Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “HAPTOGLOBINS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 541 records · Page 30Linked to original sources
PubMedDate not supplied

Repeated large-dose haptoglobin therapy in an extensively burned patient: case report.

The case of a 24-year-old man who sustained a 100% body surface area burn and inhalation injury is presented. Hemoglobinuria reappeared 2 hours after haptoglobin was first administered. In addition to individualized fluid resuscitation and plasma administration, a large dose of haptoglobin was repeatedly administered while we monitored for occult blood in the centrifuged urine. As a result, postburn shock and acute renal failure were prevented.

Acute Kidney Injury↗
PubMed1990

Three independent insertions of retrovirus-like sequences in the haptoglobin gene cluster of primates.

The human haptoglobin two-gene cluster (HP-HPR) contains two retrovirus-like elements. One (RTVL-Ia) is in the first intron of the HPR gene, and the second (RTVL-Ic) is at the 3'-end of the gene cluster. The chimpanzee three-gene cluster (HP-HPR-HPP) contains an additional, third copy (RTVL-Ib) in the intergenic region between HPR and HPP. RTVL-Ia and RTVL-Ib are essentially full size and have the general structure, 5'-LTR-gag-pol-env-3'-LTR, while RTVL-Ic lacks about one-third of its 5'-part. Although none of the elements has retained long open reading frames, we could detect stretches having amino acids identical to various parts of Moloney murine leukemia virus (Mo-MuLV) proteins. We conclude that the RTVL-I elements were derived from a virus very similar in structure to Mo-MuLV. The DNA sequences surrounding the insertion points of the three RTVL-I elements are not alike and allow the inference that they integrated into the haptoglobin gene cluster independently at some time after the initial formation of the triplicated gene cluster in primates. Comparison of the nucleotide sequences of the three elements leads to the hypothesis that foreign DNA introduced into the genome can initially accumulate mutations more rapidly than the genomic sequences surrounding it.

Amino Acid Sequence↗
PubMed2004

Haptoglobin phenotypes and malaria infection in pregnant women at delivery in western Cameroon.

Plasmodium falciparum-infected erythrocytes have been reported to sequester in the placenta by adhering to chondroitin 4-sulfate during pregnancy. Earlier studies have highlighted higher susceptibility of primigravidae to P. falciparum compared to multigravidae living within the same endemic areas. The haptoglobin phenotype (Hp1-1) has been associated with susceptibility to severe P. falciparum malaria and the presence of Hp in human endometrium has been reported. The possible role of different Hp phenotypes in susceptibility to or protection from placental infection by P. falciparum in both primigravid and multigravid women at delivery in western Cameroon was investigated in this study. Only the three major haptoglobin phenotypes; Hp1-1, Hp2-1 and Hp2-2, were found in the study population with the Hp1-1 phenotype being the predominant (53%). There was no significant difference in the distribution of the three Hp phenotypes between the two gravidity groups. Women carrying the Hp1-1 phenotype had higher parasite prevalences in both peripheral blood (21.6% against 9.1%) and placentas (42% against 16.7%) when compared to those with the Hp2-2 phenotype. The difference in the parasite density between women carrying the Hp1-1 and Hp2-2 phenotypes was statistically significant for placental infection (P=0.001) but not for maternal peripheral blood infection. Placental parasitaemias without peripheral blood parasitaemias were detected in 42.6% of all the P. falciparum positive women while 27.7% of the women had peripheral blood parasitaemias in the absence of placental infection and 29.8% of the women had both placental and peripheral blood parasitaemias. A statistically significant difference was observed between the primigravidae and multigravidae in the parasite density in placental biopsies (P=0.02) but not for maternal peripheral blood parasitaemia. Our data suggest that the Hp1-1 phenotype may play a role in susceptibility to placental infection by P. falciparum during pregnancy.

Adult↗
PubMed2004

Haptoglobin phenotype and prevalent coronary heart disease in the Framingham offspring cohort.

