Hereditary transferrin system in healthy subjects and schizophrenic patients]

Hereditary polymorphism of transferrin is studied by means of starch gel electrophoresis in a group of healthy inhabitants of Minsk (250 persons) and in a group of schizophrenic patients (128 persons). It is concluded that the inhabitants of Minsk do not differ considerably from the population, living in the European territory by distributing the frequency of transferrin alleles. No considerable differences are found between the group of healthy people and schizophrenic patients.     

A study of the mechanisms of proteinuria in nephritis and chronic renal failure

This study was carried out on 50 patients suffering from renal disorders; 30 nephritis patients and 20 chronic renal failure patients. Twenty-four healthy persons were used as a control group. In order to cast some light on the degree of the impaired glomerular permeability with respect to the blood proteins, selectivity of proteinuria was assessed by means of the clearance of albumin, ceruloplasmin, transferrin, and haptoglobin. Disturbances in the metabolism of these proteins were observed and discussed in light of the proteinuria selectivity index. The demonstration of the selective proteinuria in the presence of haptoglobin was concluded to be indicative of the degree of impaired glomerular permeability in nephritis and chronic renal failure.     

Metabolic changes in blood in pulmonary tuberculosis patients from various blood groups

285 Patients suffering from the respiratory tract organs primary tuberculosis were subjected to the tests on definition of blood groups according to AB0 system, as well as its total proteolytic activity, alpha 1-antitrypsin, ceruloplasmin, general haptoglobin, lysozyme, malonic dialdehyde and diene conjugates levels were estimated. The sick persons as compared with the healthy ones were defined to reveal a tendency to increase of the persons with 0(I)- and B(III)-blood groups and decrease of those ones with A(II)-groups. Independently on the pulmonary tuberculosis patients phenotypic index their tested blood biochemical indices levels increase. As an exception is the proteolytic activity of the persons with B(III)- blood group, and also alpha 1-antitrypsin and lysozyme--with 0(I) and AB(IV) groups, in this case their rates failed to exceed the norm confidential interval. The blood metabolic parameters were defined as independent on its group.     

N-linked glycan changes of serum haptoglobin β chain in liver disease patients

Human haptoglobin is a serum glycoprotein secreted by the liver with four potential N-glycosylation sites on its β chain. Many studies have reported glycan changes of haptoglobin in diseases such as breast cancer and pancreatic cancer. The objective of our study is to analyze N-linked glycan alterations of serum haptoglobin β chain obtained from patients with the hepatitis B virus (HBV), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). MALDI-QIT-TOF mass spectrometry revealed the intensity of m/z 1809.6, identified as a fucosylated glycan, was much higher in samples from patients with LC and HCC relative to the patients with HBV and healthy controls. Compared with LC patients, triantennary glycan was elevated and the biantennary structure was decreased in the haptoglobin β chain of HCC patients. Thus, alterations in the glycan structure of the haptoglobin β chain may constitute significant spectral signatures of cirrhosis and HCC disease.     

Haptoglobin types among the population of western Kazakhstan and their relation to humoral factors of body resistance

Among 803 healthy persons examined, 20.4% of Russians and 18.1% of Kazakhs had Hp 1-1 phenotype, 50.0 and 49.3%, respectively, had Hp 2-1 and 29.6 and 32.6% had Hp 2-2 phenotype. The frequency of Hp1 and Hp2 genes is 0.455 and 0.429, 0.545 and 0.571 (p less than 0.05) for Russians and Kazakhs, respectively. The correlation is established between the haptoglobin type and the level of haemolysins. For example, the latter is greater in number in the organisms of persons possessing the Hp2 gene, especially, when in homozygotic state.     

Galectin-1-binding glycoforms of haptoglobin with altered intracellular trafficking, and increase in metastatic breast cancer patients

