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1.
J Urol ; 210(2): 257-271, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37126232

RESUMEN

PURPOSE: Latent grade group ≥2 prostate cancer can impact the performance of active surveillance protocols. To date, molecular biomarkers for active surveillance have relied solely on RNA or protein. We trained and independently validated multimodal (mRNA abundance, DNA methylation, and/or DNA copy number) biomarkers that more accurately separate grade group 1 from grade group ≥2 cancers. MATERIALS AND METHODS: Low- and intermediate-risk prostate cancer patients were assigned to training (n=333) and validation (n=202) cohorts. We profiled the abundance of 342 mRNAs, 100 DNA copy number alteration loci, and 14 hypermethylation sites at 2 locations per tumor. Using the training cohort with cross-validation, we evaluated methods for training classifiers of pathological grade group ≥2 in centrally reviewed radical prostatectomies. We trained 2 distinct classifiers, PRONTO-e and PRONTO-m, and validated them in an independent radical prostatectomy cohort. RESULTS: PRONTO-e comprises 353 mRNA and copy number alteration features. PRONTO-m includes 94 clinical, mRNAs, copy number alterations, and methylation features at 14 and 12 loci, respectively. In independent validation, PRONTO-e and PRONTO-m predicted grade group ≥2 with respective true-positive rates of 0.81 and 0.76, and false-positive rates of 0.43 and 0.26. Both classifiers were resistant to sampling error and identified more upgrading cases than a well-validated presurgical risk calculator, CAPRA (Cancer of the Prostate Risk Assessment; P < .001). CONCLUSIONS: Two grade group classifiers with superior accuracy were developed by incorporating RNA and DNA features and validated in an independent cohort. Upon further validation in biopsy samples, classifiers with these performance characteristics could refine selection of men for active surveillance, extending their treatment-free survival and intervals between surveillance.


Asunto(s)
Neoplasias de la Próstata , Espera Vigilante , Masculino , Humanos , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Clasificación del Tumor , Prostatectomía , Antígeno Prostático Específico , Biomarcadores , ARN , ARN Mensajero
2.
Clin Exp Immunol ; 202(1): 1-10, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32415989

RESUMEN

Psoriasis is characterized by excessive growth and aberrant differentiation of epidermal keratinocytes due to persistent inflammation. However, the underlying mechanism that triggers immune activation in psoriasis is not clear. In this study, we explored excessive DNA as a potential trigger of psoriasis using cultured human keratinocytes and psoriatic skin tissues. We demonstrated that human genomic DNA fragments induced tumour necrosis factor (TNF)-α expression, hyperproliferation and over-expression of heparin-binding epidermal-like growth factor (HB-EGF) and transforming growth factor (TGF)-α, accompanied by defective expression of keratins 1 and 10 in cultured normal human epidermal keratinocytes, which have a similar phenotype to that of keratinocytes in psoriatic skin lesions. In psoriatic lesions, we found high levels of double-stranded (ds)DNA fragments, accompanying keratinocytes expressing Ki-67, HB-EGF and TNF-α. In addition, we showed that 1,25-dihydroxyvitamin D3 inhibited genomic DNA fragment-induced TNFA and interleukin-1ß (IFNB) expression in human keratinocytes, and an intact function of cathelicidin anti-microbial peptide (CAMP) was required for this effect. These results suggest that excessive dsDNA fragments probably act as a risk factor for immune activation in psoriasis, and the active form of vitamin D can prevent genomic DNA-mediated skin inflammation via CAMP.


Asunto(s)
Proliferación Celular , Fragmentación del ADN , ADN/metabolismo , Queratinocitos/metabolismo , Psoriasis/metabolismo , Línea Celular , Factor de Crecimiento Similar a EGF de Unión a Heparina/biosíntesis , Humanos , Interleucina-1beta/biosíntesis , Queratinocitos/patología , Antígeno Ki-67/biosíntesis , Psoriasis/patología , Factor de Crecimiento Transformador alfa/biosíntesis , Factor de Necrosis Tumoral alfa/biosíntesis
3.
Epidemiol Infect ; 148: e250, 2020 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-33046159

RESUMEN

We analysed associations between exposure to nightlife businesses and severe acute respiratory syndrome coronavirus 2 PCR test results at a tertiary hospital in Tokyo between March and April 2020. A nightlife group was defined as those who had worked at or visited the businesses. We included 1517 individuals; 196 (12.9%) were categorised as the nightlife group. After propensity score matching, the proportion of positive PCR tests in the nightlife group was significantly higher than that in the non-nightlife group (nightlife, 63.8%; non-nightlife, 23.0%; P < 0.001). An inclusive approach to mitigate risks related to the businesses needs to be identified.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/transmisión , Neumonía Viral/transmisión , Adulto , COVID-19 , Comercio , Infecciones por Coronavirus/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/epidemiología , SARS-CoV-2 , Tokio/epidemiología
4.
Clin Radiol ; 72(8): 665-679, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28385253

