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2.
Prostate Cancer Prostatic Dis ; 15(2): 170-6, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21912428

RESUMO

BACKGROUND: BPH and lower urinary tract symptoms (LUTS) are very common among older men in Western countries. However, the prevalence of these two conditions in the developing countries is less clear. METHODS: We assessed the age-standardized prevalence of BPH and/or LUTS among West Africans in a probability sample of 950 men aged 50-74 in Accra, Ghana, with no evidence of biopsy-confirmed prostate cancer after screening with PSA and digital rectal examination (DRE). Information on LUTS was based on self-reports of the International Prostate Symptom Score (IPSS). BPH was estimated using DRE, PSA levels and imputed prostate volume. RESULTS: The prevalence of DRE-detected enlarged prostate was 62.3%, while that of PSA≥1.5 ng ml(-1) (an estimate of prostate volume ≥ 30 cm(3)) was 35.3%. The prevalence of moderate-to-severe LUTS (IPSS≥8) was 19.9%. The prevalence of IPSS≥8 and an enlarged prostate on DRE was 13.3%. Although there is no universally agreed-upon definition of BPH/LUTS, making comparisons across populations difficult, BPH and/or LUTS appear to be quite common among older Ghanaian men. CONCLUSIONS: We found that after age standardization, the prevalence of DRE-detected enlarged prostate in Ghanaian men is higher than previously reported for American men, but the prevalence of LUTS was lower than previously reported for African Americans. Further studies are needed to confirm these findings and identify the risk factors for BPH in both Africans and African Americans.


Assuntos
Sintomas do Trato Urinário Inferior/epidemiologia , Hiperplasia Prostática/epidemiologia , Negro ou Afro-Americano , Idoso , População Negra , Exame Retal Digital , Gana/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Autorrelato
3.
Acta Anaesthesiol Scand ; 52(7): 987-90, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18477078

RESUMO

BACKGROUND: The perioperative period is psychologically as well as physically stressful for patients. Although music and sound are known to reduce patients' psychological stress, a few previous studies showed an objective outcome of music. The aim of the present study was to evaluate the relaxing effect of music during epidural anesthesia, using patients' salivary amylase activity. METHODS: Thirty-two American Society of Anesthesiologists (ASA) I or II patients presenting for inguinal hernia repair under epidural anesthesia were randomly assigned to listen to sounds of a soft wind and a twitter (S group) or to have no sounds (N group). Patients' salivary amylase activity was evaluated on arrival to the operating room and at wound closure. RESULTS: Intra-operative music significantly decreased salivary amylase activity at wound closure in the S group and the activity at wound closure of the S group was significantly smaller than that of the N group. CONCLUSION: Intra-operative natural sound significantly decreased salivary amylase activity of patients undergoing inguinal hernia repair under epidural anesthesia.


Assuntos
Estimulação Acústica/psicologia , Amilases/metabolismo , Anestesia Epidural/métodos , Hérnia Inguinal/cirurgia , Cuidados Intraoperatórios/psicologia , Saliva/metabolismo , Estimulação Acústica/métodos , Adaptação Psicológica/fisiologia , Idoso , Anestésicos Locais/administração & dosagem , Ansiolíticos/administração & dosagem , Pressão Sanguínea , Diazepam/administração & dosagem , Feminino , Frequência Cardíaca , Hérnia Inguinal/psicologia , Humanos , Cuidados Intraoperatórios/métodos , Lidocaína/administração & dosagem , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Som , Estresse Psicológico/etiologia , Estresse Psicológico/psicologia , Estresse Psicológico/terapia , Vento
4.
J Mater Sci Mater Med ; 19(4): 1581-6, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18214649

RESUMO

In order to investigate bone tissue reaction to the low rigidity titanium alloy of TNTZ in bone plate fixation, animal experiment with rabbit was performed with X-ray follow-up and histological observation. Experimental fractures were made in rabbit tibiae, and fixed by different bone plates of SUS316L, Ti-6Al-4V and TNTZ. Although there was no significant difference in fracture healing, bone atrophy was observed in cortical bone especially under the bone plate, which was different in time course among three materials. The bone atrophy under the bone plate was confirmed as porous or poor bone tissue in histological observation. In addition, the diameter of the tibia bone was increased in TNTZ as the result of bone remodeling with a new cortical bone. It is confirmed that the elastic modulus of the bone plate will naturally influence bone tissue reaction to the bone plate fixation according to the Wolff's law of functional restoration.


