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1.
J Dent Res ; 95(10): 1176-82, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27151915

RESUMO

To elucidate if microglial P2Y12 receptor (P2Y12R) mechanisms are involved in the trigeminal spinal subnucleus caudalis (Vc; also known as the medullary dorsal horn) in intraoral cancer pain, we developed a rat model of tongue cancer pain. Squamous cell carcinoma (SCC) cells were inoculated into the tongue of rats; sham control rats received the vehicle instead. Nociceptive behavior was measured as the head-withdrawal reflex threshold (HWRT) to mechanical or heat stimulation applied to the tongue under light anesthesia. On day 14 after the SCC inoculation, activated microglia and P2Y12R expression were examined immunohistochemically in the Vc. The HWRT was also studied in SCC-inoculated rats with successive intra-cisterna magna (i.c.m.) administration of specific P2Y12R antagonist (MRS2395) or intraperitoneal administration of minocycline, a microglial activation inhibitor. Tongue cancer was histologically verified in SCC-inoculated rats, within which the HWRT to mechanical stimulation of the tongue was significantly decreased, as compared with that of vehicle-inoculated rats, although the HWRT to heat stimulation was not. Microglia was strongly activated on day 14, and the administration of MRS2395 or minocycline reversed associated nocifensive behavior and microglial activation in SCC-inoculated rats for 14 d. The activity of Vc wide dynamic range nociceptive neurons was also recorded electrophysiologically in SCC-inoculated and sham rats. Background activity and noxious mechanically evoked responses of wide dynamic range neurons were significantly increased in SCC-inoculated rats versus sham rats, and background activity and mechanically evoked responses were significantly suppressed following i.c.m. administration of MRS2395 in SCC-inoculated rats as compared with sham. The present findings suggest that SCC inoculation that produces tongue cancer results in strong activation of microglia via P2Y12 signaling in the Vc, in association with increased excitability of Vc nociceptive neurons, reflecting central sensitization and resulting in tongue mechanical allodynia.


Assuntos
Dor do Câncer/metabolismo , Carcinoma de Células Escamosas/metabolismo , Microglia/metabolismo , Neuralgia/metabolismo , Receptores Purinérgicos P2Y12/metabolismo , Neoplasias da Língua/metabolismo , Núcleo Espinal do Trigêmeo/metabolismo , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Imuno-Histoquímica , Masculino , Minociclina/farmacologia , Nociceptores/metabolismo , Ratos , Ratos Endogâmicos F344 , Transdução de Sinais , Valeratos/farmacologia
2.
Minerva Anestesiol ; 78(11): 1241-7, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23132262

RESUMO

BACKGROUND: Patients with severe cardiovascular disease are frequently hemodynamically unstable during abdominal surgery. Improving the safety of such patients by stabilizing intraoperative hemodynamics remains a major concern for anesthesiologists. Transversus abdominis plane (TAP) block in combination with general anesthesia may facilitate optimum anesthetic management of these high-risk patients. METHODS: Patients with cardiovascular disease classified as American Society of Anesthesiologists (ASA) physical status 3 were enrolled. The patients were undergoing elective abdominal surgery and were randomized to a group receiving general anesthesia and TAP block (Group T, N.=33) or a group receiving general anesthesia alone (Group G, N.=35). We compared the groups for intraoperative hemodynamic stability, anesthesia emergence time, amounts of anesthetics and opioids given, and frequency of emergency treatment with cardiovascular agents. A preliminary study demonstrated that systolic blood pressure and heart rate were maintained stable within 70-110% of their preanesthesia values throughout surgery in ASA 1 elderly patients without cardiovascular disease. Thus, the hemodynamically stable time was defined as the time when systolic blood pressure and heart rate were 70-110% of their preanesthesia values. The ratio of hemodynamically stable time to total operative time was used as an index of hemodynamic stability. RESULTS: The median (minimum-maximum) percentage of hemodynamically stable time was longer in Group T (91[50-100]%) than Group G (79[40-91]%, P<0.01). The mean sevoflurane concentration, amount of fentanyl given and frequency of vasopressor use were lower in Group T than Group G (P<0.05). Anesthesia emergence time was shorter in Group T (14[4-30] min) than Group G (18[9-52] min, P<0.01). No worsening of cardiovascular complications was observed. CONCLUSION: For abdominal surgery in patients with severe cardiovascular disease, combining TAP block with general anesthesia promotes intraoperative hemodynamic stability and early emergence from anesthesia.


