RESUMO
AIMS/OBJECTIVES: The purpose of this study was to explore the molecular basis of the K0 phenotype of a Taiwanese blood donor found to have anti-Ku alloantibodies. BACKGROUND: With respect to Kell blood group antigens, almost all Taiwanese have the (K-, k+) phenotype. MATERIALS AND METHODS: Alloantibody identification and KEL antigen typing were performed. Enzymatic function assays were carried out to detect the Kell glycoprotein on RBCs. The KEL genes were sequenced to detect genetic variation. To determine the origin of this novel allele, family studies were conducted. RESULTS: The alloantibody was identified as anti-Ku. The donor was typed K0 . The KEL gene-sequencing data revealed that this K0 donor is a compound heterozygote with two different null alleles. He bears a novel 730delG mutation in one allele. Family studies suggested that the donor inherited the 730delG mutation from his father. The endothelin-converting activity assay indicated that his RBCs had no functional Kell glycoprotein. Other family members who had only one null allele with the 730delG mutation had the phenotype (K-, k+). CONCLUSION: For blood transfusion safety, it is important to establish an effective screening algorithm to identify rare phenotypes, such as the K0 phenotype, and to establish a database of rare blood groups.
Assuntos
Doadores de Sangue , Sistema do Grupo Sanguíneo de Kell/genética , Mutação , Transfusão de Sangue/normas , Análise Mutacional de DNA , Família , Heterozigoto , Humanos , Isoanticorpos/sangue , Fenótipo , TaiwanRESUMO
GABAB and GABAA binding sites were evaluated by quantitative autoradiography of 3H-GABA binding in superior frontal gyrus of persons who died with dementia of the Alzheimer's type (DAT) and of age-matched normal controls. Scatchard analysis and competition studies disclosed 48 to 68% and 25% decrements in receptor density (Bmax) for GABAB and GABAA receptors, respectively, in layers II, III, and V of DAT frontal cortex as compared with controls. No significant difference in affinity (KD) for either GABAA or GABAB receptors was found. Our data may reflect multisystem pathologic involvement in DAT neocortex.
Assuntos
Doença de Alzheimer/metabolismo , Lobo Frontal/metabolismo , Receptores de GABA-A/metabolismo , Idoso , Doença de Alzheimer/patologia , Animais , Autorradiografia , Baclofeno , Ligação Competitiva , Humanos , Ácidos Isonicotínicos , Cinética , Pessoa de Meia-Idade , Ratos , Receptores de GABA-A/classificaçãoRESUMO
[3H]GABA quantitative autoradiography was used to examine the binding kinetics and regional distribution of GABAB receptors in rat brain. The regional distribution was compared to that of GABAA receptors. At 4 degrees C, [3H]GABA binding to GABAB receptors reached equilibrium within 45 min. The association and dissociation rate constants for GABAB binding to outer neocortical layers were 2.87 +/- 0.17 X 10(5) min-1 M-1 and 0.0966 +/- 0.0118 min-1, respectively, indicating a dissociation constant of 336 +/- 40 nM. Saturation binding studies in the same region yielded a dissociation constant for GABAB receptors of 341 +/- 41 nM while that of GABAA receptors was 92 +/- 10 nM. While the affinities of each type of GABA receptor were uniform across brain regions, the maximal number of binding sites for both types of GABA receptor varied across regions. The distributions of the two receptors in rat brain were different in the olfactory bulb, cerebellum, thalamus, neocortex, medial habenula and interpeduncular nucleus. Areas high in GABAB binding included the medial and lateral geniculates, the superior colliculus and certain amygdaloid nuclei. Binding to white matter tracts and ventricles was negligible. The distribution of GABAB receptors was in agreement with previously postulated sites of action of baclofen.
Assuntos
Encéfalo/metabolismo , Receptores de GABA-A/metabolismo , Ácido gama-Aminobutírico/metabolismo , Animais , Autorradiografia , Baclofeno/metabolismo , Ligação Competitiva , Ácidos Isonicotínicos/metabolismo , Masculino , Ratos , Ratos Endogâmicos , Receptores de GABA-A/efeitos dos fármacosRESUMO
Kabuki (Niikawa-Kuroki) syndrome (KS) comprises characteristic facial changes, developmental delay, skeletal anomalies, mental retardation, and abnormal dermatoglyphics. We report on a 5-year-old Caucasian boy with KS who required surgery for a giant left temporoparietal subarachnoid cyst at age 5 1/2 years. Review of the 143 published cases shows that while malformations may be found in the endocrine, cardiac, genitourinary and skeletal systems, this is the first case of Kabuki syndrome with a major central nervous system malformation.
