RESUMO
We aimed to compare the postoperative stability of conventional bimaxillary surgery (with bilateral sagittal split osteotomy) with that of maxillary impaction surgery (with mandibular autorotation without bilateral sagittal split osteotomy) in patients with skeletal class II retrognathia. Patients were assigned to have conventional bimaxillary surgery (conventional group, n=6) or mandibular autorotation (experimental group, n=7). Measurements were made using serial lateral cephalometric radiographs taken immediately preoperatively (T0), immediately postoperatively (T1), and one year later (T2) to assess the variation in operative change (T1-T0) and relapse (T2-T1). There was no significant difference in median (range) surgical change in the anterior movement at point B (conventional group, 4.5 (3.0-11.0) mm; experimental group 4.1 (2.1-6.4) mm). However, there was a significant difference in median (range) surgical posterior movement relapse at point B (conventional group -1.7 (-2.3 to -0.5) mm; experimental group -0.6 (-1.0 to 1.0) mm; p=0.032). Mandibular advancement with mandibular autorotation is therefore a more stable procedure than mandibular advancement with bilateral sagittal split osteotomy in patients with skeletal class II retrognathia.
Assuntos
Retrognatismo , Dente Impactado , Cefalometria , Seguimentos , Humanos , Mandíbula , Avanço Mandibular , Maxila , Osteotomia de Le Fort , Osteotomia Sagital do Ramo Mandibular , RecidivaRESUMO
To identify target genes for the hemizygous deletions of chromosome 13 that are recurrently observed in malignant gliomas, we performed genome-wide DNA copy-number analysis using array-based comparative genomic hybridization and gene expression analysis using an oligonucleotide-array. The response gene to complement 32 (RGC32) at 13q14.11 was identified as a deletion target, and its expression was frequently silenced in glioma cell lines compared with normal brain. Levels of RGC32 mRNA tended to decrease toward higher grades of primary astrocytomas, especially in tumors with mutations of p53. Expression of RGC32 mRNA was dramatically increased by exogenous p53 in a p53-mutant glioma cell line, and also by endogenous p53 in response to DNA damage in p53+/+ colon-cancer cells, but not in isogenic p53-/- cells. Chromatin immunoprecipitation and reporter assays demonstrated binding of endogenous p53 protein to the promoter region of the RGC32 gene, implying p53-dependent transcriptional activity. Transiently and stably overexpressed RGC32 suppressed the growth of glioma cells, probably owing to induction of G2/M arrest. Immunocytochemical analysis revealed a concentration of RGC32 protein at the centrosome during mitosis. RGC32 formed a protein complex with polo-like kinase 1 and was phosphorylated in vitro. These observations implied a novel mechanism by which p53 might negatively regulate cell-cycle progression by way of this newly identified transcriptional target. Our results provide the first evidence that RGC32 might be a possible tumor-suppressor for glioma, that it is directly induced by p53, and that it mediates the arrest of mitotic progression.
Assuntos
Proteínas de Ciclo Celular/genética , Cromossomos Humanos Par 13/genética , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Proteínas Musculares/genética , Proteínas do Tecido Nervoso/genética , Proteína Supressora de Tumor p53/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas de Ciclo Celular/análise , Proteínas de Ciclo Celular/metabolismo , Divisão Celular , Imunoprecipitação da Cromatina , Deleção Cromossômica , Dano ao DNA , Fase G2 , Deleção de Genes , Glioma/química , Humanos , Mitose , Proteínas Musculares/análise , Proteínas Musculares/metabolismo , Proteínas do Tecido Nervoso/análise , Proteínas do Tecido Nervoso/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Elementos de Resposta , Células Tumorais Cultivadas , Proteínas Supressoras de Tumor/análise , Proteínas Supressoras de Tumor/metabolismo , Quinase 1 Polo-LikeRESUMO
Automatic threshold detection techniques are described for auditory steady-state response (ASSR) elicited with a sinusoidally amplitude-modulated tone. The reliability and frequency specificity of ASSR are discussed. When applied to awake adults and detected by phase spectral analysis, 40-Hz ASSR threshold patterns closely resemble their corresponding audiograms. However, 40-Hz ASSR is insufficiently reliable for determining hearing thresholds in young children during sleep. On the other hand, 80-Hz ASSR is detected clearly in sleeping children. Moreover, 80-Hz ASSR threshold patterns also closely resemble the corresponding audiograms. Therefore, 80-Hz ASSR appears to be useful for objective audiometry in children.
