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Effect of inhibited endocytosis in sinusoidal liver cells on catabolism of equine haptoglobin and haemoglobin in the hen.

Catabolism of equine haptoglobin (Hp), haptoglobin-haemoglobin complex (Hp-Hb) and haemoglobin (Hb) in the hen was studied in the liver reticuloendothelial system (RES) in which endocytosis of protein was inhibited by aggregated denatured albumin (Agr-Alb). Intravenous injection of Agr-Alb together with equine [125I]Hp, [125I]Hp-Hb or [125I]Hb partially inhibited elimination of these proteins from hen circulation. The decrease of clearance was less pronounced when the labelled proteins were introduced 30 min after Agr-Alb injection due to stimulation of phagocytosis in RES by Agr-Alb. Elimination of equine proteins (Hp, Hp-Hb and Hb) from hen circulation by RES is only one of the possible metabolic fates of these proteins.

Albumins↗

Plasma haptoglobin levels in vacuum extracted neonates.

In order to examine the pathogenesis of neonatal hyperbilirubinemia associated with vacuum extraction, we have compared plasma haptoglobin and bilirubin levels and blood hematocrits of vacuum extracted neonates with those of newborns who underwent a normal vaginal delivery. Plasma haptoglobin and blood hematocrits of the 12 vacuum patients measured on the third day of life were significantly lower (21.7 +/- 5.3 vs. 46.5 +/- 7.5 mg%; p value less than 0.01 and 52.3 +/- 1.3 vs. 59.7 +/- 1.8%; p value less than 0.005, respectively) than the 12 control patients (values are mean +/- SEM). This trend was apparent whether or not cephalhematoma was present after vacuum extraction: However, the mean bilirubin level was significantly higher than the controls only when cephalhematoma was present. Those results suggest that the higher incidence of neonatal hyperbilirubinemia previously observed after vacuum extraction, is the result of an increased hemolysis of blood sequestered in scalp lesions. Since evidence for enhanced RBC destruction has been demonstrated whether or not cephalhematoma was present, the possibility of hyperbilirubinemia should be anticipated in any case of vacuum delivery.

Bilirubin↗

[Decreased binding by isolated rat hepatocytes of asialo-haptoglobin after combination with hemoglobin].

The desialilation of 125I-labelled haptoglobin unmasks non-reducing galactose which has become terminal and permits its recognition and binding by isolated hepatocytes. However, the prior formation of an asialohaptoglobin-haemoglobin complex diminishes this property considerably. The explanation suggested is that there could either be a structural rearrangement of the complexed asialo-haptoglobin or steiric hindrance due to a masking of the galactose by the haemoglobin.

Animals↗

Haptoglobin types in ovarian tumors.

Haptoglobin types were determined in 132 patients with cancer of ovaries and 114 patients with nonmalignant tumors of the ovaries, respectively. In comparison with a normal population significant increase in the frequency of Hp1 gene in the both pathological groups was observed. It was mostly reflected in a lower occurrence of haptoglobin type 2-2.

Adolescent↗

[Effects of various factors on the formation and properties of sheep haptoglobin-hemoglobin complexes].

The effects of pH, urea, Na-DS and various ions on the hemoglobin-binding capacity of haptoglobin (Hp) of sheep and on the properties of the Hb-Hp complex were studied. It was found that the optimal conditions for the Hb-Hp complex formation are pH values within the range of 4.5--7.0. The peroxidase activity of the complex has its maximum at pH 4.3. A comparative study of the stabilizing effects of Hp from sheep and other species on the hemoglobin molecule was carried out. It was suggested that the properties of the Hm-Hp complex depend on specific differences of haptoglobin within the complex. Urea, Na-DS and sulfate ions produce an inactivating effect, while tetraborate anions--an activating effect on the formation and stability of the complex. This is probably due to the interaction of these compounds with the Hp molecule which changes Hp reactivity and the properties of the Hb-Hp complex.

Animals↗

Haptoglobin phenotypes in leprosy.

Serum haptoglobin phenotypes were studied in 80 patients with leprosy classified according to the criteria of Ridley and Jopling. The distribution of phenotypes was: 2-2, 65%; 2-1, 27.5%; 1-1, 1.25%; and 0-0, 6.25%. This distribution was not significantly different from the controls except for the phenotype 0-0 (p less than 0.02). Thus, although this genetic marker did not correlate with the occurrence of the variety of disease, it is possible that leprosy caused inhibition of haptoglobin synthesis and therefore an apparent increased frequency of the 0-0 phenotype. Evidence for such a secondary anhaptoglobinemia was available in one case.

