Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q0Z944 (hemoglobin)
 63,986 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Porphyromonas gingivalis (Bacteroides gingivalis) requires iron in the form of hemin for growth and virulence in vitro, but the contributions of the porphyrin ring structure, porphyrin-associated iron, host hemin-sequestering molecules, and host iron-withholding proteins to its survival are unknown. Therefore, the effects of various porphyrins, host iron transport proteins, and inorganic iron sources on the growth of P. gingivalis W50 were examined to delineate the various types of iron molecules used for cellular metabolism. Cell envelope-associated hemin and iron stores contributed to the growth of P. gingivalis in hemin-free culture, and depletion of these endogenous reserves required eight serial transfers into hemin-free medium for total suppression of growth. Comparable growth of P. gingivalis was observed with 7.7 microM equivalents of hemin as hemoglobin (HGB), methemoglobin, myoglobin, hemin-saturated serum albumin, lactoperoxidase, cytochrome c, and catalase. Unrestricted growth was recorded in the presence of haptoglobin-HGB and hemopexin-hemin complexes, indicating that these host defense proteins do not sequester HGB and hemin from P. gingivalis. The iron chelator 2,2'-bipyridyl functionally chelated hemin-associated iron, resulting in dose-dependent inhibition of growth in hemin-restricted cultures at 1 to 25 microM 2,2'-bipyridyl concentrations. In the absence of an exogenous iron source, protoporphyrin IX did not support P. gingivalis growth. These findings suggest that the iron atom in the hemin molecule is the critical constituent for growth and that the tetrapyrrole porphyrin ring structure may represent an important vehicle for delivery of iron into the P. gingivalis cell. P. gingivalis does not have a strict requirement for porphyrins, since growth occurred with nonhemin iron sources, including high concentrations (200 muM) of ferric, ferrous, and nitrogenous inorganic iron, and P. gingivalis exhibited unrestricted growth in the presence of host transferrin, lactoferrin, and serum albumin. The diversity of iron substrates utilized by P. gingivalis and the observation that growth was not affected by the bacteriostatic effects of host iron-withholding proteins, which it may encounter in the periodontal pocket, may explain why P. gingivalis is such a formidable pathogen in the periodontal disease process.
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PMID:Roles of porphyrins and host iron transport proteins in regulation of growth of Porphyromonas gingivalis W50. 165 88

The blood iron status of 44 male runners of various running specialties (18 sprinters, 13 middle- and 13 long-distance runners) is evaluated by measuring serum ferritin (SF), serum iron (Si), hemoglobin concentration (Hb), hematocrit (Ht), red blood cells content (RBC) and haptoglobin concentration (Hp). The results of these analyses (except Hp) are compared to those obtained in sedentary male subjects (control group) of the same mean age. Mean SF, SI, Hb and Ht measured in athletes are significantly lower than in control group. The remarkably low Hp values obtained in athletes suggests the occurrence of hemolysis. Using unpaired t test, it appears that the blood iron status of these runners does not depend on their running specialty.
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PMID:Iron status in runners of various running specialties. 169 84

A study was undertaken to evaluate hemolysis and subsequent renal damage in 14 patients undergoing cardiopulmonary bypass (CPB) surgery. In all patients, free haptoglobin disappeared completely 30 to 90 minutes into CPB, while free hemoglobin (Hb) levels increased progressively. The NAG index and alpha 1M index also increased progressively, indicating renal tubular injury due to hemolysis (Study 1). An additional 20 patients were monitored intraoperatively for plasma free Hb levels by a newly developed colorimetric method using a haptoglobin coated strip. Free Hb levels during CPB exceeded 30 mg/dl in 14 patients, who were immediately given haptoglobin. This treatment eliminated plasma free Hb within 30 minutes, and effectively prevented hemoglobinuria. Haptoglobin treatment brought significant decreases in the NAG index and alpha 1M index, suggesting a protective effect on renal function (Study 2).
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PMID:Administration of haptoglobin during cardiopulmonary bypass surgery. 172 15

The management of massive blood loss resulting from trauma or surgery necessitates rapid transfusion capability. Hypothermia secondary to shock, transfusion, and prolonged surgical procedures significantly increases morbidity and mortality in these patients. Transfusion at high flow rates frequently exceeds the warming capacity of conventional blood-warming devices, whose inherent resistance also limits the maximal flow rates. Microwave ovens are capable of blood warming, but have been associated with unacceptable hemolysis. We have investigated the possibility of using microwave energy to provide rapid in-line blood warming. Fresh blood from 10 human subjects was warmed from an average of 18 degrees C to temperatures ranging from 37 to 39 degrees C at flow rates from 250 to 500 mL/min. Laboratory analysis of free plasma hemoglobin, haptoglobin, hematocrit, hemoglobin, and electrolytes showed no difference between heated and control samples. LDH was elevated in those samples warmed repeatedly, but remained within the normal range. These data indicate the potential for further investigation utilizing properly controlled microwave energy for in-line blood and fluid warming.
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PMID:Rapid in-line blood warming using microwave energy: preliminary studies. 177 46

