RESUMO
BACKGROUND: In examining childhood overweight/obesity, there is a need to consider both eating quickly and eating until full. This longitudinal study investigated the influence of eating quickly and/or eating until full on anthropometric variables and becoming overweight/obese among Japanese schoolgirls. METHODS: Study participants were fourth-grade schoolgirls (aged 9 or 10 years) in Ina Town, Japan. Physical examinations and a questionnaire survey were performed at baseline (fourth grade) and after 3 years (seventh grade). Height, weight, and waist circumference were measured in the physical examinations, while the data on eating quickly and eating until full were collected in the questionnaire survey. Analysis of variance and analysis of covariance were used to compare the differences in each anthropometric variable between fourth and seventh grade among groups. RESULTS: Data on 425 non-overweight/obese schoolgirls in fourth grade were analyzed. Gains in anthropometric variables (body mass index, waist circumference, and waist-to-height ratio) from fourth to seventh grade were significantly larger in the "eating quickly and eating until full" group than in the "not eating quickly and not eating until full" group. In contrast, there were no significant differences in the gains between the "eating quickly or eating until full" group and the "not eating quickly and not eating until full" group. The proportion of overweight/obese girls in seventh grade was higher in the "eating quickly and eating until full" group than in the other groups. CONCLUSIONS: Eating quickly and eating until full had a substantial impact on excess gains in anthropometric variables among schoolgirls, suggesting that modifying these eating behaviors may help prevent non-overweight/obese girls from the excess gains. Accordingly, school health programs need to focus on not eating quickly and/or not eating until full to prevent overweight/obesity; it is necessary to emphasize "the risk of overweight/obesity associated with these eating behaviors" in schools.
Assuntos
Comportamento Alimentar/fisiologia , Sobrepeso/etiologia , Saciação/fisiologia , Aumento de Peso/fisiologia , Antropometria/métodos , Constituição Corporal/fisiologia , Índice de Massa Corporal , Criança , Feminino , Humanos , Japão , Estudos Longitudinais , Sobrepeso/fisiopatologia , Sobrepeso/prevenção & controle , Circunferência da Cintura/fisiologiaRESUMO
BACKGROUND: This study examined the relationship between rapid weight gain during infancy and/or early childhood and anthropometric measurements [body mass index (BMI), percent body fat (%BF), waist circumference (WC) and waist-to-height ratio (WHtR)] in preadolescence by sex. METHODS: Subjects were fourth-grade school children (aged 9 to 10 years) from elementary schools in Ina-town, Japan, in 2010. Measurements of height, weight, %BF and WC were conducted for each subject. We obtained data on height and weight of subjects at birth, age 1.5 years and age 3 years from the Maternal and Child Health handbook. Rapid weight gain was defined as a change in weight-for-age standard deviation score greater than 0.67 from birth to age 1.5 years (infancy) or from age 1.5 to 3 years (early childhood). RESULTS: All anthropometric variables (BMI, %BF, WC and WHtR) at age 9 to 10 years were significantly higher in the rapid weight gain during both infancy and early childhood period group than in the no rapid weight gain group, regardless of sex. When compared with the no rapid weight gain group, rapid weight gain during early childhood period had significantly higher BMI and WC in boys and BMI, %BF and WC in girls. Compared with the no rapid weight gain group, the rapid weight gain during infancy group had a significantly higher WC in boys and significantly higher BMI and WC in girls. CONCLUSION: Rapid weight gain during both infancy and early childhood was related to higher anthropometric measurements, including WHtR, among Japanese preadolescents, regardless of sex. This study suggests that rapid weight gain during infancy and early childhood may be a risk factor for general/abdominal obesity later in life.
