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Biomedical subjects

N Gu

Publications and source records attributed to N Gu.

At least 19 recordsLinked to original sources

No association between the genetic polymorphisms in the RTN4R gene and schizophrenia in the Chinese population.

The RTN4R gene is located in the 22q11 region and it encodes a subunit of the receptor complex (RTN4R-p75NTR) which results in neuronal growth inhibitory signals in response to Nogo-66, MAG or OMG signaling. Previous studies have suggested that RTN4R might act as a potential candidate for schizophrenia susceptibility loci. We genotyped four SNPs within the gene and conducted a case-control study and TDT analysis, involving 707 schizophrenic patients, 689 controls and 372 unrelated small nuclear families with schizophrenic offspring in the Chinese population. We examined allele and genotype frequencies and haplotype distributions in both family- and nonfamily-based samples. Our results suggest that there is no significant association between the genetic polymorphisms and schizophrenia in the Han Chinese population.

Case-Control Studies↗

Kv7/KCNQ/M-channels in rat glutamatergic hippocampal axons and their role in regulation of excitability and transmitter release.

M-current (I(M)) plays a key role in regulating neuronal excitability. Mutations in Kv7/KCNQ subunits, the molecular correlates of I(M), are associated with a familial human epilepsy syndrome. Kv7/KCNQ subunits are widely expressed, and I(M) has been recorded in somata of several types of neurons, but the subcellular distribution of M-channels remains elusive. By combining field-potential, whole-cell and intracellular recordings from area CA1 in rat hippocampal slices, and computational modelling, we provide evidence for functional M-channels in unmyelinated axons in the brain. Our data indicate that presynaptic M-channels can regulate axonal excitability and synaptic transmission, provided the axons are depolarized into the I(M) activation range (beyond approximately -65 mV). Here, such depolarization was achieved by increasing the extracellular K(+) concentration ([K(+)](o)). Extracellular recordings in the presence of moderately elevated [K(+)](o) (7-11 mm), showed that the specific M-channel blocker XE991 reduced the amplitude of the presynaptic fibre volley and the field EPSP in a [K(+)](o)-dependent manner, both in stratum radiatum and in stratum lacknosum moleculare. The M-channel opener, retigabine, had opposite effects. The higher the [K(+)](o), the greater the effects of XE991 and retigabine. Similar pharmacological modulation of EPSPs recorded intracellularly from CA1 pyramidal neurons, while blocking postsynaptic K(+) channels with intracellular Cs(+), confirmed that active M-channels are located presynaptically. Computational analysis with an axon model showed that presynaptic I(M) can control Na(+) channel inactivation and thereby affect the presynaptic action potential amplitude and Ca(2+) influx, provided the axonal membrane potential is sufficiently depolarized. Finally, we compared the effects of blocking I(M) on the spike after-depolarization and bursting in CA3 pyramidal neuron somata versus their axons. In standard [K(+)](o) (2.5 mm), XE991 increased the ADP and promoted burst firing at the soma, but not in the axons. However, I(M) contributed to the refractory period in the axons when spikes were broadened by a low dose 4-aminopyridine (200 microm). Our results indicate that functional Kv7/KCNQ/M-channels are present in unmyelinated axons in the brain, and that these channels may have contrasting effects on excitability depending on their subcellular localization.

4-Aminopyridine↗

MPZL1/PZR, a novel candidate predisposing schizophrenia in Han Chinese.

The MPZL1/PZR gene has been mapped to 1q23.3, located in close proximity to a recognized schizophrenia susceptibility locus. Recently, the MPZL1/PZR gene has been found to be significantly upregulated in schizophrenia brain tissue and to play an important role in cell signaling, thus indicating that MPZL1/PZR could be a potential schizophrenia marker. To test this hypothesis, we selected three single nucleotide polymorphisms (SNPs) for genotyping in 523 Han Chinese trios. We found that two individual SNPs were significant at the Bonferroni's corrected significance level P<0.017: rs3767444 (chi2=6.299, P=0.0121) and rs2051656 (chi2=9.856, P=0.0017). Haplotype transmission/disequilibrium tests revealed a significant association with the disease (global P-value=1.064 x 10(-6)), but no specific transmission distortions. Thus, we propose that the MPZL1/PZR gene may be important in the predisposition to schizophrenia among Han Chinese.

