OBJECTIVES: Neurological soft signs have been regarded as endophenotypes associated with the genetic basis of schizophrenia. This study was to investigate the intra-familial correlations of the neurological soft signs according to their genetic loading. METHODS: Schizophrenic patients(N=14) were included, who had one parent with a family history of schizophrenia and the other without it. Genetic loading was determined by the patient's family history of schizophrenia using the Family Interview for Genetic Studies(FIGS). These parents were subdivided into two groups. The first group was designated as'presumed carriers'(N=9) of genetic loading, who had one or more schizophreic first- or second-degree relatives. The second group was designated as'presumed non-carriers'(N=11) of genetic loading, who had no schizophrenic first- or second-degree relatives. Normal controls(N=12) consisted of people without schizophrenic relatives. NSS were evaluated using the Neurological Evaluation Scale-Korean Version (NES-K), and the intra-familial correlations of NSS were tested using the Intra-Class Coefficients(ICC) method. RESULTS: The scores of Motor Coordination subdimension of NES-K were significantly correlated between the patients and their presumed carriers(ICC=.804, p=.016), but not significantly correlated between the patients and their presumed noncarriers. In other subdimensions of NES-K, no significant correlation were found between the patients and their parents regardless of the genetic loading. But, there were no statistically significant differences in the scores of Motor Coordination subdimension of NES-K between the patients and controls. CONCLUSION: This study did not prove that the neurological soft signs might be an endophenotype of schizophrenia that cosegregate with the genetic loading. The future study using more subjects than this would be needed.
Endophenotypes ; Genetic Load ; Humans ; Parents ; Schizophrenia

OBJECTIVETo investigate the variations of hepatitis C virus (HCV) quasispecies and the changes in their composition in untreated patients with chronic hepatitis C.

METHODSEleven patients chronic hepatitis C without previous specific anti-HCV treatment were tracked for disease progression and blood samples were collected at multiple time points. The major clinical parameters of liver function and viral load were tested. A fragment of HCV hypervariable region 1 (HVR1) was amplified and cloned, and the positive clones were sequenced and subsequently analyzed to determine the composition variation of HCV quasispecies during disease progression in relation to the major clinical parameters.

RESULTSA total of 631 HVR1 sequences were acquired from the positive clones. The evolution of HCV HVR1 quasispecies in untreated chronic hepatitis C patients featured 3 patterns of variation in quasispecies composition, namely stable, fast and slow changes during the natural course of chronic hepatitis C. The genetic distance of the quasispecies was found to inversely correlated with ALT (R=-0.438, P=0.011) and AST level (R=-0.500, P=0.003), and sense mutation rate was also inversely correlated with ALT level (R=-0.387, P=0.026) and AST level (R=-0.410, P=0.018). No significant association was found between HCV load and any clinical or virological parameters.

CONCLUSIONDue to individual differences and immune pressure, HCV quasispecies can present with different patterns of evolution in the natural disease progression of chronic hepatitis C. HCV quasispecies evolution, due to its close correlation with the biochemical parameters, can be used to evaluate the severity and prognosis of chronic hepatitis C.

Base Sequence ; Disease Progression ; Genetic Variation ; Hepacivirus ; genetics ; Hepatitis C, Chronic ; virology ; Humans ; Viral Load

