RESUMO
BACKGROUND: Diabetic striatopathy, one of the complications of diabetes mellitus, is characterized by involuntary movements, including hemichorea and hemiballismus, and the presence of hyperintense lesions on T1-weighted magnetic resonance imaging of the striatum. CASE REPORT: We present a case of diabetic striatopathy manifesting as severe consciousness disturbance without chorea or ballismus. A 58-year-old man was admitted to our hospital in a state of unconsciousness. He was diagnosed with diabetic striatopathy as a result of extremely elevated blood glucose levels and typical magnetic resonance imaging findings in the left striatum, although involuntary movements were absent. He was treated with insulin, and his glucose levels were well maintained. His neuropsychiatric symptoms recovered, rather slowly but completely, after ~20 days. CONCLUSION: This case indicates the diversity of striatal dysfunction induced by hyperglycaemia. For good prognosis of diabetic striatopathy, prompt diagnosis and appropriate treatments are important. Physicians should be aware that this disease can cause various neurological and psychiatric symptoms other than chorea or ballismus.
Assuntos
Doenças do Sistema Nervoso Central/diagnóstico , Corpo Estriado/patologia , Complicações do Diabetes/diagnóstico , Inconsciência/diagnóstico , Doenças do Sistema Nervoso Central/etiologia , Complicações do Diabetes/patologia , Diagnóstico Diferencial , Discinesias , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Inconsciência/etiologiaRESUMO
Reduced expression in immortalized cells (REIC)/dickkopf-3 (Dkk-3), a tumor suppressor gene, is downregulated in various cancers. We previously reported the tumor-inhibitory effects of the REIC/Dkk-3 gene, delivered by a conventional adenoviral vector (Ad-CAG-REIC) in pancreatic cancer. Here, we developed an Ad-REIC vector with a novel gene expression system, termed the super gene expression (SGE) system, and assessed its therapeutic effects relative to those of Ad-CAG-REIC in pancreatic cancer cells. Human pancreatic cancer cell lines ASPC1 and MIAPaCa2 were used. REIC/Dkk-3 expression was assessed by western blot analysis. Relative cell viability and apoptotic effects were examined in vitro. The anti-tumor effects of Ad-REIC treatment were assessed in the mouse xenograft model. Compared with Ad-CAG-REIC, Ad-SGE-REIC elicited a significant increase in REIC protein expression in the cells studied. Relative to Ad-CAG-REIC, Ad-SGE-REIC reduced cell viability and induced apoptosis in the ASPC1 and MIAPaCa2 cell lines in vitro, and achieved superior tumor growth inhibition in the mouse xenograft model. Compared with conventional Ad-REIC agents, Ad-SGE-REIC provided enhanced inhibitory effects against tumor growth. Our results indicate that Ad-SGE-REIC is an innovative therapeutic tool for pancreatic cancer.
Assuntos
Adenoviridae/genética , Terapia Genética , Vetores Genéticos/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Neoplasias Pancreáticas/genética , Proteínas Adaptadoras de Transdução de Sinal , Animais , Apoptose/genética , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Quimiocinas , Modelos Animais de Doenças , Expressão Gênica , Ordem dos Genes , Vetores Genéticos/administração & dosagem , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Camundongos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Transdução de Sinais , Carga Tumoral/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Hypopharyngeal squamous cell carcinoma (HSCC) is an aggressive malignancy with one of the worst prognoses among all head and neck cancers. Greater understanding of the pertinent molecular oncogenic pathways could help improve diagnosis, therapy, and prevention of this disease. The aim of this study was to identify tumour-suppressive microRNAs (miRNAs), based on miRNA expression signatures from clinical HSCC specimens, and to predict their biological target genes. METHODS: Expression levels of 365 human mature miRNAs from 10 HSCC clinical samples were screened using stem-loop real-time quantitative PCR. Downregulated miRNAs were used in cell proliferation assays to identify a tumour-suppressive miRNA. Genome-wide gene expression analyses were then performed to identify the target genes of the tumour-suppressive miRNA. RESULTS: Expression analysis identified 11 upregulated and 31 downregulated miRNAs. Gain-of-function analysis of the downregulated miRNAs revealed that miR-489 inhibited cell growth in all head and neck cancer cell lines examined. The gene PTPN11 coding for a cytoplasmic protein tyrosine phosphatase containing two Src Homology 2 domains was identified as a miR-489-targeted gene. Knockdown of PTPN11 resulted in the inhibition of cell proliferation in head and neck SCC cells. CONCLUSION: Identification of the tumour-suppressive miRNA miR-489 and its target, PTPN11, might provide new insights into the underlying molecular mechanisms of HSCC.
Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Hipofaríngeas/genética , MicroRNAs/genética , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Idoso , Linhagem Celular Tumoral , Regulação para Baixo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Interferente Pequeno , Reação em Cadeia da Polimerase Via Transcriptase Reversa , TransfecçãoRESUMO
BACKGROUND: In recent years, many countries have experienced an increase in the prevalence of allergic rhinitis. No effective approach is currently available to prevent the onset of symptoms in allergic individuals. Pranlukast, a leukotriene receptor antagonist with a good safety and efficacy record for the management of allergic inflammation, may be appropriate for early intervention in the management of pollinosis. OBJECTIVE: To investigate the efficacy of pranlukast as an early intervention in the control of cedar pollinosis. METHODS: In a double-blind comparative study, pranlukast (n = 102) or placebo (n = 91) was administered to cedar pollinosis patients immediately before the start of the dispersion season and continued for 4 weeks. Subsequently, pranlukast was administered to all patients for 2 weeks until the end of the cedar pollen dispersion season (mid-March). All patients were carefully monitored for severity of nasal symptoms, symptom scores, medication scores, symptom-medication scores, and quality of life (QOL). RESULTS: Compared with placebo, therapy with pranlukast before and during the dispersion of cedar pollen in these patients significantly improved nasal symptoms (paroxysmal sneezing, rhinorrhea, and nasal congestion), symptom scores, and symptom-medication scores. The drug also significantly reduced deterioration of QOL, and improved nasal symptoms and QOL throughout the dispersion period. CONCLUSION: Administering pranlukast immediately before the beginning of cedar pollen dispersion is effective in reducing symptoms of allergic rhinitis throughout the dispersion period.
Assuntos
Cromonas/uso terapêutico , Cryptomeria/imunologia , Antagonistas de Leucotrienos/uso terapêutico , Pólen/imunologia , Rinite Alérgica Sazonal/tratamento farmacológico , Adulto , Cromonas/administração & dosagem , Cromonas/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Antagonistas de Leucotrienos/administração & dosagem , Antagonistas de Leucotrienos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Rinite Alérgica Sazonal/imunologiaRESUMO
BACKGROUND: Allergic rhinitis (AR) is a typical type I allergic disease that occurs through the induction of allergen-specific effector T cells. Once established, new effector T cells derive mostly from memory T cells that are capable of surviving for extended periods, although the mechanisms by which these memory functions are maintained have not yet been clarified. In particular, the exact life-span of memory T cells is still not well understood. OBJECTIVE: Pollinosis patients seemed to be suitable subjects to investigate because such patients are exposed to antigens strongly for only a limited period once a year. We compared the seasonal changes in memory T-helper type 2 (Th2) between pollinosis and perennial allergic subjects. METHODS: The clone sizes of the Japanese cedar pollen-specific memory Th cells were measured by an ELISPOT assay using specific peptides from the patients with cedar pollinosis, and the seasonal changes were noted. This study was performed for 2 years. The cedar-specific IgE levels in the peripheral blood were also studied. Mite allergy patients were also enrolled in the study. RESULTS: The Japanese cedar-specific IL-4-producing Th2 cells were detected in all patients examined, although the number of cells was low. These Th memory cells increased during the pollen season and decreased during the off-season. However, more than 60% of the cedar-specific memory Th2 cells survived up to 8 months after the pollen season. The cedar-specific IgE levels exhibited changes similar to the cedar-specific Th cells. On the other hand, there was no drifting of Th memory clone size with the mite allergics, and the IgE levels also did not change. CONCLUSIONS: While pollen-specific Th cells decreased after pollen exposure, their memory functions continued. Memory clone size maintenance therefore requires repetitive antigen irritation.