RESUMEN

In 2016, it is estimated 180,890 men are newly diagnosed with prostate cancer and 3,306,760 men live with prostate cancer in the United States. The introduction of multiparametric (mp) magnetic resonance imaging (MRI) of the prostate, standardised interpretation guidelines such as Prostate Imaging Reporting and Data System (PI-RADS version 2), and MRI-based targeted biopsy has improved detection of clinically significant prostate cancer. Accurate risk stratification (Gleason grade/score and tumour stage) using imaging and image-guided targeted biopsy has become critical for the management of patients with prostate cancer. Recent advances in MRI-guided minimally invasive ablative treatment (MIAT) utilising cryoablation, laser ablation, high-intensity focused ultrasound ablation, have allowed accurate focal or regional delivery of optimal thermal energy to the biopsy proven, MRI-detected tumour, under real-time or near simultaneous MRI monitoring of the ablation zone. A contemporary review on prostate mpMRI, MRI-based targeted biopsy, and MRI-guided ablation techniques is presented.


Asunto(s)
Técnicas de Ablación , Imagen por Resonancia Magnética , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/cirugía , Técnicas de Ablación/métodos , Humanos , Biopsia Guiada por Imagen , Masculino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Selección de Paciente , Neoplasias de la Próstata/patología , Cirugía Asistida por Computador
5.
Br J Dermatol ; 162(5): 1098-102, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-19995364

RESUMEN

BACKGROUND: Extramammary Paget disease is an uncommon skin tumour occurring mostly in the genitoperineal region. Previous reports have shown frequent expression of androgen receptor, suggesting a tumour-proliferative effect of androgens on Paget cells. Androgen-converting enzymes such as 5alpha-reductase, which locally produces a bioactive androgen, have recently gained attention in studies of the intratumoral actions of androgens. OBJECTIVES: We investigated correlations between the androgenic microenvironment and invasiveness in extramammary Paget disease, particularly in terms of sex differences. METHODS: We examined 58 cases of extramammary Paget disease (32 men, 26 women; 42 noninvasive, 16 invasive) using immunohistochemistry for androgen receptor and 5alpha-reductase. RESULTS: In all 58 cases, expression rates were 57% for androgen receptor and 55% for 5alpha-reductase, with 38% double-positivity for androgen receptor and 5alpha-reductase. Only 5alpha-reductase expression rate was significantly higher in invasive cases (81%) than in noninvasive cases (45%; P = 0.042). For invasive cases, numbers of double-positive results for androgen receptor and 5alpha-reductase were significantly higher in men (70%) than in women (17%; P = 0.039). CONCLUSIONS: Double positivity for androgen receptor and 5alpha-reductase in Paget cells suggests autocrine synthesis of androgens in extramammary Paget disease. The different hormonal microenvironments in male and female cases and intratumoral androgen levels affect the invasiveness of extramammary Paget disease.


Asunto(s)
Colestenona 5 alfa-Reductasa/metabolismo , Enfermedad de Paget Extramamaria/metabolismo , Receptores Androgénicos/metabolismo , Neoplasias Cutáneas/metabolismo , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Proteínas de Neoplasias/metabolismo , Enfermedad de Paget Extramamaria/patología , Enfermedad de Paget Extramamaria/secundario , Factores Sexuales , Neoplasias Cutáneas/patología
6.
Clin Exp Immunol ; 156(3): 495-501, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19438603

RESUMEN

Mycobacterium leprae is an intracellular pathogen that survives within the phagosome of host macrophages. Several host factors are involved in producing tolerance, while others are responsible for killing the mycobacterium. Tryptophan aspartate-containing coat protein (TACO; also known as CORO1A or coronin-1) inhibits the phagosome maturation that allows intracellular parasitization. In addition, the Toll-like receptor (TLR) activates the innate immune response. Both CORO1A and TLR-2 co-localize on the phagosomal membrane in the dermal lesions of patients with lepromatous leprosy. Therefore, we hypothesized that CORO1A and TLR-2 might interact functionally. This hypothesis was tested by investigating the effect of CORO1A in TLR-2-mediated signalling and, inversely, the effect of TLR-2-mediated signalling on CORO1A expression. We found that CORO1A suppresses TLR-mediated signal activation in human macrophages, and that TLR2-mediated activation of the innate immune response resulted in suppression of CORO1A expression. However, M. leprae infection inhibited the TLR-2-mediated CORO1A suppression and nuclear factor-kappaB activation. These results suggest that the balance between TLR-2-mediated signalling and CORO1A expression will be key in determining the fate of M. leprae following infection.


