RESUMEN
INTRODUCTION: Serum protein electrophoresis (SPE) is a well-established laboratory technique. However, reporting of results varies considerably between laboratories. The variation in reporting can cause confusion to the clinician with a potential of adversely impacting patient care. The purpose of the survey was to find out the variation in reporting and to prepare recommendations to the Malaysian laboratories based on the survey to reduce both the variation in reporting between laboratories and the risk of misinterpretation of reports. MATERIALS AND METHODS: To determine the extent of variation in reporting of protein electrophoresis results questionnaires were distributed to the pathologists of various laboratories in Malaysia regarding the method, quantification of paraprotein concentrations and immunoglobulin assays, and information regarding current laboratory electrophoresis practices. RESULTS: Variation was found in the following reporting practices: (a) screening protocol; (b) reporting of serum albumin; (c) numerical reporting of protein fractions and paraprotein; (d) co-migration of a paraprotein with a normal serum protein; (e) reporting of multiple paraprotein bands (f) appearance of small abnormal band and oligoclonal bands and (g) communication about of interferences. CONCLUSION: The pathologists of the country made recommendations on the reporting of protein electrophoresis. Harmonised reporting will reduce inconsistency, variation in reporting, improve the quality of the report and most importantly improve patient care.
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Electroforesis , Proteínas Sanguíneas , Humanos , Malasia , Paraproteínas , Encuestas y CuestionariosRESUMEN
INTRODUCTION: The Malaysian Association of Clinical Biochemists (MACB) established a Task Force for Chronic Kidney Disease. A survey was undertaken by the Task Force on the reporting of estimated glomerular filtration rate (eGFR) and urine albumin by hospital laboratories in Malaysia in both the government and private sectors. MATERIALS AND METHODS: An e-mail invitation to participate in an online survey was sent to hospital laboratories in Malaysia (n=140). Questions regarding methods for measuring creatinine, equations for calculating eGFR, eGFR reporting, the terminology used in reporting urine albumin, types of samples and the cut-off values used for normal albuminuria. RESULTS: A total of 42/140 (30%) laboratories answered the questionnaire. The prevalent method used for serum creatinine measurement was the Jaffé method (88.1%) traceable to isotope-dilution mass spectrometry. eGFR was reported along with serum creatinine by 61.9% of laboratories while 33.3% of laboratories report eGFR on request. The formula used for eGFR reporting was mainly MDRD (64.3%) and results were reported as exact numbers even when the eGFR was <60 ml/min/1.73m2. The term microalbumin is still used by 83.3% of laboratories. There is a large heterogeneity among the labs regarding the type of sample recommended for measuring urine albumin, reference interval and reporting units. CONCLUSION: It is evident that the laboratory assessment of chronic kidney disease in Malaysia is not standardised. It is essential to provide a national framework for standardised reporting of eGFR and urine albumin. Recommendations developed by the MACB CKD Task Force, if adopted by all laboratories, will lead to a reduction in this variability.
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Insuficiencia Renal Crónica , Albúminas , Creatinina , Receptores ErbB , Tasa de Filtración Glomerular , Humanos , Proteinuria , Insuficiencia Renal Crónica/diagnósticoRESUMEN
INTRODUCTION: Low 25-hydroxyvitamin D [25(OH)D] levels have not been consistently associated with bone mineral density (BMD). It has been suggested that calculation of the free/bioavailable 25(OH)D may correlate better with BMD. We examined this hypothesis in a cohort of Malaysian women. MATERIALS AND METHODS: A cross-sectional study of 77 patients with rheumatoid arthritis (RA) and 29 controls was performed. Serum 25(OH)D was measured using the Roche Cobas E170 immunoassay. Serum vitamin D binding protein (VDBP) was measured using a monoclonal enzyme-linked immunosorbent assay (ELISA). Free/bioavailable 25(OH)D were calculated using both the modified Vermuelen and Bikle formulae. RESULTS: Since there were no significant differences between RA patients and controls for VDBP and 25(OH)D, the dataset was analysed as a whole. Calculated free 25(OH)D by Vermeulen was strongly correlated with Bikle (r = 1.00, p < 0.001). A significant positive correlation was noted between measured total 25(OH)D with free/bioavailable 25(OH)D (r = 0.607, r = 0.637, respectively, p < 0.001). Median free/bioavailable 25(OH)D values were significantly higher in Chinese compared with Malays and Indians, consistent with their median total 25(OH)D. Similar to total 25(OH)D, the free/bioavailable 25(OH)D did not correlate with BMD. CONCLUSION: In this first study of a multiethnic female Malaysian population, free/bioavailable 25(OH)D were found to reflect total 25(OH)D, and was not superior to total 25(OH)D in its correlation with BMD. Should they need to be calculated, the Bikle formula is easier to use but only calculates free 25(OH)D. The Vermuelen formula calculates both free/bioavailable 25(OH)D but is more complex to use.
