorta (CoA) in 2 men, aged 19 and 30 years old, respectively. In both patients, the pressure gradients were higher than 20 mmHg across the coarctaion by cathetherization, and higher than 30 mmHg between the upper and lower limbs. The graft replacement of the coarctated aorta was performed under cardiopulmonary bypass. Postoperatively, the pressure gradients between the upper and lower limbs dropped below 20 mmHg in both cases. Since about 50% of surgically untreated patients with this disease may be expected to die before 30 years of age, repair of CoA in adults should be performed as soon as possible.


Asunto(s)
Coartación Aórtica/cirugía , Prótesis Vascular , Adulto , Puente Cardiopulmonar , Humanos , Masculino
7.
Curr HIV Res ; 18(6): 475-479, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32753017

RESUMEN

BACKGROUND: Dental professionals have so many opportunities to use injection needles and sharp instruments during dental treatment that they face an increased risk of needlestick injuries. This retrospective study reports the utilization and clinical outcomes of occupational post-exposure prophylaxis (PEP) with anti-retroviral agents after being potentially exposed to HIV at the dental departments of Hiroshima University Hospital. OBJECTIVE: This study reports the utilization and clinical outcomes of occupational post-exposure prophylaxis (PEP) with antiretroviral agents after being potentially exposed to HIV at dental departments of Hiroshima University Hospital. METHODS: Data on the clinical status of HIV-infected source patients and information on HIV-exposed dental professionals from 2007 to 2018 were collected. RESULTS: Five dentists with an average experience of 5.6 years (1-15 years) were exposed. The averaged CD4-positive cell number and HIV-RNA load were 1176 (768-1898) /µl and less than 20 copies/ml, respectively, in all the patients. Two of the five HIV exposed dentists received PEP. Three months after the exposures, all of their results were negative in HIV antibody/antigen tests. CONCLUSION: ; These data might support the concept of "undetectable equals untransmittable", although HIV exposure in this study was not through sexual transmission.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Antirretrovirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Lesiones por Pinchazo de Aguja/tratamiento farmacológico , Exposición Profesional/prevención & control , Profilaxis Posexposición/métodos , Adulto , Clínicas Odontológicas/estadística & datos numéricos , Odontólogos/estadística & datos numéricos , Femenino , Hospitales Universitarios/estadística & datos numéricos , Humanos , Japón , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo
8.
In Vitro Cell Dev Biol Anim ; 56(3): 222-233, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32185608

RESUMEN

Heparin-binding protein 17/fibroblast growth factor-binding protein-1 (HBp17/FGFBP-1) was purified from A431 cell-conditioned media based on its capacity to bind to fibroblast growth factor 1 and 2 (FGF-1 and FGF-2). HBp17/FGFBP-1 has been observed to induce the tumorigenic potential of epithelial cells and is highly expressed in oral cancer cell lines and tissues. HBp17/FGFBP-1 is also recognized as a pro-angiogenic molecule as a consequence of its interaction with FGF-2. We have previously reported that Eldecalcitol (ED-71), an analog of 1α,25(OH)2D3, downregulated the expression of HBp17/FGFBP-1 and inhibited the proliferation of squamous cell carcinoma (SCC) cells in vitro and in vivo through NF-κb inhibition. To explore the possibility of microRNA (miRNA) control of HBp17/FGFBP-1, we analyzed exosomal miRNAs from medium conditioned by A431 cells treated with ED-71. Microarray analysis revealed that 12 exosomal miRNAs were upregulated in ED-71-treated A431 cells. Among them, miR-6887-5p was identified to have a predicted mRNA target matching the 3' untranslated region (3'-UTR) of HBp17/FGFBP-1. The 3'-UTR of HBp17/FGFBP-1 was confirmed to be a direct target of miR-6887-5p in SCC/OSCC cells, as assessed with a luciferase reporter assay. Functional assessment revealed that overexpression of miR-6887-5p in SCC/OSCC cells inhibited cell proliferation and colony formation in vitro, and inhibited tumor growth in vivo compared with control. In conclusion, our present study supports a novel anti-cancer mechanism involving the regulation of HBp17/FGFBP-1 function by exosomal miR-6887-5p in SCC/OSCC cells, which has potential utility as a miRNA-based cancer therapy.


