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[Manifestations of pulmonary tuberculosis concurrent with diabetes mellitus and various haptoglobin phenotypes].

For diagnosis, detection of the specific manifestations of pulmonary tuberculosis (PT) concurrent with diabetes mellitus, 48 patients with insulin-dependent diabetes (IDD) and 132 with noninsulin-dependent diabetes (NIDD), who carry various haptoglobin (Hp) phenotypes were studied. It has been found that PT develops in IDD mainly in 5-10 years and in NIDD in 1-4 years. The gravest course of both types of diabetes is frequently encountered in those having Hp 2-2 phenotypes and slightly less frequently in those with Hp 1-1. The patients having these phenotypes have abnormalities in the levels of glycaric hemoglobin, 2.3-diphosphoglycerol phosphate, in the activity of the enzymes lactate dehydrogenase and glucose-6-phosphate dehydrogenase and acid-alkali imbalance. It is expedient to determine Hp phenotypes to evaluate the severity and prognosis and to choose a treatment policy for comorbidity and the proposed biochemical indices should be more widely used to evaluate carbohydrate metabolic disturbances in PT concurrent with diabetes mellitus.

Adolescent↗

Effect of modification on physico-chemical and biological properties of haptoglobin. Reaction with N-bromusuccinimide and 2-hydroxy-5-nitrobenzyl bromide.

N-Bromosuccinimide and 2-hydroxy-5-nitrobenzyl bromide have been used for modification of tryptophan residues in human haptoglobin (Hp) type 2-1. Modification of three exposed tryptophan residues reduced considerably both the Hp-haemoglobin interaction and binding of the antibody against the native protein. Modification of the remaining 7-8 tryptophan residues resulted in a complete loss of those properties. Antisera directed against Hp with the modified tryptophan residues appeared to be highly specific in immunological reactions.

2-Hydroxy-5-nitrobenzyl Bromide↗

Reference distributions for the positive acute phase proteins, alpha1-acid glycoprotein (orosomucoid), alpha1-antitrypsin, and haptoglobin: a comparison of a large cohort to the world's literature.

Limiting bedside use of positive acute phase protein measurements (alpha1-acid glycoprotein (orosomucoid), alpha1-antitrypsin, and haptoglobin) has been the lack of satisfactory methods for quantifying serum levels and a credible reference material. Great strides have been made in the last few years. The remaining barrier to more relevant and cost-effective use of serum protein data for diagnosis and prognosis is the availability of reliable reference intervals from birth to old age for both males and females. Sixty publications reporting reference intervals have been identified which meet the criteria used in our prior two studies, and these have been analyzed statistically. Previous small studies of these individual proteins agree on average, over their constrained age ranges, with our life-long reference ranges. This meta-analysis provides support for our reference ranges and places them in the perspective of previous publications.

Adolescent↗

In vivo and in vitro effects of magnesium deficiency on hepatic haptoglobin mRNA levels.

We previously showed that haptoglobin (Hp) was increased in the plasma of dietary magnesium (Mg)-deficient rats. The present study was performed to examine the effects of dietary Mg-deficiency and Mg2+ deficit in culture medium on Hp mRNA levels in liver and isolated hepatocytes, respectively. The Hp mRNA level in the liver increased significantly from day 10 to day 30 in rats on a Mg-deficient diet (Mg; 0.001 per cent). In the cultured hepatocytes, lowering the Mg2+ level in the culture medium from 0.92 mM to 0.46 mM did not affect the Hp mRNA level of hepatocytes. When IL-1beta or IL-6 was added to the culture medium, the Hp mRNA level increased much more in the hepatocytes cultured in low Mg2+ medium (Mg2+; 0.46 mM) than in those cultured in the control Mg2+ medium (Mg2+; 0.92 mM). These results suggest that the increase in plasma Hp level during dietary Mg deficiency depends on the increase in Hp mRNA level in the liver, and that this increase in mRNA is not only directly correlated with a low Mg level in plasma, but also indirectly correlated with cytokines.

Animals↗

Correlation between acute phase-related expression of C/EBPbeta and transcriptional regulation of the haptoglobin gene during rat liver development.

The hepatic 35 kD nucleoprotein participates in transcriptional regulation of the haptoglobin gene during the development of rat liver. The same molecular mass and trans-acting role of the above protein as the active isoform of C/EBPbeta transcription factor, made homology between them possible. We could detect C/EBPbeta in control hepatic nuclear extracts not earlier than in the second week after the birth. However, the acute-phase reaction induced the expression of 35 kD-C/EBPbeta at day 7 of postnatal development suggesting that the above trans-active nucleoprotein displays the structural and functional characteristics of C/EBPbeta isoform from that day on.