Asunto(s)
Lepra/inmunología , Proteínas de Microfilamentos/inmunología , Receptor Toll-Like 2/inmunología , Animales , Humanos , Inmunidad Innata , Ratones , Ratones Desnudos , Mycobacterium leprae/inmunología , FN-kappa B/metabolismo , Fagosomas/inmunología , Transducción de Señal/inmunología , Transfección
7.
Eur Radiol ; 19(5): 1289-95, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19153744

RESUMEN

The aim of this study was to assess the ability of dual-energy computed tomography (DECT) to classify phantom renal lesions as cysts or enhancing masses. Six cylinders ranging in diameter from 0.5 to 3.0 cm were filled with distilled water or titrated iodinated contrast solutions with CT attenuation values at 120 kVp of 0 Hounsfield units (HU) for a cyst proxy or 10, 20, or 40 HU to represent enhancing masses. These were placed in a 12-cm-diameter renal phantom containing puréed beef mixed with iodinated contrast medium to simulate enhancing renal parenchyma of 100 and 250 HU and submerged within a 28-cm water bath. These combinations produced 48 individual phantom renal lesions of differing sizes, internal and parenchymal enhancement (12 cysts and 36 enhancing masses). DECT using 80 and 140 kVp was performed on a dual-source CT scanner. Commercial software created a color-encoded overlay indicating the location of iodine within the phantom. The lesions were individually graded as a cyst or enhancing mass by blinded, consensus interpretation of two genitourinary radiologists. Thirty-five of 36 enhancing masses and 10/12 cysts were correctly identified, equating to a sensitivity and specificity of 97% (95% CI 84-100%) and 83% (95% CI 51-97%), respectively. All lesions of 20- and 40-HU enhancement and 92% of 10-HU lesions were identified correctly. In a phantom model, the DECT iodine overlay technique is highly sensitive in detecting enhancing renal masses. Refinement of the technique remains necessary to improve specificity. If validated in patients, this may obviate the need for unenhanced acquisitions for renal mass characterization.


Asunto(s)
Yodo , Riñón/patología , Imagen Radiográfica por Emisión de Doble Fotón/métodos , Tomografía Computarizada por Rayos X/métodos , Simulación por Computador , Medios de Contraste/farmacología , Humanos , Procesamiento de Imagen Asistido por Computador , Variaciones Dependientes del Observador , Fantasmas de Imagen , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Imagen Radiográfica por Emisión de Doble Fotón/instrumentación , Sensibilidad y Especificidad , Programas Informáticos , Tomografía Computarizada por Rayos X/instrumentación
8.
Cancer Gene Ther ; 24(7): 277-281, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28497777

RESUMEN

Inactivated Sendai virus particles (hemagglutinating virus of Japan envelope (HVJ-E)) have a novel antitumor effect: HVJ-E fused to prostate cancer cells via cell surface receptor causes apoptosis of prostate cancer cells in vitro and in vivo. HVJ-E also induces antitumor immunity by activating natural killer (NK) cells and cytotoxic T cells and suppressing regulatory T cells in vivo. We conducted an open-label, single-arm, phase I/II clinical trial in patients with castration-resistant prostate cancer (CRPC) to determine the safety and efficacy of intratumoral and subcutaneous injection of HVJ-E. Patients with CRPC who were docetaxel-resistant or could not receive docetaxel treatment were eligible. HVJ-E was injected directly into the prostate on day 1 and subcutaneously on days 5, 8 and 12 in two 28-day treatment cycles using a 3+3 dose-escalation design. The primary end points were to evaluate safety and tolerability of HVJ-E. The secondary end points were to analyze tumor immunity and antitumor effect. The study is registered at UMIN Clinical Trials Registry, number UMIN000006142. Seven patients were enrolled, and six patients received HVJ-E. Grade 2 or 3 adverse events (Common Terminology Criteria for Adverse Events Ver. 4.0) were urinary retention and lymphopenia from which the patients recovered spontaneously. No Grade 4 adverse events were observed. Radiographically, three patients had stable disease in the low-dose group, and one patient had stable disease and two had progressive disease in the high-dose group. The prostate-specific antigen (PSA) declined from 14 to 1.9 ng ml-1 in one patient in the low-dose group after two cycles of HVJ-E treatment, and the PSA response rate was 16.6%. NK cell activity was elevated from day 12 to day 28 after HVJ-E administration, whereas serum interleukin-6, interferon (IFN)-α, IFN-ß and IFN-γ levels were not affected by HVJ-E treatment. Intratumoral and subcutaneous injections of HVJ-E are feasible and PSA response was observed in a subgroup of CRPC patients.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración/inmunología , Neoplasias de la Próstata Resistentes a la Castración/terapia , Virus Sendai/inmunología , Vacunas de Partículas Similares a Virus/inmunología , Proteínas del Envoltorio Viral/inmunología , Anciano , Anciano de 80 o más Años , Citocinas/metabolismo , Esquema de Medicación , Humanos , Inyecciones Subcutáneas , Interleucinas , Masculino , Persona de Mediana Edad , Antígeno Prostático Específico/inmunología , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/patología , Terapéutica , Vacunas de Partículas Similares a Virus/administración & dosificación , Vacunas de Partículas Similares a Virus/efectos adversos
9.
J Thromb Haemost ; 14(9): 1788-97, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27328457