Sera from 25 metastatic breast cancer patients and 25 healthy controls were subjected to affinity chromatography using immobilized galectin-1. Serum from the healthy subjects contained on average 1.2 mg per ml (range 0.7-2.2) galectin-1 binding glycoproteins, whereas serum from the breast cancer patients contained on average 2.2 mg/ml (range 0.8-3.9), with a higher average for large primary tumours. The major bound glycoproteins were α-2-macroglobulin, IgM and haptoglobin. Both the IgM and haptoglobin concentrations were similar in cancer compared to control sera, but the percentage bound to galectin-1 was lower for IgM and higher for haptoglobin: about 50% (range 20-80) in cancer sera and about 30% (range 25-50) in healthy sera. Galectin-1 binding and non-binding fractions were separated by affinity chromatography from pooled haptoglobin from healthy sera. The N-glycans of each fraction were analyzed by mass spectrometry, and the structural differences and galectin-1 mutants were used to identify possible galectin-1 binding sites. Galectin-1 binding and non-binding fractions were also analyzed regarding their haptoglobin function. Both were similar in forming complex with haemoglobin and mediate its uptake into alternatively activated macrophages. However, after uptake there was a dramatic difference in intracellular targeting, with the galectin-1 non-binding fraction going to a LAMP-2 positive compartment (lysosomes), while the galectin-1 binding fraction went to larger galectin-1 positive granules. In conclusion, galectin-1 detects a new type of functional biomarker for cancer: a specific type of glycoform of haptoglobin, and possibly other serum glycoproteins, with a different function after uptake into tissue cells.     

Proteomic tracking of serum protein isoforms as screening biomarkers of ovarian cancer

Epithelial ovarian cancer is the fourth leading cause of cancer death among women. Due to the asymptomatic nature and poor survival characteristic of the disease, screening for specific biomarkers for ovarian cancer is a major health priority. Differentially expressed proteins in the serum of ovarian cancer patients have the potential to be used as cancer-specific biomarkers. In this study, proteomic methods were used to screen 24 serum samples from women with high-grade ovarian cancer and compared to a control group of 11 healthy women. Affigel-Blue treated serum samples were processed either by linear (pH 4-7) or narrow range (pH 5.5-6.7) IEF strips for the first dimension. Proteins separated in first dimension were resolved by 8-16% gradient SDS-PAGE. Protein spots were visualized by SYPRO Ruby staining, imaged by FX-imager and compared and analyzed by PDQuest software. Twenty-two protein spots were consistently differentially expressed between normal and ovarian cancer patients by resolving proteins in a linear pH strip of 4-7 for the first dimension. Six of the protein spots, significantly up-regulated in grade 3 ovarian cancer patients (p < 0.05), were identified by MALDI-TOF MS and Western blotting as the isoforms of haptoglobin precursor. When serum proteins were resolved on narrow pH range strips (5.5-6.7), 23 spots were consistently differentially expressed between normal and grade 3 ovarian cancer patients. Of these, 4 protein spots significantly down regulated in grade 3 ovarian cancer patients (p < 0.05) were identified by MALDI-TOF MS and Western blotting, as isoforms of transferrin precursor. Increased expression of serum haptoglobin and transferrin was also identified in peritoneal tumor fluid obtained from women diagnosed with grade 2/3 ovarian cancer (n = 7). Changes in the expression of haptoglobin and transferrin in the serum of women with different pathological grades of ovarian cancer was examined by one-dimensional Western blotting method. Serum samples collected from women suffering from benign, borderline, grade 1, grade 2 and grade 3 cancer (n = 4 for haptoglobin and n = 5 for transferrin in each group) were analyzed and compared to the serum of normal healthy women. The mean serum haptoglobin expression in grade 3 ovarian cancer patients was fourfold higher than in the control subjects (p < 0.05). On the other hand, transferrin expression in grade 3 ovarian cancer patients was decreased by twofold than in normal healthy women (p < 0.05). Haptoglobin expression in the serum of cancer patients (n = 7) decreased following chemotherapy (six cycles of taxol/carboplatin). Concomitant with the decrease of haptoglobin, transferrin expression remained constant in four patients, but increased in three out of seven patients included in the study. Changes in serum expression of haptoglobin correlated with the change of CA 125 levels before and after chemotherapy. In conclusion, proteomic profiling of differentially expressed proteins in the sera of normal women compared to women with ovarian cancer can greatly facilitate the discovery of a panel of biomarkers that may aid in the detection of ovarian cancer with greater specificity.     

