RESUMEN
The Wingless/integrase-1 (Wnt) family of protein ligands and their functional antagonists, secreted frizzled-related proteins (sFRPs), regulate various biological processes ranging from embryonic development to immunity and inflammation. Wnt5a and sFRP5 comprise a typical ligand/antagonist pair, and the former molecule was recently detected at the messenger RNA (mRNA) level in human periodontitis. The main objective of this study was to investigate the interrelationship of expression of Wnt5a and sFRP5 in human periodontitis (as compared to health) and to determine their roles in inflammation and bone loss in an animal model. We detected both Wnt5a and sFRP5 mRNA in human gingiva, with Wnt5a dominating in diseased and sFRP5 in healthy tissue. Wnt5a and sFRP5 protein colocalized in the gingival epithelium, suggesting epithelial cell expression, which was confirmed in cultured human gingival epithelial cells (HGECs). The HGEC expression of Wnt5a and sFRP5 was differentially regulated by a proinflammatory stimulus (lipopolysaccharide [LPS] from Porphyromonas gingivalis) in a manner consistent with the clinical observations (i.e., LPS upregulated Wnt5a and downregulated sFRP5). In HGECs, exogenously added Wnt5a enhanced whereas sFRP5 inhibited LPS-induced inflammation, as monitored by interleukin 8 production. Consistent with this, local treatment with sFRP5 in mice subjected to ligature-induced periodontitis inhibited inflammation and bone loss, correlating with decreased numbers of osteoclasts in bone tissue sections. As in humans, mouse periodontitis was associated with high expression of Wnt5a and low expression of sFRP5, although this profile was reversed after treatment with sFRP5. In conclusion, we demonstrated a novel reciprocal relationship between sFRP5 and Wnt5a expression in periodontal health and disease, paving the way to clinical investigation of the possibility of using the Wnt5a/sFRP5 ratio as a periodontitis biomarker. Moreover, we showed that sFRP5 blocks experimental periodontal inflammation and bone loss, suggesting a promising platform for the development of a new host modulation therapy in periodontitis.
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Glicoproteínas/metabolismo , Periodontitis/metabolismo , Proteína Wnt-5a/metabolismo , Pérdida de Hueso Alveolar/metabolismo , Animales , Biomarcadores/metabolismo , Biopsia , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Encía/citología , Humanos , Interleucina-8/metabolismo , Péptidos y Proteínas de Señalización Intracelular , Lipopolisacáridos/farmacología , Ratones , Ratones Endogámicos C57BL , Reacción en Cadena de la Polimerasa , Porphyromonas gingivalis , ARN Mensajero/metabolismoRESUMEN
Most patients diagnosed with tongue carcinoma undergo surgical resection and reconstructive surgery to preserve tongue mobility and swallowing functions. Twenty-four patients who underwent a total or subtotal glossectomy and surgical reconstruction were evaluated for residual taste sensation. The graded filter paper test for all four tastes (sweet, salt, sour, and bitter) was performed on the posterior wall of the oropharynx and on tongue remnants if they were visible from the mouth. Eleven of the 24 patients were aware of their taste disorder after surgery. Four patients with more than 1/2 residual tongue base had no taste complaints, whereas seven of 14 patients with less than 1/3 residual tongue base reported taste abnormalities. Patients who could only tolerate a poor diet or tube feeding tended to have taste complaints (P=0.017). The taste test showed that the taste threshold of the residual tongue was significantly lower compared to controls. The taste threshold was significantly correlated with the remaining volume of tongue base. Patients with >1/2 the tongue base remaining had good taste sensation, whereas those with <1/3 residual tissue had impaired taste. This study suggests that glossectomy strategies aimed at preserving at least half the tongue base may substantially reduce dysgeusia in the patients.
