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Biomedical subjects

L F Chen

Publications and source records attributed to L F Chen.

At least 19 recordsLinked to original sources
PubMed2006

Healthy-side dominance of middle- and long-latency neuromagnetic fields in idiopathic sudden sensorineural hearing loss.

Any lesion along the neural axis may induce a subsequent functional reorganization at the level above. The present study used magnetoencephalography to investigate auditory-evoked magnetic fields [a component of the middle-latency auditory evoked fields peaking at approximately 50 ms (P50m) and a component of the long-latency auditory evoked fields peaking at approximately 100 ms (N100m)] on stimulation of both healthy and affected ears in patients with acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL) of moderate degree in order to elucidate the functional plasticity of the auditory system. Sixteen right-handed, previously untreated adult patients with acute unilateral left (n = 8) or right (n = 8) ISSNHL of moderate degree were studied. Sixteen right-handed healthy volunteers with normal hearing served as control. Auditory neuromagnetic responses, measured by a whole-head 306-channel neuromagnetometer, were detected by monaural tone stimulation applied to affected and healthy ears, respectively, in different sessions. Intragroup and intergroup interhemispheric differences of peak dipole strengths and latencies of P50m and N100m, respectively, to monaural tones were evaluated. Healthy-side amplitude dominance of both P50m and N100m was found in ISSNHL, i.e. contralateral dominance was preserved on affected-ear stimulation but ipsilateral dominance was seen on healthy-ear stimulation. The phenomena could be attributed to the combined contralateral attenuation and ipsilateral enhancement of P50m and N100m activity in response to healthy-ear stimulation. Our findings confirmed that functional modulation can occur within the first few tens of milliseconds of evoked response at the auditory cortex in ISSNHL. The mechanisms of healthy-side dominance might be ascribed to a functional retune of auditory pathways, i.e. conjoined contralateral inhibition and ipsilateral excitation of the auditory pathway in response to healthy-ear stimulation. The effect could be registered in cortical responses.

Acoustic Stimulation↗
PubMed2001

Prenatal diagnosis of partial monosomy 18p(18p11.2-->pter) and trisomy 21q(21q22.3-->qter) with alobar holoprosencephaly and premaxillary agenesis.

A prenatal diagnosis of partial monosomy 18p(18p11.2-->pter) and trisomy 21q(21q22.3-->qter) in a fetus with alobar holoprosencephaly (HPE) and premaxillary agenesis (PMA) but without the classical Down syndrome phenotype is reported. A 27-year-old primigravida woman was referred for genetic counselling at 21 weeks' gestation due to sonographic findings of craniofacial abnormalities. Level II ultrasonograms manifested alobar HPE and median orofacial cleft. Cytogenetic analysis and fluorescence in situ hybridization (FISH) on cells obtained from amniocentesis revealed partial monosomy 18p and a cryptic duplication of 21q,46,XY,der(18)t(18;21)(p11.2;q22.3), resulting from a maternal t(18;21) reciprocal translocation. The breakpoints were ascertained by molecular genetic analysis. The pregnancy was terminated. Autopsy showed alobar HPE with PMA, pituitary dysplasia, clinodactyly and classical 18p deletion phenotype but without the presence of major typical phenotypic features of Down syndrome. The phenotype of this antenatally diagnosed case is compared with those observed in six previously reported cases with monosomy 18p due to 18;21 translocation. The present study is the first report of concomitant deletion of HPE critical region of chromosome 18p11.3 and cryptic duplication of a small segment of distal chromosome 21q22.3 outside Down syndrome critical region. The present study shows that cytogenetic analyses are important in detecting chromosomal aberrations in pregnancies with prenatally detected craniofacial abnormalities, and adjunctive molecular investigations are useful in elucidating the genetic pathogenesis of dysmorphism.

Adult↗
PubMed2001

[Sequence analysis of the late region of human papillomavirus type 6 genome].