Asunto(s)
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Exosomas/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , MicroARNs/genética , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Vitamina D/análogos & derivados , Animales , Secuencia de Bases , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Medios de Cultivo Condicionados/farmacología , Exosomas/efectos de los fármacos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/genética , Vitamina D/farmacología
9.
J Cell Biol ; 150(6): 1507-13, 2000 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-10995454

RESUMEN

Autophagy is a membrane trafficking to vacuole/lysosome induced by nutrient starvation. In Saccharomyces cerevisiae, Tor protein, a phosphatidylinositol kinase-related kinase, is involved in the repression of autophagy induction by a largely unknown mechanism. Here, we show that the protein kinase activity of Apg1 is enhanced by starvation or rapamycin treatment. In addition, we have also found that Apg13, which binds to and activates Apg1, is hyperphosphorylated in a Tor-dependent manner, reducing its affinity to Apg1. This Apg1-Apg13 association is required for autophagy, but not for the cytoplasm-to-vacuole targeting (Cvt) pathway, another vesicular transport mechanism in which factors essential for autophagy (Apg proteins) are also employed under vegetative growth conditions. Finally, other Apg1-associating proteins, such as Apg17 and Cvt9, are shown to function specifically in autophagy or the Cvt pathway, respectively, suggesting that the Apg1 complex plays an important role in switching between two distinct vesicular transport systems in a nutrient-dependent manner.


Asunto(s)
Autofagia/fisiología , Proteínas de Drosophila , Proteínas de Choque Térmico/metabolismo , Proteínas Quinasas , Proteínas Tirosina Quinasas Receptoras/metabolismo , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/enzimología , Proteínas Adaptadoras Transductoras de Señales , Anticuerpos/farmacología , Antifúngicos/farmacología , Autofagia/efectos de los fármacos , Proteínas Relacionadas con la Autofagia , Citoplasma/enzimología , Proteínas Fúngicas/metabolismo , Regulación Fúngica de la Expresión Génica , Proteínas de Choque Térmico/genética , Mutagénesis/fisiología , Fosfoproteínas/análisis , Fosfoproteínas/inmunología , Fosforilación , Proteínas Serina-Treonina Quinasas/análisis , Proteínas Serina-Treonina Quinasas/inmunología , Proteínas Tirosina Quinasas Receptoras/genética , Saccharomyces cerevisiae/citología , Transducción de Señal/fisiología , Sirolimus/farmacología , Inanición , Vacuolas/enzimología
10.
Science ; 293(5527): 111-5, 2001 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-11441185

RESUMEN

In the visual system, the establishment of the anteroposterior and dorsoventral axes in the retina and tectum during development is important for topographic retinotectal projection. We identified chick Ventroptin, an antagonist of bone morphogenetic protein 4 (BMP-4), which is mainly expressed in the ventral retina, not only with a ventral high-dorsal low gradient but also with a nasal high-temporal low gradient at later stages. Misexpression of Ventroptin altered expression patterns of several topographic genes in the retina and projection of the retinal axons to the tectum along both axes. Thus, the topographic retinotectal projection appears to be specified by the double-gradient molecule Ventroptin along the two axes.