Assuntos
Abdome/cirurgia , Anestesia Geral , Hemodinâmica/fisiologia , Bloqueio Nervoso , Abdome/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea/fisiologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Procedimentos Cirúrgicos Operatórios/métodos , Ultrassonografia de Intervenção
3.
Neuroscience ; 138(3): 757-64, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16310315

RESUMO

Hippocampal pyramidal neurons and granule neurons of adult male rats are equipped with a complete machinery for the synthesis of pregnenolone, dehydroepiandrosterone, testosterone, dihydrotestosterone and 17beta-estradiol. Both estrogens and androgens are synthesized in male hippocampus. These brain steroids are synthesized by cytochrome P450s (P450scc, P45017alpha and P450arom), hydroxysteroid dehydrogenases and reductases from endogenous cholesterol. The expression levels of enzymes are as low as 1/300-1/1000 of those in endocrine organs. Synthesis is dependent on the acute Ca(2+) influx upon neuron-neuron communication via NMDA receptors. Estradiol is particularly important because estradiol rapidly modulates neuronal synaptic transmission such as long-term potentiation via synaptic estrogen receptors. Xenoestrogens may also act via estrogen-driven signaling pathways.


Assuntos
Androgênios/fisiologia , Encéfalo/metabolismo , Estrogênios/fisiologia , Hipocampo/metabolismo , Plasticidade Neuronal/fisiologia , Sinapses/fisiologia , Androgênios/biossíntese , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , Estrogênios/biossíntese , Humanos , Neurônios/fisiologia , Ratos
4.
Abdom Imaging ; 30(5): 524-34, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16096870

RESUMO

Gastrointestinal tract perforation is an emergent condition that requires prompt surgery. Diagnosis largely depends on imaging examinations, and correct diagnosis of the presence, level, and cause of perforation is essential for appropriate management and surgical planning. Plain radiography remains the first imaging study and may be followed by intraluminal contrast examination; however, the high clinical efficacy of computed tomographic examination in this field has been well recognized. The advent of spiral and multidetector-row computed tomographic scanners has enabled examination of the entire abdomen in a single breath-hold by using thin-slice sections that allow precise assessment of pathology in the alimentary tract. Extraluminal air that is too small to be detected by conventional radiography can be demonstrated by computed tomography. Indirect findings of bowel perforation such as phlegmon, abscess, peritoneal fluid, or an extraluminal foreign body can also be demonstrated. Gastrointestinal mural pathology and associated adjacent inflammation are precisely assessed with thin-section images and multiplanar reformations that aid in the assessment of the site and cause of perforation.


Assuntos
Perfuração Intestinal/diagnóstico por imagem , Úlcera Péptica Perfurada/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Sulfato de Bário , Meios de Contraste , Diagnóstico Diferencial , Emergências , Enema , Extravasamento de Materiais Terapêuticos e Diagnósticos , Humanos , Achados Incidentais , Perfuração Intestinal/etiologia , Sensibilidade e Especificidade
5.
Mol Psychiatry ; 7(10): 1101-6, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12476325

RESUMO

N-methyl-D-aspartate (NMDA) receptor dysfunction is involved in the pathogenesis of schizophrenia. We determined the nucleotide sequence of the 5'-upstream region of the human NMDA receptor 2B (NR2B) subunit gene and identified a novel T-200G variant located in one of the Sp1 binding sites. To investigate the effect of this variant on the transcriptional activity of the hNR2B gene, we performed gene reporter assays using PC12 pheochromocytoma cells transiently transfected with luciferase reporter plasmids. In the absence of nerve growth factor (NGF), luciferase activities did not significantly differ between the two alleles and the control plasmid. However, luciferase reporter activity of the T allele was significantly up-regulated compared to that of the G allele in the presence of NGF (P = 0.0013), indicating that this polymorphic site is a critical region for NR2B gene regulation through NGF-induced Sp1-binding. A case control study showed that the frequency of the G allele (P = 0.0164) was significantly higher in 100 schizophrenics than in 100 controls. These findings suggest that the T-200G variant causes dysfunction of NMDA receptors consisting of the NR2B subunit and may be involved in the development of schizophrenia. Replication studies of independent samples and family-based association studies are necessary to further evaluate the significance of our findings.