Assuntos
Cryptomeria/imunologia , Rinite Alérgica Sazonal/imunologia , Rinite Alérgica Sazonal/patologia , Estações do Ano , Células Th2/imunologia , Células Th2/patologia , Adulto , Animais , Contagem de Linfócito CD4 , Células Clonais/patologia , Epitopos , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Memória Imunológica , Interleucina-4/biossíntese , Masculino , Pessoa de Meia-Idade , Pólen/imunologia , Pyroglyphidae/imunologia , Rinite Alérgica Perene/imunologia , Rinite Alérgica Perene/patologia , Células Th2/metabolismoRESUMO
BACKGROUND: Chronic sinusitis (CS) with asthma generally exhibits a high degree of sinus tissue eosinophilia and recurrence often occurs even after surgical therapy. However, the cause has not yet been fully clarified. AIMS OF THE STUDY: To elucidate the pathogenesis of this refractory disease, we examined the infiltration of natural killer T (NKT) and type 1 helper T (Th1)/type 2 helper T (Th2) cells, and the cytokine expression in the sinus mucosa. METHODS: Sinus mucosal specimens were obtained surgically from 16 CS patients with nasal polyps. The NKT cells, Th1/Th2 cells and the expression of IL-4, IL-5, IL-13 and IFN-gamma were examined by a polymerase chain reaction or flow cytometry. Nasal mucosal specimens from six other patients with allergic rhinitis (AR) were examined in a similar manner. RESULTS: The NKT cells were detected to varying degrees in the sinus mucosa from asthmatic CS patients, but neither in the nonasthmatics nor in the nasal mucosa from the patients with AR. The Th2 cells and Th2 cytokines were expressed at significantly higher levels in the sinus mucosa from the CS patients with asthma in comparison to those without asthma. However, the Th1 cell infiltration and IFN-gamma expression were not different between these groups. CONCLUSION: Natural killer T cells may, therefore, play important roles in the enhanced Th2 cytokine expression and increased infiltration of Th2 cells and eosinophils observed in the sinus mucosa from asthmatic CS patients through MHC-independent mechanisms.
Assuntos
Asma/complicações , Seio Etmoidal/imunologia , Células Matadoras Naturais/imunologia , Mucosa Nasal/imunologia , Sinusite/imunologia , Sinusite/fisiopatologia , Adulto , Idoso , Asma/imunologia , Asma/fisiopatologia , Doença Crônica , Citocinas/genética , Citocinas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/cirurgia , Reação em Cadeia da Polimerase , Rinite Alérgica Perene/etiologia , Rinite Alérgica Perene/imunologia , Rinite Alérgica Perene/fisiopatologia , Células Th1/imunologia , Células Th2/imunologiaRESUMO
BACKGROUND: The underlying relationship between viral infections and allergic diseases of the upper respiratory tract has not been well clarified. METHODS: In order to clarify the relationship between viral infection and nasal hypersensitivity, mice were sensitized with ovalbumin (OVA) and then infected intranasally with respiratory syncytial virus (RSV), after which their nasal sensitivity to histamine or antigen was examined. RESULTS: Non-sensitized mice showed transient mild nasal hypersensitivity following nasal administration of histamine after intranasal RSV inoculation. In mice sensitized with OVA, RSV infection significantly exaggerated their nasal hypersensitivity to histamine and OVA. Treatment of these mice with a neurokinin (NK)-1/NK-2 receptor antagonist, but not with anti-IL-5 antibodies, reduced their hypersensitivity. The infiltration of nasal mucosa with eosinophils was temporarily associated with accelerated rate of RSV elimination in these animals. CONCLUSION: RSV infection induced transient nasal hypersensitivity. Several mechanisms, including impairment of nasal epithelial cells are thought to mediate this effect. In allergen-sensitized mice, RSV inoculation strongly enhanced nasal hypersensitivity.
