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Biomedical subjects

S Yang

Publications and source records attributed to S Yang.

At least 19 recordsLinked to original sources
PubMed2007

Systemic lupus erythematosus: a genetic epidemiology study of 695 patients from China.

Our purpose was to explore potential genetic models for systemic lupus erythematosus (SLE) and analyze genetic epidemiologic characteristics of SLE in a Chinese population. Data for 695 patients with SLE were obtained by using a uniform questionnaire. Patients, clinical characteristics and their family history were analyzed using software. A complex segregation analysis was conducted to propose potential genetic models for SLE. The mean +/- SD age of onset were 30.2 +/- 10.5 years and mean time to progression to SLE was 32.5 +/- 44.4 months. The most frequent initial manifestations were malar rash (61.3%). During the evolution of the disease, the main clinical features were arthritis in 73.6% of our patients, followed by malar rash (68.1%), and renal involvement (56.7%). As the first symptom, the late-onset group (onset of disease beyond the age of 50 years) less often showed malar rash (45% vs. 63.4% in the early-onset group; p = 0.001). There were no significant differences in the other cumulative clinical symptoms between late-onset and early-onset group, except for a lower prevalence of malar rash, photosensitivity and alopecia and a higher prevalence of mucosal ulcers in the late-onset group. A positive family history of SLE was obtained in 50 patients (7.2%). There were no statistical differences in clinical characteristics between familial SLE and sporadic SLE patients. The heritability of SLE was 43.6%, the genetic model of SLE could be polygenetic model and major gene mode is the best fitted one. SLE could be a multifactorial disease with polygenetic model.

Adolescent↗
PubMed2007

Biochemical, molecular and behavioral phenotypes of Rab3A mutations in the mouse.

Ras-associated binding (Rab) protein 3A is a neuronal guanosine triphosphate (GTP)-binding protein that binds synaptic vesicles and regulates synaptic transmission. A mouse mutant, earlybird (Ebd), with a point mutation in the GTP-binding domain of Rab3A (D77G), exhibits anomalies in circadian behavior and homeostatic response to sleep loss. Here, we show that the D77G substitution in the Ebd allele causes reduced GTP and GDP binding, whereas GTPase activity remains intact, leading to reduced protein levels of both Rab3A and rabphilin3A. Expression profiling of the cortex and hippocampus of Ebd and Rab3a-deficient mice revealed subtle differences between wild-type and mutant mice. Although mice were backcrossed for three generations to a C57BL/6J background, the most robust changes at the transcriptional level between Rab3a(-/-) and Rab3a(+/+) mice were represented by genes from the 129/Sv-derived chromosomal region surrounding the Rab3a gene. These results showed that differences in genetic background have a stronger effect on gene expression than the mutations in the Rab3a gene. In behavioral tests, the Ebd/Ebd mice showed a more pronounced mutant phenotype than the null mice; Ebd/Ebd have reduced anxiety-like behavior in the elevated zero-maze test, reduced response to stress in the forced swim test and a deficit in cued fear conditioning (FC), whereas Rab3a(-/-) showed only a deficit in cued FC. Our data implicate Rab3A in learning and memory as well as in the regulation of emotion. A combination of forward and reverse genetics has provided multiple alleles of the Rab3a gene; our studies illustrate the power and complexities of the parallel analysis of these alleles at the biochemical, molecular and behavioral levels.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Valproate protects dopaminergic neurons in midbrain neuron/glia cultures by stimulating the release of neurotrophic factors from astrocytes.