Assuntos
Regulação da Expressão Gênica , Variação Genética , Podofilina/análogos & derivados , Receptores de N-Metil-D-Aspartato/genética , Esquizofrenia/genética , Regiões 5' não Traduzidas/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Sítios de Ligação , Primers do DNA , Frequência do Gene , Genes Reporter , Humanos , Dados de Sequência Molecular , Células PC12 , Feocromocitoma , Podofilina/metabolismo , Podofilotoxina/análogos & derivados , Ratos , Valores de Referência , Regulação para Cima
6.
J Org Chem ; 66(26): 8779-86, 2001 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-11749606

RESUMO

A remarkable effect of (C(6)F(5)O)(3)Al for promoting the rearrangement of epoxy acylates via stable cation intermediates was found, and new methods for constructing chiral benzylic, vinylic, and acetylenic quaternary carbon centers were developed. During the study, the importance of the ionic nature of the O-metal bond in the intermediates of such epoxides was addressed. This method was applied to the asymmetric total synthesis of (S)-(+)-sporochnol A.


Assuntos
Alcenos/síntese química , Alumínio , Compostos de Epóxi/química , Compostos Organometálicos/química , Fenóis/síntese química , Alcenos/química , Cátions , Eucariotos/química , Indicadores e Reagentes , Fenóis/química , Estereoisomerismo
7.
Jpn J Ophthalmol ; 45(5): 482-6, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11583669

RESUMO

BACKGROUND: The association of oblique palpebral fissures and A- or V-pattern has not been clarified. We report two cases of A-pattern esotropia with marked mongoloid slanting palpebral fissures associated with vertical displacement of the horizontal rectus muscle. CASES: Case 1 was a boy with Prader-Willi syndrome. He showed A-pattern esotropia with upward slanting palpebral fissures. Severe superior oblique muscle overaction was observed. Case 2 was a girl with meningocele. She also showed A-pattern esotropia with upward slanting palpebral fissures. OBSERVATIONS: In case 1, weakening surgery of the superior oblique muscles did not improve the A-pattern. Coronal images of computed tomography showed one-half-muscle-width upward displacement of both lateral rectus muscles. After downward transposition surgery of the lateral rectus muscles, the preoperative A-pattern of 25 prism diopters (PD) was successfully corrected to 10 PD. In case 2 also, upward displacement of both lateral rectus muscles was shown by computed tomography. The preoperative A-pattern of 26 PD was corrected to 4 PD postoperatively after upward transposition surgery of the medial rectus muscles. CONCLUSIONS: The vertical displacement of horizontal rectus muscles was considered the principal cause of A-pattern in these cases associated with marked mongoloid slanting palpebral fissures.


Assuntos
Esotropia/cirurgia , Doenças Palpebrais/complicações , Músculos Oculomotores/transplante , Pré-Escolar , Esotropia/complicações , Esotropia/diagnóstico por imagem , Feminino , Humanos , Lactente , Masculino , Meningocele/complicações , Músculos Oculomotores/diagnóstico por imagem , Síndrome de Prader-Willi/complicações , Tomografia Computadorizada por Raios X
8.
Int J Biochem Cell Biol ; 33(6): 603-12, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11378441

RESUMO

New tumor formation was suppressed by retinoic acid (RA) administration in xeroderma pigmentosum (XP) patients who have a defect in nuclear excision repair. However, the inhibition is not due to enhanced removal of UV-damaged DNA. These results prompted us to investigate whether or not RA metabolism is abnormal in XP fibroblasts and what the underlying mechanism is. Compared with wild type fibroblasts, low activities of RA synthesis were determined on HPLC in mouse fibroblasts lacking XP group A (XPA) gene and UV-induced XPA deficient cancer cells. Moreover, we observed an impaired expression of cytochrome P450 1a1 in XPA deficient fibroblasts by RT-PCR and a decreased expression of retinoic acid receptor gamma in XPA deficient cancer cells by Western blotting. Finally, pre-treatment of RA isoforms significantly protected the XPA deficient fibroblasts from UV-induced death. These results suggest that decreased structure activity of RA synthesis, resulting from impaired mRNA expression of cytochrome P450 1a1 may, at least together with UV irradiation, involve in skin carcinogenesis in XP patients.


Assuntos
Citocromo P-450 CYP1A1/biossíntese , Tretinoína/metabolismo , Xeroderma Pigmentoso/metabolismo , Alitretinoína , Animais , Linhagem Celular , Sobrevivência Celular , Sistema Enzimático do Citocromo P-450/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/fisiologia , Fibroblastos/citologia , Fibroblastos/metabolismo , Camundongos , Oxigenases/metabolismo , Receptores do Ácido Retinoico/metabolismo , Retinal Desidrogenase , Proteínas de Ligação ao Retinol/metabolismo , Tretinoína/farmacologia , Raios Ultravioleta , Proteína de Xeroderma Pigmentoso Grupo A
9.
Dis Colon Rectum ; 44(3): 418-22, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11289290

