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At Kyoto University Research Reactor Institute (KURRI), cyclotron-based epithermal neutron source was installed in December 2008, and the supplementary construction works have been performed. As of December 2010, the various irradiation characteristics important for BNCT were mostly evaluated. The whole body exposure during BNCT medical irradiation is one of the important characteristics. In this article, measurements of absorbed dose for thermal and fast neutrons and gamma-ray at ten positions corresponding to important organs are reported.
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Terapia por Captura de Neutrón de Boro , Ciclotrones , Fantasmas de Imagen , HumanosRESUMEN
PURPOSE: To examine longitudinal changes of bone mineral density (BMD) after parathyroidectomy (PTx) in patients undergoing maintenance hemodialysis (HD) with severe secondary hyperparathyroidism (HPT) to determine which factor contributes most to bone changes. METHODS: Fifteen Japanese HD patients who had been refractory to medical therapy were subject to PTx with autotransplantation. We measured BMD by dual energy X-ray absorptiometry (DXA) at the lumbar spine (L2 - 4 BMD) and the distal 1/3 region of the radius (1/3R BMD) at 1, 3, 6, 12, 24, and 36 months after PTx. RESULTS: Baseline Z-score of BMD was markedly low at 1/3R (- 3.07) and slightly low at L2 - 4 (-0.59) in this group. A significant increase in L2 - 4 BMD was observed as early as one month after PTx, which was sustained afterwards. Annual percent changes in L2 - 4 and 1/3R BMD were + 15.6 % and + 6.4 %, respectively. The annual percent changes in BMD at both sites were positively associated with preoperative intact PTH levels (L2 - 4; r = 0.642, p = 0.010, 1/3R; r = 0.884, p < 0.001) and total alkaline phosphatase (ALP) levels (L2 - 4; r = 0.663, p = 0.007, 1/3R; r = 0.858, p < 0.001). Stepwise multiple regression analysis revealed that serum levels of intact PTH and ALP were the best predictors of both percentage and net changes in radial BMD with high determination coefficients (r 2 > 0.8). CONCLUSION: Successful PTx following appropriate supplementation with vitamin D and calcium provides a marked increase in lumbar BMD and a modest increase in radial BMD in HD patients with secondary HPT. Preoperative levels of PTH and ALP are useful for predicting postoperative changes in bone mass.
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Densidad Ósea/fisiología , Hiperparatiroidismo/cirugía , Hormona Paratiroidea/sangre , Paratiroidectomía , Diálisis Renal , Absorciometría de Fotón , Adulto , Densidad Ósea/efectos de los fármacos , Calcio/farmacología , Femenino , Humanos , Hiperparatiroidismo/fisiopatología , Japón , Vértebras Lumbares/química , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios/métodos , Radioinmunoensayo , Radio (Anatomía)/química , Análisis de Regresión , Vitamina D/farmacologíaRESUMEN
Since it has been widely recognised that renal cell carcinoma is refractory to standard therapies such as chemotherapy and radiotherapy, a new modality of treatment is needed. One of the potential alternative therapies for renal cell carcinoma may be inhibition of angiogenesis. In this study, we analysed the inhibitory effects of several potential agents on expression of angiogenic factors such as vascular endothelial growth factor and basic fibroblast growth factor, which are the main mediators in angiogenesis of renal cell carcinoma. We used medroxyprogesterone acetate, interferon-alpha, interferon-gamma, minocycline hydrochrolide and genistein, which are known to be antiangiogeneic. Northern blot analyses revealed that, among the five agents examined, genistein had a strong inhibitory effect on expression of vascular endothelial growth factor mRNA and basic fibroblast growth factor mRNA. Medroxyprogesterone acetate and interferon-alpha did not significantly decrease the level of either vascular endothelial growth factor mRNA or basic fibroblast growth factor mRNA. Interferon-gamma and minocycline had mild inhibitory effects on vascular endothelial growth factor mRNA and basic fibroblast growth factor mRNA expression. Genistein also inhibited both vascular endothelial growth factor mRNA and basic fibroblast growth factor mRNA expression after treatment with epidermal growth factor and hypoxia. These findings suggest that one of the mechanisms of the inhibition of angiogenesis by genistein is suppression of the expression of the angiogenic factors vascular endothelial growth factor and basic fibroblast growth factor in renal cell carcinoma.
