Altered monocyte function in uremia

Uremia appears to suppress immune function predisposing patients to infections. When the defect in cellular immunity was studied by exposing mononuclear cells (MNC) from uremic patients and controls to tetanus toxoid, diptheria toxoid, or Candida albicans antigen in vitro, the uremic cells were far less responsive. Monocytes and T cells, which are both involved in the proliferative response to soluble antigens, were isolated from MNC of uremic patients and HLA class II matched controls and incubated with tetanus toxoid. Tetanus toxoid-pulsed uremic monocytes were unable to stimulate the proliferation of HLA identical control T lymphocytes. Lymphocytes from uremic patients, however, were stimulated by tetanus toxoid-pulsed control monocytes. Therefore, the ability of monocytes to function as accessory cells is severely affected by uremia. The uremic monocytes were FcR+, produced IL-1 beta, and expressed levels of HLA class II antigens comparable to controls. Although the biochemical defect in uremic monocytes remains unknown, the abnormality could explain many of the immunological changes of uremia.     

Control of a Candida glabrata prosthetic endovascular infection with posaconazole.

A 63-year-old man with a history of cirrhosis of the liver developed Candida glabrata fungemia after undergoing transjugular intrahepatic portosystemic shunt (TIPS) placement. Treatment with oral fluconazole was initially effective, but when the patient became neutropenic, subsequent blood cultures grew C. glabrata and a thrombus developed, which partially occluded the stent. Despite treatment with fluconazole, blood cultures remained positive for C. glabrata. Treatment with posaconazole resulted in clinical improvement and the patient had only intermittently positive fungal cultures for 6 weeks. A CT scan showed resolution of the inferior vena cava thrombus. Subsequently, the patient developed hepatocellular carcinoma and hepatic encephalopathy and became noncompliant with posaconazole. Blood cultures again became positive for C. glabrata. The patient died a few weeks after the diagnosis of hepatocellular carcinoma, but the cause of death was believed to be worsening liver dysfunction, not C. glabrata infection. Posaconazole had controlled the infection for about 3 months prior to his death. In conclusion, posaconazole may be a useful option in the management of prosthetic endovascular infections caused by C. glabrata.     

Visual motion perception from stimulation of the human medial parieto-occipital cortex

Summary Visual phenomena evoked by direct electrical stimulation of extrastriate cortex were observed in 30 epileptic patients as part of a presurgical investigation. An incremental sequence of low-level bipolar stimulation trains was delivered at medial and lateral pairs of contacts of stereotaxically-implanted multilead intracerebral electrodes in parietal, occipital and posterior temporal regions. Diffusion of stimulus afterdischarges was monitored by electrodes in temporal and frontal lobes and by the non-stimulated contacts of the stimulated electrode. Localized stimulations evoked few visual phenomena. The strongest anatomo-perceptual correlation was found for stimulation in the medial parieto-occipital fissure which evoked visual motion phenomena in all three patients stimulated in that region. The evoked motion perceptions were not associated with eye movements or any particular localization of the epileptic focus. These perceptions were only evoked once outside of the medial PO region at the 61 sites examined. The results suggest that the medial parieto-occipital region is closely linked to the human visual motion processing system.     

The role of COX-2 in angiogenesis and rheumatoid arthritis

Recent evidence suggests that cyclooxygenase (COX)-2 is a mediator of angiogenesis, and COX-2 activity is known to be upregulated in the rheumatoid arthritis (RA) synovium. We examined whether mediation of angiogenesis by COX-2 was occuring in cells of the RA synovium and in microvascular endothelial cells (ECs) that are similar to those found in the RA synovium. We demonstrate that rofecoxib, a selective COX-2 inhibitor, acts directly on human dermal microvascular ECs (HMVECs) to inhibit their chemotactic and tube forming ability. Likewise, pretreatment of HMVECs with rofecoxib significantly inhibited their ability to form tubes induced by conditioned media (CM) of activated RA synovial fibroblasts. When RA synovial fibroblasts were pretreated with rofecoxib for 16 h and then stimulated with interleukin (IL)-1beta, their CM induced significantly less HMVEC tube formation when compared with CM from vehicle-treated RA synovial fibroblasts. ELISAs performed on activated RA fibroblast CM for known proangiogenic factors demonstrated a significant reduction in bFGF, in addition to the expected decrease in PGE(2). Our studies suggest that COX-2-induced angiogenic activity is an active mechanism within diseased synovium and may provide an additional rationale for the use of COX-2 inhibitors in RA.     

Opsonophagocytosis of fluorescent polystyrene beads coupled to Neisseria meningitidis serogroup A, C, Y, or W135 polysaccharide correlates with serum bactericidal activity

We developed a polysaccharide-specific flow cytometric opsonophagocytic assay (OPA) for the simultaneous measurement of functional antibody to Neisseria meningitidis serogroups A, C, Y, and W135. OPA titers significantly correlated with serum bactericidal assay titers for all serogroups tested (mean r = 0.96; P < 0.001). OPA could be used in meningococcal vaccine evaluation.     

Expression of CD4 on peripheral blood granulocytes. a novel finding in a case of myelodysplastic syndrome in association with t(5;12)

Myelodysplastic syndromes (MDS) are associated with cell maturation defects that can manifest as abnormal surface antigen expression. We describe a patient with refractory anemia with excess blasts, who presented with infection and extensive dysplastic features in peripheral blood granulocytes. The granulocytes expressed CD11b, CD13, CD15, CD33, and CD43. The granulocytes also expressed CD4 antigen. Cytogenetic analysis showed a clonal t(5;12)(q33;p13). The patient improved on antibiotics with partial improvement in the dysplastic features. However, shortly after, the patient experienced paravertebral extramedullary blast transformation followed by a leukemia phase of acute monoblastic leukemia. The patient died a few days later. This is the first report describing anomalous expression of CD4 on granulocytes in MDS. Since the breakpoint on chromosome 12 is near the CD4 gene, which is mapped to 12p12, we hypothesize that dysregulation of the CD4 gene may have occurred resulting in its persistent expression on mature and maturing granulocytes.