Jiunn-Yi Wu

More evidence supports the association of PPP3CC with schizophrenia

Calcineurin is a calcium/calmodulin-dependent protein phosphatase composed of two subunits, a regulatory subunit of calcineurin B (CNB) and a catalytic subunit of calcineurin A (CNA). PPP3CC is the γ isoform of CNA located at the chromosome 8p21.3 region. To evaluate the association between PPP3CC and schizophrenia in the Taiwanese population, 10 single nucleotide polymorphism (SNP) markers across the gene were genotyped by the method of MALDI-TOF in 218 schizophrenia families with at least two affected siblings. One SNP (rs2272080) located around the exon 1 untranslated region was nominally associated with schizophrenia (P=0.024) and significantly associated with the expression of PPP3CC in lymphoblast cell line; the TT and TG genotype had significantly higher relative expression levels than the GG genotype (P=0.0012 and 0.015, respectively). In further endophenotype stratification, the single locus of rs2272080 and the haplotypes of both two-SNP haplotype (rs7833266–rs2272080) and seven-SNP haplotype (rs2461491–rs2469758–rs2461489–rs2469770–rs2449340–rs1482337–rs2252471) showed significant associations with the subgroup of schizophrenia with deficits of the sustained attention as tested by the continuous performance test (CPT, P<0.05) and the executive functioning as tested by the Wisconsin Card Sorting Test (WCST, P<0.05). The results suggest that PPP3CC gene may be a true susceptibility gene for schizophrenia.

Mapping of psoriasis to 17q terminus

Psoriasis is a chronic, inflammatory, hyperproliferative disease of the skin, scalp, nails, and joints, with a prevalence of up to 2% in Caucasians1,2 but well under 1% in the Mongoloid races of the Far East.3 The disease varies in severity. Some patients display mild disease with isolated scaling erythematous plaques on the elbows or knees, whereas for others most of their cutaneous surface can be affected. At the cellular level, psoriasis is characterised by markedly increased epidermal proliferation and incomplete differentiation, elongation, dilation, and leakiness of the superficial plexus of dermal capillaries, and by a mixed inflammatory and immune cell infiltrate of the epidermis and papillary dermis.1,2 Dermal infiltrates comprised of T cells and macrophages typically appear in early lesions before epidermal changes.4 The therapeutic effect of immunosuppressive agents suggests psoriasis has a primary immune pathogenic basis.5 Susceptibility to the development of psoriasis is likely to have a significant genetic component. Accumulating evidence is consistent with the idea that psoriasis is a multifactorial disorder caused by the concerted action of multiple disease genes in a single individual and triggered by environmental factors.6 Some of these genes control the severity of a variety of diseases, via their regulation of the inflammatory and immune processes (severity genes), whereas others are unique to psoriasis (specific genes). A number of genetic studies have sought to identify the psoriasis susceptibility loci. Associations between psoriasis and human lymphocyte antigen alleles were first described in 1990.7 Subsequently, genome-wide linkage scans have mapped psoriasis to several chromosomal regions including PSORS1 at 6p21,8,9 PSORS2 at 17q,8–10 PSORS3 at 4q,11 PSORS4 at 1q,12 PSORS5 at 3q,13 PSORS6 at 19p,14 and PSORS7 at 1p.15 Recently, the International Psoriasis Genetics Consortium reassessed these candidate …

A genome-wide study of preferential amplification/hybridization in microarray-based pooled DNA experiments

Microarray-based pooled DNA methods overcome the cost bottleneck of simultaneously genotyping more than 100 000 markers for numerous study individuals. The success of such methods relies on the proper adjustment of preferential amplification/hybridization to ensure accurate and reliable allele frequency estimation. We performed a hybridization-based genome-wide single nucleotide polymorphisms (SNPs) genotyping analysis to dissect preferential amplification/hybridization. The majority of SNPs had less than 2-fold signal amplification or suppression, and the lognormal distributions adequately modeled preferential amplification/hybridization across the human genome. Comparative analyses suggested that the distributions of preferential amplification/hybridization differed among genotypes and the GC content. Patterns among different ethnic populations were similar; nevertheless, there were striking differences for a small proportion of SNPs, and a slight ethnic heterogeneity was observed. To fulfill appropriate and gratuitous adjustments, databases of preferential amplification/hybridization for African Americans, Caucasians and Asians were constructed based on the Affymetrix GeneChip Human Mapping 100 K Set. The robustness of allele frequency estimation using this database was validated by a pooled DNA experiment. This study provides a genome-wide investigation of preferential amplification/hybridization and suggests guidance for the reliable use of the database. Our results constitute an objective foundation for theoretical development of preferential amplification/hybridization and provide important information for future pooled DNA analyses.

Prednisolone oral solution plus inhaled procaterol for acute asthma in children: a double-blind randomized controlled trial.

