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1.
Climacteric ; 17(4): 442-8, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24156784

RESUMO

OBJECTIVES: This study aimed to determine the prevalence and predictors of metabolic syndrome (MetS) among Congolese pre- and postmenopausal women. METHODS: In total, 200 women (100 premenopausal and 100 postmenopausal) were interviewed and underwent clinical and biological investigations searching for lipid and non-lipid cardiovascular risk factors. National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) criteria were used to define MetS. Multivariate logistic regression analysis was used to evaluate predictors of MetS. RESULTS: There were significant differences between the two groups in terms of age, plasma cholesterol, high density lipoprotein cholesterol and triglyceride levels. MetS was present in 20% and 10% of postmenopausal and premenopausal women (p = 0.07), respectively. The MetS components hypertension, elevated plasma glucose and triglycerides were more frequently observed in post- vs. premenopausal women with MetS. Menopause (adjusted odds ratio (aOR) 2.49; 95% confidence interval (CI) 1.05-5.95), overweight (aOR 6.35; 95% CI 1.66-24.23) and obesity (aOR 14.29; 95% CI: 3.84-53.06) emerged as the main independent predictors of MetS. CONCLUSION: This study showed that MetS is common among Congolese postmenopausal women; menopause and weight gain emerged as its main predictors. This suggests that an integrated therapeutic approach combining hormone replacement therapy and lifestyle change in postmenopausal women should be considered.


Assuntos
Doenças Cardiovasculares , Síndrome Metabólica , Pós-Menopausa , Pré-Menopausa , Adulto , Glicemia/análise , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , HDL-Colesterol/sangue , República Democrática do Congo/epidemiologia , Feminino , Humanos , Lipídeos/sangue , Síndrome Metabólica/sangue , Síndrome Metabólica/complicações , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Obesidade , Pós-Menopausa/sangue , Pós-Menopausa/fisiologia , Pré-Menopausa/sangue , Pré-Menopausa/fisiologia , Prevalência , Prognóstico , Fatores de Risco , Triglicerídeos/sangue
2.
Placenta ; 94: 48-53, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32421535

RESUMO

INTRODUCTION: Maternal smoking during pregnancy is a well-known risk factor for reduced birthweight. However, research investigating the association between maternal smoking and placental weight is scarce and inconsistent. Our study was conducted to evaluate the association between maternal smoking and placental weight and placental weight/birthweight ratio (PW/BW ratio). METHODS: We used data from a birth cohort study, the Japan Environment and Children's Study (JECS). Main outcome measures were placental weight, PW/BW ratio, and the risk of high PW/BW ratio. High PW/BW ratio was defined as PW/BW ratio above the 90th percentile for gestational age and sex of offspring. The association between maternal smoking and placental weight was estimated as crude and as adjusted beta coefficients by applying linear regression analyses. Logistic regression analyses were also performed to estimate the association between maternal smoking and the risk of high PW/BW ratio. RESULTS: Of the 91,951 pregnant women, the mean placental weight and the mean PW/BW ratio were lowest for the group of women who had never smoked. Smokers had higher odds ratio for high PW/BW ratio compared with non-smokers. Furthermore, among smokers, the mean placental weight and mean PW/BW ratio were lowest in women who smoked less than 5 daily cigarettes, and highest in women who smoked 20 or more daily cigarettes during pregnancy. DISCUSSION: Placental weight was greater and PW/BW ratio was higher among smokers compared with non-smokers. Moreover, the number of daily cigarettes was positively associated with heavy placental weight.


Assuntos
Peso ao Nascer , Placenta/anatomia & histologia , Fumar/efeitos adversos , Adulto , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Japão , Masculino , Tamanho do Órgão , Gravidez , Inquéritos e Questionários
3.
Planta ; 230(2): 309-17, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19455352

RESUMO

In dicotyledonous plants, nicotianamine synthase (NAS) is thought to play a role in the intercellular transport of iron (Fe). Fe is an essential metal for nitrogen-fixing root nodules of legumes, prompting us to characterize the role of the NAS gene in detail. We previously compared gene-expression profiles in ineffective nodules formed on a Lotus japonicus Fix(-) mutant, sen1, with those in wild-type-effective nodules, and showed that expression of an expressed sequence tag (EST) clone encoding an NAS (EC 2.5.1.43) homologue was repressed in the ineffective nodules. In the present study, two EST clones encoding NAS homologues were found in the EST database. We named them LjNAS1 and LjNAS2. Both were detected as single-copy genes in the L. japonicus genome, and conferred NAS activities in transformed Saccharomyces cerevisiae. LjNAS2 was expressed only in nodules, but LjNAS1 was expressed mainly in leaves, stems, and cotyledons. The level of LjNAS2 transcripts was highest in the nodules 24 days after inoculation with Mesorhizobium loti, and was localized in vascular bundles within the nodules. Expression of LjNAS2 was suppressed in ineffective nodules formed on Fix(-) mutants other than sen1. By contrast, nitrogenase activities of nodules were not influenced in LjNAS2-suppressed plants. We discuss the role of LjNAS2 from the aspect of Fe translocation in nodules.


