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Background: The use of generative artificial intelligence (AI) applications such as ChatGPT is becoming increasingly popular. In Japan, consumers can purchase most over-the-counter (OTC) drugs without having to consult a pharmacist, so they may ask generative AI applications which OTC drugs they should purchase. This study aimed to systematically evaluate responses from ChatGPT to consumer inquiries about various OTC drugs. Methods: We selected 22 popular OTC drugs and 12 typical consumer characteristics, including physical and disease conditions and concomitant medications. We input a total of 264 questions (i. e., all combinations of drugs and characteristics) to ChatGPT in Japanese, asking whether it is safe for consumers with each characteristic to take these OTC drugs. We used the generic name for 10 of the 22 drugs and the brand name for the remaining 12. Responses were evaluated based on the following three criteria: 1) coherence between the question and response, 2) scientific correctness, and 3) appropriateness of the instructed actions. When we received a response that satisfied all three criteria, we input the exact same question on a different day to assess reproducibility. Results: The proportions of ChatGPT's answers that satisfied criteria 1, 2, and 3 were 79.5%, 54.5%, and 49.6%, respectively. However, the proportion of responses that satisfied all three criteria was only 20.8% (55/264); 61.8% (34/55) of these responses were reproduced when the same question was input again on a different day. Compared with questions using generic names, those using brand names resulted in lower coherence and scientific correctness. Among the 12 characteristics, the appropriateness of the instructed actions tended to be lower in responses to questions about driving and concomitant medications. Conclusions: Our study revealed that ChatGPT was less accurate in its responses and less consistent in its instructed actions compared with the package inserts. Our findings suggest that Japanese consumers should not consult ChatGPT regarding OTC medications, especially when using brand names.
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Inteligencia Artificial , Farmacéuticos , Humanos , Reproducibilidad de los Resultados , Japón , Medicamentos sin PrescripciónRESUMEN
WHAT IS KNOWN AND OBJECTIVE: Miconazole is a strong inhibitor of CYP2C9, one of the main enzymes involved in the metabolism of warfarin. Concurrent use of the two drugs leads to potentially serious adverse effects. Although it is often assumed that use of the oral miconazole gel is acceptable with concomitant warfarin, because of the low bioavailability following buccal administration, drug-drug interactions have been reported following such use. We aimed to investigate case reports of such interactions and develop a pharmacokinetic model to model such interactions. METHODS: The Medline database from 1966 to October 2010 was used for literature search. Case reports of the potentiation of the anticoagulant effects of warfarin, such as the elevation of prothrombin time (INR), by concomitant administration of warfarin and miconazole oral gel were collected. We quantitatively estimated the extent of inhibition of warfarin metabolism by orally administered miconazole gel and compared our findings with case reports. RESULTS AND DISCUSSION: Metabolism of (S)-warfarin is inhibited potently following administration of a standard dose (200-400 mg/day in Japan) of miconazole gel. This may lead to in an increase in the blood concentration of warfarin and lead to serious adverse effects. The literature reports of clinical interactions with concomitant use of those drugs show that other factors may amplify the effects of any increase in blood concentration. WHAT IS NEW AND CONCLUSION: We summarize all reported, clinically significant, cases of drug interaction between miconazole oral gel and warfarin. Pharmacokinetic modelling shows that concomitant administration of warfarin and miconazole oral gel can lead to substantial increase in warfarin concentration. However, our PK/PD model fails to capture the dramatic increases seen in INR values, and hence bleeding complications, reported in the literature. Taken together, the evidence suggests that concomitant use of miconazole gel and warfarin should be avoided. Even over-the-counter products containing miconazole should be used with caution by patients receiving warfarin.