Assuntos
Materiais Biocompatíveis/química , Fixação de Fratura/instrumentação , Consolidação da Fratura , Tíbia/patologia , Fraturas da Tíbia/patologia , Titânio/química , Ligas , Animais , Fenômenos Biomecânicos , Remodelação Óssea , Substitutos Ósseos/química , Osso e Ossos/patologia , Coelhos , Raios X
5.
Br J Sports Med ; 42(11): 932-3, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18199629

RESUMO

OBJECTIVE AND DESIGN: Following a report that a well-known soccer player achieved a perfect score on the Block Design subtest of WAIS-R, WAIS-R was conducted on 31 skilled rugby players. PARTICIPANTS: Twenty-seven of the 31 players were recruited for further analyses. RESULTS: In 14 of 27 players, Block Design scores were the highest of the 11 subtests. In addition to Block Design scores that exceeded the scores for the other subtests, the players' Block Design scores were also better than scores for the standard sample. CONCLUSIONS: The Block Design is related to spatial cognitive ability. These results showed that highly skilled players of field and ball games possess high spatial cognitive abilities.


Assuntos
Desempenho Atlético/fisiologia , Cognição/fisiologia , Futebol Americano/fisiologia , Percepção Espacial/fisiologia , Escalas de Wechsler , Adulto , Humanos , Masculino
6.
Br J Cancer ; 97(11): 1577-82, 2007 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-18000509

RESUMO

We conducted a population-based study of 627 patients with biliary tract cancers (368 of gallbladder, 191 bile duct, and 68 ampulla of Vater), 1037 with biliary stones, and 959 healthy controls randomly selected from the Shanghai population, all personally interviewed. Gallstone status was based on information from self-reports, imaging procedures, surgical notes, and medical records. Among controls, a transabdominal ultrasound was performed to detect asymptomatic gallstones. Gallstones removed from cancer cases and gallstone patients were classified by size, weight, colour, pattern, and content of cholesterol, bilirubin, and bile acids. Of the cancer patients, 69% had gallstones compared with 23% of the population controls. Compared with subjects without gallstones, odds ratios associated with gallstones were 23.8 (95% confidence interval (CI), 17.0-33.4), 8.0 (95% CI 5.6-11.4), and 4.2 (95% CI 2.5-7.0) for cancers of the gallbladder, extrahepatic bile ducts, and ampulla of Vater, respectively, persisting when restricted to those with gallstones at least 10 years prior to cancer. Biliary cancer risks were higher among subjects with both gallstones and self-reported cholecystitis, particularly for gallbladder cancer (OR=34.3, 95% CI 19.9-59.2). Subjects with bile duct cancer were more likely to have pigment stones, and with gallbladder cancer to have cholesterol stones (P<0.001). Gallstone weight in gallbladder cancer was significantly higher than in gallstone patients (4.9 vs 2.8 grams; P=0.001). We estimate that in Shanghai 80% (95% CI 75-84%), 59% (56-61%), and 41% (29-59%) of gallbladder, bile duct, and ampulla of Vater cancers, respectively, could be attributed to gallstones.


Assuntos
Neoplasias do Sistema Biliar/epidemiologia , Sistema Biliar/patologia , Cálculos Biliares/patologia , Idoso , Ácidos e Sais Biliares/análise , Sistema Biliar/química , Bilirrubina/análise , China/epidemiologia , Colesterol/análise , Feminino , Cálculos Biliares/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Tamanho do Órgão , Vigilância da População/métodos , Fatores de Risco
7.
Ergonomics ; 48(1): 1-11, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15764302

