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1.
Ann Oncol ; 28(2): 285-291, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28426104

RESUMO

Background: Amrubicin is approved for treating non-small-cell lung cancer (NSCLC) and small-cell lung cancer. However, no direct comparisons between amrubicin and docetaxel, a standard treatment for NSCLC, have been reported. Patients and methods: We conducted a randomized phase III trial of Japanese NSCLC patients after one or two chemotherapy regimens. Patients were randomized to amrubicin (35 mg/m2 on days 1-3 every 3 weeks) or docetaxel (60 mg/m2 on day 1 every 3 weeks). Outcomes included progression-free survival, overall survival, tumor responses, and safety. Results: Between October 2010 and June 2012, 202 patients were enrolled across 32 institutions. Median progression-free survival (3.6 versus 3.0 months; P = 0.54) and overall survival (14.6 versus 13.5 months; P = 0.86) were comparable in the amrubicin and docetaxel groups, respectively. The overall response rate was 14.4% (14/97) and 19.6% (19/97) in the amrubicin and docetaxel groups, respectively (P = 0.45). The disease control rate was 55.7% in both groups. Adverse events occurred in all patients, and included grade ≥3 neutropenia occurred in 82.7% and 78.8% of patients in the amrubicin and docetaxel groups, respectively, grade ≥3 leukopenia occurred in 63.3% and 70.7%, and grade ≥3 febrile neutropenia occurred in 13.3% and 18.2% of patients in the amrubicin and docetaxel groups, respectively. Of eight cardiac-related events in the amrubicin group, three were considered related to amrubicin and resolved without treatment discontinuation. Conclusions: This was the first phase III study to compare amrubicin and docetaxel in patients with pretreated NSCLC. Amrubicin did not significantly improve the primary endpoint of PFS compared with docetaxel. Clinical trial registration: NCT01207011 (ClinicalTrials.gov).


Assuntos
Antraciclinas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Taxoides/uso terapêutico , Idoso , Antraciclinas/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Intervalo Livre de Doença , Docetaxel , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Taxoides/efeitos adversos , Resultado do Tratamento
2.
Curr Cancer Drug Targets ; 10(7): 758-71, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20578986

RESUMO

DNA topoisomerase II enzymes regulate essential cellular processes by altering the topology of chromosomal DNA. These enzymes function by creating transient double-stranded breaks in the DNA molecule that allow the DNA strands to pass through each other and unwind or unknot tangled DNA. Because of the integral role of topoisomerases in regulating DNA metabolism, these enzymes are vital for cell survival. Several clinically active antitumor agents target these enzymes. Mammalian cells contain two topoisomerase II isozymes that are encoded by different genes: topoisomerase IIα and IIß. Although, both isozymes are homologous and exhibit similar catalytic activity, they are differentially regulated and are involved in distinct biological functions. The topoisomerase IIα and topoisomerase IIß enzymes are regulated by post-translational modifications, including sumoylation, ubiquitination and phosphorylation. These post-translational modifications influence the biologic and catalytic activity of the enzyme and affect sensitivity of cells to topoisomerase II-targeted drugs. In this review, we describe how the catalytic and biologic activity of the topoisomerase II enzyme is regulated and discuss the mechanisms by which chemotherapeutic agents that target these enzymes function. Given the potential importance of site-specific modifications, in particular phosphorylation, in regulating sensitivity to topoisomerase II-targeted drugs, we discuss the potential role of altered topoisomerase II phosphorylation in development of drug resistance, which is often a limiting factor in the treatment of cancer.


