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Biomedical subjects

A G Wang

Publications and source records attributed to A G Wang.

At least 19 recordsLinked to original sources
PubMed2006

Association analyses suggest GPR24 as a shared susceptibility gene for bipolar affective disorder and schizophrenia.

Linkage analyses suggest that chromosome 22q12-13 may harbor a shared susceptibility locus for bipolar affective disorder (BPD) and schizophrenia (SZ). In a study of a sample from the Faeroe Islands we have previously reported association between both disorders and microsatellite markers in a 3.6 cM segment on 22q13. The present study investigated three candidate genes located in this segment: GPR24, ADSL, and ST13. Nine SNPs located in these genes and one microsatellite marker (D22S279) were applied in an association analysis of two samples: an extension of the previously analyzed Faeroese sample comprising 28 distantly related cases (17 BPD, 11 SZ subjects) and 44 controls, and a Scottish sample including 162 patients with BPD, 103 with SZ, and 200 controls. In both samples significant associations were observed in both disorders with predominantly GPR24 SNPs and haplotypes. In the Faeroese sample overall P-values of 0.0009, 0.0054, and 0.0023 were found for haplotypes in BPD, SZ, and combined cases, respectively, and in the Scottish sample overall P-values of 0.0003, 0.0005, and 0.016 were observed for similar groupings. Specific haplotypes showed associations with lowest P-values of 7 x 10(-5) and 0.0006 in the combined group of cases from the Faeroe Islands and Scotland, respectively. The G protein-coupled receptor 24 encoded by GPR24 binds melanin-concentrating hormone (MCH) and has been implicated with feeding behavior, energy metabolism, and regulation of stress and mood. To our knowledge this is the first study reporting association between GPR24 and BPD and SZ, suggesting that GPR24 variants may confer susceptibility to both disorders.

Bipolar Disorder↗
PubMed2006

A genome-wide search for alleles and haplotypes associated with autism and related pervasive developmental disorders on the Faroe Islands.

The involvement of genetic factors in the etiology of autism has been clearly established. We undertook a genome-wide search for regions containing susceptibility genes for autism in 12 subjects with childhood autism and related pervasive developmental disorders (PDDs) and 44 controls from the relatively isolated population of the Faroe Islands. In total, 601 microsatellite markers distributed throughout the human genome with an average distance of 5.80 cM were genotyped, including 502 markers in the initial scan. The Faroese population structure and genetic relatedness of cases and controls were also evaluated. Based on a combined approach, including an assumption-free test as implemented in CLUMP, Fisher's exact test for specific alleles and haplotypes, and IBD(0) probability calculations, we found association between autism and microsatellite markers in regions on 2q, 3p, 6q, 15q, 16p, and 18q. The most significant finding was on 3p25.3 (P(T1)=0.00003 and P(T4)=0.00007), which was also supported by other genetic studies. Furthermore, no evidence of population substructure was found, and a higher degree of relatedness among cases could not be detected, decreasing the risk of inflated P-values. Our data suggest that markers in these regions are in linkage disequilibrium with genes involved in the etiology of autism, and we hypothesize susceptibility genes for autism and related PDDs to be localized within these regions.

Adolescent↗
PubMed2006

No association between the -399 C > T polymorphism of the neuropeptide Y gene and schizophrenia, unipolar depression or panic disorder in a Danish population.

OBJECTIVE: A polymorphism in the promoter region of the NPY gene at position -399 C > T was recently reported to be associated with schizophrenia in a Japanese population and with treatment refractory unipolar depression in a Swedish population. The objective of this study was to investigate potential associations between the polymorphism and three psychiatric disorders in a Danish population. METHOD: We investigated the occurrence of the polymorphism in patients with schizophrenia (n = 291), unipolar depression (n = 256) and panic disorder (n = 142) compared with controls (n = 716). RESULTS: We detected the polymorphism -399 C > T at a frequency of 48% in controls. No significant differences were found between genotype or allele frequencies in controls vs. the patient groups. CONCLUSION: The lack of association between the -399 C > T polymorphism and schizophrenia, unipolar depression or panic disorder, respectively, suggests that the polymorphism is not involved in the etiology of these disorders in the Danish population.

