RESUMO
OBJECTIVE: We have previously reported the clinical efficacy of water-in-oil-in-water (W/O/W) emulsions, particularly for non-selective transcatheter arterial infusion (TAI) therapy. W/O/W emulsions limit damage to normal hepatic parenchyma, because of their minimal embolic effect on peripheral arteries and slow release of anticancer agent. The purpose of this study was to evaluate the safety and effectiveness of ultraselective TAI (UTI) of a W/O/W emulsion for hepatocellular carcinoma (HCC). METHODS: 11 patients with Stage I-III small HCCs (<5 cm) underwent UTI with a W/O/W emulsion at our institute. Response was assessed using the Response Evaluation Criteria in Solid Tumors. Disease-free survival time was estimated using the Kaplan-Meier method. RESULTS: All 10 patients, excluding a patient who underwent a hepatectomy after UTI, achieved complete response. The 6, 12 and 30 month cumulative disease-free survival rates for the 10 patients were 100%, 90% and 60%, respectively. The patient who underwent hepatectomy after UTI developed complete necrosis of the HCC and peritumoral non-tumorous liver parenchyma. CONCLUSION: UTI therapy using a W/O/W emulsion for patients with small HCCs results in a good local response.
Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Cateterismo Periférico , Preparações de Ação Retardada/administração & dosagem , Epirubicina/administração & dosagem , Idoso , Carcinoma Hepatocelular , Preparações de Ação Retardada/química , Intervalo Livre de Doença , Emulsões/química , Epirubicina/química , Feminino , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas , Masculino , Óleos/química , Resultado do Tratamento , Água/químicaRESUMO
PURPOSE: We have previously reported the clinical efficacy of water-in-oil-in-water (W/O/W) emulsion containing anticancer agent. The purpose of this study was to evaluate the safety and effectiveness of transcatheter arterial infusion (TAI) of W/O/W emulsion via a cystic artery for hepatocellular carcinoma (HCC). METHODS: TAI of a W/O/W emulsion was performed at our institute in five patients with Stage III or IV HCC with blood supply from the cystic artery. In all patients, 2-12 ml/O/W emulsion was infused via a cystic artery. Therapeutic effects and complications were evaluated in these patients. RESULTS: Of the five patients treated, one achieved a complete response and two achieved a partial response. After treatment, acute cholecystitis or gallbladder ischemia that required treatment was not encountered in any patient. CONCLUSIONS: W/O/W emulsion can be safely infused via a cystic artery without major complications; it is a good therapeutic option for the patients with advanced HCC fed by a cystic artery.
Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/tratamento farmacológico , Epirubicina/administração & dosagem , Infusões Intra-Arteriais/métodos , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Angiografia , Artérias , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Preparações de Ação Retardada , Emulsões , Óleo Etiodado/administração & dosagem , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Fígado/irrigação sanguínea , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética , Masculino , Recidiva Local de Neoplasia/irrigação sanguínea , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Retratamento , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND AND PURPOSE: Early evaluation of the pyramidal tract is a prerequisite in patients with intracerebral hemorrhage (ICH) in order to decide the optimal treatment or to assess appropriate rehabilitation. The aim of this study was to evaluate and predict the neuromotor and functional outcome of an ICH by using diffusion tensor imaging (DTI) in the acute phase. MATERIALS AND METHODS: Eighteen patients with a hemiparetic supratentorial ICH were prospectively studied with DTI within 2 days after onset. A region-of-interest-based analysis was performed for the fractional anisotropy (FA) of the pyramidal tract in the cerebral peduncles. The degree of paresis was assessed at day 0 and day 28 by paresis grading (PG). The functional outcome was evaluated by the modified Rankin Scale (mRS). RESULTS: The FA in the affected side was significantly lower compared with that of the unaffected side (P = .001) with the mean diffusivity remaining unchanged (P = .50). The ratio of the FA (rFA) in the affected side to the unaffected side was significantly correlated with the PG at day 0 and 28 and the mRS score at day 28 (P = .002, r = -0.674; P < .001, r = -0.767; and P = .002, r = -0.676). The rFA for the good and poor outcomes based on the PG was significantly different (P < .001). The cutoff point of the rFA for the good and poor outcomes was set at 0.85 (sensitivity, 100%, specificity, 100%). CONCLUSIONS: We conclude that DTI can evaluate the motor deficit quantitatively and may predict the functional outcome in patients with an ICH who were scanned within 2 days after the ICH onset.
