Inverted duplication of the distal short arm of chromosome 3 associated with lobar holoprosencephaly and lumbosacral meningomyelocele

A fetus with lobar holoprosencephaly and lumbosacral meningomyelocele associated with duplication of the short arm of chromosome 3 is reported. The anomalies were detected on fetal ultrasound at 20 weeks' gestation and the autopsy findings correlated well with the prenatal findings. The fetal karyotype was 46,XY,der(3)del(3)(p26) dup(3)(p26p21.3). The association of holoprosencephaly with duplication 3p is well known, but to the best of our knowledge this is the first reported association of meningomyelocele with 3p duplication. These findings suggest that a gene or genes with a crucial role in central nervous system development are located on the short arm of chromosome 3.     

The Personality Assessment Inventory in individuals with traumatic brain injury.

This study examined the Personality Assessment Inventory (PAI) in 95 individuals who had suffered a traumatic brain injury (TBI). Participants were recruited from a rehabilitation hospital (n=60) and a military hospital (n=35); despite differences in demographics and injury characteristics groups did not differ on any of the clinical scales and were thus combined. In the combined group, the highest mean clinical scale elevations were on Somatic Complaints, Depression, and Borderline Features and the most common configural profiles, based on cluster analysis, were Cluster 1 (no prominent elevations), Cluster 6 (social isolation and confused thinking), and Cluster 2 (depression and withdrawal). Factor analysis indicated a robust three-factor solution that accounted for 74.86 percent of the variance and was similar to findings from the psychiatric and non-psychiatric populations in the standardization sample. The above findings are compared with the previous literature on psychopathology in TBI, particularly in regards to the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), as well as previous psychometric research on the PAI.     

Significance of depression and cognitive impairment in patients undergoing programed stimulation of cardiac arrhythmias

Although depression and cognitive impairment have been associated with excess mortality following heart surgery, the relationship of these factors to death following treatment for cardiac arrhythmias is unknown. We prospectively examined the associations between biobehavioral factors, mortality, and arrhythmia manageability in 88 patients undergoing programed electrical stimulation for the diagnosis and treatment of supraventricular and ventricular tachyarrhythmias or syncope of unknown origin. Statistically significant relationships were identified between depression and mortality, and between cognitive impairment and mortality. No relationships were observed between cognitive impairment or psychologic profile and arrhythmia severity or treatment efficacy. Our data suggest that arrhythmia morbidity and mortality may in part be a function of cognitive and emotional impairments that lessen the individual's capacity to comply with lifesaving therapy, maintain a stable physiologic milieu, and continue an adaptive emotional life. Failure to recognize the clinical significance of these impairments in patients at risk for sudden cardiac death will contribute to the current difficulty reducing the death and disability associated with cardiac arrhythmias.     

Pharmacological analysis of extracellular dopamine and metabolites in the striatum of conscious as/agu rats, mutants with locomotor disorder

The as/agu rat is a spontaneously occurring mutation which exhibits locomotor abnormalities, reduced tyrosine hydroxylase levels in the substantia nigra and lower extracellular levels of dopamine. The animal could represent a model of some human locomotor disorders. High-potassium medium evoked a 460% rise of dopamine levels in control rats but double this in mutants. Amphetamine increased extracellular dopamine by 710% in controls and 1480% in mutants. Clorgyline produced a small increase of dopamine levels in controls but an 1170% increase in mutants. The uptake inhibitor nomifensine increased dopamine levels by 910% in controls but only 270% in mutants. After treatment with benserazide plus L-DOPA, an acute injection of L-DOPA evoked a release of dopamine which was twice as large in the as/agu rats compared with controls. The results show reduced extracellular dopamine in as/agu rats when the locomotor disorder is apparent, but there has been little loss of tyrosine hydroxylase. The responses to drugs are qualitatively different from those obtained using 6-hydroxydopamine.Overall, the effects of compounds affecting aminergic neurons suggest that one possible mechanism for the neuronal abnormality in as/agu rats is a defective regulation of dopamine release from striatal terminals.     