BACKGROUND: The haptoglobin (Hp) locus is polymorphic with two major alleles denoted 1 and 2. Several recent prospective longitudinal studies have demonstrated conflicting results regarding whether there is an increase or decrease in the relative risk of coronary heart disease (CHD) conferred on individuals homozygous for the haptoglobin 1 allele (Hp 1-1). METHODS: We sought to examine the relationship between Hp type and prevalent coronary heart disease in a cross-sectional study from a large community-based cohort, the Framingham Heart Offspring Study (n = 3273). RESULTS: Overall we found no relation between Hp type and CHD prevalence. In secondary analyses we found a different pattern of Hp type and CHD prevalence by diabetes status. In nondiabetics, compared with Hp 1-1, Hp 2-1 (OR 1.71, 95% CI 1.03, 2.83) was associated with excess prevalence of CHD. In contrast in diabetic individuals we observed the opposite pattern; Hp 2-1 (OR 0.49, 95% CI 0.24, 0.99) and Hp 2-2 (OR 0.46, 95% CI 0.22, 0.96) were associated with diminished prevalence of CHD. CONCLUSIONS: These data are consistent with an interaction between Hp type and diabetes in the prevalence of CHD. These findings will need to be confirmed in other cohorts and in longitudinal studies.

Cohort Studies↗
PubMed2004

Oxidized low-density lipoprotein, iron stores, and haptoglobin polymorphism.

BACKGROUND: In vitro experimental studies demonstrated that iron promotes free radical-induced low-density lipoprotein (LDL) oxidation. OBJECTIVE: To test the hypothesis that circulating oxidized LDL (oxLDL) levels might be associated with body iron stores (serum ferritin) and iron-related genetic markers (hemochromatosis gene C282Y mutation, haptoglobin polymorphism). METHODS: We investigated 381 (176 males, 205 females, age 45 +/- 6 years) healthy Caucasians. Serum oxLDL, assayed by a mAb-4E6-based enzyme-linked immunosorbent assay (ELISA), was expressed as oxLDL/LDL ratio to adjust for serum LDL-cholesterol concentration. Hemochromatosis gene C282Y mutation analysis was performed by a Taqman-based polymerase chain reaction (PCR) assay. Haptoglobin (Hp) phenotypes (Hp 1-1, Hp 2-1, Hp 2-2) were determined by starch gel electrophoresis. RESULTS: In stepwise multivariate regression analysis, gender (P < 0.0001), current smoking (P < 0.0001), HDL-cholesterol (P = 0.0001), ferritin (P = 0.0051), body mass index (BMI) (P = 0.0063), and Hp phenotype (P = 0.0331) independently predicted oxLDL/LDL ratio in the total group. In men, smoking (P < 0.0001), ferritin (P = 0.0052), Hp phenotype (P = 0.0063), and HDL-cholesterol (P = 0.0127) were independent determinants of oxLDL/LDL ratio. In women, only body mass index (P < 0.0001), HDL-cholesterol (P = 0.0005), and smoking (P = 0.0025) were significantly associated with oxLDL/LDL ratio. The C282Y mutation (wild-type versus C282Y heterozygotes) was not associated with oxLDL/LDL ratio in both sexes. CONCLUSION: Serum ferritin concentration and Hp polymorphism are independently associated with circulating oxLDL levels in males.

Adult↗
PubMed2004

Haptoglobin polymorphism in breast cancer patients form Jordan.

BACKGROUND: Previous reports regarding the occurrence of breast cancer and its association with Hp polymorphism are conflicting. The possible role of family history as a factor in determining the degree of association between the disease and Hp polymorphism has not been reported before. In this study, the distribution of haptoglobin phenotype among patients with familial and nonfamilial breast cancer was investigated. METHODS: Haptoglobin phenotypes were determined in serum of 128 breast cancer patients (familial, n=42; nonfamilial, n=86) and in controls (n=200) by vertical polyacrylamide gel electrophoresis. RESULTS: No significant difference of Hp phenotype distribution was observed between patients as a combined group when compared with the control group. In the familial group, the frequency of Hp1-1 and Hp2-1 phenotype distribution was higher and Hp2-2 was lower than that in the nonfamilial and the control groups. Similar but inversed Hp distribution pattern was observed in the nonfamilial group when compared with that in the other groups. An appreciable finding is the observation that Hp2-2 phenotype frequency in the nonfamilial group was significantly higher than that in the familial group (p=0.0365). CONCLUSIONS: Results of this study demonstrate that the pattern of Hp phenotype distribution in breast cancer patients is family history-dependent. Hp1 and Hp2 allele frequencies were over-represented in patients with familial and nonfamilial breast cancer, respectively. The pattern is probably attributed to genetic and oxidative stress mechanisms.