RESUMEN

UNLABELLED: Essentials A consensus methodology for assessing the effects of antiplatelet agents has not been established. Measuring platelet thrombus formation (PTF) for evaluating antiplatelet effects was assessed. PTF differentially reflected antiplatelet effects compared to other tests. PTF may be associated with the severity of carotid or intracranial arterial stenosis. Click to hear a presentation on platelet function testing in the clinic by Gresele and colleagues SUMMARY: Background A consensus methodology for assessing the effects of antiplatelet agents has not been established. Objective We investigated the usefulness of directly measuring platelet thrombus formation (PTF) using a microchip-based flow chamber system for evaluating antiplatelet therapy. Patients/Methods Platelet thrombus formation in the whole blood of 94 patients with ischemic cerebrovascular disease treated with clopidogrel and/or aspirin was measured in a flow chamber system at a shear rate of 1500 s(-1) and was compared with the results of assays for agonist-induced platelet aggregability, phosphorylation of vasodilator-stimulated phosphoprotein, platelet p-selectin expression (PS), and platelet-monocyte complexes. Results In all patients tested, area under the flow pressure curve (AUC10), which represents platelet thrombogenicity, showed weak correlation with platelet aggregation induced by either adenosine diphosphate or collagen. In addition, AUC10 was lower in patients treated with dual antiplatelet therapy (median 79.4) compared with patients treated with aspirin or clopidogrel alone (217.7 and 301.0, respectively), whereas the parameters evaluated by the other assays did not reflect the combined treatment efficacy. In clopidogrel monotherapy patients, AUC10 was associated with the severity of arterial stenosis (R(2) = 0.127, ß = 1.25), and AUC10 and PS were higher in patients with severe carotid or intracranial arterial stenosis than in those with mild stenosis. Conclusions Platelet thrombus formation measurement using a flow-chamber system was useful for evaluating the efficacy of treatment with aspirin and clopidogrel, both alone and in combination. The present findings indicate that high residual platelet thrombogenicity in patients treated with clopidogrel may be associated with the severity of carotid or intracranial arterial stenosis.


Asunto(s)
Plaquetas/citología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Trombosis/patología , Adulto , Anciano , Arterias/patología , Aspirina/uso terapéutico , Pruebas de Coagulación Sanguínea , Arterias Carótidas/patología , Moléculas de Adhesión Celular/metabolismo , Circulación Cerebrovascular , Trastornos Cerebrovasculares/terapia , Clopidogrel , Constricción Patológica/sangre , Constricción Patológica/patología , Estudios Transversales , Femenino , Humanos , Masculino , Proteínas de Microfilamentos/metabolismo , Persona de Mediana Edad , Selectina-P/metabolismo , Fosfoproteínas/metabolismo , Fosforilación , Agregación Plaquetaria , Pruebas de Función Plaquetaria/métodos , Resistencia al Corte , Trombosis/metabolismo , Ticlopidina/análogos & derivados , Ticlopidina/uso terapéutico , Vasodilatadores/farmacología , Adulto Joven
10.
Circulation ; 102(4): 399-404, 2000 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-10908211