Animals↗

[Diagnostic criteria of carbohydrate metabolism disorders in pulmonary tuberculosis complicated by diabetes mellitus in patients with various haptoglobin phenotypes].

A total of 180 patients with various haptoglobin (Hp) phenotypes were examined in order to detect specific features of carbohydrate metabolism disorders in pulmonary tuberculosis concomitant with diabetes mellitus. Blood sugar levels, G-6-PDH and LDH, acid-base balance, and 2,3-DPG and HbA1c were evaluated. LDH activity was decreased 1.3-1.7 times in comparison with the norm, G-6-PDH was decreased by 15-45% vs. the norm in 87% patients, acid-base status was imbalanced, HbA1c content was increased 1.5-1.7 times vs. the norm, and 2.3-DPG content was increased 2-3-fold in comparison with the norm in 83% patients. Increased levels of HbA1c and 2,3-DPG in the studied combination of diseases augmented disorders of O2 binding to hemoglobin, which led to hypoxia. The most pronounced shifts in the studied parameters were observed in patients with Hp 2-2 and Hp 1-1. Changes in the studied parameters should be used for the diagnosis of the severity of carbohydrate metabolism disorders in diabetics with pulmonary tuberculosis.

Carbohydrate Metabolism↗

Variability of haptoglobin and alpha 2-macroglobulin in Albino Oxford and Dark Augustin inbred strains of rats before and after trauma.

Increased synthesis of acute-phase proteins (APP) in the liver represents the most prominent aspect of acute phase reaction (APR). Haptoglobin (Hp) and alpha 2-macroglobulin (alpha 2-M) are among the most important APP in rats. In this study AO (Albino Oxford) and DA (Dark Augustin) inbred strains of rats, with different resistance to trauma, were used to compare concentrations of Hp, alpha 2-M, IL-1, IL-6 and TNF, before and after tourniquet trauma. Cytokines IL-1, IL-6 and TNF have an important role in APP gene expression. Our results showed that before trauma, more resistant AO rats had higher concentrations of Hp and alpha 2-M compared to DA rats. The influence of genetic elements of these differences is significant. Tourniquet trauma caused an early increase of IL-1, IL-6 and TNF activities in the serum which preceded the increase in the Hp and alpha 2-M concentrations but differences between strains were not found.

Animals↗

Effect of modification on physico-chemical and biological properties of haptoglobin. Acetylation, iodination and nitration.

Human haptoglobin (Hp) type 2-1 was modified with N-acetylimidazole, iodine or tetranitromethane (TNM), and the ability of the obtained derivatives to form with haemoglobin (Hb) complexes with peroxidase activity, was estimated. At low reagent to protein molar ratios, 11 tyrosine residues were nitrated, 12 acetylated and 13 iodinated. The biological activity of NO2-Hp and I-Hp amounted to 40% of the activity of native Hp whereas the activity of Ac-Hp only to 16%. The derivatives modified at high ratios of N-acetylimidazole or iodine lost the ability to bind with Hb. Deacylation. of tyrosines and partial liberation of acetylated xi-amino groups resulted in partial recovery of the activity. As demonstrated by polyacrylamide-gel electrophoresis, the modification of Hp with high excess of TNM or iodine induced polymer formation

Acetylation↗

HMG-1 as regulatory trans-acting protein in the acute phase-induced expression of the rat liver haptoglobin gene.

Expression of the haptoglobin (Hp) gene is liver specific and acute phase (AP) responsive. It was previously shown that transcriptional induction process of the rat Hp gene during turpentine induced AP response has been mediated by the liver nucleoprotein p29 which was shown to be homologous to the HMG-1 chromatin-associated protein. The results presented in this report offered further evidence for the existence of structural and functional similarities between these two proteins implicating an involvement of HMG-1 in the regulation of the rat Hp gene transcription. By DNA binding assays we found the HMG-1 binding sites in the rat Hp gene cis-regulatory subelements A and C and revealed an increase in its DNA-binding after induction of AP response. In view of our previous and here shown data we assume that this increase could be a consequence of AP-induced release of HMG-1 from the chromatin and subsequent increase in its nuclear amount.

Acute-Phase Reaction↗

Biophysical characterization of albumin preparations from blood serum of healthy donors and patients with renal diseases. Part II: evidence for the enhancement of the haptoglobin. Level at the pathological conditions.