Valproate (VPA), one of the mood stabilizers and antiepileptic drugs, was recently found to inhibit histone deacetylases (HDAC). Increasing reports demonstrate that VPA has neurotrophic effects in diverse cell types including midbrain dopaminergic (DA) neurons. However, the origin and nature of the mediator of the neurotrophic effects are unclear. We have previously demonstrated that VPA prolongs the survival of midbrain DA neurons in lipopolysaccharide (LPS)-treated neuron-glia cultures through the inhibition of the release of pro-inflammatory factors from microglia. In this study, we report that VPA upregulates the expression of neurotrophic factors, including glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) from astrocytes and these effects may play a major role in mediating VPA-induced neurotrophic effects on DA neurons. Moreover, VPA pretreatment protects midbrain DA neurons from LPS or 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity. Our study identifies astrocyte as a novel target for VPA to induce neurotrophic and neuroprotective actions in rat midbrain and shows a potential new role of cellular interactions between DA neurons and astrocytes. The neurotrophic and neuroprotective effects of VPA also suggest a utility of this drug for treating neurodegenerative disorders including Parkinson's disease. Moreover, the neurotrophic effects of VPA may contribute to the therapeutic action of this drug in treating bipolar mood disorder that involves a loss of neurons and glia in discrete brain areas.

Animals↗
PubMed2006

Downregulation of cAMP-dependent protein kinase inhibitor gamma is required for BMP-2-induced osteoblastic differentiation.

Osteoblasts, normally derived from undifferentiated mesenchymal precursor cells, acquire their characteristic phenotypes when induced by various regulatory factors, one of which is bone morphogenetic protein-2 (BMP-2). Our recent studies suggest that expression of cAMP-dependent protein kinase (PKA) inhibitor G (PKIG) is down-regulated as human mesenchymal stromal cells (MSCs) undergo BMP-2-induced osteoblastic differentiation. This raises our hypothesis that the PKA pathway is involved in osteogenesis. In this report, we demonstrated that PKIG in human MSCs and its murine homologue PKA inhibitor gamma (PKIgamma) in murine pre-myoblast C2C12 cells were down-regulated when these cells were treated with BMP-2. On the contrary, the PKA activity of C2C12 cells was increased upon BMP-2 treatment. Overexpression of PKIgamma in C2C12 cells was shown to repress mRNA expression of early osteoblastic markers osterix and type I collagen while inhibiting the PKA activity. This correlated with decreased alkaline phosphatase (ALP) activities. Furthermore, inhibition of the PKA activity using its specific inhibitor KT5720 was found to have the similar effect, whereas 8-Br-cAMP, a specific PKA activator, accelerated BMP-2-induced ALP activities. Finally, this study showed that BMP-2 treatment promoted activities of transcription regulatory elements including cAMP response element (CRE) and activating protein-1 (AP1). This effect of BMP-2 was diminished in PKIgamma-overexpressed C2C12 cells. Taken together, our results indicate that the activation of the PKA pathway may be one of key BMP-2-activated signaling events that lead to osteogenesis and that downregulation of PKIgamma may be prerequisite for the PKA activation during the osteoblastic differentiation of precursor cells.

Alkaline Phosphatase↗
PubMed2006

Trace determination of beta-lactam antibiotics in surface water and urban wastewater using liquid chromatography combined with electrospray tandem mass spectrometry.

A sensitive and reliable method using liquid chromatography-electrospray tandem mass spectrometry has been developed and validated for the trace determination of beta-lactam antibiotics in natural and wastewater matrices. Water samples were enriched by solid-phase extraction. The analytes included amoxicillin (AMOX), ampicillin (AMP), oxacillin (OXA), cloxacillin (CLOX) and cephapirin (CEP). Average recoveries of beta-lactams (BLs) in fortified samples were generally above 75% (except amoxicillin) with the standard deviations lower than 10% in water matrices. Amoxicillin was not quantified due to poor recovery (less than 40%) in the investigated water matrices. Matrix effects were found to be minimal when measuring these compounds in water matrices. The accuracy, within- and between-run precision of the assay fell within acceptable ranges of 15% absolute. The method detection limit (MDL) was estimated to range between 8 and 10 ng/L in surface water, 13 and 18 ng/L in the influent and 8 and 15 ng/L in the effluent from a wastewater treatment plant. A large number of actual water samples were analyzed using this method in order to evaluate the occurrence of the beta-lactams in a river and a wastewater treatment plant in northern Colorado. Most of the samples were negative for all analytes. These compounds were found at 15-17 ng/L in the three influent samples and at 9-11 ng/L in three surface water samples out of a total of 200 samples. This indicates that contamination by beta-lactam antibiotics is of minor importance to the small mixed-watershed.