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Glosectomía/métodos , Procedimientos de Cirugía Plástica/métodos , Trastornos del Gusto/diagnóstico , Trastornos del Gusto/prevención & control , Neoplasias de la Lengua/cirugía , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Umbral Gustativo , Lengua/cirugía , Resultado del TratamientoRESUMEN
Reduced short-interval intracortical inhibition (SICI) is reported in Parkinson's disease (PD) and is considered to reflect abnormal GABAergic inhibitory system of the primary motor cortex in PD. We have recently shown, however, that SICI using anterior-posterior directed currents in the brain was normal in focal dystonia even though that using posterior-anterior currents was abnormal, indicating that the GABAergic system of the primary motor cortex is largely normal in dystonia. Here, we studied SICI in PD to clarify whether the GABAergic system is completely impaired in PD. We used paired-pulse transcranial magnetic stimulation to study SICI at interstimulus intervals of 3 and 4 ms with anterior-posterior or posterior-anterior directed currents in eight PD patients and ten healthy volunteers. The amount of SICI with posterior-anterior directed currents was reduced in PD patients compared with healthy volunteers; in contrast, SICI studied with anterior-posterior directed currents was normal in PD patients. These observations may be due to the difference in I-wave composition generated by the two directed currents and/or the difference in responsible inhibitory interneurons for the inhibition between the two current directions. We suggest that some or a part of inhibitory interneurons are not involved in PD. This discrepancy between SICI using posterior-anterior and anterior-posterior directed currents experiments may provide additional information about the circuits of the motor cortex.
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Potenciales Evocados Motores/fisiología , Corteza Motora/fisiología , Inhibición Neural/fisiología , Enfermedad de Parkinson/fisiopatología , Adulto , Anciano , Femenino , Humanos , Interneuronas/fisiología , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico , Factores de Tiempo , Estimulación Magnética Transcraneal/métodosRESUMEN
BACKGROUND: Abnormally enhanced cortical rhythmic activities have been reported in patients with cortical myoclonus. We recently reported a new triad-conditioning transcranial magnetic stimulation (TMS) method to detect the intrinsic rhythms of the primary motor cortex (M1). Triad-conditioning TMS revealed a 40-Hz intrinsic rhythm of M1 in normal subjects. In this investigation, we study the motor cortical facilitation induced by rhythmic triple TMS pulses (triad-conditioning TMS) in patients with cortical myoclonus. METHODS: Subjects were 7 patients with cortical myoclonus (28-74 years old) and 13 healthy volunteers (30-71 years old). Three conditioning stimuli over M1 at the intensity of 110% active motor threshold preceded the test TMS at various interstimulus intervals corresponding to 10-200 Hz. The resulting amplitudes of conditioned motor evoked potentials recorded from the contralateral hand muscle were compared with those evoked by the test stimulus alone. RESULTS: The facilitation at 25 ms (40 Hz) observed in normal subjects was absent in patients with cortical myoclonus. Instead, triad-conditioning TMS induced facilitation at a 40 ms interval (25 Hz) in cortical myoclonus. DISCUSSIONS: This change in the timing of facilitation may be explained by a shift of the most preferential intrinsic rhythm of M1, or by some dysfunction in the interneuronal network in cortical myoclonus.
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Potenciales Evocados Motores/fisiología , Corteza Motora/fisiopatología , Mioclonía/patología , Estimulación Magnética Transcraneal/métodos , Adulto , Anciano , Análisis de Varianza , Biofisica , Estudios de Casos y Controles , Electromiografía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mioclonía/fisiopatología , Factores de Tiempo , Estimulación Magnética Transcraneal/clasificaciónRESUMEN
SUMMARY: The aim of this study was to determine the effect of thiamylal and propofol on heart rate-corrected QT (QTc) interval during anaesthetic induction. We studied 50 patients undergoing lumbar spine surgery. Patients were administered 3 microgxkg(-1) fentanyl and were randomly allocated to receive 5 mgxkg(-1) thiamylal or 1.5 mgxkg(-1) propofol as an induction agent. Tracheal intubation was performed after vecuronium administration. Heart rate, mean arterial pressure, bispectral index score, and 12-lead electrocardiogram were recorded at the following time points: just before (T1) and 2 min after (T2) fentanyl administration; 2 min after anaesthetic administration (T3); 2.5 min after vecuronium injection (T4); and 2 min after intubation (T5). Thiamylal prolonged (p < 0.0001), but propofol shortened (p < 0.0001), the QTc interval.
