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2.
J Nanosci Nanotechnol ; 10(6): 4095-101, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20355421

RESUMO

Carbon nanotube (CNT) growth was carried out on SiO2/Si substrates with a Co catalyst using an alcohol gas source method in an ultra-high vacuum chamber. The resulting CNTs were characterized by scanning electron microscopy (SEM), Raman spectroscopy and transmission electron microscopy (TEM). Reducing the ethanol pressure decreased the optimum growth temperature for maximum yield, enabling single-walled carbon nanotube (SWNT) growth at 400 degrees C. By employing an Al2Ox buffer layer, SWNT yield increased several times, even at 400 degrees C. Under TEM observation, the Co particle size on the Al2Ox layers did not show a significant dependence on the growth temperature between 400 and 700 degrees C. Raman and TEM results confirmed activation of Co particles with larger diameter (>1 nm) by the Al2Ox buffer layer.

3.
Science ; 278(5337): 443-6, 1997 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-9334299

RESUMO

The formation of vibrationally excited heme upon photodissociation of carbonmonoxy myoglobin and its subsequent vibrational energy relaxation was monitored by picosecond anti-Stokes resonance Raman spectroscopy. The anti-Stokes intensity of the nu4 band showed immediate generation of vibrationally excited hemes and biphasic decay of the excited populations. The best fit to double exponentials gave time constants of 1.9 +/- 0.6 and 16 +/- 9 picoseconds for vibrational population decay and 3.0 +/- 1.0 and 25 +/- 14 picoseconds for temperature relaxation of the photolyzed heme when a Boltzmann distribution was assumed. The decay of the nu4 anti-Stokes intensity was accompanied by narrowing and frequency upshift of the Stokes counterpart. This direct monitoring of the cooling dynamics of the heme cofactor within the globin matrix allows the characterization of the vibrational energy flow through the protein moiety and to the water bath.


Assuntos
Heme/química , Mioglobina/química , Monóxido de Carbono/química , Fotólise , Fótons , Análise Espectral Raman , Temperatura , Termodinâmica
4.
Clin Exp Dermatol ; 34(5): e134-6, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19508579

RESUMO

Autoerythrocyte sensitization syndrome (AES) is characterized by recurrent, painful purpura or ecchymosis. Testing for the reappearance of lesions after injection of the patient's own erythrocytes is usually useful for the diagnosis of AES, but the significance of this test is still controversial. As the lesions often appear in patients with psychiatric disorders, mental factors such as depression and stress are considered to be involved in the occurrence and exacerbation of AES. We report a 28-year-old woman who presented recurrent episodes of painful purpura with vertigo and hemilateral auditory impairment after difficulties at her workplace. After the diagnosis of AES, she was referred for psychiatric counselling, after which the symptoms disappeared. These findings suggest that treatment for psychological disorders is important in patients with AES.


Assuntos
Doenças Autoimunes/psicologia , Eritrócitos/imunologia , Transtornos da Audição/psicologia , Transtornos Psicofisiológicos/diagnóstico , Vertigem/psicologia , Adulto , Feminino , Humanos , Púrpura/psicologia , Síndrome
5.
Clin Exp Dermatol ; 34(2): 171-3, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19187297

RESUMO

We report a patient with antineutrophil cytoplasmic antibody-associated vasculitis with oculomotor nerve palsy. The patient presented with a high fever, diplopia, blepharoptosis and impairment of ocular movement of the left eye except for lateral gaze. Multiple erythematous and livedoid lesions were observed on the forehead, both cheeks and both legs. Laboratory examination showed positive results for myeloperoxidase antineutrophil cytoplasmic antibodies. Skin biopsy revealed leucocytoclastic vasculitis of the small arteries in the lower dermis. The patient was successfully treated with systemic corticosteroids.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos , Blefaroptose/patologia , Diplopia/patologia , Doenças do Nervo Oculomotor/patologia , Vasculite/patologia , Corticosteroides/administração & dosagem , Idoso , Anticorpos Anticitoplasma de Neutrófilos/análise , Blefaroptose/complicações , Blefaroptose/tratamento farmacológico , Diplopia/complicações , Diplopia/tratamento farmacológico , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Doenças do Nervo Oculomotor/complicações , Doenças do Nervo Oculomotor/imunologia , Pulsoterapia , Vasculite/tratamento farmacológico , Vasculite/imunologia
6.
Eur J Ophthalmol ; 18(5): 848-51, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18850574