Anti-Bacterial Agents↗
PubMed2006

Autism and environmental genomics.

Autism spectrum disorders (ASD) are defined by behavior and diagnosed by clinical history and observation but have no biomarkers and are presumably, etiologically and biologically heterogeneous. Given brain abnormalities and high monozygotic concordance, ASDs have been framed as neurobiologically based and highly genetic, which has shaped the research agenda and in particular criteria for choosing candidate ASD genes. Genetic studies to date have not uncovered genes of strong effect, but a move toward "genetic complexity" at the neurobiological level may not suffice, as evidence of systemic abnormalities (e.g. gastrointestinal and immune), increasing rates and less than 100% monozygotic concordance support a more inclusive reframing of autism as a multisystem disorder with genetic influence and environmental contributors. We review this evidence and also use a bioinformatic approach to explore the possibility that "environmentally responsive genes" not specifically associated with the nervous system, but potentially associated with systemic changes in autism, have not hitherto received sufficient attention in autism genetics investigations. We overlapped genes from NIEHS Environmental Genome Project, the Comparative Toxicogenomics Database, and the SeattleSNPs database of genes relevant to the human immune and inflammatory response with linkage regions identified in published autism genome scans. We identified 135 genes in overlap regions, of which 56 had never previously been studied in relation to autism and 47 had functional SNPs (in coding regions). Both our review and the bioinformatics exercise support the expansion of criteria for evaluating the relevance of genes to autism risk to include genes related to systemic impact and environmental responsiveness. This review also suggests the utility of environmental genomic resources in highlighting the potential relevance of particular genes within linkage regions. Environmental responsiveness and systems impacts consistent with system-wide findings in autism are thus supported as important considerations in identifying the numerous and complex modes of gene-environment interaction in autism.

Animals↗
PubMed2006

Up-regulation of brain ceruloplasmin in thrombin preconditioning.

Pretreatment with low-dose thrombin attenuates brain edema induced by iron or intracerebral hemorrhage (ICH). Ceruloplasmin is involved in iron metabolism by oxidizing ferrous iron to ferric iron. The present study examines whether thrombin modulates brain ceruloplasmin levels and whether exogenous ceruloplasmin reduces brain edema induced by ferrous iron in vivo. In the first set of experiments, rats received intracerebral infusion of saline or 1 U thrombin into the right basal ganglia. Rats were killed 1, 3, or 7 days later for Western blot analysis and RT-PCR analysis. In the second set of experiments, rats received either ferric iron, ferrous iron, or ferrous iron plus ceruloplasmin, then were killed 24 hours later for brain edema measurement. We found that ceruloplasmin protein levels in the ipsilateral basal ganglia increased on the first day after thrombin stimulation and peaked at day 3. Brain ceruloplasmin levels were higher after thrombin infusion than after saline injection. RT-PCR showed that brain ceruloplasmin mRNA levels were also up-regulated after thrombin injection (p < 0.05). We also found ipsilateral brain edema after intracerebral infusion of ferrous iron but not ferric iron at 24 hours. Co-injection of ferrous iron with ceruloplasmin reduced ferrous iron-induced brain edema (p < 0.05). Our results demonstrate that thrombin increases brain ceruloplasmin levels and exogenous ceruloplasmin reduces ferrous iron-induced brain edema, suggesting that ceruloplasmin up-regulation may contribute to thrombin-induced brain tolerance to ICH by limiting the injury caused by ferrous iron released from the hematoma.

Animals↗
PubMed2006

Intracerebral hemorrhage in complement C3-deficient mice.

