Differential pathways in oxy and deoxy HbC aggregation/crystallization

Hirsch, Rhoda Elison; Samuel, Raymond E.; Fataliev, Nazim A.; Pollack, Michael J.; Vekilov, Peter G.; Nagel, Ronald L.

doi:10.1002/1097-0134(20010101)42:1<99::aid-prot100>3.0.co;2-r

Cited by 11 publications

(12 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The transition from the oxygenated to the deoxygenated form, such as occurs during passage through the spleen or under in vitro conditions, may cause crystal dissolution. Moreover, storage of RBCs in the dark has been shown to enhance crystal formation 8 . In our in vitro experiment, 2 of the positive samples that formed crystals were stored in the dark for 24 hours at room temperature.…”

Section: Discussionmentioning

confidence: 92%

Peripheral Blood Smear from a Dog

Beaudoin¹,

Lanevschi²,

Dunn³

et al. 2002

Veterinary Clinical Pathol

View full text Add to dashboard Cite

A 13-year-old intact male Belgian Shepherd Dog was presented to the Dimension multi vétérinaire reference center with a history of weakness of 1-week duration and acute onset of melena. Upon presentation, the initial PCV was 0.20 L/L (reference range, 0.37-0.50 L/L). On day 2, the dog's PCV fell to 0.12 L/L, and a whole-blood transfusion was administered. Results of a leukocyte count, platelet count, total protein concentration (refractometry), clinical chemistry panel, activated clotting time, and adrenocorticotropic hormone stimulation test were within reference limits. Abdominal and thoracic radiographs and abdominal ultrasound revealed no abnormalities. Exploratory laparotomy was performed during which stomach and intestinal biopsies were taken. No gross or histologic abnormalities were noted.Seven days after initial presentation, a blood sample in an EDTA tube was sent on an ice pack by courier to the diagnostic laboratory of the Faculty of Veterinary Medicine at the University of Montreal, where it was analyzed within 24 hours of sampling. Specimens for subsequent analyses in this case were mailed under similar conditions. Results of the CBC (Table 1) revealed moderate, nonregenerative anemia (PCV = 0.20 L/L) that was normocytic and probably normochromic (the MCHC was likely overestimated because of slight hemolysis). Some RBCs appeared microcytic and hypochromic on the blood smear, suggesting iron deficiency. The dog had mild leukocytosis (20.2ϫ10 9 cells/L; reference range, 6.0-17.0ϫ10 9 /L), mild neutrophilia (16.8ϫ10 9 cells/L; reference range, 3.0-11.5ϫ10 9 /L), mild lymphopenia (0.8ϫ10 9 cells/L; reference range, 1.0-4.8ϫ 10 9 /L), mild monocytosis (2.1ϫ10 9 cells/L; reference range, 0.1-1.4ϫ10 9 /L), and a few slightly toxic neutrophils. These observations were compatible with concurrent inflammation and stress. The dog was returned home with iron supplementation (100 mg PO once daily) and metronidazole (15 mg/kg PO twice a day for 7 days). Measurement of serum iron concentration, total iron binding capacity, and ferritin concentration, although recommended, were not performed.On day 17, the dog was still anemic (PCV= 0.22 L/L),

show abstract

Section: Discussionmentioning

confidence: 92%

Peripheral Blood Smear from a Dog

Beaudoin¹,

Lanevschi²,

Dunn³

et al. 2002

Veterinary Clinical Pathol

View full text Add to dashboard Cite

show abstract

“…In these studies, the presence of such strands was the main piece of evidence supporting the conclusion of a growth mechanism of HbS crystal involving alignment of the preformed fibers in the solution. Since fibers, ribbons, and other linear objects have been observed in crystallizing solutions of CO-HbC (Hirsch et al, 2001), one may speculate that the observations of the strands support the fiber-alignment mechanism of formation of HbC crystals. However, the results in Figs.…”

Section: The Growth Mechanismmentioning

confidence: 91%

“…The procedures for isolation and purification of HbC and for preparation of the solutions of CO-HbC were identical to those described in Hirsch et al (2001).…”

Section: Experimental Procedures Preparation Of Human Hbc Solutionsmentioning

confidence: 99%

Crystallization Mechanisms of Hemoglobin C in the R State

Feeling-Taylor

Yau

Petsev

et al. 2004

Biophysical Journal

Self Cite

View full text Add to dashboard Cite

Crystallization of the mutated hemoglobin, HbC, which occurs inside red blood cells of patients expressing betaC-globin and exhibiting the homozygous CC and the heterozygous SC (in which two mutant beta-globins, S and C, are expressed) diseases, is a convenient model for processes underlying numerous condensation diseases. As a first step, we investigated the molecular-level mechanisms of crystallization of this protein from high-concentration phosphate buffer in its stable carbomonoxy form using high-resolution atomic force microscopy. We found that in conditions of equilibrium with the solution, the crystals' surface reconstructs into four-molecule-wide strands along the crystallographic a (or b) axis. However, the crystals do not grow by the alignment of such preformed strands. We found that the crystals grow by the attachment of single molecules to suitable sites on the surface. These sites are located along the edges of new layers generated by two-dimensional nucleation or by screw dislocations. During growth, the steps propagate with random velocities, with the mean being an increasing function of the crystallization driving force. These results show that the crystallization mechanisms of HbC are similar to those found for other proteins. Therefore, strategies developed to control protein crystallization in vitro may be applicable to pathology-related crystallization systems.

show abstract

“…Th e irreversible SCs have a short intravascular life span and, because of their rigid shape, may block small vascular structures, leading to ischemia and endothelial cell damage [162,166] . In Hb C, glutamic acid in the sixth position of the β -globin chain is replaced by lysine [167,168] . Th e Hb C-containing erythrocytes are more rigid than normal red cells and may form rod-like crystals in hypoxic conditions.…”

Section: Etiology and Pathogenesismentioning

confidence: 99%

Disorder of Red Blood Cells: Anemias

Naeim¹

2008

Hematopathology

View full text Add to dashboard Cite

Differential pathways in oxy and deoxy HbC aggregation/crystallization

Cited by 11 publications

References 39 publications

Peripheral Blood Smear from a Dog

Peripheral Blood Smear from a Dog

Crystallization Mechanisms of Hemoglobin C in the R State

Disorder of Red Blood Cells: Anemias

Contact Info

Product

Resources

About