RESUMO

PURPOSE: To assess the usefulness of the method of oblique-parallel trocar insertion with conjunctival displacement to the corneal side in 25-gauge (G) transconjunctival vitrectomy. METHODS: 25-G vitrectomy was performed in 77 consecutive eyes. Before making obliqueparallel trocar insertions, the conjunctiva was conventionally displaced superiorly in 35 eyes, but was displaced toward the corneal side in 42 eyes. After surgery, the distance between the scleral and conjunctival wounds was measured with calipers. The frequency of scleral wound exposure was assessed. RESULTS: After cannula removal at the end of surgery, inferior repositioning of the superiorly displaced conjunctiva was observed, while marked posterior repositioning of the corneal side caused displacement of the conjunctiva due to gravity. The superior displacement distances between the sclera and conjunctival wounds were 2.4+/-0.3 mm at the infusion port, 2.0+/-0.4 mm at the superior temporal port, and 1.9+/-0.4 mm at the superior nasal port, while the corresponding distances for corneal side displacement were 3.6+/-0.5, 3.5+/-0.5, and 2.5+/-0.5mm, and were all significantly (p<0.0001) greater with corneal side displacement. The frequency of scleral wound exposure due to conjunctival damage around the cannula (infusion port) was significantly (p=0.0164) lower for corneal side displacement (0/42; 16.7%) than superior displacement (5/35; 14.3%). There was no postoperative endophthalmitis in all 77 patients studied. CONCLUSIONS: In 25-G transconjunctival vitrectomy, using oblique-parallel trocar insertions with the conjunctiva displaced toward the corneal side results in marked posterior repositioning of the conjunctiva after cannula extraction. Corneal side conjunctival displacement is technically easy and completely covers the scleral wound. This method is expected to be effective in preventing endophthalmitis.


Assuntos
Túnica Conjuntiva/cirurgia , Microcirurgia/métodos , Vitrectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Cateterismo/métodos , Córnea/anatomia & histologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
7.
Eur J Ophthalmol ; 18(4): 659-62, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18609496

RESUMO

PURPOSE: To examine the effectiveness of excising peripheral vitreous until the cannula tip is exposed to prevent vitreous prolapse through the scleral wound in 25-gauge transconjunctival vitrectomy. METHODS: Twenty-five-gauge vitrectomy was performed in 60 consecutive eyes. Peripheral vitrectomy was conducted until the cannula tip was exposed in 30 eyes and with conservation of the vitreous around the cannula in 30 eyes. Vitreous prolapse through the scleral wound was examined using a suction stick. RESULTS: Vitreous prolapse through the scleral wound was transparent, fine and short, and detectable only with the suction stick. The incidence of vitreous prolapse through the scleral wound was 0% (0 of 30 eyes) when peripheral vitreous was excised until the cannula tip was exposed, and 20% (6 of 30 eyes) when the vitreous around the cannula was conserved, with a significant difference between two groups (p=0.0237). In two of six eyes with vitreous prolapse, the scleral wound was open, but there was no leakage of intraocular fluid and normal ocular pressure was maintained. CONCLUSIONS: If peripheral vitrectomy is performed without excising the vitreous surrounding the cannula, there is a 20% risk of the vitreous prolapsing through the scleral wound. Vitreous prolapse through the scleral wound is difficult to detect because it is transparent, fine and short, and there is no intraocular fluid leakage. Therefore, detecting vitreous prolapse with a suction stick and appropriate intervention are important for preventing endophthalmitis.


Assuntos
Oftalmopatias/prevenção & controle , Microcirurgia/métodos , Esclera/cirurgia , Vitrectomia/métodos , Corpo Vítreo , Adulto , Idoso , Idoso de 80 Anos ou mais , Túnica Conjuntiva/cirurgia , Oftalmopatias/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prolapso
8.
Eur J Ophthalmol ; 17(5): 857-9, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17932869

