Elastolytic activity of human monocytes from synovial fluid and blood of patients with arthritis. Relations to levels of interleukin 6 and soluble interleukin 2 receptor

Synovial fluid (SF) and blood from 24 patients with non-traumatic, sterile hydarthron were examined for monocyte elastolysis (M?E) and for levels of interleukin 6 (IL-6) and of soluble interleukin 2 receptor (sIL-2R). Six patients had osteoarthrosis (OA) and 18 patients had inflammatory hydarthron (IH), 10 of whom had rheumatoid arthritis (RA). Blood M?E was lower in OA than in IH, both measured as basal M?E activity and after in vitro stimulation with immune complexes and phorbol myristate acetate (PMA). SF M?E was higher than M?E in blood (p less than 0.01). This increase in SF M?E could be mimicked in vitro by prestimulation of blood M? with low levels of IC. SF IL-6 and sIL-2R were also elevated (p less than 0.01). All three parameters correlated to the degree of joint inflammation evaluated by SF leucocyte level, complement activation, blood C Reactive Protein, and to the clinical evaluation of the joint. The increase in SF M?E, IL-6 and sIL-2R in patients with IH, points to a stimulation of M? and lymphocytes in the joint.     

Risk indicators for low back trouble

A general population of 928 men and women aged 30, 40, 50 and 60 years participated in a health survey with emphasis on low back trouble (LBT). In all 135 variables were analysed to identify possible indicators for first-time experience and recurrence or persistence of LBT during a one-year follow-up. Stepwise logistic regression analyses were carried out to identify the most informative combinations of indicators for prediction of LBT. For men, a high risk for recurrence or persistence of LBT was associated with frequent LBT in the past, worsening of the LBT since its onset, sciatica and living alone. For women corresponding risk indicators were: recency of the last LBT episode, waking up during night because of LBT, aggravation of LBT when standing, rumbling of "the stomach" and smoking. The strongest risk indicators for first-time experience of LBT were epigastric pain, daily smoking and low isometric endurance of the back muscles. In addition, hospitalisations for whatever cause and a long distance from home to work showed predictive power for first-time LBT among gainfully employed participants. The results indicate that persons with either recurring or first-time LBT had more health problems and probably lived under a higher psycho-social pressure than those without LBT in the follow-up year.     

Incomplete effector/memory differentiation of antigen-primed CD8+ T cells in gene gun DNA-vaccinated mice

DNA vaccination is an efficient way to induce CD8+ T cell memory, but it is still unclear to what extent such memory responses afford protection in vivo. To study this, we induced CD8+ memory responses directed towards defined viral epitopes, using DNA vaccines encoding immunodominant MHC class I-restricted epitopes of lymphocytic choriomeningitis virus covalently linked to beta2-microglobulin. This vaccine construct primed for a stronger recall response than did a more conventional minigene construct. Despite this, vaccinated mice were only protected against systemic infection whereas protection against the consequences of peripheral challenge was limited. Phenotypic analysis revealed that DNA vaccine-primed CD8+ T cells in uninfected mice differed from virus-primed CD8+ T cells particularly regarding expression of very-late antigen (VLA)-4, an adhesion molecule important for targeting T cells to inflammatory sites. Thus, our DNA vaccine induces a long-lived memory CD8+ T cell population that provides efficient protection against high-dose systemic infection. However, viral replication in solid non-lymphoid organs is not curtailed sufficiently fast to prevent significant virus-induced inflammation. Our results suggest that this is due to qualitative limitations of the primed CD8+ T cells.     

Recombination between HLA-A and C and between HLA-B and complement locus C4 in the same individual

In a French family with 2 parents and 5 children a crossing over was found in the HLA region on both of the parental haplotypes of one of the children. The following markers were studied: HLA-A, B, C,DR, DQ(MB), DP(SB), complement allotypes C4 and Bf and glyoxalase I polymorphism. In the third child, the paternal haplotype had a recombination between HLA-A and HLA-C and the maternal haplotype a recombination between HLA-B and complement locus C4. Mixed lymphocyte cultures confirmed the serological findings and non-HLA markers (blood groups and immunoglobulin allotypes) showed no evidence of extrapaternity. The family also demonstrates a probable duplication of the C4B1 gene in one of the paternal haplotypes.     

Principal neuron spiking: neither necessary nor sufficient for cerebral blood flow in rat cerebellum

Neuronal activity, cerebral blood flow, and metabolic responses are all strongly coupled, although the mechanisms behind the coupling remain unclear. One of the key questions is whether or not increases in spiking activity in the stimulated neurons are sufficient to drive the activity-dependent rises in cerebral blood flow (CBF) that form the basis of the signals used in functional neuroimaging such as the blood oxygen level-dependent (BOLD) signal. To this end the present study examined the effect of enhanced spike activity per se on CBF in rat cerebellar cortex under conditions of disinhibition, achieved by blocking GABA_A receptors using either bicuculline or picrotoxin. Purkinje cell spiking activity and local field potentials were recorded by glass microelectrodes, and laser Doppler flowmetry was used to monitor CBF. Disinhibition increased Purkinje cell spiking rate to 200–300% of control without incurring any increase in basal CBF. This demonstrates that increased spike activity per se is not sufficient to affect basal CBF. The neurovascular coupling between excitatory synaptic activity and CBF responses evoked by inferior olive (climbing fibre) stimulation was preserved during disinhibition. Thus, the unchanged basal CBF in the presence of the dramatic rise in Purkinje cell spiking rate was not explained by impaired synaptic activity–CBF coupling. On the basis of our previous and the present studies, we conclude that increased spiking activity of principal neurons is neither sufficient nor necessary to elicit CBF responses and in turn BOLD signals, and that activation-dependent vascular signals reflect excitatory synaptic activity.     

A comparison of micropuncture and lithium clearance methods in the assessment of renal tubular function in rats with diabetes insipidus

The lithium clearance technique has been proposed as a non-invasive method whereby fluid delivery from the pars recta and pars convoluta of proximal tubules can be measured as C_Li and C_IN [0.78 C_Li/C_IN+0.22], respectively [12], C_Li being the clearance of lithium and C_IN that of inulin. In the present study, fluid delivery from proximal tubules was estimated simultaneously by micropuncture and lithium clearance techniques in anaesthetized Brattleboro rats with diabetes insipidus, under control conditions and following chronic treatment with hydrochlorothiazide. Absolute deliveries from the proximal convoluted tubules as determined by the micropuncture and lithium clearance methods were 437 and 427 μl/min, respectively, in untreated animals and 348 and 355 μl/min, respectively, in thiazide-treated animals. The individual results obtained by the two methods showed a high degree of correlation (r=0.85,P<0.001). In untreated Brattleboro rats, proximal fluid delivery as estimated by both the micropuncture and lithium clearance techniques showed significant (P<0.001) correlations with urine flow rate. These results provide further evidence for the acceptance of lithium clearance as a valid estimate of proximal tubular fluid delivery.