Concordance between symptom screening and diagnostic procedure: the Hopkins Symptom Checklist-25 and the Composite International Diagnostic Interview I

The definition of case is a core issue in psychiatric epidemiology. Psychiatric symptom screening scales have been extensively used in population studies for many decades. Structured diagnostic interviews have become available during recent years to give exact diagnoses through carefully undertaken procedures. The aim of this article was to assess how well the Hopkins Symptom Checklist-25 (HSCL-25) predicted cases by the Composite International Diagnostic Interview (CIDI), and find the optimal cut-offs on the HSCL-25 for each diagnosis and gender. Characteristics of concordant and discordant cases were explored. In a Norwegian two-stage survey mental health problems were measured by the HSCL-25 and the CIDI. Only 46% of the present CIDI diagnoses were predicted by the HSCL-25. Comorbidity between CIDI diagnoses was found more than four times as often in the concordant cases (cases agreed upon by both instruments) than in the discordant CIDI cases. Concordant cases had more depression and panic/generalized anxiety disorders. Neither the anxiety nor the depression subscales improved the prediction of anxiety or depression. The receiver operating characteristic (ROC) curves confirmed that the HSCL-25 gave best information about depression. Except for phobia it predicted best for men. Optimal HSCL-25 cut-off was 1.67 for men and 1.75 for women. Of the discordant HSCL-25 cases, one -third reported no symptoms in the CIDI, one-third reported symptoms in the CIDI anxiety module, and the rest had symptoms spread across the modules. With the exception of depression, the HSCL-25 was insufficient to select individuals for further investigation of diagnosis. The two instruments to a large extent identified different cases. Either the HSCL-25 is a very imperfect indicator of the chosen CIDI diagnoses, or the dimensions of mental illness measured by each of the instruments are different and clearly only partly overlapping. Accepted: 11 November 1997     

Sequential expression of carbohydrate antigens with precursor-product relation characterizes cellular maturation in stratified squamous epithelium

Cell surface carbohydrates are excellent markers for cellular differentiation and maturation due to great structural and antigenic diversity and to known precursor/product relations. Several blood group related carbohydrate antigens were analyzed in human labial stratified non-keratinized epithelium from 16 healthy individuals by immunohistology using monoclonal antibodies. The expression of these antigens was correlated with erythrocyte phenotype and saliva secretor status. Three distinct compartments of the epithelium were found and defined by the sequential expression of derivatives of Type 2 chain structures: lower, confined to basal cell layers (N-acetyllactosamine), middle, to parabasal cell layers (H) and upper, to spinous cell layers (Le(y)/Le(x)). Although the antigens are related to blood group antigens they are largely expressed independently of the ABO, Lewis and secretor types, and may therefore serve as "universal" markers in differentiation studies of normal and pathological epithelium.     

Do concentrations of neurotransmitters measured in lumbar cerebrospinal fluid reflect the concentrations at brain level?

Summary CSF concentrations of vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK), noradrenaline (NA) and dopamine (DA) were measured in the lateral ventricles and at the lumbar level in patients with normal pressure hydrocephalus (NPH). The concentrations of VIP (n=15), NA (n=10) and DA (n=10) were significantly higher at the lumbar level than at the ventricular level, whereas the concentrations of CCK (n=9) were similar at the two sites. A signifikant positive correlation between the concentrations measured at the two levels was found for VIP (r_s=0.65; p0.01) and DA (r_s=0.94; p0.001). The results indicate that the concentrations of transmitter substances measured in CSF at the lumbar level not necessarily are indicative for concentrations measured more centrally. The negative correlations between Evans ratio and L-CSF VIP (r_s=-0.76; p 0.001), and between resistance to outflow and V-CSF as well as L-CSF CCK (r_s=-0.75); p 0.05) might be explained by a reduction in number of cortical neurons or by disturbances in CSF dynamics in patients with NPH.     

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.     