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Miconazol/farmacología , Modelos Biológicos , Warfarina/farmacocinética , Administración Oral , Anticoagulantes/efectos adversos , Anticoagulantes/farmacocinética , Antifúngicos/efectos adversos , Antifúngicos/farmacología , Disponibilidad Biológica , Interacciones Farmacológicas , Femenino , Geles , Hemorragia/inducido químicamente , Humanos , Relación Normalizada Internacional , Miconazol/efectos adversos , Warfarina/efectos adversosRESUMEN
The neoplastic environment is generally regarded as an immunosuppressive milieu. However, a group of cancers are characterized by the abundance of tumour-infiltrating lymphocytes (TILs). Here we examined the possible roles of chemokines in the formation of lymphoid stroma in lymphocyte-rich gastric carcinomas (GCs), including EBV(+) cases and conventional GCs. Regardless of EBV positivity, TILs in lymphocyte-rich GCs predominantly expressed CXCR3, while its ligand CXCL9 was abundantly expressed by stromal cells and a portion of cancer cells. CXCL9(+) stromal cells were judged to include dendritic cells, because they partly co-expressed fascin, DC-sign, CD83, DC-lamp or HLA-DR. T cells in close contact with CXCL9(+) cells showed frequent labelling of Ki-67 (approximately 10%), suggesting the immunostimulatory activity of CXCL9(+) stromal cells. The T-cell zone of the regional lymph nodes of lymphocyte-rich GCs also abounded with CXCR3(+) T cells and CXCL9(+) stromal cells. This indicated a close similarity between cancer stroma and regional lymph nodes of lymphocyte-rich GCs. Quantitative RT-PCR also confirmed the strong expression of CXCR3, CXCL9 and IFNgamma in lymphocyte-rich GCs. In contrast, conventional GCs contained less abundant CXCR3(+) T cells and few CXCL9(+) stromal cells. Collectively, the CXCL9-CXCR3 axis plays a pivotal role in the formation of lymphoid stroma in lymphocyte-rich GCs. Given similar findings in the regional lymph nodes, the lymphoid stroma of lymphocyte-rich GCs may represent a tertiary lymphoid tissue with predominantly Th1-shifted immune responses.
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Quimiocina CXCL9/metabolismo , Células Dendríticas/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Neoplasias Gástricas/inmunología , Células del Estroma/inmunología , Proliferación Celular , Quimiocina CXCL10/genética , Quimiocina CXCL10/metabolismo , Quimiocina CXCL9/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/inmunología , Factores de Transcripción Forkhead/metabolismo , Humanos , Técnicas para Inmunoenzimas , Interferón gamma/genética , Interferón gamma/metabolismo , Ganglios Linfáticos/inmunología , Estadificación de Neoplasias , ARN Mensajero/genética , Receptores CXCR3/genética , Receptores CXCR3/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/virología , Subgrupos de Linfocitos T/inmunología , Linfocitos T Reguladores/inmunologíaRESUMEN
OBJECTIVE: Itraconazole is a potent inhibitor of cytochrome P450 (CYP) 3A with an elimination half-life of more than 30 hours. Therefore, itraconazole may cause persistent CYP3A inhibition. Triazolam is primarily metabolized by CYP3A and its plasma concentration is increased remarkably by itraconazole. Although separating their dosages by 24 hours has been shown to reduce the interaction, an appropriate dosage interval remains to be determined. The aim of this study was to identify an appropriate dosage schedule to avoid their interaction. MATERIALS AND METHODS: We developed a pharmacokinetic model based on the assumption that both itraconazole and hydroxyitraconazole competitively and reversibly inhibit the first-pass metabolism and systemic elimination of triazolam. The developed model was simultaneously fitted to the plasma concentration profiles of triazolam, taken from the literature, by using the plasma concentration-time profiles of itraconazole and hydroxyitraconazole as input functions to estimate their in vivo Ki values. Subsequently, we simulated the plasma concentration profiles of triazolam administered after itraconazole therapy with various dosing intervals. RESULTS: The model could explain and simulate the interaction between itraconazole-triazolam using a variety of dosage intervals between the administrations. CONCLUSIONS: The developed model may provide useful information with regard to the appropriate interval for triazolam administration during itraconazole therapy.
