CGA-7 and HHF, two monoclonal antibodies that recognize muscle actin and react with adherent cells in human long-term bone marrow cultures

The CGA-7, a monoclonal antibody that reacts with smooth muscle cell actin but not with endothelial cell or fibroblast actin, and HHF, a monoclonal antibody that reacts with smooth muscle, skeletal muscle, and cardiac muscle actin, both recognize microfilaments present within adherent cells from actively hematopoietic human long-term marrow cultures. Macrophages, monocytes, and cultured marrow fibroblasts do not react with either antibody. These data suggest that the anti-actin antibodies may serve as useful markers for in vitro microenvironmental cells and lend support to the hypothesis that stromal cells from long- term marrow cultures are different from marrow fibroblasts and may constitute a unique cell lineage.     

Use of risk stratification to target therapies in patients with recent onset arthritis; design of a prospective randomized multicenter controlled trial

Background  

Early and intensive treatment is important to inducing remission and preventing joint damage in patients with rheumatoid arthritis. While intensive combination therapy (Disease Modifying Anti-rheumatic Drugs and/or biologicals) is the most effective, rheumatologists in daily clinical practice prefer to start with monotherapy methotrexate and bridging corticosteroids. Intensive treatment should be started as soon as the first symptoms manifest, but at this early stage, ACR criteria may not be fulfilled, and there is a danger of over-treatment. We will therefore determine which induction therapy is most effective in the very early stage of persistent arthritis. To overcome over-treatment and under-treatment, the intensity of induction therapy will be based on a prediction model that predicts patients' propensity for persistent arthritis.     

Open‐MRI measures of cam intrusion for hips in an anterior impingement position relate to acetabular contact force

Open MRI in functional positions has potential to directly and non‐invasively assess cam femoroacetabular impingement (FAI). Our objective was to investigate whether open MRI can depict intrusion of the cam deformity into the intra‐articular joint space, and whether intrusion is associated with elevated acetabular contact force. Cadaver hips (9 cam; 3 controls) were positioned in an anterior impingement posture and imaged using open MRI with multi‐planar reformatting. The β‐angle (describing clearance between the femoral neck and acetabulum) was measured around the entire circumference of the femoral neck. We defined a binary “MRI cam‐intrusion sign” (positive if β < 0°). We then instrumented each hip with a piezoresistive sensor and conducted six repeated positioning trials, measuring acetabular contact force (F). We defined a binary “contact‐force sign” (positive if F > 20N). Cam hips were more likely than controls to have both a positive MRI cam‐intrusion sign (p = 0.0182, Fisher's exact test) and positive contact‐force sign (p = 0.0083), which represents direct experimental evidence for cam intrusion. There was also a relationship between the MRI cam‐intrusion sign and contact‐force sign (p = 0.033), representing a link between imaging and mechanics. Our findings indicate that open MRI has significant potential for in vivo investigation of the cam FAI mechanism. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:205–216, 2016.     

In vitro control of Mycobacterium bovis by macrophages.

Mycobacterium bovis is frequently seen inside macrophages in vivo. The outcome of M. bovis infection depends on T cell interactions with macrophages, however mycobacteria are thought to be relatively resistant to macrophage killing. Little is known about the immunological mechanisms which control intracellular growth of M. bovis, and in the absence of T cell help the organism is capable of intracellular survival and replication. We have investigated the role of macrophages in controlling growth of virulent M. bovis or M. bovis BCG in vitro. At a multiplicity of infection of 5:1, macrophages from a range of animal species including cattle, deer, possums, ferrets and mice restricted growth of BCG while M. bovis grew progressively. Inter-species variation in controlling growth of M. bovis by alveolar macrophages was observed. Pre-treatment of macrophages with interferon-gamma and lipopolysaccharide inhibited intracellular growth of M. bovis. Addition of freshly recruited macrophages further inhibited M. bovis, and intracellular growth was arrested by activated fresh macrophages. Our observations suggest that na?ve macrophages can prevent BCG growth, while T cell activation in conjunction with freshly recruited macrophages is required for preventing growth of M. bovis.     

