OBJECTIVETo observe the dynamic levels of serum Golgi protein 73(GP73) in patients prior to and after the onset of liver cancer, and to explore the related factors.

METHODSFrom 2007 to 2012, a periodical screening program was carried out in a group of high risk population with positive Hepatitis B surface antigens (HBsAg) , twice a year. Their serum specimens from every screening time point were kept in Qidong Biobank until liver cancer was diagnosed. Thirty-nine patients with liver cancer were recruited for the study, each of them at least had three times of specimens collected as well as B ultrasound scan (BUS) exam results at onset of disease and within 30 months before diagnosed, amongst 6 time points. In total, there were 162 specimens collected to test GP73 by double-antibody sandwich enzyme-linked immuno-sorbent assay (ELISA). Statistical analyses of time series and differences among groups were performed by stata software 10.

RESULTSThe average value of 39 patient's GP73 at the time point of liver cancer onset was (126.77 ± 73.73) µg/L, while the values at the other five time points prior to the onset were (128.32 ± 81.18) , (129.97 ± 83.62) , (127.38 ± 80.10) , (135.52 ± 97.88) and (138.24 ± 93.58) µg/L, respectively, with no significant difference (F = 0.07, P = 0.997). No obvious changing trends of GP73 were observed among the 39 liver cancer cases at the 6 time points. All 162 samples were divided into two groups: without hepatic cirrhosis (63 samples) and with cirrhosis (99 samples) according to findings of B-ultrasonic wave; whose average GP73 values were separately (97.16 ± 51.39) and (151.20 ± 91.68) µg/L. The difference showed statistical significance (F = 18.22, P < 0.01). Furthermore, if we grouped the samples by the average value of GP73 at 130.19 µg/L, then there were only 1/14 of the subjects without hepatic cirrhosis having higher GP73 values, but 12 of the 25 subjects with hepatic cirrhosis having higher GP73 values. The difference showed statistical significance (P = 0.013). The results of Linear regression model also showed that there was no correlation between GP73 and time series (t = 0.75, P = 0.455), but significant correlation between GP73 and hepatic cirrhosis (t = 4.30, P < 0.01).

CONCLUSIONNo significant changes of the dynamic levels of GP73 could be found among the liver cancer patients within 30 months prior to the onset of disease. GP73 values of the patients with liver cancer may depend on their background of hepatic diseases; and hepatic cirrhosis might be one of the main influencing factors or confounding factors.

Biomarkers, Tumor ; blood ; Carcinoma, Hepatocellular ; blood ; Humans ; Liver Neoplasms ; blood ; Membrane Proteins ; blood ; Retrospective Studies

To investigate the developmental changes of human erythrocytes, adult and fetal erythrocyte membranes prepared from adult and cord blood were analyzed in regard to their proteins, glycoproteins, enzyme activities and glucose transport systems. 1. Adult and fetal erythrocyte membranes appeared to have the same major proteins and gl-ycoproteins in the electrophoretic pattern. 2. ATPase activity in adult erythrocyte membranes was lower than that of fetal erythrocyte membranes, whereas adult cholinesterase was higher. No significant change was observed in the activities of alkaline and acid phosphatases during development. 3. Glucose uptake was higher in fetal erythrocytes than in adult erythrocytes, suggesting some loss of glucose carrier system during devlopment. The results suggest that the major structural proteins in human erythrocyte membrane relatively unchanged while some functional proteins such as membrane enzymes and carrier proteins in transport systems are markedly changed during development.
Adenosine Triphosphatases ; Adult ; Carrier Proteins ; Cholinesterases ; Erythrocyte Membrane ; Erythrocytes* ; Fetal Blood ; Glucose ; Glycoproteins ; Humans* ; Membrane Proteins* ; Membranes* ; Phosphoric Monoester Hydrolases

OBJECTIVETo investigate the value of a disintegrin and metalloproteinase 12 secreting form (ADAM12-S) as a maternal serum marker in second trimester screening for trisomy 21 (Down syndrome, DS), and to develop an appropriate prenatal DS screening protocol.