Assuntos
Alquil e Aril Transferases/metabolismo , Regulação da Expressão Gênica de Plantas , Lotus/enzimologia , Proteínas de Plantas/metabolismo , Nódulos Radiculares de Plantas/enzimologia , Alquil e Aril Transferases/classificação , Alquil e Aril Transferases/genética , Alphaproteobacteria/crescimento & desenvolvimento , Southern Blotting , Cotilédone/enzimologia , Etiquetas de Sequências Expressas , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Ferro/metabolismo , Lotus/genética , Filogenia , Folhas de Planta/enzimologia , Proteínas de Plantas/classificação , Proteínas de Plantas/genética , Caules de Planta/enzimologia , Plantas Geneticamente Modificadas/enzimologia , Plantas Geneticamente Modificadas/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Nódulos Radiculares de Plantas/genética
4.
J Cell Biol ; 109(4 Pt 1): 1429-38, 1989 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-2477377

RESUMO

Chorionic gonadotropin (CG) and lutropin (LH) are members of a family of glycoprotein hormones that share a common alpha subunit but differ in their hormone-specific beta subunits. The glycoprotein hormone beta subunits share a high degree of amino acid homology that is most evident for the LH beta and CG beta subunits having greater than 80% sequence similarity. However, transfection studies have shown that human CG beta and alpha can be secreted as monomers and can combine efficiently to form dimer, whereas secretion and assembly of human LH beta is less efficient. To determine which specific regions of the LH beta and CG beta subunits are responsible for these differences, mutant and chimeric LH beta-CG beta genes were constructed and transfected into CHO cells. Expression of these subunits showed that both the hydrophobic carboxy-terminal seven amino acids and amino acids Trp8, Ile15, Met42, and Asp77 together inhibit the secretion of LH beta. The carboxy-terminal amino acids, along with Trp8, Ile15, Met42, and Thr58 are implicated in the delayed assembly of LH beta. These unique features of LH beta may also play an important role in pituitary intracellular events and may be responsible for the differential glycosylation and sorting of LH and FSH in gonadotrophs.


Assuntos
Quimera , Gonadotropina Coriônica/genética , Genes , Hormônio Luteinizante/genética , Mutação , Fragmentos de Peptídeos/genética , Sequência de Aminoácidos , Animais , Linhagem Celular , Gonadotropina Coriônica/biossíntese , Gonadotropina Coriônica Humana Subunidade beta , Células Clonais , Variação Genética , Humanos , Cinética , Hormônio Luteinizante/biossíntese , Dados de Sequência Molecular , Fragmentos de Peptídeos/biossíntese , Transfecção
5.
Environ Sci Process Impacts ; 21(7): 1085-1098, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31165835

RESUMO

Multi-media fate and transport models (MFTMs) are invaluable tools in understanding and predicting the likely behaviour of organic pollutants in the environment. However, some parameters describing the properties of both the environmental system and the chemical pollutant under consideration are uncertain and or variable in space and time. Furthermore, model performance is often evaluated using sparse data sets on chemical concentrations in different media. This can result in equifinality - the phenomenon in which several different combinations of model parameters can result in similar predictions of environmental concentrations. We explore this idea for MFTMs for the first time using, as examples, three cyclic volatile methyl siloxanes (cVMS: D4, D5 and D6) and the QWASI lake model applied to Tokyo Bay. Monte Carlo simulation was employed with parameters selected from probability distributions representing estimated uncertainty in a large number of iterations. This generated distributions of predicted chemical concentrations in water (CW) and sediment (CS) which represent the aleatory uncertainty envelope but which also demonstrate significant equifinality. For all three compounds, the uncertainty implied in the CW was lower (coefficient of variation, CV, of the order of 20%) than for CS (CV ca. 45%), reflecting the propensity of cVMS compounds to sorb to sediment and the sensitivity of the model to KOC. Confidence intervals were particularly high for the persistence of D5 and D6 in sediment which both ranged between approximately 1.7 years and approximately 26 years for Tokyo Bay. Predicted concentration distributions matched observations well for D5 and D6 not for D4. Equifinality could be reduced by better constraining acceptable parameter sets using additional measured data from different environmental compartments.