Adult↗

Preparation of All-Trans Retinoic Acid nanosuspensions using a modified precipitation method.

All-Trans Retinoic Acid (ATRA) nanosuspensions were prepared with a modified precipitation method. The ATRA solution in acetone was injected into pure water by an air compressor under the action of ultrasonication. Photon correlation spectroscopy results showed that the mean particle size of ATRA nanoparticles in nanosuspensions reduced from 337 nm to 155 nm as the injection velocity increased and the polydispersity index was 0.45-0.50. The morphology of ATRA nanoparticles varied with the different concentration of ATRA solution in acetone. ATRA nanoparticles showed an amorphous state and stable in 6 months. It could be concluded that this modified precipitation method could produce stable and controllable ATRA nanosuspension to a certain extent, thus benefit for higher saturation solubility.

Acetone↗

Association of TPH1 with suicidal behaviour and psychiatric disorders in the Chinese population.

Tryptophan hydroxylase (TPH), the rate limiting enzyme in serotonin biosynthesis, is one of the most important regulating factors in the serotonergic system. Recently, polymorphisms of the TPH gene have been identified as being associated with suicide, but the evidence is inconsistent. To investigate the role in suicide of one of the isoforms, TPH1, we examined the association of five single nucleotide polymorphisms (SNPs) in the promoter region and in intron 7 of the TPH1 gene based on a sample from the Chinese population of 810 subjects, of whom 329 had made no suicide attempts (NSA), 297 had made suicide attempts (SA), and 184 were healthy subjects (HS). In this study, we observed statistically significant differences between NSA and HS subjects in allele distributions on one marker, -6526A (p = 0.0329; odds ratio (OR) 1.36; 95% confidence interval (CI) 1.01 to 1.81). No significant difference in genotype distribution or allele frequencies of other polymorphisms was found between the suicide victims and the controls. The overall haplotype frequency was significantly different between cases and healthy controls (p = 0.000024 NSA v HS; p < 0.000001, SA v HS; p < 0.000001, cases v HS). We found the haplotype TCAAA of -7180/-7065/-6526/218/779 to be strongly associated with suicidal behaviour and psychiatric disorders (p = 0.00243; OR = 1.62; 95% CI 1.17 to 2.24 and p = 0.018; OR = 1.41; 95% CI 1.05 to 1.91), which suggests an association of TPH1 with suicidal behaviour and indicates that TPH1 may play a significant role in the aetiology of psychiatric disorders in the Han Chinese population.

Alleles↗

Presynaptic Ca2+-activated K+ channels in glutamatergic hippocampal terminals and their role in spike repolarization and regulation of transmitter release.

Large-conductance Ca(2+)-activated K(+) channels (BK, also called Maxi-K or Slo channels) are widespread in the vertebrate nervous system, but their functional roles in synaptic transmission in the mammalian brain are largely unknown. By combining electrophysiology and immunogold cytochemistry, we demonstrate the existence of functional BK channels in presynaptic terminals in the hippocampus and compare their functional roles in somata and terminals of CA3 pyramidal cells. Double-labeling immunogold analysis with BK channel and glutamate receptor antibodies indicated that BK channels are targeted to the presynaptic membrane facing the synaptic cleft in terminals of Schaffer collaterals in stratum radiatum. Whole-cell, intracellular, and field-potential recordings from CA1 pyramidal cells showed that the presynaptic BK channels are activated by calcium influx and can contribute to repolarization of the presynaptic action potential (AP) and negative feedback control of Ca(2+) influx and transmitter release. This was observed in the presence of 4-aminopyridine (4-AP, 40-100 microm), which broadened the presynaptic compound action potential. In contrast, the presynaptic BK channels did not contribute significantly to regulation of action potentials or transmitter release under basal experimental conditions, i.e., without 4-AP, even at high stimulation frequencies. This is unlike the situation in the parent cell bodies (CA3 pyramidal cells), where BK channels contribute strongly to action potential repolarization. These results indicate that the functional role of BK channels depends on their subcellular localization.