RESUMO

To examine the effects of shift schedules on fatigue and physiological functions among firefighters a 17-day field study at a fire station was carried out. Eleven firefighters, who were engaged in firefighting emergency services, participated in this study. At the fire station, night duty (22:00-07:00) was divided into 5 periods (P1: 22:00-00:00; P2: 23:45-01:45; P3: 01:30-03:30; P4: 03:15-05:15; P5: 05:00-07:00). The participants were assigned to one of these 5 periods and awakened to answer calls from the city's central information centre. They took naps in individual rooms during night duty, except when on night shift or when called out on an emergency. Subjective complaints of fatigue, critical flicker fusion frequencies, 3-choice reaction times, and oral temperature were measured before and after work and following breaks during their 24 working hours. Heart rate variability was also recorded to evaluate autonomic nerve activity. The results show that during P3 and P4, participants who had to wake up at midnight took shorter naps. The rates of subjective complaints regarding P3 and P4 tended to be higher than those for P1, P2, and P5. The ratios of the low frequency component of heart rate variability to the high frequency component during P4 were significantly lower than those during P5. It is assumed that such an irregular sleeping pattern causes many complaints of subjective fatigue, and adversely affects physiological functions. A night-duty shift schedule ensuring undisturbed naps should be considered.


Assuntos
Fadiga/etiologia , Incêndios , Trabalho de Resgate , Sono/fisiologia , Tolerância ao Trabalho Programado/fisiologia , Adulto , Temperatura Corporal , Ritmo Circadiano/fisiologia , Frequência Cardíaca , Humanos , Japão , Descanso , Carga de Trabalho
8.
Neuroscience ; 114(3): 769-79, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12220577

RESUMO

Recent studies have reported that acute administration of the psychotomimetic drug phencyclidine results in considerable increases in the amounts of both extracellular glutamate and dopamine in the medial prefrontal cortex (mPFC). However, the effect of phencyclidine on the firing activity of mPFC neurons remains unknown. Here, we report the first data on phencyclidine-induced activation of mPFC neurons in freely moving rats. Unanesthetized rats received an intraperitoneal injection of either phencyclidine (5 mg/kg) or physiological saline (0.5 ml/kg) in order to investigate the impulse activity of mPFC neurons and behavioral activity. The phencyclidine injection induced a remarkable increase (two-fold or more) in the spontaneous discharge rate of the majority of mPFC neurons (20/23), and this increase lasted for more than 70 min. In addition, a considerable augmentation of behavioral activity was observed that nearly paralleled that of the mPFC neuronal activation. In contrast, microiontophoretically applied phencyclidine exerted little influence on the spontaneous firing activity of most mPFC neurons (25/29) in anesthetized rats, although systemically applied phencyclidine produced activation of mPFC neurons even under general anesthesia. These results suggest that the behavioral abnormalities induced by acute administration of phencyclidine may be caused by hyperactivation of mPFC neurons, and that this hyperactivation is elicited through excitatory inputs from brain regions outside the mPFC.


Assuntos
Potenciais de Ação/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fenciclidina/administração & dosagem , Córtex Pré-Frontal/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Masculino , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia , Ratos , Ratos Sprague-Dawley
9.
Bone ; 30(6): 901-8, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12052461

RESUMO

The effect of interleukin (IL)-18 on osteoclastic bone-resorbing activity was investigated in vitro. Osteoclast-enriched cells, about 70% of which were tartrate-resistant acid phosphatase (TRAP)-positive, were cultured on dentine slices, and then the total volume of resorption pits on each dentine slice was measured as bone-resorbing activity. When the effects of IL-18 alone at 1, 10, 100, and 1000 ng/mL were examined, bone-resorbing activity was significantly reduced only at 1000 ng/mL, by about 50%. However, IL-18 plus IL-12 (10 ng/mL each) reduced bone-resorbing activity by about 70%, whereas IL-12 alone had no significant effect. When the concentration of interferon (IFN)-gamma in the medium was measured, IL-18 or IL-12 was found to increase it slightly, and the combination of these two cytokines synergistically increased it. The inhibitory effect of the combination of the two cytokines was completely abolished by the addition of an anti-IFN-gamma neutralizing antibody to the medium, but IFN-gamma by itself did not inhibit osteoclastic bone resorption. IL-18 alone or in combination with IL-12 did not affect the number of TRAP-positive cells in culture of osteoclast-enriched cells. Osteoclasts prepared from osteoclast-enriched cells expressed mRNAs of IL-18 receptor, MyD88, and cathepsin K. Furthermore, IL-18 receptor protein was detected on the cell surface of osteoclasts. The present results indicate that the combination of IL-18 and IL-12 synergistically inhibits osteoclastic bone-resorbing activity, suggesting that IFN-gamma participates in the mechanism underlying this inhibition.