Assuntos
Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico , Imagem de Difusão por Ressonância Magnética/métodos , Paresia/diagnóstico , Paresia/etiologia , Tratos Piramidais/patologia , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recuperação de Função Fisiológica , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Oxygen consumption at the targeted site has a significant effect on dosimetry in photodynamic therapy (PDT). However, oxygen consumption in PDT using a pulsed laser as a light source has not been clarified. We therefore investigated the dependence of cytotoxicity on the oxygen consumption and the photosensitizer photobleaching of PDT using a pulsed laser by comparing with that using a continuous wave (CW) laser. Mouse renal carcinoma cells (Renca) were incubated with a second-generation photosensitizer, PAD-S31. The cells were then irradiated with either a 670-nm nanosecond pulsed light from the 3rd harmonics of a Nd:YAG laser-pumped optical parametric oscillator with a peak fluence rate of approximately 1 MW/cm(2) at 30 Hz or a 670-nm CW diode laser with a total light dose of 40 J/cm(2). Regardless of laser source, cytotoxic effects exhibited cumulative dose responses to the photosensitizer ranging from 12 to 96 microg/ml. However, cytotoxic effect of PDT using the pulsed light was significantly less than that using the CW light with the photosensitizer concentrations of 24 and 48 microg/ml under identical fluence rates. During PDT, the cells exposed to the pulsed light consumed oxygen more slowly, resulting in a lower amount of oxygen consumption when compared with PDT using CW light. In accordance with oxygen consumption, the pulsed light induced significantly less photobleaching of the photosensitizer than the CW light did. These results indicate that the efficiency of PDT using pulsed light is less when compared with CW light, probably being related to suppressed oxygen consumption during the pulsed light irradiation.
Assuntos
Sobrevivência Celular/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Fotodegradação/efeitos dos fármacos , Fotoquimioterapia/métodos , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Terapia com Luz de Baixa Intensidade/métodos , Camundongos , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêuticoRESUMO
Photodynamic therapy (PDT) using a pulsed laser is becoming popular, but its cytotoxic effect is still not clear. We therefore studied the cytotoxicity of PDT using a pulsed laser by changing its irradiation parameters and compared the degrees of cytotoxicity with those of PDT using continuous-wave (CW) light sources. Mice renal cell carcinoma cells were incubated with PAD-S31, a water-soluble photosensitiser of which the excitation peak is 670 nm, and were then irradiated with either a tungsten lamp, a CW diode laser, or a nanosecond pulsed Nd:YAG laser-based optical parametric oscillator system. When the PAD-S31 concentration and total light dose were constant (12 micro g/ml and 40 J/cm(2), respectively), the CW laser caused fluence rate-dependent decrease in cellular proliferation until the fluence rate reached 90 mW/cm(2), at which point inhibition of cellular proliferation was more than 80%. The cytotoxicity then became almost saturated at fluence rates of>90 mW/cm(2). On the other hand, inhibition of cellular proliferation in samples irradiated with the pulsed laser reached 80% even at the fluence rate of 15 mW/cm(2), and, interestingly, the cytotoxicity paradoxically decreased with increase in the fluence rate. Moreover, the cytotoxicity in the PDT using the pulsed laser depended on the repetition rate. The inhibition of cellular proliferation by PDT using 30-Hz irradiation was greater than that by PDT using 5-Hz irradiation when the same fluence rates were used. These results suggest that the efficacy of PDT using a pulsed laser depends considerably on fluence rate and repetition rate.
