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1.
Am J Physiol Lung Cell Mol Physiol ; 304(12): L853-62, 2013 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-23605002

RESUMO

Allergen challenges induce airway hyperresponsiveness (AHR) and increased airway smooth muscle (ASM) mass in the sensitized rat. Whether the remodeled ASM changes its phenotype is uncertain. We examined, in sensitized Brown Norway rats, the effects of multiple ovalbumin (Ova) challenges on ASM remodeling and phenotype and the role of the epidermal growth factor receptor (EGFR) in these processes. Rats were sensitized with Ova and challenged three times at 5-day intervals with phosphate-buffered saline or Ova and pretreated with the EGFR inhibitor AG-1478 (5 mg/kg) or its vehicle dimethyl sulfoxide. Ova challenges increased ASM mass in all-sized airways and in large airway mRNA expression of smooth muscle myosin heavy chain (sm-MHC), assessed by laser capture. Myosin light chain kinase and the fast myosin isoform SM-B mRNA expressions were not affected. Ova induced AHR to methacholine, and, based on the constant-phase model, this was largely attributable to the small airways and lung derecruitment at 48 h that recovered by 1 wk. The EGFR ligands amphiregulin and heparin-binding epidermal growth factor (HB-EGF) were increased in bronchoalveolar lavage fluid at 48 h after Ova exposure. AG-1478 inhibited AHR and prevented ASM growth. Epithelial gene expression of EGFR, HB-EGF, matrix metalloproteinase (MMP)-9, Gro-α, and transforming growth factor-ß was unaffected by Ova challenges. We conclude that EGFR drives remodeling of ASM, which results from repeated Ova challenge. Furthermore, the latter results in excessive small airway and, to a lesser degree, large airway narrowing to methacholine, and large airway gene expression of contractile protein is conserved.


Assuntos
Brônquios/patologia , Receptores ErbB/genética , Músculo Liso/patologia , Hipersensibilidade Respiratória/patologia , Remodelação das Vias Aéreas/efeitos dos fármacos , Remodelação das Vias Aéreas/imunologia , Alérgenos/imunologia , Alérgenos/farmacologia , Anfirregulina , Animais , Brônquios/efeitos dos fármacos , Brônquios/imunologia , Líquido da Lavagem Broncoalveolar/química , Família de Proteínas EGF , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/imunologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glicoproteínas/genética , Glicoproteínas/imunologia , Fator de Crescimento Semelhante a EGF de Ligação à Heparina , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Masculino , Cloreto de Metacolina/farmacologia , Músculo Liso/efeitos dos fármacos , Músculo Liso/imunologia , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/imunologia , Ovalbumina/imunologia , Ovalbumina/farmacologia , Quinazolinas/farmacologia , Ratos , Hipersensibilidade Respiratória/induzido quimicamente , Hipersensibilidade Respiratória/imunologia , Hipersensibilidade Respiratória/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Miosinas de Músculo Liso/genética , Miosinas de Músculo Liso/imunologia , Tirfostinas/farmacologia
2.
J Natl Cancer Inst ; 63(5): 1257-65, 1979 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-291752

RESUMO

Altered (hyperplastic) foci and neoplastic (hyperplastic) nodules identified by their resistance to iron accumulation were induced in the livers of F344 rats by limited feeding of N-2-fluorenylacetamide for three, four, or five cycles of 4-week intervals separated by 1 week of a basal diet. Foci were present by the end of three feeding cycles and increased in number with further carcinogen exposure. No nodules were present at the end of three or four cycles, but they appeared at later intervals after removal of the carcinogen. Nodules were present at the end of five cycles of feeding and increased in number later. Thus nodules were found to be persistent and to have the progressive growth ability in situ that is characteristic of neoplasms.