Assuntos
DNA Topoisomerases Tipo II/metabolismo , Neoplasias/tratamento farmacológico , Inibidores da Topoisomerase II/farmacologia , Animais , DNA Topoisomerases Tipo II/química , Resistencia a Medicamentos Antineoplásicos , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Terapia de Alvo Molecular , Neoplasias/metabolismo , Fosforilação/efeitos dos fármacos , Domínios e Motivos de Interação entre Proteínas , Inibidores da Topoisomerase II/efeitos adversos , Inibidores da Topoisomerase II/uso terapêutico
3.
Leukemia ; 20(10): 1809-18, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16932348

RESUMO

Among the topoisomerase (topo) II isozymes (alpha and beta), topo IIbeta has been suggested to regulate differentiation. In this study, we examined the role of topo IIbeta in all-trans retinoic acid (ATRA)-induced differentiation of myeloid leukemia cell lines. Inhibition of topo IIbeta activity or downregulation of protein expression enhanced ATRA-induced differentiation/growth arrest and apoptosis. ATRA-induced apoptosis in topo IIbeta-deficient cells involved activation of the caspase cascade and was rescued by ectopic expression of topo IIbeta. Gene expression profiling led to the identification of peroxiredoxin 2 (PRDX2) as a candidate gene that was downregulated in topo IIbeta-deficient cells. Reduced expression of PRDX2 validated at the mRNA and protein level, in topo IIbeta-deficient cells correlated with increased accumulation of reactive oxygen species (ROS) following ATRA-induced differentiation. Overexpression of PRDX2 in topo IIbeta-deficient cells led to reduced accumulation of ROS and partially reversed ATRA-induced apoptosis. These results support a role for topo IIbeta in survival of ATRA-differentiated myeloid leukemia cells. Reduced expression of topo IIbeta induces apoptosis in part by impairing the anti-oxidant capacity of the cell owing to downregulation of PRDX2. Thus, suppression of topo IIbeta and/or PRDX2 levels in myeloid leukemia cells provides a novel approach for improving ATRA-based differentiation therapy.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , DNA Topoisomerases Tipo II/metabolismo , Proteínas de Ligação a DNA/metabolismo , Leucemia Mieloide/metabolismo , Tretinoína/farmacologia , Apoptose/fisiologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Divisão Celular/efeitos dos fármacos , Divisão Celular/fisiologia , DNA Topoisomerases Tipo II/genética , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/genética , Dicetopiperazinas , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Inibidores Enzimáticos/farmacologia , Regulação Enzimológica da Expressão Gênica , Regulação Leucêmica da Expressão Gênica , Células HL-60 , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Leucemia Mieloide/patologia , Leucemia Mieloide/fisiopatologia , Peroxidases/genética , Peroxidases/metabolismo , Peroxirredoxinas , Piperazinas/farmacologia , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Inibidores da Topoisomerase II
4.
Kekkaku ; 76(10): 673-6, 2001 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-11712389

RESUMO

This paper describes two cases with tuberculous epididymitis. The first case was a 69-year-old man who was admitted to our hospital because of ulceration or right scrotum. Physical examination revealed a hard, rounded, a little bigger than egg-sized mass in the right scrotum. The second case was a 40-year-old man who was admitted to our hospital because of cough, fever and body weight loss. He was treated for pulmonary tuberculosis with isoniazid, rifampicin, streptomycin and pyrazinamide. Six months after admission, he complained of a painless swelling of the right scrotum. Physical examination revealed a hard, rounded, more than egg-sized mass in the right scrotum. Right orchiectomy was performed in these two cases, and they were cured.


Assuntos
Epididimite/cirurgia , Orquiectomia , Tuberculose dos Genitais Masculinos/cirurgia , Adulto , Idoso , Epididimite/complicações , Humanos , Masculino , Tuberculose dos Genitais Masculinos/complicações , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/tratamento farmacológico
5.
J Med ; 32(5-6): 301-9, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11958276

RESUMO

A 63-year-old female was admitted because of cardiogenic shock due to complete rupture of the posterior papillary muscle. The diagnosis was made by echocardiography. She was treated successfully by an emergency replacement of the mitral valve. Early diagnosis and surgical treatment are mandatory and life-saving in the case of complete papillary muscle rupture.


