RESUMEN
Mesenchymal stem cell (MSC) transplantation is an effective periodontal regenerative therapy. MSCs are multipotent, have self-renewal ability, and can differentiate into periodontal cells. However, senescence is inevitable for MSCs. In vitro, cell senescence can be induced by long-term culture with/without cell passage. However, the regulatory mechanism of MSC senescence remains unclear. Undifferentiated MSC-specific transcription factors can regulate MSC function. Herein, we identified the regulatory transcription factors involved in MSC senescence and elucidated their mechanisms of action. We cultured human MSCs (hMSCs) with repetitive cell passages to induce cell senescence and evaluated the mRNA and protein expression of cell senescence-related genes. Additionally, we silenced the cell senescence-induced transcription factors, GATA binding protein 6 (GATA6) and SRY-box 11 (SOX11), and investigated senescence-related signaling pathways. With repeated passages, the number of senescent cells increased, while the cell proliferation capacity decreased; GATA6 mRNA expression was upregulated and that of SOX11 was downregulated. Repetitive cell passages decreased Wnt and bone morphogenetic protein (BMP) signaling pathway-related gene expression. Silencing of GATA6 and SOX11 regulated Wnt and BMP signaling pathway-related genes and affected cell senescence-related genes; moreover, SOX11 silencing regulated GATA6 expression. Hence, we identified them as pair of regulatory transcription factors for cell senescence in hMSCs via the Wnt and BMP signaling pathways.
Asunto(s)
Senescencia Celular/genética , Células de la Médula Ósea/citología , Proteínas Morfogenéticas Óseas/genética , Proteínas Morfogenéticas Óseas/metabolismo , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Factor de Transcripción GATA6/antagonistas & inhibidores , Factor de Transcripción GATA6/genética , Factor de Transcripción GATA6/metabolismo , Histona Desacetilasa 2/genética , Histona Desacetilasa 2/metabolismo , Humanos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Factores de Transcripción SOXC/antagonistas & inhibidores , Factores de Transcripción SOXC/genética , Factores de Transcripción SOXC/metabolismo , Transducción de Señal/genética , Proteínas Wnt/genética , Proteínas Wnt/metabolismoRESUMEN
Reduced expression in immortalized cells (REIC)/dickkopf-3 (Dkk-3), a tumor suppressor gene, is downregulated in various cancers. We previously reported the tumor-inhibitory effects of the REIC/Dkk-3 gene, delivered by a conventional adenoviral vector (Ad-CAG-REIC) in pancreatic cancer. Here, we developed an Ad-REIC vector with a novel gene expression system, termed the super gene expression (SGE) system, and assessed its therapeutic effects relative to those of Ad-CAG-REIC in pancreatic cancer cells. Human pancreatic cancer cell lines ASPC1 and MIAPaCa2 were used. REIC/Dkk-3 expression was assessed by western blot analysis. Relative cell viability and apoptotic effects were examined in vitro. The anti-tumor effects of Ad-REIC treatment were assessed in the mouse xenograft model. Compared with Ad-CAG-REIC, Ad-SGE-REIC elicited a significant increase in REIC protein expression in the cells studied. Relative to Ad-CAG-REIC, Ad-SGE-REIC reduced cell viability and induced apoptosis in the ASPC1 and MIAPaCa2 cell lines in vitro, and achieved superior tumor growth inhibition in the mouse xenograft model. Compared with conventional Ad-REIC agents, Ad-SGE-REIC provided enhanced inhibitory effects against tumor growth. Our results indicate that Ad-SGE-REIC is an innovative therapeutic tool for pancreatic cancer.