4-Aminopyridine↗

Genetic association study between alpha 1-antichymotrypsin polymorphism and Alzheimer disease in Chinese Han population.

We investigated a common signal peptide polymorphism in the alpha 1-antichymotrypsin (ACT) gene in 125 sporadic Alzheimer disease (AD) patients and 141 healthy control subjects in Chinese Han population. We found no significant difference in the distribution of ACT polymorphism between AD cases and controls, and failed to detect any effects of ACT genotypes associated with AD. Thus, our data do not support the involvement of ACT polymorphism in the risk of AD in Chinese Han population. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:133-135, 2000.

Adult↗

Association analysis between mood disorder and monoamine oxidase gene.

To ascertain whether mood disorders, including bipolar and unipolar, are genetically associated with the monoamine oxidase A (MAOA) or monoamine oxidase B (MAOB) gene in the Chinese population, 132 cases of mood disorder and 88 normal controls were genotyped for the MAOA(CA)n, MAOB(GT)n, and MAOB(TG)n loci by the method of amplification fragment length polymorphism. Among 132 cases with mood disorder, eight alleles (size: 112-126 bp) of locus MAOA(CA)n, 12 alleles (size: 168-198 bp) of locus MAOB(GT)n, and nine alleles (size: 195-213 bp) of locus MAOB(TG)n were observed. Comparison of the allele frequency of the three loci showed no difference between mood disorder cases and normal controls on average. When each group was stratified into several subgroups, significant differences were found. On the MAOA(CA)n locus, the frequency of 116 bp allele was higher in the female bipolar disorder cases (0.2581) compared with that in the female unipolar disorder patients (0.1154) (Z=2.15, p<0. 05). On the MAOB(GT)n locus, the frequency of 180 bp allele was higher in bipolar disorder patients (0.1579) than that in normal controls (0.0678) (Z=2.05, p<0.05). The frequency of this allele was even higher in female bipolar disorder patients (0.1719) than that in female normal controls (0.0541). On the MAOB(TG)n locus, the frequency of 205 bp allele was higher in female bipolar disorder patients (0.6406) than that in female normal controls (0.4375) (Z=2. 17, p<0.05). For the unipolar disorder patients, the frequency of this allele was higher in female cases (0.5222) than that in male cases (0.1818) (Z=3.49, p<0.05). As for association studies, significant association between bipolar disorder and MAOB gene was detected. For the 180 bp allele of MAOB(GT)n, the relative risk (RR) of biploar versus normal control was 2.58 (p<0.05), and the RR of female bipolar disorder versus female normal control was 3.63 (p<0. 05). For the 205 bp allele of MAOB(TG)n, the RR of female bipolar disorder versus female normal control was 2.29 (p<0.05). Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:12-14, 2000.

Alleles↗

[The relation between alpha1-antichymotrypsin gene polymorphism and epsilon4 allele of apolipoprotein E gene in Alzheimer disease in Chinese]

OBJECTIVE: To detect the relation between alpha1-antichymotrpsin(AACT)gene polymorphism and epsilon4 allele of apolipoprotein E (ApoE) gene in Alzheimer disease (AD) in Chinese. METHODS: The gene polymorphisms of ApoE and AACT were genotyped in 125 AD cases and 140 controls with PCR methods and RFLP typing. Then the association between AACT polymorphism and ApoE epsilon4 was analysed. RESULTS: There was no association between AD and any allele or genotype of AACT polymorphism; AACT polymorphism was not associated with AD ApoE epsilon4 or without ApoE epsilon4. In AACT* AT and AACT* TT genotypes, ApoE epsilon4 allele was associated with AD, but no association was observed in AACT* AA genotype. CONCLUSION: AACT may not be associated with AD in Chinese, and this effect can not be influenced by ApoE epsilon4, but AACT gene polymorphism may affect the association between ApoE epsilon4 allele and AD.