Assuntos
Infarto do Miocárdio/complicações , Músculos Papilares/lesões , Angiografia Coronária , Ecocardiografia , Serviços Médicos de Emergência , Feminino , Próteses Valvulares Cardíacas , Humanos , Pessoa de Meia-Idade , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Mitral/cirurgia , Infarto do Miocárdio/diagnóstico por imagem , Músculos Papilares/diagnóstico por imagem , Músculos Papilares/patologia , Músculos Papilares/cirurgia , Ruptura/etiologia
6.
Biol Trace Elem Res ; 77(2): 149-58, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11101047

RESUMO

Marker elements were estimated from the red cosmetics collected from different ancient burials and mine ruins in three separate districts of Japan. Element levels were displayed in reference to the relative amount to sulfur (RA/S), by which the cosmetics were divided into five types: I--a low Hg/S with a low Fe/S; II--both moderate Hg/S and Fe/S; III--a moderate Hg/S with a high Fe/S; III 2--a high Hg/S with a moderate Fe/S; IV--a high Hg/S with a high Fe/S. The cosmetics can be further characterized by referring to other contaminants such as Zn, Cu, and Mn. These combined analyses with contaminant metals were capable of characterizing the origins of the cosmetics; it is useful to compare them to each other. The cosmetics were identified as being due to several groups of contaminants from ancient mines in Japan, and also with this system analysis of the markers it is possible to identify them from neighboring countries.


Assuntos
Arqueologia , Cosméticos , Oligoelementos/análise , Osso e Ossos/química , Humanos , Ferro/análise , Japão , Mercúrio/análise , Poluentes do Solo/análise , Enxofre/análise
7.
Acta Med Okayama ; 54(4): 179-84, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10985178

RESUMO

Although the rehabilitation of patients with chronic obstructive pulmonary disease (COPD) improves both exercise capacity and quality of life, a standard protocol for COPD patients has not been established. To clarify whether physiologic and quality-of-life improvements can be achieved by an inpatient pulmonary rehabilitation program 5 days per week for 3 weeks, 18 patients with COPD were enrolled in a rehabilitation program. The physical exercise training regimen consisted of respiratory muscle stretch gymnastics and cycle ergometer exercise training. Pulmonary function tests, an incremental ergometer exercise test, a 6-min walking test, and a quality of life assessment by the Chronic Respiratory Questionnaire were administered before and after the program. The peak VO2, an indicator of maximal exercise capacity, did not increase, although the 6-min walking distance, an indicator of functional exercise capacity, increased significantly after rehabilitation. There was a significant improvement in the quality of life in terms of dyspnea, fatigue, and emotional state. These findings suggest that even a 3-week program may be beneficial for COPD patients. Increases in functional exercise capacity, even without an increase in maximal exercise capacity, are helpful for reducing dyspnea and improving quality of life parameters in patients with COPD.


Assuntos
Pneumopatias Obstrutivas/fisiopatologia , Pneumopatias Obstrutivas/reabilitação , Resistência Física , Qualidade de Vida , Idoso , Dispneia/prevenção & controle , Teste de Esforço , Feminino , Ginástica , Humanos , Masculino , Pessoa de Meia-Idade , Educação Física e Treinamento , Testes de Função Respiratória , Fatores de Tempo , Caminhada
8.
Acta Histochem ; 102(2): 231-8, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10824615