Assuntos
Reabsorção Óssea/tratamento farmacológico , Interleucina-12/uso terapêutico , Interleucina-18/uso terapêutico , Animais , Reabsorção Óssea/metabolismo , Sinergismo Farmacológico , Interferon gama/farmacologia , Interferon gama/fisiologia , Interferon gama/uso terapêutico , Interleucina-12/farmacologia , Interleucina-12/fisiologia , Interleucina-18/farmacologia , Interleucina-18/fisiologia , Camundongos , Camundongos Endogâmicos BALB C
10.
Psychiatry Clin Neurosci ; 55(6): 629-34, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11737797

RESUMO

School refusal has become a relatively common problem of increasing magnitude in Japan. Although clarification of the relationship between 'school refusal' and 'depression with school inattendance' is crucial in light of the difference in treatment modalities involved, it is not clear whether the two are to be regarded along the same tangent or as disparate entities. For clarification, a comparison was made between clinical diagnosis, Children's Depression Inventory (CDI) scores, and scores for the three subordinate scales of the CDI in 34 cases of school refusal, 10 cases of depression with school inattendance, and normal students. Significant difference in CDI score was noted between the three groups: highest among depression cases, followed by school refusers, and lowest in normal students. A larger proportion of school refusers expressed somatic complaints together with low CDI scores. The typical case of school refusal appears to exhibit somatic complaints in the foreground rather than depression, both clinical characteristics and CDI scores indicate school refusal and depression to be separate entities. Although many approaches are being taken in the treatment of school refusal, the results appear to justify primacy of the psychotherapeutic approach with the possible adjuvant use of pharmacological agents, for the phenomenon as it presents in Japan.


Assuntos
Transtorno Depressivo Maior/diagnóstico , Transtornos Somatoformes/diagnóstico , Evasão Escolar/psicologia , Evasão Escolar/estatística & dados numéricos , Estudantes/psicologia , Inquéritos e Questionários , Adolescente , Comportamento do Adolescente/psicologia , Criança , Comportamento Infantil/psicologia , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Japão/epidemiologia , Masculino , Transtornos Somatoformes/epidemiologia , Transtornos Somatoformes/psicologia
11.
Sci Total Environ ; 277(1-3): 15-9, 2001 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-11589395

RESUMO

In order to assist in finding ways to mitigate CO2 emission and to slow the depletion of fossil fuels we have established and evaluated a representative system, which consists of three technologies developed in our laboratory. These technologies were in CO2 recovery, hydrogen production and methanol synthesis and in addition we established the necessary supporting systems. Analysis of outline designs of the large scale renewable energy power generation system and this system and energy input for building plant, energy input for running plant has been conducted based on a case using this system for a 1000-MW coal fired power plant, followed by an evaluation of the material balance and energy balance. The results are as follows. Energy efficiency is 34%, the CO2 reduction rate is 41%, the balance ratio of the energy and CO2 of the system is 2.2 and 1.8, respectively, on the assumption that the primary renewable energy is solar thermal power generation, the stationary CO2 emission source is a coal-fired power plant and the generation efficiency of the methanol power plant is 60%. By adopting the system, 3.7 million tons of CO2 can be recovered, approximately 2.7 million tons of methanol can be produced, and 15.4 billion kWh of electricity can be generated per year. Compared to generating all electrical power using only coal, approximately 2.6 million tons of coal per year can be saved and approximately 2.15 million tons of CO2 emission can be reduced. Therefore, it is clearly revealed that this system would be effective to reduce CO2 emissions and to utilize renewable energy.