Asunto(s)
Adenoviridae/genética , Terapia Genética , Vectores Genéticos/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Neoplasias Pancreáticas/genética , Proteínas Adaptadoras Transductoras de Señales , Animales , Apoptosis/genética , Línea Celular Tumoral , Supervivencia Celular/genética , Quimiocinas , Modelos Animales de Enfermedad , Expresión Génica , Orden Génico , Vectores Genéticos/administración & dosificación , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Ratones , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Transducción de Señal , Carga Tumoral/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVES: Our aim was to determine whether ablated liver parenchyma surrounding a tumour can be assessed by MRI with ferucarbotran administered prior to radiofrequency ablation (RFA) compared with enhanced CT. METHODS: 55 hepatocellular carcinomas (HCCs) in 42 patients and 5 metastatic liver cancers in 3 patients were treated by RFA after ferucarbotran administration. We then performed T(2)* weighted MRI after 1 week and enhanced CT after 1 month. T(2)* weighted MRI demonstrated the ablated parenchyma as a low-intensity rim around the high intensity of the ablated tumour in these cases. The assessment was allocated to one of three grades: margin (+), high-intensity area with continuous low-intensity rim; margin zero, high-intensity area with discontinuous low-intensity rim; and margin (-), high-intensity area extending beyond the low-intensity rim. RESULTS: Margin (+), margin zero and margin (-) were found in 17, 35 and 5 nodules, respectively. All 17 nodules with margin (+) and 13 of those with margin zero were assessed as having sufficient ablative margins on CT. The remaining 22 nodules with margin zero had insufficient margins on CT. The overall agreement between MRI and CT for the diagnosis of the ablative margin was moderate (κ = 0.507, p < 0.001). No local recurrence was found in 15 HCC nodules with margin (+), whereas local recurrence was found in 4 (11.8%) out of 34 HCC nodules with margin zero. CONCLUSION: Administration of ferucarbotran before RFA enables the ablative margin to be visualised as a low-intensity rim, and also enables the evaluation of the ablative margin to be made earlier and more easily than with enhanced CT.
Asunto(s)
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/cirugía , Ablación por Catéter , Medios de Contraste , Dextranos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirugía , Imagen por Resonancia Magnética/métodos , Nanopartículas de Magnetita , Tomografía Computarizada por Rayos X , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/patología , Femenino , Humanos , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND AND OBJECTIVE: As epithelial cells function as a mechanical barrier, the permeability of the gingival epithelial cell layer indicates a defensive capability against invasion by periodontal pathogens. We have reported the expression of claudin-1 and E-cadherin, key regulators of permeability, in the gingival junctional epithelium. Irsogladine maleate (IM) is a medication for gastric ulcers and also regulates Aggregatibacter actinomycetemcomitans-stimuated chemokine secretion and E-cadherin expression in gingival epithelium. In this study, we have further investigated the effects of IM on the barrier functions of gingival epithelial cells under inflammatory conditions. MATERIAL AND METHODS: We examined the permeability, and the expression of claudin-1 and E-cadherin, in human gingival epithelial cells (HGECs) stimulated with tumor necrosis factor (TNF)-α, with or without IM. RESULTS: TNF-α increased the permeability of HGECs, and IM abolished the increase. TNF-α reduced the expression of E-cadherin in HGECs, and IM reversed the reduction. In addition, immunofluorescence staining showed that TNF-α disrupted claudin-1 expression in HGECs, and IM reversed this effect. CONCLUSION: The results suggest that IM reverses the TNF-α-induced disruption of the gingival epithelial barrier by regulating E-cadherin and claudin-1.