Assuntos
2-Acetilaminofluoreno , Neoplasias Hepáticas Experimentais/induzido quimicamente , Lesões Pré-Cancerosas/induzido quimicamente , Animais , Ferro/metabolismo , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Masculino , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Ratos , Ratos Endogâmicos F344 , Fatores de Tempo
3.
J Natl Cancer Inst ; 69(6): 1299-304, 1982 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-6128438

RESUMO

The effect of partial hepatectomy (PH) on alteration of liver foci induced by N-nitrosodiethylamine (DENA) was studied in inbred F344 male rats. As early as 2 weeks after PH was performed 6 hours after an injection of 100 mg DENA/kg, gamma-glutamyltransferase-positive hepatocellular foci were induced, whereas DENA alone induced no foci until 12 weeks after PH. The focus counts of the group with PH performed 6 hours after an injection of 100 mg DENA/kg were consistently greater than those of a group with PH performed at 24 hours following DENA injection. At 3 and 6 weeks after PH was done at 12 weeks following treatment with 100 or 200 mg DENA/kg, the focus count was significantly increased compared with that in nonhepatectomized groups. The results indicate that increased liver cell proliferation resulting from PH enhances the conversion of persisting DNA damage to a permanent alteration in DNA. The effect at 12 weeks after exposure supports the concept that DNA damage in hepatocytes is highly persistent.


Assuntos
Dietilnitrosamina/farmacologia , Fígado/enzimologia , Nitrosaminas/farmacologia , gama-Glutamiltransferase/biossíntese , Animais , Indução Enzimática , Hepatectomia , Fígado/efeitos dos fármacos , Masculino , Ratos , Ratos Endogâmicos F344 , Fatores de Tempo
4.
J Natl Cancer Inst ; 74(6): 1275-81, 1985 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2987594

RESUMO

Comprehensive studies of carcinogenesis in newborn or preweanling SD rats were conducted under various dose schedules of cycasin (CAS: 14901-08-7) administration. When cycasin was given sc to newborn rats at day 0, tumors were detected in more than 80% of rats of both sexes; kidney tumors were by far the most common. The incidences of tumors declined in the older groups, namely, over 60% in both sexes in the 7-day group, 55% in males and 8.3% in females in 14-day rats, and 0% in 21-day groups. By multiple administration, tumor incidences elevated considerably. Administration ip of cycasin also gave rise to tumor induction in newborn rats. A total of 435 kidney tumors found in the experiments were studied pathologically. Most of them were classified as mesenchymal tumor; some of them metastasized. A few other tumors were found in the liver and colon.


Assuntos
Compostos Azo , Cicasina , Neoplasias Experimentais/induzido quimicamente , Adenocarcinoma/induzido quimicamente , Adenocarcinoma/patologia , Animais , Animais Recém-Nascidos , Animais Lactentes , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/patologia , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/patologia , Feminino , Neoplasias Renais/induzido quimicamente , Neoplasias Renais/patologia , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/patologia , Masculino , Mesenquimoma/induzido quimicamente , Mesenquimoma/patologia , Neoplasias Experimentais/patologia , Ratos , Ratos Endogâmicos
5.
J Natl Cancer Inst ; 64(1): 163-7, 1980 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-6928041

RESUMO

Treatment of a homogenate of the mackerel fish Sanma hirakl with nitrite at pH 3 led to the development of direct-acting mutagenic activity for Salmonella typhlmurium TA-1535. Repeated gastric intubation three times/week for 6 months of an extract containing this mutagenic activity into noninbred Wistar rats led to the induction of tumors in 8 of 12 rats 12-18 months later. Adenomas and adenocarcinomas were found in the glandular stomach, squamous cell carcinoma was observed in the forestomach, and adenocarcinoma was found in the small intestine and pancreas. Furthermore, precancerous lesions (including intestinal metaplasia and glandular hyperplasia of the glandular stomach as well as squamous cell hyperplasia) were noted in virtually all of the animals at risk. No tumors were seen in 8 control rats given the untreated fish extract alone; 1 rat had glandular hyperplasia and intestinal metaplasia. Thus a mutagenic extract of nitrite-treated fish was demonstrated to induce, in the rat glandular stomach, cancers identical to gastric cancer observed in man. Preventive m:asures, including reduction of the intake of pickled foods and the year-round daily availability of foods containing vitamin C, are discussed.


