Neurectodermal differentiation of extraskeletal myxoid chondrosarcoma: a classical feature?

Extraskeletal myxoid chondrosarcoma (EMC) is a phenotypically and genotypically distinct entity with a protracted course. A documented case of an extraskeletal myxoid chondrosarcoma characterized by a t(9; 17) (q22; q11) translocation with a neuroendocrine and neural differentiation is reported.     

Analysis of the genomic sequence of a human metapneumovirus

We recently described the isolation of a novel paramyxovirus from children with respiratory tract disease in The Netherlands. Based on biological properties and limited sequence information the virus was provisionally classified as the first nonavian member of the Metapneumovirus genus and named human metapneumovirus (hMPV). This report describes the analysis of the sequences of all hMPV open reading frames (ORFs) and intergenic sequences as well as partial sequences of the genomic termini. The overall percentage of amino acid sequence identity between APV and hMPV N, P, M, F, M2-1, M2-2, and L ORFs was 56 to 88%. Some nucleotide sequence identity was also found between the noncoding regions of the APV and hMPV genomes. Although no discernible amino acid sequence identity was found between two of the ORFs of hMPV and ORFs of other paramyxoviruses, the amino acid content, hydrophilicity profiles, and location of these ORFs in the viral genome suggest that they represent SH and G proteins. The high percentage of sequence identity between APV and hMPV, their similar genomic organization (3'-N-P-M-F-M2-SH-G-L-5'), and phylogenetic analyses provide evidence for the proposed classification of hMPV as the first mammalian metapneumovirus.     

On the various manifestations of spontaneous autoimmune diabetes in rodent models

Autoimmune (type 1) diabetes mellitus in mouse, rat, and humans shares several features, including T lymphocyte infiltration into pancreatic islets and a dependence on permissive class II major histocompatibility complex (MHC) alleles. We report here on an experimental model involving mice that express influenza hemagglutinin (HA) under the control of the insulin promoter and, at the same time, a transgenic class II MHC-restricted T cell receptor (TcR) specific for an HA peptide. These mice spontaneously develop islet infiltrates resembling those found in NOD mice and most animals become diabetic within 8 weeks of age. Because of the availability of a clonotypic TcR antibody, we can be confident that the Ins-HA transgene does not induce any measurable alterations in the vast majority of T cells with the transgenic TcR in primary and secondary lymphoid organs. Continuous export of large numbers of HA-specific lymphocytes from the thymus was not required for the manifestation of the disease since mice thymectomized at 3 days after birth still developed the disease albeit with smaller infiltrates.     

Acute fibrinous and organizing pneumonia: a histological pattern of lung injury and possible variant of diffuse alveolar damage

CONTEXT: The histologic patterns of diffuse alveolar damage (DAD), bronchiolitis obliterans with organizing pneumonia (BOOP), and eosinophilic pneumonia (EP) are well-recognized histologic patterns of lung injury associated with an acute or subacute clinical presentation. We have recognized acute fibrinous and organizing pneumonia (AFOP) as a histologic pattern, which also occurs in this clinical setting but does not meet the classic histologic criteria for DAD, BOOP, or EP and may represent an underreported variant. OBJECTIVE: To investigate the clinical significance of the AFOP histologic pattern and to explore its possible relationship to other disorders, including DAD and BOOP. DESIGN: Open lung biopsy specimens and autopsy specimens were selected from the consultation files of the Armed Forces Institute of Pathology, which showed a dominant histologic pattern of intra-alveolar fibrin and organizing pneumonia. Varying amounts of organizing pneumonia, type 2 pneumocyte hyperplasia, edema, acute and chronic inflammation, and interstitial widening were seen. Cases with histologic patterns of classic DAD, BOOP, abscess formation, or eosinophilic pneumonia were excluded. To determine the clinical behavior of patients with this histologic finding, clinical and radiographic information and follow-up information were obtained. Statistical analysis was performed using Kaplan-Meier and chi(2) analysis. RESULTS: Seventeen patients (10 men, 7 women) with a mean age of 62 years (range, 33-78 years) had acute-onset symptoms of dyspnea (11), fever (6), cough (3), and hemoptysis (2). Associations believed to be clinically related to the lung disease included definitive or probable collagen vascular disease (3), amiodarone (1), sputum culture positive for Haemophilus influenza (1), lung culture positive for Acinetobacter sp. (1), lymphoma (1), hairspray (1), construction work (1), coal mining (1), and zoological work (1). Six patients had no identifiable origin or association. Follow-up revealed 2 clinical patterns of disease progression: a fulminate illness with rapid progression to death (n = 9; mean survival, 0.1 year) and a more subacute illness, with recovery (n = 8). Histologic analysis and initial symptoms did not correlate with eventual outcome, but 5 of the 5 patients who required mechanical ventilation died (P =.007). CONCLUSIONS: Acute fibrinous and organizing pneumonia is a histologic pattern associated with a clinical picture of acute lung injury that differs from the classic histologic patterns of DAD, BOOP, or EP. Similar to these patterns of acute lung injury, the AFOP pattern can occur in an idiopathic setting or with a spectrum of clinical associations. The overall mortality rate is similar to DAD and therefore may represent a histologic variant; however, AFOP appears to have 2 distinct patterns of disease progression and outcome. The need for mechanical ventilation was the only parameter that correlated with prognosis. None of the patients with a subacute clinical course required mechanical ventilation.     