Assuntos
Poluição do Ar/prevenção & controle , Dióxido de Carbono/química , Efeito Estufa , Centrais Elétricas , Dióxido de Carbono/análise , Conservação dos Recursos Naturais , Hidrogênio/química , Cinética , Metanol/síntese química
12.
Biosci Biotechnol Biochem ; 65(9): 2033-6, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11676017

RESUMO

We investigated the effect of CH-19 Sweet, a non-pungent cultivar of red pepper, on body temperature and oxygen consumption in humans. CH-19 Sweet was given to 11 healthy volunteers, and core body temperature, body surface temperature and oxygen consumption were measured. The control group ingested California-Wandar, which contained neither capsaicin nor capsiate. The core body temperature in the CH-19 Sweet group was significantly higher than that in the control group (P<0.01). The forehead temperature measured by infrared thermography in the CH-19 Sweet group was significantly higher than that in the control group. The body surface temperature was increased for about 20 min after consumption of CH-19 Sweet intake, and the neck temperature was significantly higher (P<0.001) than when the subjects consumed California-Wandar. We also measured respiratory gas by indirect calorimetry while subjects wore a face mask. A significant difference was detected in oxygen consumption between the two groups, and the value was significantly higher in the CH-19 Sweet group (P<0.03). These results suggest that CH-19 Sweet increased thermogenesis and energy consumption.


Assuntos
Temperatura Corporal , Capsicum , Consumo de Oxigênio , Adulto , Feminino , Humanos , Masculino
13.
Oral Oncol ; 37(7): 579-85, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11564579

RESUMO

We investigated the immunohistochemical expression of Rb protein (pRb), which plays an important role in the regulation of the cell cycle, in rat tongue carcinoma induced by 4-nitroquinoline 1-oxide. In addition, we made an immunohistochemical investigation of cyclin D1 and cdk4, which are involved in the Rb pathway. The labeling index of pRb expression in cases with carcinoma was significantly decreased compared with that in cases with a premalignant lesion (P<0.01), while the labeling index of cyclin D1 and cdk4 increased gradually during the course of carcinogenesis. We analyzed the phosphorylation of pRb by immunoblotting using G3-245 monoclonal antibody, which recognizes both the phosphorylated and unphosphorylated forms of pRb. Although expression of the phosphorylated pRb band was notably increased in dysplastic membrane compared with the control membrane, it almost disappeared in cases with carcinoma. Unphosphorylated pRb bands were also expressed in control membrane and dysplastic membrane but not in cases with carcinoma. In conclusion, a decrease of pRb and an increase of cdk4 and cyclin D1 were shown to occur during the premalignant stage. The decrease of pRb in quantity and the increase of its phosphorylation may prevent G1 arrest and consequently accelerate proliferation of the chemically injured cells contributing to the initiation of carcinogenesis.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Proto-Oncogênicas , Proteína do Retinoblastoma/metabolismo , Neoplasias da Língua/metabolismo , 4-Nitroquinolina-1-Óxido , Animais , Western Blotting , Carcinógenos , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/patologia , Ciclina D1/metabolismo , Quinase 4 Dependente de Ciclina , Quinases Ciclina-Dependentes/metabolismo , Progressão da Doença , Técnicas Imunoenzimáticas , Masculino , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ratos Sprague-Dawley , Neoplasias da Língua/induzido quimicamente , Neoplasias da Língua/patologia
14.
Mol Ecol ; 10(8): 2095-9, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11555253

RESUMO

We investigated natural populations of three Japanese native bumblebee species to determine the status of infestation by a tracheal mite, Locustacarus buchneri, which we had earlier detected in introduced commercial colonies of the European bumblebee, Bombus terrestris. We also investigated mite infestation in commercial colonies of a Japanese native species, B. ignitus, which are mass-produced in the Netherlands and reimported into Japan. We detected the mite in both natural and commercial colonies of the Japanese species. Comparison of 555 bp sequences of the mitochondrial DNA (mtDNA) cytochrome oxidase 1 (CO1) gene from the mite showed that there were seven haplotypes, on the basis of combinations of substitutions at eight sites in the gene. The haplotypes of the mites in the Japanese native bumblebees and the haplotypes of the mites in B. terrestris did not overlap; however, mtDNA of mites detected in the commercial colonies of B. ignitus possessed the same sequence as a European haplotype. These results indicate that transportation of bumblebee colonies will cause overseas migration of parasitic mites of different origins.