OBJECTIVE: To study variations of genome late region of human papillomavirus type 6 (HPV-6) isolated from Chinese patients with condyloma acuminatum. METHODS: Using overlap PCR design, major capsid protein (L1) and minor capsid protein (L2) genes were separately amplified from clinical samples following HPV type determination, and were further assembled into HPV-6 genome late region sequences after inserting into plasmid and sequencing. RESULTS: Two sequences (GenBank accession number AY015006, AY015008) of HPV-6 late region were assembled, which are 2,869 bp long covering 35% HPV-6 genome and with complete open reading frames (ORFs) for L1 and L2. Compared with prototype sequence, nine point mutations were found, including four missense mutations, three of which were located in L2 ORF. Phylogenetic analysis indicated that the cloned sequences are classified into HPV-6b. CONCLUSIONS: HPV-6 genome late region, especially in L1 ORF, is very conserved (variation rate < 0.28%). The mutation from A to G at position 7081 in HPV-6 genome and from G to A at 7099 may represent region characteristics. This is the first report that describes sequence variations among genome late region of HPV-6 isolated from Chinese patients.

Condylomata Acuminata↗
PubMed2000

The NF-kappa B-inducing kinase induces PC12 cell differentiation and prevents apoptosis.

NF-kappa B has been implicated in the survival and differentiation of PC12 cells. In this study, we examined the effect of the NF-kappa B-inducing kinase (NIK) on these processes. When inducibly expressed in PC12 cells, a kinase-proficient but not -deficient form of NIK promoted neurite process formation and mediated anti-apoptotic signaling. As expected, NIK expression led to I kappa B kinase activation and induced nuclear translocation of NF-kappa B. However, NIK-induced neurite outgrowth was only partially blocked by concomitant expression of a nondegradable form of I kappa B alpha that completely blocks NF-kappa B induction. In search of additional signaling pathways activated by NIK, we now demonstrate that NIK activates MEK1 phosphorylation and induces the Erk1/Erk2 MAPK pathway. Treatment of PC12 cells with PD98059, a MEK1 inhibitor, potently blocked neurite process formation; however, a dominantly interfering mutant of the upstream Shc adapter failed to alter this response. These findings reveal a new function for NIK as a MEK1-dependent activator of the MAPK pathway and implicate both the I kappa B kinase and MAPK signaling cascades in NIK-induced differentiation of PC12 cells.

Animals↗
PubMed2000

Prenatal diagnosis and genetic analysis of double trisomy 48,XXX,+18.

Prenatal diagnosis of simultaneous occurrence of double trisomy involving chromosomes 18 and X is extremely rare. We report on the prenatal diagnosis, genetic analysis and clinical manifestations of a fetus with both trisomy 18 and trisomy X. A 26-year-old, para 1 woman was referred for genetic counselling at 36 weeks' gestation with the sonographic findings of intrauterine growth retardation (IUGR), polyhydramnios, ventricular septal defect, and an enlarged cisterna magna. Both cordocentesis and amniocentesis revealed a consistent karyotype of 48,XXX,+18. Quantitative fluorescent polymerase chain reaction using polymorphic small tandem repeat markers specific for chromosomes 18 and X rapidly determined that both aneuploidies arose as a result of non-disjunction in maternal meiosis II. Our case shows that two non-disjunction events can occur not only in the same parent, but also in the same cell division. Our case also shows that double trisomy, 48,XXX,+18, can demonstrate an enlarged cisterna magna, IUGR and polyhydramnios in prenatal ultrasound.

Adult↗
PubMed2000

Prenatal diagnosis and genetic analysis of X chromosome polysomy 49, XXXXY.

We report on the prenatal diagnosis, genetic analysis and clinical manifestations of a 49,XXXXY fetus. A 31-year-old, primigravida woman was referred for genetic counselling at 17 weeks' gestation with the sonographic findings of intrauterine growth retardation, generalized oedema, a large septated cystic hygroma colli measuring 5x4 cm, and abnormal posturing of the lower extremities. Quantitative fluorescent polymerase chain reaction (QF-PCR) with small tandem repeat (STR) markers specific for chromosome X and a pentanucleotide marker X22 for the Xq/Yq pseudoautosomal region PAR2 rapidly detected the X-chromosome polysomy from amniotic fluid cells. This abnormality appeared to arise from successive non-disjunction during maternal meiosis I and meiosis II. Cytogenetic analysis revealed a karyotype of 49,XXXXY. Our case shows that a 49,XXXXY fetus in the second trimester may demonstrate hydrops fetalis and a large septated cystic hygroma colli by prenatal ultrasound. Our case also shows that QF-PCR assays with sex chromosome specific STR markers provide rapid prenatal diagnosis of numerical sex chromosome aneuploidy as well as its genetic cause in fetal cystic hygroma.