RESUMO

PURPOSE: To report peripheral iridectomy using a 25-gauge vitreous cutter in a 42-year-old man with pupillary block due to adhesion of the internal iris surface to the continuous circular capsulorhexis. METHODS: A corneal opening was made at 10 o'clock during vitrectomy. A 25-gauge vitreous cutter was inserted into the anterior chamber with the port facing downward, and peripheral iridectomy at the 12 o'clock position was performed. The vitreous cutter was set at a cutting speed of 2500 cpm and the aspiration pressure at 600 mmHg. RESULTS: A 25-gauge vitreous cutter with a fine shaft could easily be inserted into the peripheral anterior chamber, and there was no contact with the corneal endothelium even when the anterior chamber became shallow in association with iridectomy. In this patient, pupillary block resolved with peripheral iridectomy, and ocular pressure was also controlled. CONCLUSIONS: 25-gauge peripheral iridectomy is a simple technique that permits iridectomy of appropriate size at any desirable location.


Assuntos
Iridectomia/métodos , Doenças da Íris/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Vitrectomia/métodos , Adulto , Capsulorrexe/efeitos adversos , Catarata/complicações , Retinopatia Diabética/complicações , Retinopatia Diabética/cirurgia , Humanos , Doenças da Íris/etiologia , Masculino , Complicações Pós-Operatórias , Acuidade Visual , Hemorragia Vítrea/complicações , Hemorragia Vítrea/cirurgia
9.
Int J Impot Res ; 18(4): 396-9, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16452997

RESUMO

The aim of the present study was to evaluate the relationship between motorcycling and erectile dysfunction (ED). We investigated the relationship between motorcycling and erectile function using the 5-items version of the International Index of Erectile Function (IIEF5) in 234 motorcyclists (response rate 75%) and 752 healthy controls (response rate 66%). In all, 161 (69%) of 234 motorcyclists were diagnosed as ED based on IIEF5. The prevalence of ED in the motorcycle group increased by age as: 58, 63, 76 and 93%, for motorcyclists in 20-29, 30-39, 40-49 and 50-59 years, respectively. There was a significant difference in the prevalence of ED between the motorcycle group and the control group in all age groups. On stepwise logistic regression analysis, motorcycling was the strongest risk factor for ED. Although the severity of ED in motorcyclists was not so severe, motorcycling may be one of risk factors for ED.


Assuntos
Disfunção Erétil/epidemiologia , Adulto , Fatores Etários , Idoso , Análise de Variância , Estudos de Casos e Controles , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Motocicletas/estatística & dados numéricos , Análise de Regressão
10.
Clin Nephrol ; 66(6): 440-6, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17176916

RESUMO

AIMS: To compare clinical data, sleep quality and health-related quality of life (HRQOL) with and without RLS in HD patients. MATERIALS AND METHODS: The international RLS study group diagnosis questionnaire was completed by 228 HD patients. The Pittsburg Sleep Quality Index (PSQI) for the evaluation of sleep quality and the Kidney Disease Quality of Life (KDQOL-SF) for the analysis of HRQOL were also used. RESULTS: 53 (23%) patients were diagnosed as RLS. Age and age at the initiation of HD were significantly younger in the RLS group. Serum calcium concentration (Ca) was significantly higher in the RLS group. Sleep quality evaluated by PSQI was significantly lower in the RLS group. In SF-36 domains of KDQOL-SF, bodily pain, general health perceptions, vitality, role functioning emotional, mental health and mental component score were significantly lower in the RLS group. In kidney targeted scales of KDQOL-SF, symptoms/problems, burden of kidney disease, cognitive function, quality of social interaction, sleep and patient satisfaction were significantly lower in the RLS group. CONCLUSION: High Ca was possibly connected to the pathophysiology of RLS which impaired sleep quality as well as HRQOL including mental health and many kidney disease related scales.


Assuntos
Cálcio/sangue , Falência Renal Crônica/terapia , Hormônio Paratireóideo/sangue , Qualidade de Vida , Diálise Renal/efeitos adversos , Síndrome das Pernas Inquietas , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/psicologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Diálise Renal/psicologia , Síndrome das Pernas Inquietas/sangue , Síndrome das Pernas Inquietas/etiologia , Síndrome das Pernas Inquietas/psicologia , Índice de Gravidade de Doença , Inquéritos e Questionários
11.
Cancer Res ; 55(3): 590-6, 1995 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-7834629