Assuntos
Abelhas/parasitologia , Ácaros/genética , Ácaros/fisiologia , Animais , DNA Mitocondrial/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Haplótipos , Interações Hospedeiro-Parasita , Japão , Dados de Sequência Molecular
15.
Mol Plant Microbe Interact ; 14(7): 848-56, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11437258

RESUMO

Lotus japonicus has been proposed as a model legume for molecular genetic studies of symbiotic plant-microbe interactions leading to the fixation of atmospheric nitrogen. Lipochitin oligosaccharides (LCOs), or Nod factors, were isolated from the culture of Mesorhizobium loti strain JRL501 (MAFF303099), an efficient microsymbiont of L. japonicus B-129 cv. Gifu. High-performance liquid chromatography and mass spectrometric analyses allowed us to identify at least five different structures of LCOs that were produced by JRL501. The major component was NodMl-V(C18:1, Me, Cb, AcFuc), an N-acetyl-glucosamine pentamer in which the nonreducing residue is N-acylated with a C18:1 acyl moiety, N-methylated, and carries a carbamoyl group and the reducing N-acetylglucosamine residue is substituted with 4-O-acetyl-fucose. Additional novel LCO structures bearing fucose instead of acetyl-fucose at the reducing end were identified. Mixtures of these LCOs could elicit abundant root hair deformation on L. japonicus roots at a concentration of 10(-7) to 10(-9) M. Spot inoculation of a few nanograms of LCOs on L. japonicus roots induced the formation of nodule primordia in which the early nodulin genes, ENOD40 and ENOD2, were expressed in a tissue-specific manner. We also observed the formation of a cytoplasmic bridge (preinfection thread) in the swollen outermost cortical cells. This is the first description of cytoplasmic bridge formation by purified LCOs alone in a legume-forming determinate nodules.


Assuntos
Lipopolissacarídeos/isolamento & purificação , Lipopolissacarídeos/farmacologia , Lotus/efeitos dos fármacos , Rhizobiaceae/química , Sequência de Carboidratos , Cromatografia Líquida de Alta Pressão , Lipopolissacarídeos/química , Lotus/genética , Lotus/crescimento & desenvolvimento , Lotus/microbiologia , Espectrometria de Massas , Modelos Biológicos , Dados de Sequência Molecular , Estrutura Molecular , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/microbiologia , Rhizobiaceae/genética , Simbiose
16.
J Antibiot (Tokyo) ; 54(4): 364-74, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11426661

RESUMO

A systematic approach for improving the water-solubility of anti-MRSA (methicillin-resistant Staphylococcus aureus) cephalosporin derivatives is described. We first tried to improve the water-solubility of 7beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-fluoromethoxyiminoacetamido]-3-[(E)-2-(1-methylimidazo[1,2-b]pyridazinium-6-yl)thiovinyl]-3-cephem-4-carboxylate (1a) by substitution of the C-3' pharmacophore. Replacement of the C-3' pharmacophore with a 1-methyl-4-pyridinio group improved the water-solubility without decreasing the anti-MRSA activity. Furthermore, we applied the N-modified prodrug strategy to the C-7 acyl group in order to enhance the water-solubility drastically. Among the compounds prepared, the N-phosphono type prodrugs 2a(1-methylimidazo[1,2-b]pyridazinium derivative) and 2b (1-methyl-4-pyridinio derivative) showed water-solubility appropriate for a product intended for intravenous injection and in vivo anti-MRSA activity comparable to that of vancomycin.