Abnormalities, Multiple↗
PubMed1999

Tomographic 3D reconstruction of quick-frozen, Ca2+-activated contracting insect flight muscle.

Motor actions of myosin were directly visualized by electron tomography of insect flight muscle quick-frozen during contraction. In 3D images, active cross-bridges are usually single myosin heads, bound preferentially to actin target zones sited midway between troponins. Active attached bridges (approximately 30% of all heads) depart markedly in axial and azimuthal angles from Rayment's rigor acto-S1 model, one-third requiring motor domain (MD) tilting on actin, and two-thirds keeping rigor contact with actin while the light chain domain (LCD) tilts axially from approximately 105 degrees to approximately 70 degrees. The results suggest the MD tilts and slews on actin from weak to strong binding, followed by swinging of the LCD through an approximately 35 degrees axial angle, giving an approximately 13 nm interaction distance and an approximately 4-6 nm working stroke.

Actins↗
PubMed1999

Interaction and functional cooperation of PEBP2/CBF with Smads. Synergistic induction of the immunoglobulin germline Calpha promoter.

Smads are signal transducers for members of the transforming growth factor-beta (TGF-beta) superfamily. Upon ligand stimulation, receptor-regulated Smads (R-Smads) are phosphorylated by serine/threonine kinase receptors, form complexes with common-partner Smad, and translocate into the nucleus, where they regulate the transcription of target genes together with other transcription factors. Polyomavirus enhancer binding protein 2/core binding factor (PEBP2/CBF) is a transcription factor complex composed of alpha and beta subunits. The alpha subunits of PEBP2/CBF, which contain the highly conserved Runt domain, play essential roles in hematopoiesis and osteogenesis. Here we show that three mammalian alpha subunits of PEBP2/CBF form complexes with R-Smads that act in TGF-beta/activin pathways as well as those acting in bone morphogenetic protein (BMP) pathways. Among them, PEBP2alphaC/CBFA3/AML2 forms a complex with Smad3 and stimulates transcription of the germline Ig Calpha promoter in a cooperative manner, for which binding of both factors to their specific binding sites is essential. PEBP2 may thus be a nuclear target of TGF-beta/BMP signaling.

Activin Receptors, Type I↗
PubMed1999

A WW domain-containing yes-associated protein (YAP) is a novel transcriptional co-activator.

A protein module called the WW domain recognizes and binds to a short oligopeptide called the PY motif, PPxY, to mediate protein-protein interactions. The PY motif is present in the transcription activation domains of a wide range of transcription factors including c-Jun, AP-2, NF-E2, C/EBPalpha and PEBP2/CBF, suggesting that it plays an important role in transcriptional activation. We show here that mutation of the PY motif in the subregion of the activation domain of the DNA-binding subunit of PEBP2, PEBP2alpha, abolishes its transactivation function. Using yeast two-hybrid screening, we demonstrate that Yes-associated protein (YAP) binds to the PY motif of PEBP2alpha through its WW domain. The C-terminal region of YAP fused to the DNA-binding domain of GAL4 showed transactivation as strong as that of GAL4-VP16. Exogenously expressed YAP conferred transcription-stimulating activity on the PY motif fused to the GAL4 DNA-binding domain as well as to native PEBP2alpha. The osteocalcin promoter was stimulated by exogenous PEBP2alphaA and a dominant negative form of YAP strongly inhibited this activity, suggesting YAP involvement in this promoter activity in vivo. These results indicate that the PY motif is a novel transcription activation domain that functions by recruiting YAP as a strong transcription activator to target genes.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Prenatal diagnosis of a fetus with distal 10q trisomy.