METHODSSerum samples were collected from 53 pregnant women carrying a trisomy 21 fetus and 621 pregnant women with matched gestational age and weight carrying a healthy fetus. ADAM12-S concentrations were determined with a time-resolved fluorescence immunoassay (TRFIA). Curve fitting by weighted regression and other statistical methods were conducted, and the model was optimized for prenatal trisomy 21 screening program in second trimester. ADAM12-S alone or in combination with other two- or three-combination test was selected as a serum marker for prenatal second-trimester screening of trisomy 21 by calculation of detection rate (DR) and false positive rate (FPR).

RESULTSBy comparison, the median multiple of the median (MoM) value of ADAM12-S in DS pregnancy group was higher than that of the control group (P< 0.01). When FPR = 5%, the DR of ADAM12-S was 28.3%, and the positive and negative likelihood ratios were 5.66 and 0.75, respectively. The DR of three-combination test of ADAM12-S, alpha-fetoprotein (AFP) and free beta subunit of human chorionic gonadotropin (β-HCG) has increased to 52.80% from 39.62% of the conventional two-combination test (AFP and free β-HCG). For women with a risk between 1/300 and 1/1000 by two-combination test for DS, the DR has increased from 39.62% to 47.12%, but FPR only increased by 0.8% after adding ADAM12-S as a maternal serum marker.

CONCLUSIONConsidering the increased DR of pregnancies with a risk between 1/300 and 1/1000 in second trimester, ADAM12-S may provide a feasible maternal serum maker when combined with AFP and free β-HCG. The cost-effectiveness ratio is reasonable.

ADAM Proteins ; blood ; ADAM12 Protein ; Biomarkers ; blood ; Disintegrins ; blood ; Down Syndrome ; blood ; diagnosis ; enzymology ; Female ; Humans ; Membrane Proteins ; blood ; Pregnancy ; Pregnancy Trimester, Second ; Prenatal Diagnosis ; methods

Objective To explore the clinical characteristics of autoimmune disease with dual seropositive antibodies of leucine-rich glioma inactivated 1(LGI1)and contactin-associated protein 2(Caspr2).Methods The clinical data of seven patients with dual seropositive LGI1 and Caspr2 antibodies who were admitted to the Neurology Department of Peking Union Medical College Hospital from July 2014 to December 2017 were retrospectively analyzed.Results Central,peripheral and autonomic nervous systems were all involved in the seven cases;100%(7/7)presented with insomnia,myokymia,neuropahic pain and hyperhydrosis;71%(5/7)showed memory decline or psychiatric and behavioral symptoms;57%(4/7)had urinary hesitation or constipation;and 43%(3/7)had seizure.Electromyography showed 100%(6/6) of the patients had prolonged afterdischarges following normal M waves and/or abnormal spontaneous firing.Electroencephalography revealed slow waves or basic rhythm slowing in 71%(5/7)of patients.Electrocardiography showed sinus tachycardia,axis deviation,and prolonged QT intervals in 71%(5/7)of patients.One patient died from arrhythmia before immunotherapy.One died from pulmonary infection after immunotherapy.Improvement with immunotherapy was documented in the other five cases.No relapse was noted during the 1-2-year follow-up.Conclusions Autoimmune disease with dual seropositive antibodies of LGI1 and Caspr2 can diffusely affect the central,peripheral,and autonomic nervous systems.The possibility of this disease should be considered in patients with acute and subacute onset of neuropsychiatric symptoms,especially in patients with accompanying insomnia,myokymia,and hyperhydrosis.
Autoantibodies ; blood ; Autoimmune Diseases ; immunology ; Humans ; Membrane Proteins ; immunology ; Nerve Tissue Proteins ; immunology ; Proteins ; immunology ; Retrospective Studies

OBJECTIVETo study the association of ORMDL3 single nucleotide polymorphisms (SNP) with lysophosphatidylcholine (LysoPC) and apolipoprotein B (apoB) levels.