Adult↗
PubMed2004

Human serum haptoglobin is toxic to Plasmodium falciparum in vitro.

Innate immune responses are important in the control of malaria, particularly in those who have not yet mounted an effective adaptive response. Here we report that the human serum acute phase protein, haptoglobin, is toxic to Plasmodium falciparum cultured in vitro. This effect is phenotype dependent and occurs during the trophozoite phase of the asexual life cycle. We propose that the increased levels of haptoglobin seen in the acute phase response may be protective against malaria in humans.

Animals↗
PubMed1988

An investigation of human oxyhemoglobin beta tetramer dissociation using haptoglobin binding.

Haptoglobin was used as a macromolecular probe to investigate the formation of human oxyhemoglobin beta chain dimers from tetramers in 0.1 M potassium phosphate buffer, 20 degrees C at pH 7 and pH 8. Monitoring of spectral changes upon mixing haptoglobin with beta heme chains (2.5 and 5 micromolar) revealed an overall decrease in absorbance accompanied by a shift of the Soret spectral peak from 415 to 417 nm. The magnitude of the absorbance decrease was proportional to the beta concentration; the time courses consistently yielded greater color at pH 8 than at pH 7. At pH 8, two exponential phases of 0.47 min-1 and 0.084 min-1 were seen whose rates remained invariant with concentration. In contrast, only one exponential process was evident at pH 7, yielding a first order rate constant of 0.21 min-1. We have spectrophotometrically followed the beta chain tetramer to dimer dissociation reaction, thus providing information about the contribution of this step to hemoglobin assembly.

Adult↗
PubMed1997

Analysis of the affinity of each haptoglobin polymer for hemoglobin by two-dimensional affinity electrophoresis.

Using polyacrylamide gel electrophoresis we have often encountered a decrease in the high molecular weight polymers of haptoglobin 2-1 in the serum of patients after transfusion and with hemolytic diseases. Using two-dimensional affinity electrophoresis we have attributed this phenomenon to the high affinity of high molecular weight polymers of the haptoglobin 2-1 for hemoglobin.

Biopolymers↗
PubMed1976

The use of o-dianisidine for serum haptoglobin electrophoresis using cellulose acetate.

1. Due to the carcinogenicity of benzidine, a method by which o-dianisidine is used to stain serum haptoglobin is described. Serum haptoglobin is determined by electrophoresis using cellulose acetate as the medium. 2. A comparison of the two staining systems demonstrates good agreement. 0-Dianisidine can be substituted for benzidine without loss of specificity.

Dianisidine↗
PubMed1999

Haptoglobin polymorphism and peripheral arterial occlusive disease.

Haptoglobin (Hp) 2-2 phenotype is a genetic risk factor in coronary atherosclerosis. In this study, haptoglobin phenotypes were determined in 141 patients with peripheral arterial occlusive disease (PAOD) and compared to a reference population (n = 1000). The relative Hp1 allele frequency was decreased among PAOD patients (0.294 vs. 0.403 for the reference population, P < 0.01) due to an overrepresentation of the Hp 2-2 phenotype (50%, odds ratio 1.82 (95% C.I. 1.28-2.60), P < 0.001). This finding was even more pronounced in non-diabetic and in non-smoking PAOD patients (Hp1 allele frequencies: 0.265 and 0.228, respectively). Serum lipids, inflammatory parameters, and blood pressure levels were comparable among the Hp phenotypes, but serum levels of the antioxidant vitamin C were lower in Hp 2-2 patients than in patients with another phenotype (P < 0.05). In PAOD patients with severe atherosclerotic lesions, maximal walking distance of patients carrying a Hp 2-2 phenotype (225-525 m) exceeded that of other Hp phenotypes (50-242 m) (interquartile ranges) (P < 0.05). The findings demonstrate that, despite an increased risk for developing PAOD, the Hp 2-2 phenotype is associated with a longer maximal walking distance which might be attributed to the earlier reported in vitro angiogenic properties of the Hp 2-2 molecule.