RESUMO

Cytotoxic chemotherapy has shown little antitumor activity against renal cell carcinoma (RCC). It has been demonstrated that RCC cells secrete interleukin 6 (IL-6) and express IL-6 receptors (IL-6Rs). IL-6 inhibits apoptosis and enhances manganese superoxide dismutase expression. Several anticancer chemotherapeutic agents exert their cytotoxic activity in part through the induction of apoptosis and the production of free radicals. Thus, the resistance of RCC cells to the anticancer agents might correlate with IL-6 expression. The present study tested this hypothesis by examining the effect of anti-IL-6 mAb and anti-IL-6R mAb on the sensitivity of human RCC cells to anticancer chemotherapeutic agents. Treatment of Caki-1 cells with anti-IL-6 mAb or anti-IL-6R mAb in combination with cis-diamminedichloroplatinum(II) (CDDP) or mitomycin C overcame their resistance to CDDP or mitomycin C. However, treatment of Caki-1 cells with anti-IL-6 mAb or anti-IL-6R mAb in combination with Adriamycin, vinblastine or 5-fluorouracil did not overcome their resistance to these anticancer agents. Treatment of CDDP-resistant Caki-1 cells (Caki-1/DDP), two other RCC cell lines (ACHN and A704), and three freshly derived RCC cells with CDDP in combination with anti-IL-6 mAb or anti-IL-6R mAb reversed the resistance to CDDP in all these tumors. We then studied the effectiveness of other platinum derivatives. Treatment of Caki-1 cells with anti-IL-6 mAb or anti-IL-6R mAb enhanced their sensitivity to carboplatin, but not to trans-diamminedichloroplatinum(II). Several experiments investigated the mechanism of the antibody-mediated sensitization of RCC cells to CDDP. Incubation of Caki-1 cells with anti-IL-6 mAb or anti-IL-6R mAb did not change the intracellular accumulation of CDDP. The expressions of the multidrug resistant phenotype (gp170) and c-myc oncogene were not affected by the antibody-mediated sensitization. Treatment of Caki-1 cells with the anti-IL-6 mAb or anti-IL-6R mAb down-regulated the expression of glutathione S-transferase pi mRNA. This study demonstrates that treatment of RCC cells with CDDP in combination with anti-IL-6 mAb or anti-IL-6R mAb can overcome their CDDP-resistance and that the down-regulation of glutathione S-transferase pi expression by anti-IL-6 mAb or anti-IL-6R mAb might play a role in the enhanced cytotoxicity obtained.(ABSTRACT TRUNCATED AT 400 WORDS)


Assuntos
Anticorpos Monoclonais/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Interleucina-6/imunologia , Receptores de Interleucina/imunologia , Carcinoma de Células Renais , Linhagem Celular , Sobrevivência Celular/imunologia , Cisplatino/metabolismo , Sinergismo Farmacológico , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Interleucina-6/análise , Interleucina-6/biossíntese , Neoplasias Renais , RNA Neoplásico/análise , Receptores de Interleucina-6 , Células Tumorais Cultivadas
12.
Cancer Res ; 60(11): 2912-8, 2000 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-10850437

RESUMO

Anti-Fas monoclonal antibody (mAb) kills Fas-expressing cells by apoptosis. Several anticancer agents also mediate apoptosis and may share common intracellular pathways leading to apoptosis with Fas. Thus, we reasoned that combination treatment of drug-resistant cells with anti-Fas mAb and drugs might overcome their resistance. We investigated whether anticancer agents enhance Fas-mediated apoptosis and cytotoxicity against renal cell carcinoma (RCC) cells. Treatment of ACHN RCC cells with anti-Fas mAb in combination with 5-fluorouracil, vinblastine, IFN-alpha, or IFN-gamma did not overcome resistance to these agents. However, combination treatment with anti-Fas mAb and Adriamycin (ADR) resulted in a synergistic cytotoxic effect. Furthermore, synergy was also obtained even when the exposure time was shortened from 24 h to 8 or 2 h. Synergy was also achieved in four other RCC cell lines and five freshly derived human RCC cells. Treatment with anti-Fas mAb in combination with epirubicin or pirarubicin also resulted in a synergistic cytotoxic effect on ACHN cells. Similar results were achieved with a combination of humanized anti-Fas mAb and ADR. Incubation of ACHN cells with ADR augmented the expression of Fas and p53, but not Bcl-2, Bax, or caspase-3. However, the activity of caspase-3 itself was apparently enhanced after treatment with ADR alone or combined treatment with anti-Fas mAb. The synergy obtained in cytotoxicity with anti-Fas mAb and ADR was also achieved in apoptosis. Exposure of ACHN cells and freshly derived RCC cells to ADR enhanced their susceptibility to lysis by peripheral blood lymphocytes and tumor-infiltrating lymphocytes. This study demonstrates that combination treatment of RCC cells with anti-Fas mAb and ADR might overcome their resistance. The sensitization required a low concentration of ADR and a short exposure time, thus supporting the potential in vivo application of a combination of ADR and anti-Fas mAb or immunotherapy in the treatment of ADR- and/or immunotherapy-resistant RCC.