Inhibition of TCR-mediated shedding of L-selectin (CD62L) on human and mouse CD4+ T cells by metalloproteinase inhibition: analysis of the regulation of Th1/Th2 function

The generation of a productive primary immune response is dependent on the ability of na?ve T lymphocytes to recirculate through peripheral lymph organs to encounter specific antigen. The process of na?ve CD4(+) T cell entry into lymph nodes correlates with cell surface expression of L-selectin (CD62L), which mediates early tethering and rolling events to endothelium prior to entry. Here, we demonstrate that surface expression of CD62L enhances CD4(+) T cell activation in vitro. The synthetic hydroxamate metalloproteinase inhibitor (BB-3103), specifically inhibits activation-induced shedding of CD62L from CD4(+) T cells by TCR cross-linking and lowers proliferation in part by reducing rapid tyrosine phosphorylation of zeta-associated protein 70 kDa (ZAP-70) and by increasing cytosolic free Ca(2+) concentration mobilization. BB-3103 also inhibited the proliferative response of both murine CD4(+) Th1 and Th2 subsets in vitro but the inhibitory effects were sustained only in Th2-type cells. Similarly, BB-3103 mediated prolonged inhibition of allergen-dependent peripheral T cell proliferation in atopic dermatitis patients but not in healthy controls. Analysis of CD62L expression on murine CD4(+) T cell subsets revealed that surface expression was maintained on Th1 cells but not Th2 cells. The differential effects of BB-3103 on primed effector CD4(+) T cells may provide new insights into generating therapeutic agents capable of redressing the Th2/Th1 imbalance in allergic diseases.     

Nutrition Screening,Reported Dietary Intake,Hospital Foods,and Malnutrition in Critical Care Patients in Malawi

In low-income countries there are few data on hospital malnutrition. Reduced food intake combined with nutrient-poor foods served in hospitals contribute to nutritional risk. This study investigated whether reported dietary intake and disease state of hospitalized adults in critical care units was related to malnutrition determined by mid-upper arm circumference (MUAC). Adult in-patients (n = 126) in tuberculosis, burn, oncology, and intensive care units in two public tertiary hospitals in Malawi were screened for nutritional status using MUAC and a question on current dietary intake. The hospital menu was reviewed; portion sizes were weighed. The prevalence of moderate and severe malnutrition was 62%. Patients with organ-related diseases and infectious diseases had the highest rates of reduced reported dietary intake, 71.4% and 57.9%, respectively; however, there was no association between reported dietary intake and MUAC. In those unable to eat, however, the rate of severe malnutrition was 50%. The menu consisted of porridge and thickened corn-based starch with fried cabbage; protein foods were provided twice weekly. There was a nutrient gap of 250 calories and 13 gm protein daily. The findings support the need for increasing dietetic/nutrition services to prevent and treat malnutrition in hospitals using simple screening tools.     