Assuntos
Peixes , Nitritos/toxicidade , Neoplasias Gástricas/etiologia , Adenocarcinoma/etiologia , Adenoma/etiologia , Animais , Carcinoma de Células Escamosas/etiologia , Peixes/metabolismo , Masculino , Mutagênicos/metabolismo , Neoplasias Experimentais/etiologia , Nitritos/metabolismo , Ratos
6.
J Natl Cancer Inst ; 60(4): 819-24, 1978 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-633391

RESUMO

The formation of tobacco-specific nitrosamines from the major tobacco alkaloid nicotine was examined. Detached leaf tobacco was fed either [2'-14C]nicotine or [2'-14C]nornicotine and air cured. The cured leaf was then analyzed for [2'-14C]N'-nitrosonornicotine ([2'-14C]NNN). The yield of [2'-14C]NNN was 0.007% from nornicotine and 0.009% from nicotine. Because the ratio of nicotine to nornicotine in conventional nicotine-type tobacco is 20-100:1, nicotine is considered to be the major precursor for the carcinogen NNN in tobacco. The formation of other nitrosamines from nicotine in vitro was then studied. Reaction of nicotine with NaNO2 gave rise to NNN, as well as to two other nitrosamines, 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 4-(N-methyl-N-nitrosamino)-4-(3-pyridyl)butanal (NNA). Analysis of market products revealed the presence of NNK (0.6-24 microgram/g) in chewing tobacco and snuff. The tumorigenic activity of NNN, NNK, and NNA in strain A mice was studied. NNK induced more lung adenomas per mouse than did NNN, whereas NNA was less active than NNN. In addition, two cases of undifferentiated carcinoma of the salivary glands occurred in the NNN experimental groups.


Assuntos
Adenoma/induzido quimicamente , Neoplasias Pulmonares/induzido quimicamente , Nicotiana/metabolismo , Nitrosaminas/metabolismo , Plantas Tóxicas , Animais , Feminino , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos A , Neoplasias Experimentais/induzido quimicamente , Nicotina/análogos & derivados , Nicotina/metabolismo , Nicotina/toxicidade , Piridinas/metabolismo
7.
Cancer Res ; 42(6): 2298-309, 1982 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7074612

RESUMO

Hepatocellular altered foci were induced in rat liver by cycles of feeding of N-2-fluorenylacetamide and were distinguished by their resistance to iron accumulation following production of hepatic siderosis by dietary administration of 8-hydroxyquinoline and ferrous gluconate. The foci were readily identified by their iron exclusion in plastic-embedded sections stained for iron. Sections from iron-free regions processed for electron microscopy permitted ultrastructural study of cells in foci identified by reduced cytoplasmic ferritin. Altered foci of the eosinophilic type produced by cyclic feeding of carcinogen for 16 weeks were composed of both normal-appearing hepatocytes and others with ultrastructural abnormalities, including increased agranular reticulum with associated glycogen particles, decreased rough endoplasmic reticulum with reduced length of cisternae, degranulated rough vesicles, altered and displaced Golgi complexes, and abnormal bile canaliculi. At 12 and 24 weeks after cessation of carcinogen exposure, cells in persistent eosinophilic foci continued to display ultrastructural abnormalities. They possessed increased rough endoplasmic reticulum with rather regular cisternal arrangement and relatively increased smooth endoplasmic reticulum. Golgi complexes were abnormal. Bile canaliculi were abnormal and occasionally increased in number. Nuclei displayed prominent nucleoli. Cells in a basophilic focus were characterized by the presence of numerous free polyribosomes diffusely scattered throughout the cytoplasm, distended rough endoplasmic reticulum with loss of parallel-stack and hypertrophic dilated Golgi complexes, and prominent marginated nucleoli. The finding that persistent foci continued to display ultrastructural abnormalities, some of which changed or progressed in the absence of further carcinogen exposure, suggests that the persistent iron-excluding foci are a permanently altered population.