RESUMO

PURPOSE: The study was undertaken to evaluate the clinical usefulness of endoscopic transanal decompression with a newly developed drainage tube for the treatment of acute colonic obstruction. METHODS: Thirty-six patients ranging in age from 46 to 87 years (average age = 69 years) with acute colorectal obstruction secondary to carcinoma were treated by means of intubation with a flexible drainage tube using combined endoscopic and fluoroscopic guidance. After tube placement, the obstructed colon was aspirated, decompressed, and cleaned with a 50 ml syringe and saline solution. The drainage tube was kept inserted and the colon was irrigated two or three times per day using 500 to 1,000 ml of saline until there were no contents in the colon. The colon was almost empty at the time of operation. The success rate, benefits, and complications of this technique were evaluated. RESULTS: Placement of the drainage tube was successful in 34 (94.4 percent) of 36 patients. Immediately after aspiration and decompression, symptoms related to obstruction were relieved in 21 patients (61.8 percent), within one hour in 9 patients (26.5 percent) and within four hours in 4 patients (11.8 percent). All 34 patients had elective single-stage surgery without severe complications at the anastomotic site such as anastomotic leakage and postanastomotic stenosis that needed treatment a few days after placement of the drainage tube. In the two cases of unsuccessful placement of the drainage tube, emergent colostomy was performed. CONCLUSION: Decompression with a transanal drainage tube is an easy and safe technique to relieve colonic obstruction effectively without any excess burden to patients. Because the procedure permits single-stage surgery in most cases, it is also cost effective.


Assuntos
Doenças do Colo/cirurgia , Colonoscópios , Neoplasias Colorretais/cirurgia , Drenagem/instrumentação , Obstrução Intestinal/cirurgia , Cuidados Pré-Operatórios , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Irrigação Terapêutica
10.
Life Sci ; 68(14): 1677-85, 2001 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-11263680

RESUMO

Mammalian NADPH-ferredoxin reductase (EC 1.18.1.2) functions in the mitochondrial electron transport chain for cytochrome P-450-dependent steroid hydroxylation. Significant homology of three-dimensional structure exists in the surroundings of FAD between NADPH-ferredoxin reductase and NADH-cytochrome b5 reductase. The latter is involved in the bioreduction of mitomycin C (MC), a prototype antitumor agent. In this study, we assessed the capacity of NADPH-ferredoxin reductase to activate MC. Mitomycin C increased the NADPH oxidase activity of NADPH-ferredoxin reductase. In the absence of ferredoxin, the Km value of NADPH-ferredoxin reductase for MC was 73.5 +/- 2.3 microM. While in the presence of 500 nM ferredoxin, a Lineweaver-Burk plot exhibited a biphasic curve. NADPH-ferredoxin reductase-mediated reduction of MC resulted in the formation of an alkylated complex of 4-(p-nitrobenzyl) pyridine and an increase in plasmide DNA single-strand breaks under hypoxic conditions. With the addition of 500 nM ferredoxin, the amount of the alkylated complex of 4-(p-nitrobenzyl) pyridine and the plasmide DNA single-strand breaks increased by 40% and 37%, respectively. However, neither alkylated complex of 4-(p-nitrobenzyl) pyridine nor DNA strand breaks was observed in the presence of SOD and catalase under aerobic conditions. These findings demonstrate that NADPH-ferredoxin reductase is capable of catalyzing the bioactivation of mitomycin C under hypoxic conditions in vitro.


Assuntos
Antibióticos Antineoplásicos/metabolismo , Ferredoxina-NADP Redutase/metabolismo , Mitomicina/metabolismo , Alquilação , Animais , Biotransformação/fisiologia , Bovinos , Dano ao DNA , Escherichia coli/genética , Escherichia coli/metabolismo , Ferredoxina-NADP Redutase/genética , Hipóxia/patologia , Oxirredução
11.
Int J Biochem Cell Biol ; 33(2): 155-62, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11240372