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Artritis Reumatoide/sangre , Densidad Ósea/fisiología , Proteína de Unión a Vitamina D/sangre , Vitamina D/análogos & derivados , Absorciometría de Fotón , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/diagnóstico por imagen , Estudios Transversales , Femenino , Humanos , Malasia , Persona de Mediana Edad , Vitamina D/sangreRESUMEN
Distinct microRNA (miRNA) and mRNA signatures were reported in nucleophosmin (NPM1)-mutated acute myeloid leukemia (AML). However, it remains unknown whether the mutation participates in the dynamic interaction between miRNA and mRNA. In this study, we aimed to investigate the role of NPM1 mutation in modulating miRNA-mRNA regulation (MMR). From the sample-paired miRNA/mRNA microarrays of 181 de novo AML patients, we found that MMR was dynamic and could be affected by NPM1 mutation. By a systematic framework, we identified 493 NPM1 mutation-modulated MMR pairs, where the strength of MMR was significantly attenuated in patients carrying NPM1 mutations, compared to those with wild-type NPM1. These miRNAs/mRNAs were associated with pathways implicated in cancer and known functions of NPM1 mutation. Such modulation of MMR was validated in two independent cohorts as well as in cells with different NPM1 mutant burdens. Furthermore, we showed that the regulatory strength of nine MMR pairs could predict patients' outcomes. Combining these pairs, a scoring system was proposed and shown to predict survival in discovery and validation data sets, independent of other known prognostic factors. Our study provides novel biological insights into the role of NPM1 mutation as a modulator of MMR, based on which a novel prognostic marker is proposed in AML.
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Leucemia Mieloide Aguda/genética , MicroARNs/análisis , Mutación , Proteínas Nucleares/genética , ARN Mensajero/análisis , Línea Celular Tumoral , Humanos , Leucemia Mieloide Aguda/mortalidad , Nucleofosmina , PronósticoRESUMEN
The etiology of systemic lupus erythematosus (SLE) involves a complex interaction of genetic and environmental factors. Investigations have shown that environmentally driven epigenetic changes contribute to the etiology of SLE. Here, we hypothesize that aberrant DNA methylation may contribute to the activation of the immune machinery and trigger lupus disease activity. A whole genome methylation array was applied to investigate the DNA methylation changes between 12 pairs of active SLE patients and healthy controls. The results were further confirmed in 66 SLE patients, 102 healthy controls. The methylation statuses of the IL10 and IL1R2 genes were significantly reduced in the SLE patient samples relative to the healthy controls (age-adjusted odds ratios, 64.2 and 16.9, respectively, P<0.0001). There was a trend toward SLE patients having hypomethylated IL10 and IL1R2 genes accompanied by greater disease activity. We observed that the methylation degree of IL10 and IL1R2 genes were reduced in the rheumatoid arthritis (RA) patients as well but the hypomethylation change was more significant in IL1R2 genes than in the IL10 genes in RA patients. This study demonstrated that DNA hypomethylation might be associated with SLE. Hypomethylated IL10 and IL1R2 genes may provide potential epigenetic markers as clinical predictors for autoimmune diseases.