Aged↗
PubMed1996

Haptoglobin polymorphism and chronic hepatitis C.

BACKGROUND/AIMS: Haptoglobin (Hp) is a hemoglobin-binding acute phase protein characterized by a genetic polymorphism due to the existence of two different alleles encoding for the alpha chain of the protein. Three phenotypes have been described: Hp 1-1, Hp 2-1 and Hp 2-2. The latter two forms are known to possess immunoglobulin-like properties and play a role in the immune response. Recently, it has been shown that in subjects suffering from hepatitis C, serum Hp concentrations were lower than in the reference population. In the present study we examined whether the haptoglobin phenotype distribution in chronic HCV patients was different from the reference population. We also looked for possible relationships between Hp phenotypes and hepatitis C virus types and response to interferon alpha therapy. Moreover, Hp concentrations were determined. METHODS: The study population consisted of 239 Caucasian patients with proven hepatitis C. Hp phenotypes were determined using starch gel electrophoresis of hemoglobin-supplemented serum, followed by peroxidase staining. Serum Hp concentrations were assayed with an immunonephelometric method. Hepatitis C virus was genotyped and classified according to an internationally accepted system. Two hundred and twenty healthy Caucasian blood-donors served as the reference population. RESULTS: In the reference population, 35 individuals (15.9%) had Hp 1-1, 106 persons (48.2%) had Hp 2-1 and 79 had Hp 2-2 (35.9%), resulting in an Hp 1 allele frequency of 0.400, which is in agreement with the Hardy-Weinberg equilibrium. Hp phenotype distributions and Hp allele frequencies in the chronic hepatitis C virus patient group differed significantly from those obtained in the reference population. In the patient population, 59 individuals (24.7%) had Hp 1-1, 112 persons (46.9%) had Hp 2-1 and 68 had Hp 2-2 (28.5%). This resulted in an Hp 1 allele frequency of 0.481, which is in agreement with the Hardy-Weinberg equilibrium. No statistically significant differences were found between Hp phenotype distribution and hepatitis C virus types or response to interferon alpha therapy. CONCLUSIONS: The observed shift in Hp phenotype distribution in chronic hepatitis C may point to a role of Hp in the natural evolution of hepatitis C.

Adult↗
PubMed1975

Studies on free or haptoglobin-bound hemoglobin and derivatives (semihemoglobins and porphyrinated semihemoglobins). Some aspects of their peroxidatic activity.

The peroxidatic activity of hemoglobin (Hb) is known to be enhanced when this hemoprotein is bound to haptoglobin (Hp). The peroxidatic reaction (H2O2, guaiacol as donor) has been kinetically studied (Steady-state) in the presence of free or rabbit-haptoglobin bound human hemoglobin and some of its derivatives, all in ferricyano-form. With free Hb+ CN, we observed linearity of Lineweaver and Burk plots in a wide range of concentrations, the donor's behaviour was therefore assumed to obey the Michaelis-Menten mechanism. When Hp-Hb+ CN is the enzyme, the donor's behaviour is more complicated, analysis shows the existence of two kinds of donor's binding sites. The possibility whether this behaviour might correspond to the intrinsic properties of Hb chains, as revealed after combination with Hp, was examined. The peroxidatic activity of free and Hp-bound alpha and beta chains of Hb were studied. The alpha chains of Hb combine with Hp whereas the beta chains fail to do so. In order to make useful comparisons, the peroxidatic activity of Hp-bound alpha and beta chains were studied by the use of Hp-semihemoglobin complexes where the semihemoglobins carried heme on only one type of chain (alpha or beta). Results did not show an evident correlation between the activities of the two free or bound types of chains and those of the two classes of binding sites revealed in Hp-Hb+ CN. Moreover, it appeared that the heme-free complementary chain might influence the activity of the heme-carrying alpha or beta chain in semihemoglobins and Hp-semihemoglobin complexes. The binding or protoporphyrin on free and Hp-bound semihemoglobins leads to species which exhibit structures close to that of Hb and Hp-Hb complex respectivley. Results of studies on these derivatives brought up new interesting data : when the porphyrin ring alone is bound to the heme deficient chains (alpha or beta), in Hp-semihemoglobin complexes, the same peculiar behaviour, already observed with Hp-Hb complex, is found again. The structural implications of these results are discussed.