Journal Article↗

[Presinilin 1 gene polymorphism and Alzheimer's disease in Chinese].

OBJECTIVE: To detect the relationship between Presinilin 1(PS1) intronic polymorphism and Alzheimer's disease(AD) in Chinese. METHODS: PS1 intronic polymorphism was genotyped in 58 early-onset AD cases(EOAD), 65 late-onset AD cases (LOAD) and 157 age-matched controls by using PCR methods and RFLP typing. Then the association between PS1 polymorphism and AD was analyzed. RESULTS: (1) In EOAD cases, the frequency of allele 1 increased and the frequencies of allele 2 and genotype 2/2 decreased markedly, but in LOAD cases, no differences were observed. (2) EOAD was significantly associated with allele 1 (RR=2.29), P< 0.05), allele 2 (RR=0.44) and genotype 2/2(RR=0.23, P<0.05) of PS1 polymorphism, while LOAD showed no association with PS1 polymorphism. (3)PS1 polymorphism was associated with AD predominantly in non-ApoE epsilon4, female, early-onset cases. CONCLUSION: PS1 polymorphism was only associated with EOAD in Chinese, and this may be influenced by age of onset and sex.

Aged↗

No association between the intronic presenilin 1 polymorphism and Alzheimer's disease in the Chinese population.

Wragg et al. [1996: Lancet 347:509-512] recorded an association between the intron-based presenilin 1 (PS1) genotype 1/1 and late-onset Alzheimer's disease (AD). This study was performed to determine if there is a similar association in the Chinese population. Ninety-one AD cases, 50 multiinfarct dementia (MID) patients, and 73 age-matched normal controls were recruited. Genotyping of PS1 and apolipoprotein E (APOE) was performed by the methods of polymerase chain reaction and restriction fragment length polymorphism. In AD, MID, and normal controls PS1 allele 1 frequency was 0.6703, 0.5600, and 0.6301, respectively; PS1 allele 2 frequency was 0.3297, 0.4400, and 0.3699, respectively. No association was detected between these diseases and any PS1 allele or genotype. There was only a nearly significant negative association between MID and PS1 genotype 1/1 in the subgroup population bearing APOE allele E4 (odds ratio = 0.2753, P = 0.0776). Our results do not support the conclusion that the intronic PS1 polymorphism is associated with Alzheimer's disease.

Aged↗

[The relation between alpha1-antichymotrypsin gene polymorphism and epsilon4 allele of apolipoprotein E gene in Alzheimer disease in Chinese].

OBJECTIVE: To detect the relation between alpha1-antichymotrpsin(AACT)gene polymorphism and epsilon4 allele of apolipoprotein E (ApoE) gene in Alzheimer disease (AD) in Chinese. METHODS: The gene polymorphisms of ApoE and AACT were genotyped in 125 AD cases and 140 controls with PCR methods and RFLP typing. Then the association between AACT polymorphism and ApoE epsilon4 was analysed. RESULTS: There was no association between AD and any allele or genotype of AACT polymorphism; AACT polymorphism was not associated with AD ApoE epsilon4 or without ApoE epsilon4. In AACT*AT and AACT*TT genotypes, ApoE epsilon4 allele was associated with AD, but no association was observed in AACT*AA genotype. CONCLUSION: AACT may not be associated with AD in Chinese, and this effect can not be influenced by ApoE epsilon4, but AACT gene polymorphism may affect the association between ApoE epsilon4 allele and AD.

Adult↗

Tentative association of the serotonin transporter with schizophrenia and unipolar depression but not with bipolar disorder in Han Chinese.

The serotonin transporter gene (SERT) plays an important role in the serotonin uptake into neurons. Recently, several polymorphisms including a variable-number-tandem-repeat (VNTR) in the second intron and an insertion/deletion polymorphism (5-HTT linked polymorphic region, 5-HTTLPR) were identified and reported to be associated with a variety of mental illnesses, including major depression, bipolar disorder, anxiety-related traits, and autism. In our study, we performed an association study between the SERT VNTR polymorphism and schizophrenia (n = 260), bipolar disorder (n = 137), and unipolar depression (n = 33) in the Han Chinese. A large group of ethnically matched control individuals (n = 362) were also genotyped. Allele 12 of the VNTR polymorphism was associated with schizophrenia (P = 0.007) and unipolar depression (P = 0.011). Bipolar disorder was not associated with the VNTR (P = 0.93). Thus, we conclude that the SERT VNTR polymorphism may be a risk factor for both schizophrenia and unipolar depression, but not for bipolar disorder, in the Han Chinese.