Assuntos
Obesidade Infantil/epidemiologia , Aumento de Peso/fisiologia , Estatura , Índice de Massa Corporal , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Japão/epidemiologia , Masculino , Obesidade Infantil/prevenção & controle , Valores de Referência , Reprodutibilidade dos Testes , Fatores de Risco , Circunferência da CinturaRESUMO
BACKGROUND: The objective of this study was to examine the relationship between rapid weight gain during early childhood and overweight in preadolescence by sex. METHOD: Study subjects were 676 boys and 620 girls in fourth grade (aged 9 or 10 years) from elementary schools in Ina-town, Japan, during 2010-2012. Height and weight of subjects at birth, age 1.5 and 3 years, were collected from the Maternal and Child Health Handbook, while values at 9-10 years were measured. Rapid weight gain was defined as a change in weight-for-age standard deviation score greater than 0.67 from birth to age 1.5 years (0-1.5 years) or from age 1.5 to 3 years (1.5-3 years). RESULTS: After adjustment for confounding factors, compared with no rapid weight gain, rapid weight gain during 0-1.5 years and 1.5-3 years or rapid weight gain during 1.5-3 years but not during 0-1.5 years significantly increased the odds ratio (OR) for overweight at age 9-10 years in boys (OR, 6.21; 95% confidence interval [CI], 2.84-13.58 and OR, 3.31; 95% CI, 1.67-6.54, respectively) and girls (OR, 7.55; 95% CI, 2.99-19.07 and OR, 3.42; 95% CI, 1.38-8.49, respectively). CONCLUSION: The present study suggests that rapid weight gain during early childhood was associated with being overweight in preadolescence, regardless of sex.
Assuntos
Sobrepeso/etiologia , Aumento de Peso , Idade de Início , Índice de Massa Corporal , Criança , Feminino , Promoção da Saúde , Humanos , Japão/epidemiologia , Estudos Longitudinais , Masculino , Razão de Chances , Sobrepeso/epidemiologia , Sobrepeso/prevenção & controle , Prevalência , Fatores de Risco , Aumento de Peso/fisiologiaRESUMO
BACKGROUND: Some cases of human papillomavirus (HPV) type 56 infection in Bowen disease have been reported. However, the incidence and clinical characteristics are still unclear. OBJECTIVE: To clarify the prevalence of HPV type 56-positive Bowen disease in our department and to characterize the clinical manifestations. METHODS: Sixty-eight specimens of Bowen disease were examined by polymerase chain reaction using HPV consensus primers, and the amplified products were subjected to DNA sequence analyses. Moreover, positive samples were investigated by in situ hybridization. These findings were used to clarify the clinical characteristics of HPV-positive Bowen disease. RESULTS: Eight out of 68 specimens (12%) of Bowen disease were HPV-positive, of which six specimens were HPV type 56-positive. The HPV type 56-positive lesions were characterized by a longitudinal melanonychia or a deeply pigmented keratotic lesion. The remaining two specimens were genital Bowen disease in which HPV type 16 was detected. In situ hybridization demonstrated the positive cells in the upper layer of epidermis. The HPV type 56 detected in the samples of longitudinal melanonychia can be divided into at least into two types. CONCLUSIONS: This study determined the prevalence of HPV type 56-positive Bowen disease. Longitudinal melanonychia is the most characteristic manifestation of HPV type 56-associated Bowen disease.
Assuntos
Doença de Bowen/virologia , Infecções por Papillomavirus/complicações , Neoplasias Cutâneas/virologia , Adulto , Idoso , Doença de Bowen/patologia , DNA Viral/análise , Feminino , Humanos , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/patologia , Reação em Cadeia da Polimerase , Neoplasias Cutâneas/patologiaRESUMO
Ohtahara syndrome (OS) is one of the most severe and earliest forms of epilepsy. We have recently identified that the de novo mutations of STXBP1 are important causes for OS. Here we report a paternal somatic mosaicism of an STXBP1 mutation. The affected daughter had onset of spasms at 1 month of age, and interictal electroencephalogram showed suppression-burst pattern, leading to the diagnosis of OS. She had a heterozygous c.902+5G>A mutation of STXBP1, which affects donor splicing of exon 10, resulting in 138-bp insertion of intron 10 sequences in the transcript. The mutant transcript had a premature stop codon, and was degraded by nonsense-mediated mRNA decay in lymphoblastoid cells derived from the patient. High-resolution melting analysis of clinically unaffected parental DNAs suggested that the father was somatic mosaic for the mutation, which was also suggested by sequencing. Cloning of PCR products amplified with the paternal DNA samples extracted from blood, saliva, buccal cells, and nails suggested that 5.3%, 8.7%, 11.9%, and 16.9% of alleles harbored the mutation, respectively. This is a first report of somatic mosaicism of an STXBP1 mutation, which has implications in genetic counseling of OS.
