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Biomedical subjects

L Ho

Publications and source records attributed to L Ho.

At least 37 records · Page 2Linked to original sources
PubMed1999

Hepatitis B carrier and perinatal outcome in singleton pregnancy.

The objective of this article is to evaluate the effect of hepatitis B antigenemia on perinatal outcome. Perinatal outcome of 824 women with hepatitis B surface antigen (HbsAg) was compared with 6281 women without hepatitis B surface antigen (control) from June 1996 to September 1998. The maternal characteristics were comparable between the two groups. Perinatal outcome was comparable between groups. The incidences of preterm birth, premature prelabor rupture of membranes, prelabor rupture of membranes, small for gestational age, neonatal jaundice, fetal distress, perinatal asphyxia, congenital abnormality, gastrointestinal tract abnormality, and perinatal mortality were similar among the two groups. We conclude that the presence of hepatitis B surface antigen in pregnant women does not pose additional risk for the pregnancy.

Adult↗
PubMed1999

Comparison of counter immunoelectrophoresis with immunoblotting for detection of anti-extractable nuclear antigen antibodies in systemic lupus erythematosus.

Anti-extractable nuclear antigen (ENA) antibodies were assayed by counter immunoelectrophoresis (CIE) and immunoblotting in patients with systemic lupus erythematosus (SLE). We found the two methods showed good concordance rates, the lowest being 67% for anti-SS-A. Immunoblotting was more sensitive in detecting anti-Sm, anti-SS-B and anti-PCNA (proliferating cell nuclear antigen); CIE was more sensitive for anti-nRNP and anti-SS-A. Overall, the prevalence of these anti-ENA antibodies in SLE was increased by 9-20% if immunoblotting was used in addition to CIE. Sera specific for the 52 kDa peptide of the SS-A antigen (anti-52kDa SS-A) were better detected by immunoblotting. Anti-PCNA antibody was found in 6.3% of SLE patients and was associated with active disease and hemolytic anemia. The positive rate of anti-Sm was 9% by CIE and 23.7% by immunoblotting and this antibody was a specific marker for SLE using either method. It was concluded that using immunoblotting in addition to CIE, the overall sensitivity of detection of anti-ENA antibodies in SLE was increased and clinically useful antibodies such as anti-52kDa SS-A and anti-PCNA could be detected.

Anemia, Hemolytic↗
PubMed1998

No association of a functional polymorphism in the dopamine D2 receptor promoter region with bipolar or unipolar affective disorders.

The dopaminergic system, along with the serotonergic and noradrenergic systems, has been implicated in the etiology of mood disorders. An association study of a functional variant in the promoter region of the dopamine D2 receptor (DRD2) with bipolar affective disorder I or unipolar major affective disorders was performed. Variable expression of the DRD2 gene in vitro has been shown with this promoter polymorphism. One hundred and thirty-one unrelated bipolar patients, 128 unrelated unipolar patients, and 262 controls were used in the study. There were no significant differences in DRD2 allele or genotype frequencies between the affective disorder and control groups. These results do not support a major role for the DRD2 gene in the etiology of either bipolar or unipolar affective disorders.

Bipolar Disorder↗
PubMed1998

Direct interaction between Rsc6 and Rsc8/Swh3,two proteins that are conserved in SWI/SNF-related complexes.

The RSC complex of Saccharomyces cerevisiae is closely related to the SWI/SNF complex. Both complexes are involved in remodeling chromatin structure and they share conserved components. The RSC proteins Sth1, Rsc8/Swh3, Sfh1 and Rsc6 are homologs of the SWI/SNF proteins Swi2/Snf2, Swi3, Snf5 and Swp73 respectively. To investigate the RSC complex, we isolated a temperature-sensitive swh3 allele. A screen for multicopy suppressors yielded plasmids carrying the RSC6 and MAK31 loci. RSC6 also suppressed the formamide sensitivity of a strain with a C-terminal truncation of SWH3 . We show that Swh3 and Rsc6 fusion proteins interact in the two-hybrid system and that the swh3-ts mutation impairs this interaction. Finally, bacterially produced Swh3 and Rsc6 fusion proteins interact in vitro , supporting the genetic evidence for direct interaction between Swh3 and Rsc6 in vivo . We have previously shown that Swh3 also interacts with Sth1. These findings, together with the conservation of these proteins in the SWI/SNF complex and in mammalian SWI/SNF-related complexes, strongly suggest that these proteins form a structural core for the complex.