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Anestésicos Intravenosos/farmacología , Electrocardiografía/efectos de los fármacos , Síndrome de QT Prolongado/inducido químicamente , Propofol/farmacología , Tiamilal/farmacología , Adulto , Anciano , Anciano de 80 o más Años , Anestésicos Intravenosos/efectos adversos , Presión Sanguínea/efectos de los fármacos , Electrocardiografía/métodos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Complicaciones Intraoperatorias/inducido químicamente , Intubación Intratraqueal/métodos , Vértebras Lumbares/cirugía , Masculino , Persona de Mediana Edad , Monitoreo Intraoperatorio/métodos , Tiamilal/efectos adversos , Adulto JovenRESUMEN
OBJECTIVES: The basal ganglia (BG) play an important role in controlling saccades. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is widely used as a treatment of Parkinson disease (PD) by altering the function of the BG. Nevertheless, the effects of STN DBS on saccade performance are not fully clarified in a systematic manner. In this study, we examined the effects of bilateral STN DBS on both the initiation and inhibition of saccades in PD. METHODS: Thirty-two patients with PD performed 4 oculomotor tasks. Two tasks (visually guided saccades and gap saccades) were reflexive and 2 (memory-guided saccades [MGS] and antisaccades) were volitional. While taking their regular doses of antiparkinsonian drugs, patients performed these tasks under 2 conditions: during DBS (DBS-on condition) and without DBS (DBS-off condition). Fifty-one age-matched subjects served as controls. RESULTS: In the DBS-on condition, parameters of saccade initiation were improved in all tasks, with shorter latencies and increased amplitudes, except for MGS latency. STN DBS improved the ability to suppress unwanted saccades to the cue stimulus in the MGS task. However, it did not suppress prosaccades during the antisaccade task. CONCLUSIONS: These results suggest that deep brain stimulation (DBS) of the subthalamic nucleus (STN) affects the neural pathway common to both reflexive and volitional saccades, possibly by acting on the STN-substantia nigra pars reticulata-superior colliculi pathway. STN DBS may set the functional level of the superior colliculi appropriate for both saccade initiation and inhibition through this pathway. These findings provide novel insights into the pathophysiology of Parkinson disease and may yield better treatment strategies.
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Estimulación Encefálica Profunda , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/terapia , Desempeño Psicomotor/fisiología , Movimientos Sacádicos/fisiología , Núcleo Subtalámico/fisiopatología , Señales (Psicología) , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vías Nerviosas/fisiopatología , Pruebas Neuropsicológicas , Tiempo de Reacción , Reflejo/fisiología , Análisis y Desempeño de Tareas , Factores de Tiempo , Volición/fisiologíaRESUMEN
INTRODUCTION: Surface protein antigen (PAc) and glucosyltransferases (GTF) are major adhesive molecules of Streptococcus mutans, though the mechanism of their regulation has not been fully elucidated. METHODS: To investigate the regulation mechanism, we determined a nucleotide sequence in the upstream region of the pac locus in S. mutans and identified two open reading frames (ORF), designated as orf1 and orf2. Each ORF was inactivated and functional analyses were performed. RESULTS: Western blot analyses revealed that the expression level of PAc was unaffected, while that of cell-associated GTF was diminished in both mutant strains. Furthermore, they showed higher hydrophobicity levels and an impaired sucrose-dependent adherence to smooth surfaces. RNA dot blot analysis demonstrated that transcriptions of the gtfB and the gtfC genes, which encode GTF-I and GTF-SI, respectively, were downregulated, while that of pac was comparable to the wild-type strain. In addition, the GTF activities of the mutant strains were significantly lower than those of the wild-type, though a greater amount of total glucan produced by the mutants was noted in culture supernatants. CONCLUSION: These findings suggest that orf1 and orf2 are associated with positive regulation of the gtfB and gtfC genes.