RESUMO

We investigated whether or not neuronal nitric oxide synthase (nNOS) (EC 1.14.13.39) was converted to the P-420 form on exposure to sodium cholate, mercury chloride or urea, and the reconversion of the P-420 to the P-450 form. Sodium cholate and mercury chloride induced the conversion of nNOS from the P-450 to the P-420 form in concentration- and incubation time-dependent manners, and the nNOS activity decreased. In the presence of glycerol, L-arginine and/or tetrahydrobiopterin, the sodium cholate-treated P-420 form could be reconverted to the P-450 form under constant experimental conditions, and the nNOS activity could also be restored. The mercury chloride-treated P-420 form of nNOS could be reconverted to the P-450 form on incubation with reduced glutathione (GSH) or L-cysteine, and the nNOS activity was recovered. However, no reconversion of the mercury chloride-treated P-420 form to the P-450 form was observed in the presence of glycerol, L-arginine, or tetrahydrobiopterin. Urea (4.0 M) dissociated nNOS into its subunits, but nNOS remained in the P-450 form. The nNOS monomer was more susceptible to sodium cholate. After removing the urea by dialysis, and supplementation of the nNOS solution with glycerol, L-arginine or BH(4), the P-420 was reconverted to the P-450 form, and the reassociation of nNOS monomers was also observed. These results suggested that nNOS was more stable as to exposure to sodium cholate, mercury chloride or urea in comparison to microsomal cytochrome P-450, which may be due to the different heme environment and protein structure.


Assuntos
Biopterinas/análogos & derivados , Sistema Enzimático do Citocromo P-450/química , Citocromos/química , Isoenzimas/química , Cloreto de Mercúrio/farmacologia , Óxido Nítrico Sintase/química , Colato de Sódio/farmacologia , Ureia/farmacologia , Animais , Arginina/farmacologia , Biopterinas/farmacologia , Cisteína/farmacologia , Escherichia coli/genética , Glicerol/farmacologia , Camundongos , Plasmídeos , Espectrofotometria , Transfecção
12.
Biochem Pharmacol ; 60(4): 571-9, 2000 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-10874132

RESUMO

Mitomycin C (MC) requires bioreduction prior to the generation of alkylating moieties. NADPH-cytochrome P450 reductase is predominant in metabolic activation of MC in hypoxic cancer cells. In this study, neuronal nitric oxide synthase (nNOS), whose reductase domain is structurally similar to that of NADPH-cytochrome P450 reductase, was assessed for its ability to activate MC. nNOS under anaerobic conditions catalyzed the reduction of MC, which was measured as the decrease in absorbance at 375 nm. Neither the heme blocker potassium cyanide (1 mM) nor the nNOS competitive inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 1 mM) affected the bioreduction of MC, whereas 0.1 mM diphenyleneiodonium chloride, which binds to the reductase domain of nNOS, inhibited MC reduction completely. The reduction of MC by nNOS was influenced by Ca(2+)/calmodulin. In the absence of Ca(2+)/calmodulin, the rate of MC reduction decreased by 28% at pH 6.6. The formation of an alkylated complex of 4-(p-nitrobenzyl)pyridine occurred in a manner analogous to that observed in MC metabolic experiments. The rate of MC reduction and the formation of the alkylated complex of 4-(p-nitrobenzyl)pyridine at pH 6.6 were increased by 43 and 54%, respectively, as compared with that at pH 7.6. nNOS-activated MC resulted in the consumption of oxygen in air. The rate of oxygen consumption decreased by 50% in the presence of 2000 U/mL of catalase. MC inhibited nNOS activity in a noncompetitive manner. These findings demonstrate that nNOS is capable of catalyzing the bioreduction of MC.


Assuntos
Antibióticos Antineoplásicos/metabolismo , Mitomicina/metabolismo , Óxido Nítrico Sintase/metabolismo , Alquilação , Animais , Biotransformação , Escherichia coli , Concentração de Íons de Hidrogênio , Camundongos , Neurônios/enzimologia , Neurônios/metabolismo , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase Tipo I , Oxirredução , Consumo de Oxigênio , Piridinas/metabolismo
13.
Cardiovasc Intervent Radiol ; 23(2): 114-20, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10795835

RESUMO

PURPOSE: To evaluate the clinical efficacy of the polyurethane-covered Nitinol Strecker stent in the treatment of patients with malignant biliary obstruction. METHODS: Twenty-three covered stents produced by us were placed in 18 patients with malignant biliary obstruction. Jaundice was caused by cholangiocarcinoma (n = 5), pancreatic cancer (n = 6), gallbladder cancer (n = 4), metastatic lymph nodes (n = 2), and tumor of the papilla (n = 1). RESULTS: The mean patency period of the stents was 37.5 weeks (5-106 weeks). Recurrent obstructive jaundice occurred in two patients (11%). Adequate biliary drainage over 50 weeks or until death was achieved in 17 of 18 patients (94.4%). Late cholangitis was observed in two patients whose stents bridged the ampulla of Vater. Other late severe complications were not encountered. CONCLUSION: Although more study is necessary, our results suggest the clinical efficacy of our covered Nitinol Strecker stent in the management of obstructive jaundice caused by malignant diseases.


