STIMULATED LYMPHOCYTE CULTURES : RESPONDER RECRUITMENT AND CELL CYCLE KINETICS

Lymphocytes, stimulated with different doses of plant mitogens or allogeneic cells, incorporate varying amounts of [³H]thymidine. Theoretically, this may be due to different numbers of responding cells, to earlier proliferative response of these cells, and/or to their more or less rapid transit through the cell cycle. Dog peripheral blood lymphocytes were stimulated in vitro with different doses of phytohemagglutinin (PHA), or with allogeneic lymphocytes. After their synchronization by incubation with hydroxyurea (4 mM), the mean durations of the cell cycle, and of the different cell cycle phases were constant and unrelated to strength or type of stimulation. PHA-stimulated lymphocyte cultures were maintained in the presence of colchicine, to prevent clonal proliferation of responding lymphocytes. DNA uptake in this setting, attributed to first generation responders, was related to the strength of proliferative lymphocyte response in control cultures without colchicine. Furthermore, cell proliferation occurred earlier with greater stimulation. It is concluded that higher [³H]thymidine uptake in vitro by stimulated lymphocytes is due to greater numbers of responding cells, which are triggered into proliferative response earlier, and not to a more rapid transit of the responding cells through the cell cycle.     

Stem and Osteotomy Length are Critical for Success of the Transfemoral Approach and Cementless Stem Revision

Background  

The transfemoral approach is an extensile surgical approach that is performed routinely to facilitate cement and implant removal and improve exposure for revision stem implantation. Previous studies have looked at clinical results of small patient groups. The factors associated with fixation failure of cementless revision stems when using this approach have not been examined.     

Differences in the stress distribution in the distal femur between patellofemoral joint replacement and total knee replacement: a finite element study

ABSTRACT: BACKGROUND: Patellofemoral joint replacement is a successful treatment option for isolated patellofemoral osteoarthritis. However, results of later conversion to total knee replacement may be compromised by periprosthetic bone loss. Previous clinical studies have demonstrated a decrease in distal femoral bone mineral density after patellofemoral joint replacement. It is unclear whether this is due to periprosthetic stress shielding. The main objective of the current study was to evaluate the stress shielding effect of prosthetic replacement with 2 different patellofemoral prosthetic designs and with a total knee prosthesis. METHODS: We developed a finite element model of an intact patellofemoral joint, and finite element models of patellofemoral joint replacement with a Journey PFJ prosthesis, a Richards II prosthesis, and a Genesis II total knee prosthesis. For each of these 4 finite element models, the average Von Mises stress in 2 clinically relevant regions of interest were evaluated during a simulated squatting movement until 120 degrees of flexion. RESULTS: During deep knee flexion, in the anterior region of interest, the average Von Mises stress with the Journey PFJ design was comparable to the physiological knee, while reduced by almost 25% for both the Richards II design and the Genesis II total knee joint replacement design. The average Von Mises stress in the supracondylar region of interest was similar for both patellofemoral prosthetic designs and the physiological model, with slightly lower stress for the Genesis II design. CONCLUSIONS: Patellofemoral joint replacement results in periprosthetic stress-shielding, although to a smaller degree than in total knee replacement. Specific patellofemoral prosthetic design properties may result in differences in femoral stress shielding.     

Advances in and Algorithms for the Treatment of Relapsing-Remitting Multiple Sclerosis

Treatment options in relapsing-remitting multiple sclerosis have increased considerably in recent years; currently, a dozen different preparations of disease-modifying therapies are available and some more are expected to be marketed soon. For the treating neurologist this broad therapeutic repertoire not only greatly improves individualized management of the disease, but also makes choices more complex and difficult. A number of factors must be considered, including disease activity and severity, safety profile, and patient preference. We here discuss the currently existing options and suggest treatment algorithms for managing relapsing-remitting multiple sclerosis.     