Assuntos
Epilepsia/genética , Mosaicismo , Proteínas Munc18/genética , Espasmos Infantis/genética , Pai , Feminino , Humanos , Lactente , Recém-Nascido , MasculinoRESUMO
BACKGROUND/AIMS: Rapid removal of plasma amyloid-ß (Aß) by blood purification may serve as a peripheral Aß sink from the brain for Alzheimer's disease therapy. We investigated the reduction of plasma Aß during hemodialysis and cognitive states. METHODS: Aß concentrations and Mini-Mental State Examinations (MMSE) were investigated in 37 hemodialysis patients (68.9 ± 4.1 years). RESULTS: The dialyzers effectively removed Aß(1-40) and Aß(1-42), 63.9 ± 14.4 and 51.6 ± 17.0% at 4 h dialysis, resulting in the reduction of Aßs in whole-body circulation by 51.1 ± 8.9 and 32.7 ± 12.0%, respectively. Although the plasma Aßs before dialysis (750.8 ± 171.3 pg/ml for Aß(1-40)) were higher than those reported for Alzheimer's disease patients, the cognitive states of hemodialysis patients were relatively normal, especially of longer dialysis vintages. CONCLUSIONS: Dialyzers effectively reduced Aßs in whole-body circulation. Repeated rapid decrease of plasma Aßs might maintain cognitive state.
Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/terapia , Peptídeos beta-Amiloides/sangue , Encéfalo/metabolismo , Fragmentos de Peptídeos/sangue , Diálise Renal/estatística & dados numéricos , Idoso , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/isolamento & purificação , Encéfalo/patologia , Encéfalo/fisiopatologia , Cognição , Ensaio de Imunoadsorção Enzimática , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fragmentos de Peptídeos/isolamento & purificaçãoRESUMO
Human immunodeficiency virus type 1 (HIV-1) infects target cells by binding to CD4 and a chemokine receptor, most commonly CCR5. CXCR4 is a frequent alternative coreceptor (CoR) in subtype B and D HIV-1 infection, but the importance of many other alternative CoRs remains elusive. We have analyzed HIV-1 envelope (Env) proteins from 66 individuals infected with the major subtypes of HIV-1 to determine if virus entry into highly permissive NP-2 cell lines expressing most known alternative CoRs differed by HIV-1 subtype. We also performed linear regression analysis to determine if virus entry via the major CoR CCR5 correlated with use of any alternative CoR and if this correlation differed by subtype. Virus pseudotyped with subtype B Env showed robust entry via CCR3 that was highly correlated with CCR5 entry efficiency. By contrast, viruses pseudotyped with subtype A and C Env proteins were able to use the recently described alternative CoR FPRL1 more efficiently than CCR3, and use of FPRL1 was correlated with CCR5 entry. Subtype D Env was unable to use either CCR3 or FPRL1 efficiently, a unique pattern of alternative CoR use. These results suggest that each subtype of circulating HIV-1 may be subject to somewhat different selective pressures for Env-mediated entry into target cells and suggest that CCR3 may be used as a surrogate CoR by subtype B while FPRL1 may be used as a surrogate CoR by subtypes A and C. These data may provide insight into development of resistance to CCR5-targeted entry inhibitors and alternative entry pathways for each HIV-1 subtype.