Assuntos
Proteínas de Bactérias , Proteínas de Transporte , Cefalosporinas/farmacologia , Resistência a Meticilina/fisiologia , Muramilpentapeptídeo Carboxipeptidase , Pró-Fármacos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Animais , Cefalosporinas/administração & dosagem , Cefalosporinas/farmacocinética , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Hexosiltransferases/metabolismo , Concentração de Íons de Hidrogênio , Injeções , Masculino , Camundongos , Camundongos Endogâmicos ICR , Testes de Sensibilidade Microbiana , Complexos Multienzimáticos/metabolismo , Proteínas de Ligação às Penicilinas , Peptidil Transferases/metabolismo , Pró-Fármacos/administração & dosagem , Pró-Fármacos/farmacocinética , Ligação Proteica , Solubilidade , Espectrofotometria Infravermelho
17.
J Cell Biol ; 153(4): 785-94, 2001 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-11352939

RESUMO

We have shown previously that epimorphin (EPM), a protein expressed on the surface of myoepithelial and fibroblast cells of the mammary gland, acts as a multifunctional morphogen of mammary epithelial cells. Here, we present the molecular mechanism by which EPM mediates luminal morphogenesis. Treatment of cells with EPM to induce lumen formation greatly increases the overall expression of transcription factor CCAAT/enhancer binding protein (C/EBP)beta and alters the relative expression of its two principal isoforms, LIP and LAP. These alterations were shown to be essential for the morphogenetic activities, since constitutive expression of LIP was sufficient to produce lumen formation, whereas constitutive expression of LAP blocked EPM-mediated luminal morphogenesis. Furthermore, in a transgenic mouse model in which EPM expression was expressed in an apolar fashion on the surface of mammary epithelial cells, we found increased expression of C/EBPbeta, increased relative expression of LIP to LAP, and enlarged ductal lumina. Together, our studies demonstrate a role for EPM in luminal morphogenesis through control of C/EBPbeta expression.


Assuntos
Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Células Epiteliais/citologia , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/fisiologia , Glicoproteínas de Membrana/genética , Animais , Comunicação Celular/fisiologia , Células Epiteliais/fisiologia , Feminino , Lactação/fisiologia , Glândulas Mamárias Animais/crescimento & desenvolvimento , Glicoproteínas de Membrana/análise , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Transgênicos , Proteínas do Leite/genética , Células Estromais/citologia , Células Estromais/fisiologia
18.
Neuropsychopharmacology ; 24(3): 330-2, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11166522

RESUMO

The use of neonatal ventral hippocampal nVH lesioned rats is well established in animal models of schizophrenia. Moreover, the dysfunction of N-methyl-D-aspartate (NMDA) neurotransmission may play a crucial role in the pathophysiology of schizophrenia. To examine the effect of glycine (GLY) in this animal model, we compared the effects of GLY (0.8 and 1.6 g/kg, IP) on locomotor activity induced by a novel environment (NOVEL) and methamphetamine (MAP, 1.5 mg/kg, IP) in lesioned and sham-operated rats. Compared with sham rats, GLY significantly reduced NOVEL- and MAP-induced locomotor activity in lesioned rats (p <.001 and p <.05, respectively). It is suggested that GLY attenuated nVH-induced hyperactivity, and that this effect was evident both in the presence and absence of MAP. The nVH lesions may result in a form of hyperactivity that differs from normal locomotion in the degree to which it is highly sensitive to regulation by GLY.


Assuntos
Glicina/uso terapêutico , Hipocampo/fisiopatologia , Hipercinese/induzido quimicamente , Metanfetamina/efeitos adversos , Receptores de N-Metil-D-Aspartato/fisiologia , Esquizofrenia/fisiopatologia , Animais , Modelos Animais de Doenças , Glicina/administração & dosagem , Glicina/farmacologia , Hipocampo/efeitos dos fármacos , Ácido Ibotênico/efeitos adversos , Metanfetamina/administração & dosagem , Metanfetamina/farmacologia , Atividade Motora/efeitos dos fármacos , Ratos , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Esquizofrenia/induzido quimicamente
19.
Genetics ; 157(2): 727-42, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11156992