Asunto(s)
Proteínas Morfogenéticas Óseas/antagonistas & inhibidores , Proteínas del Ojo/metabolismo , Regulación del Desarrollo de la Expresión Génica , Morfogénesis , Retina/embriología , Retina/metabolismo , Empalme Alternativo , Secuencia de Aminoácidos , Animales , Proteína Morfogenética Ósea 4 , Proteínas Morfogenéticas Óseas/genética , Proteínas Morfogenéticas Óseas/metabolismo , Embrión de Pollo , Clonación Molecular , Electroporación , Embrión no Mamífero/citología , Embrión no Mamífero/metabolismo , Proteínas del Ojo/química , Proteínas del Ojo/genética , Biblioteca de Genes , Humanos , Hibridación in Situ , Ratones , Microinyecciones , Datos de Secuencia Molecular , Proteínas del Tejido Nervioso , Pruebas de Precipitina , Unión Proteica , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , ARN Mensajero/análisis , ARN Mensajero/genética , Alineación de Secuencia , Resonancia por Plasmón de Superficie , Proteínas de Xenopus , Xenopus laevis/embriología , Xenopus laevis/metabolismo
11.
Kyobu Geka ; 62(12): 1032-4, 2009 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-19894564

RESUMEN

We report 6 cases of spontaneous pneumomediastinum. It is defined not to have clear etiology such as trauma, and is comparatively rare disease developing suddenly. Our patients complained of chest or neck pain, dyspnea and pain when swallowing. They were 3 men and 3 women, who were young and did not have causal disease. Chest X-ray films and computed tomography (CT) scans revealed pneumomediastinum. All of them were treated conservatively and recovered completely within 10 days hospitalization. Spontaneous pneumomediastinum is uncommon and usually benign. Most patients require only conservative treatment. However, since it possibly develops tension pneumothorax, pneumothorax, or mediastinitis, careful observation is recommended never to overlook life-threatening condition. In addition, it is important to distinguish from Boerhaave syndrome, tracheal trauma and so on.


Asunto(s)
Enfisema Mediastínico/terapia , Adolescente , Adulto , Femenino , Humanos , Masculino
12.
In Vitro Cell Dev Biol Anim ; 53(9): 810-817, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28710602

RESUMEN

Heparin-binding protein 17 (HBp17)/fibroblast growth factor-binding protein-1 (FGFBP-1) was first purified from medium conditioned by A431 cells for its capacity to bind to fibroblast growth factors 1 and 2 (FGF-1 and -2). Among FGF family members, FGF-2 is a potent mitogen for various cell types, including vascular endothelial cells, fibroblasts, and cancer cells such as oral squamous cell carcinoma (OSCC) cells. Besides being well known in bone metabolism, the active form of vitamin D3, i.e., 1α,25(OH)2D3 (1,25D3), was reported to have protective effects for heart disease and cancer. Previously, we reported that 1,25D3 inhibited HBp17/FGFBP-1 expression in OSCC cell lines through NF-κB inhibition (IκBα activation) and resulted in the inactivation of FGF-2. In this study, we examined the potential anti-tumor effect of ED-71, an analog of 1α,25(OH)2D3, for squamous cell carcinoma cells in vitro and in vivo. The cell lines used were OSCC cell lines (NA-HO-1-n-1 and UE-HO-1-u-1), established from oral cancer patients in our laboratory, and an epidermoid carcinoma/SCC cell line (A431). The growth assay in serum-free culture revealed that ED-71 inhibited the growth of the cancer cell lines in a dose-dependent manner. In addition, ED-71 suppressed HBp17/FGFBP-1 expression by inhibiting the NF-κB pathway as did 1,25D3. Furthermore, a luciferase reporter assay revealed that the promoter activity of HBp17/FGFBP-1 (region between -217 and +61) was down-regulated by ED-71. Oral administration of ED-71 significantly inhibited the growth of A431-derived tumors in athymic nude mice. Immunohistochemical analysis revealed that the expression of HBp17/FGFBP-1, FGF-2, CD31, and Ki-67 in the tumors of ED71-treated group was down-regulated in comparison to control. These results suggest that ED-71 possesses potential anti-tumor activity for SCCs both in vitro and in vivo. This compound may act directly on the tumor cells or on endothelial cells by modulating the tumor microenvironment.