Assuntos
Ferro/metabolismo , Neoplasias Hepáticas Experimentais/ultraestrutura , 2-Acetilaminofluoreno/farmacologia , Animais , Transporte Biológico/efeitos dos fármacos , Cinética , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Masculino , Ratos , Ratos Endogâmicos F344
8.
Cancer Res ; 49(24 Pt 1): 7106-9, 1989 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-2555059

RESUMO

An immunotoxin was made by conjugating a murine monoclonal antibody (B4G7) that recognizes the human epidermal growth factor (EGF) receptor with gelonin, a ribosome-inactivating protein. This B4G7-gelonin conjugate was shown to be specifically cytotoxic for EGF receptor-hyperproducing cells. The conjugate was tested in nude mice and shown to be capable of suppressing the growth of an EGF receptor-hyperproducing squamous carcinoma cell (A431) solid tumor. Nude mice bearing an A431 cell tumor that were given injections i.p. for 5 consecutive days with at least 10 micrograms of the conjugate showed significant suppression of tumor growth for about 7 days. On the other hand, an unconjugated mixture of B4G7 and gelonin showed no specific antitumor activity against the A431 cell tumor. The growth of an EGF receptor-deficient small cell lung cancer cell (H69) tumor was not suppressed by injection of the conjugate. No toxic effects were observed in histological examination of nontumorous tissues of mice treated with at least 250 micrograms of conjugate per mouse. These results suggest that the conjugate may be useful for targeting therapy to EGF receptor-hyperproducing squamous carcinoma.


Assuntos
Receptores ErbB/efeitos dos fármacos , Imunotoxinas/farmacologia , Proteínas de Plantas/farmacologia , Animais , Anticorpos Monoclonais/farmacologia , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Sobrevivência Celular/efeitos dos fármacos , Receptores ErbB/imunologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Proteínas Inativadoras de Ribossomos Tipo 1 , Células Tumorais Cultivadas , Neoplasias Vulvares/patologia
9.
Cancer Res ; 52(10): 2995-8, 1992 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-1316233

RESUMO

Kidney and esophageal tumors induced by alkylating N-nitroso compounds in rats contain a high incidence (75-100%) of G----A transition mutations in the p53 gene. These are almost selectively (89%) located in the first base of codon 204 and the second base of 213, leading to amino acid substitutions Glu----Lys and Arg----Gln, respectively. In contrast to human neoplasms, a considerable fraction of rat kidney and esophageal tumors carries multiple p53 mutations. All nephroblastomas induced by transplacental exposure to N-nitrosoethylurea and 56% of esophageal tumors induced by N-nitrosomethylurea showed double mutations in codons 204 and 213 of exon 6. The selective targeting of p53 codons by alkylating nitrosamines may provide a basis for molecular epidemiological studies on this class of chemical carcinogens.


Assuntos
Códon/genética , Genes p53/genética , Neoplasias Experimentais/genética , Compostos Nitrosos , Acilação , Alelos , Animais , Sequência de Bases , Éxons/genética , Neoplasias Renais/induzido quimicamente , Neoplasias Renais/genética , Dados de Sequência Molecular , Mutação , Neoplasias Experimentais/induzido quimicamente , Ratos , Ratos Endogâmicos , Tumor de Wilms/induzido quimicamente , Tumor de Wilms/genética
10.
Cancer Res ; 39(8): 3262-7, 1979 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-222448

RESUMO

Nonspecific adjuvant immunotherapy with Bacillus Calmette-Guérin cell wall skeleton (BCG-CWS) was given to 155 lung cancer patients. Clinical effects of the BCG-CWS treatment were estimated by comparing the survival of the BCG-CWS group with that of a historical control group on the basis of 4-year results. Significant prolongation of survival time has been observed in Clinical Stages II, III (M0) and III (M1). However, most Stage III patients who were given the BCG-CWS treatment died of cancer itself after marked prolongation of survival time. An increase in complete cure rate has been expected only in Stages I and II. Surgicopathological staging was used in resected cases. Resected cases at any stage were sensitive to treatment with BCG-CWS. Histologically, all types of lung cancer including squamous cell carcinoma, adenocarcinoma, and anaplastic carcinoma were sensitive to treatment with BCG-CWS. Intrapleural administration of BCG-CWS to patients with malignant pleurisy was effective in controlling the pleural effusion and prolonging the survival time. No serious complication has been experienced in our study.