Transition from primary Raynaud's phenomenon to secondary Raynaud's phenomenon identified by diagnosis of an associated disease: results of ten years of prospective surveillance

OBJECTIVE: To assess the early signs, risk factors, and rate of transition from primary Raynaud's phenomenon (primary RP) to secondary RP. METHODS: A clinical sample of 307 consecutive patients with RP was included in a prospective followup study. After an initial screening, 244 patients were classified as having primary RP, of whom 236 were followed up for a mean +/- SD of 11.2 +/- 3.9 years. Patients classified according to the screening as having suspected secondary RP underwent an extended screening program annually until transition to secondary RP occurred. RESULTS: The initial prevalence of secondary RP was 11%. The annual incidence of transition to suspected secondary RP was 2%, and the annual incidence of transition to secondary RP was 1%. Overall, 46 patients were classified as having suspected secondary RP, and 23 of these later were classified as having secondary RP. Older age at onset of RP (hazard ratio 2.59, 95% confidence interval [95% CI] 1.40-4.80), shorter duration of RP at enrollment (hazard ratio 0.87, 95% CI 0.81-0.94), and abnormal findings on thoracic outlet test (hazard ratio 2.69, 95% CI 1.12-6.48) were associated with an increased risk for transition to secondary RP. Compared with patients with suspected secondary RP, those diagnosed as having secondary RP had a higher number and earlier occurrence of pathologic findings. Furthermore, antinuclear antibodies at a titer of > or = 1:320 and positive findings in specific serologic subsets were associated with a significantly increased risk for developing a connective tissue disease. CONCLUSION: Patients diagnosed initially as having primary RP may actually comprise 1 of 3 groups: those with idiopathic RP, those with a rather benign disease course, and those with a more severe course of the disease.     

Differential responses of FLIPLong and FLIPShort-overexpressing human myeloid leukemia cells to TNF-alpha and TRAIL-initiated apoptotic signals

OBJECTIVE: Clonal marrow cells from patients with early myelodysplastic syndrome (MDS) undergo apoptosis in response to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). Cells from advanced MDS are resistant to TRAIL. Two isoforms of the Flice inhibitory protein (FLIP) short (FLIPS) and FLIP long (FLIPL), which modulate TRAIL signals, showed disease-stage-dependent differential regulation. Therefore, we aimed at characterizing potential differential effects of FLIPL and FLIPS, on TRAIL and TNF-alpha-induced apoptosis in model leukemic cell lines. MATERIALS AND METHODS: Using lentiviral constructs, FLIPL and FLIPS, as well as a green fluorescent protein control were overexpressed in ML-1 cells, which constitutively express very low levels of FLIP and are highly sensitive to apoptosis induction. Cells were then exposed to TRAIL or TNF-alpha, and effects on the extrinsic and intrinsic pathways of apoptosis induction were assessed. RESULTS: Overexpression of FLIP reduced TRAIL and TNF-alpha-induced apoptosis in ML-1 cells. However, while FLIPL completely abrogated apoptosis, FLIPS allowed for BID cleavage and caspase-3 activation. Concurrently, there was a decline of Bcl-xL and X-linked inhibitor of apoptosis protein (XIAP) in FLIPS cells followed by apoptosis. Further, inhibition of nuclear factor-kappaB (NF-kappaB) activation in TNF-alpha-treated cells resulted in profound apoptosis in FLIPS, but not in FLIPL-overexpressing cells, consistent with the observations in patients with early stage MDS. Inhibition of NF-kappaB had only minimal effects on TRAIL signaling. CONCLUSION: Thus, FLIPL and FLIPS exerted differential effects in myeloid leukemic cell lines in response to TRAIL and TNF-alpha. It might be possible to therapeutically exploit those differences with effector molecules specific for the FLIP isoforms.     

Immune response to capsular polysaccharide and surface proteins of Streptococcus pneumoniae in patients with invasive pneumococcal disease

The immune response to pneumococcal capsular polysaccharides (CPSs) and to the pneumococcal surface proteins cell wall-associated serine proteinase A (PrtA), pneumococcal surface protein A (PspA), and Streptococcus pneumoniae pullulanase A was evaluated in 45 patients with invasive pneumococcal disease compared with healthy adults. In serum from patients with meningitis and pneumonia, CPS antibody levels were low, compared with healthy adults; antibody levels did not differ between groups and did not change between phases. Levels of immunoglobulin G directed against the investigated pneumococcal surface proteins in patients with invasive pneumococcal disease were in the same range as in healthy adults. However, median PrtA and PspA antibody levels tended to increase during early convalescent phase. Low levels of CPS antibody, rather than of antibodies directed against the pneumococcal surface proteins, may predispose to invasive pneumococcal infection.