Alleles↗
PubMed1998

Induction of cyclooxygenase (COX)-2 but not COX-1 gene expression in apoptotic cell death.

In this study we assessed the regulation of cyclooxygenase (COX)-2 in models of apoptotic cell death in vivo and in vitro. By 6 h after hippocampal colchicine injection in rat, COX-2 (but not COX-1) mRNA expression was elevated. The induction of COX-2 mRNA expression preceded temporally and overlapped anatomically the cellular morphological features of apoptosis in the granule cell layer of the dentate gyrus. Similarly, in an established in vitro model of apoptosis in P19 cells, COX-2 induction preceded apoptosis in response to serum deprivation by 12 h. These studies suggest that COX-2 may be involved in the early mechanisms leading to apoptosis.

Animals↗
PubMed1998

No association of the tryptophan hydroxylase gene with bipolar affective disorder, unipolar affective disorder, or suicidal behaviour in major affective disorder.

Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of 5-hydroxytryptamine (5-HT). An association study in bipolar affective disorder I or unipolar major affective disorder was performed by using a Bfa I restriction site polymorphism within intron 7 of the tryptophan hydroxylase gene. A total of 118 bipolar, 125 unipolar, and 437 control subjects were used in the study (1:3.7 bipolar:control, 1:3.5 unipolar:control). There were no significant differences in TPH allele or genotype frequencies between the affective disorder and control groups. In addition, bipolar and/or unipolar subjects with or without a history of suicide attempts were compared for the TPH polymorphism. No significant differences were found between suicidal and non-suicidal groups in major affective disorder, in contrast to a previous study suggesting an association of this polymorphism with a history of suicide attempts among alcoholic violent offenders.

Bipolar Disorder↗
PubMed1998

The HPV-activating cellular transcription factor Brn-3a is overexpressed in CIN3 cervical lesions.

The cervical cellular transcription factors Brn-3a and Brn-3b have antagonistic effects on transcription of the human papilloma virus types 16 and 18 E6 and E7 oncogenes, with Brn-3a activating expression and Brn-3b repressing it. We therefore measured expression of Brn-3a and Brn-3b mRNAs in biopsies from 16 women with no detectable cervical abnormality, and in 14 women with cervical intraepithelial neoplasia grade 3 (CIN3) lesions. Although the mean level of Brn-3b expression was similar in both groups, the mean level of Brn-3a expression was over 300-fold higher in the CIN3 samples when compared with normals. Elevated expression of Brn-3a was also detected in 16 histologically normal regions of the cervix adjacent to the CIN3 lesions, indicating that elevation of Brn-3a levels is not confined to the lesion in women with CIN3, and is thus not a consequence of the oncogenic process. The elevated levels of Brn-3a in the CIN3 patient samples, together with the activating effect of Brn-3a on HPV-16 and -18 oncogene expression, suggest that induction of this factor is involved in activating HPV-16 and -18 oncogene expression in the cervix, and hence in the production of cervical cancers induced by HPV.

Base Sequence↗
PubMed1998

Analysis and meta-analysis of two serotonin transporter gene polymorphisms in bipolar and unipolar affective disorders.

The serotonin transporter is a compelling candidate gene to examine in bipolar and unipolar affective disorder, since drugs that specifically inhibit the serotonin transporter can successfully treat depression. Previous association studies of a VNTR polymorphism in intron 2 and a functional insertion/deletion polymorphism in the promoter of this gene have produced conflicting results. The present study examined allele and genotype frequencies for both of these polymorphisms and resulting haplotypes in 87 English Caucasian bipolar patients, 125 English Caucasian unipolar affective disorder patients, and 174 controls. No significant associations were detected when these unipolar or bipolar cases were compared either separately or as a pooled "affective disorder" group to the controls. A meta-analysis of over 1,400 individuals of European Caucasian origin was then performed, comprising 772 controls, 375 bipolar and 299 unipolar patients for the VNTR polymorphism, and 739 controls, 392 bipolar and 275 unipolar patients for the promoter polymorphism. A significant association of promoter allele 2 was shown with bipolar (estimated odds ratio 1.21; 95% confidence interval 1.00-1.45), unipolar (OR 1.23; 95% CI 1.01-1.42), and combined bipolar + unipolar groups (OR 1.22; 95% CI 1.04-1.42). There was no demonstrable allelic association of the VNTR polymorphism with affective disorder: for the combined bipolar + unipolar group the odds ratios for VNTR alleles 9 and 10, compared with the common allele 12 were 1.05 (95% CI 0.56-1.95) and 0.90 (95% CI 0.77-1.05). These results suggest that the promoter allele 2, which has previously been shown to result in lower levels of serotonin transporter transcription, may be associated with affective disorder risk.

