Hemoglobin Hofu (beta 126 Val is replaced by Glu) in a black American.
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Biomedical subjects
Publications and source records attributed to R G Sheehan.
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The reliability of a radioimmunometric assay of serum ferritin concentration by a packaged kit was evaluated. In addition, application of the serum ferritin assay to the clinical evaluation of selected anemias was assessed. When appropriate serum dilutions were utilized, this method was sufficiently reproducible and reliable for application to the clinical laboratory. Serum ferritin was found to be a valuable tool in the differential diagnosis of anemia accompanied by hypoferremia, although iron depletion coexisting with either the anemia of chronic disease or active hepatocellular disease may not be clearly appreciated. The primary advantage of the determination was to help characterize the iron status of the patient with a hypochromic microcytic anemia or hypoferremia who would ordinarly require a bone-marrow examination for iron stores.
To define the significance of the uptake step by unidirectional uptake of iron was measured on proximal small intestintestinal segments from Nembutal-anesthetized rats. The method employed a nonabsorbable marker of adherent incubating medium, and the studies were performed during the linear time period of instantaneous uptake. Uptake was linear over the concentration range 0.1-10 mM, from three iron complexes. The rate varied with the bioavailability of the iron in each complex. The Q10 was 1.0-1.3. Uptake rates were similar in all segments of small intestine. Uptake was not increased in segments from iron-deficient animals or rats with hemolytic anemia. Cobalt did not inhibit the uptake rate. These studies demonstrate that the uptake of nonheme iron by the small intestinal mucosal cell is by passive diffusion and further indicate that the uptake step does not contribute significantly to the mucosal control of iron absorption.
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Gastrointestinal mucosal factors controlling rates of iron absorption were studied utilizing an in vivo closed duodenal loop technique. Cellular distribution of newly absorbed radioiron was identified by molecular sieve and iron-exchange chromatography of the mucosal cell supernate. In the normal animal, iron rapidly appeared in ferritin, and this fraction accounted for greater than 90% of mucosal supernatant radioactivity after 60 min absorption time. The nonferritin radioiron appeared to be unbound iron salts. In the presence of increased iron absorption induced by iron depletion or hemolysis, the major difference from the normal distribution pattern was an increase in the proportion and quantity of the free iron salts. Incorporation of newly absorbed iron into ferritin did not correlate with the rate of iron absorption. No evidence was found for a specific soluble iron-chelating molecule within the mucosal cell. The nonheme iron content of the mucosal supernates from iron-deficient and hemolyzing animals were significantly lower than in the normal animal.The data are consistent with hypotheses which suggest that iron absorption rates may be controlled in part by the rate of initial iron uptake by the mucosal cell and that a membrane transport mechanism exists which is modulated by the nonheme iron content of the mucosal cell or some portion thereof.
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Since various agents used in cancer chemotherapy exhibit antimicrobial activity in vitro, we performed sequential quantitative cultures of saline gargles obtained from patients receiving cancer chemotherapy to determine if such chemotherapy alters the composition of the aerobic oropharyngeal flora. When we compared results of cultures obtained from 12 patients just before and at various times after receiving courses of cancer chemotherapy, we observed small, though significant reductions in the numbers of total bacteria, alpha-hemolytic streptococci and inhibitory streptococci two to seven days after courses of chemotherapy. A concomitant increase in the percentage of patients colonized by gram-negative bacilli occurred. Of the chemotherapeutic agents used to treat our subjects, only doxorubicin exhibited antimicrobial activity in vitro. All four alpha-hemolytic streptococci, but none of the seven strains of gram-negative bacilli examined, were inhibited by doxorubicin at concentrations of less than or equal to 12.5 mg/l. Doxorubicin had a modest enhancing effect on in vitro adherence of gram-negative bacilli to human embryonic lung cells. These data suggest that cancer chemotherapy might play a role in colonization of cancer patients by gram-negative bacilli by creating a microbiologic vacuum conducive to such colonization. In this way, cancer chemotherapy might contribute to the high incidence of gram-negative bacillary pneumonia among patients with malignant neoplasms.
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