Asunto(s)
Calcitriol/análogos & derivados , Carcinoma de Células Escamosas/patología , Proteínas Portadoras/metabolismo , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Neoplasias de la Boca/patología , Vitamina D/análogos & derivados , Animales , Apoptosis/efectos de los fármacos , Carcinoma de Células Escamosas/irrigación sanguínea , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/metabolismo , Proteínas Portadoras/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Péptidos y Proteínas de Señalización Intercelular/genética , Ratones Desnudos , Neoplasias de la Boca/irrigación sanguínea , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/metabolismo , Inhibidor NF-kappaB alfa/metabolismo , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/patología , Regiones Promotoras Genéticas/genética , ARN Interferente Pequeño/metabolismo , Receptores de Calcitriol/metabolismo , Transfección , Vitamina D/farmacología , Vitamina D/uso terapéutico
13.
Chem Commun (Camb) ; 53(56): 7929-7932, 2017 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-28656189

RESUMEN

Niobate nanosheets are assembled into thin membranes by a vacuum filtration. The nanosheet membranes have a dense and stable structure in water via chemical cross-linking and show higher permeance and salt rejection compared with graphene oxide membranes. A water pathway model based on the void structure is presented to explain the membrane performances.

14.
Neuroscience ; 142(4): 1081-92, 2006 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-16997488

RESUMEN

Fish CNS neurons can repair their axons following nerve injury, whereas mammalian CNS neurons cannot regenerate, and become apoptotic within 1-2 weeks after the nerve lesion. One explanation for these differences is that one, or several molecules are upregulated in fish CNS neurons during nerve regeneration, and this same molecule is downregulated in mammalian CNS neurons before the development of apoptosis caused by nerve injury. A molecule satisfying these criteria might successfully rescue and repair the mammalian CNS neurons. In this study, we looked for such a candidate molecule from goldfish retinas. Transglutaminase derived from goldfish retina (TG(R)) was characterized as a regenerating molecule after optic nerve injury. A full-length cDNA for TG(R) was isolated from the goldfish retinal cDNA library prepared from axotomized retinas. Levels of TG(R) mRNA and protein increased only in the retinal ganglion cells (RGCs) between 10 and 40 days after optic nerve transection. Recombinant TG(R) protein enhanced neurite outgrowth from adult fish RGCs in culture. Specific interference RNA and antibodies for TG(R) inhibited neurite outgrowth both in vitro and in vivo. In contrast, the level of TG(R) protein decreased in rat RGCs within 1-3 days after nerve injury. Furthermore, the addition of recombinant TG(R) to retinal cultures induced striking neurite outgrowth from adult rat RGCs. These molecular and cellular data strongly suggest that TG(R) promotes axonal elongation at the surface of injured RGCs after optic nerve injury.


Asunto(s)
Conos de Crecimiento/enzimología , Regeneración Nerviosa/fisiología , Traumatismos del Nervio Óptico/enzimología , Nervio Óptico/enzimología , Células Ganglionares de la Retina/enzimología , Transglutaminasas/metabolismo , Animales , Células Cultivadas , ADN Complementario/análisis , ADN Complementario/genética , Modelos Animales de Enfermedad , Biblioteca de Genes , Carpa Dorada , Conos de Crecimiento/efectos de los fármacos , Conos de Crecimiento/ultraestructura , Regeneración Nerviosa/efectos de los fármacos , Neuritas/efectos de los fármacos , Neuritas/enzimología , Nervio Óptico/efectos de los fármacos , Nervio Óptico/fisiopatología , Traumatismos del Nervio Óptico/fisiopatología , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Recombinantes de Fusión/farmacología , Células Ganglionares de la Retina/efectos de los fármacos , Transglutaminasas/genética , Transglutaminasas/farmacología , Regulación hacia Arriba/fisiología
15.
J Steroid Biochem Mol Biol ; 164: 79-84, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-26444325