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Proteínas Bacterianas/genética , Regulación Enzimológica de la Expresión Génica/genética , Glucosiltransferasas/genética , Streptococcus mutans/genética , Antígenos Bacterianos/genética , Adhesión Bacteriana/genética , Western Blotting , Regulación hacia Abajo/genética , Electroforesis en Gel de Poliacrilamida , Glucanos/genética , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Immunoblotting , Proteínas de la Membrana/genética , Biología Molecular , Mutación/genética , Sistemas de Lectura Abierta/genética , Polisacáridos Bacterianos/genética , SacarosaRESUMEN
BACKGROUND AND OBJECTIVE: This study was carried out to clarify the effect of the combination of acute hypervolaemic haemodilution and hypotensive anaesthesia induced with sevoflurane on human middle cerebral artery flow velocity using transcranial Doppler ultrasonography. METHODS: Thirty patients who were maintained with N2O-O2-sevoflurane anaesthesia undergoing hip surgery were randomly divided into two groups (no controlled hypotension group, Group A, and controlled hypotension group, Group B). Haemodilution was produced by acute preoperative infusion of 1000 mL of hydroxyethylstarch without removing blood in both groups. Mean arterial pressure was maintained at approximately 95 mmHg in Group A and at 55 mmHg for 80 min by increasing the inspired concentration of sevoflurane in Group B. Middle cerebral artery flow velocity was measured before haemodilution, after haemodilution, 80 min after starting hypotension, and 60 min after recovery from hypotension. RESULTS: Middle cerebral artery flow velocity significantly increased in both groups after haemodilution; by 28%, in Group A, P < 0.05 vs. before haemodilution and by 30% vs. before haemodilution in Group B, P < 0.05). During controlled hypotension, it decreased towards the pre-haemodilution value (P < 0.05 vs. after haemodilution). CONCLUSIONS: Sevoflurane-induced hypotension to a mean arterial pressure of 55 mmHg would reduce middle cerebral artery flow that had been increased by acute hypervolaemic haemodilution, such as haematocrit value of 26%, whereas it could preserve the flow in pre-haemodilution condition during normocapnia.
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Anestésicos por Inhalación , Hemodilución/métodos , Hipotensión/fisiopatología , Éteres Metílicos , Arteria Cerebral Media/efectos de los fármacos , Monitoreo Intraoperatorio/métodos , Anciano , Artroplastia de Reemplazo de Cadera , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Femenino , Humanos , Hipotensión/inducido químicamente , Masculino , Persona de Mediana Edad , Arteria Cerebral Media/fisiopatología , Sevoflurano , Método Simple Ciego , Ultrasonografía DopplerRESUMEN
OBJECTIVE: The short interval intracortical inhibition (SICI) of the motor cortex (M1) is reduced in both cortical myoclonus and focal hand dystonia. This reduction has been attributed to the dysfunction of GABAergic system within the motor cortex. However, the precise mechanisms underlying the reduction may not be entirely identical in these two disorders, being due to primary pathological involvement in M1 or secondary to functional changes outside M1. The aim of this study was to elucidate possible differences in intracortical inhibition between these two disorders. METHODS: Subjects were 11 patients with benign myoclonus epilepsy, 7 with focal hand dystonia, and 11 normal volunteers. We studied SICI using anterior-posterior (AP) directed and posterior-anterior (PA) directed induced currents in the brain. RESULTS: In both disorders, SICI with PA-directed currents was reduced as reported previously. In contrast, SICI studied with AP currents was normal in patients with focal hand dystonia, but reduced in patients with cortical myoclonus. CONCLUSIONS: The difference between the two disorders might reflect the underlying pathological difference. In cortical myoclonus, the inhibitory interneurons of the motor cortex are affected, whereas the same interneurons are intact in dystonia. The difference in SICI induced by AP and PA directed currents in dystonia may be explained by the following possibilities: the difference in composition of I-waves contributing to EMG generation and the difference in modulation of the interneuronal activity by voluntary contraction. These changes may be secondary to dysregulation of the motor cortex by the basal ganglia or related cortices in dystonia. SIGNIFICANCE: The SICI using AP directed currents together with the conventional SICI using PA directed currents was able to demonstrate some difference in the intrinsic circuits of M1 between myoclonus and focal hand dystonia. SICI using AP directed currents can provide additional information about the motor cortical excitability changes over those obtained by the previously reported methods.