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Itraconazol/farmacocinética , Modelos Biológicos , Triazolam/farmacocinética , Administración Oral , Ansiolíticos/administración & dosificación , Ansiolíticos/farmacocinética , Antifúngicos/administración & dosificación , Antifúngicos/farmacocinética , Antifúngicos/farmacología , Simulación por Computador , Citocromo P-450 CYP3A/metabolismo , Inhibidores del Citocromo P-450 CYP3A , Esquema de Medicación , Interacciones Farmacológicas , Humanos , Itraconazol/administración & dosificación , Itraconazol/análogos & derivados , Itraconazol/farmacología , Factores de Tiempo , Triazolam/administración & dosificaciónRESUMEN
Heat conduction mechanisms in nanofluids, fluids seeded with nanoparticles, have been extensively scrutinized in the past decades to explain some experimental observations of their enhanced thermal conductivity beyond the effective medium theory. Although many mechanisms such as Brownian motion, clustering, ballistic transport, and internanoparticle potential are speculated, experimental proof of any of the mechanisms has been difficult. Here, we investigate the mechanisms experimentally by thermal conductivity measurements and structural analysis for the same materials in both liquid and solid states. These studies strongly suggest that clustering holds the key to the thermal conductivity enhancement of nanofluids.
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Transferencia de Energía , Calor , Microfluídica/métodos , Modelos Teóricos , Nanoestructuras/química , Soluciones/química , Simulación por Computador , Nanoestructuras/ultraestructura , Conductividad TérmicaRESUMEN
BACKGROUND: There are three subtypes of monoclonal immunoglobulin deposition disease: light chain deposition disease (LCDD), light and heavy chain deposition disease (LHCDD), and heavy chain deposition disease (HCDD). Although it has been considered that LHCDD is a variant of LCDD, information on clinicopathological features and prognosis in LHCDD is presently limited. METHODS: We reviewed 5,443 renal biopsies, and evaluated clinicopathological features and outcomes in patients with LHCDD, in comparison with those in patients with LCDD and previously reported patients with HCDD. We also characterized paraprotein deposits in patients with LHCDD. RESULTS: We identified 6 patients with LHCDD, 6 patients with LCDD, and 1 patient with HCDD. The most common clinicopathological findings in patients with LHCDD were proteinuria, renal insufficiency, and nodular sclerosing glomerulopathy. Three patients had IgG-k deposits and 3 patients had IgG-l deposits. Heavy chain subclass analysis performed in 4 patients showed IgG3 deposits in all patients. Dual immunostaining revealed glomerular colocalization of light and heavy chains. In contrast with LCDD, glomerular C3 and C1q deposits were common findings in LHCDD and HCDD. All patients with LHCDD were treated with steroids and cytotoxic agents, but no effect on proteinuria was observed. Three patients developed end-stage renal disease requiring hemodialysis. The underlying hematological disorders in LHCDD and HCDD were milder than in LCDD. Early renal survival and overall patient survival in our patients appeared to be better in LHCDD than in LCDD. CONCLUSIONS: There are apparent differences in clinicopathological features and prognosis between LHCDD and LCDD. LHCDD is probably more similar to HCDD.
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Cadenas Pesadas de Inmunoglobulina , Cadenas Ligeras de Inmunoglobulina , Paraproteinemias/diagnóstico , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Enfermedades Renales/etiología , Enfermedades Renales/mortalidad , Enfermedades Renales/patología , Masculino , Persona de Mediana Edad , Paraproteinemias/mortalidad , Paraproteinemias/terapia , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) associated with membranoproliferative features is an extremely rare entity. Information on clinicopathological features and prognosis in this entity is limited. METHODS: We reviewed 5,443 renal biopsies processed at our department, and identified 4 patients with PGNMID associated with membranoproliferative features. We evaluated clinicopathological features and outcomes in these patients, and characterized paraprotein deposits by immunofluorescence studies. RESULTS: Three out of 4 patients had nephrotic syndrome with renal insufficiency at presentation. Cryoglobulin or monoclonal protein in serum and urine was not detected. Renal biopsy showed membranoproliferative features with or without nodular formation. Tubulointerstitial and vascular alterations were mild in three patients. All patients had glomerular IgG-kappa deposits. Heavy chain subclass analysis performed in 3 patients showed IgG3 deposits. Immunofluorescence studies using antibodies specific for gamma-heavy chain C(H)1, C(H)2, and C(H)3 domains and gamma3 hinge did not show any apparent deletion. Confocal microscopy revealed glomerular colocalization of light and heavy chains. On electron microscopy, granular deposits were predominantly mesangial and subendothelial. All patients were treated with steroids and cytotoxic agents, but no effect on proteinuria was observed. The renal outcome was progressive in all patients. Early death was observed in two elder patients. No patient had overt myeloma or lymphoma at presentation or over the course of follow-up (mean 43 months). CONCLUSIONS: Our study suggests a predominance of IgG3-kappa glomerular deposits of nondeleted whole immunoglobulin molecules in PGNMID associated with membranoproliferative features. The clinical outcome in patients with this entity appears to be poor.