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Metilación de ADN , Genoma Humano , Interleucina-10/genética , Lupus Eritematoso Sistémico/genética , Regiones Promotoras Genéticas , Receptores Tipo II de Interleucina-1/genética , Artritis Reumatoide/genética , Artritis Reumatoide/inmunología , Epigénesis Genética , Redes Reguladoras de Genes , Humanos , Interleucina-10/inmunología , Lupus Eritematoso Sistémico/inmunología , Receptores Tipo II de Interleucina-1/inmunologíaRESUMEN
Solenopsis geminata (F.) was introduced into southern Taiwan decades ago and has continued to threaten the residents. Although the venom compositions of various fire ant species have been studied, the effects of environmental cues on the secretion pattern have received relatively little attention in an area with subtropical climate and high humidity, such as Taiwan. This study characterizes the effects of temperature and season on the venom compositions of S. geminata in Taiwan. Pure venom was sampled by using a microcapillary pipette and immersing the whole ant in hexane and subjected to gas chromatography-mass spectrometry analysis. The results showed that the ratio of cis C(11) to trans C(11) alkaloids in major workers was significantly higher than that in minor workers. No significant differences could be found in either the relative alkaloids content or the ratio of cis C(11) to trans C(11) alkaloids in venom of minor workers while rearing at four temperature conditions. Nevertheless, the ratio of cis C(11) to trans C(11) alkaloids in the venom of minor workers was the highest in spring and the lowest in winter. The results also showed that the body length, abdomen length, head length, head width, and venom volume differed significantly between major workers and minor workers of S. geminata. The venom volumes of these two castes were positively correlated with their body sizes.
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Alcaloides/química , Venenos de Hormiga/química , Hormigas/química , Animales , Venenos de Hormiga/metabolismo , Hormigas/fisiología , Tamaño Corporal , Clima , Femenino , Humedad , Masculino , Estaciones del Año , Predominio Social , Taiwán , TemperaturaRESUMEN
Tumour markers are substances related to the presence or progress of a tumour. An ideal tumour marker is (1) detectable only when malignancy is present, (2) specific for the type and site of malignancy, (3) correlates with the amount of malignant tissue present and (4) responds rapidly to a change in tumour size. At present, no tumour marker fulfills all of the above criteria. The first part of the review discusses the clinical usefulness of the commonly requested serum tumour markers, namely, prostate-specific antigen (PSA), CA 19-9, carcinoembryonic antigen (CEA), CA 125, CA 15-3, human chorionic gonadotrophin (hCG) and alpha-foetoprotein (AFP). It is hoped that this review article will decrease the abuse and misuse of these commonly requested serum tumour markers. The second part of the review discusses the clinical usefulness of catecholamines and their metabolites, calcitonin, thyroglobulin, parathyroid hormone, prolactin, adrenocorticotrophic hormone, oestrogen and progesterone receptors, p53, HER-2/c-erbB2, BRCA1 and BRCA2.
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Biomarcadores de Tumor/metabolismo , Neoplasias/diagnóstico , Femenino , Humanos , Masculino , Neoplasias/metabolismo , PronósticoRESUMEN
The best therapeutic choice in the treatment of lupus nephritis remains open to debate. In addition, there have been little data on the treatment of lupus nephritis in Asian patients. The objective of this study was to look at the response rate and complications of treatment given for lupus nephritis in a group of South East Asian patients with systemic lupus erythematosus (SLE). This was a retrospective, cross-sectional study of 103 patients with lupus nephritis. Detailed analysis was done on 58 patients with Class IV disease. The median time to remission was 12.1 months for azathioprine (AZA), 15.01 months for oral cyclophosphamide (CPM) and 15.25 months for intravenous (i.v.) CPM. The percentage of patients achieving remission after the first course of treatment was 42.9% with AZA, 83.3% with oral CPM and 90.9% with i.v. CPM. Overall, 41/58 (70.7%) of patients went into remission following the first course of treatment. Seventeen (41.5%) subsequently relapsed, requiring a second course of treatment. Fifty-two (50.5%) of all patients had drug-related complications from their treatment. The most frequent complication for the group was amenorrhoea (23.3% of all patients, 40% of those who had CPM previously), which was significantly more frequent in patients given CPM. In conclusion, more patients achieve remission when treated with CPM compared with AZA alone but this is associated with a higher complication rate, especially amenorrhoea.