Assuntos
Infecções por HIV/virologia , HIV-1/fisiologia , Receptores CCR3/metabolismo , Receptores de Formil Peptídeo/metabolismo , Receptores de Lipoxinas/metabolismo , Receptores Virais/metabolismo , Internalização do Vírus , Linhagem Celular , HIV-1/genética , Humanos , Dados de Sequência Molecular , Análise de Sequência de DNA , Produtos do Gene env do Vírus da Imunodeficiência Humana/genéticaRESUMO
We report a Japanese girl affected with a neonatal-onset form of propionic acidaemia (PA). She developed severe metabolic crisis after dehydration at 2 years of age. Bradycardia with complete atrioventricular block responded to haemodiafiltration, but severe cardiac failure was refractory to inotropic treatment. She was diagnosed with acute cardiac dysfunction caused by PA-induced metabolic crisis. Extracorporeal membrane oxygenation (ECMO), a technique for providing mechanical circulatory support, was required. This is the first case report of a PA patient who recovered from a life-threatening metabolic crisis with cardiac failure by ECMO. Cardiac failure may be a cause of death, but it is occasionally an under-recognized complication. Mitochondrial dysfunction in the myocardium due to propionyl-CoA could contribute to the pathomechanism of cardiac complications of PA. We believe that ECMO should be attempted in PA patients with cardiac failure, in addition to haemodiafiltration and other therapeutic measures, because doing so may lead to the recovery of cardiac dysfunction, as was evident in our patient. In conclusion, prompt investigations and management of cardiac complications should be performed immediately during PA-induced metabolic crises.
Assuntos
Oxigenação por Membrana Extracorpórea , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Acidemia Propiônica/complicações , Pré-Escolar , Estado Terminal , Feminino , Hemodiafiltração , Humanos , Acidemia Propiônica/terapia , Fatores de TempoRESUMO
To assess oxidative stress (OS) induced by endurance exercise, concentrations of serum reactive oxygen species (ROS) were determined in 70 Japanese male amateur runners completing a two-day ultra-marathon race. Serum ROS levels were analyzed at three time points: before the race (baseline), after the 1st day race (mid-race), and after the 2nd day race (goal) (post-race). The means (SE) of ROS were 151.4(3.7) (U. CARR.), 168.7(4.4), and 156.8(4.4), respectively. Significant positive trends were noted between age and serum ROS concentrations at the three race points (p<0.05 for all). After adjusting for age, BMI and average monthly running distance, the baseline serum ROS concentrations were positively associated with completion times of the first-day race, in particular (p<0.05), suggesting that the concentrations may predict physical performance. The ROS production increased at mid-race (p<0.05), but the levels returned to baseline levels at post-race, indicating that an antioxidant defense system may develop post-race to reduce OS.
Assuntos
Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/sangue , Corrida/fisiologia , Adulto , Fatores Etários , Desempenho Atlético/fisiologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Resistência Física/fisiologiaRESUMO
BACKGROUND: As Bowen's disease of the nail apparatus is quite rare, there have been only a few reports on the prevalence of human papillomavirus (HPV) infection in this condition. OBJECTIVES: The purpose of this study was to clarify the association of HPV with this disease involving the nail apparatus. METHODS: Five patients with Bowen's disease of the nail apparatus were investigated clinically, virologically and histologically. Total DNAs extracted from excised skin lesions were analysed using polymerase chain reaction (PCR) for the presence of HPV DNA and the amplified products were subjected to DNA sequence analyses. Histological localization of HPV DNA was examined by in situ hybridization. RESULTS: In three of five patients, HPV was detected by PCR amplification, and subsequent sequence analyses of the PCR products showed the sequences of HPV type 56. A common clinical feature of the three HPV-positive patients was longitudinal melanonychia. In contrast, the two HPV-negative patients presented with a convex nail deformity and a periungual ulcerative lesion. In two of three positive cases, there was a silent point mutation in the L1 gene of each HPV. In the remaining one case, the nucleotide sequence was consistent with the consensus sequence of HPV 56. Sequence analyses of the E6 gene revealed the infection of different variants of HPV 56 among the three cases. The viral genomes were located in keratinocyte nuclei upon in situ hybridization. CONCLUSIONS: HPV 56 may be involved in the carcinogenesis of Bowen's disease affecting the nail matrix with longitudinal pigmentation.