The arylmethylaminopropanediols (AMAPs) are a new class of DNA intercalators. 773U82.HCl is the second of these compounds to enter clinical trial. Significant antitumor activity for 773U82.HCl was documented in a variety of murine and human tumor models. This phase I study examined a 1-, 2- and 6-hour infusion given every 28 days. Thirty-six patients received 58 courses of drug at doses ranging from 15 mg/m2 to 980 mg/m2. The dose-limiting toxicity of 773U82.HCl was hemolysis noted at 980 mg/m2. Change in color of the plasma and decreases in haptoglobin were correlated with drug concentrations of the infusate greater than or equal to 3 mg/ml. Clinically significant changes in hemoglobin levels requiring blood transfusions did not occur. Neurologic toxicity occurred at 720 mg/m2 with the most severe neurologic toxicity occurring in a patient with the highest peak plasma concentration (4.1 micrograms/ml). With an increase in duration of the infusion and amount of fluid administered, the neurologic toxicity resolved. Other toxicities included mild nausea and vomiting and a dose-related phlebitis. Pharmacokinetic studies were completed in 22 patients. The mean terminal t1/2 beta was 4.4 h with a mean apparent volume of distribution at steady state (Vdss) of 314 l/m2. The mean total body clearance was 72 l/h/m2. Peak plasma levels ranged from 0.04 to 4.14 micrograms/ml. Further studies with 773U82.HCl on this schedule at the doses studied are not recommended. Hematologic monitoring for evidence of intravascular hemolysis should be included in future studies with 773U82.HCl.
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PMID:Phase I evaluation of 773U82.HCl, a member of a new class of DNA intercalators. 179 91

Iron is essential for life, but iron overload is toxic and potentially fatal. The liver is a major site of iron storage and is particularly susceptible to injury from iron overload, especially when (as in primary hemochromatosis) the iron accumulates in hepatocytes. Iron can be taken up by the liver in several forms and by several pathways including: (1) receptor-mediated endocytosis of diferric or monoferric transferrin or ferritin, (2) reduction and carrier-facilitated internalization of iron from transferrin without internalization of the protein moiety of transferrin, (3) electrogenic uptake of low molecular weight, non-protein bound forms of iron, and (4) uptake of heme from heme-albumin, heme-hemopexin, or hemoglobin-haptoglobin complexes. Normally, pathway 2 is probably the major one for uptake of iron by hepatocytes. Iron is stored in the liver in the cores of ferritin shells and as hemosiderin, an insoluble product derived from iron-rich ferritin. Iron in hepatocytes stimulates translation of ferritin mRNA and represses transcription of DNA for transferrin and transferrin receptors. The major pathologic effects of chronic hepatic iron overload are: (1) fibrosis and cirrhosis, (2) porphyria cutanea tarda, and (3) hepatocellular carcinoma. Although precise pathogenetic mechanisms remain unknown, iron probably produces these and other toxic effects by increasing oxidative stress and lysosomal lability. Vigorous efforts at diagnosis and treatment of iron overload are essential since the pathologic effects of iron are totally preventable by early vigorous iron removal and prevention of iron re-accumulation.
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PMID:Iron and the liver. 184 76

Yersinia pestis is one of many microorganisms responding to environmental iron concentrations by regulating the synthesis of proteins and an iron transport system(s). In a number of bacteria, expression of iron uptake systems and other virulence determinants is controlled by the Fur regulatory protein. DNA hybridization analysis revealed that both pigmented and nonpigmented cells of Y. pestis possess a DNA locus homologous to the Escherichia coli fur gene. Introduction of a Fur-regulated beta-galactosidase reporter gene into Y. pestis KIM resulted in iron-responsive beta-galactosidase activity, indicating that Y. pestis KIM expresses a functional Fur regulatory protein. A cloned 1.9-kb ClaI fragment of Y. pestis chromosomal DNA hybridized specifically to the fur gene of E. coli. The coding region of the E. coli fur gene hybridized to a 1.1-kb region at one end of the cloned Y. pestis fragment. The failure of this clone to complement an E. coli fur mutant suggests that the 1.9-kb clone does not contain a functional promoter. Subcloning of this fragment into an inducible expression vector restored Fur regulation in an E. coli fur mutant. In addition, a larger 4.8-kb Y. pestis clone containing the putative promoter region complemented the Fur- phenotype. These results suggest that Y. pestis possesses a functional Fur regulatory protein capable of interacting with the E. coli Fur system. In Y. pestis Fur may regulate the expression of iron transport systems and other virulence factors in response to iron limitation in the environment. Possible candidates for Fur regulation in Y. pestis include genes involved in ferric iron transport as well as hemin, heme/hemopexin, heme/albumin, ferritin, hemoglobin, and hemoglobin/haptoglobin utilization.
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PMID:Identification and cloning of a fur regulatory gene in Yersinia pestis. 189 28