Assuntos
Antineoplásicos/farmacologia , Carcinoma de Células Renais/patologia , Doxorrubicina/farmacologia , Neoplasias Renais/patologia , Proteínas Proto-Oncogênicas c-bcl-2 , Receptor fas/metabolismo , Laranja de Acridina/metabolismo , Antibióticos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Caspase 3 , Caspases/metabolismo , Relação Dose-Resposta a Droga , Doxorrubicina/análogos & derivados , Interações Medicamentosas , Epirubicina/farmacologia , Corantes Fluorescentes/metabolismo , Fluoruracila/farmacologia , Humanos , Imuno-Histoquímica , Interferon-alfa/farmacologia , Interferon gama/farmacologia , Linfócitos do Interstício Tumoral/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Fatores de Tempo , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/metabolismo , Vimblastina/farmacologia , Proteína X Associada a bcl-2 , Receptor fas/imunologia
13.
Biochim Biophys Acta ; 1485(2-3): 236-46, 2000 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-10832103

RESUMO

Using cross-species sequence homology, we cloned a cDNA for rat neutral sphingomyelinase (nSMase) composed of 422 amino acids that shares 87.6 and 79.0% identity with the mouse and human forms respectively. The rat nSMase expressed in Escherichia coli catalyzed sphingomyelin hydrolysis at neutral pH in a Mg(2+)-dependent manner, and required Triton X-100, dithiothreitol, and KCl for its full activity. The cloned rat enzyme shares conserved sequences with nSMases from both eukaryotes and prokaryotes. Introduction of single mutations into either of the histidine residues at positions 136 and 272, putative active sites, entirely abolished the activity, supporting a common mechanism for the nSMase family independent of the species. However, mutation in histidine 151, conserved only in eukaryotes, also abolished the activity, suggesting eukaryote-specific control of nSMase linked to this histidine 151. This enzyme also catalyzed the hydrolysis of lyso-platelet activating factor to yield 1-alkylglycerol at a rate that is slightly lower than that with sphingomyelin.


Assuntos
Histidina/genética , Esfingomielina Fosfodiesterase/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , DNA Complementar , Escherichia coli , Expressão Gênica , Histidina/metabolismo , Humanos , Masculino , Camundongos , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Fator de Ativação de Plaquetas/análogos & derivados , Fator de Ativação de Plaquetas/metabolismo , Ratos , Ratos Sprague-Dawley , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Esfingomielina Fosfodiesterase/metabolismo
14.
Int J Impot Res ; 17(4): 339-42, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15829991

RESUMO

The aim of this study was to assess the efficacy of sildenafil as the first-step tool for erectile dysfunction (ED) in Japanese males. Between March 1999 and March 2003, 281 patients were prescribed five tablets of sildenafil (50 mg) as the first step in the therapeutic management of ED. Of the 281 patients, 206 were evaluable patients. The overall success rate in achieving sexual intercourse in subjects after taking sildenafil was 77.2% (159/206), while 22.8% (47/206) were unsuccessful. The success rates in men with functional ED and organic ED were 91.4% (85/93) and 65.5% (74/113), respectively (P<0.0001). Overall, transient adverse effects of sildenafil occurred in 16 (8%) males. Intolerable adverse effects (edema and dizziness) occurred in only 1% of patients (2/206). Sildenafil citrate may be recommended as the first choice drug for ED because of its high success rate and low invasiveness.