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Encía/efectos de los fármacos , Triazinas/farmacología , Factor de Necrosis Tumoral alfa/farmacología , Adulto , Western Blotting , Cadherinas/efectos de los fármacos , Técnicas de Cultivo de Célula , Línea Celular , Permeabilidad de la Membrana Celular/efectos de los fármacos , Claudina-1 , Impedancia Eléctrica , Inserción Epitelial/citología , Inserción Epitelial/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/inmunología , Femenino , Fluoresceína , Técnica del Anticuerpo Fluorescente , Colorantes Fluorescentes , Encía/citología , Encía/inmunología , Humanos , Masculino , Proteínas de la Membrana/efectos de los fármacos , Reacción en Cadena en Tiempo Real de la Polimerasa , Uniones Estrechas/efectos de los fármacos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto JovenRESUMEN
OBJECTIVE: The aim of this study was to evaluate tumour vascularity and Kupffer cell imaging in hepatocellular carcinoma (HCC) using contrast-enhanced ultrasonography (CEUS) with Sonazoid (perfluorobutane) and to compare performance with dynamic CT. METHODS: We studied 118 nodules in 88 patients with HCC. HCC was diagnosed as a hyperenhancement lesion in the arterial phase with washout in the portal phase on dynamic CT or by percutaneous biopsy. We observed tumour vascularity at the early vascular phase (10-30 s after contrast injection) and Kupffer imaging at the post-vascular phase (after 10 min). RESULTS: Detection of vascularity at the early vascular phase was 88% in nodules that were found to be hypervascular on dynamic CT and 28% in hypo-/isovascular nodules; the detection of local recurrence nodules was 92%. The detection of vascularity was significantly lower in nodules >9 cm deep than in those ≤9 cm deep, but was not affected by tumour size. The detection of tumours at the post-vascular phase on CEUS was 83% in nodules with low density in the portal phase on dynamic CT and 82% in nodules with isodensity. The rate did not depend on the severity of underlying liver disease; rates decreased in nodules deeper than 9 cm, those smaller than 2 cm in diameter and in iso-enhancing nodules at the early vascular phase of CEUS. CONCLUSION: CEUS with Sonazoid is a useful tool for assessing the vascularity of HCC and is equal to that of dynamic CT; however, the detectability of HCC vascularity is affected by location.
Asunto(s)
Carcinoma Hepatocelular/diagnóstico por imagen , Medios de Contraste/uso terapéutico , Fluorocarburos/uso terapéutico , Neoplasias Hepáticas/diagnóstico por imagen , Microburbujas/uso terapéutico , Anciano , Carcinoma Hepatocelular/irrigación sanguínea , Femenino , Humanos , Aumento de la Imagen , Macrófagos del Hígado/diagnóstico por imagen , Neoplasias Hepáticas/irrigación sanguínea , Masculino , Recurrencia Local de Neoplasia/irrigación sanguínea , Recurrencia Local de Neoplasia/diagnóstico por imagen , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X/métodos , UltrasonografíaRESUMEN
BACKGROUND: Factor Xa (FXa), a key serine protease that converts prothrombin to thrombin in the coagulation cascade, is a promising target enzyme for the prophylaxis and treatment of thromboembolic diseases. DU-176b is a novel antithrombotic agent that directly inhibits FXa activity. OBJECTIVE: To evaluate the in vitro pharmacological profiles and in vivo effects of DU-176b in animal models of thrombosis and bleeding. METHODS: In vitro, FXa inhibition, specificity and anticoagulant activities were examined. Oral absorption was studied in rats and cynomolgus monkeys. In vivo effects were studied in rat and rabbit models of venous thrombosis and tail bleeding. RESULTS: DU-176b inhibited FXa with Ki values of 0.561 nm for free FXa, 2.98 nm for prothrombinase, and exhibited >10 000-fold selectivity for FXa. In human plasma, DU-176b doubled prothrombin time and activated partial thromboplastin time at concentrations of 0.256 and 0.508 microm, respectively. DU-176b did not impair platelet aggregation by ADP, collagen or U46619. DU-176b was highly absorbed in rats and monkeys, as demonstrated by more potent anti-Xa activity and higher drug concentration in plasma following oral administration than a prototype FXa inhibitor, DX-9065a. In vivo, DU-176b dose-dependently inhibited thrombus formation in rat and rabbit thrombosis models, although bleeding time in rats was not significantly prolonged at an antithrombotic dose. CONCLUSIONS: DU-176b is a more potent and selective FXa inhibitor with high oral bioavailability compared with its prototype, DX-9065a. DU-176b represents a promising new anticoagulant for the prophylaxis and treatment of thromboembolic diseases.
