Spectrin-alpha I/61: a new structural variant of alpha-spectrin in a double-heterozygous form of hereditary pyropoikilocytosis

Recent biochemical studies have led to the identification of abnormal spectrins in the erythrocytes of patients with hereditary pyropoikilocytosis (HPP) and hereditary elliptocytosis (HE). In this report we describe the biochemical characterization of the erythrocytes from a proband with severe HPP who is doubly heterozygous for two mutant spectrins (Sp): Sp alpha I/74 and a new, previously undetected, mutant of alpha-spectrin designated Sp alpha I/61. The proband's erythrocytes are unstable when exposed to 45 degrees C, and her membrane skeletons exhibit instability to shear stress. The content of spectrin in the proband's erythrocyte membranes is decreased to 75% of control values. The amount of spectrin dimers in crude 4 degrees C spectrin extracts is increased (58%) as compared with control values (6% +/- 4%). Limited tryptic digestion reveals a marked decrease in the normal 80,000-dalton alpha I domain, an increase in the 74,000-dalton fragment that is characteristic of Sp alpha I/74, and an increase in a series of new fragments of 61,000, 55,000, 21,000, and 16,000 daltons. Both parents are asymptomatic, but they have increased amounts of spectrin dimers (17% to 25%). Limited tryptic digestion of the father's spectrin demonstrates the presence of a previously identified abnormal spectrin (Sp alpha I/74) that is characterized by a decrease in content of the 80,000-dalton peptide and an increase in concentration of the 74,000-dalton peptide. The mother's spectrin digests show a decrease in the amount of 80,000-dalton peptide and the formation of new peptides of 61,000, 55,000, 21,000, and 16,000 daltons. The data indicate that this severe form of HPP is due to the inheritance of two distinct abnormal spectrins, Sp alpha I/74 and a new spectrin mutant, Sp alpha I/61.     

Specificity of autoantibodies in autoimmune thrombocytopenia

In 42 patients with autoimmune thrombocytopenia (AITP) and a positive direct platelet suspension immunofluorescence test (PSIFT), the antigenic specificity of the autoantibodies was studied. Because the autoantibodies were often not detectable in the serum and additional HLA antibodies may disturb the reaction pattern with the platelet panel, we used eluates prepared from the patients' platelets for this study. Thirty-five patients had antibodies equally reactive with normal platelets, irrespective of their antigenic make-up, but not with the platelets from two Glanzmann's disease patients. Absorption and elution experiments in two patients showed that his was probably not due to the presence of a combination of anti-Zwa and anti-Zwb antibodies. Thus, the majority of autoantibodies against platelets seems to be directed against antigenic determinants not present on Glanzmann's disease platelets, but perhaps located on the platelet-membrane glycoproteins IIb and/or IIIa. In ten patients, antibodies of no, or still unknown, specificity were detected. Three of these had additional antibodies not reactive with the platelets of the two Glanzmann patients.     

A human antibody binds to alpha-galactose receptors and mimics the effects of Clostridium difficile toxin A in rat colon

BACKGROUND & AIMS: Nearly all human sera contain an immunoglobulin G antibody (antigalactose) that binds the trisaccharide Gal alpha 1-3Gal beta 1-4GlcNAc expressed on cells from most mammals but not humans. Because the Clostridium difficile toxin A receptor in rodents contains this trisaccharide, the aim of this study was to examine whether antigalactose could mimic the enterotoxic effects of toxin A and bind to receptors containing this trisaccharide. METHODS: Fluid secretion, [3H]-mannitol permeability, and release of rat mast cell protease II and prostaglandin E2 were measured after luminal exposure of rat colon to either purified human anti-galactose, control immunoglobulin G, toxin A, or buffer. RESULTS: Toxin A (5 micrograms) and antigalactose (250 micrograms) but not control immunoglobulin (250 micrograms) stimulated colonic fluid secretion and caused increased mannitol permeability and rat mast cell protease II release. Antigalactose and toxin A and, to a lesser degree, control immunoglobulin G also stimulated release of prostaglandin E2, but only toxin A produced acute inflammation of rat colonic mucosa. Antigalactose and toxin A bound specifically to a single class of colonic brush border receptors with dissociation constants of 10(-6) mol/L and 5.4 x 10(-8) mol/L, respectively. CONCLUSIONS: Fluid secretion, increased permeability, and mast cell activation occur in rat colon when toxin A or human antigalactose immunoglobulin G bind to receptors bearing the trisaccharide Gal alpha 1-3Gal beta 1-4GlcNAc. (Gastroenterology 1996 Jun;110(6):1704-12)     

Duodenal hematoma: the ring sign in MR imaging

Proper management of duodenal hematoma requires that an accurate diagnosis be made using noninvasive radiological methods. Conventional imaging may be nonspecific if there is no history of trauma or coagulopathy. Two cases of duodenal hematoma that were imaged by magnetic resonance (MR) and computed tomography (CT) are described. In both cases the hematoma had a well-defined concentric ring configuration on MR images, a finding which helped establish the diagnosis. MR imaging may provide tissue-specific characterization of duodenal hematomas.     

Biliary stricture dilatation: multicenter review of clinical management in 73 patients

Eighty-nine biliary strictures in 73 patients who had undergone percutaneous balloon dilatation were reviewed to determine long-term patency rates and clinical management problems. The majority of dilatations were performed in patients with anastomotic strictures (n = 44), iatrogenic strictures (n = 28), and strictures associated with sclerosing cholangitis (n = 17). Patency rates after 36 months or more were 67%, 76%, and 42%, respectively. Complications, mostly minor, occurred in less than 7% of patients. Of patients with significant biliary obstruction, 15% had little or no intrahepatic biliary duct dilatation demonstrated by cross-sectional imaging and/or direct cholangiography. No definite conclusions could be drawn about the utility of long-term internal/external stenting.     

Rapid MR imaging with suspended respiration: clinical application in the liver

The authors demonstrate that it is possible to obtain highly T1-weighted images of the abdomen using a suspended respiration partial saturation (SRPS) method in a breath-holding interval. T2*-weighted images, which reflect tissue T2 as well as variations in the static magnetic field, can also be rapidly obtained. The authors studied five healthy subjects and 19 patients with a variety of liver abnormalities, including benign and malignant hepatic neoplasms, fatty liver infiltration, ascites, and hematoma. On T1-weighted multisection acquisitions, the entire liver can be screened for mass lesions in a single 20-second breath-holding interval. Phase-contrast SRPS images are sensitive to fatty infiltration of the liver. SRPS images are more sensitive to variations in magnetic susceptibility than spin-echo images are, which has been proved to be of value in the detection of hemorrhage. With continued pulse sequence development and clinical study, this method has the potential to become the method of choice for evaluation of the upper abdomen.     

Ferrite particles for bowel contrast in MR imaging: design issues and feasibility studies

Diverse materials with varying physical and magnetic properties have been evaluated as gastrointestinal contrast agents for magnetic resonance (MR) imaging. Uniform marking of the small bowel remains the greatest challenge. Ferrites are magnetically active iron oxide particles that are miscible with water and cause loss of signal on MR images. The decrease in MR signal intensity produced by ferrites occurs with a wide range of iron concentrations (0.1-10 mM) and with both T1- and T2-weighted pulse sequences. These effects of ferrites are explained by predominant T2 shortening with negligible T1 effects. The ferrite preparation used in this study was stable in vitro, with little iron solubilized by acid. Intragastric administration of ferrite (5 mg of iron per kg in 6 ml) routinely marked the small bowel of rats. The authors conclude that ferrites represent a promising new class of contrast agents for gastrointestinal MR imaging.