BACKGROUND: Human serum albumin (hSA), the major component in blood plasma, fulfills a fundamental biological role as a universal carrier and reservoir in blood plasma, tissues, and secretions. Because of essential diversity in the bound ligands, hSA was shown to possess significant structural divergence. In the first paper of this series we reported on that albumin-enriched fractions isolated from serum of glomerulonephritis (GN) patients possesses essential blue shift of intrinsic fluorescence. Identification of this component was the major goal of this study. MATERIAL/METHODS: Partially purified SA preparations were isolated from blood plasma of 19 GN patients and 8 healthy donors. These preparations have been analyzed by combination of chromatographic (gel-filtration and hydrophobic sorption) and spectrofluorometric techniques. RESULTS: At least six different albumin enriched fractions were isolated from blood of GN patients. High molecular weight protein fraction with blue shifted intrinsic fluorescence spectrum was segregated. Higher concentration of this fraction may be responsible for higher parameter A values, which is characteristic of protein preparations from GN patients. Amino acid sequence showed that b-haptoglobin is one of the components of this fraction. CONCLUSIONS: Combination of chromatographic methods with monitoring intrinsic fluorescence spectra of albumin-enriched fractions from blood plasma of healthy donors and GN patients represents a useful tool for the description of hSA heterogeneity and for the detection of the changes in the level of disease-related compounds. This approach is also appropriate for the isolation of individual components, different in their parameter A values, from the blood plasma.

Chromatography↗

[Haptoglobin phenotype in patients with spondyloarthritis and healthy individuals].

Haptoglobin (Hp) phenotype distribution was evaluated in 95 patients with seronegative spondylarthritis and 100 normal controls. The incidence of three Hp types was virtually the same in acute patients and controls. Reactive arthritis was associated with Hp2-1 type, psoriatic arthritis with Hp1-1 type, ankylosing spondylarthritis with Hp2-2 type. The authors suggest that the presence of Hp2-2 type is one of genetic factors of seronegative spondylarthritis.

Adolescent↗

Serum haptoglobin concentration in swine naturally or experimentally infected with Actinobacillus pleuropneumoniae.

Serum haptoglobin (Hp) concentrations were measured in swine that were naturally or experimentally infected with Actinobacillus pleuropneumoniae. In swine from a specific-pathogen-free herd, mean serum concentration of Hp (+/- SD) was 5.79 +/- 1.06 mg of cyanmethemoglobin-binding capacity (CHBC)/dl. Serum Hp concentrations in paired samples were measured at 7-day intervals in 40 swine randomly selected from a conventional herd that was experiencing an acute episode of pneumonia and deaths caused by A pleuropneumoniae serotype-5 infection. Day-0 and -7 serum Hp concentrations were 24.58 +/- 1.38 and 23.10 +/- 1.12 mg of CHBC/dl, respectively, with no significant difference between these measurements. In a second conventional herd with a history of chronic infection with A pleuropneumoniae serotype 5, serum concentrations of Hp measured in paired samples obtained 6 days apart were 12.36 +/- 0.81 and 18.63 +/- 0.76 mg of CHBC/dl, respectively, and were significantly (P < 0.05) different from each other. Twenty-nine 12-week-old conventional swine were challenged intranasally with A pleuropneumoniae serotype 1 (n = 19) and serotype 5 (n = 10). Serum Hp concentration increased from prechallenge concentrations of 7.49 +/- 1.38 and 15.10 +/- 1.22 mg of CHBC/dl, respectively, to 41.01 +/- 1.35 and 22.37 +/- 1.78 mg of CHBC/dl, respectively, 72 hours after challenge. For these 29 swine, serum Hp concentration was positively correlated with rectal temperature (r = 0.34; P < 0.001) during the immediate postchallenge period.

Actinobacillus Infections↗

Expression of the rat liver haptoglobin gene is mediated by isoforms of C/EBPalpha, -beta and -delta proteins.

CCAAT/enhancer binding proteins (C/EBP) alpha, -beta and -delta play an important role in mediating I interleukin-6 (IL-6) dependent expression of acute-phase protein (APP) genes in liver during acute-phase (AP) response. Based on the presence of type IL-6 responsive element (IL-6 RE) in the rat haptoglobin (Hp) gene promoter we assumed that some C/EBPalpha, -beta and/or -delta isoforms could mediate the expression of this gene during turpentine-induced AP response. By Western immunoblot and Northern blot assays, we found that turpentine treatment of rats led to a coordinate induction of C/EBPbeta and -delta as well as repression of C/EBPalpha isoforms pool levels in rat liver nuclear extracts (NEs) which was preceded by an adequate alteration of their mRNAs expression in liver. Consequently, results of DNA affinity chromatography revealed that affinity of certain C/EBPalpha isoforms to bind the type I IL-6 RE within the rat Hp gene promoter decreased whereas affinities of certain C/EBPbeta isoforms and C/EBPdelta were increased and induced, respectively. Our data suggest that turpentine-induced alterations of C/EBPalpha, -beta and -delta pool levels and DNA-binding activities can be regarded as an integral part of activation of the Hp gene expression in the course of AP response.