Assuntos
Doença de Bowen/patologia , DNA Viral/isolamento & purificação , Doenças da Unha/patologia , Infecções por Papillomavirus/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Doença de Bowen/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Unha/virologia , Unhas/microbiologia , Infecções por Papillomavirus/genética , Reação em Cadeia da Polimerase/métodos , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/virologiaRESUMO
Bach2 is a B-cell- and neuron-specific transcription repressor that forms heterodimers with the Maf-related oncoproteins. We show here that Bach2 activates transcription by interacting with its novel partner MAZR. MAZR was isolated by the yeast two-hybrid screen using the BTB/POZ domain of Bach2 as bait. Besides the BTB/POZ domain, MAZR possesses Zn finger motifs that are closely related to those of the Myc-associated Zn finger (MAZ) protein. MAZR mRNA was coexpressed with Bach2 in B cells among hematopoietic cells and in developing mouse limb buds, suggesting a cooperative role for MAZR and Bach2 in these cells. MAZR forms homo- and hetero-oligomers with Bach2 through the BTB domain, which oligomers bind to guanine-rich sequences. Unlike MAZ, MAZR functioned as a strong activator of the c-myc promoter in transfection assays with B cells. However, it does not possess a typical activation domain, suggesting a role for it as an unusual type of transactivator. The fgf4 gene, which regulates morphogenesis of limb buds, contains both guanine-rich sequences and a Bach2 binding site in its regulatory region. In transfection assays using fibroblast cells, the fgf4 gene was upregulated in the presence of both MAZR and Bach2 in a BTB/POZ domain-dependent manner. The results provide a new perspective on the function of BTB/POZ domain factors and indicate that BTB/POZ domain-mediated oligomers of transcription factors may serve as combinatorial codes for gene expression.
Assuntos
Regulação da Expressão Gênica , Proteínas de Neoplasias , Proteínas Repressoras , Fatores de Transcrição/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Fatores de Transcrição de Zíper de Leucina Básica , Linhagem Celular , Proteínas de Ligação a DNA , Desenvolvimento Embrionário e Fetal/genética , Camundongos , Dados de Sequência Molecular , Alinhamento de Sequência , Análise de Sequência de DNA , TransfecçãoRESUMO
Members of the small Maf family (MafK, MafF, and MafG) are basic region leucine zipper (bZip) proteins that can function as transcriptional activators or repressors. The dimer compositions of their DNA binding forms determine whether the small Maf family proteins activate or repress transcription. Using a yeast two-hybrid screen with a GAL4-MafK fusion protein, we have identified two novel bZip transcription factors, Bach1 and Bach2, as heterodimerization partners of MafK. In addition to a Cap'n'collar-type bZip domain, these Bach proteins possess a BTB domain which is a protein interaction motif; Bach1 and Bach2 show significant similarity to each other in these regions but are otherwise divergent. Whereas expression of Bach1 appears ubiquitous, that of Bach2 is restricted to monocytes and neuronal cells. Bach proteins bind in vitro to NF-E2 binding sites, recognition elements for the hematopoietic transcription factor NF-E2, by forming heterodimers with MafK. Furthermore, a DNA binding complex that contained MafK as well as Bach2 or a protein related closely to Bach2 was found to be present in mouse brain cells. Bach1 and Bach2 function as transcription repressors in transfection assays using fibroblast cells, but they function as a transcriptional activator and repressor, respectively, in cultured erythroid cells. The results suggest that members of the Bach family play important roles in coordinating transcription activation and repression by MafK.