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Trastornos Distónicos/diagnóstico , Potenciales Evocados Motores/fisiología , Mano/patología , Corteza Motora/fisiopatología , Mioclonía/diagnóstico , Inhibición Neural/fisiología , Análisis de Varianza , Trastornos Distónicos/fisiopatología , Estimulación Eléctrica , Electroencefalografía , Electromiografía , Potenciales Evocados Motores/efectos de la radiación , Mano/inervación , Humanos , Mioclonía/fisiopatología , Inhibición Neural/efectos de la radiación , Factores de Tiempo , Estimulación Magnética TranscranealRESUMEN
OBJECTIVE: To assess corticospinal tract involvement in patients with amyotrophic lateral sclerosis (ALS) by correlating diffusion tensor imaging (DTI) measures with intra- and extracranial central motor conduction time (CMCT) and clinical features of the patients. METHODS: We investigated 31 patients with ALS and 31 normal volunteers by DTI and measured fractional anisotropy (FA) within the corticospinal tracts and in the extramotor white matter. We measured CMCT for the first dorsal interosseous muscle and segmented it into cortical-brainstem (CTX-BS CT) and brainstem-cervical root (BS-CV CT) conduction times by magnetic brainstem stimulation at the foramen magnum level. Clinical status of each patient was evaluated with the ALS Functional Rating Scale-Revised (ALSFRS-R) and upper motor neuron (UMN) score devised for this study. RESULTS: We found a significant decrease of mean FA in all regions of the corticospinal tracts in patients with ALS as compared with controls. We found that FA along the corticospinal tract decreased significantly with higher UMN scores. There was no significant correlation between FA and ALSFRS-R, to which both upper and lower motoneuron involvements contribute. FA showed a significant correlation with the intracranial part of the central motor conduction (CTX-BS CT) but not with the extracranial conduction time. CONCLUSIONS: Fractional anisotropy reflects functional abnormality of intracranial corticospinal tracts and can be used for objective evaluation of upper motor neuron impairment in amyotrophic lateral sclerosis.
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Esclerosis Amiotrófica Lateral/diagnóstico , Esclerosis Amiotrófica Lateral/fisiopatología , Imagen de Difusión por Resonancia Magnética/métodos , Electrodiagnóstico/métodos , Tractos Piramidales/patología , Tractos Piramidales/fisiopatología , Adulto , Anciano , Anisotropía , Tronco Encefálico/fisiopatología , Estimulación Eléctrica , Humanos , Persona de Mediana Edad , Corteza Motora/patología , Corteza Motora/fisiopatología , Neuronas Motoras/patología , Conducción Nerviosa/fisiología , Valor Predictivo de las Pruebas , Tiempo de Reacción , Factores de TiempoRESUMEN
Water-insoluble alpha-glucans are synthesized from sucrose by glucosyltransferase-I of mutans streptococci and play an important role in the development of dental plaque. Several types of beta-glucans in fungal cell wall components and water-soluble alpha-glucans from Streptococcus mutans are known to modulate innate immunity. In the present study, we investigated whether water-insoluble alpha-glucans also induced inflammatory innate immune responses. Our results showed that water-insoluble alpha-glucans synthesized by Streptococcus sobrinus activated mouse peritoneal exudate macrophages to produce pro-inflammatory cytokines. The immunological responses were not due to contamination by sucrose, water-soluble alpha-glucan, lipopolysaccharide, or peptidoglycan. Furthermore, human monocytes stimulated by water-insoluble alpha-glucans produced TNF-alpha and IL-8, while human polymorphonuclear cells were activated by water-insoluble alpha-glucans, resulting in chemotaxis and hydrogen peroxide production. The results demonstrated that water-soluble alpha-glucans modulate macrophage- and granulocyte-induced inflammatory immune responses, and suggest that inflammation induced by those alpha-glucans is associated with the development of periodontal diseases.
