Symptoms Of Sickle Cell Disease Research Articles

Hemoglobin S Antilles: a variant with lower solubility than hemoglobin S and producing sickle cell disease in heterozygotes.

We have found a sickling variant, Hb S Antilles, alpha 2 beta 2(6 Glu----Val, 23 Val----Ile), that has the same electrophoretic mobility as Hb S but a distinct isoelectric focus and produces sickling in the carriers of the Hb A/S Antilles trait. The carriers' erythrocytes tend to sickle at O2 partial pressures similar to those that induce sickling in Hb S/C disease. Pure deoxy-Hb S Antilles is 50% as soluble as deoxy-Hb S (saturating concentration = 11 g X dl-1 compared to 18.4 for Hb S). Dilute solutions of pure Hb S Antilles have a lower oxygen affinity than those of Hb A or Hb S (partial pressure for 50% binding is 9 mm Hg compared to 5.5 mm Hg for Hb A or S at pH 7.00). A/S Antilles erythrocytes have a much lower oxygen affinity than A/S cells; this is further decreased in dense cells fractionated on a Percoll density gradient. Their oxygen equilibrium curves had anomalous shapes like those of S/S cells. Fiber formation in the erythrocytes of Hb S Antilles carriers is clearly due to its low solubility and oxygen affinity, showing that heterozygosity for this hemoglobin presents another sickle cell syndrome and suggesting that Hb S heterozygotes who exhibit symptoms of sickle cell disease should be carefully screened for double mutations.

The effect of 2,3-diphosphoglycerate on the solubility of deoxyhemoglobin S

Although highly charged polyanions, such as inositol hexaphosphate, have been clearly shown to decrease the solubility of deoxyhemoglobin S, the effect of 2,3-diphosphoglycerate (DPG), the endogenous allosteric effector within the red cell, has been more controversial. In this work we have compared the effect of DPG on the solubility of native deoxyhemoglobin S and a derivative in which the DPG binding site is blocked by crosslinking the two β82 lysine residues. At pH 6.6 and 30 °C the solubility of deoxyhemoglobin S was found to be decreased by 15% (i.e., from 18.8 to 16.0 g/dl) in the presence of saturating concentrations of DPG. Under the same conditions DPG had no effect on the solubility of the cross-linked derivative. This result establishes unequivocally that the binding of DPG within the β cleft directly facilitates the polymerization of deoxyhemoglobin S. Under physiological conditions, the solubility of deoxyhemoglobin S was found to be decreased by 6% in the presence of an equimolar concentration of DPG. A solubility decrease of this magnitude is sufficient to enhance the tendency of SS cells to sickle and may exacerbate the clinical symptoms of sickle cell disease.

The sickling process in relation to clinical manifestations

Knowledge of the detailed molecular mechanisms of the sickling process has led to an understanding of factors precipitating crises and hence allowed a reasoned approach to therapy. At present amelioration of the symptoms of sickle cell disease rests primarily on the avoidance and prompt treatment of the basic precipitating factors of the sickling process--fever, hypoxia, acidosis, and dehydration. Over the years many drugs have been claimed to have anti-sickling properties but have not stood the test of time. The current partial success of cyanate stems directly from this molecular knowledge. As further details of the site of intermolecular binding involved in the sickling process become available the possibility of developing more specific anti-sickling drugs becomes clearer.

Sicklemia.