Acute-Phase Reaction↗

[The phenotypes of blood haptoglobin in urolithiasis patients].

Haptoglobin Hp phenotypes were determined in 104 patients with uroliths of different chemical composition and in healthy controls. 98 patients showed one of the three main phenotypes Hp (1-1, 2-1, 2-2). Electrophoretic motilities of protein fractions Hp were found out for the main phenotypes. Hp was not registered or its fraction motility was distinct from the main phenotypes in 6 patients. Hp phenotypes distribution obtained for all the examinees was compared to that of the controls. For healthy and total group of urolithiasis patients, for healthy and having CaPi and HVr nephroliths, the difference was insignificant in contrast to CaOx stones the incidence of which grew in Hp 1-1 carriers (p < 0.05). In view of this, Hp 1-1 phenotype can indicate a risk of oxalate urolithiasis.

Blood Protein Electrophoresis↗

Serum concentration of haptoglobin, adequacy of peritoneal dialysis, and nutrition status of patients with and without diabetes on peritoneal dialysis.

The aim of the present study was to establish a relationship between serum haptoglobin (HTG) concentration, peritoneal dialysis (PD) adequacy, and nutrition status in PD patients with and without diabetes. We measured serum concentrations of HTG, albumin, iron, and cholesterol; platelet count; transferrin saturation (TSAT); weekly Kt/V; and total weekly creatinine clearance (CCr) in 60 patients with and without diabetes who were being treated with continuous ambulatory PD or automated PD. The mean serum HTG concentration in PD patients without diabetes (2.5 +/- 1.2 g/L) was elevated and differed significantly from that in PD patients with diabetes (2.0 +/- 1.1 g/L). In patients without diabetes the correlation of serum HTG concentration with serum albumin level was r = -0.330 (p < 0.030), with platelet count was r = 0.320 (p < 0.040), with serum iron concentration was r = -0.450 (p < 0.002), with TSAT was r = -0.4200 (p < 0.005), and with age was r = 0.337 (p = 0.003). No such relationships were seen in patients with diabetes. In both subgroups, no dependence was seen between serum HTG concentration and weekly Kt/V, total weekly CCr, or serum cholesterol concentration. Serum HTG concentration in PD patients without diabetes may be a valid inflammatory marker. The HTG serum level displays a significant statistical dependence on age, platelet count, and markers of nutrition such as serum albumin level, iron, and TSAT. It does not depend on markers of dialysis adequacy (weekly Kt/V, total weekly CCr) or on serum cholesterol concentration. The serum HTG concentration in PD patients with diabetes is lower than that in patients without diabetes, and it is not related to examined factors of inflammation, nutrition, or adequacy of dialysis.

Adolescent↗

[Determination of phenotypes of haptoglobin and GLM(1) factor of human GM system in stains with admixtures of blood of some fish strains].

It was shown that the phenotypes of haptoglobin (Hg) can not be detected in stains of dried blood of salmon, roach and bream. The results of experimental research of blood of the above fish species are described according to the Cm system. It was proven as possible to identify the human blood in stains with admixtures of blood of the above fish by using the Hp and Cm systems.

Agglutination Tests↗

[Assessment of tuberculosis recurrence risk in phenotyping haptoglobin in patients with post-tuberculous residual changes in the lungs].

Haptoglobin (Hp) phenotyping was carried out in 223 healthy subjects of Moscow and 504 subjects from the inactive groups of a dispensary record who were earlier taken off the record due to recovery. It was found that the occurrence frequency of various Hp types among the healthy population of Moscow corresponds to that of the European region of this country. In groups of subjects with post-tuberculous residual changes accumulation of carriers of homozygous Hp 2:2 occurs at the expense of reduction of Hp 2:2 occurrence frequency. Recurrences of the disease in subjects with post-tuberculous residual changes took place significantly more often in both homozygous Hp variants carriage and had a graver course, which should be taken into consideration in formation of the most threatening high-risk groups of pulmonary tuberculosis recurrences that require special attention and preventive measures.

Adult↗