Identification of Bakb, a new platelet-specific antigen associated with posttransfusion purpura

Baka is a platelet alloantigen whose putative allele, Bakb, has not been identified previously. By using a serum, "Har," obtained from a patient with posttransfusion purpura, we describe the platelet alloantigen Bakb. The Har serum reacted with an NP-40-extractable platelet membrane protein of 142 kd with mobility similar to platelet glycoprotein IIb alpha. We found that the antigen recognized by the Har serum is inherited in an autosomal dominant mode with an apparent gene frequency of .39. Chi-square analysis of observed and expected phenotype frequencies indicated that serum Har recognizes Bakb, the anticipated allele of Baka. Our findings provide new evidence for polymorphism of glycoprotein IIb and for the association of posttransfusion purpura with alloimmunization to determinants on this glycoprotein.     

Association of the subtype 2 of the Epstein-Barr virus with T-cell non- Hodgkin's lymphoma of the midline granuloma type [see comments]

Lethal midline granuloma (LMG) is associated with Epstein-Barr virus (EBV). The latter has at least two subtypes with different biological properties. The subtypes can be identified by their genomic configuration. Using EBV-RNA (EBER) in situ hybridization and EBV polymerase chain reaction (PCR), we have looked for the presence of EBV in six LMGs and six non-Hodgkin's lymphomas (NHLs) located in the nasopharyngeal region, and determined the subtype of EBV. Six of six LMGs were positive by PCR and EBER in situ hybridization, whereas NHLs were either negative or, in three of six cases, showed few EBER- positive cells considered to be nonneoplastic lymphocytes. The subtype 2 was found in LMG lesions of three of six patients; the remaining three of six patients with LMG had the generally occurring subtype 1. The results indicate that the association of EBV with NHL may depend more on tumor type than on its localization. The occurrence of the rare subtype 2 in LMG may relate to a covert immune defect.     

Astrocyte-induced cortical vasodilation is mediated by D-serine and endothelial nitric oxide synthase

Astrocytes play a critical role in neurovascular coupling by providing a physical linkage from synapses to arterioles and releasing vaso-active gliotransmitters. We identified a gliotransmitter pathway by which astrocytes influence arteriole lumen diameter. Astrocytes synthesize and release NMDA receptor coagonist, D-serine, in response to neurotransmitter input. Mouse cortical slice astrocyte activation by metabotropic glutamate receptors or photolysis of caged Ca²⁺ produced dilation of penetrating arterioles in a manner attenuated by scavenging D-serine with D-amino acid oxidase, deleting the enzyme responsible for D-serine synthesis (serine racemase) or blocking NMDA receptor glycine coagonist sites with 5,7-dichlorokynurenic acid. We also found that dilatory responses were dramatically reduced by inhibition or elimination of endothelial nitric oxide synthase and that the vasodilatory effect of endothelial nitric oxide synthase is likely mediated by suppressing levels of the vasoconstrictor arachidonic acid metabolite, 20-hydroxy arachidonic acid. Our results provide evidence that D-serine coactivation of NMDA receptors and endothelial nitric oxide synthase is involved in astrocyte-mediated neurovascular coupling.     

Granulomatous mastitis: a report of seven cases

The clinical history and histological features of seven cases of granulomatous mastitis are presented. The lesion occurs in young parous women as a tender extra-areolar breast lump. Histologically, non-caseating discrete granulomas are present, confined to breast lobules with, in three cases, coalescence of the granulomas and microabscess formation. Pathogenesis of the changes is discussed. It is thought that granulomatous mastitis is an entity morphologically distinct from duct ectasia/plasma cell mastitis and the commoner forms of granulomatous breast diseases.     

Erythropoietin structure-function relationships: high degree of sequence homology among mammals

To investigate structure-function relationships of erythropoietin (Epo), we have obtained cDNA sequences that encode the mature Epo protein of a variety of mammals. A first set of primers, corresponding to conserved nucleotide sequences between mouse and human DNAs, allowed us to amplify by polymerase chain reaction (PCR) intron 1/exon 2 fragments from genomic DNA of the hamster, cat, lion, dog, horse, sheep, dolphin, and pig. Sequencing of these fragments permitted the design of a second generation of species-specific primers. RNA was prepared from anemic kidneys and reverse-transcribed. Using our battery of species-specific 5' primers, we were able to successfully PCR- amplify Epo cDNA from Rhesus monkey, rat, sheep, dog, cat, and pig. Deduced amino acid sequences of mature Epo proteins from these animals, in combination with known sequences for human, Cynomolgus monkey, and mouse, showed a high degree of homology, which explains the biologic and immunological cross-reactivity that has been observed in a number of species. Human Epo is 91% identical to monkey Epo, 85% to cat and dog Epo, and 80% to 82% to pig, sheep, mouse, and rat Epos. There was full conservation of (1) the disulfide bridge linking the NH2 and COOH termini; (2) N-glycosylation sites; and (3) predicted amphipathic alpha- helices. In contrast, the short disulfide bridge (C29/C33 in humans) is not invariant. Cys33 was replaced by a Pro in rodents. Most of the amino acid replacements were conservative. The C-terminal part of the loop between the C and D helices showed the most variation, with several amino acid substitutions, deletions, and/or insertions. Calculations of maximum parsimony for intron 1/exon 2 sequences as well as coding sequences enabled the construction of cladograms that are in good agreement with known phylogenetic relationships.     

Bone marrow disorders: characterization with quantitative MR imaging

Thirty patients with various hematologic disorders and 15 healthy control subjects underwent quantitative magnetic resonance (MR) imaging of the lumbar spine with spin-echo techniques. Images of patients with infiltrative bone marrow disorders showed significantly more prolonged T1 times than those of control subjects (P less than .001). It was not possible to distinguish different diffuse infiltrative bone marrow disorders on the basis of T1 values. Aplastic anemia could be distinguished from normality because of significantly shortened T1 (P less than .001). A significant correlation was seen between T1 and bone marrow cellularity (r = .74, P less than .001). T2 was of no value in the characterization of bone marrow disorders. Quantitative MR imaging dose not improve the diagnostic potential of bone marrow imaging in the detection of diffuse marrow infiltrates.