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Glomerulonefritis Membranoproliferativa/inmunología , Inmunoglobulina G/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Femenino , Técnica del Anticuerpo Fluorescente , Glomerulonefritis Membranoproliferativa/epidemiología , Glomerulonefritis Membranoproliferativa/patología , Humanos , Incidencia , Japón/epidemiología , Masculino , Microscopía Confocal , Microscopía Electrónica , Persona de Mediana EdadRESUMEN
The Japanese frog, Rana rugosa, has two distinct sex chromosome types, XX/XY and ZZ/ZW. These two types are found in localized groups, separated geographically by a boundary area predicted to lie somewhere around Lake Biwa in central Japan. To determine this precise boundary, the heterogametic sex of 18 populations around Lake Biwa was examined by genotyping sex-linked genes. Phylogenetic relationships between the populations were also analyzed using mitochondrial 12S rRNA gene. Results showed that the Suzuka-Kii mountain range located east of Lake Biwa separated the XX/XY populations from the ZZ/ZW populations. Unexpectedly, from a phylogenetic perspective, the ZZ/ZW populations around Lake Biwa belonged not to the main ZW group but to the XY group. The authors propose that the ZZ/ZW populations around Lake Biwa diverged secondarily from the XX/XY group through a change of heterogametic sex, eventually forming a new group. This group was thus named the 'Neo-ZW group'. As the main ZW group inhabiting northwestern Japan is known to have a different male heterogametic origin, this finding shows that change of heterogametic sex from male to female may have occurred twice, and independently, during the frog speciation.
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Evolución Biológica , ADN Mitocondrial/genética , Ranidae/genética , Cromosomas Sexuales/genética , Procesos de Determinación del Sexo , Animales , Cruzamientos Genéticos , Diploidia , Femenino , Genes Mitocondriales , Genes de ARNr , Genotipo , Masculino , FilogeniaRESUMEN
In this study, we suggested two types of novel metallized tip for the apertureless near-field scanning optical microscope probe. The first is a silver nanorod immobilized tip and the other is a double metallized probe. We calculated the electric field enhancement factor and the electric field distribution of a single sphere, aggregated spheres, an ellipse and a nanorod by the finite-differential time-domain method to improve the silver nanosphere immobilized tip developed in our previous studies. The enhanced field of the nanorod is localized at the external surfaces. The simulation results of the nanorod revealed that the position of the maximum peak is shifted to a longer wavelength and that its electric field enhancement factor increases as the aspect ratio increases. Thus, we developed the silver nanorod immobilized tip, and the tip-enhanced Raman spectrum of rhodamine 6G molecule on the substrate could be measured by the tip though it could not be detected by the previous nanosphere immobilized tip. Further, the finite-differential time-domain calculation predicted that the double metallized tips considerably enhance the electric field and that its enhancement factor in the longer wavelength region (500-600 nm) does not decrease when the tip is rounded. The results show that the proposed metallized tips were useful for the apertureless near-field scanning optical microscope system.
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A 63-year-old man with systemic lupus erythematosus developed tubular proteinuria. All subclasses of serum IgG increased, and the largest IgG subclass increase was IgG4. A renal biopsy showed lupus nephritis (Class II) with severe tubulointerstitial nephritis (so-called predominant tubulointerstitial lupus nephritis, an unusual form of lupus nephritis). Immunofluorescence microscopy revealed positive granular staining for IgG, C3 and C1q in the mesangium and peritubular interstitium, and along the tubular basement membranes (TBM). Electron microscopy also showed electron-dense deposits in the mesangium and TBM. Immunophenotyping of interstitial infiltrating cells disclosed a predominance of T cells. CD8-positive cytotoxic T cells infiltrated the peritubular interstitium, and some of these cells infiltrated the tubules. B cell-rich lymphoid follicles were also observed. IgG subclass analyses showed glomerular IgG1, IgG2 and IgG4 deposition, positive staining of IgG4 in the peritubular interstitium and along the TBM, and abundant IgG1-, IgG3- and IgG4-positive plasma cells in the interstitium. The patient responded well to moderate-dose steroid therapy. This is the first report of immunophenotyping of interstitial infiltrates in predominant tubulointerstitial lupus nephritis. The results suggest CD8-positive cytotoxic T cell-mediated tubular injury. Furthermore, immune complexes containing IgG4 might be one of etiologic factors.