Asunto(s)
Etnicidad/estadística & datos numéricos , Nefritis Lúpica/etnología , Nefritis Lúpica/terapia , Adulto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Oestrone sulphate is a major source of active oestrogens in the breast. It is converted to oestrone by oestrone sulphatase. Breast cyst fluid (BCF) is a rich source of sex hormones and growth factors. BCF obtained from British women has been shown to inhibit oestrone sulphatase activity in the MCF-7 oestrogen-receptor-positive breast cancer cell line. The aim of the present study was to assess whether BCF obtained from Malaysian women inhibited oestrone sulphatase activity in the MCF-7 and MDA-MB-231 breast cancer cell lines. The cell lines were grown in supplemented Dulbecco's Modified Eagle Medium for 3 days, following which a 3-day incubation with sterilised BCF was carried out. At the end of the treatment period the cell monolayers were assayed for oestrone sulphatase activity and the number of cell nuclei counted on a Coulter Counter. BCF was also fractionated on a Bio-Sil SEC 125-5 column by HPLC and the effects of the fractions collected on oestrone sulphatase activity in the MDA-MB-231 cell line were assessed. All 18 samples of BCF tested inhibited cell growth in the MDA-MB-231 cell line while 8 out of 10 samples inhibited MCF-7 cell growth; 15 out of 18 BCF samples inhibited oestrone sulphatase activity in the MDA-MB-231 cell line whereas 5 out of 10 samples stimulated oestrone sulphatase activity in the MCF-7 cell line. HPLC fractions corresponding to molecular weights of > 158 kDa and 28 kDa were found to inhibit oestrone sulphatase activity in the MDA-MB-231 cell line. Further work is required to fully characterise these substances as they may have roles to play in the prevention of breast cancer.
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Neoplasias de la Mama/enzimología , Enfermedad Fibroquística de la Mama/metabolismo , Neoplasias Hormono-Dependientes/enzimología , Sulfatasas/antagonistas & inhibidores , Neoplasias de la Mama/patología , División Celular/fisiología , Líquido Quístico/química , Femenino , Humanos , Neoplasias Hormono-Dependientes/patología , Células Tumorales CultivadasRESUMEN
Transforming growth factor beta (TGFbeta) is secreted as a large latent precursor from both normal and transformed cells which needs to be activated for biological activity. The active TGFbeta binds either directly to TbetaR-II or indirectly by binding to beta-glycan which then presents the TGFbeta to TbetaR-II. Formation of the TGFbeta-TbetaR-II complex rapidly leads to phosphorylation of TbetaR-I. TbetaR-I, in turn, phosphorylates receptor-specific Smads and induces their translocation into the nucleus. TGFbeta is able to act as a growth stimulator or inhibitor and elicits a broad spectrum of biological effects on various cell types. However, these cells may lose their sensitivity and responsiveness to TGFbeta. Down-regulation or loss of functional receptors, aberrant signal transduction pathways due to Smad mutations, loss of the cell's ability to activate latent TGFbeta, loss of the peptide itself or functional genes that control the transcription and translation of TGFbeta may contribute to development of cancer.