Assuntos
Carcinoma de Células Renais/patologia , Terapia a Laser , Fotoquimioterapia , Animais , Carcinoma de Células Renais/tratamento farmacológico , Divisão Celular/efeitos dos fármacos , Divisão Celular/efeitos da radiação , Camundongos , Porfirinas/administração & dosagem , Doses de Radiação , Radiossensibilizantes/administração & dosagem , Células Tumorais CultivadasRESUMO
The authors present a case of renal oncocytoma with numerous intracytoplasmic lumina in a 45-year-old woman, with an emphasis on the ultrastructural findings of so-called oncoblasts. The tumor was located in the upper pole of the left kidney, measuring about 3.3 cm in diameter. Histologically, it was composed of solid nests or acinar growths of so-called oncocytic tumor cells with numerous intracytoplasmic lumina and scattered foci of so-called oncoblasts. The luminal surface was positive for Hale's colloidal iron stain. A very small number of glycogen-containing cells were found scattered in a few nests. Immunohistochemically, tumor cells were positive for cytokeratin and epithelial membrane antigen, but negative for vimentin and carcinoembryonic antigen. The Ki-67 labeling index was 1.2%. All of the Ki-67-positive cells were oncocytes. So-called oncoblasts were negative for Ki-67. Ultrastructural examination revealed that the predominant tumor cells had cytoplasm packed with round mitochondria and the mitochodria had lamellar long cristae. So-called oncoblasts showed scant cytoplasm with a moderate number of small mitochondria. Some of them showed pyknosis which can be regarded as mitochondrial involution. The authors believe that so-called oncoblasts are damaged or involuted oncocytes rather than precursors of oncocytes.
Assuntos
Adenoma Oxífilo/ultraestrutura , Neoplasias Renais/ultraestrutura , Adenoma Oxífilo/química , Antígeno Carcinoembrionário/análise , Nucléolo Celular/ultraestrutura , Núcleo Celular/ultraestrutura , Citoplasma/ultraestrutura , Feminino , Humanos , Imuno-Histoquímica , Queratinas/análise , Antígeno Ki-67/análise , Neoplasias Renais/química , Microscopia Eletrônica , Pessoa de Meia-Idade , Mitose , Mucina-1/análise , Vimentina/análiseRESUMO
A case is presented of giant renal arteriovenous malformation (AVM). A 61-year-old woman was admitted to the National Defense Medical College Hospital for further evaluation of a renal cyst. Doppler ultrasonography and magnetic resonance imaging revealed a giant renal AVM, although the patient had no history nor clinical sign suggesting an AVM. Under the diagnosis of a right renal AVM, the patient underwent AVM resection.
Assuntos
Malformações Arteriovenosas/diagnóstico por imagem , Malformações Arteriovenosas/patologia , Doenças Renais Císticas/diagnóstico por imagem , Malformações Arteriovenosas/cirurgia , Feminino , Humanos , Rim/irrigação sanguínea , Angiografia por Ressonância Magnética , Pessoa de Meia-Idade , Veias Renais/diagnóstico por imagem , Veias Renais/patologia , Veias Renais/cirurgia , Ultrassonografia Doppler , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/patologia , Veia Cava Inferior/cirurgiaRESUMO
Corticosteroid-binding globulin (CBG) is the plasma transport protein that regulates the access of glucocorticoid hormones to target cells. Genetic deficiencies of CBG are rare, and only a single human CBG variant (Trancortin Leuven) has been related so far to decreased cortisol-binding affinity. We report here on a 43-yr-old woman, referred for chronic asthenia and hypotension, with repeatedly low morning serum cortisol levels (22-61 nmol/L; normal range, 204-546 nmol/L), normal plasma ACTH levels (38-49 pg/mL; normal, <50 pg/mL), and normal urinary cortisol (10-76 nmol/24 h; normal range, 10-105 nmol/24 h). An increased