RESUMO

SDH activity and its frequency distributions were determined cytophotometrically to investigate the change in respiratory oxidative energy metabolism in Paramecium caudatum (P. caudatum) cell populations during their growth in cell culture. Cells from 3 separate cultures were examined on day 2, 5 and 11 post-inoculation as measures of logarithmic, early and late stationary phases, respectively. SDH activity per individual cell is expressed as the increase in total absorbance (TA) at 590 nm of nitroblue tetrazolium (Nitro BT) formazans per min per cell area in a specimen (deltaTA/min/microm2) to exclude the influence of cell size on the data. On day 5, the mean SDH activity was higher, being approx 140% of that on day 2 and decreased significantly to only approx 11% at day 11. As the mean SDH activity rose, a certain portion of the cells demonstrated a wider range of activity than on day 2 leading to an increase in the width of the SDH activity-frequency distribution. Moreover, on day 11, approx 85% of cells shifted toward the lowest range of activity with further increase in width of the distribution as the mean activity declined. These findings suggest that the respiratory oxidative energy metabolism in P. caudatum cells rise while the cells change from logarithmic to early stationary phases and decays during late stationary phase with increase in its extent of variety within cell populations.


Assuntos
Paramecium/enzimologia , Paramecium/crescimento & desenvolvimento , Succinato Desidrogenase/metabolismo , Animais , Citofotometria , Metabolismo Energético/fisiologia , Oxirredução , Consumo de Oxigênio/fisiologia
9.
Br J Cancer ; 79(5-6): 984-90, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10070901

RESUMO

A combination chemotherapy of irinotecan (CPT-11) and cisplatin (CDDP) has been reported to be active for lung cancer. In the previous trial, however, diarrhoea and leucopenia became the major obstacle for sufficient dose escalation of CPT-11 to improve the treatment outcome. We conducted a phase I study to investigate whether the fractionated administration of CDDP and CPT-11 at escalated dose was feasible and could improve the treatment outcome. Twenty-four previously untreated patients with unresectable non-small-cell lung cancer (NSCLC) or extensive disease of small-cell lung cancer (SCLC) were eligible. Both CDDP and CPT-11 were given on days 1 and 8, and repeated every 4 weeks. The dose of CDDP was fixed at 60 mg m(-2) and given by 1-h infusion before CPT-11 administration. The starting dose of CPT-11 was 40 mg m(-2), and the dose was escalated by an increase of 10 mg m(-2). The maximally tolerated dose of CPT-11 was determined as 60 mg m(-2) because grade 4 haematological or grade 3 or 4 non-haematological toxicities developed in six patients out of 11 patients evaluated. Diarrhoea became a dose-limiting toxicity. The objective response rates were 76% for NSCLC and 100% for SCLC. The recommended dose of CPT-11 and CDDP in a phase II study will be 50 mg m(-2) and 60 mg m(-2) respectively.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/análogos & derivados , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/tratamento farmacológico , Cisplatino/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/farmacocinética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Pequenas/patologia , Cisplatino/administração & dosagem , Cisplatino/farmacocinética , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Hemoglobinas/efeitos dos fármacos , Humanos , Irinotecano , Contagem de Leucócitos/efeitos dos fármacos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Contagem de Plaquetas/efeitos dos fármacos
10.
Oncol Rep ; 6(1): 75-80, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-9864405

RESUMO

Synchronous primary lung cancer (SPLC) occurs in up to 0.5% of patients with lung cancer. Among SPLC cases, coexistence of small cell carcinoma (SCLC) and non-small cell carcinoma has been reported in a very small fraction. Futhermore, there have been no reports discussing treatment and prognosis of SPLC presenting with SCLC and NSCLC. We report on two cases of SPLC presenting SCLC in limited stage and operable NSCLC. One patient developed synchronously SCLC and adenocarcinoma of the lung, while the other SCLC and squamous cell carcinoma of the lung. The clonal origin of these synchronous lung cancers was evaluated using immunohistochemical and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analyses. Both of the patients were diagnosed based on transbronchial lung biopsy (TBLB) and mediastinoscopic biopsy. They were successfully treated with chemoradiotherapy and adjuvant surgery, and are now doing well without any signs of tumor progression for about one year. In both cases, a response of mediastinal lymph node for concurrent chemoradiotherapy was quite different from that of the mass in the lung field. In case 2, p53 mutation was observed in the SCLC tissue, but not in the NSCLC tissue by PCR-SSCP. In both cases, carcinoembryonic antigen was documented in the NSCLC tissue, but not in the SCLC tissue by immunohistochemical staining. This report indicates the importance of the accurate diagnosis of SPLC by employing TBLB and/or media-stinoscopy for the optimal treatment of patients having SPLC presenting with SCLC and NSCLC. Diagnostic criteria and standard treatment of this disease should be established.