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Neoplasias/metabolismo , Factor de Crecimiento Transformador beta/fisiología , Proteínas de Unión al ADN/metabolismo , Regulación hacia Abajo , Femenino , Humanos , Neoplasias/química , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Transducción de Señal , Proteína Smad2 , Proteína smad3 , Proteína Smad4 , Transactivadores/metabolismoRESUMEN
Oestrogens play an important role in the development of breast cancer. Oestrone sulphate (E1S) acts as a huge reservoir of oestrogens in the breast and is converted to oestrone (E1) by oestrone sulphatase (E1STS). E1 is then reversibly converted to the potent oestrogen, oestradiol (E2) by oestradiol-17beta hydroxysteroid dehydrogenase (E2DH). The aim of this study was to assess the effects of transforming growth factor-beta1 (TGFbeta1), insulin-like growth factor-I (IGF-I) and insulin-like growth factor-II (IGF-II) on cell growth, E1STS and E2DH activities in the MCF-7 and MDA-MB-231 human breast cancer cell lines. TGFbeta1, IGF-I and IGF-II alone or in combination inhibited cell growth of both cell lines but no additive or synergistic effects were observed. The treatments significantly stimulated E1STS activity in the MCF-7 cell line, except for TGFbeta1 alone and TGFbeta1 and IGF-I in combination, where no effects were seen. Only TGFbeta1 and IGF-II acted synergistically to stimulate E1STS activity in the MCF-7 cells. There was no significant effect on E1STS activity in the MDA-MB-231 cells with any of the treatments. In the MCF-7 cells, TGFbeta1 and IGF-I, IGF-I and IGF-II, and TGFbeta1, IGF-I and IGF-II acted synergistically to stimulate the reductive E2DH activity, while only TGFbeta1, IGF-I and IGF-II synergistically stimulated the oxidative E2DH activity. There were no additive or synergistic effects on both oxidative and reductive E2DH activities in the MDA-MB-231 cells. In conclusion, TGFbeta1, IGF-I and IGF-II may have effects on oestrogen metabolism, especially in the MCF-7 cell line where they stimulated the conversion of E1S to E1 and E1 to E2 and, thus, may have roles to play in the development of breast cancer.
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Estrógenos/metabolismo , Factor II del Crecimiento Similar a la Insulina/farmacología , Factor I del Crecimiento Similar a la Insulina/farmacología , Factor de Crecimiento Transformador beta/farmacología , Células Tumorales Cultivadas/efectos de los fármacos , Neoplasias de la Mama/enzimología , Neoplasias de la Mama/patología , Recuento de Células , División Celular/efectos de los fármacos , Combinación de Medicamentos , Sinergismo Farmacológico , Estradiol Deshidrogenasas/metabolismo , Femenino , Humanos , Sulfatasas/metabolismo , Factor de Crecimiento Transformador beta1 , Células Tumorales Cultivadas/enzimología , Células Tumorales Cultivadas/patologíaRESUMEN
1. We found previously that propranolol augments hyperpnoea-induced bronchoconstriction (HIB). This study was performed to investigate the underlying mechanism of this aug- menting action of propranolol. 2. In the first series, 45 young Hartley guinea-pigs were divided into five groups: control; propranolol; adrenalectomy; metoprolol and reserpine. Each animal underwent three periods: baseline, hyperpnoea, and recovery. For each animal 1 ml of arterial blood was sampled during the baseline and recovery periods. 3. Treatments of propranolol, metoprolol, and reserpine caused significant decreases in both dynamic respiratory compliance (Crs) and forced expiratory volume in 0.1 s (FEV0.1) during the baseline period. Hyperpnoea caused slight but not significant decreases in Crs, FEV0.1, and maximal expiratory flow at 50% total lung capacity (TLC) (V(max50)) during the recovery period in the control group. Propranolol, but not other treatments, significantly augmented these decreases (indicating HIB). Plasma noradrenaline and adrenaline levels in the reserpine group were not detectable. The above treatments or hyperpnoea did not induce any significant effect on the plasma noradrenaline level. Plasma adrenaline level of the control group was higher than that of either adrenalectomy or reserpine group during the baseline and the recovery periods. 4. In the second series, we avoided repeated blood samplings. Forty-eight animals were evenly divided into two groups: control and propranolol. Each group was again evenly divided into three subgroups: baseline; hyperpnoea, and recovery. Five minutes into the recovery period, we demonstrated HIB in the control group. In terms of V(max50), this HIB was significantly augmented by propranolol. Plasma noradrenaline and adrenaline levels, however, were not significantly altered by either hyperpnoea or propranolol. 5. Taken together, these data suggest that propranolol-augmented HIB has no direct relationship with decreased catecholamine activity.