percent-free (dialysable fraction) serum cortisol (8.7-9.7%, normal range, 2.9-3.9%) suggested abnormal CBG binding activity. Indeed, she had a low serum CBG concentration (24 mg/L vs. 44+/-6 mg/L in normal women), and the affinity of her CBG for cortisol was decreased (association constant, Ka = 0.12 L/nmol vs. 0.82+/-0.29 L/nmol). In her immediate family members, the serum CBG concentration and cortisol-binding activity were normal in her husband, but the four living children had slightly lower serum CBG concentrations than the reference ranges for their pre- and postpubertal status. Measurements of cortisol distribution in undiluted serum indicated that an increase in the percentage of nonprotein-bound cortisol offsets the low cortisol levels to give approximately normal concentrations of free cortisol in serum. Direct sequencing of PCR-amplified exons encoding CBG revealed that the proband was homozygous for a polymorphism (GAC-AAC) in the codon for residue 367, which results in a Asp367-->Asn substitution. Her children were heterozygous for this polymorphism. When this nucleotide change was introduced into a normal human CBG complementary DNA, for expression in Chinese hamster ovary cells, Scatchard analysis demonstrated that the Asn367 substitution reduced the affinity of human CBG for cortisol by approximately 4-fold (Ka = 0.15 L/nmol), as compared to normal recombinant CBG (Ka = 0.66 L/nmol). These results suggest that Asp367 is an important determinant of CBG steroid-binding activity and that normal negative regulation of the hypothalamic-pituitary-adrenal axis is maintained by relatively normal serum-free cortisol concentrations, despite a marked reduction in the steroid-binding affinity of this novel human CBG variant, which we have designated as CBG-Lyon.
Assuntos
Hidrocortisona/metabolismo , Transcortina/química , Doenças do Córtex Suprarrenal/genética , Doenças do Córtex Suprarrenal/psicologia , Adulto , Substituição de Aminoácidos/genética , Western Blotting , Primers do DNA , DNA Complementar/biossíntese , DNA Complementar/genética , Feminino , Hormônios/sangue , Humanos , Hidrocortisona/sangue , Mutagênese , Polimorfismo Genético/genética , Polimorfismo de Fragmento de Restrição , Ligação Proteica , Transcortina/genética , Transcortina/metabolismoRESUMO
Trypsin inhibitors secreted by human colorectal adenocarcinoma cell lines were analyzed by reverse zymography. Among eleven cell lines analyzed, the major inhibitor secreted was protease nexin-II (PN-II), a secreted form of amyloid beta protein precursor (APP) containing a Kunitz-type serine proteinase inhibitor domain. Expression of the APP gene was also confirmed in the cell lines and the main APP mRNA species were PN-II types. The APP gene expression was constant during cell growth in vitro. On the other hand, the rate of extracellular PN-II accumulation markedly increased after long-term serum-free maintenance of the confluent culture. The extracellular accumulation of PN-II was also strongly stimulated either by interleukin-1beta (IL-1beta) treatment or to a lesser extent by basic fibroblast growth factor, tumor necrosis factor-alpha, hepatocyte growth factor or epidermal growth factor. Neither serum depletion- nor IL-1beta-induced stimulation of extracellular PN-II accumulation were accompanied by obvious alteration of the levels of APP mRNA and cellular APP holoprotein, suggesting that the enhanced extracellular accumulation of PN-II might result from up-regulation of the secretory pathway of APP. The IL-1beta-induced PN-II secretion was significantly inhibited by relatively high concentrations (50-200 microg/ml) of aprotinin, a serine proteinase inhibitor, in a dose-dependent manner without obvious cell-toxic effects.