BACKGROUND To evaluate the efficacy of prednisolone sodium phosphate oral solution plus inhaled procaterol in the treatment of acute asthma in children. METHODS Forty-three patients aged 6 to 12 years with an acute exacerbation of asthma were double-blind randomized into one of two treatment groups in a 1:1 ratio:1) prednisolone oral solution +placebo tablets + procaterol MDI or 2) prednisolone tablets +placebo oral solution + procaterol MDI, all given three times daily for 7 days. Peak expiratory flow rate (PEFR), 24-hour reflective asthma symptom scores, spirometry and pulmonary index score (PIS) were recorded before and after treatment. Net changes in PEFR, symptom score, PIS, Forced Expiratory Volume in the first second (FEV1), FEV1/forced vital capacity (FVC), forced expiratory flow between 25 and 75 percent of the forced vital capacity (FEF(25-75%)) (before and after treatment) and global assessment by the investigator and the subjects or their parents were analyzed. RESULTS The two groups were statistically similar at baseline values of these parameters. After a 7-day course of treatment, the net change of PEFR before and after treatment was significantly improved in both groups, but there was no significant difference in the net change of PEFR between the two groups (57.27+/-31.44 L/min vs. 54.29 +/-30.04 L/min, difference 2.99 +/-30.76 L/min, mean +/-SD, P=0.752). The net change in PIS and total symptom score did not differ between the two groups (P=0.091 and 0.827, respectively). Similarly, the FEV1, FEV1/FVC and FEF25-75% all improved with either treatment, and neither group was significantly superior to the other group (P=0.162, 0.48 and 0.081, respectively). Global assessment by the investigator and the subjects or their parents at the end of study indicated an essentially comparable result. CONCLUSIONS Prednisolone sodium phosphate oral solution plus inhaled procaterol is as efficacious as prednisolone tablets plus inhaled procaterol in the management of acute asthma in children.

Hyper-IgM syndrome: report of one case.

The hyper-IgM syndrome (HIM) is a rare primary immunodeficiency disorder caused by defects in the CD40 ligand (CD40L)/CD40-signaling pathway. It is characterized by recurrent infections with markedly decreased IgG, IgA and IgE levels but normal or elevated serum IgM levels. A 5-month-old boy presented with rapidly progressive pneumonia which responded poorly to antibiotics. High levels of IgM and very low levels of IgG, IgE and IgA were noted in his plasma specimen (IgM, 128 mg/dl; IgG, 18 mg/dl; IgE, 1 IU/ml; IgA, 4 mg/dl). The relative proportions of immune cells were CD3 24.6%, CD4 10.3%, CD8 2.2%, CD19 30.2%, CD57 1.0% and active T cells 1.1%. After IVIG treatment, the pneumonia improved. Repeat assessment at the age of 15 months showed IgM decreased to the normal range (32 mg/dl). Whole blood flow cytometry assay for CD40L expression confirmed the diagnosis of hyper-lgM syndrome when he was 21 months old. Only a small percentage (0.48%) of the patients in vitro activated CD4+ T cells expressed CD40L, compared with 33.54% from a healthy control. The patients father, mother and sister all had a normal CD40L expression activation patterns (43.52%, 40.78%, 34.11%, respectively). On a regimen of monthly IVIG infusion and oral trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia (PCP) prophylaxis, the patient has had no recurrent infections.

Facial telangiectasia - An unusual complication of neonatal lupus erythematosus: Report of one case

Neonatal lupus erythematosus (NLE) is an uncommon passive autoimmune disease caused by transplacental passage of anti-Ro/SSA and/or anti-La/SSB or anti-U1RNP maternal autoantibodies. Common clinical manifestations include cutaneous lupus lesions, cardiac disease, notably congenital heart block, hematologic abnormalities, and hepatobiliary disease. The cutaneous lesions of NLE are usually transient, disappearing about six months after birth when maternal antibodies disappear from the infants circulation. Persistent telangiectasia is a rare complication of NLE. We report a 3-year-old female who had cutaneous lupus with persistent facial telangiectasias over the frontal area. She was diagnosed with NLE at 2 months of age. Her findings then included cutaneous lupus, hemolytic anemia, a high titer of antinuclear antibodies (1: 640) with a speckled pattern, positive anti-Ro/SSA and anti-La/SSB antibodies, and absence of anti-dsDNA antibodies. Her mother had systemic lupus erythematosus with the presence of high titer of antinuclear antibodies (1: 1260) with a speckled pattern and positive anti-Ro/SSA and anti-La/SSB antibodies. The childs cutaneous lupus and hemolytic anemia disappeared at 6 months of age, but the telangiectasia persisted.

Clinical Spectrum and Laboratory Characteristics of Neonatal Lupus Erythematosus in a Single Institute

Background: Neonatal lupus erythematosus (NLE) is a passive autoimmune disease in which maternal autoantibodies are transferred across the placenta. These anti-Ro/SSA and/or anti-La/SSB or anti-U1RNP antibodies can be detected in the affected infant for the first few months of life. Common clinical manifestations of NLE include cardiac disease, notably congenital heart block and cutaneous lupus lesions. The other features of NLE including hematologic abnormalities, hepatobiliary disease, and, rarely, CNS involvement are usually underestimated. We reviewed our experience with NLE and examined the relationship between the serology of the mothers and disease in their infants. Methods: We reviewed the records in 12 cases of NLE seen at Mackay Memorial Hospital from 1984 through 2003. Results: The female to male ratio was 1.4:1. Five of the 12 patients had congenital heart block, and 7 had cutaneous lesions. Other noncutaneous manifestations included thrombocytopenia in 2, anemia in 2, and elevated aminotransferases in 3, 1 of whom also had cholestasis without evidence of other metabolic, infectious or inherited causes. One infant had a right-sided focal seizure. Anti-SSA/Ro antibodies were detected in all 12 patients, a positive ANA in 10, and anti-SSB/La antibodies in 5. The last were among the 7 who had cutaneous NLE. Anti-SSB/La antibodies were not present in any of the infants with congenital heart block. Conclusions: In pregnant women with these antibodies, fetal echocardiographic screening is useful to look for atrioventricular heart block. Asymptomatic infants borne to these mothers should be followed carefully during the first 6 months of life, as babies with NLE may initially be asymptomatic. Pediatricians caring for such children should familiarize themselves with the typical features of the disease so that they can recognize it promptly if it occurs.