Immunopathogenesis of acute central nervous system disease produced by lymphocytic choriomeningitis virus. I. Cyclophosphamide-mediated induction by the virus-carrier state in adult mice.

A single dose of 150 mg/g of cyclophosphamide (CY), given 3 days after intracerebral (i.c.) inoculation of lymphocytic choriomeningitis (LCM) virus, protected over 90% of adult BALB/c mice against acutely fatal choriomeningitis. Surviving mice became persistently infected carriers, with high virus titers in blood and brain. Immunofluorescent examination of the brain showed that in CY-induced carriers infection was initially confined to the choroid plexus, ependyma, and leptomeninges, but over the next 30 days gradually spread to the neural parenchyma, most notably to the molecular layer of the cerebellum. By contrast, LCM virus-carrier mice produced by neonatal virus injection and examined as adults, showed a much less marked infection of choroid plexus and much more widespread infection of parenchyma, with a different distribution among brain nuclei, including heavy infection of the Purkinje cells of the cerebellum.

Stress-induced modulation of the immune response.

After mice were exposed to a daily auditory stressor for varying lengths of time, the responses of their splenic lymphoid cells in vitro were assessed. Both the blastogenic activity of concanavalin A or lipopolysaccharide and the ability of immune lymphocytes to lyse P815 target cells showed the same patterns of immunosuppression and enhancement.

Cerebellar hypoplasia in neonatal rats caused by lymphocytic choriomeningitis virus.

Lymphocytic choriomeningitis virus, strain E-350, when inoculated intracerebrally in rats 1 to 7 days old, produces an acute destructive infection of the cerebellar cortex resulting in permanent cerebellar hypoplasia and ataxia. Several other arenoviruses may produce a similar lesion in neonatal rodents.

HIV-related symptoms and psychological functioning in a cohort of homosexual men.

The authors administered the Center for Epidemiological Studies Depression (CES-D) Scale to 4,954 homosexual men in the Multicenter AIDS Cohort Study. HIV antibody status at enrollment was a less important predictor of psychological distress than were reported physical symptoms. Multivariate analysis showed an association between a high score on each CES-D Scale component and the number of self-reported possible AIDS- or HIV-related symptoms, perceived lymphadenopathy, and absence of "someone to talk to about serious problems." This relationship between self-reported physical symptoms and psychological distress suggests a possible etiologic relationship between perceived AIDS risk and psychological symptoms in men at risk of AIDS.

Chronic retinitis in rats infected as neonates with lymphocytic choriomeningitis virus: a clinical, histopathologic, and electroretinographic study.

The long-term sequelae to infection of neonatal rats with lymphocytic choriomeningitis virus were studied by a variety of approaches, including indirect ophthalmoscopic, electroretinographic, and histopathologic methods. Data from these studies demonstrated that a progressive chronic retinitis develops after the acute, virus-specific, immune-mediated retinopathy. This chronic inflammation eventually leads to a total destruction of the retinal architecture. An autoimmune reaction against normally sequestered retinal antigens, released during the acute state of necrotizing retinitis, is probably the initiating mechanism of the chronic disease. This experimental disease, triggered by infection with a relatively harmless virus, constitutes a very convenient animal model of chronic retinitis.

Incidence and remission of insomnia among elderly adults: an epidemiologic study of 6,800 persons over three years.

To determine incidence and remission rates of insomnia in older adults and associated risk factors. Three-year longitudinal study, 1982-198--East Boston, MA; New Haven, CT; Iowa and Washington counties, IA. Participants were 6,899 men and women aged 65 years and older. Self-reported difficulty falling asleep or early morning arousal (insomnia), along with physician diagnosis of heart disease, stroke, cancer, diabetes, or hip-fracture, self-report of physical disability, depressive symptomatology, perceived health status, and use of medications ascertained at both baseline and three-year follow-up. Nearly 15% of the 4,956 participants without symptoms of insomnia at baseline reported chronic difficulty falling asleep or early morning arousal at follow-up, suggesting an annual incidence rate of approximately 5%. Incident insomnia was associated with depressed mood, respiratory symptoms, fair to poor perceived health, and physical disability. In multivariate analyses, these risk factors explained the higher incidence of insomnia among those with medical conditions such as heart disease, stroke, and diabetes. Other factors associated with an increased risk of insomnia included use of prescribed sedatives, and widowhood. Only 7% of the incident cases of insomnia occurred in the absence of associated risk factors. Of the nearly 2,000 survivors with chronic insomnia at baseline, almost half no longer reported symptoms upon follow-up and were more likely to report improved self-perceived health compared to those who continued to report symptoms. Chronic disease, depressed mood, physical disability, poor perceived health, widowhood, and use of sedatives are associated with development and remission of insomnia symptoms. Because the vast majority of incident cases of insomnia were among persons with one or more of these risk factors, these data do not support a model of incident insomnia caused by the aging process per se.