Adult↗
PubMed2005

Effects on protein and mRNA expression levels of p53 induced by fluoride in human embryonic hepatocytes.

We investigated the effects of protein and mRNA expression levels on p53 induced by fluoride in human embryo hepatocyte L-02 cells. The protein and mRNA levels of p53 in L-02 cells were measured after in vitro cultured L-02 was exposed to sodium fluoride at different doses (40, 80, and 160 microg/ml) for 24 h. The results showed that the cell survival rate of L-02 cells in the high dose fluoride group was significantly lower than that of the control group. The protein expression levels of p53 in the middle and high dose fluoride group were significantly higher than in the control group and elevated with increasing fluoride concentration. The mRNA expression levels of p53 in the fluoride groups were markedly higher than in the control group. The mRNA expression level of p53 in the high dose fluoride group was however lower compared to the middle dose fluoride group, but similar to the low dose fluoride group. These finding suggest that fluoride can decrease the L-02 cells survival rate and induce protein and mRNA expressions of p53; however, there is no consistency between the protein expression level of p53 and the mRNA expression level.

Blotting, Western↗
PubMed2004

Effects of phenobarbital on metabolism and toxicity of diclofenac sodium in rat hepatocytes in vitro.

Diclofenac sodium (DF-Na) was a nonsteroidal anti-inflammatory drug used in various aspects of inflammatory disease. The purpose of this study was to examine the effects of phenobarbital (PB) on metabolism and toxicity of DF-Na in vitro and explore the potential mechanism of DF-Na induced hepatotoxicity. Rat hepatocytes were isolated by a modification of the two-step in situ collagenase perfusion technique and the harvested rat hepatocytes were cultured with sandwich method. Control or PB (2 mM) pre-treated hepatocytes were incubated with DF-Na (0.1, 0.05 or 0.01 mM) in vitro and cytosolic enzyme leakage levels, cytochrome P450 (CYP) 3A activity, and metabolite content of DF-Na in cell culture medium were measured. The results showed that without any treatment hepatocyte CYP 3A activity gradually decreased with culture time. On day four, CYP 3A activity was 53% of the initial value. The decline of CYP 3A was partially reversed by CYP inducer PB, and the maximum induction of CYP 3A was 2.2-fold over control after continuous exposure of hepatocytes to 2 mM PB for 48 h. Lactic dehydrogenase (LDH), aspartate transaminase (AST), and alanine transamine (ALT) activity and the contents of the DF-Na metabolites 4'-hydroxydiclofenac (4'-OH-DF) and 5-hydroxydiclofenac (5-OH-DF) in media appeared to increase with increasing DF-Na concentrations, though there were no significant differences between DF-Na exposed and control hepatocytes. However, if the hepatocytes first were pre-treated with 2 mM PB for 2 days and then exposed to DF-Na, the concentrations of DF-Na metabolites and the activity of LDH in the media were significantly higher than that of control group. These findings suggest that the hepatotoxicity and metabolism of DF-Na in rat hepatocytes are increased when hepatic CYP 3A activity is increased.

Animals↗
PubMed2004

Possible evidence for a common risk locus for bipolar affective disorder and schizophrenia on chromosome 4p16 in patients from the Faroe Islands.

