Community psychiatry then and now: An introduction

Allen R. Dyer is Professor of Psychiatry at Albany Medical College and Professor of Health Policy and Management at the State University of New York at Albany, Albany, New York. Effective March 1, 1992, he becomes Professor and Chairman, Department of Psychiatry and Behavioral Sciences, James H. Quillen College of Medicine, East Tennessee State University.     

No more Hiroshimas

Dyer reports on the ninth World Congress of International Physicians for the Prevention of Nuclear War (IPPNW), held in Hiroshima, Japan, in October 1989. Taking as their theme "No more Hiroshimas," IPPNW participants visited the sites of the only acts of nuclear war -- the 1945 U.S. bombings of Hiroshima and Nagasaki that ended World War II. Scientific sessions updated information on the health effects of radiation. The congress issued an appeal for "a new agenda of moral priorities" that urges the implementation of five measures: the immediate cessation of all nuclear testing; a halt to the production of bomb-grade fissile material; conversion of secret weapons laboratories to open scientific institutes addressing environmental issues; reallocation of 50% of military spending to health and environmental projects; and the establishment of a U.N. Peace Research Centre at Hiroshima and a scholarship program to educate future world leaders about nuclear war.     

Neurobehavioral phenotype in carriers of the fragile X premutation

There have been contradictory findings in the fragile X (fraX) literature about possible neurocognitive and psychological symptoms due to the fraX premutation (pM). The purpose of the present study was to investigate the relationship between CGG repeat length and neurobehavioral functioning in carriers of the fraX pM. Eighty‐five female carriers of the pM with allele sizes ranging from 59–166 were administered a comprehensive IQ test (WAIS‐III) and completed a questionnaire designed to measure psychopathology (Symptom Checklist (SCL)‐90‐R). No relationship between allele size and cognition was identified. A significant negative relationship between allele size and age was found, as well as a positive relationship between allele size and depression. Follow‐up analyses separating small and large allele sizes (below and above 100 CGG repeats) indicated that individuals with larger allele sizes scored significantly higher on the Interpersonal Sensitivity and Depression subscales of the SCL‐90‐R. Despite the limitation of few individuals with high CGG repeat lengths, our findings suggest that females with larger premutated alleles (≥ 100 repeats) display some clinical manifestations of fraX syndrome. © 2001 Wiley‐Liss, Inc.     

Increased antigen-induced local and systemic mediator release in rhinitis subjects with pulmonary symptoms in the pollen season

In order to delineate parameters that might discriminate between allergic subjects who develop R or R-P symptoms during natural antigen exposure, 26 subjects allergic to grass or ragweed pollen were classified into R or R-P groups, and then the antigen sensitivity and degree of in vivo mediator release were compared. Antigen-skin sensitivity was quantitated by dilutional skin-test titration, and bronchial sensitivity was quantitated by the amount of inhaled antigen required to receive the FEV1 by 20%. Mediator release was determined by measuring the amount of histamine that was released into skin chambers during antigen incubation and the rise in plasma histamine and serum NCA during antigen-induced bronchospasm. Compared to the 13 R subjects, the 13 R-P subjects were: (1) more sensitive to antigen by both skin-test and inhalation challenge, (2) responded to inhalation of antigen with a greater fall in FEV1 and a greater rise in serum NCA and plasma histamine, and (3) released more histamine into skin chambers after antigen incubation. Even when R and R-P subjects were matched by comparing only subjects with equal skin sensitivity to antigen, greater increases in serum NCA and plasma histamine occurred after inhalation of antigen in the R-P subjects. These data are consistent with the hypothesis that allergic rhinitis subjects who develop pulmonary symptoms during natural pollen exposure are more sensitive to antigen and release more mediators in response to antigen administration. It is therefore possible that the degree of mediator release may be an important factor in determining the pattern of clinical responses to antigen exposure.     

Definition of HLA-C alleles using sequence-specific oligonucleotide probes (PCR-SSOP)

Abstract: Many new HLA-C locus alleles have recently been identified by DNA sequencing, and a molecular based method for their detection using PCR with sequence specific primers has been reported. However, other methods may be more appropriate for the identification of C locus alleles in larger studies. Here we describe one such system, based on PCR sequence specific oligonucleotide probes, (SSOP) for C locus typing. Advantages of SSOP typing compared to SSP are that it is easier to detect new alleles, more cost effective and less time consuming. We have developed a DNA typing method to identify the broad C locus antigens (including those not yet defined serologically) using a minimum of probes with one amplification. We use a C locus specific sense primer in exon 2 and a consensus antisense primer in exon 3, in a two-step PCR, giving a product of 710 bp. Probes were designed with similar melting temperatures (54–56C) that would identify as many alleles as possible. The method was established using DNA from B lymphoid cell lines of known C locus type, mostly 10th workshop homozygous cell lines, plus as many other sequenced cell lines as possible. The system was able to correctly identify their C locus types using only 26 probes. DNA was tested from a panel of serologically typed individuals which included many different heterozygous combinations. We found a high concordance of results, with all discrepancies being additional antigens identified by molecular typing, filling in serological blanks. We can identify all common heterozygote combinations using this method.     

Immunogenetic studies in families with rheumatoid arthritis and autoimmune thyroid disease.

HLA and Gm typing were carried out in 16 families. Seven families included 10 sib pairs with rheumatoid arthritis (RA) and autoimmune thyroid disease (ATD) respectively, and nine families included 16 sib pairs with RA and circulating thyroid autoantibodies respectively. Eight, 11, and seven sib pairs with either RA or clinical or immunological evidence of ATD shared none, one, and two HLA haplotypes respectively, and two, seven, and two informative sib pairs shared none, one, and two Gm haplotypes respectively. This random haplotype sharing of HLA and Gm haplotypes suggests that non-HLA, non-Gm linked genes are likely to be involved in any genetic predisposition common to RA and ATD.     

Nucleic acid vaccines

There are no adequate vaccines against some of the new or reemerged infectious scourges such as HIV and TB. They may require strong and enduring cell-mediated immunity to be elicited. This is quite a task, as the only known basis of protection by current commercial vaccines is antibody. As DNA or RNA vaccines may induce both cell-mediated and humoral immunity, great interest has been shown in them. However, doubt remains whether their efficacy will suffice for their clinical realization. We look at the various tactics to increase the potency of nucleic acid vaccines and divided them broadly under those affecting delivery and those affecting immune induction. For delivery, we have considered ways of improving uptake and the use of bacterial, replicon or viral vectors. For immune induction, we considered aspects of immunostimulatory CpG motifs, coinjection of cytokines or costimulators and alterations of the antigen, its cellular localization and its anatomical localization including the use of ligand-targeting to lymphoid tissue. We also thought that mucosal application of DNA deserved a separate section. In this review, we have taken the liberty to discuss these enhancement methods, whenever possible, in the context of the underlying mechanisms that might argue for or against these strategies.     

Genetics of rheumatoid arthritis

The haplotype sharing distribution in affected sib pairs are used to demonstrate the linkage of a susceptibility gene for rheumatoid arthritis (RA) to the HLA region. Family and population studies suggest heterogeneity in the etiology of RA.