Article1 May 1955SICKLEMIANORMAN ENDE, M.D., PHILIP PIZZOLATO, M.D., JOSEPH ZISKIND, M.D., F.A.C.P.NORMAN ENDE, M.D.Search for more papers by this author, PHILIP PIZZOLATO, M.D.Search for more papers by this author, JOSEPH ZISKIND, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-42-5-1065 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSickle cell anemia has long been known to produce severe clinical manifestations. Only recently, however, has it been accepted that the sickle cell trait per se, or sicklemia, is also capable of producing clinical symptoms and pathologic findings.1 Although prior to 1940 some cases of sicklemia had been reported2 which showed clinical findings with no anemia, it was not until that year that Bauer3 introduced the idea that the anemic picture was but one manifestation of sickle cell disease.The most recent combined surveys show a 9.0% incidence of sickling4in the Negro population of the United States. Despite these...Bibliography1. Wintrobe MM: Clinical hematology, 3d Ed., 1951, Lea and Febiger, Philadelphia. Google Scholar2. Campbell EH: Acute abdominal pain in sickle cell anemia, Arch. Surg. 31: 607, 1935. CrossrefGoogle Scholar3. Bauer J: Sickle cell disease, Arch. Surg. 41: 1344, 1940. CrossrefGoogle Scholar4. Margolies MP: Sickle cell anemia, Medicine 30: 357, 1951. CrossrefMedlineGoogle Scholar5. GreenConley TWCL: Occurrence of symptoms of sickle cell disease in the absence of persistent anemia, Ann. Int. Med. 34: 849, 1951. LinkGoogle Scholar6. CanbyCarpenterEllmore CBGLF: Drepanocytosis (sicklemia) and an apparently acute surgical condition of the abdomen, Arch. Surg. 48: 123, 1944. CrossrefGoogle Scholar7. Sullivan BH: Danger of aeroplane flight to persons with sicklemia, Ann. Int. Med. 32: 339, 1950. Google Scholar8. AbelBrown MSCR: Sickle cell anemia with severe hematuria simulating renal neoplasm, J. A. M. A. 136: 624, 1948. CrossrefMedlineGoogle Scholar9. GoodwinAlstonSimons WEEFJH: Hematuria and sickle cell disease, J. Urol. 63: 79, 1950. CrossrefMedlineGoogle Scholar10. RyanFuller JERH: Hemorrhagic manifestations of sickle cell disease, U. S. Armed Forces M. J. 2: 623, 1951. MedlineGoogle Scholar11. ThompsonWagnerMacleod RKJACM: Sickle cell disease: report of a case with cerebral manifestations in absence of anemia, Ann. Int. Med. 29: 921, 1948. LinkGoogle Scholar12. BauerFisher JLJ: Sickle cell disease with special regard to its non-anemic variety, Arch. Surg. 47: 553, 1943. CrossrefGoogle Scholar13. Pratt-ThomasSwitzer HRPK: Sicklemia: its pathological and clinical significance, South. M. J. 42: 376-844 (May) 1949. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New Orleans, Louisiana*Received for publication September 7, 1954.From the Clinical Laboratory, Veterans Administration Hospital, and the Departments of Pathology, Tulane University School of Medicine and Louisiana State University School of Medicine, New Orleans, Louisiana.†Sponsored by the Veterans Administration and published with the approval of the Chief Medical Director. The statements and conclusions published by the authors are a result of their own study and do not necessarily reflect the opinion or policy of the Veterans Administration. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byProspective Brain Imaging Evaluation of Children with Sickle Cell Trait: Initial ObservationsStroke in a 9-year-old with sickle cell traitLarge-vessel occlusion in sickle cell disease: Pathogenesis, clinical consequences, and therapeutic implicationsCerebral infarction in sickle cell traitIschemic Colitis Complicating Sickle Cell CrisisThe morbidity of sickle cell traitOcclusion of Large Cerebral Vessels in Sickle-Cell AnemiaNeurological Manifestations in Sickle-Cell Disease With a Review of the Literature and Emphasis on the Prevalence of HemiplegiaBARRY A. PORTNOY, M.D., JOHN C. HERION, M.D.Spinal cord infarction associated with the sickle cell traitAnterior and Posterior Hypopituitarism Associated with Sickle Cell TraitROBERT A. PASTURE, JAMES W. ANDERSON, ROBERT H. HERMANPrimary cardiomyopathy in nonanemic patientsAseptic necrosis of the femoral heads in sickle-A hemoglobin diseaseSickle cell states and cardiomyopathySickle-Cell Trait and Central Retinal-Artery OcclusionThe influence of hemoglobinopathies on reproductionSickle Cell Trait and Superior Longitudinal Sinus ThrombosisERIC A. SCHENK, M.D.Avascular Necrosis of the Femoral Head Associated with Sickle Cell Trait (AS Hemoglobin)RALPH G. RATCLIFF, M.D., MELVYN D. WOLF, M.D.Fatal Intravascular Sickling in a Patient with Sickle-Cell TraitSicklemia Complicating Chest SurgeryTHE GENETICS OF HUMAN HAEMOGLOBIN DIFFERENCES: PROBLEMS and PERSPECTIVES 1 May 1955Volume 42, Issue 5Page: 1065-1075KeywordsAnemiaClinical laboratoriesHospital medicinePathology and laboratory medicineSickle cell disease Issue Published: 1 May 1955 PDF downloadLoading ...

The therapeutic response of tuberculous Negroes with the sickle cell trait.