RESUMEN

BACKGROUND: Although metallic stents are effective in preventing acute occlusion and reducing late restenosis after coronary angioplasty, many concerns still remain. Compared with metallic stents, poly-l-lactic acid (PLLA) stents are biodegradable and can deliver drugs locally. The aim of this study was to evaluate the feasibility, safety, and efficacy of the PLLA stent. METHODS AND RESULTS: Fifteen patients electively underwent PLLA Igaki-Tamai stent implantation for coronary artery stenoses. The Igaki-Tamai stent is made of a PLLA monopolymer, has a thickness of 0.17 mm, and has a zigzag helical coil pattern. A balloon-expandable covered sheath system was used, and the stent expanded by itself to its original size with an adequate temperature. A total of 25 stents were successfully implanted in 19 lesions in 15 patients, and angiographic success was achieved in all procedures. No stent thrombosis and no major cardiac event occurred within 30 days. Coronary angiography and intravascular ultrasound were serially performed 1 day, 3 months, and 6 months after the procedure. Angiographically, both the restenosis rate and target lesion revascularization rate per lesion were 10.5%; the rates per patient were 6.7% at 6 months. Intravascular ultrasound findings revealed no significant stent recoil at 1 day, and they revealed stent expansion at follow-up. No major cardiac event, except for repeat angioplasty, developed within 6 months. CONCLUSIONS: Our preliminary experience suggests that coronary PLLA biodegradable stents are feasible, safe, and effective in humans. Long-term follow-up with more patients will be required to validate the long-term efficacy of PLLA stents.


Asunto(s)
Angioplastia Coronaria con Balón/instrumentación , Materiales Biocompatibles , Ácido Láctico , Polímeros , Stents , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Poliésteres
11.
Atherosclerosis ; 101(1): 25-35, 1993 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-8216500

RESUMEN

We have previously reported that mouse peritoneal macrophages have three types of modified low density lipoprotein (LDL) receptors. One is specific for acetylated LDL (Ac-LDL), the second is for oxidized LDL (Ox-LDL), and the third recognizes both (Arai, H. et al. (1989) Biochem. Biophys. Res. Commun. 159, 1375-1382). In the current study, the characteristics of modified LDL receptors in rabbit peritoneal macrophages and Kupffer cells from rabbits were investigated. Cross-competition studies of the degradation assay between Ox-LDL and Ac-LDL in rabbit peritoneal macrophages showed that the degradation of 125I-labeled Ox-LDL was almost completely inhibited by an excess amount of unlabeled Ac-LDL. On the other hand, an excess amount of unlabeled Ox-LDL suppressed 125I-labeled Ac-LDL degradation only partially. In contrast, in Kupffer cells an excess amount of unlabeled Ox-LDL inhibited the degradation of 125I-labeled Ac-LDL almost completely, whereas the degradation of 125I-labeled Ox-LDL was inhibited only partially by Ac-LDL. Scatchard analysis of binding assay showed that rabbit peritoneal macrophages have a single class of receptor for Ox-LDL, which binds maximally 0.31 microgram/mg cellular protein (Bmax) with an apparent dissociation constant (Kd) of 19.3 micrograms/ml, and two classes of receptors for Ac-LDL; one with high affinity (Bmax 0.025 microgram/mg cellular protein, Kd 0.040 micrograms/ml) and the other with low affinity (Bmax 0.08 microgram/mg cellular protein, Kd 11.31 micrograms/ml). On the other hand, Kupffer cells have two classes for Ox-LDL; one is a high affinity receptor (Bmax 0.53 microgram/mg cellular protein, Kd 0.99 microgram/ml) and the other is a low affinity receptor (Bmax 3.71 micrograms/mg cellular protein, Kd 16.2 micrograms/ml) and a single class for Ac-LDL (Bmax 0.60 microgram/mg cellular protein, Kd 7.24 micrograms/ml). These results indicate that rabbit peritoneal macrophages have two kinds of modified LDL receptors; one is specific for Ac-LDL, and the other recognizes both Ox-LDL and Ac-LDL.


Asunto(s)
Macrófagos del Hígado/metabolismo , Macrófagos Peritoneales/metabolismo , Receptores de LDL/metabolismo , Acetilación , Animales , Células Cultivadas , Lipoproteínas LDL/metabolismo , Masculino , Oxidación-Reducción , Conejos
12.
Atherosclerosis ; 146(2): 281-90, 1999 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-10532684