Assuntos
Precursor de Proteína beta-Amiloide/metabolismo , Proteínas de Transporte/metabolismo , Neoplasias Colorretais/metabolismo , Substâncias de Crescimento/farmacologia , Interleucina-1/farmacologia , Inibidores da Tripsina/farmacologia , Adenocarcinoma/enzimologia , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Sequência de Aminoácidos , Precursor de Proteína beta-Amiloide/genética , Sequência de Bases , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/patologia , Meios de Cultura Livres de Soro , Primers do DNA , Humanos , Dados de Sequência Molecular , Nexinas de Proteases , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Superfície Celular , Células Tumorais CultivadasRESUMO
An exceptional case of Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) arising from the meninges in a 60-year-old Japanese man is presented. Computerized tomographic scans and magnetic resonance images demonstrated well-circumscribed tumorous lesions that were homogeneously enhanced with contrast medium. Systemic examination revealed no abnormalities except for a cervical lymphadenopathy and diabetes mellitus. Microscopic examination of the resected specimens showed proliferated histiocytosis and infiltration of plasma cells and lymphocytes. The histology was characterized by the presence of histiocytes demonstrating lymphophagocytosis and immunoreactivity for S-100 protein staining. Immunohistochemical studies and electron microscopy were useful in confirming the diagnosis. The clinical and histopathological features of this disease are discussed.
Assuntos
Encefalopatias/patologia , Dura-Máter/patologia , Histiocitose Sinusal/patologia , Encefalopatias/diagnóstico por imagem , Dura-Máter/diagnóstico por imagem , Dura-Máter/ultraestrutura , Histiócitos/patologia , Histiócitos/ultraestrutura , Histiocitose Sinusal/diagnóstico por imagem , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
A new cell line MGM-1 was established from a primary tumor of the left temporal lobe with histological diagnosis of glioblastoma multiforme, removed from a 64-year-old Japanese male. The patient died of recurrence and unusual extracranial metastases of the tumor 7 months after the surgery. The cultured MGM-1 cells are spindle or polygonal in shape. After serial passages, glial fibrillary acidic protein became negative immunocytochemically in vitro. The modal chromosome number was 61-64. Doubling time and soft agar colony forming efficiency were 42.9h and 0.4%, respectively (at 25th passage). MGM-1 is a highly motile cell line in vitro and its serum-free conditioned medium is chemotactic and chemokinetic for other glioma cells. Secretion of gelatinases (probably MMP-2/72-kDa type i.v. collagenase) and MMP-9/92-kDa type i.v. collagenase) and urokinase-type plasminogen activator were also investigated. MGM-1 would therefore be useful for studying the mechanisms regulating glioma-cell motility and invasion. The MGM-1 cell line has been propagated continuously by serial passages (more than 100 passages) during the past 4 years.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Divisão Celular , Movimento Celular/genética , Quimiotaxia , Gelatinases/biossíntese , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Cariotipagem , Masculino , Metaloproteinase 2 da Matriz , Metaloendopeptidases/biossíntese , Pessoa de Meia-Idade , Fenótipo , Células Tumorais Cultivadas , Ativador de Plasminogênio Tipo Uroquinase/biossínteseRESUMO
Acute acalculous cholecystitis (AAC) is a potentially life-threatening complication, which is sometimes found in patients with multiple injuries, burns, or after an operation. It is unclear, however, whether AAC occurs after cerebrovascular disease (CVD). We studied the incidence of AAC complicating CVD and the clinical characteristics of AAC that occurs after CVD. One thousand three patients with CVD were studied who had been admitted at the acute stage to Kenwakai Hospital from January 1989 through September 1995 and to Seguchi Hospital of Neurosurgery from January 1993 through September 1995. There were 557 patients with cerebral infarction, 273 with cerebral hemorrhage, 94 with subarachnoid hemorrhage, and 79 with TIA/RIND. Twelve patients developed acute cholecystitis, ten of whom had AAC. Of the ten patients with AAC, six had cerebral infarction, two cerebral hemorrhage, and two TIA/RIND. Eight of ten were male. The incidence of AAC was 1.0% in the CVD patients studied. The majority of the AAC patients showed severe hemiparesis. The time interval from CVD to the onset of AAC ranged from 1 to 89 days, with a mean of 25.1 days. AAC occurred 0 to 16 days (mean 5.8 days) after the start of oral or tube food intake in five patients. The most common initial symptom was fever (70%), whereas abdominal pain was infrequent (20%). All the patients showed elevated CRPs and abnormal ultrasonographic findings for the gallbladder and some also had leukocytosis (60%) and elevated aminotransferase of more than 100 IU/l (30%). Cholecystectomy was performed on four AAC patients, but five were successfully treated with antibiotics. The cause of AAC complicating CVD seems to be multifactorial and probably is related to fasting, increased bile concentration, and arteriosclerosis. Our results strongly suggest that AAC is an unrecognized but important complication during acute stage CVD patients.