Assuntos
Adenocarcinoma/patologia , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Pulmonares/patologia , Neoplasias Primárias Múltiplas , Adenocarcinoma/química , Adenocarcinoma/diagnóstico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Broncoscopia , Antígeno Carcinoembrionário/análise , Carcinoma de Células Pequenas/química , Carcinoma de Células Pequenas/diagnóstico , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/radioterapia , Carcinoma de Células Pequenas/cirurgia , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Cisplatino/administração & dosagem , Terapia Combinada , Etoposídeo/administração & dosagem , Evolução Fatal , Genes p53 , Humanos , Queratinas/análise , Neoplasias Pulmonares/química , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Masculino , Mediastinoscopia , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/tratamento farmacológico , Neoplasias Primárias Múltiplas/radioterapia , Neoplasias Primárias Múltiplas/cirurgia , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Isoformas de Proteínas/análise , Indução de Remissão , Proteína Supressora de Tumor p53/análise
11.
Acta Histochem ; 100(4): 395-408, 1998 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9842419

RESUMO

Phosphohydrolytic activity was cytochemically characterized in Paramecium caudatum, a ciliated protozoa, at neutral pH. We stained cells in the presence of several mononucleotides as substrates, namely adenosine 5'-monophosphate (5'-AMP), adenosine 2'-monophosphate, guanosine 5'-monophosphate (5'-GMP) and beta-glycerophosphate (beta-GLP) using a lead capture method at 37 degrees C. Cells were also incubated in the presence of 5'-AMP with the inhibitor for alkaline phosphatase, tetramisole. In all cases, varying amounts of final reaction product, lead sulfide, was observed in Paramecium cytoplasm. Tetramisole did not have any effect on Paramecium 5'-AMP hydrolytic activity. The phosphohydrolytic activity was measured as the increase in total absorbance of "test minus control" reactions at 440 nm per unit time after 20 min of incubation using a microphotometric system for image analysis that has been developed by us. From the relationship between the concentrations of 5'-AMP and activity, an apparent K(m) value was estimated to be 0.20 mM. These results suggest that mononucleotides and phosphate monoesters are hydrolyzed by one or more enzymes with wide substrate specificity in P. caudatum. All the activity distribution patterns in Paramecium cultures, that were tested, were monomodal. The mean activity for 5'-AMP hydrolysis widely varied in these cultures. To investigate substrate affinity, distribution patterns and mean activity with 5'-AMP as substrate were compared with those in the presence of 2 other substrates, 5'-GMP and beta-GLP. Affinity of the enzyme(s) was similar for 5'-AMP and 5'-GMP and lower for beta-GLP.


Assuntos
Paramecium/enzimologia , Monoéster Fosfórico Hidrolases/metabolismo , Monofosfato de Adenosina/metabolismo , Animais , Glicerofosfatos/metabolismo , Guanosina Monofosfato/metabolismo , Concentração de Íons de Hidrogênio , Processamento de Imagem Assistida por Computador , Especificidade por Substrato , Tetramizol/farmacologia
12.
Nihon Kokyuki Gakkai Zasshi ; 36(1): 18-22, 1998 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-9611971