RESUMEN

Stimulatory effects of a novel isobenzofranone, MD-700, on low density lipoprotein (LDL) receptor activity were investigated in vitro and in vivo. MD-700 at 0.03 microg/ml elevated the expression of LDL receptor in HepG2 cells within 4 h. Corresponding to this, uptake of fluorescent labeled-LDL (3,3'-dioctadecylindocarbocyanine-LDL) by the cells increased linearly in time- and dose-dependent manner by MD-700 for up to 12 h. In the experiment using HepG2 cells transiently transfected with promoter-luciferase gene constructs, MD-700 increased luciferase activity in a dose-dependent manner from 0.03 to 0.1 microg/ml. In contrast, luciferase activity was not stimulated by MD-700 in construct with a deleted sterol regulatory element (SRE)-1, suggesting importance of SRE-1 in stimulation of the LDL receptor gene promoter by MD-700. Binding experiments on liver membranes from MD-700-treated hamsters showed about a 60% increase in 125I-labeled LDL binding. A Scatchard plot revealed that MD-700 increased the maximal binding without affecting binding affinity. In contrast to findings with an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, pravastatin, MD-700 had no effect on the sterol synthesis in hamster liver homogenates. These results suggest that MD-700 stimulates the expression of LDL receptor, presumably in a manner independent of change in sterol metabolism, and thereby promotes LDL clearance. Hypocholesterolemic actions of MD-700 in hamsters were then examined. MD-700 lowered serum cholesterol levels in hamsters fed normal chow or a high-fat diet. Fractionation of serum lipoproteins demonstrated that MD-700 selectively decreased LDL and very low density lipoprotein cholesterol. Dose-dependent decrease in serum cholesterol was also seen in hypercholesterolemic rats. Thus, the hypocholesterolemic action of MD-700 may be attributed to up-regulation of the LDL receptor, based on stimulation of the transcription of the LDL receptor gene. Although pravastatin stimulates LDL uptake and lowers serum cholesterol in a manner similar to that seen with MD-700, the mechanism responsible for hypocholesterolemic action appears to differ.


Asunto(s)
Benzofuranos/farmacología , Hipercolesterolemia/metabolismo , Receptores de LDL/metabolismo , Regulación hacia Arriba , Animales , Northern Blotting , Carbocianinas/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Membrana Celular/metabolismo , Colesterol/biosíntesis , Cricetinae , Cartilla de ADN/química , Modelos Animales de Enfermedad , Colorantes Fluorescentes/metabolismo , Humanos , Hipercolesterolemia/genética , Hipercolesterolemia/patología , Lipoproteínas LDL/efectos de los fármacos , Lipoproteínas LDL/metabolismo , Lipoproteínas VLDL/efectos de los fármacos , Lipoproteínas VLDL/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Regiones Promotoras Genéticas/efectos de los fármacos , ARN Mensajero/genética , ARN Neoplásico/genética , Ratas , Ratas Wistar , Receptores de LDL/genética , Esteroles/metabolismo , Transcripción Genética/efectos de los fármacos , Células Tumorales Cultivadas
13.
Neuromuscul Disord ; 9(1): 34-7, 1999 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-10063833

RESUMEN

We identified a new mutation in the myophosphorylase gene in a Japanese family with McArdle's disease. This point mutation results in the replacement of a tryptophan at amino acid position 361 with a stop codon, the third nonsense mutation in this disorder. Our findings further expand the already wide spectrum of genetic lesions associated with McArdle's disease, and establish that molecular genetic heterogeneity is also present in the Japanese population.


Asunto(s)
Enfermedad del Almacenamiento de Glucógeno Tipo V/enzimología , Enfermedad del Almacenamiento de Glucógeno Tipo V/genética , Mutación Missense/genética , Fosforilasas/genética , Anciano , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Biología Molecular , Linaje , Fosforilasas/deficiencia , Polimorfismo de Longitud del Fragmento de Restricción , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
14.
Neuromuscul Disord ; 9(6-7): 399-402, 1999 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-10545043

RESUMEN

Muscle-specific phosphoglycerate mutase (PGAM-M) deficiency results in a metabolic myopathy (glycogenosis type X). Three mutations in the PGAM-M gene have been described thus far, two in African-American families and one in a Caucasian family. In two of them, manifesting heterozygotes were documented. We found a new PGAM-M mutation in a Japanese family with partial PGAM deficiency: a G-to-A transition at nucleotide position 209, resulting in the substitution of a highly conserved glycine at codon 97 with aspartic acid (G97D). Two heterozygous family members for the G97D mutation presented with exercise intolerance and muscle cramps. We describe the first PGAM-M mutation in the Japanese population and confirm that heterozygous individuals can be symptomatic.


Asunto(s)
Tamización de Portadores Genéticos , Enfermedad del Almacenamiento de Glucógeno/genética , Músculo Esquelético/enzimología , Mutación Missense , Fosfoglicerato Mutasa/genética , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Pueblo Asiatico/genética , Población Negra , Femenino , Enfermedad del Almacenamiento de Glucógeno/enzimología , Humanos , Japón , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Linaje , Fosfoglicerato Mutasa/química , Reacción en Cadena de la Polimerasa , Alineación de Secuencia , Población Blanca
15.
J Nucl Med ; 29(7): 1279-82, 1988 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-3164753

RESUMEN

The scintigraphic findings on bone imaging in two patients with extensive lower extremity periostitis secondary to venous insufficiency are presented. One of these patients had bilateral disease. The use of [67Ga]citrate scanning in an attempt to exclude concurrent osteomyelitis is also addressed.