Animals↗
PubMed1998

Internalization study using EDTA-prepared hepatocytes for receptor-mediated endocytosis of haemoglobin-haptoglobin complex.

We have demonstrated the internalization of haemoglobin-haptoglobin (Hb-Hp) complex using rat hepatocytes prepared by EDTA perfusion, followed by Percoll. The isolated hepatocytes exhibited a saturation curve of the binding of fluorescein isothiocyanate-labelled haemoglobin-haptoglobin complex (FITC-Hb-Hp. Furthermore, competition between the binding of FITC-Hb-Hp and unlabelled Hb to the hepatocytes, was observed. The cells exhibited approximately 9 x 10(4) 'high affinity sites' (Kd approximately 1.2 microM) for the Hb-Hp complex. The data in toto suggest the presence of only one type of receptor i.e. the high affinity receptor (in both affinity and number of sites per cell). The results were similar to those obtained from rat hepatocytes prepared by collagenase digestion [1]. In order to verify whether EDTA-prepared hepatocytes could be used for the study of receptor-mediated endocytosis, the internalization of pre-bound Hb-Hp in the isolated hepatocytes was assessed by two methods. First, acid-insensitive FITC-Hb-Hp time-dependently increased following incubation at 37 degrees C. Secondly, Hb-Hp became inaccessible to the exogenous FITC-anti-haemoglobin antibody. These processes were dependent on ATP, but independent of Ca2+ and stimulated by GTP. The results demonstrate that the receptor-mediated endocytosis of Hb-Hp occurred in the EDTA-prepared hepatocytes.

Adenosine Triphosphate↗
PubMed1976

Kinetics of deoxyhemoglobin subunit dissociation determined by haptoglobin binding: estimation of the equilibrium constant from forward and reverse rates.

Deoxyhemoglobin tetramers dissociate into dimers very slowly, with half-times on the order of several hours. It is demonstrated that absorbance changes in the Soret region which accompany this dissociation and persist upon binding of haptoglobin 1-1 to the dissociated dimers can be used for accurate kinetic determinations over the necessarily long periods required for study. This method of study for the slow reactions depends upon long-term spectral integrity of the reaction mixtures and upon accurate measurement. The variation in rate constants determined by this procedure has been correlated with variations in structural constraints at the dimer-dimer contact region. In the presence of 2,3-diphosphoglycerate the rate constant is decreased, consistent with the role of this effector in binding to both beta chains and stabilizing the constrained deoxy tetramer against dissociation into alphabeta dimers. With hemoglobin specifically modified (des-Arg-141alpha) to eliminate half the constraining salt links within the dimer-dimer contact region, the dissociation rate is increased by approximately three orders of magnitude. In hemoglobin S where the amino acid substitution is not directly in the intersubunit contact region of interest, the dissociation rate is found to be approximately the same as that for hemoglobin A. Combination of the dissociation rate constants determined by haptoglobin binding with stopped-flow determinations of the rate constant for reassociation of dissociated dimers provides an estimate of the equilibrium constant, 0K2, for the deoxyhemoglobin dimer-tetramer equilibrium. This estimate is independent of any assumptions regarding other energetic quantities, and yields a value of 2.54 +/- 0.7 X 10(10)M-1 (heme) in 0.1 M Tris-HCl, 0.1 M NaCl, and 1 mM EDTA, pH 7.4, 21.5 degrees C. Thus the intersubunit contact energy is -14.0 +/- 0.2 kcal/mol of heme. The stabilization energy between deoxy and oxy tetramers is found to be approximately 6.4 kcal/mol, under these conditions.

Binding Sites↗
PubMed2004

Haptoglobin phenotypes differ in their ability to inhibit heme transfer from hemoglobin to LDL.