Asunto(s)
Inhibidores del Factor Xa , Piridinas/farmacología , Inhibidores de Serina Proteinasa/farmacología , Tiazoles/farmacología , Administración Oral , Animales , Área Bajo la Curva , Coagulación Sanguínea/efectos de los fármacos , Femenino , Macaca fascicularis , Masculino , Agregación Plaquetaria/efectos de los fármacos , Piridinas/administración & dosificación , Piridinas/farmacocinética , Ratas , Ratas Wistar , Inhibidores de Serina Proteinasa/administración & dosificación , Inhibidores de Serina Proteinasa/farmacocinética , Tiazoles/administración & dosificación , Tiazoles/farmacocinéticaRESUMEN
Nedaplatin (254-S), which is a cisplatin (CDDP) analog, is an effective agent for head and neck squamous cell carcinoma (HNSCC). 254-S is expected to play an important role in neo-adjuvant chemotherapy (NAC) for HNSCC in place of CDDP. We have been using combination chemotherapy including CDDP, 5-FU, MTX and LV. The response rate and CR rate of this 4-drug combined chemotherapy are 87% and 33%. Thirty-six patients with HNSCC were treated with 5-FU, 800 mg/m2/day for 5 days and 254-S, 100 mg/m2 on day 4. Chemotherapy was discontinued in one patient because of allergic shock. Three patients showed a CR and 10 patients showed a PR. The response rate and CR rate of 254-S plus 5-FU chemotherapy were 37.1% and 8.6%. These were inferior to those with the 4-drug combined chemotherapy. Fourteen percent of patients showed grade 3 leukocytopenia, and 17% showed more than grade 3 thrombocytopenia. The effect of combination chemotherapy of 254-S and 5-FU was inferior to that of the previous chemotherapy including CDDP, 5-FU, MTX and LV. Further study or another combination therapy including 254-S will be essential for improving efficacy against HNSCC.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Esquema de Medicación , Fluorouracilo/administración & dosificación , Humanos , Compuestos Organoplatinos/administración & dosificaciónRESUMEN
Angiotensin-(1-7) has been suggested to be a novel vasodilating peptide. We investigated the direct vascular effect of angiotensin-(1-7) in human forearm resistant vessels, particularly with regard to the interaction with angiotensin II, in healthy normotensive men by strain-gauge venous occlusion plethysmography with intra-arterial infusions of peptides. Intra-arterial infusion of angiotensin-(1-7) at 0.1 to 2000 pmol/min did not cause vasodilatation but rather reduced forearm blood flow by approximately 10% at the highest dose. A placebo-controlled study showed that angiotensin-(1-7) at 0.5 to 40 nmol/min caused weak but significant vasoconstriction (P=0.0016 by ANOVA). Angiotensin-(1-7) at 100 pmol/min, but not at 10 pmol/min, significantly shifted the angiotensin II dose-response curve toward the right (mean+/-SD of percent changes in forearm blood flow: -19+/-17%, -33+/-22%, -55+/-12%, -63+/-10%, and -68+/-5% at 5, 10, 25, 50, and 100 pmol/min of angiotensin II, respectively, with saline; 5+/-13%, 0. 9+/-18%, -40+/-16%, -54+/-9%, and -61+/-6% with angiotensin-(1-7), P=0.0021 by ANOVA). Angiotensin-(1-7) did not affect the dose-response curve of noradrenaline [3+/-12%, 5+/-16%, -20+/-22%, -31+/-18%, and -40+/-12% at 25, 50, 100, 300, and 600 pmol/min of noradrenaline, respectively, with saline; -4+/-15%, -2+/-23%, -29+/-22%, -34+/-16%, and -42+/-9% with angiotensin-(1-7)]. Our results suggest that angiotensin-(1-7) antagonizes vasoconstriction by angiotensin II in human resistant vessels and might act as an endogenous angiotensin II antagonist.