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Broncoconstricción/fisiología , Catecolaminas/sangre , Hiperventilación/fisiopatología , Adrenalectomía , Inhibidores de Captación Adrenérgica/farmacología , Antagonistas Adrenérgicos beta/farmacología , Resistencia de las Vías Respiratorias/efectos de los fármacos , Resistencia de las Vías Respiratorias/fisiología , Animales , Broncoconstricción/efectos de los fármacos , CobayasRESUMEN
Breast cancer is the most common cancer in women worldwide. The growth of breast cancer cells is either hormone-dependent or hormone-independent. Both types are represented in vitro by the estrogen-receptor positive (ER+) MCF-7 and the estrogen-receptor negative (ER-) MDA-MB-231 cell lines, respectively. The pS2 gene is an estrogen-regulated gene and serves as a marker for the ER+ tumours. Carotenoids are pigments with anti-cancer properties besides having pro-vitamin A, antioxidant and free-radical quenching effects. This study was designed firstly, to compare the effect of palm oil carotene concentrate with retinoic acid on the growth of the ER+ MCF-7 and the ER- MDA-MB-231 cells; and secondly to evaluate the effect of the palm oil carotene concentrate on the regulation of pS2 mRNA. The growth experiments were performed with monolayer cells seeded in phenol red free RPMI 1640 culture media and subsequently treated with varying concentrations of either retinoic acid or palm oil carotenoids. The cell numbers were determined at the start of each experiment and then at successive time intervals. The results showed that the palm oil carotene concentrate caused dose-dependent inhibition of estradiol-stimulated growth of MCF-7 cells but did not affect the proliferation of MDA-MB-231 cells. Retinoic acid caused similar, albeit more potent effects, as significant inhibition was observed at lower concentrations than the palm oil carotenoids. In the pS2 gene expression experiment, cell monolayers were treated with the carotene concentrate (10(-6) M), either with or without supplemented estradiol (10(-8) M), and subsequently the RNA was extracted. Northern blotting was performed and the regulation of pS2 mRNA determined using a 32P-labelled pS2 cDNA probe. The results showed that the palm oil carotene concentrate did not affect the expression of pS2 mRNA and are therefore independent of the estrogen-regulated pathway.
Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Carotenoides/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Proteínas/genética , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Biomarcadores de Tumor , Carotenoides/aislamiento & purificación , Recuento de Células , División Celular/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Proteínas de Choque Térmico/biosíntesis , Proteínas de Choque Térmico/genética , Humanos , Aceite de Palma , Aceites de Plantas/química , ARN Neoplásico/biosíntesis , ARN Neoplásico/genética , Receptores de Estrógenos/biosíntesis , Receptores de Estrógenos/genética , Factor Trefoil-1 , Tretinoina/aislamiento & purificación , Tretinoina/farmacología , Células Tumorales Cultivadas , Proteínas Supresoras de TumorRESUMEN
Oestrogen is important in the development of breast cancer. Oestrogen receptor positive breast cancers are associated with a better prognosis than oestrogen-receptor negative breast cancers since they are more responsive to hormonal treatment. Oestrone sulphate acts as a huge reservoir for oestrogens in the breast. It is converted to the potent oestrogen, oestradiol (E(2)) by the enzymes oestrone sulphatase and oestradiol-17beta hydroxysteroid dehydrogenase (E(2)DH). Retinoic acid and carotenoids have been shown to have chemopreventive activity against some cancers. The aim of our study was to determine and compare the effects of retinoic acid and palm oil carotenoids on growth of and oestrone sulphatase and E(2)DH activities in the oestrogen receptor positive, MCF-7 and oestrogen receptor negative, MDA-MB-231 breast cancer cell lines. Retinoic acid and carotenoids inhibited MCF-7 cell growth but had no effect on MDA-MB-231 cell growth. Both retinoic acid and carotenoids stimulated oestrone sulphatase activity in the MCF-7 cell line. E(1) to E(2) conversion was inhibited by 10(-7) M carotenoids but was stimulated at 10(-6) M in the MCF-7 cell line. Retinoic acid had no effect on E(1) to E(2) conversion at 10(-7) M but stimulated E(1) to E(2) conversion at 10(-6) M. Retinoic acid and carotenoids had no effect on E(2) to E(1) conversion in the MCF-7 cell line. Retinoic acid stimulated E(1) to E(2) conversion in the MDA-MB-231 cell line but had no effect on oestrone sulphatase activity or E(2) to E(1) conversion in this cell line. Both oestrone sulphatase and E(2)DH activity were not affected by carotenoids in the MDA-MB-231 cell line. In conclusion, retinoic acid and carotenoids may prevent the development of hormone-dependent breast cancers since they inhibit the growth of the MCF-7 cell line.