The complement cascade is activated and contributes to brain damage after intracerebral hemorrhage (ICH). The present study investigated ICH-induced brain damage in complement C3-deficient mice. This study was divided into 2 parts. Male C3-deficient and C3-sufficient mice received an infusion of 30-microl autologous whole blood into the right basal ganglia. In the first part of our study, mice were killed 3 days later for brain water content measurement. Behavioral assessments including forelimb use asymmetry and corner turn tests were also preformed before and after ICH. In the second part of the study, brain heme oxygenase-1 (HO-1) was measured by Western blot analysis and immunohistochemistry 3 days after the infusion. We found that brain water content in the ipsilateral basal ganglia 3 days after ICH was less in C3-deficient mice compared to C3-sufficient mice (p < 0.05). The C3-deficient mice had reduced ICH-induced forelimb use asymmetry deficits compared with C3-sufficient mice (p < 0.05), although there was no significant difference in the corner turn test score. Western blot analysis showed that HO-1 contents were significantly lower in C3-deficient mice (day 3: 2024 +/- 560 vs. 5140 +/- 1151 pixels in the C3-sufficient mice, p < 0.05). We conclude that ICH causes less brain edema and behavioral deficits in complement C3-deficient mice. These results suggest that complement C3 is a key factor contributing to brain injury following ICH.

Animals↗
PubMed2006

Influence of mizolastine on antigen-induced activation of signalling pathways in murine mast cells.

BACKGROUND: There is accumulating evidence that some antihistamines can interrupt intermediate signalling events that regulate cell function. The effect of mizolastine on both the generation and release process of many cytokines in mast cells further implies that the inhibition by mizolastine may target signalling pathways. AIM: To observe the influence of mizolastine on antigen-induced activation of signalling pathways in murine mast cells. METHODS: Western blot analysis and enzyme assay were performed. Immunoblots were prepared from whole cell lysates and probed with antibodies against Fyn, Akt, ERK, p38, phospho-Fyn, phospho-Akt, phospho-ERK and phospho-p38, respectively. RESULTS: Our study showed that signalling molecules such as IP3, Fyn, p38 and ERK were enhanced when mast cells were stimulated by antigen, and that this was not inhibited by treatment with mizolastine. Mizolastine at concentrations from 10(-9) to 10(-5) mol/L could inhibit activation of the PI3K kinase downstream signalling molecule Akt to antigen stimulation. The study also demonstrated that mizolastine exerted inhibitory ability on protein kinase C (PKC) activation in a dose-dependent manner. CONCLUSION: PKC-mediated phosphorylation of Akt can be blocked by mizolastine. There may be a PKC-independent pathway effectively activating MAPK pathways in mast cells in response to antigen induction, which cannot be affected by mizolastine.

Animals↗
PubMed2006

Genetic heterogeneity in acrokeratosis verruciformis of Hopf.

BACKGROUND: Acrokeratosis verruciformis of Hopf (AKV) is a rare genodermatosis characterized by multiple flat-topped, flesh-coloured papules on the dorsa of hands and feet, and punctuate keratoses on the palms and soles. A mutation in the ATP2A2 gene has been shown to be associated with AKV and with Darier's disease (DD). OBJECTIVES: To explore the molecular aetiology of AKV and DD. METHODS: We investigated the clinical and histological information in two families and a sporadic case with AKV and one family and a sporadic case with DD in China. Mutation analysis of ATP2A2 was performed by PCR and direct sequencing, and genotyping and linkage analysis performed using six polymorphic microsatellite markers spanning the locus at 12q23-12q24 containing ATP2A2. RESULTS: Mutational analysis showed no mutation in ATP2A2 among the AKV patients, but we found two novel mutations (p.C318F and p.M719fs) in the DD patients. The genotyping and linkage analysis results revealed no linkage evidence of the locus at 12q23-12q24 in a large AKV family. CONCLUSIONS: Our findings provide evidence for the genetic heterogeneity of AKV and demonstrate that mutations in genes other than ATP2A2 are responsible for AKV in a proportion of the Chinese population.