OBJECTIVE: This study examined gender differences on sociodemographic factor and clinical feature among patients with schizophrenia and the impact of family history on gender differences of clinical course and clinical characteristics. METHOD: Patients who admitted to Seoul National Mental Hospital from March 1996 to September 1996 and met the diagnostic criteria for schizophrenia by DSM-N were studied. The number of patients was 177(92 men and 85 women), among them with family history of first degree relatives schizophrenia was 33(13 men 20 women). Sociodemographic factor, age of onset, duration of illness, number of admission, dosage of antipsychotics(chlorprormazine equivalent), past history of suicidal attempts and clinical symptoms assessed by Brief psychiatric Rating Scale(BFRS) and Positive and Negative Syndrome Scale(PANSS) were compared by gender. Furthermore, gender differences of clinical features were compared by presene or absence of family history. RESULTS: There were no gender differences in education, religions, occupational status, family history, duration of illness, number of admission, dosage of drugs, suicidal attempts and clinical subtypes, but more female schizophrenic patients were married and age of onset was significantly earlier in male patients. In clinical symptoms were compared with PANSS, negative type is significantly more in male patients but positive type is more in female, with BPRS, perceptul-thought disturbance factor and anxiety-depression factor were significantly higher in female patients. The age of onset was no significantly different in family history positive group but significantly earlier onset of male patients in negative group. Clinical symptoms with BFRS were no significant differences in family history positive group, but perceptual-thought disturbance factor and anxiety-depression factor were higher in female patients in negative group. CONCLUSIONS: The findings coupled with reports from other investigators, support that both gender and genetic loading contribute to the heterogeneity of schizophrenia.
Age Factors ; Age of Onset ; Education ; Employment ; Female ; Genetic Load ; Hospitals, Psychiatric ; Humans ; Male ; Population Characteristics ; Research Personnel ; Schizophrenia ; Seoul

OBJECTIVETo evaluate polymorphisms and forensic efficiency of 22 non-binary single nucleotide polymorphism (SNP) loci.

METHODSOne hundred ethnic Han Chinese individuals were recruited from Dongguan, Guangdong. The 22 loci were genotyped with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS).

RESULTSNine loci were found with a single allele, 4 loci were found to be biallelic, whilst 9 loci were found to have 3 alleles. For 13 polymorphic loci, the combined discrimination power and power of exclusion were 0.999 98 and 0.9330, respectively. For the 9 non-biallelic loci, the combined discrimination power and power of exclusion were 0.9998 and 0.8956, respectively. For motherless cases, the combined power of exclusion was 0.6405 for 13 polymorphic SNPs and 0.6405 for 9 non-binary SNPs.

CONCLUSIONNon-binary loci have a greater discrimination power and exclusion power per SNP.

Alleles ; Asian Continental Ancestry Group ; genetics ; China ; Female ; Gene Frequency ; Genetic Load ; Genetics, Population ; Genotype ; Humans ; Male ; Polymorphism, Single Nucleotide

BACKGROUND: Dopamine and serotonin receptors are candidate genes for the genetic study of schizophrenia because of their implication in the pathophysiology and etiology of schizophrenia (serotonine- dopamin hypothesis). A population-based association study was performed between schizophrenics and normal controls to identify the susceptibility genes. METHODS: A total of 145 schizophrenics and 242 normal controls were recruited. Ser9Gly polymorphism of DRD3, 12 bp repeat of DRD4, and 102T/C of HTR2A were selected as candidate polymorphism. The molecular techniques such as polymerase chain reaction (PCR)-restriction fragment length polymorphism and PCR-polyacrylamide gel electrophoresis were used. Chi-square analysis was performed to find any differences between two groups and logistic linear regression was tested to evaluate the interaction between three genes. RESULTS: There were no significant differences in allele frequencies and genotype frequencies of the three genetic polymorphism. Stratified by sex, the difference of DRD4 allele (P=0.065) and HTR2A allele (P=0.083) and genotype (P=0.054) was observed between male patients and controls; also noted was the difference of HTR2A genotype (P=0.080) between female patients and controls. Stratified by age of onset, the difference in the linear trend of DRD3 between early-onset patients and normal control (P=0.003) was observed. Stratified by family history, the difference in the linear trend of DRD4 (P=0.008) was also observed. Logistic linear regression with 90 patients who had early-onset phenotype (< or =20 year-old) or family history showed a significant result in interaction term (P=0.053). CONCLUSIONS: The finding that there were significant results only after stratification may imply a different genetic load on each subgroup of the disease. The interaction of genes between DRD3, DRD4, and HTR2A in a subgroup with supposedly high genetic background may support the serotonindopamine hypothesis. This, however, should be verified hereafter in large-scale studies.
Age of Onset ; Alleles ; Dopamine ; Electrophoresis ; Female ; Gene Frequency ; Genetic Load ; Genotype ; Humans ; Linear Models ; Male ; Phenotype ; Polymerase Chain Reaction ; Polymorphism, Genetic* ; Receptors, Serotonin ; Schizophrenia*

OBJECTIVETo determine the complementary determining region 3 (CDR3) length diversity of T cell receptor Vbeta repertoires of CD8+ T lymphocytes and to explore its association with viral load in individuals with HIV-1 infection.

