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Biomedical subjects

M E Conrad

Publications and source records attributed to M E Conrad.

At least 19 recordsLinked to original sources

Newly identified iron-binding protein in human duodenal mucosa.

Studies were undertaken using human duodenal mucosa to determine whether it contained a counterpart to a newly identified iron-binding protein recently isolated from rat duodenum and named mobilferrin. Water-soluble homogenates were prepared from duodena of patients undergoing surgery for pancreatic carcinoma. An iron-binding protein with an approximate molecular mass of 56 Kd was purified to homogeneity using 60% ammonium sulfate and serial chromatographic steps. The protein was biochemically and immunologically distinct from transferrin and ferritin, and competitively bound to zinc, cobalt, and lead. Each molecule bound one molecule of iron with a kd of 8.9 x 10(-5). Human isolates reacted in an enzyme-linked immunosorbent assay with a polyclonal antibody raised in rabbits against a similar duodenal protein isolated from rat duodenum. It is postulated that mobilferrin plays a significant role in the absorption of iron and other metals and may explain partially the competition between certain metals for absorption in the small intestine.

Ammonium Sulfate

Sickle cell disease and hemochromatosis.

A 50 year-old patient with sickle cell anemia was seen who had received only two units of blood during his lifetime. He had marked iron overloading, cirrhosis of the liver, arthralgia, and mild glucose intolerance. We believe the iron overloading was associated with hereditary hemochromatosis rather than sickle cell anemia because he had HLA-A3 and B7 antigens, and hepatic iron deposits were primarily in parenchymal cells rather than Kupfer cells. The coexistence of either homozygous or heterozygous hemochromatosis should be suspected in sickle cell patients with organ damage from iron overloading.

Anemia, Sickle Cell

A role for mucin in the absorption of inorganic iron and other metal cations. A study in rats.

The steps involved in iron absorption are poorly understood. Although transferrin and ferritin are water soluble, most radioiron in gut homogenates after an intraluminal dose of radioiron is recovered in water-insoluble precipitates. Most radioiron in the precipitates was insoluble in detergents and organic solvents and was characterized as mucins. These isolates bound iron in vitro with a Kd of 9.09 x 10(-5). Similar iron binding was observed with commercial mucins. Iron binding to mucin occurred at acid pH and maintained the iron available for absorption with alkalinization. Similar pH-dependent binding to mucin was observed with zinc, cobalt, and lead. Iron competitively inhibited binding of these metals to mucin. However, iron chelates of ascorbate, fructose, and histidine donated iron to mucin at neutral pH. These data provided a role for gastric HCl and intestinal mucin in absorption of iron and metal cations and partial explanation of the competition for absorption between certain metals from the gut lumen. It is postulated that intestinal mucin delivers inorganic iron to intestinal absorptive cells in an acceptable form for absorption.

Animals

A newly identified iron binding protein in duodenal mucosa of rats. Purification and characterization of mobilferrin.

An iron binding protein with an approximate molecular mass of 56,000 daltons was purified to homogeneity from homogenates of rat duodenal mucosa. The protein was biochemically and immunologically distinct from transferrin and ferritin and competitively bound cobalt, copper, zinc, and lead. Each molecule bound one molecule of iron with a Kd of 9 X 10(-5). Dissociation of iron and the protein was accelerated at acid pH. Using an immunogold method, the protein was identified in the apical cytoplasm of proximal small intestinal cells and was not observed elsewhere in the intestinal mucosa and in other body organs. It was named mobilferrin from its city of origin and to differentiate it from other previously identified iron binding proteins.

Amino Acids

Ehrlichia canis: a tick-borne rickettsial-like infection in humans living in the southeastern United States.

During the past two years, sporadic cases of a rickettsial-like illness were reported in humans living in the Southeastern United States. The illness was serologically similar to Ehrlichia canis infections in dogs. It resembled spotless Rocky Mountain Spotted Fever but was differentiated from this infection serologically with acute and convalescent sera showing increasing titers to Ehrlichia canis. E. canis infection should be suspected in patients with fever, headache, malaise, myalgia, gastrointestinal symptoms, relative bradycardia, leukopenia, thrombocytopenia, and a recent exposure to either dogs or ticks. Although recovery has been observed in humans without treatment, prompt therapy with tetracycline is advised before obtaining results of serologic studies because an immunologically similar illness in untreated dogs has been lethal.

Animals

Ehrlichiosis: a cause of bone marrow hypoplasia in humans.