Asunto(s)
Angiotensina II/farmacología , Angiotensina I/farmacología , Norepinefrina/farmacología , Fragmentos de Péptidos/farmacología , Vasoconstricción/efectos de los fármacos , Vasoconstrictores/farmacología , Vasodilatadores/farmacología , Arterias/efectos de los fármacos , Arterias/fisiología , Interacciones Farmacológicas , Antebrazo/irrigación sanguínea , Humanos , Masculino , Flujo Sanguíneo Regional/efectos de los fármacosRESUMEN
We cloned the genomic DNA and cDNA of bglA, which encodes beta-glucosidase in Aspergillus kawachii, based on a partial amino acid sequence of purified cell wall-bound beta-glucosidase CB-1. The nucleotide sequence of the cloned bglA gene revealed a 2,933-bp open reading frame with six introns that encodes an 860-amino-acid protein. Based on the deduced amino acid sequence, we concluded that the bglA gene encodes cell wall-bound beta-glucosidase CB-1. The amino acid sequence exhibited high levels of homology with the amino acid sequences of fungal beta-glucosidases classified in subfamily B. We expressed the bglA cDNA in Saccharomyces cerevisiae and detected the recombinant beta-glucosidase in the periplasm fraction of the recombinant yeast. A. kawachii can produce two extracellular beta-glucosidases (EX-1 and EX-2) in addition to the cell wall-bound beta-glucosidase. A. kawachii in which the bglA gene was disrupted produced none of the three beta-glucosidases, as determined by enzyme assays and a Western blot analysis. Thus, we concluded that the bglA gene encodes both extracellular and cell wall-bound beta-glucosidases in A. kawachii.
Asunto(s)
Aspergillus/enzimología , Aspergillus/genética , Glucosidasas/genética , Glucosidasas/metabolismo , beta-Glucosidasa/genética , Secuencia de Aminoácidos , Pared Celular/enzimología , Clonación Molecular , Genes Fúngicos , Glucosidasas/química , Intrones , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Mapeo Restrictivo , Saccharomyces cerevisiae/genética , Alineación de Secuencia , Homología de Secuencia de Aminoácido , beta-Glucosidasa/químicaRESUMEN
The distribution and abundance of substance P (SP) and calcitonin gene-related peptide (CGRP) immunoreactive nerve fibers in four different regions of the laryngeal mucosa were compared between normoxic and chronically hypoxic rats (10% O2 and 3.0-4.0% CO2 for 3 months). In the chronically hypoxic laryngeal mucosa, the number of SP and CGRP fibers within and just beneath the epithelium, and around the laryngeal gland was increased in comparison with those in the normoxic controls. Especially in the epiglottic and arytenoid regions, the number of intraepithelial SP fibers was increased remarkably. Most intraepithelial SP and CGRP fibers penetrated into the epithelium to extend to the luminal surface. There was no distinct difference in the distribution and abundance of these peptidergic fibers in the mucosa of the normoxic and chronically hypoxic vocal cord regions. These results suggest that the increased density of SP and CGRP fibers within the epithelium of the upper laryngeal mucosa is a predominant feature of hypoxic adaptation, and this may be involved in airway protection, swallowing, and other functions in the chronically hypoxic environment. In addition, the increased SP and CGRP fibers around the laryngeal gland suggest an enhanced mucous secretion, and this may participate in the airway defense mechanism in low O2 conditions.
Asunto(s)
Péptido Relacionado con Gen de Calcitonina/metabolismo , Hipoxia/metabolismo , Nervios Laríngeos/metabolismo , Fibras Nerviosas/metabolismo , Sustancia P/metabolismo , Animales , Hipoxia/patología , Mucosa Laríngea/inervación , Nervios Laríngeos/patología , Fibras Nerviosas/patología , RatasRESUMEN
We analyzed the relationship between clinical response to neo-adjuvant chemotherapy including 5-fluorouracil (5-FU) in patients with hypopharyngeal carcinoma (HPC) and thymidylate synthase (TS) expression in their tumors. TS expression was evaluated with immunohistochemical staining techniques on biopsy specimens from HPC patients. TS immunostaining was divided into four levels (TS0-TS3) according to its level and pattern. The relationship between prognosis, tumor size, nodal status, differentiation of tumor cells and TS expression were also investigated. There was a statistically significant association between the level of TS expression and tumor size (p < 0.01). In terms of the effectiveness of chemotherapy, tumor differentiation, nodal status and prognosis, a statistical difference was not found in TS expression. These results suggest that the level of TS expression may show the degree of tumor proliferation, but may not necessarily be useful to obtain a response to chemotherapy including other drugs, e.g., cisplatin and other derivatives of platinum.