Assuntos
Audiometria/métodos , Limiar Auditivo/fisiologia , Audição/fisiologia , Audiologia/métodos , Humanos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To evaluate the expression of human glucocorticoid receptors (hGRs), such as hGR (4H2), hGR-alpha, and hGR-beta, in non-neoplastic lymphoid follicles and B cell type malignant lymphomas. METHODS: The expression of hGRs in non-neoplastic lymphoid follicles and malignant lymphomas, including diffuse large cell lymphoma, mantle cell lymphoma, and follicular lymphoma, was examined immunohistochemically. HGR (4H2) expression was confirmed by double immunostaining of tissues and in isolated cells from tonsillar germinal centres, and by immunoelectronmicroscopy. RESULTS: In secondary lymphoid follicles of any non-neoplastic diseases--such as chronic tonsillitis, reactive lymphadenitis, and Kimura's disease--the germinal centre cells often expressed hGR (4H2) and hGR-alpha. Double immunocytochemical staining of isolated germinal centre cells showed that the majority of hGR (4H2) positive cells were CD20 positive B cells, and that follicular dendritic cells also expressed hGR. Immunoelectronmicroscopy revealed the presence of nuclear hGR (4H2) in the binucleated follicular dendritic cells and germinal centre cells. The frequency of hGR (4H2) expression in diffuse large B cell lymphoma was higher, that in mantle cell lymphoma was lower, and that in follicular lymphoma was intermediate among the types of malignant lymphoma. The hGR (4H2) expression was less frequent in cases of grade I follicular lymphoma. CONCLUSIONS: There are differences in hGR expression between the germinal centre and the mantle zone in non-neoplastic lymphoid follicles, and differences of hGR (4H2) expression among the types of malignant lymphoma and grades of follicular lymphoma, which probably contribute to the different steroid sensitivities.
Assuntos
Linfoma de Células B/química , Proteínas de Neoplasias/análise , Tonsila Palatina/química , Isoformas de Proteínas/análise , Receptores de Glucocorticoides/análise , Linfócitos B/química , Estudos de Casos e Controles , Contagem de Células , Células Dendríticas/química , Centro Germinativo/química , Humanos , Imuno-Histoquímica/métodos , Linfoma/química , Microscopia Imunoeletrônica , Tonsila Palatina/ultraestrutura , Estatísticas não ParamétricasRESUMO
Moyamoya disease is a progressive cerebrovascular occlusive disease that primarily affects children. The cause is unknown. We examined the production of prostanoids and the expression of cyclooxygenase-2 (COX-2) in cultured arterial smooth muscle cells (SMCs) derived from patients with moyamoya disease. Twelve moyamoya and 8 control cell strains were examined. The steady-state levels of prostanoids in the culture medium did not differ between moyamoya and control SMCs. When the cells were stimulated with interleukin-1beta (IL-1beta), prostaglandin E(2) (PGE(2)) release into the medium was significantly greater from moyamoya SMCs than from control SMCs, whereas the amounts of prostacyclin and thromboxane B(2) did not differ. IL-1beta-induced PGE(2) production by moyamoya SMCs was completely blocked by the addition of indomethacin or NS-398. IL-1beta significantly stimulated cell migration and DNA synthesis in control SMCs but had an inhibitory effect on moyamoya SMCs. The inhibitory effects on the growth and migration of moyamoya SMCs were caused by excessive secretion of PGE(2) and was reversed with indomethacin treatment. Immunofluorescence studies and Western blot analysis showed greater amounts of COX-2 protein expression in IL-1beta-stimulated moyamoya SMCs. These findings suggest that moyamoya SMCs respond to inflammatory stimuli to produce excess amounts of PGE(2) through the activation of COX-2, which increases vascular permeability and decreases vascular tone. This facilitates the exposure of vessels to blood constituents and promotes the development of intimal thickening in moyamoya disease.