Incidence and remission of insomnia among elderly adults in a biracial cohort.

OBJECTIVES: To determine the incidence and remission rates of insomnia in older adults according to race and associated risk factors in a three-year longitudinal study. METHODS: 2,971 men and women, aged 65 years and older, completed questionnaires administered by trained interviewers at baseline and three years later. Data concerning difficulty falling asleep or early morning arousal (insomnia), along with self-reports of physical disability, respiratory symptoms, depressive symptomatology, perceived health status, and use of prescribed sedative medication, were collected and analyzed. RESULTS: Overall, 15% of the participants without symptoms of insomnia at baseline reported chronic difficulty falling asleep or early morning arousal three years later in follow-up interviews. African-American women had a significantly (p < 0.01) higher incidence of insomnia (19%) compared with African-American men (12%) or with white men and women (both 14%). Men were more likely than women to no longer report symptoms at follow-up (64% vs 42%; p < 0.01). For both races, the presence of depressed mood was a risk factor for the incidence of insomnia, and the absence of depressed mood was a predictor of remission. CONCLUSIONS: Insomnia occurs more frequently in African-American women than in African-American men or than in white men or women. Regardless of race, women are less likely than men to resolve their insomnia. The high prevalence and incidence of morbidity in elderly African-American women may contribute to their high rate of insomnia.

Sleep complaints among elderly persons: an epidemiologic study of three communities.

The frequencies of five common sleep complaints--trouble falling asleep, waking up, awaking too early, needing to nap and not feeling rested--were assessed in over 9,000 participants aged 65 years and older in the National Institute on Aging's multicentered study entitled "Established Populations for Epidemiologic Studies of the Elderly" (EPESE). Less than 20% of the participants in each community rarely or never had any complaints, whereas over half reported at least one of these complaints as occurring most of the time. Between 23% and 34% had symptoms of insomnia, and between 7% and 15% percent rarely or never felt rested after waking up in the morning. In multivariate analyses, sleep complaints were associated with an increasing number of respiratory symptoms, physical disabilities, nonprescription medications, depressive symptoms and poorer self-perceived health. Sleep disturbances, particularly among older persons, oftentimes may be secondary to coexisting diseases. Determining the prevalence of specific sleep disorders, independent of health status, will require the development of more sophisticated and objective measures of sleep disturbances.

Daytime sleepiness is associated with 3-year incident dementia and cognitive decline in older Japanese-American men.

OBJECTIVES: To assess the longitudinal association between sleep disturbances (insomnia and daytime sleepiness) and incidence of dementia and cognitive decline in older men. DESIGN: Community-based longitudinal cohort study. SETTING: The Honolulu-Asia Aging Study of dementia that is linked to the Honolulu Heart Program's fourth examination, conducted 1991-1993, and the 3-year follow-up fifth examination, conducted 1994-1996. PARTICIPANTS: Two thousand three hundred forty-six Japanese-American men age 71 to 93 years who screened negative for prevalent dementia at baseline and were screened again for dementia incidence in a 3-year follow-up examination. MEASUREMENTS: Baseline self-reports of trouble falling asleep or early morning awakening (insomnia) and being sleepy during the day (daytime sleepiness); Cognitive Abilities Screening Instrument (CASI) scores from baseline and followup; clinical diagnosis of incident dementia; and other baseline measures including age, years of education, body mass index, depressive symptoms, and history of hypertension, heart disease, diabetes mellitus, asthma, and use of benzodiazepines. RESULTS: After adjusting for age and other factors, persons reporting excessive daytime sleepiness at baseline (8%) were twice as likely to be diagnosed with incident dementia than were those not reporting daytime sleepiness (odds ratio (OR)=2.19, 95% confidence interval (CI)=1.37-3.50) and about 40% more likely to have >or=9 point drop in their CASI score between examinations (OR=1.44, 95% CI=1.01-2.08). In contrast, insomnia was not associated with cognitive decline or incidence of dementia. CONCLUSIONS: Daytime sleepiness in older adults may be an early indicator of decline in cognitive functioning and onset of dementia.

Associations of symptoms of sleep apnea with cardiovascular disease, cognitive impairment, and mortality among older Japanese-American men.