METHODSSeparation of CD8+ T cells from peripheral blood mononuclear cells (PBMCs) was carried out by using immunomagnetic beads coated with anti-CD8 antibody. Total RNAs from the purified CD8+ T lymphocytes were isolated and used to perform polymerase chain reaction (PCR) amplifications in CDR3 of 22 T cell receptor (TCR) gene families. CDR3 diversity and its association with viral load in individuals with HIV-1 infection were analyzed.

RESULTSAn average diversity for all CDR3 profiles in CD8+ T cells from 9 HIV-infected individuals was significantly different as compared to 7 age-matched healthy donors (P<0.05) with the HIV-infected individuals losing diversity in the CDR3 profiles. There was positive correlation between changes in TCR CDR3 diversity and viral load (r=0.771, P<0.05). The changes in CDR3 length diversity of Vbeta families in HIV-infected individuals, particular in Vbeta2, Vbeta4, Vbeta5, Vbeta17, Vbeta20, Vbeta21, Vbeta23, Vbeta24, were statistically different from the healthy controls.

CONCLUSIONHIV-1 infection might induce the loss of TCR Vbeta repertoire diversity and disrupt the CDR3 distributions within CD8+ T cells. There should be positive correlation between changes in TCR CDR3 diversity and the viral load in HIV-1 infected patients.

CD8-Positive T-Lymphocytes ; immunology ; HIV Infections ; genetics ; virology ; HIV-1 ; immunology ; Humans ; Polymorphism, Genetic ; Receptors, Antigen, T-Cell ; genetics ; Viral Load

Adult ; CD4 Lymphocyte Count ; Cell Line, Tumor ; Female ; HIV-1 ; classification ; physiology ; Humans ; Male ; Middle Aged ; Receptors, CCR5 ; physiology ; Receptors, CXCR4 ; physiology ; Recombination, Genetic ; Viral Load

OBJECTIVETo study the relationship between metastasis or recurrence of hepatocellular carcinoma (HCC) and hepatitis B virus (HBV) DNA load or the presence of double mutation at 1762/1764 in the basic core promoter (BCP).

METHODSOne-hundred-and-fifty-seven patients with HCC were included in the study. Events of tumor metastasis or recurrence were recorded during 120 weeks of clinical follow-up after treatment by surgery or transarterial chemoembolization (TACE). The 1-year follow-up included monthly alpha fetoprotein (AFP) measurement and abdominal ultrasonography (US), as well as helical computed tomographic (CT) scan performed every 3 months. Follow-up beyond 1-year (surveillance) included AFP measurement and abdominal US every 2 months and helical CT scan every 6 months. Suspected metastasis or recurrence was investigated by hepatic angiography and confirmed according to the combined imaging findings. Serum HBV DNA level was measured by real-time PCR. HBV genotypes were determined by PCR-restriction fragment length polymorphism analysis.