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Linfocitos T CD8-positivos/inmunología , Inmunoglobulina G/inmunología , Riñón/patología , Nefritis Lúpica/patología , Nefritis Intersticial/patología , Biopsia , Linfocitos T CD8-positivos/patología , Humanos , Inmunoglobulina G/análisis , Inmunohistoquímica , Nefritis Lúpica/inmunología , Masculino , Persona de Mediana Edad , Nefritis Intersticial/inmunologíaRESUMEN
Rapid and simple capillary electrophoresis (CE) methods were developed for the simultaneous determinations of cinnarizine and domperidone (CN/DOM) and cinnarizine and nicergoline (CN/NIC) in their co-formulated tablets. The optimized CE conditions were as follows: running buffer, methanol-acetate buffer (pH 3.0, 10 mM) (80:20 and 85:15 (v/v) for CN/DOM and CN/NIC, respectively); applied voltage, 20 kV; UV detection wavelengths, 215 and 227 nm for CN/DOM and CN/NIC, respectively; hydrodynamic injection was performed at a height of 25 mm for 30 s. Quinine hydrochloride and nicardipine hydrochloride were used as internal standards for the determination of CN/DOM and CN/NIC, respectively. Calibration curves were linear over the ranges 0.25-20/0.375-15 microg/ml (CN/DOM) and 0.25-25/0.4-10 microg/ml (CN/NIC) in each optimized condition. Detection limits were 0.074/0.119 microg/ml and 0.072/0.116 microg/ml for CN/DOM and CN/NIC, respectively. The proposed methods were successfully applied for the simultaneous determination of both CN/DOM and CN/NIC in their co-formulated tablets without interfering peaks due to the excipients present in the pharmaceutical tablets. The estimated amounts of CN/DOM and CN/NIC were almost identical with the certified values, and their percentage relative standard deviation values (%R.S.D.) were found to be < or =2.34% (n=3).
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Cinarizina/análisis , Electroforesis Capilar/métodos , Tampones (Química) , Química Farmacéutica , Cinarizina/química , Estabilidad de Medicamentos , Concentración de Iones de Hidrógeno , ComprimidosRESUMEN
A 69-year-old female with a 3-year history of polycythemia vera (PV) developed nephrotic syndrome. A renal biopsy showed focal and segmental glomerulosclerosis (FSGS). The patient was treated with prednisolone and myelosuppressive agents. Thereafter, parallel improvement of the two conditions was observed. After 4-year treatment, proteinuria disappeared. To our knowledge, there are five reported cases of FSGS associated with PV. Among them, three patients suffered from progressive azotemia. We suggest that steroid therapy with myelosuppressive agents can resolve the renal lesion in patients with PV.