Assuntos
Monitoramento Ambiental/métodos , Modelos Teóricos , Siloxanas/análise , Compostos Orgânicos Voláteis/análise , Poluentes Químicos da Água/análise , Baías/química , Monitoramento Ambiental/estatística & dados numéricos , Japão , Lagos/química , Método de Monte Carlo , Incerteza
6.
Trop Biomed ; 36(4): 938-957, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33597465

RESUMO

Genetic variation based on mitochondrial cytochrome c oxidase I (COI) and II (COII) sequences was investigated for three black fly nominal species, Simulium metallicum Bellardi complex, S. callidum Dyar and Shannon, and S. ochraceum Walker complex, which are vectors of human onchocerciasis from Guatemala. High levels of genetic diversity were found in S. metallicum complex and S. ochraceum complex with maximum intraspecific genetic divergences of 11.39% and 4.25%, respectively. Levels of genetic diversity of these nominal species are consistent with species status for both of them as they are cytologically complexes of species. Phylogenetic analyses revealed that the S. metallicum complex from Guatemala divided into three distinct clades, two with members of this species from several Central and South American countries and another exclusively from Mexico. The Simulium ochraceum complex from Guatemala formed a clade with members of this species from Mexico and Costa Rica while those from Ecuador and Colombia formed another distinct clade. Very low diversity in S. callidum was found for both genes with maximum intraspecific genetic divergence of 0.68% for COI and 0.88% for COII. Low genetic diversity in S. callidum might be a consequence of the result being informative of only recent population history of the species.


Assuntos
Variação Genética , Filogenia , Simuliidae/genética , Animais , Código de Barras de DNA Taxonômico , Guatemala , Insetos Vetores/genética , Insetos Vetores/parasitologia , Oncocercose/transmissão , Simuliidae/parasitologia
7.
Kyobu Geka ; 60(12): 1122-5, 2007 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-18018659

RESUMO

A 6-year-old girl who had been diagnosed as hyper immunoglobulin-E syndrome, was admitted to the department of pediatrics of our institute in May 2006, because of pulmonary aspergillosis. The chest X-ray showed bilateral cavities with niveau and fungus ball in the left middle lung field. In spite of medical treatment by antibiotics and antimycotics, the lesions did not improve. Therefore, bilateral lobectomy was done. After surgery, she needed re-operation twice, because of prolonged air leakage. There are few reports of lung surgery for the patient with the hyper immunoglobulin-E syndrome, and we present our case and review previous 2 case reports in the Japanese literature.


Assuntos
Aspergilose/cirurgia , Hipergamaglobulinemia/complicações , Imunoglobulina E , Pneumopatias Fúngicas/cirurgia , Aspergilose/diagnóstico , Aspergilose/etiologia , Criança , Suscetibilidade a Doenças , Feminino , Humanos , Interleucina-6/fisiologia , Pneumopatias Fúngicas/diagnóstico , Pneumopatias Fúngicas/etiologia , Pneumonectomia , Reoperação , Síndrome , Resultado do Tratamento
8.
Cancer Res ; 57(23): 5416-20, 1997 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-9393769

RESUMO

Our previous study showed that human peritoneal conditioned medium (CM) increased the matrix metalloproteinase-9 (MMP-9) secretion and invasiveness of ovarian cancer cells (NOM1). In an effort to identify this MMP-9-stimulating factor, we examined the effects of extracellular matrix components, such as type IV collagen, laminin, and fibronectin, on ovarian cancer cells. We found that fibronectin increased the MMP-9 activity of NOM1 cell CM in a concentration-dependent manner and that the peritoneal CM contained high level of fibronectin. An increase of MMP-9 activity in NOM1 cell CM by the peritoneal CM was almost completely blocked by 20 microg/ml of anti-integrin alpha5/FnR antibody and RGD polypeptides. Furthermore, after immunoprecipitation by antifibronectin antibody supernatant of the peritoneal CM did not increase MMP-9 activity in NOM1 cells. Fibronectin and the peritoneal CM also increased MMP-9 activity and expression in NOM1 cell lysate, and these effects were blocked by anti-integrin alpha5/FnR antibody. Invasiveness of NOM1 cells was enhanced by fibronectin and the peritoneal CM in a concentration-dependent manner, and anti-integrin alpha5/FnR antibody blocked these effects. These results suggested that fibronectin secreted from peritoneum increased MMP-9 activity and expression, and, in turn, invasiveness of ovarian cancer cells.


