Hereditary spherocytosis with spectrin deficiency due to an unstable truncated beta spectrin.

Red cell membrane protein analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and direct quantitation by radioimmunoassay or cytofluorometry defines four distinct subsets of patients with hereditary spherocytosis: Patients with isolated spectrin deficiency, combined spectrin and ankyrin deficiency, band 3 deficiency, and protein 4.2 deficiency. In regard to the first group, only one mutation of beta spectrin has been reported in the literature.

A novel mobile element inserted in the alpha spectrin gene: spectrin dayton. A truncated alpha spectrin associated with hereditary elliptocytosis.

Nonviral retrotransposons, retropseudogenes, and short interspersed nuclear elements (SINEs) are mobile DNA segments capable of transposition to new genomic locations, where they may alter gene expression. De novo integration into specific genes has been described in both germ and somatic cells. We report a family with hereditary elliptocytosis and pyropoikilocytosis associated with a truncated alpha-spectrin protein.

Primary structure, ligand binding, and localization of the human type 3 inositol 1,4,5-trisphosphate receptor expressed in intestinal epithelium.

The second messenger, inositol 1,4,5-trisphosphate (InsP3) transduces many hormonal signals which regulate Ca(2+)-dependent processes in the intestinal epithelium. To study the receptors for InsP3 (InsP3Rs), which function as intracellular Ca2+ channels, cDNA clones encoding InsP3Rs were isolated from a human colon adenocarcinoma cell line, HT29. The majority of clones encoded the type 3 InsP3R, the product of the ITPR3 gene on chromosome 6, for which only a 147-amino-acid fragment was known previously (Ozcelik, T.

Spectrin cagliari. an Ala-->Gly substitution in helix 1 of beta spectrin repeat 17 that severely disrupts the structure and self-association of the erythrocyte spectrin heterodimer.

The spectrin tetramer, the principal structural element of the red cell membrane skeleton, is formed by stable head-to-head self-association of two spectrin heterodimers. The self-association site appears to be formed by interactions between helices 1 and 2 of beta spectrin repeat 17 of one dimer with helix 3 of alpha spectrin repeat 1 of the other dimer to form two combined alpha-beta triple-helical segments. The head of the heterodimer appears to involve similar intradimer interactions.

Molecular basis of spectrin deficiency in hereditary pyropoikilocytosis.

Hereditary pyropoikilocytosis (HPP) is a recessively inherited hemolytic anemia characterized by severe poikilocytosis and red blood cell fragmentation. HPP red blood cells are partially deficient in spectrin and contain a mutant alpha or beta-spectrin that is defective in terms of spectrin self-association. Although the nature of the latter defect has been studied in considerable detail and many mutations of alpha-spectrin and beta spectrin have been identified, the molecular basis of spectrin deficiency is unknown.

Structural domain mapping and phosphorylation of human erythrocyte pallidin (band 4.2).

Pallidin (band 4.2) is a major protein of the human erythrocyte membrane, and plays an important but as yet undefined role in maintaining the normal shape and lifespan of the erythrocyte. The pallidin protein has been purified by a new procedure which yields a protein which is > 97% pure as judged by gel electrophoresis, while pallidin purified by our original procedure is only approx.

Biogenesis of erythrocyte membrane skeleton in health and disease.

To study the biogenesis of red cell membrane skeleton at various stages of erythroid differentiation, we have chosen the following model systems: a) Rauscher erythroleukemia cell line representing the early stages of differentiation, b) Friend erythroleukemia cells, and c) in vitro cultured human erythroblasts. The latter two systems represent terminally differentiated erythroblasts. Using these model systems, we have shown asynchronous synthesis of membrane proteins during erythroid differentiation.

Successful management of paraprotein-associated peripheral polyneuropathies by immunoadsorption of plasma with staphylococcal protein A.

Two patients with paraprotein-associated peripheral polyneuropathy were treated successfully using immunoadsorption of patient's plasma with staphylococcal protein A. Both had previously been treated with immunosuppressive agents or plasma exchange, and were rapidly relapsing at the time of their protein A immunoadsorption therapy. One patient was treated "on-line" with a blood cell separator, and one was treated "off-line.

Metastatic breast carcinoma presenting as persistent diarrhea.

Patients with breast carcinoma metastatic to the colon generally present with multiple symptoms, usually pain, vomiting, nausea, and ascites. We describe a patient who presented only with persistent diarrhea, underwent surgery for colon cancer, and, on pathological evaluation of the surgical specimen, was found to have metastatic breast cancer affecting the colon. Metastatic breast cancer should therefore be suspected in patients with a history of breast cancer and diarrhea of unknown cause that is not accompanied by other symptoms.

Prognostic factors in sterile pancreatic necrosis.