METHODSA total of 300 children diagnosed with bronchial asthma between January 2010 and December 2012 were selected for the asthma group, and 298 children diagnosed with upper respiratory tract infection in the same period were selected for the control group. Serum LysoPC and apoB levels were measured using enzyme-linked immunosorbent assay. Genotype analysis was performed using the TaqMan probe.

RESULTSLysoPC and apoB levels were significantly higher in the asthma group than in the control group (P<0.01). Among children with various genotypes of ORMDL3 gene at locus rs12603332, the asthma group had significantly higher LysoPC and apoB levels than the control group (P<0.01). Among the children with asthma, those with CC genotype had significantly higher LysoPC and apoB levels than those with CT and TT genotypes (P<0.01).

CONCLUSIONSLysoPC and apoB may intervene in the pathological process of asthma. Pro-inflammatory gene ORMDL3 SNP rs12603332 may be associated with high LysoPC and apoB levels, which leads to the occurrence of childhood asthma.

Apolipoproteins B ; blood ; Asthma ; blood ; genetics ; Child ; Child, Preschool ; Female ; Humans ; Lysophosphatidylcholines ; blood ; Male ; Membrane Proteins ; genetics ; Polymorphism, Single Nucleotide

OBJECTIVETo investigate changes in endogenous bactericidal/permeability-increasing protein (BPI) levels and their significance in patients with surgical sepsis.

METHODSIn the prospective study, 19 surgical patients with infection were involved. The plasma BPI, lipopolysaccharide-binding protein (LBP) and interleukin-6 levels were measured on post-infected days 1, 3, 5, 7 and 14 by an enzyme-linked immunosorbent assay (ELISA). Plasma endotoxin concentrations were determined by the modified chromogenic Limulus Amebocyte Lysate (LAL).

RESULTSCompared with normal controls, significant lower plasma BPI/LBP ratios were observed in septic patients on days 1 to 5 after infection (P < 0.01), and in severe septic patients on days 1 to 7 (P < 0.01). Moreover, plasma BPI/LBP ratios were much lower in severe sepsis than those in sepsis on days 1 to 3 after infection (P < 0.05).

CONCLUSIONSPlasma BPI and LBP levels increased rapidly after infection, but BPI/LBP ratios were significantly decreased during sepsis. Plasma BPI/LBP ratios appear to be closely related to the severity of sepsis in patients complicated by surgical infection.

Acute-Phase Proteins ; Adolescent ; Adult ; Antimicrobial Cationic Peptides ; blood ; Blood Proteins ; Carrier Proteins ; blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Interleukin-6 ; blood ; Male ; Membrane Glycoproteins ; blood ; Middle Aged ; Postoperative Complications ; blood ; microbiology ; Prognosis ; Prospective Studies ; Sepsis ; blood

Hypertension is closely related to salt and water retention. The kidney plays an important role in the blood pressure regulation primarily to modulating tubular sodium and water reabsorption. The regulation of the salt and water balance depends upon an array of solute and water channels in the renal tubules. An altered regulation of sodium and water channels in the kidney may be related to various pathological conditions associated with altered salt and water retention. This review will discuss renal handling of sodium and water, with particular emphasis on aquaporins and renal sodium transporters and channels.
Aquaporins ; Blood Pressure ; Handling (Psychology) ; Hypertension ; Kidney ; Membrane Transport Proteins ; Retention (Psychology) ; Sodium ; Water

OBJECTIVETo explore whether SLC25A13 gene mutation exists and what is its mutation spectrum in mainland Chinese infants with intrahepatic cholestasis and abnormal blood amino acids.

METHODSBlood amino acids were analyzed by mass chromatographic analysis in infants referred to Fudan University Children's Hospital from June 2003 to June 2007 for investigations of intrahepatic cholestasis of unknown origin. SLC25A13 gene mutations were studied in 14 children whose serum levels of citrulline and/or methionine were at least two times above the upper normal range. In patients in whom only one mutation was detected, all other exons and their neighboring sequences were then analyzed.