Assuntos
Transtornos Cerebrovasculares/complicações , Colecistite/etiologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Colecistectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
A 16-year-old girl presented to our clinic with right-sided tongue atrophy and fasciculations of 1-year duration. Enlargement of the outer opening of the hypoglossal canal was reveal by conventional and computed tomography of the skull. Magnetic resonance imaging disclosed an enlarged venous system extending from the jugular vein to the internal jugular vein on the right, with low signal density suggestive of a flow void. A right-sided occipital craniotomy was performed. When the hypoglossal canal was opened, an enlarged emissary vein compressing the hypoglossal nerve was identified. This is the first reported case of unilateral tongue atrophy and an enlarged hypoglossal canal due to an enlarged emissary vein.
Assuntos
Nervo Hipoglosso/patologia , Doenças da Língua/patologia , Adolescente , Atrofia/diagnóstico por imagem , Atrofia/patologia , Feminino , Humanos , Nervo Hipoglosso/diagnóstico por imagem , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Doenças da Língua/diagnóstico por imagemRESUMO
Expression of c-Met, the receptor for hepatocyte growth factor (HGF), and the biological roles of HGF were examined in cultured human glioma cells. All of the 5 glioma cell lines examined expressed c-Met protein as well as the c-met gene. Expression of the c-met gene was also confirmed in a glioblastoma tissue. Three cell lines (MGM-3, U251, KG-1-C) demonstrated chemotactic response to HGF in a dose-dependent manner. The response was not only chemotactic but also chemokinetic as judged by a checkerboard analysis. The amounts of c-Met mRNA and protein were abundant in the cell lines which showed a migratory response to HGF. Moreover, c-Met protein expression was highest in U251 with the highest migratory response to HGF. Among the cell lines, KG-1-C produced notable amounts of HGF protein as well as of c-Met, suggesting that HGF may act in an autocrine fashion in this case. HGF did not act as an apparent growth factor in the glioma cell lines examined. Furthermore, HGF stimulated the production of metalloproteinase, probably gelatinase A, in U251 cells.
Assuntos
Fatores Quimiotáticos/farmacologia , Glioblastoma/patologia , Fator de Crescimento de Hepatócito/farmacologia , Divisão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Gelatinases/biossíntese , Expressão Gênica , Glioblastoma/metabolismo , Glioblastoma/ultraestrutura , Humanos , Metaloproteinase 2 da Matriz , Metaloendopeptidases/biossíntese , Proteínas Proto-Oncogênicas c-met , RNA Mensageiro/metabolismo , Receptores Proteína Tirosina Quinases/biossíntese , Receptores Proteína Tirosina Quinases/genética , Proteínas Recombinantes/farmacologia , Estimulação Química , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
Six members of the chicken H1 gene family, all of which are located in two major histone gene clusters, have been shown to encode six different protein variants. The intracellular mRNA level from one of them, 01H1, encoding the 01H1 variant composed of 218 amino acid residues, constitutes 9.9% of the total H1 mRNA in the DT40 chicken B cell line. To study the specific role of this particular H1 variant, besides its well-known functions as a linker in chromatin maintenance and as a general repressor of transcription, we used targeted integration to construct heterozygous and homozygous DT40 mutants with disruption of one and two 01H1 alleles, respectively. Analyses of the stable transfectants showed that the growth rate of DT40 was unchanged in the absence of two 01H1 alleles. Moreover, the remaining H1 genes were shown to be expressed more in these mutants than in the wild-type cell lines. Two-dimensional polyacrylamide gel electrophoresis showed that within an almost constant background in the homozygous mutants several cellular proteins newly appeared or increased, while some other proteins disappeared or decreased quantitatively. These variable proteins all differed from those that varied in DT40 mutants deprived of one of the eight chicken H2B genes, H2B-V, encoding a particular H2B variant. These results suggest that the 01H1 variant is involved in the regulation of expression of genes that encode the proteins that vary in 01H1-deleted mutants of DT40 cells.