RESUMEN

We have previously reported that 1,25(OH)2D3 inhibits NF-κB activity and thus inhibits growth of OSCC cells in serum-free culture and down-regulates HBp17/FGFBP-1 expression, which is important for cancer cell growth and angiogenesis. Here, we have investigated the effects of ED-71, an analog of vitamin D3 (VD) on OSCC cell lines in serum-free culture. It is known that ED-71 has a stronger inhibitory effect on bone resorption compared to VD and other VD analogs. To the best of our knowledge, there was no report examining the potential of ED-71 as an anti-cancer agent for OSCC. We found that ED-71 is able to inhibit the growth of cancer cell lines at a concentration of hundred times lower than calcitriol. As Cyp24A1 was reportedly induced in cancer cells, we measured the expression of CYP24A1 in OSCC cell lines (NA and UE), A431 epidermoid carcinoma and normal fibroblast cell (gfi) in serum-free culture. As a result, CYP24A1 mRNA and the protein expression in the OSCC cells treated with ED-71 increased in a dose-dependent manner. However, in vivo experiment, in which the A431 cells were implanted in mice, tumor formation was reduced by the ED-71 treatment with no significant difference between Cyp24A1 expression in the tumors of ED-71-treated and control group, as analyzed by western blotting and immunohistochemistry. These results suggest that ED-71 is a potential anti-cancer agent for OSCC.


Asunto(s)
Antineoplásicos/química , Calcitriol/análogos & derivados , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias de la Boca/tratamiento farmacológico , Animales , Antineoplásicos/farmacología , Calcitriol/química , Línea Celular Tumoral , Medio de Cultivo Libre de Suero , Relación Dosis-Respuesta a Droga , Fibroblastos/metabolismo , Encía/metabolismo , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Vitamina D/análogos & derivados , Vitamina D3 24-Hidroxilasa/metabolismo
16.
Biochim Biophys Acta ; 1204(2): 257-64, 1994 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-8142467

RESUMEN

The coding region of the aspergillopepsin I (EC 3.4.23.18) gene occupies 1340 base pairs of the genomic DNA and is separated into four exons by three introns. The predicted amino-acid sequence of aspergillopepsin I consists of 325 residues and is 32% and 27% homologous with those of human pepsin and calf chymosin. The cDNA of the gene prepared from mRNA has been cloned and expressed in yeast cells. To identify the residue of the substrate binding pocket in determining the specificity of aspergillopepsin I towards basic substrates, this residue was replaced with a serine residue by site-directed mutagenesis. The mutation is a single amino-acid change, Asp-76 converted to Ser-D76S, in the enzyme. The striking feature of this is that only the trypsinogen activating activity was destroyed. We therefore concluded that Asp-76 is the binding site towards basic substrates.


Asunto(s)
Ácido Aspártico Endopeptidasas/química , Ácido Aspártico , Tripsinógeno/metabolismo , Secuencia de Aminoácidos , Ácido Aspártico Endopeptidasas/genética , Ácido Aspártico Endopeptidasas/metabolismo , Aspergillus/metabolismo , Secuencia de Bases , Sitios de Unión , Genes Fúngicos , Humanos , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Pepsina A/química , Serina , Especificidad por Sustrato
17.
Biochim Biophys Acta ; 917(3): 356-64, 1987 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-3467796