Assuntos
Dinoprostona/biossíntese , Interleucina-1/farmacologia , Doença de Moyamoya/metabolismo , Músculo Liso Vascular/metabolismo , Adolescente , Artérias/metabolismo , Artérias/patologia , Artérias/fisiopatologia , Movimento Celular , Células Cultivadas , Criança , Pré-Escolar , Meios de Cultura/metabolismo , Ciclo-Oxigenase 2 , DNA/biossíntese , Feminino , Humanos , Lactente , Isoenzimas/metabolismo , Masculino , Proteínas de Membrana , Doença de Moyamoya/patologia , Músculo Liso Vascular/patologia , Músculo Liso Vascular/fisiopatologia , Prostaglandina-Endoperóxido Sintases/metabolismo , Prostaglandinas/biossínteseRESUMO
Sodium nitrate was given to male noninbred Wistar rats at levels of 800 ppm and 1,600 ppm in a pellet diet for 646 experimental days. The first tum or was found on day 441 in the liver of a rat given a diet containing 800 ppm sodium nitrite. On day 646, liver tumors were found in 1 of 22 rats (4.5%) on an 800-ppm sodium nitrite diet and in 5 of 19 rats (26.3%) on a 1,600-ppm sodium nitrite diet. The incidence of liver tumors in the rats fed 1,600 ppm sodium nitrite was significantly different from that in controls as judged by the t-test (P < 0.05). A hepatocellular carcinoma and a hemangioendothelial sarcoma of the liver were found on day 646 in 2 rats fed 1,600 ppm sodium nitrite. One mammary tumor but no liver tumors were found in the 19 control rats. The concentration of sodium nitrite decreased after preparation of the pellet diet, but it was still at least 70% of the initial amount when the pellets were given to the rats. Volatile N-nitroso compounds, especially dimehylnitrosamine, at ppm levels were detected in the pellet diet with a gas chromatography-thermal energy analyzer.
Assuntos
Carcinógenos , Neoplasias Hepáticas/induzido quimicamente , Nitritos/toxicidade , Nitrito de Sódio/toxicidade , Adenoma/induzido quimicamente , Animais , Carcinoma/induzido quimicamente , Carcinoma/patologia , Dieta , Relação Dose-Resposta a Droga , Hemangiossarcoma/induzido quimicamente , Hemangiossarcoma/patologia , Neoplasias Hepáticas/patologia , Masculino , Neoplasias Experimentais/induzido quimicamente , Compostos Nitrosos/toxicidade , Ratos , Fatores de TempoRESUMO
Intestinal metaplasia of the human stomach was classified into two types, complete and incomplete. The complete type was associated with the intestinal marker enzymes sucrose alpha-D-glucohydrolase, alpha, alpha-trehalase, aminopeptidase (microsomal) (APM), and alkaline phosphatase (ALP). Tissue of this type contained goblet cells and Paneth's cells but not high-iron diamine (HID)-positive mucin staining with HID-Alcian blue. The incomplete type of intestinal metaplasia was associated with sucrose alpha-D-glucohydrolase, APM, goblet cells, and HID-positive mucin but not with alpha, alpha-trehalase, ALP, or Paneth's cells. For the examination of the distribution of the complete and incomplete types in 84, 27, and 16 resected specimens of human stomach with gastric carcinoma, gastric ulcer, and duodenal ulcer, respectively, disaccharidases were located with Tes-Tape. Specimens with intestinal metaplasia were divided into three classes: complete type only (class I), incomplete type only (class II), and a mixture of areas of the complete and incomplete types (class III). Of the 84 specimens from patients with gastric carcinoma, intestinal metaplasia was found in 76 (01%), and the percentages of specimens of classes I, II, and III were 32, 22, and 46, respectively. In these specimens, the percent incidence of class I increased and that of class II decreased with age. Of the 27 specimens from patients with gastric ulcer, 16 (59%) shopwed intestinal metaplasia and 10 of the 16 (63%) specimens were of class II. Of the 16 specimens from patients with duodenal ulcer, only 3 (19%) specimens showed intestinal metaplasia and all of them were of class II. The relationships of the complete and incomplete types of intestinal metaplasia to gastric carcinoma wre studied in 26 foci of minute carcinoma of the stomach less than 5 mm in largest diameter. Nineteen of 20 (05%) foci of the intestinal type of minute carcinoma were surrounded by intestinal metaplasia and 16 foci (80%) were surrounded by the incomplete type of intestinal metaplasia.