Assuntos
Linfócitos B/metabolismo , Histonas/genética , RNA Mensageiro/genética , Transcrição Gênica , Alelos , Animais , Linhagem Celular , Galinhas , Eletroforese em Gel Bidimensional , Técnicas de Transferência de Genes , Heterozigoto , Histonas/metabolismo , Homozigoto , Mutação , RNA Mensageiro/biossínteseRESUMO
Gnathostomiasis is primarily a disease of the skin characterized as creeping eruption or mobile erythema. However, larval Gnathostoma sometimes migrate into an unexpected site to elicit serious illness. Here we describe a case of colonic ileus caused by Gnathostoma doloresi. The patient was a 57-year-old man living in Miyazaki Prefecture, Japan, which is known as an area endemic for this parasite. One week after having eaten a few slices of the flesh of a snake (Agkistrodon halys), he developed severe abdominal pain. An abdominal radiograph revealed multiple gas-fluid levels with a distended bowel of an inverted U shape. A barium enema revealed a tumor in the ascending colon near the hepatic flexure that was surgically removed by simple colonic resection. An oblique section of a parasite surrounded by massive infiltration of eosinophils was found by postoperative histopathologic examination. The entire body of the advanced third-stage larva of G. doloresi was dissected from a specimen-embedded paraffin block.
Assuntos
Doenças do Colo/etiologia , Eosinófilos/imunologia , Gnathostoma/isolamento & purificação , Obstrução Intestinal/etiologia , Infecções por Spirurida/complicações , Animais , Anticorpos Anti-Helmínticos/análise , Anticorpos Anti-Helmínticos/imunologia , Antígenos de Helmintos/imunologia , Doenças do Colo/imunologia , Doenças do Colo/parasitologia , Ensaio de Imunoadsorção Enzimática , Parasitologia de Alimentos , Gnathostoma/imunologia , Humanos , Obstrução Intestinal/imunologia , Obstrução Intestinal/parasitologia , Masculino , Pessoa de Meia-Idade , Infecções por Spirurida/imunologia , Infecções por Spirurida/parasitologiaRESUMO
A new human cell line MRT-1 was established from a metastatic lymph node of renal cell carcinoma of a 47 years old Japanese male. The cultured MRT-1 cells exhibit an epithelial appearance and contain lipid vacuoles in their cytoplasm in vitro. The modal chromosome number was 70. Doubling time and plating efficiency were 32.5 h and 5%, respectively (at the 47th passage). Injection of 1X10(6) MRT-1 cells beneath the renal capsule of nude mice resulted in tumor formation resembling the original tumor. Serine proteinase inhibitors produced by the cell line were analyzed. The cultured cells produced alpha 1-antitrypsin (alpha 1-AT) and plasminogen activator inhibitor-1 (PAl-1) into the conditioned medium. Most of the MRT-1 derived alpha 1-AT had lost the affinity to Concanavalin A when compared to the normal plasma alpha 1-AT.