Assuntos
Anormalidades Múltiplas , Cistos Aracnóideos/congênito , Encéfalo/anormalidades , Cistos Aracnóideos/diagnóstico por imagem , Cistos Aracnóideos/cirurgia , Pré-Escolar , Fácies , Humanos , Masculino , Síndrome , Tomografia Computadorizada por Raios XRESUMO
Alpha-thalassemia has been estimated to account for over 60% of hydrops fetalis cases in Taiwan. The most common genotypic lesion found in alpha-thalassemia-1 cases in Taiwan is deletion of a large segment of the alpha-globin gene cluster, termed the Southeast Asian-type deletion (-SEA/; further referred to as SEA-type deletion). Seven chorionic villus samples (CVS) from pregnancies of couples both heterozygous for SEA-type deletion were studied. Non-radioactive Southern-blot hybridization using the dig-alkaline phosphatase detection system was developed to fulfill this purpose. The results were compared with corresponding polymerase chain reaction (PCR) data to elucidate the effectiveness of these two protocols in the diagnosis of the SEA-type deletion. The data showed that of the seven CVS, three demonstrated a distinctive band pattern, indicating their homozygous status of SEA-type deletion, whereas two showed heterozygous patterns, and the other two were free of the deletion. Homozygosity of the deletion was confirmed by Southern-blot hybridization performed on DNA samples extracted from the abortus tissue. However, two of the three cases with SEA-type deletion showed heterozygous PCR results. Maternal cell contamination could be responsible for the artifacts in the PCR results, but the influence due to the contamination is minimal in non-radioactive Southern-blot hybridization. We concluded that PCR is suitable for screening of carrier adults with SEA-type deletion, and non-radioactive Southern hybridization is ideal for early prenatal diagnosis of the SEA-type deletion.
Assuntos
Southern Blotting/métodos , Deleção de Genes , Complicações Hematológicas na Gravidez/diagnóstico , Talassemia alfa/diagnóstico , Talassemia alfa/genética , Sudeste Asiático , Amostra da Vilosidade Coriônica , Digoxigenina , Feminino , Triagem de Portadores Genéticos , Testes Genéticos , Humanos , Masculino , Reação em Cadeia da Polimerase , Gravidez , Complicações Hematológicas na Gravidez/epidemiologia , Taiwan , Talassemia alfa/epidemiologiaRESUMO
OBJECTIVE: To assess the ability of second-trimester maternal serum free beta-hCG to detect fetal Down syndrome and to compare free beta-hCG to intact hCG in the multiple-marker screening test for Down syndrome. METHODS: From our bank of stored maternal sera, we selected 40-50 samples from euploid pregnancies at each week of gestation from 14 to 20 weeks and 31 samples from Down syndrome pregnancies. Free beta-hCG was measured by enzyme-linked immunosorbent assay, and week-specific multiples of the median (MoM) were derived. The free beta-hCG Down syndrome detection and false-positive rates were determined. Free beta-hCG was then substituted for intact hCG in the multiple-marker screening test, and the Down syndrome detection and false-positive rates at various risk cutoffs were compared. RESULTS: The mean (+/-standard deviation) maternal age of all study samples was 35.6 +/- 5.3 years. The mean Down syndrome free beta-hCG MoM was significantly higher than the mean euploid MoM (2.4 +/- 1.1 versus 1.2 +/- 1.0; P < .001). A free beta-hCG level of at least 1.7 MoM identified 68% of Down syndrome pregnancies at a false-positive rate of 20%. When intact hCG was replaced with free beta-hCG in the multiple-marker screening test, a higher Down syndrome detection rate was achieved at a lower false-positive rate at each of several screen positive risk cutoffs. CONCLUSION: Elevated free beta-hCG levels identify Down syndrome pregnancies. Replacing intact hCG with free beta-hCG in the multiple-marker screening test results in a higher Down syndrome detection rate at a lower false-positive rate.