Acrodermatitis↗
PubMed2006

MHC haplotypic association in Chinese Han patients with vitiligo.

BACKGROUND: Serological typing of the human leucocyte antigen (HLA) has shown discrepancies in HLA associations with vitiligo in different ethnic populations. OBJECTIVE: To evaluate the distributions of HLA at class I and II loci that may contribute to the genetic susceptibility of vitiligo patients in Chinese Hans population. METHODS: We analysed the allelic frequencies of HLA class I and II by using the polymerase chain reaction sequence-specific primer (PCR-SSP) method in 187 patients with vitiligo and 273 controls in Chinese Hans. The linkage disequilibrium was calculated from a 2 x 2 table. RESULTS: Two-locus haplotypes including HLA-A25-B13, HLA-A25-B27, HLA-A25-Cw*0602, HLA-A25-DQA1*0302, HLA-A25-DQA1*0601, HLA-A25-DQB1*0303, HLA-B13-Cw*0602, HLA-B13-DQA1*0302, HLA-B13-DQA1*0601, HLA-B27-Cw*0602, HLA-B27-DQA1*0302, HLA-B27-DQA1*0601, HLA-B27-DQB1*0303, HLA-B27-DQB1*0503, HLA-Cw*0602-DQA1*0302, HLA-Cw*0602-DQA1*0601, HLA-Cw*0602-DQB1*0303, HLA-Cw*0602-DQB1*0503 and HLA-DQA1*0302-DQB1*0503 were associated with all types of vitiligo in Chinese Hans. The extended haplotypes HLA-A25-B13-Cw*0602, HLA-A25-B27-Cw*0602, HLA-DQA1*0302-DQB1*0303-Cw*0602 and HLA-B13-DQB1*0303-Cw*0602 were found to be associated with all types of vitiligo in Chinese Hans, whereas the frequency of HLA-A25-Cw*0602-DQA1*0302 was significantly increased in generalized vitiligo but not in localized vitiligo. The frequencies of HLA-A25-DQA1*0302-DQB1*0503 and HLA-A30-DQA1*0302-DQB1*0303 were higher in childhood vitiligo than in adult vitiligo, and the frequency of HLA-A25-B13-DQB1*0303-Cw*0602 was shown to be associated with adult vitiligo but not childhood vitiligo. CONCLUSION: This study demonstrates not only the differential association between HLA markers and types of vitiligo according to distribution or age at onset but also newly found high-risk haplotypes in Chinese vitiligo patients.

Adolescent↗
PubMed2006

Association of HLA haplotype with alopecia areata in Chinese Hans.

BACKGROUND: Some studies have shown discrepancies in human leucocyte antigen (HLA) associated with alopecia areata (AA) between different ethnic populations. OBJECTIVE: To investigate whether HLA-I, -DQA1 and -DQB1 alleles and the HLA haplotype are associated with AA, and the correlation between the HLA haplotype profile, age of onset and severity of AA in Chinese Hans. METHODS: The polymerase chain reaction-sequence specific primer (PCR-SSP) method was used to analyse the frequencies of HLA class I, -DQA1 and -DQB1 alleles in 192 patients with AA and 252 controls in Chinese Hans. The linkage disequilibrium was calculated using the 2 x 2 table. RESULTS: The 24 two-locus haplotypes [including A*02-B*18, A*02-B*27, A*02-B*52, A*02-Cw*0704, A*02-DQA1*0104, A*02-DQB1*0604, A*02-DQB1*0606, B*18-Cw*0704, B*18-DQA1*0104, B*18-DQA1*0302, B*18-DQB1*0606, B*27-Cw*0704, B*27-DQA1*0104, B*27-DQA1*0302, B*52-Cw*0704, B*52-DQA1*0104, B*52-DQA1*0302, B52-DQB1*0606, Cw*0704-DQA1*0104, Cw*0704-DQA1*0302, Cw*0704-DQB1*0606, DQA1*0104-DQB1*0604, DQA1*0104-DQB1*0606, DQA1*0302-DQB1*0606 (P<0.05)] were associated with AA, while eight extended haplotypes (A*02-B*18-DQA1*0104, A*02-B*27-DQA1*0104, A*02-B*52-DQA1*0104, A*02-B*52-DQA1*0302, A*02-B*52-DQB1*0606, B*52-Cw*0704-DQA1*0104, B*52-Cw*0704-DQA1*0302, A*02-B*52-DQA1*0302-DQB1*0606) were found to be related to AA in Chinese Hans. Through stratified analysis, we found that the extended haplotype B*52-Cw*0704-DQA1*0302 was related to early onset of AA, and no haplotype was only associated with severe AA. CONCLUSION: This is the first detailed report to elucidate HLA haplotypes associated with AA and that demonstrates the significant HLA haplotypes in Chinese Hans AA. The haplotype B*52-Cw*0704-DQA1*0302 was identified to be related to early onset of AA. Our results provide some information for future research on predisposing genes in HLA regions in Chinese Hans.