Assuntos
Encéfalo/metabolismo , Proteínas de Ligação a DNA/metabolismo , Neurônios/metabolismo , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Transcrição Gênica , Sequência de Aminoácidos , Animais , Sequência de Bases , Fatores de Transcrição de Zíper de Leucina Básica , Sítios de Ligação , Clonagem Molecular , Sequência Consenso , Dimerização , Fatores de Ligação de DNA Eritroide Específicos , Zíper de Leucina , Fator de Transcrição MafK , Camundongos , Dados de Sequência Molecular , Monócitos/metabolismo , Fator de Transcrição NF-E2 , Subunidade p45 do Fator de Transcrição NF-E2 , Proteínas Nucleares/química , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , Saccharomyces cerevisiae , Homologia de Sequência de Aminoácidos , Fatores de Transcrição/química , Dedos de ZincoRESUMO
To construct a mammalian artificial chromosome (MAC), telomere repeats and selectable markers were introduced into a 100 kb yeast artificial chromosome (YAC) containing human centromeric DNA. This YAC, which has a regular repeat structure of alpha-satellite DNA and centromere protein B (CENP-B) boxes, efficiently formed MACs that segregated accurately and bound CENP-B, CENP-C, and CENP-E. The MACs appear to be about 1-5 Mb in size and contain YAC multimers. Structural analyses suggest that the MACs have not acquired host sequences and were formed by a de novo mechanism. The accurate segregation of the MACs suggests they have potential as vectors for introducing genes into mammals.
Assuntos
Autoantígenos , Cromossomos Artificiais de Levedura/genética , Cromossomos/genética , Proteínas de Ligação a DNA , Animais , Linhagem Celular , Linhagem Celular Transformada , Centrômero/genética , Proteína B de Centrômero , Proteínas Cromossômicas não Histona/química , Proteínas Cromossômicas não Histona/genética , Cromossomos Humanos Par 21/genética , Clonagem Molecular , DNA Satélite/química , DNA Satélite/genética , Vetores Genéticos/genética , Humanos , Hibridização in Situ Fluorescente , Cinetocoros , Reação em Cadeia da Polimerase , Telômero/genética , TransfecçãoRESUMO
Mice fed a diet containing 0.3 or 0.03% triethanolamine developed malignant tumors. Females showed a high incidence of tumors in lymphoid tissues, while this type was absent in males. Tumors in other tissues were produced at a considerable rate in both sexes, but no hepatoma was found. Triethanolamine was not mutagenic to Bacillus subtilis by itself, but it became mutagenic after reacting with sodium nitrite under acidic conditions or when the mixture was heated. Although N-nitrosodiethanolamine, a known carcinogen and mutagen, was detected in the reaction mixture by thin-layer chromatography, it may not be the main mutagenic product, because the product was a stable and direct mutagen and its mutagenic activity was destroyed by liver enzymes, unlike N-nitrosodiethanolamine. The lethal and mutagenic DNA damages produced by this unidentified product were susceptible to some extent to the repair functions of the bacteria.
Assuntos
Carcinógenos , Etanolaminas/toxicidade , Mutagênicos , Neoplasias Experimentais/induzido quimicamente , Nitritos/farmacologia , Nitrito de Sódio/farmacologia , Animais , Bacillus subtilis/efeitos dos fármacos , Biotransformação , Interações Medicamentosas , Etanolaminas/metabolismo , Feminino , Linfoma/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos ICR , Nitrito de Sódio/metabolismoRESUMO
Skin tumors were produced in female ICR mice by 90Sr-90Y beta-irradiation and subsequent 4-nitroquinoline 1-oxide painting. The doses were chosen so as to produce no tumors with a single agent alone; the interval between two treatments ranged from 11 to 408 days. The tumor induction rate was found to be at almost the same level (average, 12.4%) for each interval. The results indicate the persistence of the latent carcinogenic alterations in the beta-irradiated mouse skin.