Assuntos
Ligas , Colestase/terapia , Poliuretanos , Stents , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/complicações , Colestase/etiologia , Colestase/mortalidade , Desenho de Equipamento , Feminino , Neoplasias da Vesícula Biliar/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Taxa de Sobrevida , Grau de Desobstrução Vascular
14.
Radiat Med ; 17(2): 91-6, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10399775

RESUMO

Transient hepatic attenuation difference (THAD) is a valuable finding in detecting hypervascular lesions. However, similar findings are also observed in patients even without known hepatic diseases. We elucidate the characteristic findings and the causes of THAD in patients without hepatic neoplasm in this article. Dual-phased contrast-enhanced CT studies performed in 450 patients were reviewed, and THAD was observed in 42 (9.3%). THAD was linear or wedge-shaped and was seen contiguous to the liver surface with a relatively obscure margin in 40 of the 42 cases. The most common cause of THAD was chronic cholecystitis followed by previous biliary surgery. THAD was also seen in 30 patients with no hepatic diseases in whom it had a tendency to locate around the gallbladder fossa or in the periphery of the liver particularly in the left lobe. The knowledge of the prevalence, shape, distribution and causes of THAD is essential for the evaluation of contrast-enhanced CT images obtained during the arterial phase.


Assuntos
Artéria Hepática/diagnóstico por imagem , Hepatopatias/diagnóstico por imagem , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia , Colecistite/diagnóstico por imagem , Colecistografia , Meios de Contraste , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Circulação Hepática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomógrafos Computadorizados
15.
Metabolism ; 48(6): 689-92, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10381141

RESUMO

Benzo(a)pyrene, a well-known procarcinogen, is believed to be activated by microsomal cytochrome P-450 1A1 (CYP 1A1). We recently reported that rat CYP 1A1 induced by 3-methylcholanthrene (3-MC) catalyzed the conversion of retinal to retinoic acid. In this study, we investigated retinoid inhibition of the metabolism of benzo(a)pyrene and 7-ethoxyresorufin, another specific substrate of CYP 1A1, using liver microsomes prepared from control and 3-MC-pretreated rats as the enzyme source. In 3-MC-treated rats, retinal and retinol, but not retinoic acid, inhibited benzo(a)pyrene metabolism. The 50% inhibitory concentration (IC50) of retinal was about 11.5 micromol/L and the inhibition was competitive, with a Ki value of 5.8 micromol/L. Retinol is a more potent inhibitor than retinal. The IC50 was about 5 micromol/L and the inhibition was mixed, with a Ki value of 19.2 micromol/L and a Ki' value of 4.2 micromol/L. Almost the same results were obtained for the reaction of 7-ethoxyresorufin deethylation. In contrast, the metabolic activity of both benzo(a)pyrene and 7-ethoxyresorufin was much lower in untreated versus 3-MC-treated rats, and only weak inhibition by the retinoids was observed. The results suggest that retinoids inhibit the activation of benzo(a)pyrene and that the substrate specificity of cytochrome P-450 isozymes associated with retinoid metabolism should be taken into account when studying the anticarcinogenic action of retinoids.


Assuntos
Anticarcinógenos/farmacologia , Benzo(a)pireno/antagonistas & inibidores , Carcinógenos/antagonistas & inibidores , Citocromo P-450 CYP1A1/metabolismo , Microssomos Hepáticos/metabolismo , Retinoides/farmacologia , Animais , Benzo(a)pireno/metabolismo , Carcinógenos/metabolismo , Citocromo P-450 CYP1A1/biossíntese , Indução Enzimática/efeitos dos fármacos , Masculino , Metilcolantreno , Microssomos Hepáticos/enzimologia , Ratos , Ratos Sprague-Dawley , Retinaldeído/farmacologia , Tretinoína/farmacologia , Vitamina A/farmacologia
16.
Arch Biochem Biophys ; 364(2): 264-72, 1999 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-10190983