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Inhibidores de la Angiogénesis/farmacología , Antineoplásicos/farmacología , Carcinoma de Células Renales/genética , Factores de Crecimiento Endotelial/biosíntesis , Factor 2 de Crecimiento de Fibroblastos/biosíntesis , Genisteína/farmacología , Neoplasias Renales/genética , Linfocinas/biosíntesis , Neovascularización Patológica , Northern Blotting , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/fisiopatología , Humanos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/fisiopatología , ARN Mensajero , Células Tumorales Cultivadas , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
UNLABELLED: OBJECTIVESz: To study the clinical and urodynamic effects of oral distigmine bromide (distigmine) by using pressure-flow studies in patients who were persistently poor voiders after transurethral resection of the prostate. METHODS: The study included 14 poor voiders after transurethral resection of the prostate who were 50 years old or older. Their poor voiding conditions were characterized by a mean International Prostate Symptom Score of 18.9 or a mean quality-of-life index of 4.6 and a mean maximum flow rate of 8.9 mL/s. All patients underwent symptomatic and urodynamic investigations before and after 4 weeks of daily treatment with 15 mg oral distigmine. RESULTS: In the baseline pressure-flow studies, all patients had weak detrusor contractility as demonstrated by Schäfer's diagram and the maximum Watts factor but did not have bladder outlet obstruction. They had symptomatic improvements after oral distigmine treatment, with the International Prostate Symptom Score reduced to a mean of less than 10 and the quality-of-life index reduced to a mean of less than 3. In the urodynamic investigations, the maximum flow rate improved significantly to a mean of more than 12 mL/s in parallel with a significant increase in the maximum Watts factor. Detrusor contractility according to Schäfer's diagram also tended to improve after oral distigmine treatment. However, no significant changes were found in any of the parameters of bladder outlet obstruction. CONCLUSIONS: Poor voiders after transurethral resection of the prostate who have weak detrusor contractility without bladder outlet obstruction may benefit clinically from treatment with distigmine because of its efficacy in increasing detrusor contractility without enhancing bladder outlet obstruction.
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Inhibidores de la Colinesterasa/uso terapéutico , Contracción Muscular/efectos de los fármacos , Compuestos de Piridinio/uso terapéutico , Resección Transuretral de la Próstata/efectos adversos , Trastornos Urinarios/tratamiento farmacológico , Trastornos Urinarios/etiología , Urodinámica/efectos de los fármacos , Administración Oral , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Resección Transuretral de la Próstata/métodos , Trastornos Urinarios/fisiopatologíaRESUMEN
We evaluated the usefulness of adjuvant chemotherapy with low-dose epirubicin (EPI) as a key drug in patients with axially-node positive breast cancer. All the 24 patients who were entered in the study between January 1991 and December 1992 were shown histologically to have more than 4 axially-node involvement and underwent curable resection for the breast lesions. Twenty mg/m2 of EPI was administered intravenously every 4 weeks as ambulatory treatment for 1 year and 5-fluorouracil (5-FU) and tamoxifen (TAM) were concomitantly administered at a dose of 150 mg/day and 20-40 mg/day, respectively, daily for 2 years. The median follow-up period was 70 months with a 55.1% 5-year relapse-free survival and 67.4% 5-year survival rate. One patient developed Grade 3 nausea.vomiting, anorexia and general fatigue; however, the other toxicities were mild, such as Grade 1 leukopenia, liver dysfunction, nausea.vomiting, anorexia and general fatigue. This adjuvant therapy with low-dose EPI was safely administered to outpatients, and is considered to be useful for the treatment of axially-node positive breast cancer.
