Effect of anti-interferon-γ and anti-interleukin-2 monoclonal antibody treatment on the development of actively and passively induced experimental allergic encephalomyelitis in the SJL/J mouse

SJL/J mice challenged with myelin basic protein (MBP) in complete Freund's adjuvant (CFA) developed only mild chronic-relapsing experimental allergic encephalomyelitis (EAE) with very low incidence. However, treatment of challenged mice with anti-infeferonγ (IFN-γ) monoclonal antibody (mAb) determined severe disease in all cases. Similarly, in passive EAE, the addition of anti-IFN-γ to the in vitro MBP-activated cells at the time of transfer led to significant disease exacerbation in all recipients. The disease enhancing effect was observed only when the mAb was given at the time of active challenge or of passive transfer, but not at later times. Anti-interleukin-2 (IL-2) antibody had only a marginal effect in the active induction, but drastically reduced the manifestations of passive EAE, even when mixed with a disease-enhancing dose of anti-IFN-γ. These findings support the notion that IL-2 is required for disease induction whereas IFN-γ plays a disease-limiting role early in the development of EAE.     

Partial replication of a DRD4 association in ADHD individuals using a statistically derived quantitative trait for ADHD in a family-based association test.

BACKGROUND: Previous research found an association between single nucleotide polymorphisms (SNPs) in the promoter region of DRD4 and statistically derived phenotypes generated from attention-deficit/hyperactivity disorder (ADHD) symptoms. We sought to replicate this finding by using the same methodology in an independent sample of ADHD individuals. METHODS: Four SNPs were genotyped in and around DRD4 in 2631 individuals in 642 families. We developed a quantitative phenotype at each SNP by weighting nine inattentive and nine hyperactive-impulsive symptoms. The weights were selected to maximize the heritability at each SNP. Once a quantitative phenotype was generated at each SNP, the screening procedure implemented in PBAT was used to select and test the five SNPs/genetic model combinations with the greatest power to detect an association for DRD4. RESULTS: One of the four SNPs was associated with the quantitative phenotypes generated from the ADHD symptoms (corrected p-values = .02). A rank ordering of the correlation between each of the ADHD symptoms and the quantitative phenotype suggested that hyperactive-impulsive symptoms were more strongly correlated with the phenotype; however, including inattentive symptoms was necessary to achieve a significant result. CONCLUSIONS: This study partially replicated a previous finding by identifying an association between rs7124601 and a quantitative trait generated from ADHD symptoms. The rs7124601 is in linkage disequilibrium (LD) with the SNPs identified previously. In contrast to the previous study, this finding suggests that both hyperactive-impulsive and inattentive symptoms are important in the association.     

Functional genomics and schizophrenia: endophenotypes and mutant models.

This article summarizes the rationale, methods, and results of gene discovery programs in schizophrenia research and describes functional methods of investigating potential candidate genes. It focuses next on the most prominent current candidate genes and describes (1) evidence for their association with schizophrenia and research into the function of each gene; (2) investigation of the clinical phenotypes and endophenotypes associated with each gene, at the levels of psychopathologic, neurocognitive, electrophysiologic, neuroimaging, and neuropathologic findings; and (3) research into the ethologic, cognitive, social, and psychopharmacologic phenotype of mutants with targeted deletion of each gene. It examines gene-gene and gene-environment interactions. Finally, it looks at future directions for research.     

The neuroprotective actions of kynurenic acid and MK-801 in gerbils are synergistic and not related to hypothermia

The broad spectrum excitatory amino acid antagonist, kynurenic acid was evaluated in a transient forebrain ischaemia model in gerbils. When administered i.p., 15 min prior to a 5 min period of ischaemia, a dose-related neuroprotective effect was seen with 800 mg/kg of kynurenic acid showing very good protection. A combination of kynurenic acid (200 or 400 mg/kg) and MK-801 (0.1 mg/kg) gave a synergistic neuroprotective effect. Neither kynurenic acid (200 or 400 mg/kg) nor MK-801 (0.3 mg/kg) was neuroprotective when administered by itself 30 min post-ischaemically, but when co-administered significant protection of the CA1 pyramidal neurones of the hippocampus was seen. In addition, we examined the effect of maintaining core body temperature on the neuroprotective action of MK-801 and kynurenic acid following the suggestion that it was a hypothermic effect of MK-801 which resulted in neuroprotection in gerbils. When the body temperature of the gerbils was maintained at 37 degrees C for a period of 24 h it did not affect the neuroprotective action of MK-801 (0.1 or 10 mg/kg) or kynurenic acid (200 mg/kg).     

Sexuality Training,Education and Therapy in the Healthcare Environment: Taboo,Avoidance, Discomfort or Ignorance?

Multiple sources of resistance are present in the healthcare environment to comprehensive assessment and intervention efforts in regard to sexuality. The authors survey both the diversity of needs and values presented by consumers, and encourage providers to equip themselves educationally, emotionally and ethically so that they can deliver relevant, holistic services to consumers.     

Stressful family life events and nonspecific somatic complaints in school children.

The relationship between stressful family life events and somatic complaints in 477 school children was studied. There was a significant association between life events and somatic complaints, with a general trend for somatic complaints to increase in almost direct proportion to the number of family life events. Overall occurrence of these nonspecific symptoms was more in girls. The somatic complaints were significantly more in children from nuclear families and of illiterate or poorly educated mothers. No significant association was observed between somatic complaints and number of children in the family or socio-economic status. Assessment of psychodevelopmental tasks and family environment during routine check up of children by the school health teams and their appropriate training in this field should be stressed upon.     

New reference allelic ladders to improve allelic designation in a multiplex STR system

This paper reports the composition of a new reference allelic ladder mixture for use with a multiplex DNA profiling system consisting of six short tandem repeat loci. The loci included in this mixture are HUMTH01, D21S11, D18S51, D8S1179, HUMVWAF31/A, HUMFIBRA/FGA and an amelogenin sex test. Sequence analysis of individual ladder alleles was carried out and allelic designations made in accordance with the recommendations of the International Society of Forensic Haemogenetics (1992; 1994). A series of rare alleles which increase the range of alleles previously reported were identified. By including some of the rare alleles into the ladder marker system, we have significantly improved the ability to identify new alleles in unknown samples. Received: 12 August 1997 / Received in revised form: 7 November 1997     

Resistance of Drosophila to cadmium: biochemical factors in resistant and sensitive strains

With regard to cadmium toxicity, Drosophila strains v;bw and Austin represent extremes in resistance and sensitivity, respectively. Both strains produced metallothionein (MT) in response to Cd ions in their diet. Austin produced more metallothionein than v;bw at Cd ion levels below 0.2 mM, when both strains were allowed lifetime development on Cd2+-containing media. When the rate of MT appearance was measured for 4 days in young adults the results showed no clear trend with time within a strain or between strains. The plot of LC50 vs. MT levels for identical developmental conditions revealed that for v;bw small increases in MT corresponded to large increases in resistance whereas for the sensitive Austin even large increases in MT had comparatively little effect on increasing LC50. Results given here suggest that differences in total MT content do not explain the genetically demonstrable difference in Cd2+-resistance between v;bw and Austin. However, since two MT genes are identified in Drosophila, differences in resistance could be reflective of greater relative amounts of one "more important" MT in the resistant fly.