Endothelial progenitor cell capture by stents coated with antibody against CD34: the HEALING-FIM (Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth-First In Man) Registry

OBJECTIVES: This study was designed to evaluate whether rapid endothelialization of stainless steel stents with a functional endothelium prevents stent thrombosis and reduces the restenotic process. BACKGROUND: A "pro-healing" approach for prevention of post-stenting restenosis is theoretically favored over the use of cytotoxic or cytostatic local pharmacologic therapies. It is believed that the central role of the vascular endothelium is to maintain quiescence of the underlying media and adventitia. METHODS: Sixteen patients with de novo coronary artery disease were successfully treated with implantation of endothelial progenitor cell (EPC) capture stents. RESULTS: Complete procedural and angiographic success was achieved in all 16 patients. The nine-month composite major adverse cardiac and cerebrovascular events (MACCE) rate was 6.3% as a result of a symptom-driven target vessel revascularization in a single patient. There were no other MACCE despite only one month of clopidogrel treatment. At six-month follow-up, mean angiographic late luminal loss was 0.63 +/- 0.52 mm, and percent stent volume obstruction by intravascular ultrasound analysis was 27.2 +/- 20.9%. CONCLUSIONS: This first human clinical investigation of this technology demonstrates that the EPC capture coronary stent is safe and feasible for the treatment of de novo coronary artery disease. Further developments in this technology are warranted to evaluate the efficacy of this device for the treatment of coronary artery disease.     

The Mr 95,000 gelatin-binding protein in differentiated human macrophages and granulocytes

Cultured adherent human macrophages and a promonocytic cell line, U 937, were previously shown to produce a Mr 95,000 gelatin-binding protein. The protein has no immunologic cross-reactivity with the well- characterized gelatin-binding protein fibronectin and the Mr 70,000 gelatin-binding protein produced by a variety of mesenchymal or epithelial cell types (T. Vartio et al, J Biol Chem 257:8862, 1982). In the present study the Mr 95,000 protein was found in Triton X-100 extracts of granulocytes purified from human blood buffy coat. The protein, as isolated by gelatin-agarose, was immunologically cross- reactive with the corresponding macrophage protein in immunoblotting assay. When peripheral blood and bone marrow cells were examined for the presence of the Mr 95,000 protein by indirect immunofluorescence, positive staining was detected only in differentiated granulocytes but not to any significant extent in metamyelocytes, myelocytes, promyelocytes, or in normal or leukemic blasts. In granulocytes the protein had a granular cytoplasmic distribution. In freshly prepared monocyte cultures, the Mr 95,000 protein was detected in low amounts in the cytoplasm, while along with differentiation of the cells into macrophages, the immunofluorescence increased in a reticular and vesicular cytoplasmic pattern and in a juxtanuclear cap, probably representing the Golgi complex. In conclusion, the Mr 95,000 gelatin- binding protein was specifically detected in macrophages and granulocytes and may thus serve as a differentiation marker for these phagocytic cells.     

Juror perceptions of false confessions versus witness recantations

In false confessions, someone confesses to a crime but then later retracts that confession, whereas in witness recantations, an eyewitness testifies but then later revokes that testimony. The revocations are conceptually similar, but they differ in the author of the revocation – the defendant versus a third party. The current study examines differences in juror perceptions of the legitimacy of false confessions versus witness recantations, and also takes contextual influences (coercion and crime severity) into account. False confessions were found to be judged more harshly than witness recantations, but, surprisingly, levels of coercion and the severity of the crime did not influence decision-making in the manner that the original hypotheses predicted. Implications for the application of this research are discussed.     

Peripheral T-cell lymphoma emerging in a patient with aggressive polymyositis: molecular evidence for neoplastic transformation of an oligoclonal T-cell infiltrate

We report a rare case of peripheral T-cell lymphoma arising in a 52-year-old man with biopsy-proven aggressive polymyositis, who had cardiac involvement, progressive bulbar symptoms, and died 11 months post diagnosis due to multiorgan failure. Using a multimodality approach including immunohistochemistry, genome-wide single nucleotide polymorphism (SNP)-array analysis, and high-throughput sequencing of the complementary determining region 3 (CDR3) of T-cell receptor beta (TCRβ) genes, our study demonstrates a molecular link between polymyositis and T-cell lymphoma, and provides evidence of the rapid and possibly late occurrence of genomic instability during neoplastic transformation of an oligoclonal T-cell population. Immunohistochemical analysis revealed loss of CD5, CD7, and CD8 antigen expression in autopsy tissue samples, as well as the occurrence of aberrant CD56 expression, not seen in pre-mortem biopsies, supporting the emergence of a neoplastic T-cell population. Multiplex polymerase chain reaction and next-generation sequencing of the TCRβ CDR3 region displayed two unique T-cell clones in both the diagnostic biopsy confirming polymyositis and the autopsy muscle tissue exhibiting T-cell lymphoma, linking the two pathological processes. SNP-array analysis revealed complex genomic abnormalities at autopsy but not in the pre-mortem muscle biopsies displaying polymyositis, confirming malignant transformation of the oligoclonal T-cell infiltrate. Our findings raise the possibility that clinically aggressive polymyositis might represent a preneoplastic condition in some instances, similar to certain other autoimmune and inflammatory disorders.     

Development of cortical influences on superior colliculus multisensory neurons: effects of dark‐rearing

Rearing cats from birth to adulthood in darkness prevents neurons in the superior colliculus (SC) from developing the capability to integrate visual and non‐visual (e.g. visual‐auditory) inputs. Presumably, this developmental anomaly is due to a lack of experience with the combination of those cues, which is essential to form associative links between them. The visual‐auditory multisensory integration capacity of SC neurons has also been shown to depend on the functional integrity of converging visual and auditory inputs from the ipsilateral association cortex. Disrupting these cortico‐collicular projections at any stage of life results in a pattern of outcomes similar to those found after dark‐rearing; SC neurons respond to stimuli in both sensory modalities, but cannot integrate the information they provide. Thus, it is possible that dark‐rearing compromises the development of these descending tecto‐petal connections and the essential influences they convey. However, the results of the present experiments, using cortical deactivation to assess the presence of cortico‐collicular influences, demonstrate that dark‐rearing does not prevent the association cortex from developing robust influences over SC multisensory responses. In fact, dark‐rearing may increase their potency over that observed in normally‐reared animals. Nevertheless, their influences are still insufficient to support SC multisensory integration. It appears that cross‐modal experience shapes the cortical influence to selectively enhance responses to cross‐modal stimulus combinations that are likely to be derived from the same event. In the absence of this experience, the cortex develops an indiscriminate excitatory influence over its multisensory SC target neurons.     

Treatment of recurrent,multiloculated, obstructive hydrocephalus with suprahepatic peritoneal catheter placement

The suprahepatic space represents a potential reservoir for cerebrospinal fluid absorption and becomes critical when extensive abdominal adhesions prevent passage of a peritoneal shunt catheter toward the pelvis. We present a patient with refractory hydrocephalus in which a multishunt system with drainage into the suprahepatic space was ultimately successful in decompressing the patient’s trapped ventricular spaces.