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Atención Ambulatoria , Antibióticos Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Epirrubicina/administración & dosificación , Ganglios Linfáticos/patología , Adulto , Axila , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Metástasis Linfática , Persona de Mediana Edad , Tasa de Supervivencia , Tamoxifeno/administración & dosificaciónRESUMEN
This study aimed to evaluate the efficacy and safety of oral antibacterial treatment with fluoroquinilone for acute uncomplicated pyelonephritis Thirteen female patients with acute uncomplicated pyelonephritis were treated with oral fluoroquinilone (ciprofloxacin; CPFX). They received 200 mg of the drug three times a day while febrile (3-5 days). Once they become afebrile, the same dose of the drug, given twice a day, was given for another 9-11 days. The mean duration of the course of CPFX was 14 days. Symptoms were evaluated, and laboratory examinations, including urine culture and measurement of the minimal inhibitory concentration (MIC) of CPFX were conducted before treatment, and 3, 7, 14, 21, and/or 28 days after the initiation of the treatment. Of the 13 patients, only 5 needed to be hospitalized, and the period of hospitalization was only a few days. On the 14th day after the commencement of treatment, bacteriologic and clinical cure rates were 100%. Escherichia coli was the most common uropathogen, being isolated from the urine of 8 patients. No clinical relapse of the disease was found during a follow-up period of up to 4 weeks. The patients tolerated the drug well without developing any serious adverse effects. Oral antimicrobial chemotherapy with fluoroquinolone, given on an outpatient or short-term hospitalization basis, achieved satisfactory bacteriological and clinical outcomes in the treatment of acute uncomplicated pyelonephritis. This treatment regimen is indicated for patients with this disease who are not in a serious condition with complications such as shock.
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Antiinfecciosos/uso terapéutico , Ciprofloxacina/uso terapéutico , Pielonefritis/tratamiento farmacológico , Enfermedad Aguda , Administración Oral , Adulto , Anciano , Antiinfecciosos/administración & dosificación , Ciprofloxacina/administración & dosificación , Esquema de Medicación , Femenino , Humanos , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND: While fluoroquinolone-resistant Chlamydia trachomatis strains have not been clinically isolated, they were isolated in an in vitro study recently. METHODS: To determine whether C. trachomatis strains develop resistance under sub-MIC antibacterial exposure in a clinical therapeutic term, C. trachomatis strains were exposed to sub-MIC levofloxacin (LVFX) for about 2 weeks. The MIC of LVFX was measured and DNA fingerprinting was performed every 72 h by PCR using random primers. RESULTS: There was almost no change in the MIC under exposure to 0.125 microg/ml LVFX. However, some mutational changes in DNA fingerprints developed. CONCLUSIONS: In clinical therapeutic terms, resistant strains of C. trachomatis will probably not develop, even if sub-MIC LVFX is employed.
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Antiinfecciosos/farmacología , Chlamydia trachomatis/efectos de los fármacos , Levofloxacino , Pruebas de Sensibilidad Microbiana , Ofloxacino/farmacología , Chlamydia trachomatis/genética , Cartilla de ADN , Farmacorresistencia Microbiana/genética , Pruebas de Sensibilidad Microbiana/métodos , Técnica del ADN Polimorfo Amplificado Aleatorio , Selección GenéticaRESUMEN
In vitro mRNA synthesis of Sendai virus is almost entirely dependent on the addition of cellular proteins (host factors). Previous studies indicated that the host factor activity from bovine brain was resolved into at least two complementary fractions, one of which may be tubulin. In this study, the host factor activity that stimulates the transcription in the presence of tubulin was further purified from bovine brain. This fraction was found to contain at least two complementary factors, and one of them was purified to a single polypeptide chain with an apparent M(r) of 46,000 (p46). From the amino acid sequence, biochemical, and immunological analyses, p46 was identified as a glycolytic enzyme, phosphoglycerate kinase (PGK). Purified native PGK from rabbit and yeast, and a recombinant human PGK substituted for p46. Although, as previously suggested, tubulin was involved in the transcription initiation complex formation by being integrated into the complex, p46 and its complementary factor had little effect on the complex formation. On the other hand, when p46 and the complementary factor were added to the RNA chain elongation reaction from the isolated initiation complex formed with tubulin, mRNA synthesis was dramatically stimulated. The enzymatic activity per se of PGK did not seem to be required for its activity. West-Western blot analysis showed that PGK could directly interact with tubulin. These data suggest that PGK stimulates Sendai virus mRNA synthesis at the elongation step, probably through its interaction with tubulin in the initiation complex.