Assuntos
Disfunção Erétil/tratamento farmacológico , Piperazinas/administração & dosagem , Vasodilatadores/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Piperazinas/efeitos adversos , Purinas , Citrato de Sildenafila , Sulfonas , Resultado do Tratamento , Vasodilatadores/efeitos adversos
15.
Clin Cancer Res ; 5(9): 2605-12, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10499639

RESUMO

Resistance to conventional anticancer chemotherapeutic agents remains one of the major problems in the treatment of bladder cancer. Hence, new therapeutic modalities are necessary to treat the drug-resistant cancers. Apo-2 ligand (Apo-2L) is member of the tumor necrosis factor ligand family, and it induces apoptosis in cancer cells. Several cytotoxic anticancer drugs, including Adriamycin (ADR), also mediate apoptosis and may share the common intracellular pathways leading to cell death. We reasoned that combination treatment of the drug-resistant cancer cells with Apo-2L and drugs might overcome their resistance. Here, we examined whether bladder cancer cells are sensitive to Apo-2L-mediated cytotoxicity and whether Apo-2L can synergize with ADR in cytotoxicity and apoptosis against bladder cancer cells. Recombinant human soluble Apo-2L (sApo-2L), which carries the extracellular domain of Apo-2L, was used as a ligand. Cytotoxicity was determined by a 1-day microculture tetrazolium dye assay. Synergy was assessed by isobolographic analysis. Human T24 bladder cancer line was relatively resistant to sApo-2L. Treatment of T24 line with combination of sApo-2L and ADR resulted in a synergistic cytotoxic effect. Synergy was also achieved in the ADR-resistant T24 line (T24/ADR), two other bladder cancer lines, and three freshly derived human bladder cancer cell samples. In addition, T24 cells were sensitive to treatment with sApo-2L combined with epirubicin or pirarubicin. The synergy achieved in cytotoxicity with sApo-2L and ADR was also achieved in apoptosis. Intracellular accumulation of ADR was not affected by sApo-2L. Incubation of T24 cells with sApo-2L down-regulated the expression of glutathione S-transferase-pi mRNA. This study demonstrates that combination treatment of bladder cancer cells with sApo-2L and ADR overcomes their resistance. The sensitization obtained with established ADR-resistant bladder cancer cells and freshly isolated bladder cancer cells required low subtoxic concentrations of ADR, thus supporting the in vivo potential application of combination of sApo-2L and ADR in the treatment of ADR-resistant bladder cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Apoptose/efeitos dos fármacos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Proteínas Reguladoras de Apoptose , Bisbenzimidazol , Regulação para Baixo , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Doxorrubicina/farmacocinética , Sinergismo Farmacológico , Epirubicina/administração & dosagem , Corantes Fluorescentes , Glutationa S-Transferase pi , Glutationa Transferase/biossíntese , Glutationa Transferase/metabolismo , Humanos , Isoenzimas/biossíntese , Isoenzimas/metabolismo , Glicoproteínas de Membrana/administração & dosagem , RNA Mensageiro/biossíntese , RNA Mensageiro/metabolismo , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/metabolismo , Coloração e Rotulagem/métodos , Ligante Indutor de Apoptose Relacionado a TNF , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/administração & dosagem , Neoplasias da Bexiga Urinária/patologia
16.
Clin Cancer Res ; 3(6): 963-72, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9815772