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Citocinas/biosíntesis , Glucanos/farmacología , Mediadores de Inflamación/metabolismo , Macrófagos Peritoneales/efectos de los fármacos , Monocitos/efectos de los fármacos , Animales , Proteínas Bacterianas/inmunología , Proteínas Bacterianas/farmacología , Línea Celular , Quimiotaxis de Leucocito , Femenino , Glucanos/inmunología , Humanos , Ratones , Ratones Endogámicos BALB C , Activación Neutrófila , Solubilidad , Estreptococos Viridans/fisiologíaRESUMEN
Arylmalonate decarboxylase (EC 4.1.1.76) catalyzes enantioselective decarboxylation of alpha-aryl-alpha-methylmalonates to give optically pure alpha-arylpropionates. Recently, we have succeeded in creating a double mutant enzyme that gave opposite enantionmer as the product. Unfortunately, however, the activity of the mutant decreased far lower than that of the native enzyme. Thus, we performed the directed evolution of the mutant via the random mutagenesis method employing the mutator strain Escherichia coli XL1-Red. About 50,000 mutants were screened on color assay plate, and one mutant with higher activity was obtained. Gene analysis of this mutant indicated that the obtained enzyme had an S36N mutation in addition to its original G74C/C188S mutations. The activity of the triple mutant enzyme was tenfold higher than that of the starting doubly mutated enzyme.
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Alcaligenes/enzimología , Carboxiliasas/genética , Carboxiliasas/metabolismo , Evolución Molecular Dirigida , Mutagénesis , Sustitución de Aminoácidos , Carboxiliasas/química , Carboxiliasas/aislamiento & purificación , Escherichia coli/genética , Cinética , Mutación , Ingeniería de Proteínas , Estereoisomerismo , Especificidad por Sustrato , Transformación BacterianaRESUMEN
2,2-bis (4-hydroxyphenyl) propane or Bisphenol A (BPA), has been reported to behave as an endocrine disrupter below acute toxic levels, and is widely present in the water environment. Although BPA is easily chlorinated, very little is reported on the effect of chlorinated BPA to the aquatic organisms. In this study, the estrogenic activities of BPA and its chlorinated derivatives were evaluated by the induction of vitellogenin (VTG) in the serum of mature male Japanese medaka. In addition, the effect of sodium hypochlorite on the decomposition of BPA was tested. The relative potencies of estrogenic activities of chlorinated BPA descended in the order 3,3'-diCIBPA>BPA> or =3-CIBPA>3,3',5-triCIBPA, and no estrogenic activity was observed in 3,3',5,5'-tetraCIBPA. Lowest Observed Effect Concentration (LOEC) and No Observed Effect Concentration (NOEC) for both 3-CIBPA and 3,3'-diCIBPA were 500 microg/L and 200 microg/L, respectively. LOEC for 3,3',5-triCIBPA was >500 microg/L. When BPA was reacted with sodium hypochlorite (24 hours; residual chlorine at 1 ppm), however, complete decomposition of BPA and its chlorinated derivatives was observed. The decrease in BPA and its chlorinated derivatives paralleled the decrease in estrogenic potency evaluated by the induction of vitellogenin (VTG) in the serum of mature male Japanese medaka.
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Cloro/química , Fenoles/toxicidad , Vitelogeninas/sangre , Contaminantes Químicos del Agua/toxicidad , Animales , Compuestos de Bencidrilo , Sistema Endocrino/efectos de los fármacos , Exposición a Riesgos Ambientales , Masculino , Oryzias , Fenoles/química , Hipoclorito de Sodio/análisis , Hipoclorito de Sodio/química , Factores de Tiempo , Vitelogénesis/efectos de los fármacosRESUMEN
The purpose of this study was to examine characteristic profiles of Streptococcus pyogenes clinical isolates isolated in Japan during 1994-9. Genotyping of the M protein (emm typing) revealed that emm types 12 and 28 were the most common among 316 isolates. Most of the emm12 isolates were isolated from mucosa, while emm58 and emm89 were from skin. Moreover, the emm3 isolates were dominant in invasive infections. The distribution of 6 superantigen genes showed that all isolates harboured the mf gene and many had the speG gene. Invasive isolates were shown to have the ssa gene at a higher rate (76%) than noninvasive (37%). The distribution of superantigens was significantly different between emm types, but not between isolation sites. These results suggest that the distribution of emm types is related to isolation site, whereas superantigen distribution is related to clinical features of S. pyogenes infections.