Haptoglobins↗

Purification and characterization of a haptoglobin-hemoglobin complex isolated from human fetuses.

A haptoglobin-hemoglobin complex was purified from human fetuses (10-week-old pregnancies). The yield was 12% and the purification factor was about 450. The purified complex appears to have a molecular weight of 850,000 daltons. It cross-reacts with human adult haptoglobins. Its electrophoretic mobility was reduced from alpha 2- to beta-globulin when compared with the adult molecule.

Female↗

[Study of various serum proteins in lung cancer. Immunoglobulins A, G, M, haptoglobin, alpha-1-antitrypsin, alpha-2-macroglobulin].

A statistical study of the plasma concentration of immunoglobulin, alpha-1-antitrypsin, haptoglobin, and alpha-2-macroglobulin in 153 patients with primary carcinoma of the lung showed a strong increase in alpha-1-antitrypsin, haptoglobin and A and C immunoglobulins, whilst alpha-2-macroglobulin increases very moderately, and IgM does not vary. The relationships between variables are also modified, thus there appears a correlation between IgA and IgG to the detriment of the IgG/IgM relationship. Furthermore the coefficient of the correlation IgG/alpha-2-macroblobulin is lower in cancer patients.

Female↗

[Concentrations of haptoglobin and free hemoglobin in preserved whole blood].

In bank blood, red blood cells are destroyed and free hemoglobin increases during preservation. Concentrations of haptoglobin and free hemoglobin were measured in 73 packages of preserved whole blood which had been kept for various periods, 1 to 21 days. Those blood samples were divided into 7 groups depending on preserved period, 1 to 3, 4 to 6, 7 to 9 days, and so on. Total haptoglobin decreased to less than 100 mg.dl-1 in the blood preserved over 7 days. Total hemoglobin increased with the passage of preserved period. Free hemoglobin appeared in 40% or more of the blood preserved over 7 days and its concentration increased depending on preserved time. Free hemoglobin of 10 mg.dl-1 or more was detected in the blood preserved over 7 days. It is recommended that for massive blood transfusion the whole bank blood under 7 days of preservation should be used.

Blood Preservation↗

[Quantitative study of the genetics of haptoglobin levels].

A quantitative study, based on several African and Pyrenean populations led to the estimate of the effect of some factors on haptoglobin rate: it shows an influence of age and electrophoretic phenotype, but no apparent effect of sex. Moreover, this study led to the conclusion that there is heritability of haptoglobin rate.

Age Factors↗

[Genetic polymorphism of haptoglobin and quantitative changes in its levels during exposure to asbestos].

The polymorphism and serum levels of haptoglobin were studied in asbestosis patients, in the control and the workers exposed to asbest. Hp1-1 has the highest, Hp2-2--the lowest and Hp2-1 has the intermediate concentration of this protein. In the course of contact with asbest, and especially in asbestosis patients, the haptoglobin levels are higher (for all phenotypes). The standard deviation from the Hp concentration in asbestosis patients was significantly higher. The phenotypes Hp1-1 were found more often in asbestosis patients than among asbest-exposed workers.

Asbestos↗

Possible involvement of protein kinase C with induction of haptoglobin in cows by treatment with dexamethasone and by starvation.

Haptoglobin (Hp), an acute-phase protein, is detected in serum of cows with hepatic lipidosis (fatty liver). To assess the relevance of Hp in fatty liver, induction of Hp was examined, using conditions similar to those involving development of fatty liver in cows. Induction of Hp was achieved by a combination of dexamethasone administration (0.1 mg/kg of body weight) and 2 days' starvation. Haptoglobin appearance in serum was not associated with the increase of alpha 1-acid glycoprotein (a marker for inflammation). This treatment increased serum nonesterified fatty acids concentration and decreased serum triglycerides concentration. Protein kinase C activity was decreased in the cytosolic fractions of liver and mononuclear cells. Reduction of protein kinase C-catalyzed endogenous protein phosphorylation also was observed, particularly in the cytosolic fractions of the tissue and cells. Detection of Hp in serum of cows with fatty liver appears to be explained by the fact that Hp is induced by dexamethasone administration and starvation, which are similar to the condition responsible for fatty liver development. The change of protein kinase C-catalyzed phosphorylation was suggested to be involved in the induction of Hp in cows.

Animals↗

Haptoglobin. A potential reporter molecule for glycosylation changes in disease.