Asunto(s)
Carcinoma de Células Escamosas/enzimología , Neoplasias Hipofaríngeas/enzimología , Timidilato Sintasa/metabolismo , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/mortalidad , Cisplatino/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Neoplasias Hipofaríngeas/tratamiento farmacológico , Neoplasias Hipofaríngeas/mortalidad , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Tasa de SupervivenciaRESUMEN
The angiotensinogen (AGT) gene M235T variant is associated with essential hypertension and elevated plasma AGT concentrations, although the underlying mechanisms are unknown. Recent studies have suggested that AGCE 1 (human AGT gene core promoter element 1) located in the 5' upstream core promoter region (position -25 to -1) of the human AGT gene has an important part in the expression of AGT mRNA by binding with transcription factor AGCF 1 (human AGT gene core promoter element binding factor 1), and a mutation at -20 from adenine to cytosine (A-20C) increases the level of expression of this transcript. We therefore examined subjects with this mutation to study the association with increased plasma AGT concentrations and with essential hypertension. One hundred eighty-eight subjects receiving no antihypertensive medication were examined with regard to the correlation between A-20C and plasma AGT concentrations, and 234 subjects were studied with respect to the association between A-20C and essential hypertension. A-20C was determined by polymerase chain reaction-restriction fragment length polymorphism analysis with EcoOR 109I. Multiple regression analysis showed a weak but significant correlation between A-20C and plasma AGT concentrations (P=.047) and essential hypertension (P=.049). The results suggest that A-20C may underlie the increase in plasma AGT concentrations and be involved in the development of essential hypertension.
Asunto(s)
Angiotensinógeno/biosíntesis , Angiotensinógeno/genética , Hipertensión/genética , Mutación Puntual , Regiones Promotoras Genéticas , Angiotensinógeno/sangre , Presión Sanguínea , Colesterol/sangre , HDL-Colesterol/sangre , Frecuencia de los Genes , Variación Genética , Genotipo , Humanos , Hipertensión/sangre , Hipertensión/fisiopatología , Persona de Mediana Edad , Oportunidad Relativa , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , ARN Mensajero/biosíntesis , Valores de Referencia , Factores de Transcripción/metabolismo , Transcripción Genética , Triglicéridos/sangreRESUMEN
The occurrence and distribution of neuropeptide-containing fibres in the human parotid gland were examined by the peroxidase-antiperoxidase method with attention to the quality of fixation and the condition of patients. Many fibres immunoreactive for neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) and a moderate number of galanin-positive (GAL) fibres were distributed around the acini. A moderate number of NPY and VIP fibres were distributed around the intercalated ducts. The semiquantitative mean densities (+/- SD) of periacinar NPY, VIP and GAL fibres expressed as a percentage of the total protein gene product (PGP) 9.5 immunoreactive fibres were 75.62 +/- 7.25%, 70.52 +/- 9.33% and 41.76 +/- 5.45%, respectively, whereas those of substance P (SP), calcitonin gene-related peptide (CGRP) and FMRF amide (FMRF) fibres were below 10%. The mean densities of NPY and VIP fibres around the intercalated ducts expressed as the percentage of PGP 9.5 fibres associated with these ducts were 52.37 +/- 6.19% and 59.62 +/- 7.02% respectively. Those of SP, CGRP, GAL, and FMRF fibres were below 10%. The densities of NPY, VIP, SP, CGRP, GAL and FMRF fibres around the striated and excretory ducts were also below 10%. In the vasculature, NPY fibres were the most prominent. Similarly, the mean density of perivascular NPY fibres was 93.76 +/- 2.03%. No somatostatin or leucine or methionine enkephalin immunoreactivity was detected around the acini, duct system or blood vessels. These findings suggest that, in this gland, the periacinar NPY, VIP and GAL fibres may participate in regulating the synthesis of saliva and its secretion and that perivascular peptidergic fibres, especially NPY fibres, may be involved in controlling local blood flow.