Assuntos
Nariz/imunologia , Hipersensibilidade Respiratória/virologia , Infecções por Vírus Respiratório Sincicial/imunologia , Administração Intranasal , Animais , Anticorpos/imunologia , Eosinófilos/imunologia , Histamina/administração & dosagem , Histamina/imunologia , Interleucina-5/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mucosa Nasal/imunologia , Antagonistas dos Receptores de Neurocinina-1 , Ovalbumina/imunologia , Receptores da Neurocinina-1/imunologia , Receptores da Neurocinina-2/antagonistas & inibidores , Receptores da Neurocinina-2/imunologia , Hipersensibilidade Respiratória/imunologia , Replicação Viral/imunologiaRESUMO
Vascular endothelial growth factor (VEGF) receptors consist of three cell-membrane type receptors (VEGFR-1, VEGFR-2 and VEGFR-3), and soluble form of VEGFR-1 (sVEGFR-1), an intrinsic negative counterpart of the VEGF. In this study, we measured intratumoral protein levels of free and total VEGF, VEGFR-2 and sVEGFR-1 from 202 primary breast cancer tissues and examined their prognostic values. A significant inverse correlation was found between free or total VEGF and oestrogen receptor (ER) status (P=0.042 and 0.032, respectively). A univariate analysis showed that low sVEGFR-1 and high total VEGF were significantly associated with poor prognosis in disease-free survival (DFS) and overall survival (OS). The ratio of sVEGFR-1 to total VEGF was a strong prognostic indicator (DFS: P=0.008; OS: P=0.0002). A multivariate analysis confirmed the independent prognostic values of total VEGF and the ratio of sVEGFR-1 to total VEGF. In subgroup analysis, total VEGF was a significant prognostic indicator for ER-positive tumours but not for ER-negative tumours, whereas sVEGFR-1 was significant for ER-negative tumours but not for ER-positive tumours. In conclusion, the intratumoral sVEGFR-1 level, VEGF level and the ratio of sVEGFR-1 to total VEGF are potent prognostic indicators of primary breast cancer, and might be relevant to ER status.
Assuntos
Neoplasias da Mama/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Fatores de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Intervalo Livre de Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Pessoa de Meia-Idade , Neovascularização Fisiológica , PrognósticoRESUMO
The combination effect of docetaxel and capecitabine on tumour response rate and survival was demonstrated recently in metastatic breast cancer patients. This combination was based on an experimental hypothesis that taxane can increase tumour sensitivity to the effect of capecitabine through the upregulation of thymidine phosphorylase (TP), which is responsible for the metabolism of 5-fluorouracil (5-FU) and its derivatives, including capecitabine. To examine the alteration in TP expression before and after neoadjuvant chemotherapy, 92 patients with primary breast cancer (T2-4N0-1M0) were enrolled in this study; 14 were treated with adriamycin and cyclophosphamide (AC) or epirubicin and cyclophosphamide (EC); 58 with 5-FU, adriamycin, and cyclophosphamide (FAC) or 5-FU, epirubicin, and cyclophosphamide (FEC); and 20 with FEC followed by docetaxel/taxotere (TXT-containing regimen). Thymidine phosphorylase upregulation was seen in 54.4% and 32.6% of patients in tumour cells and stromal cells, respectively. Increases in TP expression were found only in the AC/EC and TXT-containing regimen groups. In conclusion, it was strongly suggested that unlike 5-FU-containing regimens, the taxane and AC combination therapies upregulate TP expression in primary breast cancer. Thymidine phosphorylase upregulation by several anticancer drugs implies the importance of individualised strategies for sensitisation of tumour tissues to 5-FU and its derivatives.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/enzimologia , Timidina Fosforilase/biossíntese , Timidina Fosforilase/efeitos dos fármacos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Docetaxel , Doxorrubicina/administração & dosagem , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Terapia Neoadjuvante , Taxoides/administração & dosagem , Regulação para CimaRESUMO