Adult↗
PubMed1998

An evolutionary conserved element is essential for somite and adjacent mesenchymal expression of the Hoxa1 gene.

The murine Hoxa1 gene is a member of the vertebrate Hox complex and plays a role in defining the body plan during development. At day 8.0-9.0 post coitus, Hoxa1 transcripts are detected extensively throughout the embryo in the neural tube, adjacent mesenchyme, paraxial mesoderm, somites and gut epithelium; expression extends from the most caudal region of the embryo to the rhombomere 3/4 border. This spatiotemporal expression of Hoxa1 mRNA is critical for normal embryonic development. We have previously identified a 10 bp element, called CE2, which is located approximately 3 kilobases 3' of the Hoxa1 coding region in the RAIDR5 enhancer, and which binds to an approximately 170 kd protein in retinoic acid treated P19 embryonal carcinoma cells. CE2 elements were also identified 3' of the murine Hoxb1 gene, the chicken Hoxb1 gene and the human Hoxa1 gene. To examine the role of this CE2 element in regulating Hoxa1 expression in vivo, transgenic mice were generated which express a Hoxa1 beta-galactosidase reporter gene that contains a mutation in the CE2 element. Relative to transgenic mice bearing a wild type CE2 element, the mutant CE2 construct recapitulated rhombomeric, neural, and gut epithelium expression but failed to show beta-galactosidase expression in somites and adjacent mesenchymal tissue. Gel shift analysis showed that binding activity similar to that detected in extracts prepared from retinoic acid treated P19 cells was present in nuclear extracts prepared from day 9.0 embryos. However, an additional binding complex not detected in P19 cells was also observed. These results indicate that in transgenic animals, the evolutionary conserved CE2 element is a somite and adjacent mesenchymal enhancer of Hoxa1 expression.

Animals↗
PubMed1998

Mutation analysis of patients with Hermansky-Pudlak syndrome: a frameshift hot spot in the HPS gene and apparent locus heterogeneity.

Hermansky-Pudlak syndrome (HPS) is a rare, autosomal recessive disorder in which oculocutaneous albinism, bleeding, and lysosomal ceroid storage result from defects of multiple cytoplasmic organelles-melanosomes, platelet-dense granules, and lysosomes. As reported elsewhere, we mapped the human HPS gene to chromosome segment 10q23, positionally cloned the gene, and identified three pathologic mutations of the gene, in patients from Puerto Rico, Japan, and Europe. Here, we describe mutation analysis of 44 unrelated Puerto Rican and 24 unrelated non-Puerto Rican HPS patients. A 16-bp frameshift duplication, the result of an apparent founder effect, is nearly ubiquitous among Puerto Rican patients. A frameshift at codon 322 may be the most frequent HPS mutation in Europeans. We also describe six novel HPS mutations: a 5' splice-junction mutation of IVS5, three frameshifts, a nonsense mutation, and a one-codon in-frame deletion. These mutations define an apparent frameshift hot spot at codons 321-322. Overall, however, we detected mutations in the HPS gene in only about half of non-Puerto Rican patients, and we present evidence that suggests locus heterogeneity for HPS.

Albinism, Oculocutaneous↗
PubMed1998

A gene for autosomal dominant hypohidrotic ectodermal dysplasia (EDA3) maps to chromosome 2q11-q13.

Autosomal dominant hypohidrotic ectodermal dysplasia (ADHED) is a disorder characterized by fine, slow-growing scalp and body hair, sparse eyebrows and eyelashes, decreased sweating, hypodontia, and nail anomalies. By genetic linkage analysis of a large ADHED kindred, we have mapped a gene for ADHED (EDA3) to the proximal long arm of chromosome 2 (q11-q13). Obligate recombinations localize EDA3 to an approximately 9-cM interval between D2S1321 and D2S308, with no apparent recombinations with markers D2S1343, D2S436, D2S293, D2S1894, D2S1784, D2S1890, D2S274, and CHLC.GAAT11C03.