RESUMO

Seventeen cases of benign asbestos pleurisy were evaluated clinically. All cases were male and almost all cases were more than 60 years-old. Most cases presented with chief complaints of chest pain and dyspnea, but 2 cases had no complaints. Pleural effusion appeared predominantly in the right side. Six cases had 2 or 3 episodes of pleural effusion, and 1 case had 5. Ten cases had an occupational history of asbestos exposure in shipyards and 5 other cases had a history in building construction. Almost all cases had more than 30 years of exposure to asbestos and benign asbestos pleurisy appeared after more than 30 years from the first exposure to asbestos. Among the patients, 6 cases had diffuse pleural thickening and 2 cases had malignancies. Pleural fluid was bloody in 14 of 17 cases (82%) and all pleural fluid showed an exudate. Lymphocytes represented 70% and eosinophils 15% of the cellular population of the pleural fluid. Hyaluronic acid in pleural fluid in cases of benign asbestos pleurisy averaged 29.5 micrograms/ml, which was significantly (p < 0.05) lower than in malignant pleural mesothelioma. Leukocytosis in peripheral blood and a high CRP value were uncommon in benign asbestos pleurisy.


Assuntos
Asbestose/complicações , Exposição Ocupacional , Derrame Pleural/etiologia , Idoso , Biomarcadores/análise , Proteína C-Reativa/análise , Humanos , Ácido Hialurônico/análise , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Derrame Pleural/metabolismo , Fatores de Tempo
13.
Acta Histochem ; 100(1): 25-36, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9542579

RESUMO

We measured in situ the activity of succinate dehydrogenase (SDH), one of the mitochondrial marker enzymes, in single Paramecium cells. SDH activity was detected with nitroblue tetrazolium (Nitro BT). Images of cells were captured every 30 sec at 590 nm, nearly the isosbestic wavelength of two reduction products of Nitro BT, by using a microphotometric system for image analysis. Activity was estimated by the slope of linear regression lines representing the relationship between total absorbance of the processed image and delta reaction time (real reaction time minus 30 sec). To investigate individual differences in Paramecium cell populations, SDH activity was measured in cells at various succinate concentrations. Paramecium SDH showed bimodal activity distribution patterns at three of four succinate concentrations tested. This result suggests that there are two groups of Paramecium populations with different SDH activity under control culture conditions. On the basis of the relationship between SDH activity and succinate concentration, mean Vmax and apparent Km values were estimated. A Km of 3.2 mM was found for Paramecium.


Assuntos
Paramecium/enzimologia , Succinato Desidrogenase/metabolismo , Animais , Ativação Enzimática , Processamento de Imagem Assistida por Computador , Cinética , Mitocôndrias/enzimologia , Nitroazul de Tetrazólio/metabolismo , Oxirredução , Paramecium/citologia
14.
Am J Otol ; 18(3): 332-5, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9149827

RESUMO

OBJECTIVE: The aim of this study was to investigate audiologic features and the lesion site of sensorineural deafness with mitochondrial DNA mutation at position 3243. STUDY DESIGN: Case review. SETTING: The study was conducted at the Kochi Medical School. PATIENTS: A case of sensorineural deafness in a patient who had a mitochondrial DNA mutation was presented. The incidence of deafness and diabetes mellitus (DM) was very high in the patient's family, but she did not have DM. MAIN OUTCOME MEASURES: The patient's mitochondrial DNA was examined. Furthermore, the pure-tone audiogram, the Bekesy audiogram, an auditory brain stem response, and the electrocochleogram were analyzed. RESULTS: The patient's mitochondrial DNA had a point mutation at codon 3243 (A-->G). The pure-tone audiogram showed moderate sensorineural deafness. An auditory brain stem response showed normal latencies. The electrocochleogram showed an enhanced negative summating potential. CONCLUSIONS: It was speculated that the lesion site of the auditory system was the inner ear. The possible sites in the inner ear were hair cells, the stria vascularis, and the endolymphatic sac.