RESULTSEight patients with SLC25A13 gene mutations, including 2 with compound heterozygous mutation 851del4/1638ins23, one with homozygous mutation 851del4/851del4, one with compound heterozygous mutation 851del4/R184X, one with homozygous mutation IVS6+1G more than A/IVS6+1G more than A, and 3 with heterozygous mutation 851del4 were found.

CONCLUSIONSSLC25A13 gene mutations exist in Chinese infants with intrahepatic cholestasis and abnormal blood amino acids. Their mutation spectrum is different from that in Japan. 851del4 is the most common mutation in our study. IVS6+1G more than A is a mutation that has not been reported before.

Amino Acids ; blood ; Cholestasis, Intrahepatic ; blood ; genetics ; DNA Mutational Analysis ; Humans ; Infant ; Infant, Newborn ; Mitochondrial Membrane Transport Proteins ; genetics ; Mutation

Citrin is a liver-type mitochondrial aspartate-glutamate carrier encoded by the SLC25A13 gene, and its deficiency causes adult-onset type II citrullinemia and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). Here, the authors investigated clinical findings in Korean infants with NICCD and performed mutation analysis on the SLC25A13 gene. Of 47 patients with neonatal cholestasis, three infants had multiple aminoacidemia (involving citrulline, methionine, and arginine) and galactosemia, and thus were diagnosed as having NICCD. Two of these three showed failure to thrive. The laboratory findings showed hypoproteinemia and hyperammonemia, and liver biopsies revealed micro-macrovesicular fatty liver and cholestasis. The three patients each harbored compound heterozygous 1,638-1,660 dup/ S225X mutation, compound heterozygous 851del4/S225X mutation, and heterozygous 1,638-1,660 dup mutation, respectively. With nutritional manipulation, liver functions were normalized and catch-up growth was achieved. NICCD should be considered in the differential diagnosis of cholestatic jaundice in Korean infants.
Amino Acids/blood ; Calcium-Binding Proteins/*deficiency ; Cholestasis, Intrahepatic/*etiology/genetics ; Citrullinemia/genetics ; Humans ; Infant ; Membrane Transport Proteins/genetics ; Mitochondrial Proteins/genetics ; Mutation ; Organic Anion Transporters/*deficiency

OBJECTIVETo investigate ORMDL3 polymorphisms in children with asthma in Hunan, China, and to determine the relationship between ORMDL3 polymorphisms and serum osteopontin (OPN) and transforming growth factor-β1 (TGF-β1) levels.

METHODSPeripheral blood samples were collected in children with asthma (n=98; astma group) or without asthma (n=30; control group) from Hunan, China. The asthma group was subdivided into atopic (n=62) and non-atopic (n=36) subgroups. Single nucleotide polymorphism (SNP) analysis was performed, and serum OPN and TGF-β1 levels were measured.

RESULTSThere were no significant differences in genotype and allele frequencies of rs7216389 of the ORMDL3 gene between the asthma and control groups. The serum level of OPN in the asthma group was significantly higher than in the control group (P<0.05). Both the atopic and non-atopic subgroups showed increased serum levels of OPN compared with the control group (P<0.05). The serum level of TGF-β1 in the atopic subgroup was significantly higher than in the control group (P<0.05). The serum levels of OPN and TGF-β1 showed no significant differences in asthmatic children with different genotypes. The serum levels of OPN and TGF-β1 were in a positive linear correlation in the asthma group (r=0.620; P<0.01) and its two subgroups (r=0.734, 0.649 respectively; P<0.01).

CONCLUSIONSIn children from Hunan, China, the SNP (rs7216389) of ORMDL3 is not related to asthma susceptibility. OPN and TGF-β1 may be involved in the development of asthma, and they are in a positive linear correlation. The SNP (rs7216389) of ORMDL3 does not influence the expression of OPN and TGF-β1, suggesting that it may not be associated with airway remodeling.

Airway Remodeling ; Asthma ; blood ; genetics ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Membrane Proteins ; genetics ; Osteopontin ; blood ; Polymorphism, Single Nucleotide ; Transforming Growth Factor beta1 ; blood