Chromosomes, Human, Pair 2↗
PubMed1998

Accidental ingestions in childhood.

One-hundred and twelve cases of accidental poisoning were admitted over a 2-year study period (December 1990 to December 1992). Data was collected upon admission and patients were subsequently followed-up. Fifty-four percent of admission were boys. Majority of them were toddlers between the ages of 1 and 3 years. Thirty percent of accidental ingestions occurred during the school/public holidays. These occurred when the caretakers were preoccupied. Forty-nine percent of patients ingested oral medication; 16% ingested household liquids and the rest ingested other household products like cockroach tablets and thermometer mercury. The most commonly ingested medications were paracetamol, salicylate and bronchodilators, whilst chlorox, kerosene and detergents were the common household liquids ingested. The ability of the caregivers to quantitate the ingested product was poor. The mean hospital stay of the patients was 2.5 days. The majority of them were admitted for observation which did not require antidotes. Four cases were observed in the intensive care unit. There were no fatalities during the study period. Forty-four percent of the patients had samples taken for toxicology analysis, of which, less than half had positive results. All the patients were advised on the safety measures to look out for after admission. Less than 10% of cases had prior knowledge of such measures before the accidents occurred.

Child↗
PubMed1997

Analysis of E2 amino acid variants of human papillomavirus types 16 and 18 and their associations with lesion grade and HLA DR/DQ type.

Human papillomavirus (HPV) 16 and HPV 18 E2 amino acid variants and host HLA DR/DQ haplotypes have been identified by direct nucleic acid sequencing from cervical scrapes. HPV16 E2 variants co-segregate with a nucleotide variant at nt350 (in E6), which previously has been associated with persistent infections. Both HPV16 and HPV18 E2 variants occur relatively more frequently in individuals with HLA DR/DQ haplotypes 0401/0301 and 1101/0301 but are not related to lesion grade.

Amino Acids↗
PubMed1997

Sensitivity to jerky gene dosage underlies epileptic seizures in mice.

Animals with one deleted jerky allele are more susceptible to chemically induced seizures than wild-type mice and display recurrent behavioral seizures. The phenotype of these hemizygotes is characterized by no apparent neurological symptoms other than recurrent seizures reminiscent of human idiopathic epilepsy. The jerky gene encodes a 60 kDa protein resembling a number of DNA-binding proteins. Here, we show that the jerky gene is expressed in all tissues examined, including brain, liver, lung, spleen, testis, and ovary, and study an apparent paradox of how an allelic deletion of the ubiquitously expressed jerky gene can lead to hyperexcitability and seizures but not to other symptoms. We demonstrate that jerky has a dosage-sensitive function (haploinsufficiency) in brain and that this sensitivity to reduced jerky dosage could explain the occurrence of seizures in hemizygotes. However, jerky has a nondosage-sensitive function as well, because the total absence of jerky in homozygotes results in abnormalities of somatic and sexual development. A number of idiopathic epilepsies are dominantly inherited, such as benign familial neonatal convulsions, juvenile myoclonic epilepsy, as well as benign epilepsy with centrotemporal spikes, and the pathomechanism of these epilepsies may be based on haploinsufficiency in the brain.

Aging↗
PubMed1997

Apparent digenic inheritance of Waardenburg syndrome type 2 (WS2) and autosomal recessive ocular albinism (AROA).

Waardenburg syndrome (WS) is a clinically and genetically heterogeneous disease accounting for >2% of the congenitally deaf population. It is characterized by deafness in association with pigmentary anomalies and various defects of neural crest-derived tissues. At least four types are recognized (WS1, WS2, WS3 and WS4) on the basis of clinical and genetic criteria. Two previously described families seemed to delineate a new subtype characterized by WS2 in conjunction with ocular albinism (OA). Since mutations in the MITF gene are responsible for some instances of WS2, we screened for mutations in one of the WS2-OA families and discovered a 1 bp deletion in exon 8 of MITF. OA previously has been associated with compound heterozygosity for a mutant TYR allele and the TYR(R402Q) allele, a functionally significant polymorphism that is associated with moderately reduced tyrosinase catalytic activity. In this family, all of the individuals with the OA phenotype are either homozygous or heterozygous for TYR(R402Q), and heterozyous for the 1 bp deletion in MITF This suggests that the WS2-OA phenotype may result from digenic interaction between a gene for a transcription factor (MITF) and a gene that it regulates (TYR).

Albinism, Ocular↗