Dynamics of immunological indices in patients with chronic viral hepatitis B and the effect of thymalin therapy

The work deals with the results of the study of T-lymphocytes and their subpopulations (active, thermostable, theophylline-sensitive and theophylline-resistant) in 102 children with chronic viral hepatitis B, depending on the effectiveness of thymalin therapy. The sensitization of lymphocytes to specific antigens was studied. Among patients with chronic viral hepatitis B and cirrhosis of the liver the homozygous phenotype of haptoglobin is registered essentially more frequently (63.6% and 82.4% respectively) than among healthy persons (44.0%). The patients of this group showed a decrease in the number of T-lymphocytes, disturbances in the suppressor/helper ratio: hypersuppression in persisting hepatitis and hyposuppression in active hepatitis. In 71.6% of cases thymalin therapy produced an effect manifested by clinico-biochemical remission, an increase in the number of T-lymphocytes, thermostable cells and the normalization of the T-suppressor/T-helper ratio. In these patients sensitization to HBsAg essentially decreased (from 30.5% to 13.9%), while sensitization to human liver lipoprotein retained its high level even after treatment with thymalin.     

Reevaluation of <Emphasis Type="Italic">Pholiota squarrosa</Emphasis> lectin-reactive haptoglobin as a pancreatic cancer biomarker using an improved ELISA system

An increase in Lewis- and core-type fucosylation of haptoglobin has been reported in patients with pancreatic cancer (PC), suggesting that fucosylated haptoglobin is a candidate PC biomarker. Previously, we developed a Pholiota squarrosa lectin antibody enzyme-linked immunosorbent assay (PhoSL-ELISA) system for the detection of core-fucosylated haptoglobin. However, with this methodology, positive results were only obtained for some patients with PC, demonstrating the need for a more sensitive detection system. In the current study, we developed an improved PhoSL-ELISA system with higher sensitivity to detect core-fucosylated haptoglobin using high-concentration urea as a denaturing agent with lectin to facilitate detection. We then reevaluated the performance of PhoSL reactive-core-fucosylated haptoglobin (PhoSL-HP) as a PC biomarker using the improved PhoSL-ELISA system. PhoSL-HP levels in the sera of patients with PC were significantly higher than those in healthy volunteers, with an area under the curve (AUC) value of 0.753. Furthermore, the AUC value of CA19–9 improved from 0.793 to 0.907 when combined with PhoSL-HP. Additionally, several CA19–9-negative cases among the patients with PC were diagnosed as positive for PhoSL-HP. In conclusion, PhoSL-HP detection using our improved ELISA system might allow PhoSL-HP to serve as a potential biomarker for PC and thus might be useful to complement the detection of CA19–9 in PC diagnosis.     

Proteomic Analysis of Haptoglobin and Amyloid A Protein Levels in Patients with Vivax Malaria

Advancements in the field of proteomics have provided great opportunities for the development of diagnostic and therapeutic tools against human diseases. In this study, we analyzed haptoglobin and amyloid A protein levels of vivax malaria patients with combinations of depletion of the abundant plasma proteins, 2-dimensional gel electrophoresis (2-DE), image analysis, and mass spectrometry in the plasma between normal healthy donors and vivax malaria patients. The results showed that the expression level of haptoglobin had become significantly lower or undetectable in the plasma of vivax malaria patients due to proteolytic cleavage when compared to healthy donors on 2-DE gels. Meanwhile, serum amyloid A protein was significantly increased in vivax malaria patient''s plasma with high statistical values. These 2 proteins are common acute phase reactants and further large scale evaluation with a larger number of patient''s will be necessary to establish the possible clinical meaning of the existential changes of these proteins in vivax malaria patients. However, our proteomic analysis suggests the feasible values of some plasma proteins, such as haptoglobin and serum amyloid A, as associating factor candidates for vivax malaria.     

Polymorphic blood systems in children with bronchial asthma

Predisposition to bronchial asthma depends to a large extent on the genotype norm of the children organism reaction, associates with the phenotype of blood group A and haptoglobin Nr 2-2. Persons with blood group B and haptoglobin Nr 1-1 are predisposed to the development of inflammation in the lungs to a greater extent than persons with other blood groups of the ABO system and haptoglobin.     

Identification of disease-associated proteins by proteomic approach in ankylosing spondylitis

Ankylosing spondylitis (AS) is a chronic systemic inflammatory disorder of the axial skeleton and shows significant inherited susceptibility. Auto-immune responses have been traditionally considered as a putative pathogenetic event in AS. However, no consistent self-antigen has been identified to responsible for the disorders in AS to this day. In this study, serum protein profiles of AS patients and healthy controls from a large Chinese AS family were investigated by two dimensional electrophoresis analysis. A group of four highly expressed protein spots was observed in all AS patients' profiles and subsequently identified as isoforms of haptoglobin precursor (pre-Hp) by ESI-Q-TOF MS/MS. Increased expression of haptoglobin precursor were also observed in sera of sporadic AS patients. Moreover, bioinformatics analysis revealed epitopes derived from haptoglobin precursor with high affinity binding to HLA-B( *)2705, a primary subtype associated with AS. These results indicate that pre-Hp may be involved in the pathogenesis of AS.     