LDL oxidation plays a pivotal role in atherosclerosis. Excellular hemoglobin (Hb) is a trigger of LDL oxidation. By virtue of its ability to bind hemoglobin, haptoglobin (Hp) serves as an antioxidant. Oxidation of LDL by hemoglobin was analyzed to occur by heme displacement from methemoglobin lodged in LDL. The LDL-associated heme is disintegrated, and iron inserted this way in LDL triggers formation of lipid peroxides. The genetic polymorphism of haptoglobin was found to be a risk factor in the pathogenesis of atherosclerosis. Individuals with Hp2-2 have more vascular incidences as compared to those with Hp1-1. In the current study, oxidation of LDL by metHb was carried out at physiological pH without addition of external peroxides. Hb-derived oxidation of lipids and protein was found to be practically inhibited by Hp1-1 but only partially by Hp2-2. Heme transfer from metHb to LDL was almost completely omitted by Hp1-1 and only partially by Hp2-2. We concluded that partial heme transfer from the Hb-Hp2-2 complex to LDL is the reason for oxidation of LDL lipids as well as protein. These findings provide a molecular basis for Hp2-2 atherogenic properties.

Alkadienes↗
PubMed2006

Study of serum haptoglobin and its glycoforms in the diagnosis of hepatocellular carcinoma: a glycoproteomic approach.

Increased serum haptoglobin concentration and changes in its glycosylation have been reported in certain cancer types. Information for hepatocellular carcinoma (HCC) has not yet been available. In this study, we aimed to carry out a systematic analysis of serum concentrations of haptoglobin (Hp) and its glycoforms in the patients with HCC and noncancer patients only with chronic liver diseases (CLD) and to examine their clinical values. This study was divided into two major parts, (1) measurement of serum Hp concentration, and investigation of its value in the diagnosis of HCC, and (2) quantitative analysis of Hp glycoforms with alpha-2,6-sialylation and/or alpha-1,6-fucosylation by using lectin affinity purification and 2D gel electrophoresis and investigation of their relationships with tumor stage. The concentrations of serum Hp in HCC patients were significantly higher than those in noncancer patients with CLD. With the use of serum concentrations of Hp and alpha-fetoprotein, a logistic regression (LR) model was developed from the training data set and used to classify the validation cases. At a specificity of 95%, the sensitivity for HCC detection was 79%. Comparing serum concentrations of alpha-2,6-sialylated Hp (S-Hp) and alpha-1,6-fucosylated Hp (F-Hp) between HCC and CLD patients suggests that purification of S-Hp and F-Hp could enrich the glycosylation variants associated with HCC. 2D gel analysis of S-Hp and F-Hp identified a total of 18 glycoforms. A unique pattern of Hp glycoforms comprising both hypersialylated fucosylated and hyposialylated fucosylated species was found in the HCC patients. Serum concentrations of these glycoproteins were significantly higher in the patients with advanced tumors, suggesting their tumor-specific nature. We have shown that serum Hp is a potential biomarker in the diagnosis of HCC. The combined use of Hp and AFP could greatly improve the diagnostic accuracy. A unique pattern of Hp glycoforms with altered sialylation and fucosylation is specific to HCC and associated tumor progression.

Adult↗
PubMed1998

Inflammation-induced expression of sialyl LewisX is not restricted to alpha1-acid glycoprotein but also occurs to a lesser extent on alpha1-antichymotrypsin and haptoglobin.

Acute and chronic inflammation-induced expression of sialyl LewisX has already been shown to occur on alpha1-acid glycoprotein. We now demonstrate that this phenomenon is not restricted to alpha1-acid glycoprotein but also occurs on two other acute-phase proteins. ie on alpha1-antichymotrypsin and on haptoglobin. The level of expression of sialyl LewisX on these proteins was lower than on alpha1-acid glycoprotein, in all likelihood because alpha1-acid glycoprotein is the only acute-phase protein containing tetraantennary glycans. No expression of sialyl LewisX was detectable on alpha1-protease inhibitor, a protein with a high diantennary glycan content. Non-sialylated LewisX was not detectable on these major acute-phase proteins in any of the conditions studied. This indicates that the majority of the a3-linked fucose residues are present as sialyl LewisX on alpha1-acid glycoprotein, alpha1-antichymotrypsin and haptoglobin. The absolute contribution to the total phenotype in plasma of protein containing this determinant in a multivalent form was highest for alpha1-acid glycoprotein. This leads us to propose that alpha1-acid glycoprotein is, among the acute-phase proteins studied, the one with the highest potential for interference with the extravasation of leukocytes by binding to the selectins.

Acute-Phase Proteins↗