The contribution of the Na+/Ca2+ exchanger to the myogenic vascular tone was examined in rat isolated skeletal muscle small arteries (ASK) with pronounced myogenic tone and mesenteric small arteries (AMS) with little myogenic tone. Myogenic tone was assessed by the vascular inner diameter at transmural pressures of 40 and 100 mmHg. To depress the Na+/Ca2+ exchanger, the extracellular Na+ concentration ([Na+]o) was lowered from 143 to 1.2 mM by substituting choline-Cl for NaCl. The ASK developed significant myogenic tone and constricted further in low [Na+]o. Nifedipine (1 microM) reduced both myogenic tone and low [Na+]o-induced contraction. Because the membrane potential of ASK was not changed by low [Na+]o (-35 +/- 2 mV at 143 mM [Na+]o, -37 +/- 3 mV at 1.2 mM [Na+]o), depolarization-induced Ca2+ influx was not a cause of the low [Na+]o-induced contraction. The AMS did not develop significant myogenic tone. Although low [Na+]o also constricted AMS, the magnitude of constriction was significantly weaker than that in ASK (17 +/- 4 vs. 47 +/- 6%, P < 0.01, at 58 mM Na+). With Bay K 8644, AMS developed myogenic tone, and low [Na+]o-induced constriction was significantly increased. In conclusion, Na+/Ca2+ exchanger may play an important role in regulating myogenic tone, likely via mediating Ca2+-extrusion.
Assuntos
Artérias Mesentéricas/fisiologia , Tono Muscular/fisiologia , Trocador de Sódio e Cálcio/metabolismo , Vasoconstrição/fisiologia , Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil)/farmacologia , Animais , Cálcio/farmacocinética , Agonistas dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Tono Muscular/efeitos dos fármacos , Músculo Esquelético/irrigação sanguínea , Nifedipino/farmacologia , Ratos , Ratos Wistar , Sódio/farmacocinética , Vasoconstrição/efeitos dos fármacosRESUMO
Induction of procoagulant factors in malignant cells is considered to be the major cause of coagulation disorders in cancer. Thrombomodulin (TM), a negative regulator of coagulation was also found to be expressed in cancer cells. We report here evidence for another anticoagulant, the endothelial cell protein C receptor (EPCR), in cancer cells. EPCR was detected in several cell lines derived from various types of cancer. Significant levels of protein C (PC) activation were detected only with cell lines expressed both EPCR and TM. Anti-EPCR monoclonal antibodies (mAbs) specifically inhibited the activation. Thus, EPCR function appears to be important for PC activation by cancer cells. In addition, we detected EPCR expression in tumor cells from breast cancer patients, with an extremely high frequency. EPCR function may contribute to progression or pathogenesis of some types of cancer, and may explain the complexity of coagulopathy in cancer patients.
Assuntos
Fatores de Coagulação Sanguínea , Receptores de Superfície Celular/metabolismo , Células Tumorais Cultivadas/metabolismo , Anticoagulantes/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Ativação Enzimática/efeitos dos fármacos , Feminino , Citometria de Fluxo , Glioblastoma/metabolismo , Glicosilação , Humanos , Imuno-Histoquímica , Leucemia/metabolismo , Leucemia/patologia , Masculino , Proteínas de Neoplasias/metabolismo , Proteína C/efeitos dos fármacos , Proteína C/metabolismo , Receptores de Superfície Celular/fisiologia , Trombomodulina/metabolismo , Células Tumorais Cultivadas/químicaRESUMO
Laryngeal granuloma is a rather common pathological entity, but its therapeutic strategy is still controversial. In general, therapeutic strategy consists of medications such as steroids or tranilast, in addition to vocal hygiene and surgery. Surgical removal is most commonly performed. However, it has recently been reported that recurrence after surgery is high.We successfully treated 19 of 20 cases of laryngeal granuloma without surgical removal. It took 28-328 days for the granulomas to disappear. Therefore conservative treatments should be the first choice of treatment.