RESUMEN

The metabolic transformation of exogenous prostaglandin D2 was investigated in isolated perfused rat lung. Dose-dependent formation (2-150 ng) of 9 alpha,11 beta-prostaglandin F2, corresponding to about 0.1% of the perfused dose of prostaglandin D2, was observed by specific radioimmunoassay both in the perfusate and in lung tissue after a 5-min perfusion. To investigate the reason for this low conversion ratio, we analyzed the metabolites of tritium-labeled 9 alpha,11 beta-prostaglandin F2 and prostaglandin D2 by boric acid-impregnated TLC and HPLC. By 5 min after the start of perfusion, 9 alpha,11 beta-prostaglandin F2 disappeared completely from the perfusate and the major product formed remained unchanged during the remainder of the 30-min perfusion. The major product was separated by TLC and identified as 13,14-dihydro-15-keto-9 alpha,11 beta-prostaglandin F2 by GC/MS. In contrast, pulmonary breakdown of prostaglandin D2 was slow and two major metabolites in the perfusate increased with time, each representing 56% and 11% of the total radioactivity at the end of the perfusion. The major product (56%) was identified as 13,14-dihydro-15-ketoprostaglandin D2 and the minor one (11%) was tentatively identified as 13,14-dihydro-15-keto-9 alpha,11 beta-prostaglandin F2 based on the results from radioimmunoassays, TLC, HPLC, and the time course of pulmonary breakdown. These results demonstrate that the metabolism of prostaglandin D2 in rat lung involves at least two pathways, one by 15-hydroxyprostaglandin dehydrogenase and the other by 11-ketoreductase, and that the 9 alpha,11 beta-prostaglandin F2 formed is rapidly metabolized to 13,14-dihydro-15-keto-9 alpha,11 beta-prostaglandin F2.


Asunto(s)
Pulmón/metabolismo , Prostaglandinas D/metabolismo , Prostaglandinas F/biosíntesis , Animales , Cromatografía Líquida de Alta Presión , Cromatografía en Capa Delgada , Dinoprost , Cromatografía de Gases y Espectrometría de Masas , Técnicas In Vitro , Masculino , Perfusión , Prostaglandina D2 , Prostaglandinas D/análisis , Prostaglandinas F/análisis , Radioinmunoensayo , Ratas , Ratas Endogámicas , Estereoisomerismo
18.
Mech Dev ; 98(1-2): 37-50, 2000 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11044606

RESUMEN

In the developing retina, a retinoic acid (RA) gradient along the dorso-ventral axis is believed to be a prerequisite for the establishment of dorso-ventral asymmetry. This RA gradient is thought to result from the asymmetrical distribution of RA-generating aldehyde dehydrogenases along the dorso-ventral axis. Here, we identified a novel aldehyde dehydrogenase specifically expressed in the chick ventral retina, using restriction landmark cDNA scanning (RLCS). Since this molecule showed enzymatic activity to produce RA from retinaldehyde, we designated it retinaldehyde dehydrogenase 3 (RALDH-3). Structural similarity suggested that RALDH-3 is the orthologue of human aldehyde dehydrogenase 6. We also isolated RALDH-1 which is expressed in the chick dorsal retina and implicated in RA formation. Raldh-3 was preferentially expressed first in the surface ectoderm overlying the ventral portion of the prospective eye region and then in the ventral retina, earlier than Raldh-1 in chick and mouse embryos. High level expression of Raldh-3 was also observed in the nasal region. In addition, we found that Pax6 mutants are devoid of Raldh-3 expression. These results suggested that Raldh-3 is the key enzyme in the formation of an RA gradient along the dorso-ventral axis during the early eye development, and also in the development of the olfactory system.


Asunto(s)
Aldehído Oxidorreductasas/genética , Aldehído Oxidorreductasas/metabolismo , Retina/embriología , Retina/enzimología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Embrión de Pollo , Clonación Molecular , Cartilla de ADN/genética , Proteínas del Ojo , Regulación del Desarrollo de la Expresión Génica , Regulación Enzimológica de la Expresión Génica , Proteínas de Homeodominio/genética , Humanos , Hibridación in Situ , Isoenzimas/genética , Isoenzimas/metabolismo , Ratones , Ratones Mutantes , Datos de Secuencia Molecular , Factor de Transcripción PAX6 , Factores de Transcripción Paired Box , Proteínas Represoras , Retinal-Deshidrogenasa , Retinaldehído/biosíntesis , Homología de Secuencia de Aminoácido
19.
Leukemia ; 12(4): 510-6, 1998 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9557609