Assuntos
Colagenases/biossíntese , Fibronectinas/fisiologia , Regulação Neoplásica da Expressão Gênica/fisiologia , Invasividade Neoplásica , Neoplasias Ovarianas/enzimologia , Neoplasias Ovarianas/patologia , Peritônio/fisiologia , Anticorpos Monoclonais/farmacologia , Antígenos CD/imunologia , Antígenos CD/fisiologia , Meios de Cultivo Condicionados , Cistadenocarcinoma/enzimologia , Cistadenocarcinoma/patologia , Indução Enzimática , Feminino , Fibronectinas/metabolismo , Fibronectinas/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/fisiologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Integrina alfa5 , Cinética , Metaloproteinase 9 da Matriz , Peso Molecular , Peritônio/citologia , Peritônio/patologia , Receptores de Fibronectina/imunologia , Receptores de Fibronectina/fisiologia , Células Tumorais Cultivadas
9.
Afr Health Sci ; 16(4): 979-985, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28479890

RESUMO

OBJECTIVES: We aimed to assess the prevalence of prehypertension and its associated factors in a population of Congolese pre and postmenopausal women. METHODS: We had consecutively recruited 200 women (100 premenopausal and 100 postmenopausal) aged 40 - 60 years at the department of Gynecology and Obstetrics, University of Kinshasa Hospital, and AKRAM Medical Center in Kinshasa, DRC. An interview was carried out using a questionnaire that comprised questions related to lifestyle, menses characteristics, medical history of diabetes, CVD, hypertension, current antihypertensive medication and use of traditional medicine. In addition, physical examination and biological measurements were performed. Multivariate logistic regression analysis was used to assess associated factors with prehypertension. RESULTS: Of the participants, 34% were normotensive, 38.5 % prehypertensive and 27.5% hypertensive. Compared to normal blood pressure, prehypertension was common in the older (age>50 years of age) women. Menopause, the use of traditional medicine and older age were associated with prehypertension. However, only menopause (aOR: 2.71; 95%CI: 1.10-3.52) and the use of traditional medicine (aOR: 2.24; 95% CI: 1.07-4.7) remained associated with prehypertension in a multivariate logistic regression analysis. CONCLUSION: This study showed that prehypertension is common among Congolese menopausal women, and that menopause and the use of traditional medicine were the main factors associated with prehypertension.


Assuntos
Pós-Menopausa , Pré-Hipertensão/epidemiologia , Pré-Menopausa , Adulto , Fatores Etários , Consumo de Bebidas Alcoólicas/epidemiologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , República Democrática do Congo/epidemiologia , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Estilo de Vida , Modelos Logísticos , Medicinas Tradicionais Africanas/estatística & dados numéricos , Pessoa de Meia-Idade , Pré-Hipertensão/terapia , Prevalência , Fatores de Risco , Fumar/epidemiologia , Fatores Socioeconômicos
10.
Endocrinology ; 137(10): 4196-200, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8828477

RESUMO

CG, LH, FSH, and TSH are a family of heterodimeric glycoprotein hormones that contain a common alpha-subunit but differ in their hormone-specific beta-subunits. Both subunits have five and six disulfide bonds, respectively, which consists of cystine knot structure. We previously eliminated the disulfide bonds 7-31 and 59-87 in alpha-subunit without significantly affecting assembly with human CG beta-subunit. To study the role of these disulfide bonds in dimerization with other beta-subunits, the wild-type or mutated alpha gene was contransfected with the wild-type human LH beta or FSH beta gene into Chinese hamster ovary (CHO) cells or GH3 cells, and assembly was assessed by continuous labeling with [35S]methionine/cysteine, immunoprecipitation with anti-alpha or-beta serum, and SDS-PAGE. Our data revealed that disruption of either disulfide bond 7-31 or 59-87 in the alpha-subunit markedly reduced the dimer formation with LH beta-subunit in both CHO and GH3 cells, whereas it did not significantly affect the assembly of FSH. This suggests that the regions in the alpha-subunit recognized by beta-subunits for assembly are different among gonadotropins.


