Linkage and association of adrenergic and dopamine receptor genes in the distal portion of the long arm of chromosome 5 with systolic blood pressure variation

Elevated blood pressure is an important risk factor for renal-, cerebro- and cardiovascular diseases. We used an efficient discordant sib-pair ascertainment scheme to investigate the impact of the distal end of the long arm of human chromosome 5 (chromosomal region 5q31.1-qter) containing genes for the alpha1B and beta2 adrenergic receptors and the dopamine receptor type 1A on variation of systolic blood pressure in young Caucasians. We measured eight highly polymorphic markers spanning this positional candidate gene-rich region in 427 individuals from 55 three-generation pedigrees containing 69 discordant sibling pairs, and calculated multipoint identity by descent (MIBD) probabilities. The results of genetic linkage and association tests indicate that the region between markers D5S2093 and D5S462 is significantly linked to one or more polymorphic genes influencing interindividual variation in systolic blood pressure levels. Since the alpha1B adrenergic receptor and dopamine receptor type 1A genes are located close to these markers, these data suggest that genetic variation in one or both of these G protein-coupled receptors, which participate in the control of vascular tone, plays an important role in influencing interindividual variation in systolic blood pressure levels.      

THE INTERACTION OF RESPONSES IN THE BRAIN TO SEMANTIC STIMULI

Long time-constant EEG recording during paired stimuli has led to the discovery of the contingent negative variation or expectancy wave (Walter, 1964). This effect is produced when a conditional stimulus signals that an imperative stimulus demanding action, decision, or attention will follow at a short, constant time interval. Symbolic and meaningful stimuli were presented to subjects tachistoscopically, and the evoked responses in the brain were electronically averaged. The cerebral evoked responses to such psychological stimuli are more complex than to flashes. A slow negative DC potential shift (CNV) was seen during the interval between an auditory ready signal and the visual exposure if recognition of the stimulus was required, or if it was interesting. Following the visual exposure, a slow positive DC shift occurred. The method has been developed to study the brain responses to psychological stimuli. The amplitude of the responses relates to the information content and subjective factors rather than to the physical strength of the stimulus.     

Effects of depressive symptoms and mental health quality of life on use of highly active antiretroviral therapy among HIV-seropositive women

This study examines the effects of depressive symptoms and mental health quality of life on utilization of highly active antiretroviral therapy (HAART) among HIV-seropositive women. Data were collected biannually from 1996 through 1998 in a prospective cohort study. Women reported use of antiretroviral therapy, health and mental health status, demographics, and social and behavioral factors; CD4 count and viral load also were assessed. Random effects regression models estimated the longitudinal effects of depressive symptoms and mental health quality of life on the probability of HAART utilization, controlling for clinical indicators (CD4 count, viral load, symptom presence), demographics (race, age, education), behavioral factors (drug/alcohol use, clinical trials participation), service features (insurance status, mental health service utilization), and study site. High levels of depressive symptoms and poor mental health quality of life were found, and they significantly reduced the probability of HAART utilization. Receiving mental health services significantly increased the probability of utilizing HAART. HIV-seropositive women characterized as being in poor mental health were less likely to use HAART, whereas those receiving treatment of mental health difficulties were more likely to use HAART. These findings suggest that efforts to enhance women's access to psychological treatment may increase their use of the latest HIV therapies.     

THE ARDEN GRATINGS IN OPTOMETRIC PRACTICE

The use of the Arden gratings (AO contrast sensitivity system) in optometric practice is evaluated. A total of 320 patients presenting for eye examination were screened with the gratings. Sixty-four eyes (10%) gave abnormal grating scores although results from conventional examination techniques revealed no abnormality. Of the 110 abnormal eyes detected by routine examination techniques, 8 presented with normal grating scores, 6 with "borderline suspect" scores and 96 with abnormal scores. Used in isolation, the failure rate of the Arden gratings to detect ocular abnormality in the patient population was 1.3% and the "false positive" referral rate was 10%.     

Inhibition of antigen presentation in vitro and in vivo by MHC antagonist peptides

A series of analogue peptides have been generated, using as a template the core region of the OVA 323-339 peptide identified as critical in determining binding to I-Ad. Several of these "core extended" peptides had increased affinities for the I-Ad molecule compared to the native sequence, and were able to inhibit activation of an I-Ad-restricted T cell hybridoma in vitro. The induction of a T cell proliferative response to a peptide antigen could be inhibited by co-administration of core-extended peptide with antigen in the same adjuvant emulsion. Furthermore, inhibition also occurred when the inhibitor molecule was delivered separately one day before immunization. Finally, the induction of the autoimmune disease, experimental allergic encephalomyelitis (EAE), in susceptible mice could be reduced by the administration of a core-extended peptide with high affinity for the appropriate class II molecule. These findings have implications for the use of MHC antagonists in the control and treatment of MHC-associated autoimmune conditions in humans.