Assuntos
Intestinos/patologia , Metaplasia/enzimologia , Mucinas/análise , Neoplasias Gástricas/enzimologia , Adulto , Fatores Etários , Idoso , Fosfatase Alcalina/análise , Aminopeptidases/análise , Úlcera Duodenal/enzimologia , Feminino , Histocitoquímica , Humanos , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/enzimologia , Estômago/análise , Estômago/enzimologia , Úlcera Gástrica/enzimologia , Sacarase/análise , Trealase/análiseRESUMO
Vaccination with irradiated tumor cells genetically modified to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF tumor vaccine) induces a potent systemic antitumor immunity. To develop a protocol for cancer therapy to further augment the host immune response, we examined the effects of the GM-CSF tumor vaccines simultaneously producing additional cytokines. We prepared cancer vaccines expressing double cytokines by sequential recombinant retrovirus-mediated genetic transductions. We then used a murine intracerebral tumor model in which the GM-CSF tumor vaccine was less effective in immunopotentiation and evaluated tumor vaccines producing various cytokines in conjunction with GM-CSF. The cytokine combination of GM-CSF and interleukin 4 induced more potent antitumor immunity than GM-CSF alone. An in vivo depletion test showed that CD4+, CD8+, and asialoGM1+ cells were required for the optimum function of the GM-CSF plus interleukin 4 tumor vaccine. Histological examinations revealed infiltration of inflammatory cells at the site of tumor cell challenge as well as at the site of vaccination, indicating the induction of a systemic antitumor immune response which reached the central nervous system. Our findings suggest the feasibility of applying the intensified vaccination strategy to treat human cancers including malignant brain tumors.
Assuntos
Neoplasias Encefálicas/terapia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/biossíntese , Imunoterapia , Interleucina-4/biossíntese , Melanoma Experimental/secundário , Vacinas Sintéticas , Células 3T3 , Animais , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/secundário , Citocinas/biossíntese , Feminino , Vetores Genéticos , Humanos , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Melanoma Experimental/terapia , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase , RetroviridaeRESUMO
Adoptive immunogene therapy of cancer is not widely studied, although it has been proposed as a promising strategy for cancer gene therapy. One of the major obstacles to this approach is the difficulty in introducing cytokine genes efficiently into T lymphocytes. In this report, we developed an adoptive immunotherapy model with murine tumor-specific cytotoxic T lymphocytes. By using an adenoviral vector, we achieved up to 100% gene transduction of murine T lymphocytes. Treatment of mice with the cytotoxic T lymphocytes genetically modified to produce interleukin 2 resulted in reduction of tumor metastasis and longer survival from intracerebral tumor death, providing a hopeful strategy for treatments of human cancers.