Infectious salmon anemia virus (ISAV) genomic segment 3 encodes the viral nucleoprotein (NP), an RNA-binding protein with two monopartite nuclear localization signals (NLS)

Infectious salmon anemia virus (ISAV) is the type species of the genus Isavirus belonging to the Orthomyxoviridae, and causes serious disease in Atlantic salmon (Salmo salar). This study presents the expression and functional analysis of the ISAV genome segment 3, and provides further evidence that it encodes the viral nucleoprotein (NP). The encoded protein was expressed in a baculovirus system, and Western blot analysis showed that it corresponds to the 66-71 kDa structural protein previously found in purified ISAV preparations. RNA-binding activity was established by the interaction of viral and recombinant NP with single-stranded RNA transcribed in vitro. Immunofluorescence studies of infected cells showed the ISAV NP to be an early protein. It locates to the nucleus of infected cells before it is transported to the cytoplasm prior to virus assembly. A similar localization pattern was observed in cells transfected with the NP gene, confirming that the encoded protein has an intrinsic ability to be imported into the nucleus. Two monopartite nuclear localization signals (NLS) at amino acids (230)RPKR(233) and (473)KPKK(476) were identified by computer analysis, and validated by site-directed mutagenesis. In contrast to other orthomyxovirus-NPs, that have several NLSs that function independent of each other, both NLSs had to be present for the ISAV NP protein to be transported into the nucleus, indicating that these motifs cooperate to target the protein to the nucleus.     

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.     

Intravascular "mulberry-like" bodies: morphological, immunohistochemical, and ultrastructural observations of an incidental finding caused by autolysis?

Intravascular "mulberry-like" bodies in a stillborn female infant with moderate maceration are reported. The histogenesis of these structures is discussed based on light-microscopic, immunohistochemical and ultrastructural findings. No demonstrable causal relation between the intravascular lesions and fetal death was found, the cause of death being attributed to intrauterine asphyxia. It is concluded, that intravascular "mulberry-bodies" most likely represent artifacts due to red blood cell autolysis.     

Mutation analysis of NR0B2 among 1545 Danish men identifies a novel c.278G>A (p.G93D) variant with reduced functional activity

Variations of the small heterodimer partner (SHP, NR0B2) gene, an atypical nuclear receptor that inhibits transactivation by hepatocyte nuclear factor (HNF)-4alpha, are associated with obesity among Japanese. The purpose of the study was to evaluate the prevalence of SHP variants among obese Danish men. Using combined SSCP and heteroduplex analysis, we analyzed the entire coding region of SHP for variants in a cohort of 750 Danish men with early-onset obesity and genotyped a cohort of 795 nonobese control subjects using PCR-RFLP. Functional analyses of the identified coding region variants were performed in both MIN6-m9 and HepG2 cell lines. A total of five novel variants, including three missense variants (c.100C>G [p.R34G], c.278G>A [p.G93D], and c.415C>A [p.P139H]) and two silent variants (c.65C>T [p.Y22Y] and c.339G>A [p.P113P]) were identified. Moreover, the previously reported c.512G>C [p.G171A] polymorphism was identified. The 171A allele was not associated with obesity (p = 0.07). The 34G, 93D, and 139H-alleles were rare variants, which were found only among obese subjects. Among the four coding region variants, the 93D-allele showed a reduced in vitro inhibition of the HNF-4alpha transactivation of the HNF-1alpha promoter expression when expressed in MIN6-m9 and HepG2 cell lines (p<0.01). In contrast to reported findings among obese Japanese, functional variants are rare among Danish men. A functional 93D variant of SHP was identified in 1 out of 750 obese and in none of 795 nonobese control subjects. Further large-scale population studies are necessary to assess the clinical impact of this rare variant on obesity risk among European subjects.     

Real-time PCR methods for independent quantitation of TTV and TLMV

There is considerable interest in the possible clinical effects of the human circoviruses TT virus (TTV) and TTV-like mini virus (TLMV). Most people appear to have at least one of these viruses replicating actively in their bodies, thus mere correlation of the presence of virus and disease states are probably less informative than a quantitative analysis of viraemia. Real-time PCR based methods, with either SYBR Green or TaqMan probe, designed to quantitate selectively TTV and TLMV are described. The suggested TaqMan-based protocols were suitable for quantitation of viruses in the range of 10(2)-10(9) copies/ml of sample; and proved, by sequencing of PCR products, to be specific for each of the two viruses.