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Glomeruloesclerosis Focal y Segmentaria/complicaciones , Policitemia Vera/complicaciones , Anciano , Femenino , Glomeruloesclerosis Focal y Segmentaria/patología , Humanos , Policitemia Vera/patologíaRESUMEN
OBJECTIVE: New quinolones (NQs) are widely used to treat various infections. However, concomitant oral administration of metal cations may decrease absorption of NQs and consequently decrease their blood concentration and pharmacological effect. A convenient approach to avoid this interaction is to separate the dosages by a certain interval. In this study, we aimed to develop a novel pharmacokinetic model to describe NQs-metal cation interactions in order to estimate the optimal dosing interval. METHODS: Plasma concentration-time profiles of NQs after administration without or with metal cations at various dosing intervals were collected from the literature and analyzed with a pharmacokinetic model incorporating the formation ofNQs-metal cations complex. The model was fitted to the reported time profiles ofciprofloxacin (CPFX) plasma concentration after concomitant administration with aluminum hydroxide/magnesium hydroxide antacid (Al/Mg antacid; Maalox, Maalox70) at various dosing intervals to obtain the pharmacokinetic parameters of CPFX. Model analysis was also carried out for gatifloxacin (GFLX) and norfloxacin (NFLX). RESULTS: The developed model could adequately explain the interactions in all the combinations investigated. The model predicted, in the cases of usual doses of CPFX with Maalox, GFLX with Maalox70 and NFLX with sucralfate, that the NQ should be administered 4.5, 4.5 and 3.5 hours after, or 1, 1 and 0.5 hours before the administration of metal cations, respectively, to ensure 90% of control absorption. CONCLUSIONS: The developed model can adequately describe the extent of interaction between NQs and metal cations, and should be clinically useful to design dosage regimens to circumvent the interaction.
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Antiácidos/administración & dosificación , Antiinfecciosos/administración & dosificación , Antiinfecciosos/farmacocinética , Fluoroquinolonas/administración & dosificación , Fluoroquinolonas/farmacocinética , Administración Oral , Hidróxido de Aluminio/administración & dosificación , Antiinfecciosos/sangre , Disponibilidad Biológica , Cationes/administración & dosificación , Ciprofloxacina/administración & dosificación , Ciprofloxacina/farmacocinética , Esquema de Medicación , Combinación de Medicamentos , Interacciones Farmacológicas , Fluoroquinolonas/sangre , Gatifloxacina , Humanos , Absorción Intestinal/efectos de los fármacos , Hidróxido de Magnesio/administración & dosificación , Modelos Biológicos , Norfloxacino/administración & dosificación , Norfloxacino/farmacocinética , Valores de Referencia , Sucralfato/administración & dosificaciónRESUMEN
Successful case studies for waste recycling in Japan have not been evaluated. The evaluation of economic efficiency and environmental effects were lacking at the time the actual network was established. A waste/resource input/output (I/O) coincidence retrieval system called ZENESYS was developed to examine the usefulness of a waste-exchange network in a nonmanufacturing district. We analyzed data from the Miyagi prefecture, a region without heavy industry. The data were collected from 77 companies using a questionnaire and interviews. A total of 33 possible waste exchange links arose after analysis using ZENESYS. However, these were frail networks that relied heavily on the construction industry. Two waste recycling technologies were selected from the ZENESYS database: reclaiming fuel from waste plastic and making construction materials from bottom ash. Evaluation of the environmental effects and economics of these two technologies showed they were both suitable for the environment, but no profit was made from reclaiming fuel from waste plastics. We concluded that in an area with no heavy industry, it may be difficult to adopt recycling technologies that have high environmental and economic performance. Materials are difficult to circulate among manufacturing industries even if a waste-exchange network exists, and resources are consumed during transportation and recycling.
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Conservación de los Recursos Naturales , Eliminación de Residuos , Administración de Residuos , JapónRESUMEN
BACKGROUND: Increased serum levels of S100A12, a proinflammatory protein secreted by activated neutrophils, have recently been shown in patients with active inflammatory diseases, such as rheumatoid arthritis and Kawasaki disease. In this study, we investigated serum levels of S100A 12 in patients with small-vessel vasculitis, myeloperoxidase anti-neutrophil cytoplasmic antibodies- (MPO-ANCA) associated pauci-immune glomerulonephritis. METHODS: Serum S100A12 concentrations were measured by a sandwich enzyme-linked immunosorbent assay (ELISA) in 46 patients with MPO-ANCA-associated glomerulonephritis and 29 healthy controls. We analyzed correlations between serum S100A12 levels and a clinical index of vasculitis activity, the Birmingham Vasculitis Activity Score (BVAS), various laboratory parameters, and pathological activity scores in the patients. We also analyzed changes of serum S100A12 levels in 10 patients after treatment. RESULTS: ELISA showed about 4-fold higher levels of serum S100A12 in patients with MPO-ANCA-associated glomerulonephritis than healthy controls. Serum S100A12 levels correlated with the BVAS scores, the peripheral white blood cell count, levels of serum C-reactive protein and creatinine, and pathological activity scores in the patients, but did not correlate with serum MPO-ANCA titers. Serum S100A12 levels after treatment decreased in all the 10 patients examined. CONCLUSION: We demonstrated that increased serum S100A12 levels correlate with clinical, laboratory and pathological parameters of disease activity in patients with MPO-ANCA-associated glomerulonephritis. Serum S100A12 level may be one of the useful markers of disease activity in MPO-ANCA-associated glomerulonephritis.