Article1 March 1953THE THERAPEUTIC RESPONSE OF TUBERCULOUS NEGROES WITH THE SICKLE CELL TRAITWILLIAM WEISS, M.D.WILLIAM WEISS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-38-3-523 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTuberculosis in the Negro race is more often acute and more often leads to death than in the white race. This is true even when environmental factors are similar in both races.1 Therefore, constitutional factors must be important in the Negro's reaction to tuberculous infection.These constitutional factors are not easily defined and their influence is not readily measured in most cases. However, the sickling phenomenon, which is almost peculiar to the Negro, requires only a simple test to uncover its presence. Since blood supply is important in inflammatory diseases such as tuberculosis, it seems reasonable that sickling of red...Bibliography1. West JB: An inquiry into the importance of the racial factor in the epidemiology of tuberculosis, Supplement to Am. Rev. Tuberc. 41: 114, 1940. Google Scholar2. WeissWaife WSO: Tuberculosis and sickle cell anemia, Am. Rev. Tuberc. 65: 735, 1952. MedlineGoogle Scholar3. LangeMinnichMoore RDVCV: Effect of oxygen tension and of pH on the sickling and mechanical fragility of erythrocytes from patients with sickle cell anemia and the sickle cell trait, J. Lab. and Clin. Med. 37: 789, 1951. MedlineGoogle Scholar4. Wintrobe MM: Clinical hematology, 1942, Lea and Febiger, Philadelphia, p. 467. Google Scholar5. Sturgis CC: Hematology, 1948, C. C. Thomas, Springfield, Ill., p. 329. Google Scholar6. Margolies MP: The incidence of sickling, Am. J. M. Sc. 221: 270, 1951. CrossrefMedlineGoogle Scholar7. WeissStecher WW: Tuberculosis and the sickle cell trait, Arch. Int. Med 89: 914, 1952. CrossrefGoogle Scholar8. GreenConley TWCL: Occurrence of symptoms of sickle cell disease in the absence of persistent anemia, Ann. Int. Med. 34: 849, 1951. LinkGoogle Scholar9. BauerFisher JLJ: Sickle cell disease with special regard to its nonanemic variety, Arch. Surg. 47: 553, 1943. CrossrefGoogle Scholar10. Sullivan BH: Danger of airplane flight to persons with sicklemia, Ann. Int. Med. 32: 338, 1950. LinkGoogle Scholar11. ThompsonWagnerMacLeod RKJACM: Sickle cell disease: report of a case with cerebral manifestations in the absence of anemia, Ann. Int. Med. 29: 921, 1948. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Philadelphia, Pennsylvania*Presented in part at the Fourteenth Annual Round-up of Eastern Pennsylvanians, American College of Physicians, Philadelphia, January 25, 1952. Received for publication August 5, 1952.From the Department of Chronic Diseases of the Chest, Philadelphia General Hospital, and the Woman's Medical College of Pennsylvania. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHemopoietic SystemNOTES ON SICKLE-CELL POLYMOKPHISM. 1 March 1953Volume 38, Issue 3Page: 523-527KeywordsBloodRacial and ethnic issuesThorax ePublished: 1 December 2008 Issue Published: 1 March 1953 PDF downloadLoading ...

Further electroencephalographic studies in sickle cell anemia.

IN A PREVIOUS communication,1the electroencephalographic findings in sickle cell anemia were reported. Included in this study were eight patients who presented an exacerbation of the symptomatology of sickle cell disease and who, therefore, were considered to be in a state of sickle cell crisis. Since the electroencephalograms were abnormal for all eight of these patients, we felt that further evaluation of electroencephalographic patterns of patients with sickle cell crisis was indicated. It is the purpose of this paper to present a heretofore unreported electroencephalographic finding and to analyze the electroencephalograms of 12 additional patients who had been hospitalized with signs and symptoms of sickle cell crisis. Evidence has been presented previously to correlate the nature of brain potentials with clinical manifestations in those patients with central nervous system symptoms of sickle cell anemia. METHODS The diagnosis of sickle cell anemia was established definitely in each case before it

Sickle cell anemia and pregnancy.

A study was made of 18 cases of sickle cell anemia, 4 of which were complicated by pregnancy. These 4 cases are reported in detail, including the postmortem findings for one of them. The frequency of the various symptoms of sickle cell anemia and a summary of the cases complicated by pregnancy are presented in tabulated form.

LONG BONE INVOLVEMENT IN SICKLE CELL ANEMIA

Two types of pathologic changes may occur in the long bones of patients with sickle cell anemia. A hyperplastic bone marrow represents the response to continued destruction of erythrocytes and this produces a wide medullary cavity and a thin cortex. The thromboses of vessels in the marrow and bone result in abnormal areas of calcification and new bone formation producing a thick cortex and a small medullary cavity. The findings on roentgenographic examination will depend upon which of the two processes is dominant. A 21 month old Negro infant whose symptoms of sickle cell anemia began at 4 months of age showed typical roentgenographic findings resulting from a hyperplastic marrow. The cortex in the femur had become so thin that a pathologic fracture resulted. This is the first reported instance of the occurrence of a pathologic fracture in sickle cell anemia.