Evidence for relationships between antiperinuclear and IgG rheumatoid factor

Summary Antiperinuclear factor (APF) and IgG-rheumatoid factor (IgG-RF) has been found in 64% and 48% of cases of rheumatoid arthritis, 36% and 50% of cases of psoriasis and 31% and 45% of cases of primary Sjögren's syndrome. A close relationship between APF and IgG-RF is suggested by statistical and experimental data. Purified IgG-RF has some degree of APF activity.     

Clinical risk factors related to failures with zirconia-based restorations: An up to 9-year retrospective study

Objectives

The first objective of this study was to retrospectively evaluate zirconia-based restorations (ZBR). The second was to correlate failures with clinical parameters and to identify and to analyse chipping failures using fractographic analysis.

Methods

147 ZBR (tooth- and implant-supported crowns and fixed partial dentures (FPDs)) were evaluated after a mean observation period of 41.5 ± 31.8 months. Accessorily, zirconia implant abutments (n = 46) were also observed. The technical (USPHS criteria) and the biological outcomes of the ZBR were evaluated. Occlusal risk factors were examined: occlusal relationships, parafunctional habits, and the presence of occlusal nightguard. SEM fractographic analysis was performed using the intra-oral replica technique.

Results

The survival rate of crowns and FPDs was 93.2%, the success rate was 81.63% and the 9-year Kaplan–Meier estimated success rate was 52.66%. The chipping rate was 15% and the framework fracture rate was 2.7%. Most fractographic analyses revealed that veneer fractures originated from occlusal surface roughness. Several parameters were shown to significantly influence veneer fracture: the absence of occlusal nightguard (p = 0.0048), the presence of a ceramic restoration as an antagonist (p = 0.013), the presence of parafunctional activity (p = 0.018), and the presence of implants as support (p = 0.026). The implant abutments success rate was 100%.

Conclusions

The results of the present study confirm that chipping is the first cause of ZBR failure. They also underline the importance of clinical parameters in regards to the explanation of this complex problem. This issue should be considered in future prospective clinical studies.

Clinical significance

Practitioners can reduce chipping failures by taking into account several risk parameters, such as the presence of a ceramic restoration as an antagonist, the presence of parafunctional activity and the presence of implants as support. The use of an occlusal nightguard can also decrease failure rate.     

Endothelial leukocyte adhesion molecule 1: direct expression cloning and functional interactions.

A cDNA for endothelial leukocyte adhesion molecule 1 (ELAM-1) was isolated by transient expression in COS-7 cells of a subtracted cDNA library from cytokine-treated human umbilical vein endothelial cells (HUVECs), with selection of ELAM-1-expressing clones by adhesion of transfected cells to the human promyelocytic cell line HL-60. This cloning method requires neither antibody nor purified ligand. ELAM-1-expressing COS cells bind the promyelocytic cell line HL-60 by a Ca2(+)-dependent but temperature-independent mechanism. Although ELAM-1 is homologous to mammalian lectins, its interaction with HL-60 cells is not inhibited by simple carbohydrate structures. ELAM-1-expressing COS cells also bind human neutrophils and the human colon carcinoma cell line HT-29, but not the B-cell line Ramos. However, Ramos cells adhere to cytokine-treated HUVECs but not control HUVECs, confirming the existence of other inducible adhesion molecules. In addition, the binding of HL-60 cells or neutrophils to ELAM-1-expressing COS cells is not inhibited by a monoclonal antibody (60.3) directed to an inhibitory epitope on CD18, indicating that the ELAM-1 ligand, although uncharacterized, is not a member of the CD11/CD18 family.     

Advancing age results in reduction of intestinal and bone 1,25-dihydroxyvitamin D receptor

Target tissue 1,25-dihydroxyvitamin D [1,25-(OH)2D] receptor was monitored in adult (15- to 18-month-old) and young (4- to 5-week-old) male Holtzman rats. The concentration of unoccupied receptor (femtomoles per mg protein) was significantly higher in the intestine (666 +/- 19 vs. 162 +/- 43) and bone (61 +/- 3.7 vs. 18 +/- 2.5) of young rats compared to that in adults. The dissociation constant (Kd) of the intestinal receptor, however, remained very similar at both ages (young, 0.24 nM; adult, 0.53 nM). A similar age-related decline in unoccupied intestinal receptor was also observed in Fischer 344 rats and cows. Infusion of young and adult Holtzman rats with about 72 ng/kg BW 1,25-(OH)2D3 resulted in similar changes in the concentrations of plasma 1,25-(OH)2D3 (150-160 pg/ml) in both age groups. The 1,25-(OH)2D3 infusions also resulted in significant up-regulation of unoccupied intestinal receptor (femtomoles per mg protein) from 512 +/- 27 to 780 +/- 61 in the young rats and 68 +/- 9.4 to 194 +/- 15 in the adult rats. Receptor up-regulation by 1,25-(OH)2D3 (change from control) was significantly higher (P less than 0.05) in young rats (268 +/- 51 fmol/mg protein) than in adults (125 +/- 8.2 fmol/mg protein). These data suggest that the differences in receptor number in young and adult rats may be responsible for functional changes in target tissue response to 1,25-(OH)2D3 associated with advancing age.     