Adolescent↗
PubMed2006

High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis.

The aim of this prospective study was to determine the prevalence and characteristics of acid gastro-oesophageal reflux (GER) in patients with idiopathic pulmonary fibrosis (IPF). Sixty-five consecutive patients with well-defined IPF were subjected to 24-h pH monitoring and oesophageal manometry. A total of 133 consecutive patients with intractable asthma and symptoms of GER were used as comparisons. The prevalence of abnormal acid GER in IPF patients was 87%, with 76% and 63% demonstrating abnormal distal and proximal oesophageal acid exposures, respectively. Abnormal acid GER was significantly more common in IPF patients than asthma patients. Only 47% of IPF patients experienced classic GER symptoms. Despite treatment with standard doses of proton pump inhibitors (PPIs), 12 out of 19 patients receiving PPIs during the 24-h pH monitoring had abnormal oesophageal acid exposures by pH probe. There was no correlation between IPF severity and acid GER severity. In conclusion, abnormal acid gastro-oesophageal reflux is highly prevalent, but often clinically occult in patients with idiopathic pulmonary fibrosis. Standard doses of proton pump inhibitors may not suppress the acid gastro-oesophageal reflux in this population. Therefore, further studies are needed to determine if acid abnormal gastro-oesophageal reflux represents an important risk factor for idiopathic pulmonary fibrosis development or progression, and if optimal suppression of acid gastro-oesophageal reflux slows the progression of idiopathic pulmonary fibrosis and/or decreases episodic exacerbations of idiopathic pulmonary fibrosis.

Adult↗
PubMed2005

An SNP in protamine 1: a possible genetic cause of male infertility?

Gene targeting of the sperm nuclear proteins, the protamines, in mice leads to haploinsufficiency, abnormal chromatin compaction, sperm DNA damage, and male infertility. In order to investigate whether changes in amount or structure of the protamines could be a cause of human infertility, we sequenced the protamine genes of infertile men whose sperm appeared phenotypically similar to those of protamine deficient mice. We identified a heterozygous single nucleotide polymorphism (SNP) in the protamine (PRM1) gene in three infertile men (10% of the total infertile men analysed). This SNP disrupts one of the highly conserved arginine clusters needed for normal DNA binding. To rapidly screen for this SNP in infertile patients, we developed a simple PCR restriction fragment length polymorphism assay. This is the first report of a SNP in the PRM1 gene that appears associated with human male infertility.

Amino Acid Sequence↗
PubMed2005

Rapid analysis of trace levels of antibiotic polyether ionophores in surface water by solid-phase extraction and liquid chromatography with ion trap tandem mass spectrometric detection.