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Antígenos Bacterianos , Proteínas de la Membrana Bacteriana Externa/genética , Proteínas Portadoras/genética , Infecciones Estreptocócicas/patología , Streptococcus pyogenes/genética , Streptococcus pyogenes/patogenicidad , Superantígenos/análisis , Genotipo , Humanos , Reacción en Cadena de la Polimerasa , Infecciones Estreptocócicas/genética , Streptococcus pyogenes/inmunologíaRESUMEN
We used microarray analysis to investigate expression profiles of 589 known genes committed to cell growth control to characterize regulatory circuitry for cell proliferation in complete moles (CMs). CMs are characterized by hyperplastic trophoblast and have a high propensity to give rise to choriocarcinoma. Characteristic alterations in gene expression profiles were observed when compared with normal villi. Fifty-seven genes were significantly up-regulated in CMs and involved the Ras-Map kinase 3, Jak-STAT5, and Wnt signal pathways, implicating growth factor or cytokine-mediated signal pathways in the trophoblastic hyperplasia of CMs. Several genes associated with anti-apoptosis, cell structuring, and/or cell attachment were also up-regulated in CMs. In contrast, relatively fewer genes were down-regulated and these involved IGFBPs, versican, interleukin-1, tumor necrosis factor receptor, CD44, and RAD52. Genes identified in this study may elucidate regulation mechanisms of trophoblastic proliferation and mechanisms causing a pathological phenotype in CMs.
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Vellosidades Coriónicas/metabolismo , Mola Hidatiforme/genética , Mola Hidatiforme/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Trofoblastos/metabolismo , Neoplasias Uterinas/genética , Neoplasias Uterinas/metabolismo , Apoptosis/genética , Apoptosis/fisiología , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/metabolismo , Femenino , Genes cdc/fisiología , Sustancias de Crecimiento/genética , Sustancias de Crecimiento/metabolismo , Humanos , EmbarazoRESUMEN
Light scattering, sedimentation equilibrium, viscosity, circular dichroism (CD), and UV absorption (UV) measurements were made on dilute solutions of poly([(R)-3,7-dimethyloctyl]-[(S)-3-methylpentyl]silylene)(PRS) as functions of molecular weight. From light scattering and viscosity data, PRS is found to be a very stiff polymer of persistence length q as large as 103 nm at 25 degrees C, essentially a 7(3) helix found in the solid state; q increases only gradually with lowering temperature between -15 and 25 degrees C. The CD data show that PRS undergoes a conformational transition around 3 degrees C in isooctane (transition temperature T(c)). The CD signal is largely positive at low temperatures, passes through zero at T(c), and becomes largely negative at higher temperatures; T(c) is independent of sample's chain length N. This is a highly cooperative helix (M)-to-helix (P) transition depending remarkably on N, as PRS is substantially rodlike. The CD data are converted to the fraction f(P) of P helix as a function of N and analyzed successfully by a statistical mechanical theory based on a helix reversal model, where a polymer chain consists of M and P helices intervened by helix reversals, with the result that the free energy difference DeltaG(h) between P and M shows a temperature dependence similar to that of 2f(P) - 1, whereas the helix reversal energy is substantially constant at 1.2 x 10(4) J mol(-1); the latter value means that the helix reversal occurs only once in 100 Si units or less. This DeltaG(h) change and solvent dependence of T(c) are explained by a double-well potential for the rotation about Si-Si bonds, which incorporates into DeltaG(h) the solvent interactions with the helical grooves of side chains surrounding the main chain. Detailed features of UV absorption spectra at different temperature and molecular weights are also presented.
RESUMEN
We demonstrated here the growth-suppressing effects of sodium butyrate (NaB) on human endometrial and ovarian cancer cells. The arrest of cells at the G1 checkpoint accounted for this effect. NaB-mediated p21 might arrest endometrial and ovarian cancer cells at the G0/G1 phase by eliciting pRb unphosphorylation. To demonstrate the role of pRb regulation by p21, we measured the sensitivity to NaB of cervical cancer cells in which pRb had been inactivated by HPV E7. The cervical cancer cells displayed a sensitivity in NaB-mediated G2/M arrest in addition to their sensitivity in G0/G1 arrest. Arrest at G0/G1 and G2/M accompanied induction of senescence-like phenotypes (SLPs). Most importantly, the effect of NaB on senescence induction was not coupled with the predominance of hypophosphorylated pRb forms in the cervical cancer cells. This suggested that NaB had the potential to elicit SLPs through p21-mediated withdrawal from cell cycle progression. The consequences of p21 induction were manifold. The effects of NaB on gynecologic cancer cell growth indicated its potential use in cancer treatment. NaB was effective even in the cancer cells with mutant p53 and/or Rb genes by eliciting cell senescence.