Although the overall mortality in sterile pancreatic necrosis is low, patients who experience systemic complications may have a higher mortality. To study the impact of systemic complications and other factors on survival, possible prognostic factors were evaluated among 26 patients who experienced at least one systemic complication. Mortality was 38%.

Noninvasive carotid duplex ultrasound imaging for the evaluation and management of carotid atherosclerotic disease.

Renewed interest in surgical management of atherosclerotic disease of the carotid bifurcation underscores the necessity for accurate and efficacious means for diagnostic evaluation of patients with suspected carotid disease. Noninvasive testing by carotid duplex ultrasound, which combines high-resolution B-mode imaging with pulsed Doppler spectral analysis, is the method of choice. Noninvasive testing permits identification of potentially significant carotid stenosis, occlusion, or unstable plaque morphology with virtually no significant morbidity from the testing itself.

Endometriosis causing colon obstruction in two postmenopausal women.

Colonic endometriosis is an uncommon lesion usually found in premenopausal women. We describe two postmenopausal women with colonic endometriosis that resulted in colonic obstruction. One of the women was receiving estrogen-replacement therapy.

Maturation of murine erythroleukemia cells committed to differentiation requires protein kinase C.

Treatment of murine erythroleukemia cells (MELC) attached to fibronectin-coated dishes with dimethyl sulfoxide causes the cells to become committed to the erythroid differentiation pathway. These cells mature extensively and acquire the characteristics of erythroid cells. The cells lose their cell-surface fibronectin receptors and accumulate red cell-specific membrane proteins, such as band 3, in amounts comparable to those in erythrocytes.

Asynchronous synthesis of membrane skeletal proteins during terminal maturation of murine erythroblasts.

To study the changes in the synthesis of the major membrane skeletal proteins, their assembly on the membrane, and their turnover during terminal red blood cell maturation in vivo, we have compared early proerythroblasts and late erythroblasts obtained from the spleens of mice at different times after infection with the anemia-inducing strain of Friend virus (FVA). Metabolic labeling of these cells indicates striking differences between early and late erythroblasts. In early erythroblasts, spectrin and ankyrin are synthesized in large amounts in the cytosol with proportionately high levels of spectrin and ankyrin messenger RNA (mRNA).

Band 3 Tuscaloosa: Pro327----Arg327 substitution in the cytoplasmic domain of erythrocyte band 3 protein associated with spherocytic hemolytic anemia and partial deficiency of protein 4.2.

Protein 4.2 is a major red blood cell (RBC) protein that interacts with the band 3 protein and with ankyrin. Inherited deficiencies of this protein are associated with spherocytic hemolytic anemia, but the molecular basis of this defect is unknown.

Urinoma masquerading as pancreatic pseudocyst.

In this article, we report on a patient with recurrent pancreatitis who had received multiple celiac plexus injections for control of pain, and then developed a cystic mass adjacent to the body and tail of the pancreas suggestive of a pancreatic pseudocyst. The cystic mass proved to be a urinoma. The distinction between pancreatic pseudocyst and urinoma was made by CT scan with intravenous contrast utilizing delayed films, which demonstrated leakage of contrast into the cystic structure.

Obesity as a predictor of severity in acute pancreatitis.

In order to determine whether the presence of obesity, defined as increased body mass index, would serve as a predictor of severity in acute pancreatitis, we have reviewed the medical records of 27 patients with severe acute pancreatitis. All patients had at least four positive Ranson's signs; all but three patients had at least five Ranson's signs. When the 13 patients with a fatal outcome were compared with the 14 who lived, neither obesity nor respiratory failure was an independent predictor of death.

Four different mutations in codon 28 of alpha spectrin are associated with structurally and functionally abnormal spectrin alpha I/74 in hereditary elliptocytosis.

Hereditary elliptocytosis (HE) Sp alpha I/74 is a disorder associated with defective spectrin (Sp) heterodimer self-association and an abnormal tryptic cleavage of the 80-kD alpha I domain of Sp resulting in increased amounts of a 74-kD peptide. The molecular basis of this disorder is heterogeneous and mutations in codons 28, 46, 48, and 49 (codons 22, 40, 42, and 43 in the previous nomenclature which did not include the six NH2-terminal amino acids) have been reported. In this study we present data on seven unrelated HE Sp alpha I/74 kindred from diverse racial backgrounds in whom we identified four different mutations all occurring in exon 2 of alpha Sp at codon 28.

Spinal cord compression secondary to extramedullary hematopoiesis: a noninvasive management based on MRI.

We report the first case of spinal cord compression secondary to extramedullary hematopoiesis in which the diagnosis was made by magnetic resonance imaging (MRI). Based on the great advantage of this imaging test that visualizes the entire spine, the noninvasive approach to such patients, using low-dose radiation therapy and guided by MRI is discussed. This management appears to be both efficacious and safe.