Distal 10q trisomy is a well-defined but rare syndrome. Most cases are diagnosed in infancy or in childhood and rarely include prenatal findings. We present a case of fetal distal 10q trisomy with abnormal prenatal sonographic findings. A 19-year-old primigravida was referred for genetic counselling at 18 gestational weeks because her husband had a familial history of congenital anomalies. Genetic amniocentesis was thus performed and showed fetal distal 10q trisomy (10q24.1-->qter), 46,XX,der(22)t(10;22)(q24.1;p11.2)pat, resulting from paternal t(10;22) reciprocal translocation. Level II ultrasonograms further demonstrated bilateral hydronephrosis, ventricular septal defect and facial dysmorphism ascertained by three-dimensional ultrasound. The pregnancy was terminated at 22 gestational weeks. Post-mortem autopsy confirmed the sonographic findings. We suggest that abnormal prenatal sonographic findings such as cardio-vascular, renal and facial malformations should alert cytogeneticists to search for subtle chromosomal abnormalities.

Adult↗
PubMed1998

Intrinsic transcriptional activation-inhibition domains of the polyomavirus enhancer binding protein 2/core binding factor alpha subunit revealed in the presence of the beta subunit.

A member of the polyomavirus enhancer binding protein 2/core binding factor (PEBP2/CBF) is composed of PEBP2 alphaB1/AML1 (as the alpha subunit) and a beta subunit. It plays an essential role in definitive hematopoiesis and is frequently involved in the chromosomal abnormalities associated with leukemia. In the present study, we report functionally separable modular structures in PEBP2 alphaB1 for DNA binding and for transcriptional activation. DNA binding through the Runt domain of PEBP2 alphaB1 was hindered by the adjacent carboxy-terminal region, and this inhibition was relieved by interaction with the beta subunit. Utilizing a reporter assay system in which both the alpha and beta subunits are required to achieve strong transactivation, we uncovered the presence of transcriptional activation and inhibitory domains in PEBP2 alphaB1 that were only apparent in the presence of the beta subunit. The inhibitory domain keeps the full transactivation potential of full-length PEBP2 alphaB1 below its maximum potential. Fusion of the transactivation domain of PEBP2 alphaB1 to the yeast GAL4 DNA-binding domain conferred transactivation potential, but further addition of the inhibitory domain diminished the activity. These results suggest that the activity of the alpha subunit as a transcriptional activator is regulated intramolecularly as well as by the beta subunit. PEBP2 alphaB1 and the beta subunit were targeted to the nuclear matrix via signals distinct from the nuclear localization signal. Moreover, the transactivation domain by itself was capable of associating with the nuclear matrix, which implies the existence of a relationship between transactivation and nuclear matrix attachment.

Amino Acid Sequence↗
PubMed1998

The capacity of polyomavirus enhancer binding protein 2alphaB (AML1/Cbfa2) to stimulate polyomavirus DNA replication is related to its affinity for the nuclear matrix.

The nuclear matrix is thought to play an important role in the DNA replication of eukaryotic cells, although direct evidence for such a role is still lacking. A nuclear matrix-associated transcription factor, polyomavirus (Py) enhancer binding protein 2alphaB1 (PEBP2alphaB1) (AML1/Cbfa2), was found to stimulate Py replication through its cognate binding site. The minimal replication activation domain (RAD) was identified between amino acid (aa) 302 and aa 371 by using a fusion protein containing the GAL4 DNA binding domain (GAL4-RAD). In addition, the region showed affinity for the nuclear matrix and, on the basis of competition studies, binding activity for one or more proteins involved in the initiation of Py DNA replication. A leukemogenic chimeric protein, AML1/ETO(MTG8), which does not contain this region of PEBP2alphaB1/AML1, was also localized in the nuclear matrix fraction and competed for nuclear matrix association with PEBP2alphaB1 and GAL4-RAD. Moreover, AML1/ETO inhibited Py DNA replication stimulated by PEBP2alphaB1 and GAL4-RAD. The inhibition was specific for replication mediated by PEBP2alphaB1 and GAL4-RAD, and proportional to the degree of loss of these activators from the nuclear matrix, suggesting a requirement for nuclear matrix targeting in the stimulation of Py DNA replication by RAD. These results are the first to suggest a molecular link between the initiation of DNA replication and the nuclear matrix compartment.