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Regulación Fúngica de la Expresión Génica , Fosfoglicerato Quinasa/metabolismo , Respirovirus/genética , Transcripción Genética , Virus de la Estomatitis Vesicular Indiana/genética , Secuencia de Aminoácidos , Animales , Encéfalo/metabolismo , Bovinos , Embrión de Pollo , Cromatografía , Cromatografía de Afinidad , Durapatita , Glucólisis , Humanos , Ratones , Datos de Secuencia Molecular , Peso Molecular , Fragmentos de Péptidos/química , Fosfoglicerato Quinasa/química , Fosfoglicerato Quinasa/aislamiento & purificación , ARN Mensajero/genética , Conejos , Proteínas Recombinantes/metabolismo , Ribonucleoproteínas/aislamiento & purificación , Ribonucleoproteínas/metabolismo , Saccharomyces cerevisiae/enzimología , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Tubulina (Proteína)/aislamiento & purificación , Tubulina (Proteína)/metabolismoRESUMEN
We studied the clinical efficacy of oral treatment with ciprofloxacin (CPFX) alone and combined with clarithromycin (CAM) in patients with complicated urinary tract infection with or without an indwelling catheter. Patients were randomly allocated to 600 mg CPFX (CPFX group) or to 600 mg CPFX plus 600 mg CAM (combination group) for 14 days. Evaluation was done on day 14 according to the criteria advocated by the Japanese Urinary Tract Infection Committee. In patients with a urinary catheter, the combination achieved a higher complete bacterial elimination rate (50.0%) and clinical efficacy rate (83.9%) than CPFX alone (30.0 and 61.5%, respectively). While no significant difference was found in the bacterial elimination rate between the two groups, the clinical efficacy of the combination (40.0%) was superior to that of CPFX alone (23.3%) in patients with an indwelling catheter. The better clinical efficacy of the combination may partly be attributed to the antibiofilm effect of CAM in the clinical setting. The results also indicate that difficulties still remain in the treatment of complicated urinary tract infections in patients with an indwelling catheter.
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Antibacterianos/uso terapéutico , Antiinfecciosos/uso terapéutico , Biopelículas , Ciprofloxacina/uso terapéutico , Claritromicina/uso terapéutico , Infecciones Urinarias/tratamiento farmacológico , Adulto , Anciano , Quimioterapia Combinada , Humanos , Persona de Mediana Edad , Cateterismo Urinario , Infecciones Urinarias/complicacionesRESUMEN
Rat PEX12 cDNA was isolated by functional complementation of peroxisome deficiency of a mutant CHO cell line, ZP109 (K. Okumoto, A. Bogaki, K. Tateishi, T. Tsukamoto, T. Osumi, N. Shimozawa, Y. Suzuki, T. Orii, and Y. Fujiki, Exp. Cell Res. 233:11-20, 1997), using a transient transfection assay and an ectopic, readily visible marker, green fluorescent protein. This cDNA encodes a 359-amino-acid membrane protein of peroxisomes with two transmembrane segments and a cysteine-rich zinc finger, the RING motif. A stable transformant of ZP109 with the PEX12 was morphologically and biochemically restored for peroxisome biogenesis. Pex12p was shown by expression of bona fide as well as epitope-tagged Pex12p to expose both N- and C-terminal regions to the cytosol. Fibroblasts derived from patients with the peroxisome deficiency Zellweger syndrome of complementation group III (CG-III) were also complemented for peroxisome biogenesis with PEX12. Two unrelated patients of this group manifesting peroxisome deficiency disorders possessed homozygous, inactivating PEX12 mutations: in one, Arg180Thr by one point mutation, and in the other, deletion of two nucleotides in codons for 291Asn and 292Ser, creating an apparently unchanged codon for Asn and a codon 292 for termination. These results indicate that the gene encoding peroxisome assembly factor Pex12p is a pathogenic gene of CG-III peroxisome deficiency. Moreover, truncation and site mutation studies, including patient PEX12 analysis, demonstrated that the cytoplasmically oriented N- and C-terminal parts of Pex12p are essential for biological function.