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Antineoplásicos/farmacología , Neoplasias de la Mama/enzimología , Carotenoides/farmacología , Estradiol Deshidrogenasas/metabolismo , Aceites de Plantas/farmacología , Sulfatasas/metabolismo , Neoplasias de la Mama/patología , División Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Aceite de Palma , Receptores de Estrógenos/fisiología , Tretinoina/farmacología , Células Tumorales CultivadasRESUMEN
Transforming growth factor beta (TGF-beta) is a multifunctional regulator of cellular growth and differentiation in many cell types and has a growth inhibitory effect on mammary epithelial cells. The TGF-beta 2 isoform has been shown to be present in high concentrations in breast cyst fluid and might have a protective role in breast cancer. In addition, oestrogens play an important role in breast cancer development, and oestrone sulphate (E1S) might be the main source of active oestrogens in the breast. The aim of this study was to assess the effect of TGF-beta 2 on oestrogen synthesis in an attempt to understand the mechanism by which TGF-beta 2 may exert a protective effect in breast cancer. In this study, higher concentrations of TGF-beta 2 significantly inhibited the conversion of E1S to oestrone (E1) and the conversion of E1 to the potent oestrogen, oestradiol (E2). TGF-beta 2 did not have any effect on MCF-7 cell growth or on E2 to E1 conversion. In conclusion, TGF-beta 2 might exert a protective role in breast cancer by reducing the amount of active oestrogens present in the breast.
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Estradiol/biosíntesis , Antagonistas de Estrógenos/farmacología , Estrona/metabolismo , Factor de Crecimiento Transformador beta/farmacología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Femenino , Humanos , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/metabolismoRESUMEN
The mechanisms by which bacteria resist cell-mediated immune responses to cause chronic infections are largely unknown. We report the identification of a large gene present in enteropathogenic strains of Escherichia coli (EPEC) that encodes a toxin that specifically inhibits lymphocyte proliferation and interleukin-2 (IL-2), IL-4, and gamma interferon production in response to a variety of stimuli. Lymphostatin, the product of this gene, is predicted to be 366 kDa and shares significant homology with the catalytic domains of the large clostridial cytotoxins. A mutant EPEC strain that has a disruption in this gene lacks the ability to inhibit lymphokine production and lymphocyte proliferation. Enterohemorrhagic E. coli strains of serotype O157:H7 possess a similar gene located on a large plasmid. Loss of the plasmid is associated with loss of the ability to inhibit IL-2 expression while transfer of the plasmid to a nonpathogenic strain of E. coli is associated with gain of this activity. Among 89 strains of E. coli and related bacteria tested, lifA sequences were detected exclusively in strains capable of attaching and effacing activity. Lymphostatin represents a new class of large bacterial toxins that blocks lymphocyte activation.
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Toxinas Bacterianas/genética , Proteínas de Escherichia coli , Escherichia coli/patogenicidad , Activación de Linfocitos , Toxinas Bacterianas/análisis , Células CACO-2 , División Celular , Relación Dosis-Respuesta a Droga , Escherichia coli/metabolismo , Humanos , Interferón gamma/biosíntesis , Interleucina-2/biosíntesis , Interleucina-4/biosíntesis , Interleucina-5/biosíntesis , Interleucina-8/biosíntesis , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/microbiología , Datos de Secuencia Molecular , Mutagénesis , PlásmidosRESUMEN
An association of herpesvirus and atherosclerosis has been suggested by seroepidemiologic studies and detection of the virus in arterial tissues. To facilitate the studies of the pathogenic role of herpesvirus in atherosclerosis, we established a rabbit model of atherosclerosis with bovine herpesvirus type-4 (BHV-4). Forty New Zealand White rabbits were randomly divided into six groups. Groups 1, 2, and 3 were inoculated iv with BHV-4 and control Groups 4, 5, and 6 with normal saline. Groups 1 and 4 were fed a regular diet throughout the experiment; Groups 2 and 5 were fed a diet supplemented with 2% cholesterol for 3 weeks starting at 3 weeks postinoculation; and Groups 3 and 6 with a diet supplemented with 2% cholesterol for 6 weeks starting at 3 days postinoculation. Extensive atherosclerotic lesions in Groups 2, 3, and 6, and small lesions in two rabbits in Group 1 were observed, but no obvious lesions were observed in Groups 4 and 5. BHV-4 DNA was demonstrated by polymerase chain reaction and liquid hybridization in aortic sections, various tissue samples, and peripheral blood mononuclear cells of all infected rabbits. Our studies demonstrated that BHV-4 can accelerate the atherosclerotic process in rabbits, and that experimental infection of rabbits with BHV-4 can be a useful atherosclerosis model.