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Fibras Nerviosas/química , Proteínas del Tejido Nervioso/análisis , Glándula Parótida/inervación , Tioléster Hidrolasas/análisis , Adulto , Anciano , Anciano de 80 o más Años , Péptido Relacionado con Gen de Calcitonina/análisis , Encefalina Leucina/análisis , Encefalina Metionina/análisis , FMRFamida , Femenino , Galanina/análisis , Humanos , Masculino , Persona de Mediana Edad , Neuropéptido Y/análisis , Neuropéptidos/análisis , Somatostatina/análisis , Sustancia P/análisis , Tioléster Hidrolasas/inmunología , Ubiquitina Tiolesterasa , Péptido Intestinal Vasoactivo/análisisRESUMEN
The occurrence and distribution of several neuropeptides were studied in human von Ebner's glands. Immunoreactivity for substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), galanin, and somatostatin was found in the nerve fibers around the acini, ducts, and blood vessels. VIP-immunoreactive varicose fibers were numerous compared with the other five neuropeptides. Most NPY fibers were associated with the vasculature in the gland. These findings suggest that the neuropeptides may regulate the secretion and vascular tone in human von Ebner's glands.
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Neuropéptidos/análisis , Glándulas Salivales/inervación , Lengua/anatomía & histología , Humanos , Técnicas para Inmunoenzimas , Fibras Nerviosas/químicaRESUMEN
The relationships between angiotensin-converting enzyme (ACE) gene insertion (I) / deletion (D) polymorphism and left ventricular hypertrophy induced by hypertension or idiopathic hypertrophic cardiomyopathy have been studied. However, little is known about the association between this polymorphism and left ventricular hypertrophy induced by volume overload. The relationship between left ventricular hypertrophy and the ACE gene I/D polymorphism was examined in 80 maintenance hemodialysis patients (mean age: 60.1+/-1.4
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Hipertrofia Ventricular Izquierda/genética , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Diálisis Renal , Adulto , Anciano , Elementos Transponibles de ADN , Ecocardiografía , Femenino , Eliminación de Gen , Genotipo , Humanos , Hipertensión/complicaciones , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/enzimología , Enfermedades Renales/complicaciones , Enfermedades Renales/terapia , Masculino , Persona de Mediana Edad , Análisis de RegresiónRESUMEN
Two children with otogenic facial palsy are reported. The tympanic membranes of a 15-month-old boy and a girl of the same age were hyperemic, dull, and bulging, and the children suffered from masked mastoiditis. The facial palsy had not been improved by myringotomy, and parenteral administration of antibiotics and steroids. Finally, tympanomastoidectomy and facial nerve decompression was performed and a tympanostomy tube was inserted. Both patients completely recovered facial nerve function within two months after the operation. On the basis of the results of those operations tympanomastoidectomy and the facial nerve decompression may become necessary in such cases as those caused by masked mastoiditis.
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Parálisis Facial/etiología , Mastoiditis/complicaciones , Nervio Facial/cirugía , Parálisis Facial/cirugía , Femenino , Humanos , Lactante , Masculino , Apófisis Mastoides/cirugía , Mastoiditis/cirugía , Ventilación del Oído Medio , Membrana Timpánica/cirugíaRESUMEN
Multi-element analysis by neutron activation analysis (NAA) in respect to medical applications is discussed. Examples of trace element determinations in pathological human liver tissues, human serum, and rat liver are given. A very sensitive method for determining fluorinated drug in very small samples of human serum by neutron activation is also described. Each biological samples (ca. 100-200 mg, lyophilized matter) was irradiated for short time (10 s or 5 min.) and for long time (24 hrs) in Rikkyo University Research Reactor or Musashi Institute of Technology Research Reactor. Concentration of 12 elements (127I, 55Mn, 26Mn, 65Cu, 23Na, 41K, 37Cl, 27Al, 48Ca, 36S, 58Fe, 64Zn) in human pathological liver, Futraful (19F) (anti-cancer fluorinated drug) clearance of human serum, and calcium uptake (48Ca) in liver of rats were determined by NAA.