A macromolecular hemoglobin-binding protein, which was not detectable in normal bovine sera but appeared during acute phase inflammation, was purified, characterized, and designated as bovine haptoglobin (Hp). The purified protein had a molecular mass of 1,000-2,000 kDa, and was composed of two kinds of peptides, a 20-kDa peptide (alpha chain) and a 35-kDa glycopeptide (beta chain) linked by disulfide bonds. Amino acid composition and N-terminal sequence analyses revealed that both peptides were homologous to each counterpart of human Hp. Studies using some reducing reagents proved that highly polymerized Hp in serum was composed of 2-20 polymerized forms of alpha 2 beta 2 tetramer. Hp could bind one molecule of hemoglobin/alpha 2 beta 2 unit. Hp with smaller sizes obtained from native Hp by partial reduction with cysteine showed almost the same Hb-binding capacity.
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PMID:Isolation and characterization of bovine haptoglobin from acute phase sera. 190 72

Ultrafiltration is well known as a useful method of hemoconcentration of the blood after cardiopulmonary bypass, but free hemoglobin increase is a problem in autotransfusion. The purpose of this study was to investigate the effect of haptoglobin administration for hemolysis with autotransfused blood ultrafiltered after cardiopulmonary bypass. By means of haptoglobin administration, autotransfusion of blood ultrafiltered with Hemocon (CD Medical Inc.) composed cellulose acetate membrane was performed in patients over a long period (max 313 min) of cardiopulmonary bypass, and with high serum free hemoglobin levels (max 128 mg/dl) at the end of the cardiopulmonary bypass. Comparing the prophylactic administration with the therapeutic administration of haptoglobin, both methods effectively prevented the increment of serum free hemoglobin level, but prophylactic administration (priming administration) was safer and more useful considering free hemoglobin level in ultrafiltered blood and changes of serum free haptoglobin, free hemoglobin and creatinine clearance during and after the operation.
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PMID:[Haptoglobin administration for hemolysis with autotransfusion of blood ultrafiltered after cardiopulmonary bypass]. 202 Jan 44

The effects of 7 successive days of prolonged jogging on aerobic performance and biochemical markers of muscle and red blood cell damage were examined in 10 moderately fit men, ages 27 +/- 2 yr (mean +/- SE). The subjects jogged for 2 h per day at 78 +/- 4% of maximal heart rates and covered a total of 129 +/- 2 km, nearly eight times their regular weekly training distance. At baseline, maximal oxygen uptake (VO2max) during treadmill tests averaged 3.45 +/- 0.24 L/min, or 44.7 +/- 1.4 ml/kg/min. On follow-up tests 2d after the week of increased training, VO2max (3.56 +/- 0.17 L/min) and treadmill performance were not significantly improved. Body weight declined from 79.5 +/- 4.6 kg to 77.8 +/- 4.4 kg (p less than 0.05) because of reduced body fatness (16.8 +/- 2.3% to 13.6 +/- 1.7%, p less than 0.05). Weight-adjusted VO2max increased to 46.4 +/- 2.0 ml/kg/min (p less than 0.05). However, heart rate and systolic blood pressure were not significantly changed at rest, or during submaximal and maximal treadmill exercise. Mean hemoglobin concentration at treadmill testing declined from 14.9 +/- 0.3 g/dl to 13.3 +/- 0.3 g/dl (p less than 0.05). Leg muscle soreness, especially in the thigh region, persisted in all subjects after 3 d. Soreness was accompanied by chronic elevations (p less than 0.05) in serum levels of myoglobin, creatine kinase (CK), lactic dehydrogenase (LD), aminoaspartate, and the isoenzymes CK-MB and LD1,2. Serum haptoglobin levels after jogging fell from 86 +/- 9 mg/dl to 60 +/- 8 mg/dl (p less than 0.05), suggestive of footstrike hemolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of 7 successive days of unaccustomed prolonged exercise on aerobic performance and tissue damage in fitness joggers. 203 61


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