Assuntos
Vacina BCG/uso terapêutico , Neoplasias Pulmonares/terapia , Adenocarcinoma/terapia , Idoso , Vacina BCG/administração & dosagem , Vacina BCG/efeitos adversos , Carcinoma de Células Pequenas/terapia , Carcinoma de Células Escamosas/terapia , Feminino , Febre/etiologia , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Pleurisia/complicações , Pleurisia/terapia , Fatores de Tempo
11.
Biochim Biophys Acta ; 1080(2): 165-72, 1991 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-1932093

RESUMO

Rabbit liver and kidney tissues are known to produce an intestinal-like alkaline phosphatase (IAP-like enzyme) as a dominant isozyme, with a minor isozyme of tissue-unspecific type (UAP), unlike humans and other mammalians. We investigated immunohistochemically and biochemically these unique isozymes in the rabbit liver and bone, and compared them with the human isozyme. In rabbit liver, UAP was found to be localized only in the apical part of the membrane of cells lining the bile duct, whereas IAP-like enzyme was found in the sinusoidal membrane of hepatocytes. Rabbit liver UAP was separated from IAP-like enzyme by DEAE-cellulose column chromatography. Rabbit bone tissue contained only one UAP isozyme. The two UAPs were biochemically and physicochemically compared with human liver AP. Both UAPs reacted with an anti-human liver AP monoclonal antibody, not with an anti-human bone AP monoclonal antibody, indicating that both enzymes have the same antigenicity as human liver AP. Rabbit liver and bone UAPs had similar N-linked sugar-chain heterogeneities to the respective human enzymes. In addition, rabbit bone AP also had an O-linked sugar chain, as did human bone AP, unlike rabbit and human liver APs.


Assuntos
Fosfatase Alcalina/análise , Osso e Ossos/enzimologia , Isoenzimas/análise , Fígado/enzimologia , Fosfatase Alcalina/isolamento & purificação , Animais , Anticorpos Monoclonais , Cromatografia de Afinidade , Cromatografia DEAE-Celulose , Eletroforese em Gel de Poliacrilamida , Humanos , Immunoblotting , Imuno-Histoquímica , Isoenzimas/isolamento & purificação , Fígado/citologia , Peso Molecular , Especificidade de Órgãos , Coelhos
12.
Pharmacol Ther ; 73(2): 147-71, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9131722

RESUMO

As a new approach to predicting in vivo drug metabolism in humans, scaling of in vivo metabolic clearance from in vitro data obtained using human liver microsomes or hepatocytes is described in this review, based on the large number of literature data. Successful predictions were obtained for verapamil, loxtidine (lavoltidine), diazepam, lidocaine, phenacetin and some other compounds where CLint,in vitro is comparable with CLint,in vivo. On the other hand, for some metabolic reactions, differences in CLint,in vitro and CLint,in vivo greater than 5-fold were observed. The following factors are considered to be the cause of the differences: (1) metabolism in tissues other than liver, (2) incorrect assumption of rapid equilibrium of drugs between blood and hepatocytes, (3) presence of active transport through the sinusoidal membrane, and (4) interindividual variability. Furthermore, the possibility of predicting in vivo drug metabolic clearance from results obtained using a recombinant system of human P450 isozyme was described for a model compound, YM796, where the predicted metabolic clearances obtained from the recombinant system, taking account of the content of the P450 isozyme CYP3A4 in the human microsomes, were comparable with the observed clearances using human liver microsomes containing different amounts of CYP3A4. Even in the case where the first-pass metabolism exhibits nonlinearity, it appears to be possible to predict in vivo metabolic clearance from in vitro metabolic data.


