IgA levels are predictors of mortality in Finnish nonagenarians

It has been demonstrated that in obviously healthy, very old people increased levels of inflammatory markers as well as some defects in T lymphocyte populations are strong predictors of mortality. Very little is known about the role of possible functional defects in antibody formation. To examine this, we now measured IgM, IgG and IgA concentrations in a cohort of 285 nonagenarians (67 males, 218 females). IgG and IgA levels were significantly higher than those of healthy middle-aged controls. The analyzed serum samples were taken at the age of 90-91 years. After 4 years, 20 males and 94 females had survived. To analyze the role in predicting mortality, the immunoglobulin data (as well as the measured CRP and IL-6 concentrations) were stratified according to this survival data. IgA levels (and CRP and IL-6 levels) were clearly higher in the nonsurvivors than in the survivors. These data imply that elevated serum IgA level, i.e. indicator of intestinal inflammation and/or defect in mucosal defence, is a strong mortality predicting factor.     

Susceptibility to primary Epstein-Barr virus infection is associated with interleukin-10 gene promoter polymorphism

In total, 116 children were investigated to determine whether the interleukin (IL)-10 polymorphism influences the age at primary Epstein-Barr virus (EBV) infection. The promoter of IL-10 is polymorphic, with 3 known single base substitutions (G/A at -1082, C/T at -819, and C/A at -592), which form 3 haplotypes: GCC, ACC, and ATA. This study found that carriage of the ATA haplotype protects against early EBV infection. The presence of the ATA haplotype was associated with EBV seronegativity (odds ratio, 2.6; 95% confidence interval, 1.04-6.7; P=.04), when controlled by age. To examine the effect of haplotypes on IL-10 production, IL-10 plasma levels were measured in 50 newborns and 400 adults and were correlated with the IL-10 haplotype. The IL-10 levels were significantly higher in the ATA carriers than in the noncarriers. These data suggest that the IL-10 ATA haplotype confers protection against primary EBV infection and that the effect is mediated by high IL-10 levels.     

The expression of intermediate filament protein nestin as related to vimentin and desmin in regenerating skeletal muscle

Intermediate filament (IF) proteins show specific spatial and temporal expression during development of skeletal muscle. Nestin, the least known muscle IF, has an important role in neuronal regeneration. Therefore, we analyzed the expression pattern of nestin as related to that of vimentin and desmin during skeletal muscle regeneration. Nestin and vimentin appear at 6 h post-injury in myoblasts, with maximum expression around day 3-5 post-injury. Thereafter, vimentin expression ceases completely, whereas that of nestin is downregulated to remain only in the sarcoplasm next to neuromuscular and myotendinous junctions. Desmin appears at 6-12 h post-injury and becomes the predominant IF in myofibers simultaneously with the appearance of cross-striations. The expression pattern and colocalization of nestin and vimentin, known to form heteropolymers, suggests that they are essential during the early dynamic phase of the myofiber regeneration when migration, fusion, and structural modeling of myogenic cells occurs, whereas desmin is responsible for keeping myofibrils in register in mature myofibers. In conclusion, the expression of nestin is dynamically orchestrated with that of vimentin and desmin during skeletal muscle regeneration and recapitulates that seen during myogenesis, i.e. these IFs have key functional roles in the construction and restoration of skeletal myofibers.     

Interleukin-1B genotype modulates the improvement of coronary artery reactivity by lipid-lowering therapy with pravastatin: a placebo-controlled positron emission tomography study in young healthy men

A polymorphism at position -511 of interleukin-1B (IL-1B) gene promoter regulates IL-1B levels, immune and inflammatory responses and possible atherogenesis. We used positron emission tomography (PET) to study whether coronary reactivity or its response to pravastatin is related to this IL-1B polymorphism. The study comprised a randomized, double-blind, placebo-controlled trial with two treatment groups: (i) pravastatin (40 mg/day, n=14) and (ii) placebo (n=20) for 6 months (baseline mean cholesterol 5.5 +/- 0.8 mmol/l; age 35 +/- 4 years). Myocardial blood flow was measured by PET at rest and during adenosine infusion using 15O-labelled water. PET studies, lipid, IL-1beta and C-reactive protein analyses were performed at baseline and after 6 months of therapy. IL-1B genotype was determined by polymerase chain reaction. There were no differences between IL-1B allele 2 carriers (A2+) and non-carriers (A2-) in basal or adenosine-stimulated myocardial flow (ASMF), at baseline. Regarding the change in ASMF and coronary flow reserve, there was a significant IL-1B genotype-by-treatment group interaction (analysis of covariance, P=0.028 and P=0.002, respectively) during follow-up. In the pravastatin group, the ASMF increased by 18.0% in subjects with IL-1B A2- (n=7), but decreased by 2% in subjects with IL-1B A2+ (n=7). There were no significant changes from the baseline values in placebo recipients. After treatment, both genotype groups showed a similar decrease in serum total and low density lipoprotein cholesterol (P<0.0001 for both). In conclusion, coronary function improves after 6 months of pravastatin therapy in subjects with the IL-1B A2- allele but not in those with the IL-1B A2+ allele.     