Assuntos
Gonadotropina Coriônica/química , Dissulfetos/química , Subunidade alfa de Hormônios Glicoproteicos/química , Subunidade alfa de Hormônios Glicoproteicos/fisiologia , Hormônio Luteinizante/química , Animais , Células CHO , Linhagem Celular , Cricetinae , Dimerização , Humanos , Dobramento de Proteína
11.
Endocrinology ; 136(5): 2270-5, 1995 May.
Artigo em Inglês | MEDLINE | ID: mdl-7536667

RESUMO

CG, LH, FSH, and TSH are a family of heterodimeric glycoprotein hormones that contain a common alpha-subunit, but differ in their hormone-specific beta-subunit. Processing of the N-linked oligosaccharide of the glycoprotein family is both tissue and dimer specific. LH, TSH, and free alpha synthesized in pituitary bear oligosaccharide terminating with sulfate (SO4) and N-acetylgalactosamine (GalNAc), whereas the termination of oligosaccharide in CG synthesized in placenta and FSH is sialic acid and galactose (Gal). Using site-directed mutagenesis and gene transfer, we studied the role of the Pro-Leu-Arg motif, which has been shown to be a recognition marker of glycoprotein hormone-specific GalNAc transferase, in sulfation of N-linked oligosaccharide in alpha-subunit. The wild-type or mutated alpha gene was transfected into GH3 cells. Our data revealed that substitution of the Pro-Leu-Arg motif by Ala-Leu-Ala did not affect the sulfation of N-linked oligosaccharide, but generated the attachment of O-linked oligosaccharide. alpha-Subunit containing either of the two N-linked glycosylations is also sulfated. We conclude that in GH3 cells, the Pro-Leu-Arg motif plays no role in the sulfation of oligosaccharide in alpha-subunit, and both N-glycosylations are terminated with SO4.


Assuntos
Subunidade alfa de Hormônios Glicoproteicos/metabolismo , Oligopeptídeos , Sequência de Aminoácidos , Animais , Sequência de Bases , Sítios de Ligação , Linhagem Celular , Clonagem Molecular , Feminino , Subunidade alfa de Hormônios Glicoproteicos/biossíntese , Subunidade alfa de Hormônios Glicoproteicos/química , Glicosilação , Humanos , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Oligodesoxirribonucleotídeos , Oligossacarídeos/biossíntese , Oligossacarídeos/química , Hipófise/metabolismo , Placenta/metabolismo , Mutação Puntual , Gravidez , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Transfecção
12.
Endocrinology ; 137(3): 831-8, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8603592

RESUMO

The mutations (Trp8 --> Arg and Ile15 --> Thr) in the human LHbeta -subunit caused by nucleotide point mutations in the LHbeta gene were reported in women with immunologically anomalous LH and menstrual disorders. To estimate the effects of the mutations on LH bioactivity in vitro and in vivo, we constructed a LHbeta gene containing this nucleotide mutation in each site or in both sites by site- directed mutagenesis and analyzed the bioactivities of the mutant LH expressed in Chinese hamster ovary cells. Although no alterations were noted in the receptor-binding activity of LH due to the mutations, the LHs containing the mutations at Trp8 --> Arg and at both sites in the beta-subunit showed a higher biopotency of progesterone production in vitro. The clearance rate from the circulation was faster in vivo in all mutant LHs, which were induced primarily by the mutation at Trp8 --> Arg. However, the mutations did not affect the ability of LH to induce ovulation in vivo. These results indicate that LH consisting of the mutant beta-subunit exhibits hyperbioactivity on steroidogenesis and has a short turnover rate. This may affect the endocrine pathway among women with the mutant LH and lead to menstrual disorders.


Assuntos
Hormônio Luteinizante/genética , Receptores do LH/metabolismo , Animais , Sequência de Bases , Células CHO , Cricetinae , Feminino , Técnicas de Transferência de Genes , Humanos , Hormônio Luteinizante/metabolismo , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Mutação Puntual , Ratos , Ratos Wistar
13.
J Clin Endocrinol Metab ; 78(1): 107-13, 1994 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7904610

RESUMO

To analyze the structure of LH in three patients with immunologically anomalous LH, the whole coding region of the LH beta-subunit gene was examined. These patients were infertile, and their serum LH levels could not be measured with an immunoassay kit. Immunoblotting of the LH beta-subunit showed no marked changes in the molecular size of LH beta. Genomic DNA was extracted from peripheral lymphocytes of the patients and normal controls, and LH beta genes were amplified by the polymerase chain reaction technique, using primer pairs that are capable of specifically amplifying only the LH beta gene without interference by the CG beta genes. No deletions were observed in the coding regions of the LH beta gene of the patients. Nucleotide sequencing revealed two nucleotide substitutions in the LH beta gene of the patients, which cause amino acid replacements from Trp8 (TGG) to Arg8 (CGG) and Ile15 (ATC) to Thr15 (ACC). Restriction fragment length polymorphism analysis in three families indicated that the affected probands were homozygous, and their family members were heterozygous, except for their husbands. The heterozygotes showed reduced detectability with the LH immunoassay kit. These results suggest that these amino acid replacements are responsible for this immunologically anomalous variant.