Identification of haptoglobin and apolipoprotein A-I as biomarkers for high altitude pulmonary edema

We have investigated the plasma proteome using 2D gel electrophoresis and matrix-assisted laser desorption/ionization tandem time of flight from patients with high altitude pulmonary edema (HAPE). A complete proteomic analysis was performed on 20 patients with HAPE and ten healthy sea level controls. In total, we have identified 25 protein spots in human plasma and found that 14 of them showed altered changes in HAPE patients, which mainly were acute phase proteins (APPs), compliment components, and apolipoproteins among others. Among the APPs, haptoglobin α2 chain, haptoglobin β chain, transthyretin, and plasma retinol binding precursor showed overexpression in HAPE patients as compared to controls. To validate the result of proteomic analysis, two proteins were selected for enzyme-linked immunosorbent assay and Western blotting analysis. Our data conclusively shows that two proteins, haptoglobin and apolipoprotein A-I are upregulated in plasma of HAPE patients. These proteins may provide a fast and effective control of inflammatory damage until the subsequent mechanisms can begin to operate. Taken together, our findings further support the hypothesis that inflammatory response system is linked to the pathophysiology of HAPE.     

Clinical significance of oxidation and acetylation genetic polymorphism in patients with hyperthyreosis

INTRODUCTION: The relationship between genetically determined polymorphic oxidation and acetylation and susceptibility to some disease was aroused much interest. The aim of our study was to evaluate whether patients with hyperthyreosis differ from healthy persons in their ability to oxidize sparteine and acetylate sulphadimidine as model drugs. Oxidation and acetylation were estimated in 48 patients with hiperthyreosis. MATERIAL AND METHODS: The control group consisted of 160 healthy volunteers for comparison of oxidation phenotype and 60 healthy volunteers for comparison of acetylation phenotype. The phenotyping of oxidation revealed two distinct populations among 40 patients with hyperthyreosis: 38 persons (95%) were extensive metabolizers (EM) of sparteine and 2 persons (5%) was poor metabolizers (PM). In 160 healthy persons (91.2%) were EM and 14 persons (8.8%) were PM. The difference between frequency distribution of PM and EM in healthy persons and in patients with hyperthyreosis was not statistically significant. RESULTS: The phenotyping of acetylation showed among 48 patients with hyperthyreosis 8 persons (13%) were rapid acetylators (RA) and 40 persons (87%) were slow acetylators (SA). In 60 healthy volunteers the phenotype of rapid acetylation was observed in 31 persons (51%) and slow acetylation in 29 persons (49%). Relative risk (odds ratio) of development of thyroid diseases was 5.34 times higher for SA in comparison to RA. The prevalence of SA among patients with hyperthyreosis in comparison to healthy volunteers was statistically significant (p < 0.0002). CONCLUSIONS: The results of our study may suggest that slow acetylation phenotype is associated with increased risk of the development of hyperthyreosis.     

Qualitative and quantitative variation of serum proteins in fluorosis patients

Comparison between patients with occupational fluorosis, a group of healthy workers, and a sample from the general population revealed differences in concentrations of some polymorphic serum proteins. These differences depended on phenotypes of patients. TF 1-2, PI 1-2, and HP 2-1 patients exhibited a decreased concentration of transferrin (TF), a decreased concentration of proteinase inhibitor (PI), and an increased concentration of haptoglobin (HP), respectively.     

Epidemiological problems of ozena and the means for controlling this infection

Clinical, bacteriological, serological and epidemiological studies of ozena morbidity among the population of Minsk were carried out in 1970-1980. On January 1, 1981, the ozena morbidity rate among the inhabitants of Minsk was 26.72%. Ozena was found to affect mainly children and women. A wide spread of the family foci of this disease (31.68%) was revealed. The results of this study indicate that the source of K. ozaenae is a sick person who begins to excrete the bacteria in the prodromal period of the disease and may continue to excrete them for many years. The transfer of K. ozaenae occurs probably by droplet or contact infection. The droplet infection is less active in the absence of symptoms (coughing, sneezing) facilitating excretion of the infective agent into the air and in cases of the low susceptibility of persons to ozena. The main measures for controlling ozena are the timely detection and sanitation of the sources of ozena, as well as the current disinfection of the infection foci in apartments.     