RESULTSOf the 157 HCC cases 110 experienced tumor metastasis or recurrence; the cumulative probability of post-treatment HCC metastasis or recurrence was 4 (2.55%) at week 12, 14 (8.92%) at week 24, 28 (17.83%) at week 48, 64 (40.76%) at week 72, 92 (58.60%) at week 96, and 110 (70.06%) at week 120. Multivariate analysis indicated that both the BCP 1762/1764 double mutations and HBV DNA levels were risk factors for HCC recurrence or metastasis. In particular, the incidence of HCC recurrence or metastasis increased with baseline serum HBV DNA levels in a dose-response manner, ranging from 8/19 (42.1%) for less than 3 log10 copies/ml HBV DNA to 35/61 (57.3%) for 3-5 log10 copies/ml and 67/77 (87.0%) for more than 5 log10 copies/ml. After adjusting for potential confounders, serum HBV DNA level remained independently associated with HCC metastasis or recurrence. HCC recurrence or metastasis occurred in 22/43 (51.2%) of patients without BCP 1762/1764 mutations and 88/114 (77.2%) of patients with BCP 1762/1764 mutations. The adjusted odds ratio for patients infected with BCP 1762/1764 double mutation HBV, compared with those infected with non-BCP 1762/1764 mutation HBV, was 5.264 (95% CI: 1.436-12.574, P less than 0.05).

CONCLUSIONInfection with HBV carrying the BCP 1762/1764 double mutation and presence of high HBV DNA load are independent risk factors for developing HCC metastasis or recurrence after surgery or TACE.

Adult ; Aged ; Carcinoma, Hepatocellular ; pathology ; virology ; DNA, Viral ; blood ; Female ; Genotype ; Hepatitis B Core Antigens ; genetics ; Hepatitis B virus ; genetics ; Humans ; Liver Neoplasms ; pathology ; virology ; Male ; Middle Aged ; Mutation ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Promoter Regions, Genetic ; Viral Load

OBJECTIVETo study the polymorphisms and secondary structure of human immunodeficiency virus (HIV-1) tat exon 1 among subtype B' and B'/C HIV-1 infected people in China and to explore the relationship between the polymorphism of tat exon 1 and the disease progression.

METHODS8 subtype B' and 5 B'/C HIV-1 infected patients with slow disease progression were selected from Liaoning, Jilin and Yunnan province. 26 subtype B' and 9 B'/C HIV-1 infected patients with similar sex, age but with typical disease progression were selected. Provirus was extracted from the whole blood. The gene sequences of the Tat exon 1 were amplified by nest-polymerase chain reaction (nest-PCR). Products were purified and sequenced directly. The sequences were aligned, translated, amino acid substitution were analyzed and secondary structures were predicted.

RESULTSMany amino acid substitution could be found in the exon 1 of Tat in HIV-1 subtype B' and B'/C recombinant strain infected persons with different disease progression except A58T,none of them showed definitely relationship with HIV viral load and disease progression. 23N, 31S, 32Y and 46F were subtype-specific substitutions. No characteristic secondary structure of exon 1 of Tat was found.

CONCLUSIONSome of the mutations of tat exon 1 might be related to HIV viral load and disease progression. However, there was no relationship found between the secondary structure of Tat protein and the disease progression.

Acquired Immunodeficiency Syndrome ; genetics ; pathology ; Amino Acid Substitution ; Disease Progression ; Exons ; genetics ; Genes, tat ; genetics ; HIV Infections ; genetics ; pathology ; Human Immunodeficiency Virus Proteins ; genetics ; Humans ; Polymorphism, Genetic ; Viral Load

OBJECTIVETo investigate the variations of HCV core and E2 region epitopes during transfusion of activated immune cells.

METHODSFour patients receiving transfusion of activated immune cells were under continuously observation. HCV titers were measured by quantitive PCR. HCV core and E2 regions were cloned and sequences were analyzed by computer software.

RESULTSDuring the follow-up the serum ALT levels and the HCV virus titers fluctuated greatly in each of these persons. After transfusion, no significant variations were observed in HCV core and E2 coding regions.

CONCLUSIONSThe alteration of host immune attacks could induce the fluctuations of HCV load without any mutations in the currently observed coding genes of the epitopes.

Adult ; Aged ; Alanine Transaminase ; blood ; Epitopes ; genetics ; Female ; Genetic Variation ; Hepacivirus ; genetics ; Hepatitis C, Chronic ; blood ; therapy ; virology ; Humans ; Immunotherapy ; Male ; Middle Aged ; Viral Core Proteins ; genetics ; Viral Envelope Proteins ; genetics ; Viral Load