Assuntos
Fígado/metabolismo , Preparações Farmacêuticas/metabolismo , Transporte Biológico Ativo , Humanos , Técnicas In Vitro , Taxa de Depuração Metabólica , Microssomos Hepáticos/metabolismo , Modelos Biológicos , Farmacocinética
13.
J Mol Biol ; 275(2): 365-78, 1998 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-9466915

RESUMO

Detailed analysis of the effects of alcohols on proteins and peptides is important because of its wide range of applications in many fields. Whereas melittin, a major component of honeybee venom, is unfolded in an aqueous environment, the addition of alcohols induces an alpha-helical structure. We used circular dichroism (CD) to compare the effects of various alcohols on melittin. Whereas the alpha-helical state was basically independent of alcohol species, the effectiveness of alcohols varied significantly. Among alkanols, the effectiveness was proportional to the bulkiness of hydrocarbon groups, indicating that the hydrocarbon group contributes positively to the alcohol effects. Comparison of alcohols with the same hydrocarbon group but a different number of hydroxyl groups showed that the hydroxyl groups contribute negatively to the alcohol effects. Comparison of several halogenols indicated that halogen increases the effectiveness in the order of F < Cl < Br. These results suggested that the effects of alcohol can be interpreted by the additive contributions of each of the constituent groups of the alcohol, which are proportional to the solvent-accessible surface area. However, for markedly effective alcohols such as 1,1,1,3,3,3-hexafluoro-2-propanol, the aggregation of alcohols was suggested to further enhance these effects. We have constructed equations for estimating the effectiveness of alcohols in inducing alpha-helical structure, which should also be useful for predicting the other effects of alcohols on proteins.


Assuntos
Álcoois/farmacologia , Meliteno/química , Estrutura Secundária de Proteína/efeitos dos fármacos , Sequência de Aminoácidos , Dicroísmo Circular , Simulação por Computador , Modelos Moleculares , Dados de Sequência Molecular , Relação Estrutura-Atividade
14.
Eur J Clin Nutr ; 69(8): 907-13, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25626408

RESUMO

BACKGROUND/OBJECTIVES: To examine the influence of season and climate (air temperature and humidity) on water intake by the food group in a sample of free-living Japanese adults. SUBJECTS/METHODS: Four-nonconsecutive-day, semi-weighed dietary records were collected from each of the four seasons in a single 12-month period (16 days in total). The influence of season and climate on individual water intake by the food group was analyzed using a mixed linear model. Participants were 242 healthy adults (121 women aged 30-69 years and 121 men aged 30-76 years) from four areas in Japan. RESULTS: For women and men together, the mean total water intake was 2230 g/day (highest in summer: 2331 g/day; lowest in winter: 2134 g/day). Fifty-one percent of water was derived from foods and the rest from beverages. In a mixed linear model adjusted for sex, age and body mass index, intake of water from foods decreased by 3.1 g/day and that from beverages increased by 8.4 g/day, with an increase in the mean outdoor air temperature on the survey day of 1 °C (both P < 0.0001). The influence of humidity was nonsignificant. CONCLUSIONS: In contrast to previous findings in Western countries, half of water intake in Japanese adults was derived from foods. Water intake from beverages was positively associated with air temperature, whereas that from foods was inversely associated with air temperature.


Assuntos
Bebidas/análise , Comportamento de Ingestão de Líquido , Ingestão de Líquidos , Análise de Alimentos , Estações do Ano , Temperatura , Adulto , Idoso , Registros de Dieta , Inquéritos sobre Dietas/métodos , Feminino , Voluntários Saudáveis , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Características de Residência
15.
Protein Sci ; 6(2): 416-21, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9041644

RESUMO

Alcohols denature the native state of proteins, and also stabilize the alpha-helical conformation in unfolded proteins and peptides. Among various alcohols, trifluoroethanol (TFE) and hexafluoroisopropanol (HFIP) are often used because of their high potential to induce such effects. However, the reason why TFE and HFIP are more effective than other alcohols is unknown. Using CD, we studied the effects of TFE and HFIP as well as reference alcohols, i.e., methanol, ethanol, and isopropanol, on the conformation of bovine beta-lactoglobulin and the bee venom melittin at pH 2. Upon addition of alcohols, beta-lactoglobulin exhibited a transformation from the native state, consisting of beta-sheets, to the alpha-helical state, whereas melittin folded from the unfolded state to the alpha-helical state. In both cases, the order of effectiveness of alcohols was shown to be: HFIP > TFE > isopropanol > ethanol > methanol. The alcohol-induced transitions were analyzed assuming a two-state mechanism to obtain the m value, a measure of the dependence of the free energy change on alcohol concentration. Comparison of the m values indicates that the high potential of TFE can be explained by the additive contribution of constituent groups, i.e., F atoms and alkyl group. On the other hand, the high potential of HFIP is more than that expected from the additive effects, suggesting that the cooperative formation of micelle-like clusters of HFIP is important.