RESUMO

Retinal oxidase (EC 1.2.3.11) is a molybdenum-containing flavoenzyme with high enzymatic activity as to retinoic acid synthesis. In this study, we provide direct evidence that retinal oxidase is identical to aldehyde oxidase (EC 1.2.3.1) by cDNA cloning. Retinal oxidase and aldehyde oxidase, purified from rabbit liver cytosol using the original methods, showed completely identical HPLC patterns and amino acid sequences for three corresponding polypeptides (103 amino residues). The primary structural information obtained from the cleaved polypeptides permitted molecular cloning of the full-length cDNA of rabbit liver retinal oxidase (aldehyde oxidase). We also cloned and sequenced the full-length cDNA of mouse retinal oxidase. The cDNAs of rabbit and mouse retinal oxidase have a common sequence approximately 4.6 kb long, comprising 4-kb coding regions. The open reading frames of the cDNAs predict single polypeptides of 1334 and 1333 amino acids; the calculated minimum molecular mass of each is approximately 147,000. Northern blot analysis showed that the rabbit retinal oxidase mRNA was widely expressed in tissues. Finally, we successfully constructed a prokaryotic expression system for mouse retinal oxidase. The purified recombinant retinal oxidase from Escherichia coli showed a typical spectrum of aldehyde oxidases and a lower Km (3.8 microM) for retinal and a higher Vmax (807 nmol/min/mg protein) for retinoic acid synthesis than those of rabbit retinal oxidase (8 microM and 496 nmol/min/mg protein). This represents the first eukaryotic molybdenum-containing flavoprotein to be expressed in an active form in a prokaryotic system.


Assuntos
Aldeído Oxirredutases/genética , Fígado/enzimologia , Retina/enzimologia , Aldeído Oxirredutases/biossíntese , Sequência de Aminoácidos , Animais , Cromatografia Líquida de Alta Pressão , Clonagem Molecular , Brometo de Cianogênio/química , DNA Complementar/análise , DNA Complementar/genética , Escherichia coli , Camundongos , Dados de Sequência Molecular , Plasmídeos/genética , Coelhos , Proteínas Recombinantes/biossíntese , Retinal Desidrogenase , Análise de Sequência , Homologia de Sequência de Aminoácidos , Distribuição Tecidual
17.
Int J Radiat Biol ; 73(5): 529-33, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9652810

RESUMO

PURPOSE: To develop and validate non-fluorescent chromosome painting for bright-field microscopy using the peroxidase/diaminobenzidine (DAB) reaction. MATERIALS AND METHODS: Peripheral blood lymphocytes were taken from patients with uterine cancer who had received heavy-ion radiation therapy. Chromosome slides were treated with RNase and pepsin, denatured mildly, hybridized with a biotinylated DNA probe specific for whole-chromosome 4 and stained using the peroxidase/DAB reaction with an avidin-biotin amplification. The slides were analysed under a bright-field microscope and an atomic force microscope. The detection rate of chromosome aberrations by DAB painting was compared with that obtained by dual analysis of Giemsa staining and FISH painting. RESULTS: When chromosomes 4 were painted, 11.5% of unstable aberrations were detected by DAB painting, while 10.8% of them were found by dual analysis of Giemsa staining and FISH painting. CONCLUSION: A DAB painting method that can effectively detect rearranged aberrations was established. It has advantages over FISH painting: the preparations can be analysed by bright-field microscope, can be preserved permanently and are suitable for analysis by an automated system.


Assuntos
Cromossomos Humanos Par 4/efeitos da radiação , Peroxidases , 3,3'-Diaminobenzidina , Idoso , Aberrações Cromossômicas , Sondas de DNA , Feminino , Humanos , Hibridização In Situ , Linfócitos/efeitos da radiação , Linfócitos/ultraestrutura , Microscopia/métodos , Pessoa de Meia-Idade , Neoplasias Uterinas/sangue , Neoplasias Uterinas/genética , Neoplasias Uterinas/radioterapia
18.
Urology ; 51(5): 849-53, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9610608

RESUMO

OBJECTIVES: To elucidate the role of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in human urothelial cancers, we studied gene expressions of MMPs, TIMPs, and membrane-type 1 matrix metalloproteinase (MT1-MMP) in noninvasive or invasive tumor lines transplanted in mice with severe combined immunodeficiency (SCID). METHODS: The UCT-1 tumor line, derived from bladder cancer, is a noninvasive transplantable tumor with no evidence of metastasis. The UCT-2 tumor line, derived from a renal pelvic tumor, extensively invades without metastasis. We examined gene expressions of MMPs-1, 2, 3, 7, 8, 9, 10, and 11, TIMPs-1, 2, and 3, and MT1-MMP in UCT-1 and 2 by semiquantitative polymerase chain reaction analysis. RESULTS: Significantly higher gene expression of MMP-2 was detected in the invasive UCT-2 tumor line than in the noninvasive UCT-1 tumor line. Although both tumor lines expressed TIMP-1 and MT1-MMP, stronger gene expression of MT1-MMP was observed in the UCT-2 tumor line than in the UCT-1 tumor line. The other MMPs or TIMPs were not detected in either of the lines. CONCLUSIONS: MMP-2 and MT1-MMP may have an important role in the invasion mechanism of urothelial cancers.