Assuntos
Gonadotropina Coriônica Humana Subunidade beta/sangue , Gonadotropina Coriônica/sangue , Síndrome de Down/diagnóstico , Diagnóstico Pré-Natal , Adulto , Reações Falso-Positivas , Feminino , Humanos , Gravidez , Segundo Trimestre da Gravidez , Kit de Reagentes para DiagnósticoRESUMO
OBJECTIVE: To study the usefulness of maternal serum insulin-like growth factor binding protein-3, a potential cell growth inhibitor, in second trimester prenatal screening for fetal Down syndrome. METHODS: Three hundred and forty-two samples from normal pregnancies and nine fetal Down syndrome pregnancies were analyzed for insulin-like growth factor binding protein-3 levels by radioimmunoassay. Data were converted to multiples of median (MoM) and analyzed statistically to compare the differences between control and Down syndrome pregnancies. RESULTS: The mean insulin-like growth factor binding protein-3 MoM of Down syndrome-affected pregnancies (1.09) was significantly higher than that of the normal pregnancies (1.00) (P < .01). Insulin-like growth factor binding protein-3, in combination with maternal serum alpha-fetoprotein (MSAFP), hCG, and maternal age, detected 89% of Down syndrome pregnancies at a screen positive rate of 2.1%. This compares favorably to the standard combination of MSAFP, hCG, and unconjugated estriol (E3), which had a 66.7% Down syndrome detection rate and a 4.1% screen positive rate in our study samples. CONCLUSION: This retrospective analysis suggested that the inclusion of insulin-like growth factor binding protein-3 into the triple screen program to replace unconjugated E3 might enhance the detection rate of fetal Down syndrome pregnancies. These data need to be confirmed by a larger prospective study.
Assuntos
Biomarcadores/sangue , Síndrome de Down/diagnóstico , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Diagnóstico Pré-Natal , Adulto , Gonadotropina Coriônica/sangue , Estriol/sangue , Feminino , Doenças Fetais/diagnóstico , Humanos , Recém-Nascido , Modelos Logísticos , Gravidez , Segundo Trimestre da Gravidez , Radioimunoensaio , Estudos Retrospectivos , alfa-Fetoproteínas/análiseRESUMO
The neuronal localization of glutamate and phencyclidine (PCP) receptors was evaluated in the cerebral cortex and hippocampal formation of rat CNS using quantitative autoradiography. Scatchard analysis of [3H]glutamate binding in the cortex (layers I and II and V and VI) showed no difference in the total number of binding sites (Bmax) or apparent affinity (Kd) 1 week, 1 month and 2 months following unilateral ibotenate lesions to nucleus basalis of Meynert (nbM) compared to the non-lesioned side. Quisqualic acid displacement of [3H]glutamate in layers I and II, 1 week following nbM destruction, revealed both high- and low-affinity binding sites (representing the quisqualate (QA) and N-methyl-D-aspartate (NMDA) sites, respectively). Compared to the control side, there was no difference in binding parameters for either of the receptor sites. In similarly lesioned animals, the NMDA receptor was specifically labelled with [3H]glutamate and the associated PCP receptor labelled with [3H]N-(1-[2-thienyl]cyclohexyl)3,4-piperidine ([3H]TCP) in adjacent brain sections. For both receptors, there was no change in the total number of binding sites in the cortex following destruction of nbM. On the other hand, virtually all binding to NMDA and PCP receptors was eliminated following chemical destruction of intrinsic cortical neurons. These results suggest that the NMDA/PCP receptor complex does not exist on the terminals of cortical cholinergic afferents. One week after knife cuts of the glutamatergic entorhinal pathway to the hippocampal formation only an approximate 10% reduction of NMDA and PCP receptors was seen in the dentate gyrus. Conversely, selective destruction of the dentate granule cells using colchicine caused a near identical loss of NMDA and PCP receptors (84% vs 92% respectively). It is concluded from these experiments that glutamate and PCP receptors exist almost exclusively on neurons intrinsic to the hippocampal formation and that no more than 10% of NMDA and PCP receptors exist as autoreceptors on glutamatergic terminals.