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Glomerulonefritis/sangre , Proteínas S100/sangre , Adolescente , Adulto , Anciano , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Biomarcadores/sangre , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Glomerulonefritis/enzimología , Humanos , Masculino , Persona de Mediana Edad , Peroxidasa/sangre , Proteína S100A12RESUMEN
BACKGROUND: Mutations in 3 genes (NPHP1, NPHP3 and NPHP4) have been identified in patients with juvenile or adolescent nephronophthisis (NPHP) without extrarenal involvement, mainly in patients from western countries. In this study, we analyzed mutations in the NPHP genes of 2 Japanese patients with suspected sporadic juvenile or adolescent NPHP without extrarenal involvement. METHODS: A renal biopsy was performed in the 2 patients. Genomic DNA was prepared from peripheral blood mononuclear cells of the patients and their family members. The above NPHP genes were examined by deletion analysis or direct automated sequencing of polymerase chain reaction-amplified DNA products. RESULTS: Histological findings in the patients were compatible with those of NPHP. In 1 patient, we identified a novel deletion mutation including about half of exons of the NPHP1 gene. In another patient, there was no mutation in the NPHP genes examined. CONCLUSIONS: We found a novel NPHP1 deletion in 1 patient. To our knowledge, this is the second Japanese NPHP case in which genetic diagnosis was made.
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Nefritis Intersticial/genética , Proteínas/genética , Proteínas Adaptadoras Transductoras de Señales , Adolescente , Adulto , Secuencia de Bases , Proteínas del Citoesqueleto , ADN/genética , Análisis Mutacional de ADN , Femenino , Humanos , Japón , Proteínas de la Membrana , Mutación , Nefritis Intersticial/diagnóstico , Nefritis Intersticial/patología , Eliminación de SecuenciaRESUMEN
The aim of this study was to verify an approach for calculating pharmacokinetic parameters suitable for adjusting dosage regimens in patients with renal dysfunction. We carried out a retrospective analysis of the pharmacokinetic profiles of 12 new quinolone antibiotics and 11 angiotensin-converting enzyme inhibitors (ACEIs) in patients with normal and impaired renal function to obtain the renal excretion ratio (R(renal)) of each drug. We demonstrated that the pharmacokinetics of each drug in a patient with renal dysfunction can be adequately estimated using the R(renaI) value of each drug together with the creatinine clearance as an index of the individual's renal function. Using the R(renaI) value obtained, we could successfully simulate pharmacokinetic profiles of the drugs in publications other than that used to obtain the R(renal) values. On the other hand, age-related changes in the pharmacokinetics of new quinolone antibiotics are not always adequately predicted using the R(renal) value compared to using creatinine clearance alone as an index, and the reasons for this are not fully understood. These results demonstrate that dosage regimens of quinolone antibiotics and ACEIs in patients with renal dysfunction can be adequately optimized using the R(renal) value for each drug using the present approach.