Assuntos
Lactoglobulinas/química , Meliteno/química , Propanóis , 1-Propanol/química , Álcoois/química , Conformação Proteica , Desnaturação Proteica
16.
Neuropharmacology ; 24(6): 567-70, 1985 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2410807

RESUMO

The effects of locally applied opioids on the release of immunoreactive Substance P (iSP), induced by mechanical stimuli, from the dorsal horn of the rabbit in situ, were investigated. Morphine and met-enkephalin (met-enk), but not dynorphin A (1-17) (DYN), in a concentration of 10 microM, significantly inhibited the evoked release. These inhibitory effects of morphine and met-enkephalin were antagonized by the local application of naloxone (10 microM) to the dorsal horn. These results suggest that the inhibition of the release of Substance P induced by noxious mechanical stimuli may be mediated by mu and delta, but not by kappa opioid receptors.


Assuntos
Células do Corno Anterior/efeitos dos fármacos , Dinorfinas/farmacologia , Encefalina Metionina/farmacologia , Morfina/farmacologia , Neurônios Motores/efeitos dos fármacos , Substância P/metabolismo , Animais , Estado de Descerebração , Masculino , Neurônios/efeitos dos fármacos , Estimulação Física , Coelhos
17.
Neuroscience ; 30(1): 241-50, 1989.
Artigo em Inglês | MEDLINE | ID: mdl-2473412

RESUMO

Characteristics of in situ substance P release from the lumbar dorsal horn were investigated in decerebrated rabbits. Noxious mechanical stimuli produced by pinching the skin of a hind leg ipsilateral to the perfusion site remarkably and significantly increased the release of immunoreactive substance P, which was identified as substance P itself, using separation with high-performance liquid chromatography and radioimmunoassay. The noxious pinch did not affect the release of immunoreactive substance P, when applied to the contralateral hind leg. Both the basal and pinch-evoked release of immunoreactive substance P were largest in the dorsolateral part of the dorsal horn. The pinch-evoked release of immunoreactive substance P was abolished when the dorsal horn was perfused with a Ca2+-free medium containing 7 mM Mg2+ or with a medium with 10 microM tetrodotoxin added. The evoked release of immunoreactive substance P was also abolished following pretreatment of a stimulated region with the local anesthetic dibucaine, a procedure which inhibited the pinch-evoked aversive behavior in freely-moving rabbits. Among a variety of natural stimuli applied to the hind leg, noxious pinch and a subcutaneous injection of formaldehyde solution significantly evoked the release of immunoreactive substance P from the dorsal horn. The most intense heat or scalding stimulation increased the immunoreactive substance P release in two out of five experiments. However, other natural stimuli such as ice-cold, warm, noxious heat and innocuous mechanical stimuli produced no apparent changes in the release of immunoreactive substance P. These results suggest that among the noxious stimuli, only mechanical and inflammatory but not thermal stimuli lead to a release of substance P from the primary afferent terminals in the dorsal horn. The present findings suggest that, at least in rabbits, substance P-containing primary afferents have high-threshold mechanoreceptors. Substance P may participate in the transmission of information related to noxious mechanical and inflammatory stimulation from the periphery to the dorsal horn.


