[Bone marrow transplantation in thalassemia]. / Transplantatsiia kostnogo mozga pri talassemii.

Thalassemia major is a progressive disease. Modern therapy with transfusions and iron chelation has greatly improved both the quality and length of thalassemics life. Nevertheless, progressive overload of iron in the organs, hepatitis and other infections acquired randomly imply the risk of mortality that increases with age. Bone marrow transplant from an HLA identical donor (a possibility for about 45%) represents the only form of radical cure of the disease. With the classification of the classes of risk we know today that a thalassemic child has a chance to die from transplant 3 to 100 with probability of being cured 94%. Thalassemics that receive the transplant at a more advanced stage of complications of the disease have a major risk of death due to the transplant of class 2 (14% probability of death due to the transplant against 83% chance of being cured). Class 43 patients have 9 chances out of 100 to die of transplant and 60% probability of being cured of thalassemia.

Structure and function of urodele myelin lacking alpha-hydroxy fatty acid-containing galactosphingolipids: slow nerve conduction and unusual myelin thickness.

Myelin of several Caudata (Urodela) species appears to be unique in the fact that it lacks hydroxycerebrosides and hydroxysulfatides although it contains their non-hydroxy counterparts. Comparison of the nerve conduction velocities in the Urodeles Necturus (salamander) and Notophthalmus (newt) with that in a reptile, Anolis (chameleon) which contains hydroxycerebrosides and -sulfatides indicated that the values were significantly reduced in the urodeles. Furthermore, urodele myelin thickness remained uniformly the same regardless of the size of the nerve fiber. Despite these differences the myelins appeared structurally similar. Electron microscopic and X-ray diffraction studies did not disclose any structural difference between the two orders. A teased fiber technique established that the ratio of internodal distance and fiber diameter in urodele nerves was essentially similar to that in Anolis. These findings suggest that the absence of hydroxycerebroside and -sulfatide may be related to the reduction in nerve conduction velocity and unusual myelin thickness in the urodele nervous system.

Carboxyl-terminal domain of the Epstein-Barr virus nuclear antigen is highly immunogenic in man.

The carboxyl-terminal one-third of the Epstein-Barr virus nuclear antigen (EBNA-1) encoded by the BamHI restriction fragment K was synthesized in Escherichia coli by use of a high-expression plasmid. The resultant 28-kDa EBNA fusion polypeptide, comprising 5-10% of the total soluble bacterial protein, was purified to apparent homogeneity by phosphocellulose and hydroxylapatite column chromatography. Both rabbit monospecific antibodies and mouse monoclonal antibodies against 28-kDa EBNA gave nuclear immunofluorescence staining on Epstein-Barr virus (EBV)-infected lymphoblastoid cell lines and recognized the appropriate intact EBNA polypeptide bands on immunoblots. An ELISA with the purified 28-kDa EBNA as antigen was used to quantitate anti-EBNA antibody in human serum samples. The ELISA method was approximately 100-fold more sensitive than the classical anticomplement immunofluorescence assay. Anti-EBNA antibody was detected in sera from 100% of normal individuals who were seropositive for the viral capsid antigen, and low anti-EBNA titers were detected in serum from most patients with acute infectious mononucleosis. The assay gave the expected pattern of titers in sera from patients with rheumatoid arthritis, Burkitt lymphoma, or nasopharyngeal carcinoma, thus confirming the validity of this purified reagent for assessing EBNA antibody status. Approximately 10% of normal individuals and rheumatoid arthritis patients had anti-EBNA titers as high as those seen in nasopharyngeal carcinoma patients. In these high-titer individuals, greater than 1% of the total IgG are antibodies that recognize 28-kDa EBNA, which indicates that the carboxyl-terminal domain of EBNA is highly immunogenic.

Capsaicin lowers plasma cholesterol and triglycerides of lagomorphs.

The present study determines the effect on plasma total cholesterol, triglycerides, and HDL-C values when capsaicin (8-methyl-N-vanillyl-6-nonenamide) is administered at the dose of 8mg/animal/day to young female rabbits maintained on a 0.5% cholesterol diet over a five week experimental period. Our data indicate that mammals of the order Lagomorpha fed cholesterol rich diets and supplemented with capsaicin show decreased plasma total cholesterol, triglycerides, and total cholesterol to HDL-C ratio as compared to cholesterol level of controls. The mechanism of this effect is probably due to decreased intestinal absorption of the lipids.

The lipid composition of urodele myelin which lacks hydroxycerebroside and hydroxysulfatide.

The concentrations of cerebrosides and sulfatides were measured in the nervous systems of urodeles and related orders with a high performance liquid chromatographic technique. The peripheral and central nervous systems of all three urodele species, Necturus maculosis (mud puppy, a salamander), Notophthalmus viridescens (eastern red spot newt), and Desmognathus ochropheus (mountain salamander), were found to be completely devoid of alpha-hydroxy fatty acid-containing cerebrosides and sulfatides. All species of reptiles and fish classes close to urodeles contain these galactolipids. The levels of nonhydroxy fatty acid-containing cerebrosides and sulfatides are essentially similar in both urodeles and reptiles. Myelin isolated from Necturus spinal cord had a specific density of 1.07, lighter than mammalian myelin. Except for the absence of hydroxycerebrosides and hydroxysulfatides, the lipid composition of Necturus spinal cord myelin is essentially similar to that of frog and rat myelin. The fatty acids of nonhydroxycerebrosides are rich in monounsaturated homologs of C22-C25, and the sphingoid base consists of both sphinganine and sphingosine. Electron microscopic examination of the sciatic nerve showed that the general structure and interlamellar distances of salamander and newt myelin are identical to those of frog, chameleon, and rat. Necturus myelin, therefore, can be used as a model for the study of the functional and structural role of hydroxygalactolipids.