Assuntos
Imunoterapia Adotiva/métodos , Interleucina-2/metabolismo , Linfócitos do Interstício Tumoral/transplante , Melanoma Experimental/terapia , Subpopulações de Linfócitos T/transplante , Adenoviridae/genética , Animais , Epitopos , Feminino , Marcadores Genéticos , Interleucina-2/análise , Interleucina-2/genética , Interleucina-7/genética , Interleucina-7/metabolismo , Óperon Lac/genética , Linfócitos do Interstício Tumoral/metabolismo , Melanoma Experimental/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , TransfecçãoRESUMO
The objective of this study was to determine if a diet supplemented simultaneously with vitamins C and E would alleviate the negative effects of heat stress, applied between 28 and 42 days of age, on performance, carcass and meat quality traits of broiler chickens. A total of 384 male broiler chickens were assigned to a completely randomized design, with a 2×3 factorial arrangement (diet with or without vitamin supplementation and two ambient temperatures plus a pair-feeding group) and 16 replicates. Chickens were kept in thermoneutral conditions up to 28 days of age. They were then housed in groups of four per cage, in three environmentally controlled chambers: two thermoneutral (22.5 and 22.6°C) and one for heat stress (32°C). Half the chickens were fed a diet supplemented with vitamins C (257 to 288 mg/kg) and E (93 to 109 mg/kg). In the thermoneutral chambers, half of the chickens were pair-fed to heat stressed chickens, receiving each day the average feed intake recorded in the heat stress chamber in the previous day. Meat physical quality analyses were performed on the pectoralis major muscle. No ambient temperature×diet supplementation interaction effects were detected on performance, carcass, or meat quality traits. The supplemented diet resulted in lower growth performance, attributed either to a carry-over effect of the lower initial BW, or to a possible catabolic effect of vitamins C and E when supplemented simultaneously at high levels. Heat stress reduced slaughter and carcass weights, average daily gain and feed intake, and increased feed conversion. Growth performance of pair-fed chickens was similar to that of heat stressed chickens. Exposure to heat stress increased carcass and abdominal fat percentages, but reduced breast, liver and heart percentages. Pair-fed chickens showed the lowest fat percentage and their breast percentage was similar to controls. Heat stress increased meat pH and negatively affected meat color and cooking loss. In pair-fed chickens, meat color was similar to the heat stressed group. Shear force was not influenced by heat stress, but pair-fed chickens showed the tenderest meat. In conclusion, reduction in growth performance and negative changes in meat color in heat stressed chickens were attributed to depression in feed intake, whereas negative changes in body composition, higher meat pH and cooking loss were credited to high ambient temperature per se. Diet supplementation with vitamins C and E as antioxidants did not mitigate any of these negative effects.
Assuntos
Antioxidantes/administração & dosagem , Galinhas/fisiologia , Suplementos Nutricionais , Carne/normas , Vitaminas/administração & dosagem , Criação de Animais Domésticos , Animais , Ácido Ascórbico/administração & dosagem , Composição Corporal/fisiologia , Dieta , Ingestão de Alimentos , Transtornos de Estresse por Calor/fisiopatologia , Transtornos de Estresse por Calor/veterinária , Temperatura Alta , Masculino , Doenças das Aves Domésticas/fisiopatologia , Vitamina E/administração & dosagemRESUMO
We studied ganglioside expression in 12 human metastatic brain tumors metastasized from colon (4), renal (3), lung (2), esophagus (1), pancreas (1), and mammary (1) carcinomas. GM3 was the major common ganglioside expressed in brain metastatic tumor tissues, and GT1b was also present in all the metastatic brain tumor tissues. The latter was identified by TLC-immunostaining and characterized structurally by secondary ion mass spectrometry combined with 'Far-Eastern blot'. The immunohistochemical analysis of frozen tissue sections confirmed localization of GT1b in the tumor cell membrane or cytosol. GT1b was shown to be expressed both in the primary colon carcinoma and the metastasis of a single patient by immunohistochemical procedure. In systemic carcinomas without brain metastasis, GM3 was a common major component, but no GT1b was detected. These findings indicate that GT1b is a brain metastasis-associated ganglioside. We speculate that the presence of GT1b would be a useful marker for estimating metastatic potentials to the brain.