Assuntos
Córtex Cerebral/fisiologia , Hipocampo/fisiologia , Fenciclidina/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores de Neurotransmissores/metabolismo , Acetilcolinesterase/metabolismo , Animais , Autorradiografia , Ligação Competitiva , Radioisótopos de Carbono , Córtex Cerebral/metabolismo , Colina O-Acetiltransferase/metabolismo , Lateralidade Funcional , Glutamatos/metabolismo , Hipocampo/metabolismo , Cinética , Masculino , Ácido Quisquálico/farmacologia , Ratos , Ratos Endogâmicos , Receptores de Glutamato , Receptores da Fenciclidina , TrítioRESUMO
GABAB and GABAA receptors were examined by quantitative [3H]GABA autoradiography in postmortem human hippocampus from 6 histopathologically verified cases of dementia of the Alzheimer type (DAT) and 6 normal controls. Significant decrements in the Bmax for both types of GABA receptors were observed in DAT hippocampus as compared to normal controls. No significant differences in Kd values were revealed. As compared to controls, DAT hippocampus exhibited fewer GABAB receptors in stratum moleculare of the dentate gyrus, stratum lacunosum-moleculare and stratum pyramidale of CA1. Significant loss of GABAA receptors in DAT hippocampus was also observed in the CA1 pyramidal cell region. These changes could not be correlated with differences in age nor in postmortem delay between the two groups. These findings may reflect the neuronal pathologies in CA1 region, in dentate gyrus, and in projections from the entorhinal cortex which are associated with the memory impairment in DAT.
Assuntos
Doença de Alzheimer , Hipocampo/análise , Receptores de GABA-A/análise , Idoso , Autorradiografia , Humanos , Pessoa de Meia-IdadeRESUMO
We have previously demonstrated a marked loss in N-methyl-D-aspartate (NMDA) receptors in the hippocampus and cerebral cortex of patients dying with dementia of the Alzheimer type (DAT). In addition, we have found that the dissociative anesthetic N-(1-[2-thienyl]cyclohexyl)3,4-piperidine ([3H]TCP) binds to a site whose regional distribution is highly correlated with that of NMDA receptor sites. We studied the binding of [3H]TCP to sections of hippocampi from 8 controls, 12 patients with DAT and 7 patients with other dementias. [3H]TCP binding was significantly reduced in strata pyramidalia of CA1/CA2, CA3 and subiculum of DAT hippocampal formation compared to that of control. Labelled dissociative anesthetics could potentially be used with positron emission tomography in the diagnosis of DAT.
Assuntos
Doença de Alzheimer/metabolismo , Hipocampo/metabolismo , Fenciclidina/análogos & derivados , Autorradiografia , Sítios de Ligação , Humanos , Fenciclidina/metabolismo , Receptores de N-Metil-D-Aspartato , Receptores de Neurotransmissores/metabolismoRESUMO
Para-Bombay phenotype, with an estimated incidence of 1 in 8000 in Taiwanese residents based on serological analysis, is caused by aberrant alpha(1,2)-fucosyltransferase function and hence diminished H-antigen synthesis. In an individual with para-Bombay phenotype, DNA sequencing revealed two missense mutations previously reported C658T mutation and a novel G659A mutation. Haplotype analysis with restriction enzyme digestion showed that the two mutations are located on opposing alleles of the H (FUT1) gene and lead to compound heterozygosity. Since no other known genetic changes were evident, it appears that the new missense mutation, G659A, is deleterious to the alpha(1,2)-fucosyltransferase function encoded by the H (FUT1) gene.
Assuntos
Sistema ABO de Grupos Sanguíneos/genética , Fucosiltransferases/genética , Mutação de Sentido Incorreto , Antígenos de Bactérias/imunologia , Sequência de Bases , Análise Mutacional de DNA , Etnicidade/genética , Éxons , Haplótipos , Humanos , Masculino , Fenótipo , Taiwan , Galactosídeo 2-alfa-L-FucosiltransferaseRESUMO
The preventive effect of partially hydrolyzed guar gum (PHGG) on the colonization of Salmonella enteritidis (SE) in young and laying hens was investigated. The effects of feed supplemented with 0.025, 0.05, and 0.1% PHGG was examined on young hens orally infected with SE. The incidence of SE in organs was decreased, the excretion of SE into feces was increased, and the agglutinating antibody titer to SE in serum was decreased by the administration of PHGG to young hens. In particular, feed supplemented with 0.025% PHGG was the most effective. It was also shown that feed supplemented with 0.025% PHGG increased the number of Bifidobacterium spp. and Lactobacillus spp., the most numerous intestinal bacteria in the cecum of young hen. The effect of the excretion of SE via feces was also observed in an experiment using laying hens. The incidence of SE on the surface of the eggshell and in egg white and egg yolk was also decreased when the feed of laying hens was supplemented with 0.025% PHGG. These results show that the administration of feed supplemented with PHGG can prevent the colonization of SE in young and laying hens, which, in turn, could be related to improvement in the balance of intestinal microflora.