An unusual glucocerebroside in the crustacean nervous system.

High concentrations of glucocerebroside (glucosylceramide) were found in the ventral nerve cord, brain, optic nerve, and antenna, but not in the nonneural tissue, of the brown shrimp Penaeus aztecus aztecus. This lipid contained unusual sphingoid bases consisting of 14-, 15-, and 16-carbon sphinganines and sphingenines. The fatty acids were mainly nonhydroxylated homologs 22 carbons long and longer, similar to those found in galactocerebroside but differing from those in glucocerebroside in mammalian nervous systems.

Suppressor cells in transplantation tolerance. II. maturation of suppressor cells in the bone marrow chimera.

Histoincompatible bone marrow allografts were established in lethally irradiated rats. At various times after transplantation, the spleen cells were harvested, subjected to mixed lymphocyte cultures, and assayed for suppressor cells in vitro and in vivo by adoptive transfer studies. Alloantigen-nonspecific suppressor cells appeared in the chimera at 40 days after grafting, coinciding with the resolution of graft-versus-host disease (GVHD). At 250 days the nonspecific suppressor cells were replaced by suppressor cells specifically suppressing donor-versus-host alloantigen responses. At 720 days suppressor cells could no longer be identified by in vitro methods but were identified by in vivo adoptive transfer of transplantation tolerance. After injection of host-type antigen into chimeras, the suppressor cells could be again demonstrated by in vitro methods.

The effect of bile acids and lipase on absorption of tallow in young chicks.

White leghorn chicks were fed diets with 4% tallow supplemented with one of the following bile acids at .04%: cholic acid, chenodeoxycholic acid, dehydrocholic acid, deoxycholic acid, or sodium taurocholate. Cholic acid improved the absorption of tallow but not significantly; chenodeoxycholic acid significantly improved tallow absorption during days 0 to 7 but decreased it during days 14 to 21. The bile acids, dehydrocholic acid, deoxycholic acid, and sodium taurocholate had no significant effect on absorption of tallow. In a 2 x 3 factorial design involving cholic acid and lipase, .04% cholic acid and/or .10% lipase significantly improved the absorption of tallow by 8 and 4% in chicks 1 and 3 weeks of age, respectively. Dry matter digestibility and efficiency appeared to be improved with the improvement of lipid absorption.

Constituents of the human ventricular myocardium: connective tissue hyperplasia accompanying muscular hypertrophy.

Left-sided congestive heart failure may be secondary to decreased left ventricular myocardial compliance in some patients. To investigate the anatomic basis for altered wall stiffness, morphometric determinations of muscle cell nuclear density and percent of myocardium consisting of muscle cells were made for right and left ventricular free wall and septum in 127 hearts with normal coronary arteries. The hearts were normal (33 patients), had left ventricular hypertrophy (28 patients), right ventricular hypertrophy (25 patients), or chronic dilatation (41 patients). With cardiac enlargement, the average percent of myocardium consisting of muscle did not change from the approximately 75% value characteristic of normal hearts. In contrast, muscle cell nuclear density decreased proportionate to cardiac enlargement, demonstrating that muscle cell hypertrophy, not hyperplasia, is the basis for weight increase. Some hearts with marked longstanding dilatation also had perivascular and interstitital "striae" of connective tissue differing from replacement fibrosis. An increase in epicardial coronary artery caliber commensurate with increased heart weight suggests that ischemia is not the basis of connective tissue increase. The results show that cardiac muscle cell hypertrophy is accompanied by commensurate increase in interstitial connective tissues. This pattern of myocardial growth with cardiac enlargement may produce increased myocardial stiffness simply as a result of increased wall thickness, and may lead to left-sided congestive heart failure.

Effect of cytomegalovirus infection on metabolism of WI-38 cell cultures: concise communication.

The effect of cytomegalovirus on the metabolism in monolayers of human embryonic lung fibroblasts (WI-38 cells) was studied. Effects of viral infection were examined by comparing [3H] thymidine incorporation in infected cells with that in uninfected cells. The time for detecting changes in cellular metabolism using the radiometric method was compared with that for observing cytopathic effects in infected cells. Compared with uninfected cells, cells infected with 10(4) TCID50 of virus showed nearly 400% increased in [3H] thymidine uptake 48 hr after infection. The radiometric method was able to detect 10(3) TCID50 of virus, with about 250% stimulation, 24--48 hr before visible signs of cytopathic effects. Our results suggest that with further development, radiometric measurement of metabolism in cytomegalovirus-infected cell cultures might provide a means of detecting viral presence in clinical assays. The radiometric method has the advantage of objectivity and potential for automation.