RESUMEN

Fluorescence in situ hybridization (FISH) was performed in 17 myeloid leukemia patients and seven lymphoid leukemia/ lymphoma patients who exhibited chromosomal abnormalities on the short arm of chromosome 17, in order to detect a commonly deleted region on chromosome band 17p13. Twenty-four leukemia/lymphoma patients studied cytogenetically at our institution over a period of 10 years had detectable 17p abnormalities such as translocation (six patients), addition (11 patients) and deletion of 17p13 (seven patients). A 17p abnormality was the only abnormality present in three patients. Most of the patients had additional complex cytogenetic abnormalities. The diagnosis was acute myeloid leukemia (AML) in 10 patients, two each with chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL) and myelodysplastic syndrome (MDS) and the remaining three with malignant lymphoma (ML). Seven cosmid probes (D17S34, cCI17-624, cCI17-453, D17S379, cCI17-636, cCI17-732 and TP53) which mapped on 17p13 were used to analyze the allelic deletion. Eighty percent (19 out of 24) of the informative leukemia patients exhibited allelic loss in 17p13.3 at cC17-624. The smallest region of an overlapping deletion was observed on chromosome band 17p13.3 between cCI17-624 and cCI17-453. Patients with translocation involving 17p also showed deletion at cCI17-624 and cCI17-453. We hypothesize that this region contains a novel tumor suppressor gene(s) that is involved in leukemogenesis.


Asunto(s)
Alelos , Cromosomas Humanos Par 17 , Eliminación de Gen , Leucemia Linfoide/genética , Leucemia Mieloide/genética , Linfoma no Hodgkin/genética , Adulto , Anciano , Anciano de 80 o más Años , Mapeo Cromosómico , Femenino , Genes p53 , Humanos , Hibridación Fluorescente in Situ , Interfase/fisiología , Cariotipificación , Masculino , Metafase/fisiología , Persona de Mediana Edad , Síndromes Mielodisplásicos/genética
20.
Int J Oral Maxillofac Surg ; 44(7): 840-4, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25861974

RESUMEN

Bisphosphonates (BPs) have been used in medical practice for the treatment of osteoporosis, bone metastasis, and multiple myeloma. Although many studies have been published, the treatment and prognosis of bisphosphonate-related osteonecrosis of the jaw (BRONJ) remain unclear. This study included 59 patients with BRONJ: 29 had taken oral BPs and 30 had taken intravenous (IV) BPs. All received conservative treatments. When separated sequestra were seen, a sequestrectomy was performed. Segmental mandibular resection was performed when pathological fractures were diagnosed. The outcomes of treatments were compared between groups. For patients treated with oral rinses or mandibular resection, the number in whom clinical healing was observed did not differ between the oral BP and IV BP groups. With regard to sequestrectomy, 94% of patients in the oral BP group showed improvement with this treatment compared to 50% in the IV BP group. The number of patients in whom clinical healing of BRONJ was achieved was statistically better in the oral BP group than in the IV BP group after 6 months of treatment (P<0.001). The results showed that >90% of patients treated with oral BPs could be cured. However, 50% of patients treated with IV BPs did not show an improvement. Additional research is needed to further increase the therapeutic efficacy for the resolution of BRONJ.


Asunto(s)
Osteonecrosis de los Maxilares Asociada a Difosfonatos/terapia , Conservadores de la Densidad Ósea/administración & dosificación , Conservadores de la Densidad Ósea/efectos adversos , Difosfonatos/administración & dosificación , Difosfonatos/efectos adversos , Administración Oral , Anciano , Anciano de 80 o más Años , Osteonecrosis de los Maxilares Asociada a Difosfonatos/patología , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Pronóstico , Resultado del Tratamiento
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