Study Sickle Cell Anemia

The amino acid sequence of the pol5q)eptide primary structure is very important. Any changes in the normal sequence can have severe effects 

FIGURE 3.28. The mutation occurs at the number 6 position of the 146-member amino acid chain. 

FIGURE 3.29. Top normal red blood cells bottom sickle cells (K.R. Bridges, Harvard U). 

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After World War II Pauling studied sickle cell anemia, and theorized that it was the result of a genetically based defect in the patient s hemoglobin molecules. In 1949 he and Harvey Itano confirmed this theory they had identified what they called a molecular disease, one that could be defined by a molecular abnormality. In 1954 Pauling received the Nobel Prize in chemistry for his research on the chemical bond and its appfication to the elucidation of the structure of complex substances. ... 

Early detection of ischemic stroke can be done with the use of transcranial Doppler ultrasonography. In the Stroke Prevention Trial in Sickle Cell Anemia (STOP) study, screening with this method followed by transfusion significantly reduced the incidence of stroke.29 Screening is recommended in all patients over 2 years of age. 

Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, McMahon RP, Bonds DR. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia [see comments). 

Mr Robert Heflin again came to our rescue to link me up with funds to study in Cambridge via Ms. Ruth White, the then director of the Sickle-Cell Anemia Society in Pittsburgh. In one day, Ms. White arranged for me to get a Heinz Foundation grant to travel and work in Perutz s laboratory. 

Reported applications of DMA include the cross-linking of bovine pancreatic ribonuclease A (Hartman and Wold, 1967), treatment of erythrocyte membranes to reduce the effects of sickle cell anemia (Waterman et al., 1975), conjugation and analysis of the outer membrane proteins of Neisseria gonorrhoeae (Newhall et al., 1980), protein structural studies of bovine a-crystalline (Siezen et al., 1980), cross-linking of hemoglobin S (Pennathur-Das et al., 1982), and forming S-carbomethoxy-valeramidine during hydrolysis of DMA (Mentzer et al., 1982). 

In later years, I met Pauling again perhaps a dozen times, in a variety of situations. Particularly, I remember a fascinating lecture he gave at the Harvard Medical School, about his seminal work on sickle-cell anemia and kindred studies and a passionate speech, delivered from the pulpit of a Cambridge church, against the Vietnam war. 

Singer, H., Chemoff, A. I., and Singer, L., Studies on abnormal hemoglobin. I. Their demonstration in sickle cell anemia and other hematologic disorders by means of alkali denaturation. Blood 6, 413-428 (1951). 

Mefloquine (125 or 250 mg/week n — 56) has been compared with proguanil (100 or 200 mg/day n — 57) for short-term (6 months) malaria chemoprophylaxis in Nigerians with sickle cell anemia in a non-blinded, randomized study (9). Efficacy was similar (89% for mefloquine and 82% for proguanil). Adverse events were reported by 32% of those who took proguanil and 20% of those who took mefloquine. Surprisingly, only 3.6% of the mefloquine group reported neuropsychiatric adverse events. 

Two studies have suggested that the overall incidence of clinical nephrotoxicity with NSAIDs is small (148,149). However, some patients (see below) are at increased risk of particular effects (SEDA-11, 82), and patients with sickle cell anemia can probably be added to the list (SEDA-15, 97). 

The immunogenicity and safety of pneumococcal polysaccharide vaccine have been studied in renal allograft recipients, dialysis patients (19), children and adolescents with sickle-cell anemia (SED-11, 682) (SEDA-12, 277), people with diabetes mellitus (SED-11, 682), and children with nephrotic syndrome (20). When comparing the results with healthy persons there were no significant differences. 

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