Patients with schizophrenia (n=11) and bipolar affective disorder (n=17) from the relatively isolated population of the Faroe Islands were genotyped for 34 polymorphic markers on chromosome 4 in a search for allelic association and haplotype sharing among distantly related patients. When considering bipolar patients only, there was no clearcut support for any region on chromosome 4. The two-marker segment D4S394-D4S2983 at 4p16.1 was, however, supported by a P-value of 0.0162. For patients with schizophrenia, there was reasonable support for 4p16.1 as marker D4S2281 (P=0.0019), a two-marker segment (D4S2281-D4S1605, P=0.0009) and a three-marker segment (D4S2923-D4S2928-D4S1582, P-0.0005) appeared to be associated with schizophrenia, with some alleles/haplotypes occurring with different frequencies in patients compared to controls. When combining both psychiatric disorders, chromosome 4p16.1 received further support from five partially overlapping two- and three-marker segments (D4S394-D4S2983, P=0.0039; D4S2281-D4S1605, P=0.0027 and D4S394-D4S2983-D4S2923, P=0.006; D4S2923-D4S2928-D4S1582, P=0.00007; D4S1582-D4S1599-D4S2281, P=0.005). Increased haplotype sharing in patients with schizophrenia and in the combined data set was partly supported by Fisher's exact test and tests based on the genealogy. Our study yields support for a common risk gene for schizophrenia and bipolar affective disorder on the short arm of chromosome 4, as suggested by previous findings in the neighbouring Scottish population.

Bipolar Disorder↗
PubMed2003

Comorbid personality disorder predicts suicide after major depression: a 10-year follow-up.

OBJECTIVE: To identify psychopathological predictors for suicide in a population of major depressed Diagnostic Statistical Manual-III (DSM-III) in-patients. METHOD: A total of 210 previous participants in multicentre antidepressant drug trials, carried out in a randomized double-blind design, were followed prospectively through a maximum of 10 years. Patients with a drug or alcohol abuse were excluded. The association between suicide and the pretreatment psychopathological profile was analysed using survival statistics. RESULTS: The suicide rate for non-melancholic depressed patients was significantly higher than for melancholic depressed patients. Comorbid personality disorder was independently associated with an increased suicide rate [relative hazard 3.41(CI: 1.15-10.10)]. CONCLUSION: The study indicates that the non-melancholic aspect of depression, and especially comorbid personality disorder, is associated with an increased suicidal vulnerability.

Adult↗
PubMed2002

Search for common haplotypes on chromosome 22q in patients with schizophrenia or bipolar disorder from the Faroe Islands.

Chromosome 22q may harbor risk genes for schizophrenia and bipolar affective disorder. This is evidenced through genetic mapping studies, investigations of cytogenetic abnormalities, and direct examination of candidate genes. Patients with schizophrenia and bipolar affective disorder from the Faroe Islands were typed for 35 evenly distributed polymorphic markers on 22q in a search for shared risk genes in the two disorders. No single marker was strongly associated with either disease, but five two-marker segments that cluster within two regions on the chromosome have haplotypes occurring with different frequencies in patients compared to controls. Two segments were of most interest when the results of the association tests were combined with the probabilities of identity by descent of single haplotypes. For bipolar patients, the strongest evidence for a candidate region harboring a risk gene was found at a segment of at least 1.1 cM including markers D22S1161 and D22S922 (P=0.0081 in the test for association). Our results also support the a priori evidence of a susceptibility gene to schizophrenia at a segment of at least 0.45 cM including markers D22S279 and D22S276 (P=0.0075). Patients were tested for the presence of a missense mutation in the WKL1 gene encoding a putative cation channel close to segment D22S1161--D22S922, which has been associated with schizophrenia. We did not find this mutation in schizophrenic or bipolar patients or the controls from the Faroe Islands.

Bipolar Disorder↗
PubMed2000

[From psychiatric hospital to residential home for younger psychiatric patients. A cross-over study of residents in Sundbygaard in Copenhagen]].