Assuntos
Genes , Doenças do Sistema Imunitário/genética , Hormônio Luteinizante/genética , Hormônio Luteinizante/imunologia , Mutação Puntual , Adulto , Sequência de Bases , Bioensaio , Western Blotting , Feminino , Humanos , Imunoensaio , Hormônio Luteinizante/análise , Dados de Sequência Molecular , Peso Molecular , Linhagem , Polimorfismo de Fragmento de Restrição
14.
J Clin Endocrinol Metab ; 63(1): 156-61, 1986 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-2423548

RESUMO

To study the ontogenesis of PRL synthesis and secretion in the human fetus, PRL mRNA was measured in 12 pituitaries from fetuses of 16-27 weeks of gestation by hybridization of cytosol RNA with 125I-labeled single stranded complementary DNA (cDNA). Pituitary PRL content and serum PRL concentration were assessed by RIA. Pituitary weight increased with fetal age, ranging from 12 mg at 16 weeks of gestation to 41 mg at 27 weeks. The increased weight was due to an increase in cell number. PRL mRNA content did not change during weeks 16-20 of gestation. However, it increased rapidly after 21 weeks, reaching 11.5 times the 16-20 week value at 27 weeks. Pituitary PRL content was constant at a low level until 21 weeks, but thereafter it increased markedly. The increase was greater than that in PRL mRNA, and therefore, the PRL to PRL mRNA ratio was 10-fold greater at 27 weeks of gestation. Serum PRL concentrations also gradually increased after 21 weeks of gestation. These results indicate that marked increases in fetal pituitary PRL synthesis and release occur after 21 weeks of gestation.


Assuntos
Feto/metabolismo , Adeno-Hipófise/embriologia , Prolactina/biossíntese , Sequência de Bases , DNA/metabolismo , DNA de Cadeia Simples , Densitometria , Estradiol/sangue , Idade Gestacional , Humanos , Hibridização de Ácido Nucleico , Tamanho do Órgão , Adeno-Hipófise/metabolismo , Neoplasias Hipofisárias/metabolismo , Poli A/metabolismo , Prolactina/sangue , Prolactina/metabolismo , RNA/metabolismo , RNA Mensageiro/metabolismo , Tiroxina/sangue
15.
Clin Exp Metastasis ; 15(6): 612-9, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9344045

RESUMO

Ovarian cancer cells disseminate by attachment to the peritoneal mesothelial cell surface of the abdominal cavity. We therefore investigated the influence of conditioned medium (CM) from human peritoneal tissues and mesothelial cells on the secretion of matrix metalloproteinases (MMPs) by ovarian cancer cells. The molecular weights of MMPs stimulating factors derived from human peritoneal tissues and mesothelial cells were estimated using microconcentrators with various cut-off membranes. Human peritoneal tissues were obtained from 12 surgical patients, and mesothelial cells were isolated from three peritoneal specimens. Exposure to CM from peritoneal tissue caused a concentration-dependent increase of the MMP-2 and MMP-9 bands in CM from NOM1 ovarian cancer cells, as shown by zymography. There was a significant difference in the increase of MMP-2 and MMP-9 (2.46-fold and 7.14-fold, respectively, at 0.4 mg/ml protein; P < 0.005). CM from mesothelial cells also significantly increased the secretion of MMP-9 by NOM1 cells. The molecular size of possible MMP-9-stimulating factors secreted by peritoneal tissues and mesothelial cells was above M(r) 100000. Further, CM of peritoneal tissues and mesothelial cells also induced the invasiveness of NOM1 cells. These findings suggest that mesothelial cells may secrete some factors which predominantly induce the MMP-9 production and increase invading cell numbers.


Assuntos
Colagenases/metabolismo , Neoplasias Ovarianas/enzimologia , Peritônio/fisiologia , Meios de Cultivo Condicionados , Epitélio/fisiologia , Feminino , Humanos , Metaloproteinase 9 da Matriz , Peso Molecular , Células Tumorais Cultivadas
16.
Eur J Cancer ; 30A(6): 773-8, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-7917536