Assuntos
Dor/metabolismo , Medula Espinal/metabolismo , Substância P/metabolismo , Animais , Formaldeído , Temperatura Alta , Masculino , Estimulação Física , Coelhos , Medula Espinal/fisiologia , Substância P/fisiologia
18.
Cancer Lett ; 6(6): 365-9, 1979 May.
Artigo em Inglês | MEDLINE | ID: mdl-455275

RESUMO

Undifferentiated carcinomas of the salivary glands were found in 2 of 44 (4.5%) strain A mice injected intraperitoneally with a tobacco specific nitrosamine, N-nitrosonornicotine (NNN). The presence of intranuclear rodlets (INR) in the salivary carcinomas provided the first demonstration of such structures in a non-neuronal tumor in mice. Two types of rodlets were exhibited; one was composed of fibrillar filaments arranged in bundles, and the other was much thicker, branching in form. These INR appeared to be closely associated with nuclear chromatin or nucleoli.


Assuntos
Núcleo Celular/ultraestrutura , Nicotiana , Nicotina/análogos & derivados , Nitrosaminas , Plantas Tóxicas , Neoplasias das Glândulas Salivares/ultraestrutura , Animais , Nucléolo Celular/ultraestrutura , Cromatina/ultraestrutura , Feminino , Camundongos , Camundongos Endogâmicos A , Microscopia Eletrônica , Neoplasias Experimentais/ultraestrutura , Neoplasias das Glândulas Salivares/induzido quimicamente
19.
Cancer Lett ; 5(3): 179-83, 1978 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-688199

RESUMO

The tumor initiating activity on mouse skin of benzo[a]pyrene (BaP), 7,10-dimethylBaP, and 10-methylBaP was determined. Each compound was tested at initiating doses of 50 microgram and 100 microgram with promotion by application 3 times weekly of 2.5 microgram tetradecanoylphorbol acetate. BaP induced tumors in 40% (100 microgram) and 25% (50 microgram) of the animals. No tumors were observed in either group treated with 7,10-dimethylBaP. In the groups treated with 10-methyl-Bap, the incidence of tumor bearing animals was 20% at both doses. These results and the results of previous studies on other methylated BaP derivatives suggest that the mechanism of activation of these compounds is similar to that observed for the parent hydrocarbon and probably involves formation of an angular ring diol-epoxide or epoxide.


Assuntos
Benzopirenos/toxicidade , Neoplasias Cutâneas/induzido quimicamente , Animais , Benzopirenos/metabolismo , Biotransformação , Feminino , Ceratoacantoma/induzido quimicamente , Camundongos , Neoplasias Experimentais/induzido quimicamente , Papiloma/induzido quimicamente , Pele/metabolismo , Relação Estrutura-Atividade , Acetato de Tetradecanoilforbol/administração & dosagem
20.
Lung Cancer ; 11(1-2): 43-50, 1994 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7521732

RESUMO

We conducted a trial to clarify what Japanese clinical doctors think about the present status of therapy for non-small cell lung cancer, as well as to clarify which problems are still unresolved. One-hundred five Japanese doctors who treat lung cancer patients were asked how they would choose to be treated, if they suffered from non-small cell lung cancer. Six scenarios were presented and the doctors had to choose one treatment method for each of the six scenarios. Adjuvant chemotherapy or radiotherapy after complete resection, increase with progression of the pathological stage. Ninety-three per cent of Japanese doctors wanted surgery, even if mediastinal lymph node metastases were present. In the scenario of only one distant metastasis to the brain, 44% of doctors wanted surgery while 39% wanted chemotherapy and/or radiotherapy. In the scenario of multiple bone metastases, 33% wanted chemotherapy, 77% did not. It was concluded therefore that Japanese doctors choose surgery as the number one treatment modality when all lesions are considered resectable.


Assuntos
Atitude do Pessoal de Saúde , Carcinoma Pulmonar de Células não Pequenas/psicologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimioterapia Adjuvante/psicologia , Neoplasias Pulmonares/psicologia , Neoplasias Pulmonares/terapia , Médicos/psicologia , Pneumonectomia/psicologia , Radioterapia/psicologia , Adulto , Fatores Etários , Neoplasias Ósseas/secundário , Neoplasias Ósseas/terapia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Carcinoma Pulmonar de Células não Pequenas/secundário , Terapia Combinada/psicologia , Humanos , Medicina Interna , Japão , Metástase Linfática , Pessoa de Meia-Idade , Cuidados Paliativos/psicologia , Cirurgia Torácica
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