Assuntos
Adenocarcinoma/secundário , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/secundário , Gangliosídeos/análise , Adenocarcinoma/química , Neoplasias Encefálicas/química , Cromatografia em Camada Fina , Neoplasias do Colo/química , Secções Congeladas , Gangliosídeo G(M3)/análise , Gangliosídeo G(M3)/isolamento & purificação , Gangliosídeos/isolamento & purificação , Humanos , Imuno-Histoquímica , Neoplasias Renais/química , Espectrometria de Massas , Metástase NeoplásicaRESUMO
Estrogen deficiency causes a marked bone loss by stimulating osteoclastic bone resorption. To explore the endogenous bone-resorbing factors involved in estrogen deficiency, we examined the bone-resorbing activity present in the supernatant fraction of mouse bone marrow collected from ovariectomized (OVX) mice. Adding bone marrow supernatants at 20-80% to organ cultures of mouse long bones dose-dependently stimulated bone resorption. The endogenous bone-resorbing activity present in bone marrow supernatants from OVX mice was much higher than that from sham-operated mice 2-4 weeks after surgery, and it was significantly diminished by indomethacin in vitro. Anti-IL-1 alpha antibody completely neutralized the bone-resorbing activity present in bone marrow supernatants from OVX mice. Antibodies against IL-1 beta, IL-6, and IL-6 receptors also neutralized it, but partially. The concentration of IL-1 alpha measured by ELISA was much higher in bone marrow supernatants than in sera, but it was not appreciably changed before or after OVX. The concentration of IL-1 beta in bone marrow supernatants from OVX mice was less than the detection limit. OVX stimulated IL-1 activity in bone marrow supernatants measured by means of the proliferation of thymocytes. However, the level of IL-1 alpha present in bone marrow supernatants from OVX mice was insufficient to stimulate bone resorption. Compared with the serum concentration, bone marrow supernatants contained a much higher level of IL-6 as well, and it was further increased by OVX. However, IL-6 alone present in bone marrow supernatants from OVX mice again did not stimulate bone resorption.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Reabsorção Óssea/metabolismo , Estrogênios/deficiência , Interleucina-1/fisiologia , Interleucina-6/fisiologia , Ovário/fisiologia , Animais , Medula Óssea , Dinoprostona/fisiologia , Feminino , Camundongos , Camundongos Endogâmicos , Tamanho do Órgão , Ovariectomia , Útero/patologiaRESUMO
Prolapsus uteri in pelvic support disorders are common in elderly women. The etiology is unclear and more likely to be multifactorial. We examined changes in biological characteristics and responsiveness to growth factors during the in vitro cellular aging of cardinal ligamental fibroblasts derived from patients with prolapsus uteri (HPLiF), and compared them with those of cells from age-matched control subjects (HCLiF). HPLiF and HCLiF had almost the same in vitro life span and the age-related patterns of biological parameters were essentially the same. However, the saturation density was significantly higher in HPLiF than in HCLiF. Furthermore, the high proliferative activity of HPLiF to serum mitogens, especially to platelet-derived growth factor, was retained throughout the in vitro life span. p53 protein levels in HPLiF increased at late passages, but were significantly less than in aged HCLiF. These results indicate that the higher proliferative activity in prolapsus fibroblasts may result from the decreased expression of p53 protein and may lead to a decrease in the synthesis and deposition of extracellular matrix components. These results support the hypothesis that functional alterations in ligament fibroblasts are involved in the mechanism of the development of prolapsus uteri.
Assuntos
Senescência Celular , Ligamentos/patologia , Prolapso Uterino/patologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Senescência Celular/genética , Senescência Celular/fisiologia , DNA/biossíntese , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Expressão Gênica , Genes p53 , Humanos , Técnicas In Vitro , Ligamentos/metabolismo , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Prolapso Uterino/genética , Prolapso Uterino/metabolismoRESUMO
Moyamoya disease is a progressive cerebrovascular occlusive disease that occurs frequently in children. The etiology is unknown. We examined changes in biological characteristics and responsiveness to serum mitogens during the in vitro cellular aging of arterial smooth muscle cell strains derived from patients with moyamoya disease (HMSMC) and compared them with those of cells from age-matched control patients (HCSMC). HMSMC had a normal human diploid chromosome constitution. HMSMC and HCSMC had almost the same in vitro life span and the age-related patterns of biological parameters were essentially the same. However, the doubling time at the early passages was significantly longer in moyamoya SMC than control SMC, although there was no significant difference at the late passages. Furthermore, the poor responsiveness of moyamoya SMC to platelet-derived growth factor was retained throughout the life span in vitro. These results support the hypothesis that functional alterations in vascular cells are involved in the mechanism of development of intimal thickening in moyamoya disease.