Asunto(s)
Análisis de Activación de Neutrones , Oligoelementos/análisis , Animales , Humanos , Hígado/química , Neoplasias Hepáticas/química , RatasRESUMEN
The reliability of brainstem evoked response audiometry (ERA) as an objective audiometric study was evaluated in long term follow-up infants with moderate to severe sensorineural hearing loss. None of the infants had either brain damage (cerebral palsy, mental retardation) or other severe complications (genetic diseases). The thresholds of ERA at 1 kHz and 4 kHz were measured in 234 infants below one year of age, from 1983 to 1990, in our hospital. These infants were followed-up to the age when conditioned oriented response audiometry (COR) and play audiometry could be conducted. Pure tone thresholds obtained by COR and play audiometry were compared with those of ERA. In addition, speech problems in these patients were evaluated. In all of those infants, hearing aids were fitted before one year of age to achieve early habilitation. As a results, ERA was found to be a reliable and efficacious test for determining auditory thresholds, and providing hearing aids for early habilitation in one-year old infants with moderate to severe sensorineural hearing loss.
Asunto(s)
Audiometría de Respuesta Evocada , Pérdida Auditiva Sensorineural/diagnóstico , Umbral Auditivo , Niño , Preescolar , Estudios de Seguimiento , Audífonos , Pérdida Auditiva Sensorineural/fisiopatología , Humanos , Lactante , Desarrollo del Lenguaje , Reproducibilidad de los ResultadosRESUMEN
We investigated the development of substance P immunoreactivity in mouse vomeronasal organs in embryos, juveniles, and adults. In all stages, substance P fibers were found in the receptor-free epithelial area, but never in the neuroepithelium. Substance P fibers were found sparsely in the lamina propria of 15-day-old embryos. Although buds of the vomeronasal glands in the cavernous tissue were observed in 17-day-old embryos, and gradually grew in size and numbers, the substance P fibers around them decreased after about the 13th day. Thus, substance P may be a trophic factor for the development of the vomeronasal glands in the cavernous tissue. We first recognized substance P fibers reaching the surface of the receptor-free epithelium in 13-day-old pups. In 21-day-old mice, substance P fibers were as well developed as in adult mice. Considering the development of the substance P fibers in the receptor-free epithelium and the cavernous tissue, they probably cause the vasodilation of the cavernous tissue via local axon reflexes. These structures may then act as a defense system, eliminating noxious stimulus substances sucked into the vomeronasal organ.
Asunto(s)
Tabique Nasal/inervación , Fibras Nerviosas/química , Mucosa Olfatoria/inervación , Sustancia P/análisis , Animales , Animales Recién Nacidos , Femenino , Inmunohistoquímica , Masculino , Ratones , Tabique Nasal/embriología , Tabique Nasal/crecimiento & desarrollo , Mucosa Olfatoria/embriología , Mucosa Olfatoria/crecimiento & desarrollo , Embarazo , Sustancia P/inmunología , Factores de TiempoRESUMEN
Since activated factor X (FXa) is a coagulant enzyme that generates thrombin and participates in both intrinsic and extrinsic coagulation pathways, inhibition of FXa may be more effective than inactivation of thrombin for interrupting blood coagulation. To assess the possible effectiveness of FXa inhibition as an anticoagulant, we designed and synthesized 3-(amidinoaryl)-2-[4-[(3S)-3-pyrrolidinyloxy]phenyl]propanoi c acid derivatives as low molecular weight, nonpeptidic, orally active FXa inhibitors. These derivatives exhibited potent and highly selective anti-FXa activity in vitro and anticoagulant activity on oral administration. The most promising compound, (2S)-2-[4-[[(3S)-1-acetimidoyl-3-pyrrolidinyl]oxy]phenyl]- 3-(7-amidino-2-naphthyl)propanoic acid hydrochloride pentahydrate (4,DX-9065a), inhibited 50% of FXa activity (IC50) at 0.07 microM, doubled plasma recalcification time (PRCT) at 0.5 microM, and significantly prolonged activated partial thromboplastin time (APTT) at a dose of 100 mg/kg on oral administration. In contrast with FXa inhibition, 4 showed no activity against thrombin (IC50 > 2000 microM).