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Proteínas de la Membrana/genética , Mutación , Síndrome de Zellweger/genética , Dedos de Zinc , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Células CHO , Línea Celular , Línea Celular Transformada , Clonación Molecular , Cricetinae , Citosol , ADN Complementario , Fibroblastos , Humanos , Microcuerpos/metabolismo , Datos de Secuencia Molecular , Mutagénesis , Trastorno Peroxisomal/veterinaria , Ratas , Homología de Secuencia de AminoácidoRESUMEN
Ten complementation groups of generalized peroxisome biogenesis disorders (PBD), (excluding rhizomelic chondrodysplasia punctata) have been identified using complementation analysis. Four of the genes involved have been identified using two different methods of (1) genetic functional complementation of peroxisome deficient CHO cell mutants and (2) homology searches for human dbEST, based on yeast genes involved in peroxisome biogenesis (PEX genes). We report here the first identification of a new complementation group which is genetically different from peroxisome deficient CHO mutants. There were no complementations by the human PEX 13 gene. The nature of the related gene is being investigated.
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Prueba de Complementación Genética , Proteínas de la Membrana/genética , Trastorno Peroxisomal/genética , Animales , Células CHO , Catalasa/inmunología , Mapeo Cromosómico , Clonación Molecular , Cricetinae , ADN Complementario/genética , Fibroblastos , Técnica del Anticuerpo Fluorescente , Humanos , Lactante , Masculino , Fenotipo , Transfección/genéticaRESUMEN
OBJECTIVES: To investigate the effect of limaprost, an oral prostaglandin E1 (PGE1) derivative, on erectile dysfunction and to compare the effects of limaprost with a Chinese herbal drug, gosyajinki-gan. PATIENTS AND METHODS: The study comprised 50 consecutive patients with mild erectile dysfunction who showed a good erectile response to intracavernosal injection with 20 micrograms of PGE1. Limaprost was administered to the first 25 patients (30 micrograms three times daily) and gosyajinki-gan (7.5 g three times daily) to the next 25 patients, for 8 consecutive weeks. Patients were evaluated by their ability to achieve vaginal penetration and by a subjective assessment of erectile function (penile rigidity and maintenance of erection) before and after the treatment, using a self-administered questionnaire. Objective measurements (nocturnal penile tumescence, NPT, values) were also evaluated. RESULTS: Eleven of the 24 patients who received limaprost without interruption and four of the 24 taking gosyajinki-gan succeeded in vaginal penetration; the difference in the positive response rate was significant. The mean increment of NPT was significantly higher with limaprost treatment. However, all positive responders in both groups did not experience a full erection. There were no side-effects in any patient except one in the limaprost group who developed a facial flush. Thus the treatment was mild enough to be tolerated. CONCLUSION: Limaprost was more effective for mild erectile dysfunction than was gosyajinki-gan.
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Alprostadil/análogos & derivados , Medicamentos Herbarios Chinos , Disfunción Eréctil/tratamiento farmacológico , Vasodilatadores/administración & dosificación , Administración Oral , Adulto , Anciano , Alprostadil/administración & dosificación , Coito , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
PURPOSE: To confirm the clinical efficacy of the combined therapy to complicated urinary tract infection (UTI), we conducted a comparative clinical study of the combined therapy with ciprofloxacin (CPFX) and clarithromycin (CAM) acting an biofilm elimination or CPFX alone in patients with complicated UTI. PATIENTS AND METHODS: The study was carried out in patients with complicated UTI having WBCs with 5/hpf or more in urinary sediment and bacteriuria at least 10(4) CFU/ml. The combined therapy was CPFX and CAM, each 600 mg/day, for 14 days, and the single therapy group CPFX, 600 mg/day, for 14 days. On Day 7 and 14, the eradication rate and efficacy rate (according to the criteria of the Japanese UTI committee) were determined. In the patients with indwelling catheter, the surface of the catheter tip was observed under a scanning electron microscope (SEM) on Day 14. RESULTS: In both cases with and without catheters, clinical efficacy was higher in the combined therapy group than in the single therapy group. In particular, the efficacy rates at 14 Day were significantly higher in the former group. Furthermore, we investigated the therapeutic effect in the below MIC breakpoint of CPFX in complicated UTI. The combined therapy group showed a higher clinical efficacy in both cases with and without indwelling catheter than the single therapy group, although there was not statistically significant. Biofilm on the surface of the catheter tip was eliminated in 75% of the combined therapy group. However, none of the biofilm was eliminated in the single therapy group. CONCLUSION: From the above results, we surmise that the combined use of CPFX and CAM will show some degree of efficacy in eliminating both the causative organism and its biofilm in the complicated UTI.