Scanning laser ophthalmoscope imaging of fluorescein-labelled blood cells

Purpose: To demonstrate the feasibility of a technique for the visualization by scanning laser ophthalmoscope (SLO) of fluores cein-labelled autologous leukocytes and platelets in retinal vessels. Method: Individual blood samples from rats and rabbits were centrifuged to isolate platelets and leukocytes, then passively labelled with fluorescein and reinjected into the same animal. An SLO was used to visualize and record cell displacement in the retinal circulation. Labelled platelets were analysed by flow cytometry. Results: By SLO, platelets appeared as a heterogeneous particle flow, and individual leukocytes appearing as brighter spots could easily be traced. Flow cytometry showed that after labelling platelets were well individualized and their size was slightly increased. Conclusion: Circulating blood cells can be visualized in retinal vessels by a simple method consisting of passive labelling of autologous platelets and leukocytes by fluorescein. No platelet toxicity was detected. This method could be applied to the study of blood cell movement in human retinal vascular diseases.Proprietary interest category: N     

Binding of antidepressants to human brain receptors: focus on newer generation compounds

Using radioligand binding assays and postmortem normal human brain tissue, we obtained equilibrium dissociation constants (K_ds) for 17 antidepressants and two of their metabolites at histamine H₁, muscarinic, ₁-adrenergic, ₂-adrenergic, dopamine D₂, serotonin 5-HT_1A, and serotonin 5-HT₂ receptors. Several newer antidepressants were compared with older drugs. In addition, we studied some antimuscarinic, antiparkinson, antihistamine, and neuroleptic compounds at some of these receptors. For the antidepressants, classical tricyclic antidepressants were the most potent drugs at five of the seven receptors (all but ₂-adrenergic and 5-HT_1A receptors). The chlorophenylpiperazine derivative antidepressants (etoperidone, nefazodone, trazodone) were the most potent antidepressants at ₂-adrenergic and 5-HT_1A receptors. Of ten antihistamines tested, none was more potent than doxepin at histamine H₁ receptors. At muscarinic receptors antidepressants and antihistamines had a range of potencies, which were mostly weaker than those for antimuscarinics. From the in vitro data, we expect adinazolam, bupropion, fluoxetine, sertraline, tomoxetine, and venlafaxine not to block any of these five receptors in vivo. An antidepressant's potency for blocking a specific receptor is predictive of certain side effects and drug-drug interactions. These studies can provide guidelines for the clinician in the choice of antidepressant.     

The Use of Seclusions and Physical Restraints: Just How Consistent Are We?

Research has yet to verify whether children with greater problems, in more restrictive settings such as inpatient units actually receive more protective interventions such as seclusions/restraints than children in less intrusive settings who should have less need. Despite many strong and conflicting opinions about how these interventions should be used, very little is actually known about when and how seclusions/restraints are in fact used. It is unclear what professions use seclusions/restraints most, in what settings, for which children, how consistently, and with what outcomes. The present research found significant variability in use across the continuum of care which could not be attributed to the severity of children's problems or to the restrictiveness of the setting. The two most similar settings differed the most in their use of these procedures. Patterns of utilization are difficult to explain and are a cause for concern because they suggest possible inconsistencies and use which does not depend upon client needs. Use was significantly but only weakly predicted by age and gender of children with younger males being more likely to receive these interventions. The finding that child and youth care workers in the settings studied were the professionals most likely by far to use these procedures, indicates needs for increased worker involvement in both quality assurance and supportive activities that explore potential for burnout and injury associated with high use.     

Role of CD18-dependent and CD18-independent mechanisms in the increased leukocyte adhesiveness and in the variations of circulating white blood cell populations induced by anti-CD3 monoclonal antibodies

Anti-CD3 antibodies induce a quick and profound depletion of peripheral blood mononuclear cells (PBMCs) that is not well understood. We studied the effect of OKT3, a mouse monoclonal antibody againts the human CD3 complex, on the in vitro adhesion of human PBMCs to monolayers of fresh and fixed human umbilical vein endothelial cells (HUVECs). OKT3 induced an increased adhesiveness of PBMCs. This phenomenon was blocked with anti-CD18 antibodies, indicating the participation of 2 integrins. As this increased adhesiveness could explain the lymphopenia by adhesion of PBMCs to endothelial cells and their sequestration in some peripheral vascular beds, we studied the effect of anti-CD18 antibodies in vivo on mice injected with 145/2C11, a hamster monoclonal antibody against murine CD3. Mice treated with 145/2C11 presented with a transient granulocytopenia and a sustained reduction in PBMCs. A monoclonal anti-CD18 antibody prevented the granulocytopenia but had no effect the drop in PBMCs. Consequently, the in vivo depletion of PBMCs after administration of an anti-CD3 monoclonal antibody involves CD18-independent mechanisms, while the transient drop in polymorphonuclear cells appears to be CD18-dependent.