Differential cyclophosphamide sensitivity of precursor cells in allogeneic and H-2 restricted cytotoxic responses

Spleen cells from cyclophosphamide-treated mice responded in vitro to allogeneic stimulator cells but not to TNP-coupled syngeneic spleen cells. Similarly, cells from female mice, primed in vivo with syngeneic male cells, could not respond in vitro to male spleen cell stimulation if the mice were pretreated with cyclophosphamide. These results suggest that the precursor cells for H-2-restricted cytotoxic responses belong to a different T-cell subpopulation than the precursor cells for allogeneic responses.     

Indicators of inflammation after recent tonic-clonic epileptic seizures correlate with plasma interleukin-6 levels.

Cerebrospinal fluid (CSF) and peripheral blood pleocytosis have been observed after epileptic seizures without any evidence of infections, but no systematic studies on the acute phase reaction in such patients have been performed. We have previously reported increased levels of interleukin-6 (IL-6) in patients with recent tonic--clonic seizures. Because IL-6 is a major inducer of the systemic acute phase reaction, we decided to study various indicators of inflammation in the blood as well as their correlation with plasma and CSF IL-6 levels. CSF and blood samples were studied from 37 patients with previously undiagnosed and untreated tonic-clonic seizures without any clinical evidence of systemic or central nervous system infections as well as from 40 controls. The mean peripheral blood and CSF-leukocyte counts were significantly higher in patients compared with controls ( 7.9 x 10(9)vs. 6.1 x 10(9), P= 0.002 and 1.9 x 10(6)vs. 1.1 x 10(6), P= 0.032, respectively). There was some indication of increased concentration of C-reactive protein (CRP) and no difference in haptoglobin levels. There was a significant correlation between plasma but not CSF IL-6 concentration and those of both B-leukocyte count ( r= 0.051, P= 0.009) and CRP ( r= 0.42, P= 0.009). Epileptic seizures provoke a production of cytokines such as IL-6 that may in turn cause an activation of the acute phase reaction. Thus, CSF pleocytosis and increase in some indicators of inflammation should not automatically be attributed to systemic or CNS infections in patients with acute seizures.     

A prospective study of patients with sciatica. A comparison between conservatively treated patients and patients who have undergone operation, Part I: Patient characteristics and differences between groups

Based on a prospective study on 342 sciatica patients examined with rhizography, the aim was to determine which factors others than the rhizography finding and the grade and duration of symptoms were related to the selection of patients to undergo operation. Compared with surgically treated patients, conservatively treated patients who did not undergo operation and who had pathologic rhizography findings had pessimistic attitudes to possible surgery, often expressed a desire to retire, and considered their work as physically stressful. The women in this group were older and had lower pain indices than women who underwent operation. Conservatively treated patients with negative rhizography had more severe occupational handicaps, minor expectations of possible surgery, physically more strenuous jobs requiring difficult physical positions, and lower indices for pain and ADL than did the operated patients. The social and ergonomic background problems are emphasized in sciatica patients conservatively treated after rhizography.     

Leisure time physical activities and the results of surgery of lumbar disc herniation

The aim of this study was to elucidate the consequences of leisure time physical activities on the one-year results of surgery of lumbar intervertebral disc herniation. Pre- and postoperative leisure time physical activities and severity of occupation handicap were analyzed from 212 patients. Only to a certain degree the findings support the claim that a high preoperative level of physical activities during leisure time is linked with good postoperative results.     

Prolactin and cortisol in cerebrospinal fluid: sex-related associations with clinical and psychological characteristics of patients with low back pain

Clinical and psychological characteristics of 33 patients with low back pain were correlated with prolactin and cortisol concentrations in cerebrospinal fluid (CSF). A significant sex difference was found in CSF prolactin levels: women secreted more prolactin into the CSF than did men. High CSF cortisol levels were associated with a rhizographically-demonstrable abnormality, suggesting a relationship between cortisol and an 'organic' origin of pain symptoms. Impairment-disability indices also were associated with CSF hormone levels. Moreover, the two hormones had dissociated psychological correlates. Prolactin was related to depression and anxiety, whereas cortisol was related to somatization. Sex differences were observed in the cortisol response to the symptoms of chronic low back pain, especially in the presence of anxiety and somatization. The sex differences in psychoneuroendocrine and emotional responses suggest that male and female pain patients have different coping mechanisms.