OBJECTIVES: To examine the association between symptoms of sleep apnea and prevalent cardiovascular disease, cognitive impairment, and subsequent 3-year mortality. DESIGN: A longitudinal study. SETTING: Participants lived in the community on Oahu, Hawaii. PARTICIPANTS: A total of 2905 older Japanese-American men participating in the fourth examination of the Honolulu Heart Program cohort study from 1991-1993, which is the baseline for the Honolulu-Asia Aging Study of dementia. MEASUREMENTS: Self-reported snoring, daytime sleepiness, and breathing pauses; diagnosed cardiovascular disease and dementia; cognitive functioning and vital status approximately 3 years later. RESULTS: More than 12% of the participants reported that they often or always snored loudly, and 8% reported being sleepy most of the day. Fewer than 2% reported that they stop breathing when sleeping, and this was found more frequently among habitual snorers (7%, P < .001) and those sleepy during the day (5%, P < .001). The prevalence of habitual snoring declined in the older age groups, was higher among those with greater Body Mass Index scores, and was not associated with the reporting of daytime sleepiness, diagnosis of heart disease, stroke, dementia, or cognitive impairment. Daytime sleepiness was more prevalent at older ages and was associated with a higher prevalence of heart disease and with cognitive impairment and dementia, chronic obstructive pulmonary disease, and diabetes. Self-reported apnea was associated only with a history of pneumonia. Three-year mortality was not associated with these symptoms after adjusting for prevalent heart disease and cognitive impairment. CONCLUSION: Symptoms of sleep apnea are reported less frequently in older Japanese-American men. Excessive daytime sleepiness is associated with poor cognition and dementia, but whether it also is an indicator for sleep apnea in this age group remains unclear. Epidemiologic studies of sleep apnea in older adults will require polysomnography to determine accurately the correlates and consequences of this condition.

Estrogen replacement therapy for the potential treatment or prevention of Alzheimer's disease.

Alzheimer's disease (AD) is an irreversible, progressive brain disorder that occurs gradually and results in memory loss, behavior and personality changes, and a decline in cognitive abilities. Although basic biological data suggest that estrogen may have neuroprotective and neuroenhancing functions, a number of studies have produced conflicting findings on the use of estrogen for maintaining cognitive function in older people. This review summarizes clinical studies that have examined the effects of estrogen in women with AD.

Manipulation of mobile phase parameters for the HPLC separation of endogenous monoamines in rat brain tissue.

Multi-component mobile phases are common in ion pair reverse phase high performance liquid chromatography for the analysis of endogenous monoamines in rat brain tissue. By examining the effects of each component of a mobile phase on the separation of a number of monoamines and their metabolites, we show how optimization of parameters can achieve and/or maintain a separation both within and between different octadecyl columns. The assay itself is rapid, sensitive, demands minimal sample preparation, and results in complete resolution of the amines. More importantly, the basis for the manipulation of mobile phase components is discussed with regard to practical utilization in selective amine separation. We conclude that knowledge of mobile phase parameters, their mechanism, and manipulation is as important as the assay itself.

Delayed-type hypersensitivity response in mice to Treponema pallidum.

C3H/HeJ mice which had been primed with either virulent or killed T. pallidum were studied for in vivo delayed-type hypersensitivity (DTH) responses to T. pallidum following local footpad challenge. Mice sustaining a chronic infection of 5 months duration failed to develop a DTH to treponemal antigens, whereas priming by a single intravenous injection with killed organisms resulted in a significant DTH response in mice when challenged 5 days later. Treatment of mice prior to priming with a single sublethal dose of cyclophosphamide (100 mg/kg body weight) not only failed to potentiate T. pallidum-DTH, but abrogated the response observed in untreated primed animals.

High-performance liquid chromatographic (HPLC) separation and quantitation of endogenous glucocorticoids after solid-phase extraction from plasma.

This study describes a method for the extraction and simultaneous measurement of cortisone, cortisol and corticosterone using dexamethasone as an internal standard. Solid-phase extraction of plasma steroids with C18 columns allows the samples to be extracted, washed and concentrated in a single step with minimal sample handling and without the use of large volumes of organic solvents. HPLC separation of the steroids is accomplished within 10 min and the individual steroid peaks are quantitated by UV detection at 239 nm. This assay was examined for linearity, extraction efficiency, precision and potential interference by commonly used drugs. Plasma values of glucocorticoids are reported for samples obtained from human subjects as well as from rats. HPLC was also compared to RIA for the determination of plasma levels of corticosterone in the rat. Solid-phase extraction and assay by HPLC provides a rapid and specific method for the simultaneous determination of plasma glucocorticoids.