RESUMO

Androgen ablation has been an effective treatment in patients with advanced prostate cancer. However, most treated patients develop hormonally resistant disease and do not respond to conventional chemotherapy. Immunotherapy against prostate cancer is an alternative approach in overcoming hormonal/drug-resistant prostate cancer. Cytotoxic immune lymphocytes kill target cells via the perforin/granzyme and the Fas-ligand (Fas-L) pathways. We hypothesize that tumor cells respond poorly to immunotherapy by developing resistance to killing by the Fas-L mechanism. This study investigated whether prostate tumor cells are sensitive to Fas-mediated killing. The human prostate carcinoma cell lines DU145, PC-3, and LnCAP were examined for their sensitivity to killing and apoptosis by the Fas-L agonist anti-Fas antibody and CTLs. All three lines moderately expressed the Fas antigen on the cell surface; however, all three lines were relatively resistant to cytotoxicity mediated by anti-Fas (CH-11) antibody. Pretreatment of DU145 and PC-3 with subtoxic concentrations of drugs followed by anti-Fas antibody resulted in synergistic cytotoxicity and apoptosis, whereas only an additive effect was obtained with LnCAP. Chemosensitization with drugs and anti-Fas was completely blocked by the addition of neutralizing anti-Fas antibody. The murine CTL hybridoma, PMMI, which kills only via the Fas-L pathway, was able to kill chemosensitized PC-3 and DU145 but not LnCAP cells. Furthermore, this cytotoxicity was blocked by anti-Fas neutralizing antibody. Chemosensitization of PC-3 and DU145 prostate tumor cells was not due to up-regulation of Fas-receptor antigen expression. Treatment of tumor cells with cisplatin did not down-regulate the antiapoptotic genes bcl-2, FAP-1, and c-myc. Further, there was no induction by cisplatin of Fas-L on the tumor cells, thus ruling out Fas/Fas-L-mediated autologous killing. These findings demonstrate that pretreatment of drug-resistant/CTL-resistant prostate DU145 and PC-3 tumor cells with subtoxic concentrations of certain chemotherapeutic drugs sensitizes the tumor cells to Fas-mediated cytotoxicity. These findings suggest that chemosensitization of tumor cells should optimize the response to immunotherapeutic interventions in the treatment of hormone-resistant/drug-resistant prostate cancer.


Assuntos
Apoptose , Sobrevivência Celular , Cisplatino/toxicidade , Glicoproteínas de Membrana/imunologia , Neoplasias da Próstata/patologia , Animais , Anticorpos/toxicidade , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citotoxicidade Imunológica , Doxorrubicina/toxicidade , Sinergismo Farmacológico , Etoposídeo/toxicidade , Proteína Ligante Fas , Humanos , Imunoterapia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias da Próstata/imunologia , Linfócitos T Citotóxicos/imunologia , Células Tumorais Cultivadas , Receptor fas/imunologia
17.
Clin Cancer Res ; 4(4): 979-83, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9563893

RESUMO

Patients without any evidence of lymph node metastases are supposed to have a fair prognosis, but some of these patients develop recurrent disease unexpectedly after surgery. The object of this study is to examine whether the detection of human papilloma virus (HPV) DNA could be used as a diagnostic marker to predict such recurrences. Two hundred and thirty-six patients undergoing radical hysterectomy and pelvic lymphadenectomy for stage Ib and II cervical cancer at Okayama University Hospital (Japan) from 1988-1994 were reviewed, and only those cases positive for HPV-16 or HPV-18 in primary sites were included in this survey. The E6-E7 region of the HPV genome was amplified by a sensitive nested PCR from archival pelvic lymph node specimens. HPV sequences identical to those of the primary sites were detected in histologically confirmed negative lymph nodes, regardless of histological type or HPV type of the primary lesion, in 9 of 10 patients who recurred within 4 years of surgery. In contrast, histologically confirmed negative lymph nodes from 12 patients with stage IIb disease without evidence of recurrent disease were all negative for the presence of HPV, except for 1 lymph node. The presence of HPV DNA in histologically negative nodes implies the possibility of early nodal involvement or coexistence of undetectable hematogenic dissemination and could therefore be used as a diagnostic marker to predict the unexpected recurrence of these patients.


Assuntos
DNA Viral/isolamento & purificação , Linfonodos/virologia , Papillomaviridae/isolamento & purificação , Neoplasias do Colo do Útero/virologia , Adulto , Idoso , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Pelve/virologia , Reação em Cadeia da Polimerase , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia
18.
J Comp Pathol ; 133(1): 14-22, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15899493

RESUMO

Immunohistochemical and ultrastructural analysis of canine brain tissue was performed to determine whether cerebral capillaries, which form the blood--brain barrier (BBB), display age-related morphological changes in the white matter (WM). A slight decrease in laminin immunolabelling was detected in the basement membranes (BMs) of capillaries in the WM of old dogs, as compared with that in the brains of young dogs. The Prussian blue DAB post-DAB enhancement method detected iron present in macrophages and astrocytes in the WM. Copper/zinc superoxide dismutase, MT-I and -II and MT-III immunoreactivity was detected mainly in reactive astrocytes in the WM of aged dogs. Ultrastructurally, collagen-like fibrils were detected to a variable degree in the spaces between the BMs of capillary endothelial cells and astrocytes in the WM of some aged dogs. These results suggest that age-related morphological changes in capillaries of the WM are associated with BBB dysfunction, leading to the exudation of serum constituents, including harmful substances (e.g., iron), thereby causing tissue damage by oxidative injury. These factors may play a role in the pathogenesis of severe degenerative changes in the WM of aged dogs.