Polyethylene glycol-modified ragweed pollen extract in rhinoconjunctivitis

Sixty-two ragweed-sensitive adult subjects volunteered to take part in a 2-year, placebo-controlled efficacy study of polyethylene glycol (PEG)-modified ragweed extract, in ragweed pollen-induced rhinoconjunctivitis. At the beginning of the study, subjects were stratified according to skin sensitivity to ragweed extract and PEG-modified ragweed and the severity of hay fever in the previous year. There was random allocation of half to active treatment and half to placebo treatment. Before the first ragweed pollen season the 36 most sensitive subjects received 10 weekly injections (group 1), and the remaining 26 received six injections (group 2). Before the second season all subjects received 10 injections. Doses increased by half a log concentration each week unless there were adverse reactions. The mean total dose received by group 1 in year 1 was 385 micrograms of protein (28.9 micrograms AgE) and received by group 2 was 218 micrograms of protein (16.4 micrograms AgE). In year 2 the mean total dose was 1829 micrograms (137.2 micrograms AgE). Sixty-six percent of injections elicited no reaction or a mild local reaction; the remaining injections produced local redness and swelling more than 2 inches in diameter. Four percent of injections produced systemic symptoms. PEG-modified ragweed stimulated increases in ragweed specific IgG antibody both years, but increases in ragweed specific IgE antibody were significant only in group 1 in year 1. The magnitude of the IgG antibody changes was directly related to the total dose injected. At the beginning of the second year, PEG-modified ragweed-treated subjects still had elevated IgG antibody levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Association of Epstein-Barr virus with sinonasal angiocentric T cell lymphoma.

AIM--To investigate whether non-Hodgkin's lymphomas arising in the sinonasal region or Waldeyer's ring contain the Epstein-Barr virus (EBV) genome in lesional tissue. METHOD--Sections from paraffin wax blocks of 22 lymphoid proliferations arising in the sinonasal region or Waldeyer's ring were studied with EBV encoded RNAs (EBER-1 and -2) using in situ hybridisation. RESULTS--EBV was detected in nuclei of tumour cells of five of seven T cell lymphomas and in nuclei of two of seven diffuse, large cell immunoblastic lymphomas of B phenotype in the sinonasal region. Of tumours arising in Waldeyer's ring, two of 10 non-Hodgkin's lymphomas (both large cell) were positive, as was a single case of Hodgkin's disease. Lymphoma of other types, including Western type Burkitt's lymphoma, and nodular and diffuse small cleaved cell lymphoma, were negative. CONCLUSION--EBV is highly associated with large cell lymphomas especially T cell lymphomas of sinonasal origin in the indigenous Irish population, underlining the importance of this virus in nasopharyngeal lymphomas in Northern European as well as Asian populations.     

DLA-DRB1 polymorphisms in dogs defined by sequence-specific oligonucleotide probes (SSOP)

To date, DNA sequences for 29 dog DLA-DRB1 alleles have been reported. However, no data exists on the frequencies of these alleles within the general dog population, nor is there any indication of whether there is interbreed variation of allele distribution. We have addressed this by establishing a molecular based sequence-specific oligonucleotide probing (SSOP) method to identify all of the known broad DRB1 types and we have used this to type a random panel of dogs. A series of oligonucleotide probes were designed to detect known polymorphisms in the three DRB1 hypervariable regions, together with two distinctive motifs in other regions of exon 2. This set of probes enabled us to assign broad DRB1 types. Two hundred and eighteen dogs were SSOP typed for DRB1. All but 4 of the published DLA-DRB1 alleles were identified in these animals. Interbreed variation in both allele distributions and allele frequencies were observed, which may be useful in the study of genetic variation between breeds. This variation also has implications for the selection of control groups for studies aimed at identifying MHC associations with disease susceptibility in the dog.     

Genetic association analysis of behavioral inhibition using candidate loci from mouse models

Genes influence the development of anxiety disorders, but the specific loci involved are not known. Genetic association studies of anxiety disorders are complicated by the complexity of the phenotypes and the difficulty in identifying appropriate candidate loci. We have begun to examine the genetics of behavioral inhibition to the unfamiliar (BI), a heritable temperamental predisposition that is a developmental and familial risk factor for panic and phobic disorders. Specific loci associated with homologous phenotypes in mouse models provide compelling candidate genes for human BI. We conducted family-based association analyses of BI using four genes derived from genetic studies of mouse models with features of behavioral inhibition. The sample included families of 72 children classified as inhibited by structured behavioral assessments. We observed modest evidence of association (P = 0.05) between BI and the glutamic acid decarboxylase gene (65 kDA isoform), which encodes an enzyme involved in GABA synthesis. No significant evidence of association was observed for the genes encoding the adenosine A(1A) receptor, the adenosine A(2A) receptor, or preproenkephalin. This study illustrates the potential utility of using candidate genes derived from mouse models to dissect the genetic basis of BI, a possible intermediate phenotype for panic and phobic disorders.