Alleles↗

[Long-term results of surgical treatment of intractable Menière's disease for control of vertigo].

OBJECTIVE: To acquire the long-term (an average of over 10 years follow-up) results of surgical treatment of patients with Meniere's disease for control of vertigo. METHOD: Endolymphatic sac surgery was done in 6 cases (1 case of endolymphatic sac decompression and 5 cases of sac-mastoid shunting) and translabyrinth vestibular neurotomy was operated on 6 cases. RESULT: Complete relief from symptoms of vertigo occurred in the 6 cases through vestibular neurotomy and there were no recurrence in 11-13 years follow-up. Three of 6 cases with endolymphatic sac surgery had complete control of vertigo and were cured clinically. Symptoms of vertigo of the rest 3 cases were effectively controlled. CONCLUSION: Endolymphatic sac surgery and translabyrinth vestibular neurotomy are effective way for control of vertigo of patients with intractable Meniere's disease. Translabyrinth vestibular neurotomy are more effective for control of vertigo for appropriately selected patients.

Adult↗

[Association of VNTR region of the human serotonin transporter gene with bipolar disorder among the Han Chinese].

OBJECTIVE: The serotonin transporter gene (SERT) plays an important role in the serotonin uptake into neurons. This paper reports a population and association study among the Han Chinese. METHODS: DNA were extracted from peripheral blood samples of 50 patients with bipolar disorder (DSM-IIIR), 170 unrelated healthy Han Chinese individuals and 10 healthy trios for polymerase chain reaction. The VNTR locus was amplified and PCR products were separated on the 2% agrose gel. RESULTS: All the three alleles(9,10 and 12 copies of repeat unit) reported in other studies were observed in this study with frequency 0.0029, 0.0676 and 0.9294, respectively. Four genotypes distributed in Caucasian: 12/12, 12/10, 12/9 and 10/10 were also found in the Han Chinese population. A significant difference in the allele frequency between the Han Chinese and Caucasian populations was found(P 0.000000001). No disequilibrium was observed after checking the Hardy-Weinberg equilibrium (P=0. 9995). The hereditary stability of this locus in accordance with the rules of Mendelian inheritance was demonstrated in the analysis of ten trios. In addition, a significant increase of frequency of the allele 10 in female patients with bipolar disorder was found (P=0. 043). CONCLUSION: The data of association study might indicate a different mechanism of aetiology of bipolar disorder in male and female.

Asian People↗

[Trans-ethmoidal optic nerve decompression in traumatic optic neuropathy].

UNLABELLED: To evaluate the outcome of trans-ethmoidal optic nerve decompression (TOND). METHOD: Between November 1984 and May 1996, 35 patients with traumatic optic neuropathy (TON) underwent TOND. While 6 patients were treated with high dose corticosteroids (HDC). RESULTS: 13(37.14%) cases of 35 patients who underwent TOND showed improvement in vision. 1 (16.67%) of 6 patients who were treated with HDC showed improvement in vision. Of the 12 patients with some initial vision, 8 patients underwent TOND and 7(87.5%) patients showed improvement in vision. Another 4 patients treated with HDC, 1(25.0%) patient showed improvement in vision. Of the 29 patients who presented with no light perception, 27 patients underwent TOND and 6(22.22%) patients showed improvement in vision. 2 patients treated with HDC failed to get vision improvement. CONCLUSION: TOND can improve vision in patients with TON. It is rational to perform surgical decompression early. Using of HDC before and after surgery may improve the outcome of TON. No light perception and absence of waveform on visual evoked response is not contradict, some patients may show improvement in vision.

Adolescent↗