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Antibacterianos/administración & dosificación , Claritromicina/administración & dosificación , Infecciones Urinarias/tratamiento farmacológico , Adulto , Antiinfecciosos/administración & dosificación , Ciprofloxacina/administración & dosificación , Quimioterapia Combinada , Humanos , Persona de Mediana EdadRESUMEN
BACKGROUND: Twelve patients with benign prostatic hyperplasia and urinary retention, who were considered to be poor candidates for prostatectomy, were treated by transurethral balloon laser thermotherapy (TUBAL-T). The mean patient age was 78.9 years (range, 66 to 93 years) and the mean duration of bladder catheterization was 11 weeks (range, 2 to 48 weeks). METHODS: Irradiation into the prostatic tissue was done through 360 degrees with a neodymium: yttrium aluminum garnet (Nd:YAG) laser balloon placed in the prostatic urethra, with pain relief provided by using local topical anesthesia. The total laser dose was from 45,000 to 123,376 J, with an average of 73,089 J. The irradiation time was from 40 to 54 minutes, with an average of 45.2 minutes. RESULTS: Spontaneous voiding became possible in all patients at a mean of 2.8 days (range, 1 to 7 days) after irradiation. The mean catheter-free period was 20.5 months (range, 6 to 34 months), with the longest being 34 months. The international prostatic symptom scores, quality-of-life scores, and peak uroflow rates showed substantial improvement after laser thermotherapy. To date, long-term resumption of spontaneous voiding was successfully achieved in 9 of 12 cases (75%). CONCLUSION: TUBAL-T is safe and effective alternative for treatment of urinary retention in patients with benign prostatic hyperplasia who are considered to be at high surgical risk.
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Hipertermia Inducida/métodos , Hiperplasia Prostática/terapia , Trastornos Urinarios/terapia , Anciano , Anciano de 80 o más Años , Estudios de Seguimiento , Humanos , Rayos Láser , Masculino , Hiperplasia Prostática/complicaciones , Hiperplasia Prostática/psicología , Calidad de Vida , Resultado del Tratamiento , Trastornos Urinarios/etiología , Trastornos Urinarios/psicología , UrodinámicaRESUMEN
The yeast two-hybrid screening was applied to cloning cDNAs of proteins that interact with peroxisome proliferator-activated receptor alpha (PPAR alpha). We obtained from a rat liver cDNA library a clone encoding a protein related to the ligand-binding domain of the members of nuclear hormone receptor superfamily, whereas apparently lacking the zinc-finger DNA-binding domain. This protein interacted with the activated forms of several nuclear receptors, and thus is a novel type of heterodimer-forming nuclear receptor.
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Proteínas de Unión al ADN/genética , Hígado/metabolismo , Receptores Citoplasmáticos y Nucleares/genética , Factores de Transcripción/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Clonación Molecular , ADN Complementario , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/metabolismo , Biblioteca de Genes , Humanos , Datos de Secuencia Molecular , Especificidad de Órganos , Ratas , Receptores Citoplasmáticos y Nucleares/química , Receptores Citoplasmáticos y Nucleares/metabolismo , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/química , Mapeo Restrictivo , Homología de Secuencia de Aminoácido , Factores de Transcripción/química , Factores de Transcripción/metabolismo , Dedos de ZincRESUMEN
Zellweger syndrome is a prototype of peroxisomal biogenesis disorders and a fatal autosomal recessive disease with no effective therapy. We identified nine genetic complementation groups of these disorders, and mutations in peroxisome assembly factor-1 (PAF-1) and the 70-kD peroxisomal membrane protein (PMP70) genes have been detected by our group F and Roscher's group 1, respectively. We now describe permanent recovery from generalized peroxisomal abnormalities in fibroblasts of a Zellweger patient from group F, such as biochemical defects of peroxisomal beta-oxidation, plasmalogen biosynthesis, and morphologic absence of peroxisomes, by stable transfection of human cDNA encoding PAF-1. In the light of these observations, we designed a gene expression system using fibroblasts from patients with peroxisomal biogenesis disorders. In Zellweger fibroblasts obtained from Roscher's group 1 and transfected with human cDNA encoding PMP70, peroxisomes were not morphologically identifiable, and peroxisomal function did not normalize.