Assuntos
Galinhas , Ovos/microbiologia , Galactanos/administração & dosagem , Mananas/administração & dosagem , Doenças das Aves Domésticas/prevenção & controle , Salmonelose Animal/prevenção & controle , Salmonella enteritidis/crescimento & desenvolvimento , Testes de Aglutinação/veterinária , Ração Animal , Animais , Anticorpos Antibacterianos/sangue , Bifidobacterium/isolamento & purificação , Contagem de Colônia Microbiana , Casca de Ovo/microbiologia , Clara de Ovo/microbiologia , Gema de Ovo/microbiologia , Fezes/microbiologia , Feminino , Galactanos/química , Hidrólise , Intestinos/microbiologia , Lactobacillus/isolamento & purificação , Mananas/química , Antígenos O/química , Oviposição , Gomas Vegetais , Doenças das Aves Domésticas/microbiologia , Salmonelose Animal/sangue , Salmonelose Animal/microbiologia , Salmonella enteritidis/isolamento & purificaçãoRESUMO
BACKGROUND: Excessive greater splanchnic nerve (GSN) activation contributes to the progression of gastric ischemia-reperfusion (GI-R) injury. This study was designed to investigate the protective mechanism of cerebellar fastigial nucleus (FN) stimulation against GI-R injury. METHODS: The GI-R injury model was induced in rats by clamping the celiac artery for 30 min, and then reperfusion for 30 min, 1, 3, 6, or 24 h, respectively. KEY RESULTS: Microinjection of L-Glu (3, 6, 12 µg) into the FN dose-dependently attenuated GI-R injury and GSN activity. In addition, there was an enhancement of gastric mucosal blood flow in GI-R rats. Pretreatment with the glutamic acid decarboxylase antagonist into the FN, the GABAA receptor antagonist into the lateral hypothalamic area or lesion of superior cerebellar peduncle all reversed the protective effects of the FN stimulation. Furthermore, the FN stimulation reduced the TUNEL-positive gastric mucosal cell and Bax-positive gastric mucosal cell in GI-R rats. CONCLUSIONS & INFERENCES: These results indicate that the protective effects of the FN stimulation against GI-R injury may be mediated by attenuation of the excessive GSN activation, gastric mucosal cell apoptosis, and Bax expression in GI-R rats.
Assuntos
Cerebelo/fisiologia , Mucosa Gástrica/lesões , Hipotálamo/fisiologia , Rede Nervosa/fisiologia , Traumatismo por Reperfusão/fisiopatologia , Ácido gama-Aminobutírico/fisiologia , Animais , Artéria Celíaca/patologia , Artéria Celíaca/fisiologia , Cerebelo/efeitos dos fármacos , Estimulação Elétrica/métodos , Antagonistas GABAérgicos/administração & dosagem , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/fisiologia , Glutamina/administração & dosagem , Hipotálamo/efeitos dos fármacos , Masculino , Microinjeções/métodos , Rede Nervosa/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/prevenção & controle , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologiaAssuntos
Ácido Aspártico/análogos & derivados , Fenciclidina/análogos & derivados , Receptores de Neurotransmissores/metabolismo , Animais , Ácido Aspártico/metabolismo , Autorradiografia , Encéfalo/metabolismo , N-Metilaspartato , Fenciclidina/metabolismo , Ratos , Receptores de N-Metil-D-AspartatoRESUMO
For certain types of digitally generated holographic memories, it is important that the Fourier components to be stored have a constant, or nearly constant, modulus. It is shown that by interlacing two sequences of complex numbers, one a data sequence representing the information to be stored and the second a parity sequence, derivable from the data sequence, the discrete Fourier transform of the combined sequence can be made to have a constant modulus. A slight variation of the method leads to a spectrum with varying modulus but only a discrete set of phases. The sequences may be one-dimensional or multidimensional.