Assuntos
4-Nitroquinolina-1-Óxido , Neoplasias Induzidas por Radiação , Nitroquinolinas , Efeitos da Radiação , Neoplasias Cutâneas/etiologia , 4-Nitroquinolina-1-Óxido/administração & dosagem , Administração Tópica , Animais , Feminino , Camundongos , Camundongos Endogâmicos ICR , Neoplasias Experimentais/induzido quimicamente , Pele/efeitos da radiação , Neoplasias Cutâneas/induzido quimicamente , Radioisótopos de Estrôncio , Radioisótopos de ÍtrioRESUMO
The radiation response of autochthonous tumors induced by s.c. injection of 3-methylcholanthrene in ICR/JCL mice was studied. The tumors were mostly fibrosarcomas and grew with an average volume-doubling time of 2.6 days, independently of the time tumor appearance or dose of the chemical used. The tumors were locally and singly irradiated with 6-MV X-rays through a filter. Autochthonous tumors were similar to their transplants in postirradiation regression and gross cellular radiosensitivity (Do, 400 rads), as estimated from regrowth time. However, most of the autochthonous tumors irradiated with single doses of up to 7.4 kilorads recurred within 120 days, whie in identically irradiated tumor transplants a complete cure was obtained with doses of 6.5 kilorads or more. The 50% tumor control dose with no recurrence within 120 days was 4.4 kilorads for the transplants. Transplantation of 26 irradiated autochthonous fibrosarcomas produced only a few tumors in autochthonous hosts, and they were completely rejected in other, previously tumor-free mice; a 48% recurrence was noted even after resection of the irradiated tumor. Two possibilities for the apparent radioresistance of autochthonous tumors were suggested: (a) existence of radioresistant cells in autochthonous tumors; and (b) induction of a second new tumor by the additive effect of the chemical and radiation. Although our results are preliminary, the second possibility is not favored since autochthonous tumors induced with low doses of 3-methylcholanthrene recurred with high frequency after irradiation. Moreover, irradiation of tumor-free mouse skin that had been treated with the carcinogen produced tumors at a very low frequency.
Assuntos
Metilcolantreno , Neoplasias Cutâneas/radioterapia , Animais , Feminino , Fibrossarcoma/induzido quimicamente , Fibrossarcoma/radioterapia , Injeções Subcutâneas , Camundongos , Transplante de Neoplasias , Neoplasias Experimentais/induzido quimicamente , Neoplasias Experimentais/radioterapia , Prognóstico , Tolerância a Radiação , Neoplasias Cutâneas/induzido quimicamente , Fatores de Tempo , Transplante Autólogo , Raios XRESUMO
We have studied the ability of some phospholipids (PLs) and phospholipases (PLases) to interfere with infection of human T-cell leukemia virus type I (HTLV-I). Plating of pseudotype of vesicular stomatitis virus (VSV) bearing envelope antigens of HTLV-I, VSV(HTLV-I), was markedly inhibited by treatment of the cells with cardiolipin (CL) after, but not before, infection. Treatment of the cells with CL after infection also inhibited the plating of VSV pseudotype of bovine leukemia virus (BLV), but scarcely affected VSV infection. Furthermore, the plating of VSV(HTLV-I) was markedly enhanced by treatment with PLCase after infection. Treatment with PLCase, however, did not affect the plating of VSV. These results were also confirmed by polymerase chain reaction (PCR): Formation of proviral DNA was inhibited when indicator cells were treated with CL after cell-free infection of HTLV-I, but not before, and enhanced when indicator cells were treated with PLCase after HTLV-I infection. These findings suggested that PLs might play a role at the early stage of HTLV-I infection.
Assuntos
Vírus Linfotrópico T Tipo 1 Humano/efeitos dos fármacos , Fosfolipídeos/farmacologia , Adsorção , Animais , Cardiolipinas/farmacologia , Gatos , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Humanos , Reação em Cadeia da Polimerase , Coelhos , Fosfolipases Tipo C/farmacologiaRESUMO
We have investigated the protective effect of human T-cell leukemia virus I (HTLV-I) immune globulin (HTLVIG) against HTLV-I in rabbits. HTLVIG containing 77 mg/ml of IgG was prepared from pooled plasma from seropositive healthy persons. In the first experiment, four groups (A, B, C, and D) of three rabbits were transfused with 5 ml blood from an HTLV-I-infected rabbit. Groups A, B, and C were infused 24 h later with 10, 5, and 2 ml HTLVIG, respectively, while group D was infused with 10 ml HTLVIG 48 h later. Seroconversion for HTLV-I occurred in none of group A, one of group B, and all of groups C and D after 2-5 weeks. In the second experiment, four litters (E, F, G, and H) born to another virus-infected rabbit and consisting of 7, 5, 7, and 7 newborns, respectively, were used. Litters E and H were allowed to grow normally as controls, while litters F and G were given intraperitoneal inoculation of 3 ml/kg of HTLVIG weekly four times until weaning. Although three of litters E and H each seroconverted after 5-8 weeks, none of litters F, and one of litter G became antibody-positive after 10 weeks. Presence or absence of HTLV-I infection in all these animals was confirmed by transfusion assay or gene amplification. These results indicate that passive immunization protects rabbits against blood- and milk-borne transmission of HTLV-I.