RESUMO
OBJECTIVE: To investigate whether metabolic interactions exist between hexane (HEX) and other solvents when co-exposed at the levels below occupational exposure limits. METHODS: Workers, 219 men in ten workshops in total, volunteered to participate in the study. They were occupationally exposed to mixtures of HEX and one or more of toluene (TOL), ethyl acetate (EA) and acetone (ACE). Time-weighted average intensity of vapor exposures was monitored by diffusive personal sampling. 'Free'- and 'total'-2,5-hexanedione (HD) levels in the end-of-shift urine samples were determined by gas chromatography (GC) before and after acid hydrolysis of urine, respectively, and expressed as observed (HDob) or after correction for creatinine concentration (HDcr) or urine specific gravity (HDsg). Possible interaction was examined by multiple regression analysis (MRA), taking either free- or total-HD as a dependent variable, and the four solvent concentrations as independent variables. RESULTS: In most cases, exposure intensity did not exceed the current occupational exposure limits even when additiveness was assumed. In addition that HEX was the most influential independent variable in all cases as expected, the MRA showed that, in cases of free-HD, ACE was also influential to HDob although weakly, but not to HDcr or HDsg. With regard to total-HD, ACE was weakly influential to HDob and HDsg, and EA also weakly to HDcr. The effect of ACE on free- or total-HD was not detected, however, when 22 men exposed only to HEX and ACE were subjected to the same analysis. Similarly, the effect of EA on total-HD was not observed among the remaining 197 men exposed to HEX, TOL and EA only. CONCLUSIONS: When the exposures were below occupational exposure limits, the free-HD levels in urine after HEX exposure will not be modified by co-exposures to TOL, EA or ACE.
Assuntos
Hexanos/metabolismo , Hexanonas/urina , Neurotoxinas/metabolismo , Exposição Ocupacional , Solventes/metabolismo , Acetatos/metabolismo , Acetatos/farmacologia , Acetona/metabolismo , Acetona/farmacologia , Adesivos/metabolismo , Cromatografia Gasosa , Interações Medicamentosas , Humanos , Masculino , Neurotoxinas/farmacologia , Solventes/farmacologia , Tolueno/metabolismo , Tolueno/farmacologiaRESUMO
A dysfunction of the sarcoplasmic reticulum (SR) causes an increase in the myogenic tone of rat skeletal muscle small arteries (A(SK)), but not that of mesenteric small arteries (A(MS)). We hypothesized that the difference depends on the activity of voltage-dependent Ca2+ channels in these vessels. To test this, we measured the membrane potential of these vessels and examined ryanodine-induced constrictions by manipulating the activity of voltage-dependent Ca2+ channels. The isolated vessels were cannulated to control the transmural pressure. To assess the vascular tone, the inner diameter was measured with a video-digitizing system. The membrane potential of A(SK) was more depolarized between 20 to 100 mm Hg of transmural pressure. A(MS) was not constricted by the Ca2+ channel agonist Bay K 8644 (1 nM(-1) microM) alone, but substantially constricted in the presence of ryanodine (1 microM). Ryanodine also augmented the KCl (20 mM)-induced constriction. In A(SK), the Ca2+ channel blocker nisoldipine fully dilated the ryanodine-induced constriction: however, the ryanodine-induced constriction was less susceptible to nisoldipine than was the myogenic and phenylephrine-induced constriction caused mainly by increased Ca2+ influx. In conclusion, the contribution of the SR function to Ca2+ metabolism depends on the activity of dihydropyridine-sensitive Ca2+ channels. The dysfunction of SR by ryanodine may impair the Ca2+ extrusion rather than increase Ca2+ influx in rat small arteries.