The acute-phase protein, haptoglobin, is elevated in many diseases; however, its glycosylation also changes, and the type of change observed can vary with disease. Increased fucosylation is a common finding, and the fucose-specific lectin, lotus tetragonolobus, can be used to differentiate different diseases (eg inflammatory conditions, liver diseases), and to monitor disease activity in cancer. Changes in N-acetyl neuraminic acid and N-acetylglucosamine suggest that particular carbohydrate structures predominate in certain diseases. Because haptoglobin glycosylation provides a record of previous intracellular events, it will help to improve our understanding of pathological processes and provide potential clinical markers for the future.

Acute-Phase Reaction↗

Haptoglobin concentration in serum and other body fluids measured by comparison of its reactivity with hemoglobin and concanavalin A.

Haptoglobin (Hp) concentration in normal human sera was determined either by means of the reaction with hemoglobin (Hb) or by reaction with the lectin concanavalin A (Con A). The ratio of Hp-Con A (1.02 +/- 0.68 g/l) to Hp-Hb (1.10 +/- 0.58 g/l) equal 0.96 +/- 0.32 was found to be characteristic for sera from healthy subjects. Measurements were also carried out for some pathological body fluids. Values of the ratio Hp-Con A/Hp-Hb in ascitic fluid, pleural effusion and cerebrospinal fluid were 1.72 +/- 1.13, 0.42 +/- 0.23 and 0.15 +/- 0.18. respectively. Haptoglobin present in urine and saliva was not recognized by Con A, whereas could form a complex with hemoglobin. Hp concentration determined by this method reached 2 mg/l.

Body Fluids↗

Cell cycle inhibition in human BE-13 T cell leukemia cells by haptoglobin-related (HPR) antisense cDNA.

We have recently cloned and sequenced a human haptoglobin-related cDNA. Hpr expression was found in various tumor cell lines. To determine whether the haptoglobin related protein (hpr) affects the growth of an established T-cell leukemia cell line, an Hpr antisense expression vector that specifically reduces hpr production was constructed. The vector was transfected into BE-13 cells, an established T-cell leukemia cell line in which Hpr is expressed. Three stable clones were isolated in which hpr protein expression was reduced. These established cell lines proliferated more slowly than vector transfected cells in proportion to Hpr antisense mRNA expression and the reduction in hpr protein production. Following a BrdU pulse, flow cytometric analysis was performed to estimate the fraction of cells in S phase. Hpr antisense transfected cells contained less cells in S phase compared to vector transfected cells. Also in soft agar, cells expressing the antisense cDNA insert, formed on average at least 7-fold fewer colonies than cells transfected with the vector alone. The data suggest that Hpr inhibitors might be of therapeutic value for T-cell leukemia.

Base Sequence↗

[Serum haptoglobin and sialic acid content and the spontaneous rosette test values as indices of the activity of the disease process in chronic glomerulonephritis].

The diagnostic significance of haptoglobin is studied as well as of sialic acid and spontaneous rosette test (SRT) and ESR as indices of the morbid process activity in 74 patients with chronic hephritis with manifested and oligospymptomatic course and in a stage of therapeutic remission and in 14 patients with acute protracted nephritis. The parallelism of the changes in all parameters studied is proved in acute protracted nephritis and in chronic nephritis with manifested course. In patients with oligosymtomatically advancing chronic nephritis, in spite of the normal values of ESR and the rest of the routine indices for determination of the morbid process activity, haptoglobin, sialic acid and SRT were established to be increased. They were hardly normalized after the advancement of a lasting therpeutic remission. That all gives grounds to the authors to think, that the significance of the studied indices for the assessment of the morbid process activity in oligosymptomatically advancing chronic glomerulonephritis, is superior, to a certain extent, to the diagnostic signficance of ESR. Their follow up in dynamics permits their application in the determination of the immunosuppressive treatment efficiency.

Acute Disease↗

Analysis of mouse beta-haptoglobin chain by lectin affinoblotting detection.

Two different human mammary carcinoma cell lines were xenotransplanted into nude mice. Serum samples were obtained prior to and after transplantation and investigated by two-dimensional electrophoresis (2-DE). By comparison of these silver-stained patterns additional protein spots were detected resulting either from proteins secreted or shed by the tumor itself or from mouse proteins induced by the tumor or the transplantation procedure. One group of spots detectable in post-transplantation serum as well as in control serum after mock-transplantation but not in pretransplantation serum was microsequenced and identified as mouse beta-haptoglobin. The carbohydrate structures of beta-haptoglobin were characterized by two different immunochemical glycoprotein staining procedures to detect differential terminal glycan modifications.

Acute-Phase Proteins↗