Assuntos
Infecções por HTLV-I/prevenção & controle , Imunização Passiva , Animais , Anticorpos Antideltaretrovirus/análise , Modelos Animais de Doenças , Amplificação de Genes , Infecções por HTLV-I/genética , Infecções por HTLV-I/transmissão , Humanos , CoelhosRESUMO
Human T cell leukemia virus type I (HTLV-I) or its transcriptional transactivator, Tax1, was introduced into a human osteosarcoma cell line, HOS, and a Moloney murine sarcoma virus-positive HOS cell line, S+L-HOS. These HTLV-I- or Tax1-expressing cells were injected subcutaneously into nude mice to investigate the effects of HTLV-I on their tumorigenicities. HOS cells did not form any tumors even in the presence of HTLV-I or Tax1. S+L-HOS cells did form small tumors in two-thirds of nude mice. Infection of S+L-HOS cells with HTLV-I, or transduction of Tax1 into S+L-HOS cells markedly facilitated the tumor formation, and the tumor-bearing mice showed marked splenomegaly and neutrophilia. Elevated levels of granulocyte colony-stimulating factor (G-CSF) were detected in sera of these mice and also in the culture supernatants of Tax1-expressing human cells, suggesting that G-CSF in the mouse sera was produced by the human cells. In sera of some mice with splenomegaly and neutrophilia, high levels of murine granulocyte-macrophage colony-stimulating factor (mGM-CSF) were observed, suggesting that Tax1 produced by human cells induced mouse cells to produce mGM-CSF. Only S+L-HOS cell lines expressing Tax1 showed high tumorigenicity in nude mice. Thus, this system will be a useful model of tumor formation, splenomegaly and neutrophilia dependent on Tax1.
Assuntos
Transplante de Células , Produtos do Gene tax/fisiologia , Vírus Linfotrópico T Tipo 1 Humano/patogenicidade , Infiltração de Neutrófilos , Esplenomegalia/virologia , Animais , Feminino , Fator Estimulador de Colônias de Granulócitos/sangue , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Hematopoese , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células Tumorais CultivadasRESUMO
Prophylaxis against human T cell lymphotropic virus type I (HTLV-I) is of primary importance for the eradication of adult T cell leukemia and other diseases associated with this virus. Hyperimmune globulin (H-IgG) prepared from healthy blood donors with high antibody titers for HTLV-I was evaluated for its prophylactic effect against HTLV-I in Japanese macaques (Macaca fuscata). Normal IgG (N-IgG) prepared from seronegative healthy blood donors was used as control. Both preparations contained 50 mg/ml IgG and H-IgG had a neutralizing antibody titer of 1:7100 by vesicular stomatitis virus (HTLV-I) pseudotype neutralization assay. Two macaques were infused with 2 ml/kg N-IgG and three macaques were immunized with 2-0.5 ml/kg H-IgG. They were immediately challenged by inoculation of 8 x 10(6)/kg cells from an HTLV-I-producing rabbit lymphoid cell line (Ra-1). Another macaque was immunized with 1 ml/kg H-IgG 24h after inoculation of 8 x 10(6)/kg Ra-1 cells. HTLV-I infection, as determined by seroconversion and verified by polymerase chain reaction, occurred in both of the N-IgG-injected macaques but in none of the four H-IgG-injected macaques. These results demonstrate the protective efficacy of H-IgG against HTLV-I infection in a primate model and provide an experimental basis for passive immunization trials in humans.