Abnormalities of serum cholinesterase isozyme in liver cirrhosis and hepatoma (Part II)

The pattern of serum cholinesterase (ChE) isozyme appeared to be characteristically abnormal in liver cirrhosis and hepatoma. In liver cirrhosis an abnormal fast moving peak was observed in 92.5% of fifty three patients studied. Further, diminishing activities of ChE 3 and 4, accompanied by an emergence of weak bands with unusual rates of flow, were noted in 58.5%. The latter abnormality was always associated with the former one. The pattern in hepatoma was essentially the same with liver cirrhosis, though diversity of bands was also present in some cases. It was ascertained that these abnormalities was due to sialic acid content bound to the enzyme, but was not due to production of abnormal enzyme protein moiety. It was suggested by clinical analysis that the degree of the abnormality of the isozyme may be useful for the diagnosis and prognostic evaluation of liver cirrhosis.     

A variant of erythrocyte membrane skeletal protein band 4.1 associated with hereditary elliptocytosis

A family comprising three patients (a mother and two children) with mild hereditary elliptocytosis was studied. Each patient had prominent elliptocytosis, reduced red cell deformability, and normal erythrocyte thermal sensitivity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of the erythrocyte membranes in each patient showed decreased levels of band 4.1 (approximately half of the normal value) and the presence of an additional band migrating below protein band 4.2. This additional band was shown to derive from protein 4.1. Comparative partial proteolytic mapping of protein 4.1 and the additional band revealed a number of common peptides. Enzyme-linked immunoelectrotransfer blots of the patients' erythrocyte membranes using a monoclonal antibody to protein 4.1 revealed that, in addition to protein 4.1, two other bands below protein 4.2 were stained; one of these bands migrated in the same position as the additional band detected in the Coomassie Blue-stained gels. Immunoblotting of the patients' whole cells using the antibody to protein 4.1 revealed that this altered band 4.1 occurred as such in the intact red cell. SDS-PAGE of protein 4.1 purified from one patient showed the presence of two lower molecular weight bands below protein 4.1; the lower band migrated in the same position as the additional band found on SDS-PAGE of the patients' erythrocyte membranes. The patient's purified protein 4.1 displayed a decrease of about 40% in the binding activity with crude spectrin extracted from normal controls. Spectrin-spectrin interactions were normal in the three patients. The additional band present in the patients' red cell membranes probably represents a proteolytic degradation product. This alteration, present both in whole cells and isolated membranes, might affect the intact cells in vivo. We suggest that the patients' erythrocyte membrane instability may be related to the presence of an abnormal protein 4.1 whose modulatory influence on the spectrin-actin interaction in the skeleton is defective.     

肺结核患者血清胆碱酯酶的变化

我们观察了 50例浸润型肺结核患者的血清胆碱酯酶的活性 ,发现肺结核患者血清胆碱酶活力在进展期明显降低 ,而在好转期复升。对象与方法1 .对象 :本组 50例肺结核患者均随机选自我科住院及门诊病人 ,其中男性 33例 ,女性 1 7例 ,平均年龄 39.9岁。均以临床症状、体征、Ｘ线检查及痰抗酸杆菌检查为诊断依据。按照1 998年全国肺结核的分类标准 ,50例患者均属于浸润型肺结核 ,其中进展期 32例 ,好转期 1 0例 ,稳定期 8例。所有患者均排除肝脏疾病以及其它可能引起血清胆碱酯酶活力变化的疾病。以 2 7例健康体检者作为对照组 ,均经过较系统全面…     

A novel variant of transthyretin (Glu89Lys) associated with familial amyloidotic polyneuropathy

We detected a point mutation in the transthyretin (TTR) gene associated with familial amyloidotic polyneuropathy (FAP) in a 57-year old male presenting with sensorimotor polyneuropathy, severe autonomic dysfunction and cardiomyopathy using a non-isotopic RNase cleavage assay (NIRCA). NIRCA suggested that the mutation site was near either amino acid position 58 of mature TTR or the 3′ end of exon 3. Direct DNA sequencing showed both a normal GA G (Glu) and a variantAAG (Lys) codon at amino acid position 89 of mature TTR, which has not been previously reported. The site of this mutation is near the 3′ end of exon 3, consistent with the result of NIRCA. This mutation was also confirmed by polymerase chain reaction-induced mutation restriction analysis (PCR-IMRA).     

Common null variant, Arg192Stop, in a G-protein coupled receptor, olfactory receptor 1B1, associated with decreased serum cholinesterase activity

Aim: Non-functioning single nucleotide polymorphisms (nSNPs) that result in premature termination codons, that is null-alleles of the respective genes, may have phenotypic effects on clinical parameters. We conducted association studies involving several G-protein coupled receptors (GPCRs) that harbor nSNPs, using clinical parameters of liver function in a general population consisting of 2969 Japanese adults. Methods: SNP typings were performed with TaqMan and Invader assays. Quantitative associations between genotypes and clinical parameters were analyzed by analysis of variance. Linkage disequilibrium (LD) was tested by Haploview Version 3.3. Haplotype-based association was performed using the haplo.stats program. Results: A significant correlation (P = 0.0057) was identified between serum cholinesterase activity (CHE) and an nSNP (Arg192Stop) in the olfactory receptor (OR) 1B1 gene, a member of the GPCR gene family. This nSNP was associated with decreased serum CHE (P = 0.0013). LD analysis based on eight selected SNPs at the locus revealed three LD blocks. The Arg192Stop nSNP was located on the second LD block, which covered one-third of the 3'-portion of the gene. Conclusion: These results suggested that the null-allele of OR1B1 might affect metabolism of serum cholinesterase in carriers of this nSNP.     