Asunto(s)
Butiratos/farmacología , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Animales , Ciclo Celular/efectos de los fármacos , Senescencia Celular/efectos de los fármacos , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Ciclinas/biosíntesis , Femenino , Neoplasias de los Genitales Femeninos/patología , Humanos , Ratones , Ratones Endogámicos BALB C , Fenotipo , Células Tumorales CultivadasRESUMEN
We previously determined the chemical structures of four 2-phenylbenzotriazole mutagens (PBTA-1, -2, -3 and -4) in blue rayon-adsorbed material from the Nishitakase River in Kyoto prefecture and the Nikko River in Aichi prefecture in Japan. On the basis of a synthesis study, these four PBTA derivatives were deduced to have originated from corresponding dinitrophenylazo dyes by reduction and chlorination. 2-[(2-Bromo-4,6-dinitrophenyl)azo]-5-[bis(2-acetoxyethyl) amino]-4-methoxyacetanilide (Color Index Name, Disperse Blue 79:1; CAS Registry Number, 75497-74-4) is a very common dinitrophenylazo dye used in textile dyeing factories. In the present study, we synthesized 2-[4-[bis(2-acetoxyethyl)amino]-2-(acetylamino)-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-5) from Disperse Blue 79:1 by reduction with sodium hydrosulfite and subsequent chlorination with sodium hypochlorite. On hydrolysis of PBTA-5 with alkali, 2-[2-(acetylamino)-4-[bis(2-hydroxyethyl)amino]-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-6) was obtained. Both PBTA-5 and -6 were potent mutagens, inducing 723,000 revertants and 485,000 revertants per microgram of Salmonella typhimurium YG1024, respectively, in the presence of S9 mix. To clarify whether PBTA-5 and -6 exist in the environment, water samples were collected from five rivers flowing through regions where textile dyeing industries are developed. PBTA-6 was detected at levels of 3-134 ng/g blue rayon in all water samples that were examined. On the other hand, the amount of PBTA-5 in the samples was less than the detection limit.
Asunto(s)
Celulosa/análogos & derivados , Triazoles/análisis , Triazoles/química , Triazoles/síntesis química , Adsorción , Celulosa/química , Cromatografía Líquida de Alta Presión , Colorantes/química , Agua Dulce/química , Indoles/química , Japón , Pruebas de Mutagenicidad , Mutágenos/análisis , Mutágenos/síntesis química , Mutágenos/toxicidad , Compuestos Organometálicos/química , Triazoles/toxicidadRESUMEN
OBJECTIVES: To study changes in the excitability of the sensory cortex by repetitive transcranial magnetic stimulation (rTMS) in humans. METHODS: Somatosensory evoked potentials (SEPs) and antidromic sensory nerve action potentials (SNAPs) were elicited by right median nerve stimulation at the wrist before and after low frequency (1 Hz) rTMS over the left motor cortex, lateral premotor cortex, sensory cortex, and also after sham stimulation. The intensity of rTMS was fixed at 1.1 times the active motor threshold at the hand area of motor cortex. RESULTS: N20 peak (N20p)-P25 and P25-N33 amplitudes were suppressed after rTMS over the motor cortex, whereas the N20 onset (N20o)-N20p and SNAP amplitudes were not affected. They recovered to the baseline about 100 min after the rTMS. rTMS over the premotor cortex or sensory cortex or sham stimulation had no suppressive effect on SEPs. CONCLUSIONS: The reduction of N20p-P25 and P25-N33 components without any changes of N20o-N20p amplitude suggests that the suppression occurs in the sensory cortex. rTMS (1 Hz) of the motor cortex induces a long-lasting suppression of the ipsilateral sensory cortex even at an intensity as low as 1.1 times the active motor threshold, probably via cortico-cortical pathways between motor and sensory cortex.