Assuntos
Artérias/patologia , Doença de Moyamoya/patologia , Músculo Liso Vascular/patologia , Adolescente , Adulto , Artérias/metabolismo , Divisão Celular , Células Cultivadas , Senescência Celular , Criança , Pré-Escolar , DNA/biossíntese , Feminino , Humanos , Masculino , Doença de Moyamoya/genética , Músculo Liso Vascular/metabolismo , Valores de ReferênciaRESUMO
The loss of trabecular bone in the ovariectomized (OVX) rat provides a useful experimental model of postmenopausal osteoporosis. In this study, two bone-modulating compounds, an NSAID (flurbiprofen: FBP) and a chemically modified nonantimicrobial tetracycline (CMT), were tested either individually or in combination in this model. Ninety days after OVX, 6-month-old female rats were distributed into the following groups: sham-operated controls, untreated OVX, CMT-treated OVX (5 mg P.O./day), FBP-treated OVX (0.3 mg P.O./day), and combination (CMT plus FBP)-treated OVX (COMBO) groups. Untreated 3-month-old rats were used as pretreatment group. After 21 days of therapy, the dissected distal femurs were processed for light and fluorescence microscopic and backscattered electron microscopic examinations. Net trabecular bone values showed that all the treatment groups lost trabecular bone over the 111 day protocol compared to pretreatment group. In the untreated OVX rats, trabecular bone volume/unit area was reduced by 56% compared to that in the sham-operated controls, this bone loss associated with increased numbers of osteoclasts (p < 0.05). Cortical bone volume was, however, not significantly reduced in OVX rats. Both FBP-alone and COMBO therapy showed marginal, but significant, (p < 0.05, p < 0.01, respectively) inhibition of trabecular bone loss, and osteoclast numbers were also decreased (p < 0.05). Both CMT alone and COMBO therapy appeared to increase bone deposition (p < 0.01) at the endosteal surfaces of cortical bone. These results suggest that, in this animal model, (a) cortical bone volume increases by CMT; (b) FBP inhibits osteoclastic bone resorption in the trabecular area, and (c) a combination of these drugs may synergistically prevent bone loss.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Flurbiprofeno/uso terapêutico , Inibidores da Síntese de Proteínas/uso terapêutico , Tetraciclina/uso terapêutico , Animais , Osso e Ossos/patologia , Quimioterapia Combinada , Feminino , Fêmur/química , Fêmur/ultraestrutura , Microscopia Eletrônica de Varredura , Osteoporose/tratamento farmacológico , Ovariectomia , Ratos , Ratos Sprague-DawleyRESUMO
Irradiated tumor cells genetically modified to secrete granulocyte/macrophage-colony-stimulating factor (GM-CSF tumor vaccine) are potent stimulators of systemic antitumor immunity. For the preparation of a GM-CSF gene-modified tumor vaccine, it is important to achieve efficient genetic transduction of tumor cells, leading to an appropriate expression of the induced gene. In this report, with a view to developing a protocol for an effective cancer vaccination therapy, we examined the vaccination efficacies of tumor cells secreting GM-CSF by either adenovirus- or retrovirus-mediated genetic transduction. By using an adenoviral vector, Adex1CAmGMCSF, a highly efficient gene delivery and a high-level expression of the GM-CSF gene were achieved. Unexpectedly, animal vaccination studies showed that the GM-CSF tumor vaccine transduced with the Adex1CAmGMCSF recombinant adenovirus (adenoviral GM-CSF tumor vaccine) was less efficacious than that transduced with the MFGmGMCSF recombinant retrovirus (retroviral GM-CSF tumor vaccine). The GM-CSF serum concentration attained by the adenoviral GM-CSF tumor vaccine was much higher than that obtained by the retroviral GM-CSF tumor vaccine. Our findings indicate that an optimal level of GM-CSF production is important for the tumor vaccine to elicit an adequate response in the host antitumor immunity.
Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Melanoma Experimental/prevenção & controle , Adenoviridae/genética , Animais , Feminino , Vetores Genéticos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Melanoma Experimental/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Recombinantes/administração & dosagem , Retroviridae/genética , Transdução Genética , Células Tumorais Cultivadas , Vacinação , Vacinas/imunologiaRESUMO
A real time biomolecular interaction assay system involving an optical sensor was applied to the quantitative analysis of the binding of herpes simplex virus type 1 (HSV-1) to Vero cells, and the neutralization antibody titer against this virus with a commercially available sulfonated human immunoglobulin preparation. The virus titers in a viral solution and the neutralizing antibody titer in the human immunoglobulin preparation could be successfully estimated in a short time with this system without any difficult cytopathic effect analysis of cultured cells.
Assuntos
Herpesvirus Humano 1/imunologia , Herpesvirus Humano 1/metabolismo , Imunoglobulina G/farmacologia , Rim/metabolismo , Animais , Anticorpos/metabolismo , Técnicas Biossensoriais , Células Cultivadas , Relação Dose-Resposta a Droga , Haplorrinos , Herpesvirus Humano 1/efeitos dos fármacos , Humanos , Soros Imunes/metabolismo , Rim/citologia , Rim/virologia , Fatores de TempoRESUMO
A real time biomolecular interaction assay system involving an optical sensor was applied to quantitative analysis of the binding of herpes simplex virus type 1 (HSV-1) to immobilized heparan sulfate, a cellular receptor component of HSV-1, and the neutralization antibody titer against this virus with a commercially available sulfonated human immunoglobulin preparation. The virus titer in a viral solution and the neutralizing antibody titer in the human immunoglobulin preparation could be successfully estimated in a short time with this system without any difficult cell culture.
Assuntos
Anticorpos Antivirais/metabolismo , Heparitina Sulfato/metabolismo , Herpesvirus Humano 1/imunologia , Herpesvirus Humano 1/metabolismo , Animais , Anticorpos Bloqueadores/metabolismo , Técnicas Biossensoriais , Chlorocebus aethiops , Humanos , Técnicas In Vitro , Cinética , Testes de Neutralização , Receptores Virais/metabolismo , Células VeroRESUMO
The sequence of about 4,500 nucleotides of the internal part of tobacco mosaic virus (TMV)-tomato strain (L) RNA has been newly determined using cloned cDNAs. Together with the previously determined partial sequences at both ends, the entire sequence of the 6,384 nucleotide genome has been completed. The 130K (1,115 amino acids), 180K (1,615 amino acids), 30K (263 amino acids) and coat protein (158 amino acids) cistrons are located at residues 72-3442, 72-4922, 4906-5700, and 5703-6182 on the genome, respectively. Sequence polymorphism was not observed except for heterogeneity in the length of the A cluster near the 3' end. The homology of the nucleotide sequences of TMV-L and TMV-vulgare, a common strain, is about 80% on average. Remarkable differences between them were found in a part of the N-terminal portion of the 130K/180K protein and the C-terminal portion of the 30K protein. A new method for cDNA cloning was developed by which the cDNA of the 5'-terminus of viral RNA can be cloned efficiently.
Assuntos
Genes Virais , RNA Viral/análise , Vírus do Mosaico do Tabaco/genética , Sequência de Bases , Clonagem Molecular , DNA , DNA Recombinante/biossíntese , Especificidade da EspécieRESUMO
We studied the capacity for sound localization in the horizontal plane with measurement of the ocular position of the listener. The eye position responses elicited by tonal sound were asymmetrical in all six subjects and there was individual variation of frequency dependence. The sound pressure level and the angle of the loudspeaker also affected the accuracy of localization. Sound localization was more accurate, and individual variation lower, when the sound pressure level and the angle of the sound source were in the range 50 dBSL and 30 degrees, respectively. In the monoaural condition, the ear on the occluded side consistently showed displacement of responses toward the side of the non-occluded ear. Sound localization on the non-occluded side, however, showed various patterns of change in the monaural condition relative to the binaural condition. Cues as to the sound localization thus seem to differ with the side of the sound source.