Along with the implementation of community psychiatry, an increasing number of younger psychiatric patients live in social institutions, with psychiatric treatment offered on a consultation basis. On the basis of hospital records and interviews with staff members, the study describes two groups of patients in a former psychiatric nursing hospital, group 1 offered time-limited stay with the aim of social rehabilitation, and group 2 offered permanent stay. Patients of group 1 were younger and more frequently treated with atypical antipsychotics. Apart from this, no differences were found. The vast majority of both groups suffered from schizophrenia. The intensity of symptoms was high, despite extensive medication. The two groups might represent the same category of the most severely disabled patients, seen at different ages. More intensive psychiatric consultant service is found necessary, and the process of rehabilitation should be evaluated prospectively.

Adult↗
PubMed2000

Ethambutol retinal toxicity: an electrophysiologic study.

BACKGROUND AND PURPOSE: In animal studies, ethambutol (EMB) has been shown to be toxic to cone pedicles and to cause their degeneration in the retinas of fish. The purpose of this study was to determine whether EMB is toxic to retinas in humans. METHODS: Twenty-seven patients with EMB-induced optic neuropathy and 20 normal control subjects were included in this study. The following details were recorded: age, sex, and systemic condition of the patients, daily dosage of EMB, duration of EMB treatment, visual function at the time of electrophysiologic investigation, time from the onset of blurred vision to the discontinuation of EMB treatment (symptom duration), and time from termination of EMB treatment until electrophysiologic investigation. RESULTS: The electroretinograms were normal in 25 patients. Twelve patients had normal electro-oculogram (EOG) findings in both eyes and the remaining 15 patients had abnormal EOG findings in at least one eye. Ten eyes showed supranormal EOG (light/dark (L/D)) ratios of more than 2.33, and 13 eyes had decreased L/D ratios (< 1.65). The symptom duration was shorter in the supranormal EOG group. CONCLUSIONS: The results suggest that a supranormal EOG may be indicative of an early toxic state during EMB therapy and that EMB may cause dysfunction of the retinal pigment epithelium.

Adult↗
PubMed2000

False positive molecular diagnosis of Leber's hereditary optic neuropathy.

BACKGROUND: The most common pathogenic mitochondrial DNA (mtDNA) mutation associated with Leber's hereditary optic neuropathy (LHON) is at the 11,778 nucleotide (nt) position and is usually detected by loss of an Sfa NI restriction site. However, Sfa NI restriction site includes five nucleotides. Substitution of any of the five nucleotides leads to loss of the cutting site and causes a false-positive result. We investigated the false-positive diagnosis of LHON by loss of the Sfa NI restriction site using Sfa NI restriction site analysis and single-strand conformation polymorphism (SSCP) analysis. METHODS: Mae III restriction analysis for double confirmation of the Sfa NI restriction site and direct sequencing for final confirmation of SSCP analysis were performed. RESULTS: The sensitivity of Sfa NI test was 100% and the specificity of the Sfa NI test was 97%. The false-positive rate of Sfa NI test was 3%. SSCP analysis showed 100% sensitivity. Direct sequencing showed 32 patients had a mutation at nt 11,778 of mtDNA and one patient had a silent mutation at nt 11,782 of mtDNA. CONCLUSIONS: These results suggest that restriction enzyme digestion analysis requires double confirmation to avoid a false-positive diagnosis and that DNA sequencing is needed for the confirmation of the mutation detected by SSCP.

Adolescent↗
PubMed1999

Positron emission tomography scan in cortical visual loss in patients with organophosphate intoxication.

OBJECTIVE: To determine the cerebral metabolism of patients with cortical visual loss. DESIGN: Two observational case studies. TESTING: Two patients who survived acute organophosphate poisoning with respiratory failure experienced severe visual loss despite relatively normal ophthalmic examination results. Magnetic resonance imaging of the brain revealed no abnormality of the visual system in either patient. Positron emission tomography (PET) was performed in these 2 patients and in 12 normal subjects with fluorine-18 fluorodeoxyglucose (FDG) as a tracer to measure cerebral glucose metabolism for the estimation of neurologic deficit in the visual cortex. MAIN OUTCOME MEASURES: The FDG uptake values were measured as nanoCurie per cubic centimeters of tissue (nCi/cc). The relative uptake index in visual cortex was computed as the ratio of uptake of FDG in each region of visual cortex to that of cerebellum (regional visual cortex/cerebellum). RESULTS: Hypometabolism was observed in the visual cortex of both patients. The relative uptake index of FDG in visual cortex (visual cortex/cerebellum) was significantly decreased in those patients compared with normal subjects. CONCLUSIONS: In patients with cortical visual loss, conventional neuroimaging techniques can fail to visualize damage that can be detected by PET scanning, and PET analysis may be helpful in estimating the metabolic deficit of visual cortex and in establishing the organic nature of cortical visual loss in these patients.