RESUMO
OBJECTIVE: The purpose of this study was to determine, among six second-trimester maternal serum analytes, the best three-analyte combination for fetal Down syndrome detection. STUDY DESIGN: With use of commercially available assay kits, medians for free beta-human chorionic gonadotropin, CA 125, and dimeric inhibin A were established in stored sera from 45 to 50 euploid pregnancies at each week of gestation from 14 to 22 weeks and from 33 Down syndrome pregnancies. Maternal serum alpha-fetoprotein, unconjugated estriol, and intact human chorionic gonadotropin levels measured in each sample before storage were retrieved. All 20 possible three-analyte combinations were evaluated in the multiple-marker screening test for Down syndrome. RESULTS: The mean maternal age of the study population was 35.6 +/- 5.3 years. The best three-analyte combination was maternal serum alpha-fetoprotein, free beta-human chorionic gonadotropin, and dimeric inhibin A: 97% of Down syndrome cases were detected at a false-positive rate of 16%. At a slightly higher false-positive rate (18%) maternal serum alpha-fetoprotein, estriol, and intact human chorionic gonadotropin detected only 79% of cases. CONCLUSIONS: Of six second-trimester maternal serum analytes, the best three-analyte combination for fetal Down syndrome detection was maternal serum alpha-fetoprotein, free beta-human chorionic gonadotropin, and dimeric inhibin A. This retrospective analysis should now be confirmed prospectively.
Assuntos
Gonadotropina Coriônica Humana Subunidade beta/sangue , Síndrome de Down/diagnóstico , Inibinas/sangue , Diagnóstico Pré-Natal , alfa-Fetoproteínas/análise , Adulto , Biomarcadores , Dimerização , Feminino , Humanos , Gravidez , Estudos RetrospectivosRESUMO
OBJECTIVE: Our purpose was to determine whether second-trimester dimeric inhibin A levels distinguish Down syndrome pregnancies from euploid pregnancies. STUDY DESIGN: With use of a commercially available enzyme-linked immunosorbent assay (Serotec, Oxford) inhibin A medians were established in stored sera from 40 to 50 euploid pregnancies at each week of gestation from 14 to 20 weeks and from 33 Down syndrome pregnancies. Maternal serum alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin levels measured in each sample before storage were retrieved. The performance of inhibin A in the multiple-marker screening test was evaluated. RESULTS: The mean inhibin A multiple of the median was significantly higher in the Down syndrome group than in the euploid group (2.84 +/- 2.0 vs 1.22 +/- 1.0, p = 0.0001). An inhibin A level > or = 1.6 multiples of the median identified 70% of all Down syndrome pregnancies at a false-positive rate of 22%. Replacing estriol with inhibin A in the multiple-marker screening test resulted in a higher Down syndrome detection rate at a lower screen-positive rate. CONCLUSION: Elevated second-trimester maternal serum inhibin A levels identify Down syndrome pregnancies; replacing estriol with inhibin A in the multiple-marker screening test improves test performance.
Assuntos
Síndrome de Down/diagnóstico , Inibinas/sangue , Diagnóstico Pré-Natal , Adulto , Gonadotropina Coriônica/sangue , Dimerização , Reações Falso-Positivas , Feminino , Humanos , Gravidez , Segundo Trimestre da Gravidez , alfa-Fetoproteínas/análiseRESUMO
OBJECTIVE: Our purpose was to determine whether the combination of maternal serum alpha-fetoprotein, free human chorionic gonadotropin-beta, dimeric inhibin A, and maternal age detects aneuploidies other than Down syndrome. STUDY DESIGN: We retrieved stored serum from pregnancies complicated by aneuploidies other than Down syndrome from 1988 to 1997 (n = 55, mean maternal age 35.2 +/- 5.6 years). Alpha-fetoprotein levels were obtained from our database, and free human chorionic gonadotropin-beta and dimeric inhibin A levels were measured in the thawed serum with use of commercial assays. Analyte values were used in both 3-analyte and 2-analyte multiple-marker screening tests; detection rates were determined at several different Down syndrome risk-positive cutoff values. RESULTS: In the 3-analyte test 58% (32/55) of all aneuploidies were detected with use of both the Down syndrome protocol at a screen-positive risk cutoff value of 1:300 (false-positive rate 17%) and a novel trisomy 18 screening algorithm. However, 67% (37/55) detection was obtained with use of the 2-analyte combination of alpha-fetoprotein and dimeric inhibin A, with both the Down syndrome protocol (screen positive cutoff value 1:300) and the trisomy 18 algorithm: 12 of 13 trisomy 18 (92%), 9 of 17 Turner's syndrome (53%), 10 of 17 other sex chromosome aneuploidies (59%), 1 of 1 trisomy 22 (100%), and 5 of 7 trisomy 13 (71%). CONCLUSIONS: The combination of maternal serum alpha-fetoprotein, dimeric inhibin A, and maternal age detects autosomal trisomies other than Down syndrome at a rate superior to that of the traditional analyte combination.