Animals↗
PubMed1998

Prenatal diagnosis of de novo isochromosome 13q associated with microcephaly, alobar holoprosencephaly and cebocephaly in a fetus.

We report on the prenatal diagnosis, genetic studies, and pathology of a case with de novo isochromosome 13q. A 31-year-old primigravida was referred for genetic counselling at 26 weeks' gestation due to the sonographic findings of intrauterine growth retardation and microcephaly. Level II ultrasonograms further demonstrated alobar holoprosencephaly, hypotelorism, polydactyly, a ventricular septal defect, and a single nostril. A diagnosis of cebocephaly was made. Genetic amniocentesis and cord blood sampling revealed translocation trisomy 13 with a de novo t(13q13q) rearrangement. Chromosomal analysis using G- and C-banding techniques and fluorescence in situ hybridization (FISH) showed an apparent monocentric isochromosome. Molecular analyses using polymorphic molecular markers showed that the rearrangement was consistent with an isochromosome of maternal chromosome 13q[46,XX,i(13)(q10)]. Necropsy confirmed cebocephaly and the prenatally detected anomalies.

Adult↗
PubMed1998

Prenatal diagnosis of de novo interstitial 16q deletion in a fetus associated with sonographic findings of prominent coronal sutures, a prominent frontal bone, and shortening of the long bones.

De novo interstitial 16q deletion diagnosed in utero has not previously been reported. We present a case of fetal de novo interstitial 16q deletion associated with the sonographic findings of prominent coronal sutures, a prominent frontal bone, and shortening of the long bones. Genetic amniocentesis at 23 weeks' gestation revealed a de novo deletion of 16q13-q22. At birth, the fetus manifested a dysmorphic phenotype correlated with monosomy 16q syndrome. Linkage analysis of the family confirmed the maternal origin and the extent of the deletion. We suggest that prenatal detection of a prominent frontal bone with prominent cranial sutures and shortening of the long bones should prompt cytogenetic analysis looking for a deletion in the long arm of chromosome 16.

Adult↗
PubMed1997

Identification and purification of a spinach chloroplast DNA-binding protein that interacts specifically with the plastid psaA-psaB-rps14 promoter region.

We have previously shown the presence in chloroplasts of sequence-specific DNA-binding proteins that interact specifically with two regions located downstream and upstream from the 5'-transcription start site of the plastid psaA-psaB-rps14 operon. As part of an effort to elucidate the regulatory mechanism of plastid transcription during plant development, we report here the purification and characterization of the chloroplast DNA-binding protein from spinach (Spinacia oleracea L. var. spinosa Ashers et Graeden) leaves that specifically recognizes sequences between positions +64 to +83 relative to the transcription start site. This DNA-binding protein has been highly purified from chloroplasts by using a combination of high-salt extraction, ammonium sulfate precipitation, heparin-agarose chromatography, and sequence-specific DNA-affinity chromatography. The protein exhibited an apparent molecular weight of 59-60 kDa on the basis of gel filtration. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by Southwestern blot analysis further indicated that this DNA-binding protein is dimeric and composed of two approximately 31-kDa subunits. We discuss the properties of this protein in relation to the known chloroplast DNA-binding factors for plastid gene expression.

Base Sequence↗
PubMed1997

Prenatal diagnosis of de novo proximal interstitial deletion of 14q associated with cebocephaly.

We report on the prenatal diagnosis of a case of cebocephaly, alobar holoprosencephaly, and microcephaly associated with a de novo proximal interstitial deletion of the long arm of chromosome 14: del(14)(q13q21.1) or (q13q21.2). This is the third case of holoprosencephaly in association with a deletion in this region. The present report concerns the association between prenatal craniofacial development, a holoprosencephaly locus, and the chromosomal segment 14q13.

Abnormalities, Multiple↗