Adult↗
PubMed1999

A haplotype-based study of lithium responding patients with bipolar affective disorder on the Faroe Islands.

The Faroe Islands are a small group of islands in the North Atlantic Ocean, situated between Norway, Iceland and Scotland. The origin of the population is thought to be a mixture of Norwegian, Danish and British. The islands were populated at the same time as Iceland, i.e. around 1100 years ago, and the size of the population was around, and occasionally below, 4000 inhabitants until 1800, after which it increased to its present-day level of around 45,000. The population is descended from Scandinavian and British ancestors. Because of the low number of founders and small size for many centuries, the Faroese population is perhaps the most valuable European population for genetic mapping of complex disease genes. The present study searched for haplotype sharing on chromosome 18 among eight lithium responding patients with bipolar affective disorder related, on average, 6.2 generations ago, using 30 DNA markers. In order to obtain as homogeneous a sample as possible, strict inclusion criteria based on severity of phenotype, geography and treatment response, were applied. Evidence suggestive of increased haplotype sharing on the distal part of chromosome 18q23 in the region implicated by Freimer and co-workers was found. However, methods of genetic analysis which might provide a conclusive result are not yet available.

Adolescent↗
PubMed1998

Bacterial corneal ulcer: a multivariate study.

A retrospective clinicomicrobiological review of 314 patients with bacterial corneal ulcers from January 1982 to December 1992 was performed. Multivariate statistical analysis was done with multiple logistic regression using PROC LOGIST of SAS statistical software. Positive cultures were grown from 134 (42.7%) of the patients. Pseudomonas aeruginosa, staphylococci, and Acinetobacter spp. were the most frequent pathogens. Significant associations between contact lens use and P. aeruginosa (odds ratio, OR 8.16), between previous herpes simplex keratitis and Streptococcus spp. (OR 18.2) were found. Acinetobacter spp. occurred more frequently in eyes with burn and/or lagophthalmos (OR 13.1/26.2). Staphylococcus aureus was associated with trauma (OR 6.27) and age under 50 (OR 5.08-13.6). Nonpseudomonal gram-negative bacilli were associated with age over 50 (OR 3.24). Drug sensitivity tests for these isolated microorganisms showed that vancomycin and ceftazidime were the most effective agents.

Adolescent↗
PubMed1994

[Mortality--suicide and natural death--among depressed patients. Relation to type of depression].

A total of 219 inpatients with a DSM-III diagnosis of major depression, (150 women and 69 men), were followed prospectively for three to ten years and mortality was recorded. The patients were previous participants in psychopharmacological multicentre trials, which were carried out for the purpose of comparing the antidepressant effect of newer selective serotonin reuptake inhibitors (SSRI), citalopram and paroxetine, with that of the tricyclic antidepressant drug, clomipramine. Diagnostic classification according to the Newcastle-I Scale into endogenous and nonendogenous depression was performed. The observed mortality was significantly greater than that expected. The increased mortality was essentially due to suicides and mainly found among women. Patients scored as being nonendogenously depressed had a significantly higher suicide rate than endogenously depressed patients. The excess number of suicides in the nonendogenous group largely occurred within the first year of observation. No association was found between response to the antidepressant treatment in the trial and the suicide risk during the first three years of observation.

Adult↗