Assuntos
Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil)/farmacologia , Agonistas dos Canais de Cálcio/farmacologia , Canais de Cálcio/efeitos dos fármacos , Potenciais da Membrana/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Rianodina/farmacologia , Vasoconstrição/efeitos dos fármacos , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Interações Medicamentosas , Artérias Mesentéricas , Nisoldipino/farmacologia , Técnicas de Patch-Clamp , Ratos , Ratos WistarAssuntos
Embolia Pulmonar/cirurgia , Trombectomia/métodos , Idoso , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Immune system-based approaches for the treatment of malignant disease over the past decades have often focused on cytolytic effector cells such as cytotoxic T lymphocytes (CTL), and natural killer (NK) cells. It has also been demonstrated that tumor-bearing mice can be cured using a wide variety of approaches, some of which involve cytokine-mediated enhancement of CTL and NK cell activity. However, the apparent success in mice stands in contrast to the current situation in the clinic, wherein only a minority of patients have thus far benefited from CTL- or NK cell-based antitumor approaches. The underlying causes of tumor-associated immune suppression of CTL and NK cell activity are discussed, and features of interest shared with HIV infection, leprosy, and rheumatoid arthritis are also be mentioned. Remarkable and very recent observations have shed more light upon the causes of dysfunctional alterations in CTL and NK cells often associated with these diseases, that in turn have suggested new immunotherapeutic approaches for cancer and infectious disease.
Assuntos
Doenças do Sistema Imunitário/imunologia , Imunidade Celular/imunologia , Neoplasias Experimentais/imunologia , Neoplasias/imunologia , Animais , Antígenos de Neoplasias/imunologia , Apoptose , Humanos , Doenças do Sistema Imunitário/complicações , Tolerância Imunológica/imunologia , Inflamação/imunologia , Células Matadoras Naturais/imunologia , Linfócitos do Interstício Tumoral , Camundongos , Neoplasias/complicações , Neoplasias Experimentais/complicações , Oxirredução , Transdução de Sinais/imunologia , Linfócitos T Citotóxicos/imunologiaRESUMO
Whereas transplantable tumors can be readily cured with immunotherapeutic approaches, similar therapies in cancer patients have been less effective. This difference may be explained by an immunosuppression resulting from the presence of a slowly growing primary tumor in the patient, whereas the immune system in a mouse with a rapidly proliferating transplantable tumor would be less affected. As a more appropriate model to the immune dysfunction in patients, slowly progressing primary tumors were induced by the carcinogen methylcholanthrene (MC) in mice. Their ability to induce immunosuppression in T cells and natural killer (NK) cells was compared to that of rapidly growing transplanted MC-induced tumors. The results demonstrate that mice bearing primary MC tumors had significantly diminished T-cell and NK-cell functions, impaired capacity to produce Th1 cytokines, and markedly reduced levels of the signal-transducing zeta chain in T cells and NK cells, similar to that described in cancer patients. Moreover, a substantial number of CD8+ T cells in mice with large primary MC tumors were undergoing apoptosis, correlating with alterations in CD4/CD8 ratios. In contrast, T cells and NK cells from mice bearing rapidly growing transplanted tumors were only marginally affected. These findings could explain the apparent discrepancy between the consistent findings of a diminished immune response and alterations in signal transduction in cancer patients as compared to the less reproducible observations in murine transplantable tumors. In addition, they could explain the differences in the high efficacy of immunotherapy in mice with transplantable tumors and the low therapeutic results in cancer patients.