Alterations of serum cholinesterase in patients with gastric cancer

AIM:To understand the correlation of serum cholinesterase (CHE) activity with gastric cancer and to assess their clinical significance. METHODS:The velocity method was adopted to detect the activity of serum CHE in patients with gastric cancer and in patients with non-malignant tumor as controls. RESULTS:The serum CHE activity in the treatment group was significantly lower than that in the control group with a very significant difference between the two groups (83.3:113.1,P=0.0003). Age was significantly associated with the incidence of gastric caner. CONCLUSION:Serum CHE activity has a close relation with the incidence of gastric cancer.     

OCTN1 variant L503F is associated with familial and sporadic inflammatory bowel disease

PurposeA two-allele haplotype of TC (OCTN1 rs1050152 and OCTN2 -207G→C) is associated with Crohn's disease (CD). The association has been replicated in different populations, but also failed in some studies. The present study is to replicate the association of OCTN1 rs1050152 and examine another variant rs272879 with familial and sporadic inflammatory bowel disease (IBD) in a cohort from central Pennsylvania, USA.MethodsThe study samples (n = 465) included 212 inflammatory bowel disease patients (CD = 115, UC = 97), including 103 familial (CD = 55, UC = 46) and 111 sporadic (CD = 60, UC = 51) IBD, 139 non-IBD family members from a familial IBD registry, and 114 unrelated healthy controls. A total of 12 OCTN1 variants within exonic sequences were examined. Two nonsynonymous SNPs, rs1050152 (L503F) and rs272879 (L395V) were genotyped by a PCR-based RFLP/cRFLP method and statistically analyzed. These samples with an additional 141 unrelated healthy samples were also genotyped for rs1050152 using the SNPlex? Genotyping System.ResultsThe OCTN1 rs1050152 is associated with CD (OR = 1.745, 95% CI = 1.019–2.990, χ² = 4.129, p = 0.042) and with IBD (OR = 1.68, 95% CI = 1.052–2.676, χ² = 4.732, p = 0.030); while the variant rs272879 is not associated with IBD, CD or ulcerative colitis (UC). The distribution of the rs1050152 variant showed a high level of the T allele in male UC (OR = 2.585, 95% CI = 1.139–5.869, p = 0.023) and IBD (OR = 2.039, 95% CI = 1.024–4.059, p = 0.042) patients, and in female CD patients (OR = 2.329, 95% CI = 1.038–5.226, ρ value = 0.039).ConclusionThe present results replicated the association of the OCTN1 rs1050152 (L503F) variant with CD and IBD overall. A weak gender-specific effect of rs1050152 (L503F) on male UC and female CD was observed.     

A novel variant of transthyretin (Glu89Lys) associated with familial amyloidotic polyneuropathy.

We detected a point mutation in the transthyretin (TTR) gene associated with familial amyloidotic polyneuropathy (FAP) in a 57-year old male presenting with sensorimotor polyneuropathy, severe autonomic dysfunction and cardiomyopathy using a non-isotopic RNase cleavage assay (NIRCA). NIRCA suggested that the mutation site was near either amino acid position 58 of mature TTR or the 3' end of exon 3. Direct DNA sequencing showed both a normal GAG (Glu) and a variant AAG (Lys) codon at amino acid position 89 of mature TTR, which has not been previously reported. The site of this mutation is near the 3' end of exon 3, consistent with the result of NIRCA. This mutation was also confirmed by polymerase chain reaction-induced mutation restriction analysis (PCR-IMRA).     

A new transthyretin variant (Ser23Asn) associated with familial amyloidosis in a Portuguese patient.

The detection and characterization of a new transthyretin (ATTR) variant, Ser23Asn, associated with cardiomyopathy in a Portuguese patient with familial amyloidosis is described. Isoelectric focusing (IEF) of serum from the propositus demonstrated heterozygosity for the presence of wild type and variant ATTR. A combination of mass spectrometric (MS) analyses, including electrospray ionization mass spectrometry (ESI MS), high performance liquid chromatography (HPLC)/ESI MS and matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) performed on the serum-derived TTR were used to identify and locate the amino acid replacement in the variant protein. Genetic mutation analysis by DNA sequencing and allele-specific PCR confirmed this finding.     

Family of a patient with serum cholinesterase deficiency.

A-39-year-old man was admitted to our hospital because of a markedly decreased level of serum cholinesterase found incidentally by a blood test. Detailed examination did not reveal severe liver disease, malignant tumor, infection or organophosphate compound poisoning. Investigation of three generations of his family revealed two homozygous and five heterozygous family members with the cholinesterase deficiency gene E1s indicating familial serum cholinesterase deficiency.     

Primary structure of an amyloid prealbumin variant in familial polyneuropathy of Jewish origin.

The complete amino acid sequence of three related amyloid proteins (Mr 14,000, 10,000, and 5,000) derived from tissues of a Jewish patient who suffered from a variant of familial polyneuropathic amyloidosis was determined. The protein, which contains 127 residues, is identical to a human serum prealbumin subunit. Only one amino acid substitution, glycine for threonine, was detected at position 49, where enzymatic cleavage occurred, yielding Mr 5,000 and 10,000 fragments which represent the amino terminus (residues 1-48) and carboxyl terminus (residues 49-127) of the molecule, respectively. Thus, a prealbumin variant and its fragments constitute the amyloid fibrils in a heredofamilial amyloidosis syndrome of dominant inheritance.