Assuntos
Envelhecimento , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/ultraestrutura , Capilares/patologia , Córtex Cerebral/irrigação sanguínea , Albuminas/metabolismo , Animais , Astrócitos/metabolismo , Astrócitos/ultraestrutura , Capilares/ultraestrutura , Córtex Cerebral/patologia , Circulação Cerebrovascular/fisiologia , Cães , Feminino , Fibrinogênio/metabolismo , Imuno-Histoquímica , Corpos de Inclusão/ultraestrutura , Ferro/metabolismo , Laminina/metabolismo , Macrófagos/metabolismo , Macrófagos/ultraestrutura , Masculino , Metalotioneína/metabolismo , Microscopia Eletrônica de Transmissão , Superóxido Dismutase/metabolismo
19.
Rev Sci Instrum ; 86(4): 043110, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25933844

RESUMO

We have constructed an improved version of a photon-counting phase-modulation fluorometer (PC-PMF) with a maximum modulation frequency of 1.0 GHz, where a phase domain measurement is conducted with a time-correlated single-photon-counting electronics. While the basic concept of the PC-PMF has been reported previously by one of the authors, little attention has been paid to its significance, other than its weak fluorescence measurement capability. Recently, we have recognized the importance of the PC-PMF and its potential for fluorescence lifetime measurements. One important aspect of the PC-PMF is that it enables us to perform high-speed measurements that exceed the frequency bandwidths of the photomultiplier tubes that are commonly used as fluorescence detectors. We describe the advantages of the PC-PMF and demonstrate its usefulness based on fundamental performance tests. In our new version of the PC-PMF, we have used a laser diode (LD) as an excitation light source rather than the light-emitting diode that was used in the primary version. We have also designed a simple and stable LD driver to modulate the device. Additionally, we have obtained a sinusoidal histogram waveform that has multiple cycles within a time span to be measured, which is indispensable for precise phase measurements. With focus on the fluorescence intensity and the resolution time, we have compared the performance of the PC-PMF with that of a conventional PMF using the analogue light detection method.

20.
Am J Psychiatry ; 150(7): 1053-8, 1993 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8317575

RESUMO

OBJECTIVE: The authors sought to delineate the characteristics of female alcoholics with eating disorders. METHOD: The study subjects were 29 female Japanese outpatients and inpatients, 30 years of age or younger, with DSM-III-R diagnoses of either alcohol dependence or alcohol abuse and eating disorders. Twenty-one female alcoholics within the same age range who did not have eating disorders served as the comparison group. The social and familial backgrounds, clinical course, and clinical symptoms of the two groups were compared with the use of a structured interview form developed for the study. RESULTS: Ninety-three percent of the subjects with eating disorders had bulimia nervosa; 52% had anorexia nervosa. In all cases, both disorders continued after the onset of problem drinking. The age distributions of the two groups of alcoholic subjects clearly differed: no one in the comparison group was under the age of 24, and the number of comparison subjects increased with age after age 24, whereas the subjects with eating disorders ranged in age from 19 to 30 years, with the greatest number at age 26. More of the alcoholic subjects with eating disorders had never been married, they had had an earlier onset of alcoholism, and they had lower body weights than those without eating disorders. Also, more of them had depression and borderline personality disorder. CONCLUSIONS: The findings suggest that young female alcoholics with eating disorders constitute a clinical subgroup of alcoholics with distinct sociodemographic characteristics and a clinical course and symptoms that differ from those of both younger and older female alcoholics without eating disorders.


Assuntos
Alcoolismo/epidemiologia , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Adulto , Fatores Etários , Alcoolismo/diagnóstico , Anorexia Nervosa/diagnóstico , Anorexia Nervosa/epidemiologia , Peso Corporal , Bulimia/diagnóstico , Bulimia/epidemiologia , Comorbidade , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Feminino , Humanos , Japão/epidemiologia , Estado Civil , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , Prevalência , Escalas de Graduação Psiquiátrica , Fatores Sexuais
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