Serum proteome of leprosy patients undergoing erythema nodosum leprosum reaction: regulation of expression of the isoforms of haptoglobin

Validated proteome profile allows better understanding of disease progression, subtype classification, susceptibility patterns, and disease prognosis. Leprosy is a spectral disease, with clinically, histologically, immunologically, and bacteriologically distinguishable subtypes. In addition, a significant fraction of patients undergo immune mediated reactions even after multidrug therapy (MDT). Erythema nodosum leprosum (ENL) is an immune complex mediated reactional condition in leprosy, characterized by a systemic inflammatory condition afflicting borderline lepromatous (BL) and lepromatous leprosy patients (LL). In this study, we have analyzed serum proteome of leprosy patients undergoing ENL reactions and compared it with that of healthy noncontact controls. Depletion of albumin and immunoglobulin G (IgG) was optimized using Aurum serum protein mini kit (Bio-Rad), and then two-dimensional gel electrophoresis (2-DE) of these serum samples was performed. Differentially expressed proteins were identified by MALDI-TOF and MALDI-TOF MS/MS mass spectrometry. Significant increase in one of the isoforms of alpha2 chain of haptoglobin was observed in ENL condition. In addition, haptoglobin phenotype was determined for healthy controls and leprosy patients. Hp 0-0 phenotype was detected in 21.4% of the ENL patients undergoing treatment, which on follow up examination showed typable phenotype, thus showing a condition of acquired anhaptoglobinemia. Since ENL still remains a threat to leprosy disease management, the above findings may provide new insights in understanding the development and progression of this inflammatory condition.     

Serum antibodies of periodontitis patients compared to the lipopolysaccharides of Porphyromonas gingivalis and Fusobacterium nucleatum

Serum antibody titers against the lipopolysaccharides (LPSs) of Porphyromonas gingivalis and Fusobacterium nucleatum were compared between 9 periodontitis patients and 24 healthy persons. The IgG titers against the LPSs of P. gingivalis ATCC 33277(T) and W50 were clearly higher in the patients than in the healthy persons. However, IgM titers against the LPSs of P. gingivalis strains were relatively low, and no significant difference was observed between the patients and healthy persons. On the other hand, IgG and IgM titers against the LPS of Fusobacterium nucleatum JCM 8532(T) in some patients were significantly higher than those in the healthy persons, although the difference in IgG titers was not large compared to that of the LPS of P. gingivalis. These results suggest that the antibody measurement of patients' sera against the LPS of periodontal bacteria can be applied for the diagnosis of periodontitis.     

Acute-phase response in dairy cows with acute postpartum metritis

The diagnostic value of 2 plasma acute-phase proteins, haptoglobin and alpha1-acid glycoprotein, and plasma N-acetyl-beta-D-glucosaminidase enzyme activity were studied in 29 newly calved dairy cows. Nineteen had developed acute metritis with putrid vaginal discharge within 2 wk after calving; 10 were clinically healthy controls. Plasma haptoglobin concentration remained low in most cows with acute postpartum metritis. Only the 3 most severely affected cows exhibited a strong haptoglobin response. These were later culled due to poor condition and reduced fertility. This suggests that in acute uterine infection a highly increased haptoglobin concentration indicates poor prognosis for repeat conception. Plasma alpha1-acid glycoprotein concentration increased in acute postpartum metritis, the response pattern being less prominent than that for haptoglobin. The alpha1-acid glycoprotein concentrations did not correlate with severity of disease, and, consequently, the capacity of alpha1-acid glycoprotein in differentiating genital infections was relatively poor. The highest alpha1-acid glycoprotein concentrations were detected in cows with retained placenta and/or dystocia. Plasma N-acetyl-beta-D-glucosaminidase activity levels did not differ between the cows with acute postpartum metritis and healthy control cows.     

Serum protein polymorphisms in patients with primary Sj?gren's syndrome

The distribution of 4 serum proteins, the protease inhibitor alpha-1-antitrypsin, haptoglobin, transferrin and group-specific component or vitamin D-binding protein, were examined in 26 patients with primary Sj?gren's syndrome and 208 healthy donor controls. No significant associations were found between any of the 4 systems and susceptibility to primary Sj?gren's syndrome.