Infection with Ehrlichia canis should be suspected in patients with fever, headache, malaise, leukopenia, thrombocytopenia, and a history of recent exposure to ticks. The cytopenia is caused by bone marrow hypoplasia which may be severe. The disease may be confused with spotless Rocky Mountain spotted fever but can be differentiated from this infection serologically with acute and convalescent sea. In humans, recovery has occurred with and without antibiotic therapy. However, prompt antibiotic therapy is advised prior to serologic studies, especially in immunocompromised individuals, splenectomized persons, and patients with AIDS-who may develop a more overwhelming rickettsial infection.

Bone Marrow

Aplastic crisis in sickle cell disorders: bone marrow necrosis and human parvovirus infection.

Aplastic crisis in patients with sickle cell disease who develop a parvovirus infection may be associated with extensive bone marrow necrosis as well as acute selective erythroblastopenia. This illness may be manifested by pyrexia, lymphadenopathy, bone tenderness and significant hypoxemia with minimal roentgenographic findings in the lungs. It is uncertain whether the hypoxemia is caused by the effects of the viral infection on the lungs or is secondary to sickling of red blood cells in the pulmonary vasculature or both. The hypoxia may be sufficiently severe to require treatment with both oxygen and transfusion. The physical damage to the bone marrow associated with bone marrow necrosis may be more important than selective acute erythroblastopenia in inducing aplastic crisis in patients with sickle cell disorders. Studies of bone marrow biopsy specimens collected during parvovirus-associated aplastic crisis in patients with nonsickle cell hemolytic disorders would be helpful in determining the pathophysiology of parvovirus-associated disorders.

Acute Disease

Systemic necrotizing vasculitis in sickle cell disease.

A patient with sickle cell disease and systemic necrotizing vasculitis is reported. Although there are a number of immune defects in patients with sickle cell disorders, this association has not been previously reported. We suspect that immunologic disorders frequently are unrecognized in these patients because the symptoms are attributed to complications of sickle cell disease.

Adult

Prevention of endemic icteric viral hepatitis by administration of immune serum gamma globulin.

In a further analysis of a randomized, double-blind study of 107,803 U.S. soldiers receiving either immune serum gamma globulin (ISG) or placebo, serum specimens from the first week of clinical illness from 210 soldiers consecutively hospitalized with icteric hepatitis were reexamined by using modern immunologic methods to test for evidence of hepatitis A and B. Prophylactic intramuscular injection of 5 or 10 ml of ISG containing antibody to hepatitis A virus and antibody to hepatitis B surface antigen provided significant protection against development of endemic type A, type B, and non-A, non-B icteric hepatitis for six months if it was administered before exposure. Failure to receive a second injection of either 5 or 10 ml of ISG permitted an occurrence of hepatitis that was not significantly different from that among subjects who failed to receive a second placebo injection. ISG at 2 ml appeared equally effective in preventing hepatitis A but may be less effective in preventing hepatitis B and non-A, non-B hepatitis.

Hepatitis A

Mycosis fungoides: carcinogens and cerebral involvement.

Three patients with mycosis fungoides, who were long-term employees of a manufacturer of solid fuel propellants, were seen. Two of these patients had tumorous involvement of the central nervous system, which was successfully treated with radiation therapy. The potential relationship of carcinogens is discussed.

Brain Neoplasms

Small intestinal regulation of iron absorption in the rat.

Ultrastructural, biochemical, and immunologic studies of the small intestinal mucosa of rats were undertaken to investigate factors associated with the regulation of iron absorption. The quantity of iron within mucosal cells was proportionate to the degree of iron repletion. Although the quantity of iron-binding substances was similar in iron-deficient and iron-loaded animals, the unsaturated iron-binding capacity of mucosal cells varied inversely with the state of iron repletion of animals in ultrastructural, biochemical, and immunologic observations. Although only certain mucosal cells contained iron-binding substances, their number was not increased in iron-deficient animals. Greater quantities of iron and iron-binding substances were observed in duodenal mucosa than in ileal mucosa. These findings are consistent with the hypothesis that the quantity of unsaturated iron-binding substances within intestinal mucosal cells regulates iron absorption. These findings are only partially explained by changes observed in the concentration of ferritin and transferrin within intestinal mucosa and suggest that other iron-binding substances may also participate in the regulation of iron absorption.

Animals

Treatment of thrombotic thrombocytopenic purpura. Plasmapheresis, plasma transfusion, and vincristine.

In four patients with thrombotic thrombocytopenic purpura (TTP), the administration of plasma exchange and vincristine sulfate was associated with reversal of clinical and hematologic evidence of disease. Plasmapheresis with fresh frozen plasma replacement appears effective in acutely improving neurologic and hematologic abnormalities of patients with TTP and provides time for vincristine to become effective and induce lasting remissions. One patient with early relapse responded to a second short course of vincristine without other therapy. These data suggest that these treatment modalities should be considered as the initial treatment of TTP.

Adolescent