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Transportadoras de Casetes de Unión a ATP , Expresión Génica , Síndrome de Zellweger/genética , Síndrome de Zellweger/metabolismo , Aciltransferasas/metabolismo , Línea Celular , ADN Complementario/genética , Ácidos Grasos/metabolismo , Fibroblastos/metabolismo , Prueba de Complementación Genética , Terapia Genética , Humanos , Proteínas de la Membrana/genética , Microcuerpos/metabolismo , Oxidación-Reducción , Factor 2 de la Biogénesis del Peroxisoma , Transfección , Síndrome de Zellweger/terapiaRESUMEN
Rat peroxisome assembly factor-2 (PAF-2) cDNA was isolated by functional complementation of peroxisome deficiency of a mutant CHO cell line, ZP92, using transient transfection assay. This cDNA encodes a 978-amino acid protein with two putative ATP-binding sites. PAF-2 is a member of a putative ATPase family, including two yeast gene products essential for peroxisome assembly. A stable transformant of ZP92 with the cDNA was morphologically and biochemically restored for peroxisome biogenesis. Fibroblasts derived from patients deficient in peroxisome biogenesis (complementation group C) were also complemented with PAF-2 cDNA, indicating that PAF-2 is a strong candidate for the pathogenic gene of group C peroxisome deficiency.
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Adenosina Trifosfatasas/genética , Prueba de Complementación Genética , Microcuerpos/enzimología , ATPasas Asociadas con Actividades Celulares Diversas , Acil-CoA Oxidasa , Aciltransferasas/metabolismo , Adenosina Trifosfatasas/análisis , Adenosina Trifosfatasas/química , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Sitios de Unión , Células CHO , Catalasa/análisis , Clonación Molecular/métodos , Cricetinae , Citosol/enzimología , ADN Complementario/genética , Fibroblastos , Humanos , Hígado/química , Datos de Secuencia Molecular , Mutación , Oxidorreductasas/análisis , Trastorno Peroxisomal/genética , Trastorno Peroxisomal/metabolismo , ARN Mensajero/análisis , Ratas , Análisis de Secuencia de ADN , Homología de Secuencia de AminoácidoRESUMEN
Between April 1993 and May 1994, 66 patients were treated with transurethral balloon laser thermotherapy (TUBAL-T) for the relief of bladder outlet obstruction secondary to benign prostatic hyperplasia. TUBAL-T, with a urethral cooling system, employs a balloon catheter and irradiating laser through 360 degrees to produce deep coagulation and necrosis of the prostatic tissue while preserving the urethral mucosa. The procedure was implemented under local topical anesthesia. Baseline AUA Symptom Scores, peak uroflow rates, postvoiding residual urine volumes (PVR), and prostatic volumes were measured before and at 1, 3, 6, and 12 months after treatment. The mean symptom score decreased from 18.8 preoperatively to 9.8, 6.9, 7.4, and 4.8 at 1, 3, 6, and 12 months, respectively. The mean peak uroflow rate increased from 6.4 mL/sec to 9.1, 11.2, 10.1, and 10.4 mL/sec at 1, 3, 6, and 12 months, respectively. As for the mean PVR, statistically significant reductions were clearly observed at 3 and 6 months after treatment. However, at 1 and 12 months, the difference was not statistically significant. In follow-up for as long as 12 months after the procedure, 23 of 26 patients (88%) showed an improvement of 50% or more in the AUA Symptom Scores. Of 20 available patients, 12 (60%) showed an improvement of 50% or higher in the peak uroflow rates, and 10 (50%) showed an improvement of 50% or higher in PVR. The mean prostatic volume reductions at 3, 6, and 9 months were 12%, 16%, and 14%, respectively. The serum prostate specific antigen concentration increased to four times the baseline concentration on the 7th day.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Cateterismo , Hipertermia Inducida/métodos , Terapia por Láser , Hiperplasia Prostática/terapia , Obstrucción del Cuello de la Vejiga Urinaria/terapia , Anciano , Anciano de 80 o más Años , Estudios de Seguimiento , Humanos , Hipertermia Inducida/efectos adversos , Masculino , Persona de Mediana Edad , Hiperplasia Prostática/complicaciones , Obstrucción del Cuello de la Vejiga Urinaria/etiologíaRESUMEN