Assuntos
Apoptose , Tolerância Imunológica , Células Matadoras Naturais/imunologia , Sarcoma Experimental/imunologia , Transdução de Sinais , Linfócitos T/imunologia , Animais , Complexo CD3/imunologia , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos/efeitos dos fármacos , Carcinógenos , Citocinas/biossíntese , Citocinas/imunologia , Citotoxicidade Imunológica , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/patologia , Metilcolantreno , Camundongos , Transplante de Neoplasias , Receptores de Antígenos de Linfócitos T gama-delta/biossíntese , Sarcoma Experimental/etiologia , Sarcoma Experimental/patologia , Baço/efeitos dos fármacos , Baço/imunologia , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/patologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia , Células Th1/efeitos dos fármacos , Células Th1/imunologiaRESUMO
Benign paroxysmal positional vertigo (BPPV) is one of the common vestibular disorders. Canalolithiasis is thought to be a likely lesion. A canalith repositioning procedure (CRP by Epley) generally yields good resolution of vertigo and nystagmus. The authors confirmed the efficacy of this procedure on typical BPPV of the posterior semicircular canal type. We designed a new procedure for BPPV of the lateral canal type, which also yielded satisfactory results. BPPV sometimes presents a nystagmus pattern, which suggests multiple lesions. We have seen eight cases of BPPV showing nystagmus that combines both the posterior and the lateral canal types. Combined CRP was performed on these cases, which again gave good clinical results. Other BPPV cases were associated with central lesions. We must be aware that BPPV may involve multiple canals and may be associated with central lesions.
Assuntos
Postura/fisiologia , Vertigem/diagnóstico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nistagmo Patológico/fisiopatologia , Modalidades de Fisioterapia , Canais Semicirculares/fisiopatologia , Vertigem/fisiopatologia , Vertigem/reabilitaçãoRESUMO
To clarify the effect of lead exposure on peripheral hemodynamics, acceleration plethysmography (APG) was performed for 48 male subjects occupationally exposed to lead (exposure group) and 43 male subjects with no history of occupational exposure to lead (control group). In the exposure group, the blood lead concentration (Pb-B) was also measured. Each APG parameter was assessed by comparing measured data with the standard aging curves. A significant negative correlation was obtained between the parameter--b/a and Pb-B. The exposure group showed significantly lower values of parameters--b/a (p < 0.01) and d/a (p < 0.05) than the control group. The parameter--b/a in the exposure group dose-dependently decreased with increases in length of working career (duration of exposure to lead) and Pb-B. The parameter--b/a significantly (p < 0.05) decreased in subjects with working careers of 5 years or more and in subjects whose Pb-B was 40 micrograms/100 ml or more. These results suggest that lead exposure affects peripheral hemodynamics as evaluated by APG.
Assuntos
Hemodinâmica/efeitos dos fármacos , Chumbo/efeitos adversos , Exposição Ocupacional , Adulto , Fatores Etários , Relação Dose-Resposta a Droga , Humanos , Chumbo/sangue , Masculino , Pessoa de Meia-Idade , Pletismografia/métodosRESUMO
The purpose of this study was to evaluate selective caries removal using an air-abrasive technique. Alumina powders, glass beads, crushed glass powders, and crushed powders of polycarbonate resin were applied to intact human enamel, dentin, and artificially demineralized dentin (caries-model dentin). Furthermore, the effect of the particle size of abrasives and air pressures on the abraded depths was examined. When alumina powders and glass beads were used, the abraded depths of enamel, dentin, and caries model increased as the particle size and air pressure increased. Alumina powders and crushed glass powders abraded intact enamel and dentin more than the caries-model dentin, whereas glass beads abraded the caries-model dentin more than the intact enamel and dentin. Only crushed powders of polycarbonate resin abraded the caries-model dentin without reducing intact enamel and dentin. With hard particles, such as alumina powders, glass beads, or crushed glass powders, selective caries removal by the air-abrasive technique appeared to be difficult to achieve, even if the particle size and the air pressure were changed. Crushed powders of polycarbonate resin that reduced only the caries-model dentin are harder than caries-model dentin, but softer than intact enamel and dentin. This study elucidated the possibility of selective carious dentin removal with the air-abrasive technique.