Primary dural lymphoma: A novel concept of heterogeneous disease

Spinal primary dural lymphoma (PDL) is uncommon with a total of 37 previous well‐documented cases reported, including one diagnosed in the authors' institution. More recently we encountered an additional case of spinal PDL that, similarly to our previous case, was grade 1–2 follicular B‐cell PDL. Our two cases were diagnosed over a 3‐year interval in a 72‐year‐old female and a 74‐year‐old male, respectively. An exhaustive literature review on PDL was performed consequently to reveal that: (i) spinal and cerebral sites of involvement by PDL are constantly mutually exclusive; and (ii) unlike cerebral PDL, which is usually of marginal zone B‐cell type, only two of the 38 cases of spinal PDL were diagnosed as such, diffuse large B‐cell lymphoma being the most commonly encountered type in the spine. This divergence infers that, in contrast to the prevailing concept that PDL is a unique disease group, PDL appears to be rather heterogeneous with a difference in predilection of lymphoma type for the anatomical site of dural involvement. Such a site‐specific lymphoma‐type predilection phenomenon, well‐recognized in other organ systems, has not been acknowledged in PDL. This report brings new insights into PDL, and may contribute to a better understanding of nervous system pathophysiology and lymphoma classification.     

Failure of recombinant human interleukin-3 therapy to induce erythropoiesis in patients with refractory Diamond-Blackfan anemia [see comments]

In two previous studies, we observed that recombinant human interleukin- 3 (IL-3) induced an increase in marrow burst-forming unit-erythroid- derived colonies in vitro in some patients with Diamond-Blackfan anemia (DBA). To determine whether a similar erythropoietic response could be induced in vivo, we treated 13 patients with DBA (aged 4 to 19 years) with two preparations of IL-3. All patients had absent absolute reticulocyte counts and markedly reduced to absent recognizable bone marrow erythroid elements; patients with circulating reticulocytes in the previous 12 months were excluded from study. All patients except 1 had failed steroid therapy and had been transfusion-dependent since infancy; 1 patient was maintained on high-dose prednisone at the time of enrollment. On the first arm of the study, IL-3 (Immunex Corp, Seattle, WA) was administered subcutaneously using a dose escalation regimen of 125 to 500 micrograms/m2/day in divided dosage at 12-hour intervals, coadministered with 1.5 mg/kg/d of oral ferrous sulphate. Of the 13 patients that entered the trial, 4 stopped prematurely because of adverse side effects. In the other 9 evaluable cases, reticulocytes increased transiently in 1 patient from 0 to 65 x 10(9)/L after 35 days of IL-3 therapy at 250 micrograms/m2, but transfusion dependency persisted. One transient peak in absolute reticulocyte count was noted in 6 other patients, but no erythroid response was observed after completion of a full course of IL-3. Oral prednisone at 0.5 mg/kg/d was then coadministered with IL-3 at 500 micrograms/m2 to 5 of the patients without effect, and treatment was stopped. In 2 patients, a second preparation of IL-3 (Sandoz Canada Inc, Dorval, Quebec, Canada) was initiated in a dose escalation regimen of 2.5 to 10 micrograms/kg and was coadministered with ferrous sulphate. No erythroid response was observed in either patient, and in one of the two, alternate-day subcutaneous recombinant erythropoietin at 300 U/kg was administered for 3 weeks in combination with daily IL-3 at 10 micrograms/kg, but no increased erythropoiesis was seen. Significant increases in white blood cell and eosinophil counts during administration of both preparations of IL-3 were observed in all patients. These data show that the response of DBA patients to IL-3 in vivo is heterogeneous and cannot be predicted from in vitro studies. The absence of a corrective effect of IL-3 in these patients with DBA indicates that a deficiency of the cytokine is not central in the pathogenesis of the disorder.