RESUMO

A gene-trap system is established for Drosophila. Unlike the conventional enhancer-trap system, the gene-trap system allows the recovery only of fly lines whose genes are inactivated by a P-element insertion, i.e., mutants. In the gene-trap system, the reporter gene expression reflects precisely the spatial and temporal expression pattern of the trapped gene. Flies in which gene trap occurred are identified by a two-step screening process using two independent markers, mini-w and Gal4, each indicating the integration of the vector downstream of the promoter of a gene (dual tagging). mini-w has its own promoter but lacks a polyadenylation signal. Therefore, mini-w mRNA is transcribed from its own promoter regardless of the vector integration site in the genome. However, the eyes of flies are not orange or red unless the vector is incorporated into a gene enabling mini-w to be spliced to a downstream exon of the host gene and polyadenylated at the 3' end. The promoter-less Gal4 reporter is expressed as a fusion mRNA only when it is integrated downstream of the promoter of a host gene. The exons of trapped genes can be readily cloned by vectorette RT-PCR, followed by RACE and PCR using cDNA libraries. Thus, the dual-tagging gene-trap system provides a means for (i) efficient mutagenesis, (ii) unequivocal identification of genes responsible for mutant phenotypes, (iii) precise detection of expression patterns of trapped genes, and (iv) rapid cloning of trapped genes.


Assuntos
Drosophila melanogaster/genética , Técnicas Genéticas , Animais , Sequência de Bases , Cromossomos/metabolismo , Cruzamentos Genéticos , DNA Complementar/metabolismo , Elementos Facilitadores Genéticos , Éxons , Feminino , Biblioteca Gênica , Genes Reporter , Vetores Genéticos , Hibridização In Situ , Masculino , Microscopia Eletrônica de Varredura , Modelos Genéticos , Dados de Sequência Molecular , Mutagênese , Fenótipo , Células Fotorreceptoras de Invertebrados/embriologia , Células Fotorreceptoras de Invertebrados/patologia , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
20.
J Clin Microbiol ; 39(2): 419-29, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11158085

RESUMO

The involvement of Borna disease virus (BDV) in psychiatric diseases in humans remains controversial. T-cell memory response and seroprevalence of BDV in patients with psychiatric disorders and blood donors in Japan were evaluated collectively by Western blot (WB) analysis with inhibition test, electrochemiluminescence immunoassay, immunofluorescence assay, and T-cell proliferative response as well as detection of BDV p24 RNA in peripheral blood mononuclear cells (PBMCs). Positive proliferative responses to both BDV p40 and p24 proteins were detected in 9% of patients with mood disorders (4 of 45), 4% of schizophrenic patients (2 of 45), and 2% of blood donors (1 of 45). By WB analysis, the antibody to BDV p40 was detected only in 2% of patients with mood disorders (1 of 45). The BDV p24 antibody was detected in 2% of patients with mood disorders (1 of 45) and 9% of schizophrenic patients. (4 of 45) No plasma reacted with both BDV proteins. The finding of a lower seroprevalence than previously reported suggests the presence of false-positive cases in the previous report. BDV RNA was detected only in 2% of patients with mood disorders (1 of 45). In these three serological assays, T-cell responses, and PCR analysis, there was no significant difference in the prevalence among the three groups. However, we found three psychiatric patients who were positive for both BDV antibodies and T-cell proliferative responses and one patient who was positive for BDV RNA in PBMCs. These findings suggest the usefulness of the proliferative T-cell response and that certain individuals are infected with BDV or a BDV-related virus.


Assuntos
Doadores de Sangue , Doença de Borna/diagnóstico , Vírus da Doença de Borna/isolamento & purificação , Transtornos Mentais/virologia , Adolescente , Adulto , Idoso , Anticorpos Antivirais/sangue , Western Blotting/métodos , Criança , Pré-Escolar , Feminino , Imunofluorescência , Humanos , Imunoensaio , Memória Imunológica , Japão , Medições Luminescentes , Ativação Linfocitária , Masculino , Transtornos Mentais/complicações , Pessoa de Meia-Idade , Transtornos do Humor/virologia , Reação em Cadeia da Polimerase/métodos , RNA Viral/sangue , Esquizofrenia/virologia , Linfócitos T/imunologia , Linfócitos T/virologia
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