RESUMO

Human ovarian carcinoma cells (HRA) were sensitised to cis-diamminedichloroplatinum (II) (CDDP) 2.7-, 5.5- and 12.1-fold by treatment with amphotericin B (AMB) at concentrations of 2.1, 5.4 and 10.8 microM, respectively. Moreover, intracellular accumulation of platinum after a 2-h exposure to CDDP was increased significantly with AMB treatment. We prepared HRA cell-inoculated nude mice as an experimental therapeutic model for human advanced ovarian carcinoma. Ascites was evident after 7 to 9 days of intra-peritoneal (i.p.) inoculation of HRA cells, and mice died due to intra-abdominal carcinomatosis after 11 to 14 days [mean survival time (MST): 12.4 +/- 1.1 days]. Treatment with AMB (2.0 mg/kg) alone 4 days after inoculation increased MST by only 1.4 days. Simultaneous treatment with CDDP (1.0 to 2.0 mg/kg) and AMB (0.5 to 2.0 mg/kg) produced a significant increase in MST compared to treatment with CDDP alone. Maximal MST (30.1 days) was observed by treatment with 2.0 mg/kg CDDP plus 2.0 mg/kg AMB, whereas MST with 2.0 mg/kg CDDP alone was 16.4 days. A further drug accumulation study demonstrated that platinum accumulation in tumour tissues in nude mice treated with CDDP and AMB increased significantly compared to treatment with CDDP alone. These results indicate that intraperitoneal combination chemotherapy with CDDP and AMB is effective in an experimental animal model of advanced ovarian carcinoma.


Assuntos
Anfotericina B/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Animais , Divisão Celular/efeitos dos fármacos , Cisplatino/farmacocinética , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Neoplasias Ovarianas/mortalidade , Transplante Heterólogo , Células Tumorais Cultivadas
17.
Cancer Lett ; 120(1): 109-15, 1997 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-9570393

RESUMO

To investigate the relation between matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in malignant ovarian tumor, MMP and TIMP activities in conditioned media of 16 malignant ovarian tumor tissues and six normal ovaries were detected by zymography and reverse zymography, respectively and were quantitated with a densitometer. TIMP-1 and TIMP-2 were detected in all normal and malignant ovarian tumor tissues by reverse zymography. In normal ovaries, the intensity of TIMP-2 bands was stronger than TIMP-1, but in malignant tumor tissues those of TIMP-1 were stronger. The ratios of TIMP-1 to TIMP-2 and MMP-9 to MMP-2 were significantly higher in malignant tumor tissues than in normal ovaries (P < 0.001). TIMP activity consisting of TIMP-1 and TIMP-2 correlated significantly to MMP activity of MMP-2 and MMP-9 (r = 0.67, P < 0.005). There was a significant correlation between TIMP-1 activity and MMP activity (r = 0.72, P < 0.001), but no correlation was observed between TIMP-2 activity and MMP activity. The high level of TIMP-1 appeared to be related to malignant phenotype in ovaries as well as the high level of MMP-9.


Assuntos
Colagenases/metabolismo , Gelatinases/metabolismo , Metaloendopeptidases/metabolismo , Neoplasias Ovarianas/enzimologia , Ovário/enzimologia , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Adolescente , Adulto , Idoso , Feminino , Humanos , Metaloproteinase 2 da Matriz , Metaloproteinase 9 da Matriz , Pessoa de Meia-Idade
18.
Mol Cell Endocrinol ; 160(1-2): 157-63, 2000 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-10715549

RESUMO

CG, LH, FSH, and TSH are a family of heterodimeric glycoprotein hormones that contain a common alpha-subunit, but differ in their hormone-specific beta-subunits. Despite the considerable homology between LHbeta and CGbeta, we previously demonstrated that, when expressed in GH(3) cells, the secreted form of LHbeta showed mispaired disulfide-linked aggregation in addition to monomer, whereas no aggregation was observed in CGbeta. To determine the domains which are associated with the LHbeta-aggregation and which prevent CGbeta-aggregation, mutant beta-subunits in glycosylation and carboxy-terminus were expressed in GH(3) cells, and the occurrence of aggregation was assessed by continuous labeling with [35S]methionine/cysteine, immunoprecipitation with anti-hCGbeta serum, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis in a non-reducing condition. No aggregation was seen when N-linked oligosaccharides were attached to the Asn(13) of LHbeta. Removal of the carbohydrate unit at the Asn(13) of CGbeta caused aggregation, although the amount was less than 10% of monomer. The carboxy-terminal regions of neither LHbeta nor CGbeta were associated with their aggregation. Both CGbeta wild-type (WT) and CGbeta lacking N-glycosylation at Asn(13) (CGbeta-N13) showed aggregates in lysate. However, in contrast to CGbeta-N13, CGbetaWT revealed no aggregation in medium. These results indicate that the backbone structure consisting of 114 amino acids and N-linked glycosylation at Asn(30) is involved in the aggregation of LHbeta. Moreover, N-glycosylation at Asn(13) does not prevent such aggregation, but instead plays an important role in correct folding for both LHbeta- and CGbeta-subunits to be secreted as monomer.