Asunto(s)
Pierna/irrigación sanguínea , Periostitis/diagnóstico por imagen , Insuficiencia Venosa/complicaciones , Anciano , Anciano de 80 o más Años , Femenino , Radioisótopos de Galio , Humanos , Persona de Mediana Edad , Periostitis/etiología , Cintigrafía , Medronato de Tecnecio Tc 99m
16.
J Nucl Med ; 41(7): 1244-9, 2000 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10914917

RESUMEN

UNLABELLED: Induced hypertension and kininase inhibition can enhance tumor targeting of radiolabeled monoclonal antibody (MAb) by altering tumor circulation. This study investigated the effect of this manipulation on the antitumor efficacy of radioimmunotherapy (RIT). METHODS: Mice bearing human colon cancer xenografts were administered 2.0 microg/kg/min of angiotensin II (AT-II) for 1 h and 30 microg of a kininase inhibitor, enalapril maleate, before the administration of 3.7 MBq (131)I-A7, an IgG1 against 45-kDa glycoprotein on colorectal cancer, and tumor growth was observed thereafter. The mechanism of the manipulation effect was investigated by estimation of the tissue absorbed dose and radioluminography of tumors. RESULTS: The pharmacologic manipulation with AT-II and enalapril improved the tumor quadrupling time (Tq) of 3.7 MBq RIT from 24.3 +/- 2.75 d to 33.1 +/- 2.83 d (P < 0.05). Addition of this manipulation made 3.7 MBq RIT as effective as 9.25 MBq RIT alone (Tq, 37.2 +/- 2.97 d). Dose estimation showed that the manipulation increased the tumor absorbed dose 1.55-fold without affecting the doses to normal tissues. Uniform intratumoral distribution in the manipulated tumors was shown by radioluminography. CONCLUSION: Larger and more uniform tumor radiation produced by this pharmacologic manipulation can benefit RIT with (131)I-MAb.


Asunto(s)
Angiotensina II/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Neoplasias del Colon/radioterapia , Enalapril/administración & dosificación , Radioinmunoterapia , Vasoconstrictores/administración & dosificación , Animales , Anticuerpos Monoclonales/farmacocinética , Neoplasias del Colon/irrigación sanguínea , Neoplasias del Colon/diagnóstico por imagen , Femenino , Humanos , Radioisótopos de Yodo/farmacocinética , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Cintigrafía , Dosificación Radioterapéutica
17.
Am J Cardiol ; 83(1): 32-7, 1999 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-10073781

RESUMEN

Angioplasty of the unprotected left main coronary artery (LMCA) has been controversial. Although recent single-center studies suggest that new devices may change the situation, many questions and problems remain. Therefore, the results of unprotected left main coronary angioplasty of 175 procedures in 107 patients were analyzed to evaluate its feasibility and effectiveness. The treatment of the initial 107 cases included balloon angioplasty (39 cases, 36%), directional coronary atherectomy (53 cases, 50%), and stents (15 cases, 14%). They were divided into 3 major subgroups: (1) acute group (n = 14), in which LMCA angioplasty was performed in patients with acute myocardial infarction; (2) emergency group (n = 10); and (3) elective group (n = 83). In-hospital mortality was higher in the acute (35.7%) and emergency (40.0%) groups than in the elective group (3.6%; p <0.0001). Angiographic follow-up was routinely performed and the restenosis rate including in-hospital restenosis was 70% in the acute group, 37.5% in the emergency group, and 40% in the elective group (p = NS). The mean clinical follow-up period was 2.9 years, and the estimated 5-year survival rates of the acute and emergency groups were 50% and 48.2%, respectively. However the 5-year survival rate of the elective group was higher than that seen in the acute or emergency group (77.5%; p <0.05). Repeat LMCA angioplasty was performed in 37 of 68 patients with 8.8% mortality (38.5% of acute and emergency cases and 1.8% of elective cases). The results indicated that elective unprotected LMCA angioplasty is relatively feasible and effective under scheduled angiographic follow-up.