Human thymocyte development in mouse organ cultures

A novel system to study human thymocyte development is described in which embryonic mouse thymic rudiments are seeded with human precursor cells in vitro. In these cultures human thymocytes proliferate extensively (greater than 20-fold increase in cell number) and mature, as evidenced by the accumulation of double and single positive (CD4+ and/or CD8+) cells. Data presented here suggest that the survival and ordered development of the mature human thymocytes in chimeric thymuses is dependent on human stromal elements. Immature CD4-CD8- human thymocytes failed to colonize or minimally recolonized mouse thymic lobes unless provided with high density (greater than 1.077 g/ml) human thymic cell fractions. These fractions contain multicellular complexes of epithelial/nurse cells, thymocytes, and dendritic cells/macrophages which dramatically enhanced the recolonizing capacity of purified CD4-CD8- thymocytes. The chimeric organ culture system described here provides not only a new approach for studying human T cell ontogeny but also a direct means for the future dissection of stromal interactions necessary for successful transition of precursor cells (CD4-CD8-) to immature double positive (CD4+CD8+) and mature single positive cells (CD4+ or CD8+) in the thymus.     

Subjective Unmet Need for Mental Health Services in Depressed Children Grown Up

Background Limited attention has been devoted to characterizing unmet need for treatment among individuals with mental disorders. A longitudinal follow-up of depressed, anxious, and psychiatrically normal children into adulthood provided an opportunity to examine factors associated with subjective unmet need.Methods Respondents (n = 208) comprise a subsample of a cohort ascertained between 1977 and 1985 consisting of three subgroups: one with major depressive disorder (MDD), one with anxiety disorders but no MDD, and controls with no psychiatric disorder up to ascertainment. Psychiatric status was reassessed in adulthood using the SADS-LA by interviewers blind to childhood diagnoses. Best-estimate diagnoses describing participants’ lifetime clinical course were formulated by senior clinicians. Participants who completed SADS-LA interviews about themselves were invited to complete an additional interview about experiences with health care, including subjective unmet need for and barriers to mental health treatment.Results About 37% of respondents reported lifetime histories of subjective unmet need for mental health services. Unmet need was associated with female gender and lifetime mood and substance dependence disorders. The most commonly cited barriers included attitudes toward treatment, not knowing where to obtain it, and financial concerns.Conclusions Subjective unmet need was common in this sample. Approaches to reducing it might include public health initiatives to foster more favorable attitudes toward treatment, increase knowledge of where to obtain it, and lower financial barriers.     

Genetic Variation Throughout the Folate Metabolic Pathway Influences Negative Symptom Severity in Schizophrenia

Low serum folate levels previously have been associated with negative symptom risk in schizophrenia, as has the hypofunctional 677C>T variant of the MTHFR gene. This study examined whether other missense polymorphisms in folate-regulating enzymes, in concert with MTHFR, influence negative symptoms in schizophrenia, and whether total risk allele load interacts with serum folate status to further stratify negative symptom risk. Medicated outpatients with schizophrenia (n = 219), all of European origin and some included in a previous report, were rated with the Positive and Negative Syndrome Scale. A subset of 82 patients also underwent nonfasting serum folate testing. Patients were genotyped for the MTHFR 677C>T (rs1801133), MTHFR 1298A>C (rs1801131), MTR 2756A>G (rs1805087), MTRR 203A>G (rs1801394), FOLH1 484T>C (rs202676), RFC 80A>G (rs1051266), and COMT 675G>A (rs4680) polymorphisms. All genotypes were entered into a linear regression model to determine significant predictors of negative symptoms, and risk scores were calculated based on total risk allele dose. Four variants, MTHFR 677T, MTR 2756A, FOLH1 484C, and COMT 675A, emerged as significant independent predictors of negative symptom severity, accounting for significantly greater variance in negative symptoms than MTHFR 677C>T alone. Total allele dose across the 4 variants predicted negative symptom severity only among patients with low folate levels. These findings indicate that multiple genetic variants within the folate metabolic pathway contribute to negative symptoms of schizophrenia. A relationship between folate level and negative symptom severity among patients with greater genetic vulnerability is biologically plausible and suggests the utility of folate supplementation in these patients.     

Chronic high-frequency stimulation of the subthalamic nucleus and L-DOPA treatment in experimental parkinsonism: effects on motor behaviour and striatal glutamate transmission

Hyperactivity of striatal glutamatergic synaptic transmission in response to dopamine depletion plays a major role in the pathogenesis of parkinsonian motor symptoms. In the present study we investigated the impact, on this hyperactivity, of chronic dyskinesiogenic L-DOPA treatment, combined or not with high-frequency stimulation (HFS) of the subthalamic nucleus (STN). In vitro patch-clamp recordings were performed from striatal spiny neurons of hemiparkinsonian rats (intranigral 6-OHDA injection). Here we show that dyskinesiogenic L-DOPA treatment exacerbated striatal glutamatergic hyperactivity induced by 6-OHDA lesion. Chronic 5-day STN HFS had the opposite effect, reducing striatal glutamatergic transmission in both parkinsonian and dyskinetic animals. Consistently, chronic HFS stimulation could progressively ameliorate motor parkinsonian signs (akinesia) but, conversely, did not improve L-DOPA-induced dyskinesia (LID). Thus, the effects of L-DOPA and HFS on corticostriatal transmission seem to be dissociated. These data show for the first time that dyskinesiogenic L-DOPA treatment and chronic STN HFS with antiakinetic effects induce opposite plastic rearrangements in the striatum. The interaction between these two treatments provides further evidence that striatal glutamatergic hyperactivity is a pathophysiological correlate of akinesia rather than LID.