Assuntos
Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Inibidores de Serina Proteinase/biossíntese , Animais , Sequência de Bases , Carcinoma de Células Renais/secundário , Divisão Celular , Humanos , Neoplasias Renais/patologia , Metástase Linfática , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Dados de Sequência Molecular , Células Tumorais CultivadasRESUMO
Trypsin inhibitors in serum-free conditioned media (SFCM) of various human carcinoma cell lines were analyzed by reverse zymography. Most of the cells secreted high-molecular-weight trypsin inhibitors (HMTI) larger than 100 kDa. The cell lines of colorectal carcinoma origin had a tendency to secrete HMTI whose molecular weight was a little higher than that of the other cell lines. Analysis of SFCM of subclones with different histological differentiation and metastatic/invasive potentials derived from a single pancreatic carcinoma cell line SUIT-2 showed that the HMTI activity in SFCM was correlated to the degree of histological differentiation in vivo and tended to be inversely correlated to their metastatic/invasive capabilities. Immunoblotting analysis revealed that these HMTI were protease nexin-II/amyloid beta protein precursors (PN-II/APP). Semi-quantificative reverse-transcriptase/polymerase-chain reaction study for PN-II/APP mRNAs suggested that the differences in PN-II/APP activities in SFCM between the subclones might be post-transcriptional or post-secretional events. In addition, SFCM of a highly metastatic subclone contained 43-kDa protein which reacted to anti-APP monoclonal antibody (MAb) suggesting that the subclone may have APP-degrading activity.
Assuntos
Adenocarcinoma/enzimologia , Adenocarcinoma/patologia , Precursor de Proteína beta-Amiloide/análise , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células de Transição/enzimologia , Carcinoma de Células de Transição/patologia , Neoplasias/enzimologia , Neoplasias/patologia , Adenocarcinoma/secundário , Sequência de Bases , Carcinoma de Células Escamosas/secundário , Carcinoma de Células de Transição/secundário , Diferenciação Celular , Meios de Cultura Livres de Soro , Humanos , Dados de Sequência Molecular , Metástase Neoplásica/genética , Neoplasias Pancreáticas/enzimologia , Neoplasias Pancreáticas/patologia , Fenótipo , Inibidores de Serina Proteinase/análise , Inibidores da Tripsina/análise , Células Tumorais CultivadasRESUMO
A human pancreatic cancer cell line (SUIT-2), usually cultured in serum-supplemented medium (DMEM/FBS), was adapted to protein-free conditions using a 1:1 mixture of DMEM and Ham's F12 medium (DMEM/F12). The cells have been maintained in DMEM/F12 for more than 2 years, with over 50 passages. The SUIT-2 cells grew in DMEM/F12 with a doubling time of 35.7 h, which was similar to that in DMEM/FBS (35.0 h). The cellular morphology was similar in both media. Type IV collagenolytic activity was detected in the conditioned media from cells grown in DMEM/F12. The secretion of CEA and CA19-9 initially decreased in DMEM/F12. CEA was not detected after passage 5 (p5) but the concentration of CA19-9 did not decrease further after the first few serial passages in protein-free medium. Xenografts of SUIT-2 cells cultured in DMEM/F12 remained tumorigenic and could form metastatic tumors in nude mice. In conclusion, SUIT-2 cells grown in protein-free media continued to produce CA19-9 and type IV collagenase in vitro and formed metastatic tumors in vivo.
Assuntos
Neoplasias Pancreáticas/patologia , Animais , Divisão Celular , Colágeno/metabolismo , Meios de Cultura , Humanos , Metástase Linfática , Camundongos , Camundongos Nus , Metástase Neoplásica , Transplante de Neoplasias , Neoplasias Pancreáticas/metabolismo , Proteínas , Células Tumorais CultivadasRESUMO
The authors describe a rare case in which an infundibular dilation at the origin of a circumflex branch of the P1 segment of the posterior cerebral artery caused subarachnoid hemorrhage. Wrapping was performed by a subtemporal approach in the delayed stage. At the time of surgery, the rupture point was found in the infundibular dilation.