The occurrence of antibiotics in surface and ground water is an emerging area of interest due to the potential impacts of these compounds on the environment. This paper details a rapid, sensitive and reliable analytical method for the determination of monensin A and B, salinomycin and narasin A in surface water using solid-phase extraction (SPE) and liquid chromatography-ion trap tandem mass spectrometry (LC-MS-MS) with selected reaction monitoring (SRM). Several product ions as sodiated sodium salts for MS-MS detection have been identified and documented with their proposed fragmentation pathways. Statistical analysis for determination of the method detection limit (MDL), accuracy and precision of the method is described. The average recovery of ionophore antibiotics in pristine and wastewater-influenced water was 96.0+/-8.3% and 93.8+/-9.1%, respectively. No matrix effect was seen with the surface water. MDL was between 0.03 and 0.05 microg/L for these antibiotic compounds in the surface water. The accuracy and day-to-day variation of method fell within acceptable ranges. The method is applied to evaluate to the occurrence of these compounds in a small watershed in Northern Colorado. The method verified the presence of trace levels of these antibiotics in urban and agricultural land use dominated sections of the river.

Anti-Bacterial Agents↗
PubMed2005

Basiliximab (Simulect) reduces acute rejection among sensitized kidney allograft recipients.

AIMS: Our goal was to evaluate the efficacy and safety of basiliximab (Simulect) as immunosuppressive induction therapy for the prevention of acute allograft rejection among sensitized kidney recipients. METHODS: Fifty-six adult recipients receiving cadaveric kidney transplant with panel reactive antibody class I ranging from 30% to 50% and or class II 30% to 80% were randomized at about a 2:1 ratio to the Simulect group (36 patients) or matching control group (20 patients). All patients received baseline triple immunosuppressive therapy with cyclosporine (Neoral), mycophenolate mofetil, and steroids. Simulect was given in two doses of 20 mg each on day 0 (2 hours before operation) and day 4 after transplantation. RESULTS: There was no hyperacute rejection in either group and delayed graft function occurred in three control patients. The incidence of acute rejection during the first 3 months was 11.1% in the Simulect group compared with 50% in the placebo group (77.8% reduction, P < .01). No apparent adverse and toxic events were recorded in the Simulect group. The mean daily dose of steroids was significantly higher in the control group 2 to 4 weeks posttransplantation. No clinically meaningful differences in the mean dose of cyclosporine were observed between the two groups; in addition, there were no statistically significant differences in the rate of patient or graft survival. CONCLUSIONS: On the basis of appropriate selection of the donor and recipient, Simulect is effective and safety for the sensitized recipients as immunosuppressive induction therapy.

Acute Disease↗
PubMed2005

Refined localization of a punctate palmoplantar keratoderma gene to a 5.06-cM region at 15q22.2-15q22.31.

BACKGROUND: Punctate palmoplantar keratoderma (PPK) is a rare autosomal dominant cutaneous disorder characterized by numerous hyperkeratotic papules distributed on the palms and soles. Two loci for punctate PPK were recently found to be located on 8q24.13-8q24.21 and 15q22-15q24. However, no genes for this disease have been identified to date. Objectives To refine the previously mapped regions and to identify the disease gene locus in a four-generation Chinese family with punctate PPK. METHODS: Genetic linkage analysis was carried out in this family using microsatellite markers on chromosomes 8q and 15q. Two-point linkage analysis was performed using Linkage programs version 5.10 and the haplotype was constructed using Cyrillic version 2.02 software. RESULTS: We failed to confirm our previous locus at 8q24.13-8q24.21, but significant evidence for linkage was observed in the region of 15q with a maximum two-point LOD score of 5.38 at D15S153 (theta = 0.00). Haplotype analysis localized the punctate PPK locus within the region defined by D15S651 and D15S988. This region overlaps by 5.06 cM with the previously reported punctate PPK region. CONCLUSIONS: This study refines a disease gene causing punctate PPK to a 5.06-cM interval at 15q22.2-15q22.31.

Adolescent↗