Assuntos
Carcinoma de Células de Transição/enzimologia , Metaloendopeptidases/fisiologia , Inibidores de Proteases/farmacologia , Inibidores Teciduais de Metaloproteinases/fisiologia , Neoplasias da Bexiga Urinária/enzimologia , Idoso , Animais , Carcinoma de Células de Transição/secundário , Colagenases/análise , Colagenases/genética , Gelatinases/análise , Gelatinases/genética , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Glicoproteínas/análise , Glicoproteínas/genética , Humanos , Masculino , Metaloproteinase 1 da Matriz , Metaloproteinase 10 da Matriz , Metaloproteinase 11 da Matriz , Metaloproteinase 14 da Matriz , Metaloproteinase 2 da Matriz , Metaloproteinase 3 da Matriz/análise , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 7 da Matriz , Metaloproteinase 8 da Matriz , Metaloproteinase 9 da Matriz , Metaloproteinases da Matriz Associadas à Membrana , Metaloendopeptidases/análise , Metaloendopeptidases/genética , Camundongos , Camundongos SCID , Invasividade Neoplásica , Transplante de Neoplasias , Inibidores de Proteases/análise , Inibidor Tecidual de Metaloproteinase-1/análise , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-2/análise , Inibidor Tecidual de Metaloproteinase-2/genética , Inibidores Teciduais de Metaloproteinases/análise , Inibidores Teciduais de Metaloproteinases/genética , Células Tumorais Cultivadas
19.
Urology ; 51(1): 145-9, 1998 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9457310

RESUMO

OBJECTIVES: To evaluate increased serum soluble interleukin-2 receptor (sIL-2R) levels in patients with renal cell carcinoma (RCC). METHODS: Serum sIL-2R levels were measured in 52 patients with RCC and 10 control subjects by an enzyme-linked immunosorbent assay (ELISA) technique. The correlation between serum sIL-2R levels and clinical stage, disease prognostic value, and inflammatory marker levels was analyzed. RESULTS: Serum sIL-2R levels in patients with RCC were significantly higher than those in normal control subjects (857.2 +/- 660.0 versus 291.3 +/- 76.4 U/mL, P < 0.0001). High serum sIL-2R levels appeared to be related to advanced clinical stage (596.0 +/- 276.5 U/mL in Stage II, 776.1 +/- 398.8 U/mL in Stage III, and 1310.0 +/- 926.7 U/mL in Stage IV: Stage II vs. Stage III, P = 0.0078; Stage II vs. Stage IV, P < 0.0001). The overall cause-specific survival curves showed that patients with high sIL-2R levels (more than 1000 U/mL) had a significantly lower survival rate than those with low (less than 500 U/mL, P = 0.0003) or intermediate levels (500 to 1000 U/mL, P = 0.0007). C-reactive protein levels apparently increased in patients with high sIL-2R concentrations. CONCLUSIONS: Measurement of serum sIL-2R concentrations in patients with RCC provides useful information for predicting the extent of disease and length of survival.


Assuntos
Carcinoma de Células Renais/sangue , Neoplasias Renais/sangue , Receptores de Interleucina-2/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Feminino , Humanos , Interleucina-6/sangue , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida
20.
Am J Ophthalmol ; 123(1): 142-4, 1997 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9186119

RESUMO

PURPOSE: To study a case of rhabdomyoma of the orbit in a 16-month-old boy. METHOD: The child had progressive right proptosis for 1 month. He underwent a computed tomographic scan, which showed an irregular right retrobulbar mass and partial resection. RESULTS: Histologic examination disclosed well-differentiated striated muscle cells with a mixture of collagen fibers and immature striated muscle cells with centrally placed nuclei. The specimen lacked nuclear atypia, indicating benign rhabdomyoma of the orbit. During the 1 1/2-year follow-up, the patient did not receive additional treatment, and no regrowth occurred. CONCLUSION: Rhabdomyoma can occur in the orbit of a child. Because of differences in treatment, rhabdomyoma must be distinguished from rhabdomyosarcoma.


Assuntos
Neoplasias Orbitárias/diagnóstico por imagem , Neoplasias Orbitárias/patologia , Rabdomioma/diagnóstico por imagem , Rabdomioma/patologia , Humanos , Lactente , Masculino , Neoplasias Orbitárias/cirurgia , Rabdomioma/cirurgia , Tomografia Computadorizada por Raios X
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