Assuntos
Aneuploidia , Inibinas/sangue , Diagnóstico Pré-Natal/métodos , alfa-Fetoproteínas/análise , Adulto , Gonadotropina Coriônica Humana Subunidade beta/sangue , Cromossomos Humanos Par 18 , Dimerização , Síndrome de Down/diagnóstico , Feminino , Idade Gestacional , Humanos , Gravidez , Aberrações dos Cromossomos Sexuais/diagnóstico , Trissomia , Síndrome de Turner/diagnósticoRESUMO
OBJECTIVE: Our goal was to prospectively evaluate the use of the free beta-subunit of human chorionic gonadotropin and dimeric inhibin A for the detection of fetal Down syndrome and other aneuploidies. STUDY DESIGN: Women who had a second-trimester multiple-marker screening test (alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin) and genetic amniocentesis from August 1996 to August 1998 were included. Serum was also analyzed for inhibin and the free beta-subunit of human chorionic gonadotropin. Detection and false-positive rates for 4 analyte combinations at 5 different screening risk cutoff points for Down syndrome were determined and compared. RESULTS: We evaluated 1256 patients, including 23 with aneuploidy (13 with Down syndrome, 10 others). The maternal age was 35.9 +/- 4.6 years (mean +/- SD). At the optimal risk cutoff point for Down syndrome detection (1:190; false-positive rate, 19%), the multiple-marker screening test plus inhibin was superior, detecting 85% of Down syndrome cases, in comparison with 69% when the multiple-marker screening test alone was used and 62% when the other 2 combinations were used. The multiple-marker screening test plus inhibin also detected 60% of the other aneuploidies. CONCLUSIONS: When evaluated prospectively in a high-risk population, the multiple-marker screening test plus inhibin was superior to the traditional multiple-marker screening test and 2 other analyte combinations, with a lower false-positive rate and increased detection of all aneuploidies in a high-risk population.
Assuntos
Aneuploidia , Gonadotropina Coriônica Humana Subunidade beta/sangue , Inibinas/sangue , Diagnóstico Pré-Natal/métodos , Amniocentese , Gonadotropina Coriônica/sangue , Dimerização , Síndrome de Down/diagnóstico , Estriol/sangue , Reações Falso-Positivas , Feminino , Deleção de Genes , Humanos , Gravidez , Estudos Prospectivos , Translocação Genética , Trissomia , alfa-Fetoproteínas/análiseRESUMO
BACKGROUND: The ABO system includes many variant subgroups. Some of them are difficult to identify serologically, leading to mistyping of blood groups. For example, Bel is often typed as O blood group. STUDY DESIGN AND METHODS: DNA sequencing and a molecular approach were explored to accurately determine the genotypes of Bel subgroups. Seven Bel blood donors and 106 individuals with other blood groups were analyzed serologically and molecularly. RESULTS: The serologic results of these seven Bel blood donors showed that their RBCs do not react with anti-B or anti-A,B, and their B antigen was detected by adsorption and elution methods. Sequencing results for exons 6 and 7 of ABO genes showed a new Bel allele with a C>T substitution at nucleotide position 502 in exon 7 of the ABO gene in all seven cases but not in other blood groups. Consequently, an amplification-created restriction site protocol was designed to detect the 502C>T genotype in Bel subgroup cases. CONCLUSION: A novel 502C>T mutation was found in the Bel subgroup in Taiwan and successfully developed a rapid and accurate molecular protocol to detect this mutation. To our knowledge, the new Bel allele that was found is unique in Taiwanese residents.