The present study was performed to clarify second messenger signaling in parathyroid hormone (PTH)-induced c-fos gene expression, to characterize the participation of the c-fos gene in the regulation of osteoblast proliferation and function as well as osteoclast-like cell formation by PTH and to compare these effects of PTH with those of PTH-related peptide (PTHrP). Both human (h) PTH-(1-34) and hPTHrP-(1-34) at 10(-8) M induced a transient c-fos gene expression to a similar degree in osteoblastic osteosarcoma cells, UMR-106. N6,O2'-dibutyryl adenosine 3',5'-cyclic monophosphate (dbcAMP) as well as Sp-diastereoisomer of adenosine cyclic 3',5'-phosphorothioate (Sp-cAMPS), an activator of cAMP-dependent protein kinase (PKA), induced a weak c-fos gene expression. Although Rp-diastereoisomer of adenosine cyclic 3',5'-phosphorothioate (Rp-cAMPS), an inhibitor of PKA, almost completely antagonized dbCAMP- and Sp-cAMPS-induced expression of c-fos gene, it did not cause an obvious inhibition of PTH- or PTHrP-induced expression. Phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC), induced an intense expression of the c-fos gene, while 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD), incapable of activating PKC, and calcium ionophores (A23187 and ionomycin) did not. Protein kinase C inhibitor (H-7, 50 microM) completely blocked the expression of the c-fos gene by PTH as well as by PTHrP). Antisense oligodeoxynucleotides (as-ODN) complementary to c-fos mRNA, which have been shown to inhibit its mRNA translation, at 1 microM significantly antagonized PTH- and PTHrP-induced inhibition of [3H] thymidine incorporation and stimulation of osteoclast-like cell formation in the presence of osteoblasts, but not an increase in alkaline phosphatase activity, compared to control oligodeoxynucleotides with same nucleotides as as-ODN but with a random sequence. The present study indicates the involvement of PKC system in c-fos gene expression by PTH as well as PTHrP and also indicates the involvement of the c-fos gene in the regulation of bone cell physiology by PTH and PTHrP.
Asunto(s)
Genes fos , Osteoblastos/metabolismo , Hormona Paratiroidea/farmacología , Proteínas/farmacología , Sistemas de Mensajero Secundario , Transducción de Señal , División Celular , Humanos , Osteoclastos/patología , Osteosarcoma/metabolismo , Osteosarcoma/patología , Proteína Relacionada con la Hormona Paratiroidea , Células Tumorales CultivadasRESUMEN
Treatment of infections by the use of antimicrobial agents should be made essentially in a dose close to the minimally required dose. Acute uncomplicated cystitis in female fits as the subject for a single-dose therapy since it is an infection reactive relatively easily to antimicrobial agents. Accordingly, an assessment has been made regarding the therapeutic results of the single-dose therapy in 76 female cases of acute uncomplicated cystitis by the use of LVFX 200 mg which is a new quinolone. The urinary concentration more than MIC90 to Escherichia coli is sustained for about 3 days by this single-dose therapy. As a result of judging the therapeutic results from the reactions of the three clinical findings of pain on micturition, pyuria and bacteriuria, excellent therapeutic results were obtained with effective rates being 100% (76/76) on the day 3, 93.9% (46/49) on the day 7 and 94.4% (34/36) on the day 14. The rate of cystitic symptoms which recurred posed no problem, being 12.5% (5/40) up to three months, as investigated by a questionnaire. As a result of performing close urological examinations such as cystoscopy on six cases with insufficient results or recurrence, we could detect mild underlying conditions which are considered to be intractable factors in the bladder in three cases. From the above results, the single-dose therapy of acute uncomplicated cystitis in the female by LVFX which is a new quinolone was considered to be an excellent therapeutic drug from its characteristics such as its therapeutic results being the same as the conventional therapy by daily administration, excellent drug compliance, low cost, hard selectiveness of resistant strains, less side effects and furthermore it gives the opportunity of detecting a latent and mild underlying condition.