Assuntos
DNA Mitocondrial , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/genética , Mutação Puntual , Adulto , Audiometria de Resposta Evocada , Audiometria de Tons Puros , Sequência de Bases , Códon , Diabetes Mellitus Tipo 1 , Potenciais Evocados Auditivos do Tronco Encefálico , Feminino , Humanos , Dados de Sequência Molecular
15.
Nihon Kyobu Shikkan Gakkai Zasshi ; 34 Suppl: 87-91, 1996 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-9216192

RESUMO

Here we review the current treatments for small-cell lung cancer. Cisplatin and etoposide, combined with concurrent or alternating thoracic irradiation, have been considered to be the standard therapy for patients with limited disease. Dose-intensive weekly chemotherapy and high-dose chemotherapy with autologous stem cell transplantation have failed to increase survival in patients with extensive disease. Promising new drugs such as irinotecan and taxol may improve survival in patients with extensive disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Irinotecano , Paclitaxel/administração & dosagem
16.
Clin Chem ; 42(10): 1616-20, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8855144

RESUMO

The serum concentration of free thyroxine (FT4) is often low in patients with chronic renal failure (CRF) with low serum concentrations of triiodothyronine (T3). We evaluated the serum FT4 concentration by using both an equilibrium dialysis RIA kit (D-FT4) and a labeled-antibody kit (M-FT4) in two different groups of CRF patients, undergoing chronic hemodialysis (HD, n = 145) or not (non-HD, n = 30), and in a group of normal healthy subjects (n = 58). Thyroid peroxidase antibodies and thyroglobulin antibodies were not detected in any patient. Serum FT4 concentrations (mean +/- SD, pmol/L) by the D- and M-FT4 assays were, respectively, 21.5 +/- 4.6 and 16.6 +/- 2.0 in the healthy subjects, 17.8 +/- 4.3 and 13.9 +/- 3.6 in the non-HD patients, and 16.9 +/- 4.9 and 10.7 +/- 1.9 in the HD patients. By the D-FT4 assay, results for both CRF groups were significantly different from those for the healthy group (P <0.01), as were the results for each pair of groups by the M-FT4 assay (P <0.01). FT4 values were reported as being within the healthy reference range by D-FT4 in 73 of 113 HD subjects who had low T3 and low M-FT4 values. Serum FT4 concentrations measured by both assay kits showed a significant inverse correlation with the serum concentration of creatinine (P <0.01), but the serum concentrations of sex-hormone-binding globulin did not differ significantly among the three groups. Our results indicate that the low FT4 concentration measured by D-FT4 in patients with CRF, particularly those on HD, probably reflects the actual, mild nonthyroidal illness of renal failure.


Assuntos
Diálise/métodos , Falência Renal Crônica/sangue , Tiroxina/sangue , Adulto , Ácidos Graxos não Esterificados/sangue , Feminino , Heparina/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Radioimunoensaio , Kit de Reagentes para Diagnóstico , Valores de Referência , Tireotropina/sangue , Tri-Iodotironina/sangue
17.
Nihon Ronen Igakkai Zasshi ; 32(11): 747-55, 1995 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-8598631

RESUMO

The aim of this study was to clarify whether the control state of fasting blood sugar can influence the occurrence of diabetic microangiopathy and macroangiopathy even in elderly patients with diabetes mellitus. In Kochi Prefecture 18 internal physicians participated in evaluating clinical courses of 898 patients, consisting of 466 males and 432 females, for an average of 69 months. Elderly cases aged 65 years or more old (group 1) consisted of patients who were aged 71.8 +/- 5.2 years old (M +/- SD). The average age of 481 adult cases under 65 years of age (group II) was 54.4 +/- 8.4 years old. Between the good and poor control groups, there was no difference in terms of blood pressure, body mass index (BMI) and serum lipids. Arteriosclerotic diseases such as myocardial infarction, cerebral infarction and arteriosclerosis obliterans appeared about as frequently in both the good and the poor control groups, while microangiopathies such as retinopathy, nephropathy and neuropathy were significantly more frequent in the poor control group compared to the good control group. The same tendency concerning these complications was seen in group II. Concerning treatment, diet treatment without drug treatment was significantly more frequent in the good control group compared to the poor control group, while hypoglycemic agents and subcutaneous insulin injection were used more often in the poor control group, the more severe state of diabetes mellitus in the latter group. Concerning the main reasons for good control, successful diet treatment was cited most often, followed by regular intake of medications. On the other hand disturbed diet treatment was the most frequent reason for poor control, indicating the strategic importance of diet treatment. Arteriosclerotic diseases were found more often in group I than group II, while the frequency of microangiopathies was similar. Concerning sexes, male patients tended to suffer more often from arteriosclerotic diseases than female patients, but the frequency of microangiopathy was similar. From the above findings it was concluded that poor control of fasting blood sugar level was related to microangiopathies in both non-elderly adult and elderly patients.


