CD154 is expressed during treatment with calcineurin inhibitors after organ transplantation

BACKGROUND: CD154 (CD40 ligand) monoclonal antibody prevents allograft rejection in rodents and monkeys. Inasmuch as calcineurin inhibitors (CI) inhibit CD154 expression by pharmacologic agents in vitro, we investigated whether CD154 is also inhibited by CI in vivo and in vitro during allogeneic stimulation. METHODS: CD154 expression was determined by immunohistochemistry and flow cytometry in human lymph nodes and spleen sections from rhesus monkeys with or without CI treatment. The effect of CI on induction of CD154 expression was studied by stimulating lymphocytes with phorbol 12-myristate 13-acetate (PMA) and ionomycin or with allogeneic monocyte-derived mature dendritic cells. RESULTS: Lymph nodes from patients with or without CI cyclosporine (CsA) or FK506 (FK) treatment showed comparable CD154 expression, which was present on the cell surface of T cells. CD154-expressing cells were also present in spleens from monkeys treated with CsA in comparable numbers to those in the nontreated group. Moreover, in several liver transplant rejection biopsies taken during CI therapy CD154-expressing cells were observed. In vitro, CsA and FK strongly inhibited induction of CD154 expression on peripheral blood mononuclear cells by pharmacologic stimuli. Maximum inhibition was found at 50 ng/ml CsA and 20 ng/ml FK. CD154 expression induced by dendritic cells in peripheral blood mononuclear cells or spleen cells was also almost completely inhibited by CsA. CONCLUSION: Although CI strongly suppressed pharmacologic and allogeneic induction of CD154 expression on T cells in vitro at concentrations at approximately clinical trough levels, CD154 is prominently expressed during CI therapy in lymphoid tissue and (sporadically) in liver allografts. This suggests that the CD154-CD40 pathway remains functional during CI therapy, which may contribute to allograft rejections in the clinical setting.     

The accuracy of medicare claims data in identifying Alzheimer's disease

We linked Medicare claims data to information on 417 patients with a clinical diagnosis of Alzheimer's disease in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) to determine what proportion of them were identified as having Alzheimer's disease (AD) in Medicare claims records. Seventy-nine percent of these patients were identified as having AD using 5 years of claims data; 87% were identified as demented when a broader set of ICD-9-CM codes was used. An Anderson-Gill counting process approach was used to model the "hazard" of patients being identified as having AD in Medicare claims data. CERAD patients with mild dementia were less likely to be identified in the claims data as having AD. Once identified in Medicare claims as having AD, patients were more likely to be so identified again. When using only the physician supplier and institutional outpatient files, approximately 75% of CERAD patients were identified as having AD; hospital files used alone identified less than one-third (29%) of the CERAD patients as having AD. The data indicate that at least 3 consecutive years of physician supplier and physician outpatient claim files should be used to identify Medicare beneficiaries with AD using Medicare claims.     

The Saccharomyces cerevisiae Fin1 protein forms cell cycle-specific filaments between spindle pole bodies

The FIN1 gene from the yeast Saccharomyces cerevisiae encodes a basic protein with putative coiled-coil regions. Here we show that in large-budded cells a green fluorescent protein-Fin1 fusion protein is visible as a filament between the two spindle pole bodies. In resting cells the protein is undetectable, and in small-budded cells it is localized in the nucleus. During late mitosis it localizes on the spindle pole bodies. Filaments of cyano fluorescent protein-tagged Fin1 colocalize with filaments of green fluorescent protein-tagged Tub1 only in large-budded cells. By electron and atomic force microscopy we showed that purified recombinant Fin1p self-assembles into filaments with a diameter of approximately 10 nm. Our results indicate that the Fin1 protein forms a cell cycle-specific filament, additional to the microtubules, between the spindle pole bodies of dividing yeast cells.     