Assuntos
Hormônio Luteinizante/química , Sequência de Aminoácidos , Asparagina/química , Sequência de Bases , Linhagem Celular , Gonadotropina Coriônica Humana Subunidade beta/química , Gonadotropina Coriônica Humana Subunidade beta/genética , Gonadotropina Coriônica Humana Subunidade beta/metabolismo , Primers do DNA/genética , Glicosilação , Humanos , Hormônio Luteinizante/genética , Hormônio Luteinizante/metabolismo , Substâncias Macromoleculares , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Dobramento de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
19.
Obstet Gynecol ; 89(6): 1017-22, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9170484

RESUMO

OBJECTIVE: There have been few studies concerning the clinical pathology of squamous cell carcinoma arising from ovarian mature cystic teratoma. Thus, the objective of this study is to determine clinicopathologic factors affecting survival in this rare tumor. METHODS: From September 1979 to June 1996, 37 patients with squamous cell carcinoma arising from ovarian mature cystic teratoma were treated by the Tokai Ovarian Tumor Study Group. A retrospective clinicopathologic and survival analysis of these patients was performed. The mode of infiltration was classified into expansive, moderately diffused, and diffused patterns. RESULTS: Although the 5-year survival rate was 94.7% and 80.0% for stage I and II patients, respectively, 12 of 13 patients with stage III died within 20 months (P = .0001). A significant difference was also observed between the survival of the groups with and without residual tumor at surgery (P = .0001). Pathologic features, grade, mode of infiltration, and vascular involvement were significant factors by univariate analysis. Multivariate analysis showed significant differences in survival related to grade (P = .0154) and mode of infiltration (P = .0053). The preoperative squamous cell carcinoma antigen level was significantly higher in the patients with squamous cell carcinoma arising from mature cystic teratoma than in patients with mature cystic teratoma (P < .0001). CONCLUSION: This study suggests that pathologic factors, grade, and mode of infiltration can provide valuable information for predicting the survival of patients with squamous cell carcinoma arising from mature cystic teratoma. In addition, squamous cell carcinoma antigen may be a useful marker to detect this disease preoperatively.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Ovarianas/patologia , Teratoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/epidemiologia , Neoplasias Ovarianas/epidemiologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Teratoma/epidemiologia
20.
Fertil Steril ; 63(5): 989-95, 1995 May.
Artigo em Inglês | MEDLINE | ID: mdl-7720944

RESUMO

OBJECTIVE: To evaluate the clinical significance of the LH consisting of a mutant beta-subunit (Trp8 to Arg8 and Ile15 to Thr15). DESIGN: Clinical and biochemical studies. SETTING: Fertility center at the University Hospital and its research laboratory. PATIENTS: Fifty-one patients with menstrual disorders and three homozygote cases and two heterozygote cases of the mutant LH who were reported previously. INTERVENTIONS: Nucleotide mutations of the LH beta gene in patients with menstrual disorders were screened using techniques of the polymerase chain reaction and restriction fragment length polymorphism. Immunologic and biologic activities of the mutant LH and endocrinologic profiles in the affected women were evaluated. MAIN OUTCOME MEASURES: Serum LH levels measured with different immunoassay kits; serum FSH and LH on the GnRH test; serum thyroid-stimulating hormone, PRL, T, and androstenedione; ultrasound examination of the ovaries; clinical hyperandrogenic symptoms; and biologic activity of LH. RESULTS: Two cases of homozygotes and four of heterozygotes affected by the LH beta gene mutations were discovered in the current study through screening of patients with menstrual disorders. Serum LH levels in the homozygote cases were undetectable using a LH immunoassay kit, whereas levels in the heterozygote cases showed reduced detectability with the kit. However, the ratio of the mutant LH values in the bioassay to those in the immunoassay was higher in the homozygote group than that in the control subjects. Response patterns of serum gonadotropins to GnRH in the homozygote were similar to those in patients with polycystic ovary syndrome. CONCLUSION: The mutations of LH beta-subunit might be related to menstrual disorder in some patients.


Assuntos
Hormônio Luteinizante/genética , Distúrbios Menstruais/genética , Mutação , Adolescente , Adulto , Sequência de Bases , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina , Heterozigoto , Homozigoto , Humanos , Imunoensaio , Hormônio Luteinizante/sangue , Dados de Sequência Molecular , Síndrome do Ovário Policístico/sangue , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Prolactina/sangue
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