Asunto(s)
Angioplastia Coronaria con Balón , Enfermedad Coronaria/terapia , Vasos Coronarios/patología , Adulto , Anciano , Anciano de 80 o más Años , Angiografía Coronaria , Enfermedad Coronaria/mortalidad , Enfermedad Coronaria/patología , Femenino , Estudios de Seguimiento , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Resultado del Tratamiento
18.
Cancer Lett ; 158(1): 93-8, 2000 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-10940514

RESUMEN

Lipiodol, an iodine adduct lipid, has been used as a targeting carrier of anticancer drugs in experimental animals and humans. In most studies, the concentrations of the anticancer drugs in tissues and organs have been monitored, but not of the carrier because a simple method for measuring lipiodol in biological organs did not exist. Here we present an analytical method for the quantitative determination of lipiodol in tissue. This method is based on the measurement of iodine released from lipiodol by an oxidative reaction. The released iodine was measured spectrophotometrically by monitoring the iodo-starch reaction. Using this method, we were able to demonstrate the tumor specificity of lipiodol using rabbits bearing VX2 tumors in the liver. The present method is also expected to be applicable to human cancers, such as hepatic and colon cancer.


Asunto(s)
Clorobenzoatos/química , Aceite Yodado/análisis , Neoplasias/química , Animales , Humanos , Yodo/química , Hígado/química , Masculino , Control de Calidad , Conejos , Estándares de Referencia , Reproducibilidad de los Resultados , Almidón/química
19.
Invest Radiol ; 28(2): 146-9, 1993 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-8444571

RESUMEN

RATIONALE AND OBJECTIVES: The objective of this study is to determine whether the use of edge-enhancement post-processing filters was useful in the computed tomographic (CT) multiplanar evaluation of skeletal trauma. METHODS: The group consisted of a series of 10 cases of skeletal trauma (3 cases of acetabular fractures, 3 cases of tibial plateau fractures, and 4 cases of ankle fractures). All patients had a CT scan using a scan protocol of 4-mm collimation and 3-mm interscan interval. All transaxial images were reconstructed with both a standard algorithm and with an edge-enhancement filter. The images from each group were then reconstructed into coronal and sagittal planes. Three individuals independently reviewed each case and compared image pairs to determine whether images using an edge-enhancement filter were of better or worse quality than standard images. RESULTS: The reviewers found the images with edge-enhancement to be equal to or superior to images reconstructed with a standard algorithm, regardless of the image plane chosen. This bias was especially true in cases of hip and ankle trauma. CONCLUSIONS: When CT supplemented by multiplanar imaging is used in patients with skeletal trauma, image data reconstruction should be done with an edge-enhancement filter to optimize image detail.


Asunto(s)
Fracturas Óseas/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador , Tomografía Computarizada por Rayos X , Acetábulo/diagnóstico por imagen , Acetábulo/lesiones , Algoritmos , Traumatismos del Tobillo/diagnóstico por imagen , Humanos , Fracturas de la Tibia/diagnóstico por imagen
20.
J Cancer Res Clin Oncol ; 119(6): 363-8, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-8449973

RESUMEN

We reviewed histological and clinical findings of six cases of borderline chondrosarcoma and examined the expression of collagen types I, II, III, V, and VI by immunohistochemical analysis of these tumors. Borderline chondrosarcoma is defined as a cartilaginous tumor of bone resembling enchondroma on the basis of histomorphology. Clinically the tumor causes intermittent vague pain unrelated to physical activities. On radiographs borderline chondrosarcoma is characterized by evidence of endosteal erosion. We observed local recurrences in two cases treated by intralesional excision and marginal excision, and one of those cases died of inoperable local tumor recurrence. In our histological analysis based on tissue patterns, there were enchondromatous patterns in five cases, and chondrosarcomatous patterns in four cases. In the second recurrent tumor in one case, a chondrosarcomatous pattern was newly observed, and the recurrent tumor was found to be a low-grade chondrosarcoma cytologically in the other case. In the tumor matrix immunoreactivity for collagen types II and VI was predominant, with collagen types I, III, and V showing heterogeneous expression in some cases. In all cases rimming of tumor lobules with collagen types I and V was absent. Immunoreactivity for collagen type II in the cytoplasm of tumor cells was found in four cases and all three recurrent tumors. Borderline chondrosarcoma, as defined by histology, clinical symptoms and radiological appearance, shows a collagen distribution pattern similar to that of low-grade chondrosarcoma. These findings are in accordance with the clinical outcome of borderline chondrosarcoma which parallels that of low-grade chondrosarcoma. Thus borderline chondrosarcoma may be best treated by wide en-bloc excision rather than curettage.


Asunto(s)
Neoplasias Óseas/diagnóstico , Condrosarcoma/diagnóstico , Adulto , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Condrosarcoma/metabolismo , Condrosarcoma/patología , Colágeno/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad
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