Assuntos
Glicemia/metabolismo , Angiopatias Diabéticas/sangue , Idoso , Arteriosclerose/complicações , Angiopatias Diabéticas/dietoterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Eur J Appl Physiol Occup Physiol ; 60(6): 407-11, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-2390979

RESUMO

Secreta from the palm and forearm was sampled for 1-min periods by a new technique, using a glass cylinder. Subjects exercised for 10-min periods at successive intensities of 40%, 50% and 65% VO2max with a leg ergometer operated in the supine position. Changes in the concentrations (values) of Na+, K+ and Cl- in their secreta during exercise were investigated. Significant positive correlations were found between the values of any two electrolytes in samples from the palm or the forearm, but the correlations between values for any one of the three electrolytes from the two sites were not significant. Values for concentrations of the electrolytes were significantly higher in samples from the palm than in those from the forearm at rest, 10 min after the beginning of exercise and at the end of exercise. No significant correlation was found between values for electrolytes in samples from the palm and the exercise intensity, but values for Na+ in samples from the forearm increased stepwise with increase in exercise intensity, and similar tendencies were observed for values of K+ and Cl-. The values for the three electrolytes in samples from the forearm, but not the palm, were significantly correlated with values for blood lactate, the percentage of VO2max and the heart rate. These results suggest that the present technique is suitable for successive samplings of secreta from the forearm, and that values for the electrolytes in samples are useful indices of exercise intensity.


Assuntos
Eletrólitos/metabolismo , Exercício Físico , Pele/metabolismo , Cloretos/metabolismo , Antebraço , Mãos , Humanos , Lactatos/sangue , Ácido Láctico , Masculino , Concentração Osmolar , Consumo de Oxigênio , Potássio/metabolismo , Sódio/metabolismo
19.
Scand J Clin Lab Invest ; 48(2): 177-82, 1988 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-3358097

RESUMO

Six patients were found to have increased serum chloride concentrations when these concentrations were determined with an ion-selective electrode, but not when determined by continuous flow mercuric thiocyanate colorimetry or amperometric-coulometric titration. Their serum bromide levels of 1.8-8.0 mmol/l were much higher than those of 0.07-0.13 mmol/l in normal controls. The urinary bromide excretion, measured in two of these patients, was higher than that in normal subjects. No common symptoms or abnormalities in laboratory findings except hyperbromidaemia were found in these patients, who claimed not to have taken any drugs containing bromide. For determination of the incidence of subclinical hyperbromidaemia, the serum bromide concentrations were measured in sera of 1,323 outpatients sent to Tokushima University Hospital for routine measurements of blood chemistry over a one-month period. Five samples showed abnormally high bromide levels. It is concluded that subclinical hyperbromidaemia is not as rare as generally thought, though the aetiology of this state is unknown. Chloride determination with an ion-selective electrode can be used to screen for hyperbromidaemia, since increased levels of bromide ion result in apparently high chloride values.


Assuntos
Brometos/urina , Cloretos/sangue , Adulto , Idoso , Cromatografia por Troca Iônica , Colorimetria , Feminino , Humanos , Masculino , Microeletrodos , Pessoa de Meia-Idade , Espectrometria por Raios X
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