Asunto(s)
Arteriosclerosis/virología , Infecciones por Herpesviridae/patología , Varicellovirus/patogenicidad , Animales , Aorta Torácica/patología , Arteriosclerosis/patología , Secuencia de Bases , Colesterol en la Dieta/administración & dosificación , Cartilla de ADN , ADN Viral/análisis , Masculino , Reacción en Cadena de la Polimerasa , Conejos , Varicellovirus/genéticaRESUMEN
The present study on the prevalence of intestinal parasites infection, from September to December 1999, was conducted among school children in Taoyuan Hsiang, Kaohsiung county. The investigated areas included three (Jiannshan, Shingjong and Taoyuan) primary schools. The overall infection rate in 305 children determined by Merthiolate-Iodine-Formaldehyde Concentration method of stools was 17%. Four confirmed species of helminthes (Ascaris lumbricoides, Hookworm, Trichuris trichiura and Hymenolepis nana) and three species of protozoa (Giardia lamblia, Entamoeba coli and Blastocystis hominis) were detected. Males and females had the infection rates of 24% and 11%. The infection rates of aboriginal and non-aboriginal children were 17% and 14%, respectively. Grade 1 and Grade 6 had the highest infection rate (21%). Following tape perianal examination of 302 children, the overall infection rate of Enterobius vermicularis was 25%. Males and females had the infection rates of 24% and 26%. The infection rates of aboriginal and non-aboriginal children were 27% and 11%, respectively. Grade 1 had the highest infection rate (37%). Based on these data, the infection rate of intestinal parasites among rural primary school children in Kaohsiung county remains high.
Asunto(s)
Parasitosis Intestinales/epidemiología , Niño , Femenino , Humanos , Masculino , Prevalencia , Salud Rural , Taiwán/epidemiologíaRESUMEN
Oestrogens play an important role in the development of breast cancer. A very important source of active oestrogens in the breast is oestrone sulphate which is converted to oestrone by oestrone sulphatase. The aim of this study was to assess the effects of IGF-I and IGF-II on oestrone sulphatase activity in, as well as cell growth of, MCF-7 and MDA-MB-231 human breast cancer cell lines. Cells were grown in supplemented DMEM and treated with varying concentrations of IGFs. At the end of the treatment period, intact cell monolayers were washed and assayed for oestrone sulphatase activity and the number of cell nuclei determined on a Coulter Counter. Oestrone sulphatase activity was significantly stimulated by IGF-I and II at concentrations of 100 ng/ml and 200 ng/ml in MCF-7 cells. IGF-I had no effect on oestrone sulphatase activity in MDA-MB-231 cells over the range of concentrations tested. Significant inhibition of oestrone sulphatase was observed in MDA-MB-231 cells at higher concentrations of IGF-II (50 ng/ml, 100 ng/ml and 200 ng/ml). Both IGF-I and IGF-II at higher concentrations (100 ng/ml and 200 ng/ml) significantly inhibited MCF-7 and stimulated MDA-MB-231 cell growth. Since IGF-I and II have effects on cell growth and oestrone sulphatase activity in breast cancer cell lines they may play a role in the development and progression of human breast cancer.