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Inhibidores de la Enzima Convertidora de Angiotensina/farmacocinética , Antibacterianos/farmacocinética , Enfermedades Renales/metabolismo , Quinolonas/farmacocinética , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antibacterianos/uso terapéutico , Creatinina/metabolismo , Humanos , Enfermedades Renales/tratamiento farmacológico , Quinolonas/uso terapéuticoRESUMEN
We characterized the fluorescence resonance energy transfer (FRET) from pyrene (donor) to perylene (acceptor) for nucleic acid assays under homogeneous solution conditions. We used the hybridization between a target 32 mer and its complementary two sequential 16 mer deoxyribonucleotides whose neighboring terminals were each respectively labeled with a pyrene and a perylene residue. A transfer efficiency of approximately 100% was attained upon the hybridization when observing perylene fluorescence at 459 nm with 347-nm excitation of a pyrene absorption peak. The Förster distance between two dye residues was 22.3 A (the orientation factor of 2/3). We could change the distance between the residues by inserting various numbers of nucleotides into the center of the target, thus creating a gap between the dye residues on a hybrid. Assuming that the number of inserted nucleo-tides is proportional to the distance between the dye residues, the energy transfer efficiency versus number of inserted nucleotides strictly obeyed the Förster theory. The mean inter-nucleotide distance of the single-stranded portion was estimated to be 2.1 A. Comparison between the fluorescent properties of a pyrene-perylene pair with those of a widely used fluorescein-rhodamine pair showed that the pyrene-perylene FRET is suitable for hybridization assays.
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Colorantes Fluorescentes/química , Hibridación de Ácido Nucleico , Perileno/química , Pirenos/química , ADN Bacteriano/genética , Escherichia coli/genética , Fluoresceínas/química , Desnaturalización de Ácido Nucleico , Oligodesoxirribonucleótidos/análisis , Oligodesoxirribonucleótidos/química , Sondas de Oligonucleótidos , Rodaminas/química , Soluciones , Espectrometría de Fluorescencia , Espectrofotometría , TemperaturaRESUMEN
We performed immunohistochemical examination of serial sections of human fetal and adult renal tissue as well as human renal carcinoma tissue, using monoclonal antibodies T5A7, 1B2, FH2, FH4, and FH6. These monoclonal antibodies were directed to lacto series type 2 antigens with sugar-chain structures: lactosylceramide, lactoneotetraosylceramide (paragloboside), Lex (a chemically well-defined fucosyl carbohydrate antigen), difucosyl Lex, and sialosyl-difucosyl Lex, respectively. The staining pattern in fetal renal tissue changed significantly according to the stage of organogenesis. In addition, expression of the antigens, especially paragloboside and sialosyl-difucosyl Lex, was closely related to the prognosis of the patient. These results suggest that the expression of a series of oncofetal antigens in development or differentiation of organs is reflected in the reversion to an immature pattern of antigenic expression in tumor tissue. The pattern of antigen expression in renal tumors offers a good criterion for ascertaining the degree of tumor differentiation and malignancy and is valuable for determining prognosis.
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Antígenos CD , Antígenos de Neoplasias/análisis , Carcinoma de Células Renales/análisis , Glucolípidos/análisis , Neoplasias Renales/análisis , Lactosilceramidos , Adulto , Anticuerpos Monoclonales , Carcinoma de Células Renales/mortalidad , Embrión de Mamíferos/análisis , Femenino , Feto/análisis , Globósidos/análisis , Glucolípidos/inmunología , Glicoesfingolípidos/análisis , Humanos , Inmunohistoquímica , Riñón/análisis , Riñón/embriología , Neoplasias Renales/mortalidad , Antígeno Lewis X , Estadificación de Neoplasias , Embarazo , PronósticoRESUMEN
A general transcription factor IID which binds to the TATA box promoter element on RNA polymerase II genes regulates and initiates eukaryotic mRNA synthesis. A quantitative polymerase chain reaction procedure was developed and the human transcription factor IID (hTFIID) transcript was measured in normal human tissues, lung carcinomas, lung carcinoma cell lines, and breast carcinomas. In some normal tissues such as liver, fetal lung, and placenta, relatively low to moderate levels of hTFIID mRNA were detected. In contrast, hTFIID transcript was highly expressed in nearly all solid lung carcinomas and cell lines including both small cell lung cancer and non-small cell lung cancer. hTFIID mRNA was present to a greater extent in small cell lung cancer than non-small cell lung cancer in solid tumors and cell lines. In solid carcinomas of breast, overexpression of hTFIID was also detected. A serum induction study using a serum-starved small cell lung cancer cell line, Lu134BS, indicated hTFIID transcription to be rapidly induced at 15 min following stimulation and its response essentially similar to that of protooncogene, c-fos. These results indicate the involvement of the expression of the general transcription factor hTFIID in lung and breast carcinoma, such as being associated with poor differentiation and high mitotic activity.