MR imaging of the brain in pediatric patients: diagnostic value of HASTE sequences

OBJECTIVE: The objective of this study was to determine the diagnostic value of half-Fourier single-shot turbo spin-echo (HASTE) sequences in MR imaging of the brain in pediatric patients. SUBJECTS AND METHODS: HASTE sequences were performed in 80 infants and children. Two radiologists who were unaware of the patients' medical histories independently reviewed the images for the presence of nine findings: defects of the parenchyma, hypoplasia or agenesis of the corpus callosum, edema, signs of increased intracranial pressure, myelination disorders, migration disorders, malformations, tumors, and widening of spaces of the cerebrospinal fluid. A conventional MR imaging examination that served as the reference examination was evaluated by the same two radiologists in a final consensus interpretation. The findings detected on the HASTE images were compared with the findings seen on the conventional MR images. The sensitivity and specificity of HASTE sequences were calculated, and Cohen's kappa statistic was used to determine interobserver agreement. RESULTS: Both radiologists correctly diagnosed all 20 defects of the parenchyma that were present in the patients. Radiologist 1 correctly identified 20 and radiologist 2 correctly identified 21 of the 22 patients with hypoplasia or agenesis of the corpus callosum. Both radiologists correctly diagnosed edema in eight of the nine patients in whom edema was present, and both correctly identified signs of increased intracranial pressure in eight of the nine children who had this condition. Radiologist 1 correctly diagnosed seven and radiologist 2 correctly identified nine of the 11 cases of myelination disorders. Both radiologists correctly diagnosed six of the 14 cases with migration disorders. All 13 brain malformations present in the patients were correctly identified by both reviewers. Both radiologists correctly identified all 11 patients with tumors, and both correctly identified all 35 patients with widening of spaces of the cerebrospinal fluid. CONCLUSION: HASTE images are highly sensitive for excluding the presence of brain tumor, hydrocephalus, or malformations of the brain. HASTE images are not reliable for evaluating patients with suspected myelination disorders or migration disorders.     

Punctate white-matter lesions in the full-term newborn: Underlying aetiology and outcome

Background

Punctate white matter lesions (PWMLs) are small focal patches of increased signal intensity (SI) on T1- and decreased SI on T2-weighted magnetic resonance imaging (MRI). To date, there have been few reports of PWMLs in term born infants.

2-Aminobenzo[b]thiophencarbonsäureester aus 3-Hydroxy-2-nitro-1-thiochromon

2-Aminobenzo[b]thiophenecarboxylic esters from 3-Hydroxy-2-nitro-1-thiochromone 3-Hydroxy-2-nitro-1-thiochromone (1b) , when mixed with bases in alcoholic solution, yields the 2-nitro-benzothiophene-3-carboxylates 4a and 4b as well as the 2-amino-3-benzothiophene-3-carboxylates 11a and 11b . Under the same conditions, 3-methoxy-2-nitro-1-thiochromone (1c) yields 3-amino-2-nitro-1-thiochromone (12) . Compound 1b reacts with morpholine in dioxane to give 2-nitro-benzothiophene-3-carboxamide (10) .     

Immune recovery after conventional and non-myeloablative allogeneic stem cell transplantation

The immune recovery of 66 patients undergoing allogeneic stem cell transplantation with either conventional or non-myeloablative conditioning regimen was studied. Infections post-transplant were enumerated and quantitative immunoglobuilins (IgG, IgA, IgM) and lymphocyte sub-sets 3, 6 and 12 months post-transplant were measured. A significant difference was found in the immunologic recovery of non-myeloablative and conventional ASCT in the patient population. The T-helper cell reconstitution was significantly faster after NMA than conventional transplantation and the recovery of B cells was faster after conventional transplantation. Regarding immunoglobulin levels, a faster recovery of IgM levels after NMA-ASCT and a delayed recovery of IgA levels was observed in both groups. These were accompanied by a significant difference in the frequency and severity of infectious episodes.