Generation and characterization of a human monoclonal antibody that neutralizes diverse HIV-1 isolates in vitro.

OBJECTIVE: The purpose of this study was to develop and characterize human monoclonal antibodies (HuMAb) that neutralize HIV-1. DESIGN: Based upon previous studies involving the generation of HuMAb that neutralize other enveloped viruses, we thought it feasible to generate HuMAb that might neutralize HIV-1. METHODS: A HuMAb was generated by fusing splenic B-cells from an HIV-positive patient with a mouse myeloma cell line. Flow cytometry was used to determine surface reactivity of the HuMAb on HIV-infected and non-infected cells. Radioimmunoprecipitation was employed to elucidate the antigen recognized by the HuMAb. A cell survival assay was used to determine the ability of the HuMAb to neutralize divergent isolates of HIV-1 in the presence or absence of complement. A gp120-CD4 inhibition enzyme-linked immunosorbent assay (ELISA) was developed in order to initiate studies to determine the mechanism of neutralization by the HuMAb. RESULTS: An anti-HIV HuMAb was generated that neutralized two HIV-1 isolates (IIIB and MN) without complement and which neutralized one divergent isolate (RF) and one clinical isolate in the presence of complement. This HuMAb, designated S1-1, was found, by flow cytometric analysis, to react with the surface of HIV-1-infected but not with uninfected cells. Radioimmunoprecipitation analysis demonstrated that S1-1 binds to native HIV gp120, but not dithiothreitol (DTT)-treated gp120. In addition, HuMAb S1-1 did not bind to denatured HIV antigens in Western blot analysis. HuMAb S1-1 effectively inhibited the binding of gp120 to soluble CD4 in ELISA. CONCLUSIONS: These results suggest that the epitope recognized by S1-1 is conformational and conserved among diverse HIV-1 isolates and may represent an uncharacterized HIV neutralizing domain within or close to the CD4 binding domain on gp120. HuMAb S1-1 might have a role to play in vaccine development or passive immunotherapy.     

Eating attitudes as related to demographic and personality characteristics: a high school survey

A survey of 577 high school students was conducted to assess attitudes toward eating and their relationship to demographic and personality characteristics. Students completed a demographic questionnaire, and Eating Attitude Test (EAT-26) and the Basic Personality Inventory (A-BPI). When a cut-off score of 20 on EAT-26 was applied, overall prevalence of disordered eating attitude was found to be 7.5%. Groups scoring in pathological versus normal ranges showed no significant difference in mean age, socioeconomic status or race. The former group reported significantly shorter height and lower body weight. Of the subjects, 6.06% reported weight below the 10th percentile. This subgroup did not vary from those above the 10th percentile on sociodemographic and psychopathological variables, nor in prevalence of abnormal eating attitudes. Analysis of the A-BPI data showed subjects with abnormal eating attitudes had increased psychopathology in several areas, with greater neurotic tendencies, lower self-esteem and higher levels of deviant thinking and behaviour.     

The geographic distribution of measles in the United States, 1980 through 1989.

OBJECTIVE--To describe the geographic distribution of measles cases in the United States by county for the 10-year period from 1980 through 1989. DESIGN--Ecological analysis of national measles surveillance data. METHODS--Measles cases reported to the Morbidity and Mortality Weekly Report from 1980 through 1989 were analyzed. Data from the 1980 and 1990 US censuses were used to produce demographic profiles for each of the 3137 countries. Outcome variables examined included mean annual incidence and number of years reporting measles, with use of Spearman's rank correlation coefficients to examine the association between the demographic and the two outcome variables. RESULTS--A total of 56,775 measles cases were reported during the decade. Of the nation's 3137 counties, 1690 (53.9%) did not report any cases; only 17 (0.5%) reported measles in all 10 years. Counties reporting measles more frequently during the decade had higher median populations, population densities, and percentage of black and Hispanic populations than those counties reporting less frequently. Population size, population density, and percentage of Hispanic population were associated with number of years reporting measles and mean annual measles incidence rate. Measles cases in counties reporting measles every year predominantly occurred in unvaccinated preschoolers; cases in counties reporting less frequently predominantly occurred in vaccinated school-aged children. CONCLUSIONS--This analysis illustrates the focal nature of measles in the United States during the past decade. Most counties have not reported a single case of measles during the entire decade, and only 17 counties reported measles every year. Targeted strategies are needed to improve age-appropriate immunization levels among preschool-aged children living in large inner-city areas.     

The types of drugs used by HIV-infected injection drug users in a multistate surveillance project: implications for intervention.

OBJECTIVES. This study sought to describe the drugs used by drug injectors infected with human immunodeficiency virus (HIV) and to determine factors associated with the primary injection drug used. METHODS. A cross-section of persons 18 years of age or older reported with HIV or acquired immunodeficiency syndrome (AIDS) to local health departments in 11 US states and cities was surveyed. RESULTS. Of 4162 persons interviewed, 1147 (28%) reported ever having injected drugs. Of these 1147 injectors, 72% primarily injected a drug other than heroin. However, the types of drugs injected varied notably by place of residence. Heroin was the most commonly injected drug in Detroit (94%) and Connecticut (48%); cocaine was the most common in South Carolina (64%), Atlanta (56%), Delaware (55%), Denver (46%), and Arizona (44%); speedball was most common in Florida (46%); and amphetamines were most common in Washington (56%). Other determinants of the type of drug primarily injected were often similar by region of residence, except for heroin use. Polysubstance abuse was common; 75% injected more than one type of drug, and 85% reported noninjected drug use. CONCLUSIONS. Preventing the further spread of HIV will require more drug abuse treatment programs that go beyond methadone, address polysubstance abuse, and adapt to local correlates of the primary drug used.     

Correlates of Control in Pediatric Cancer Patients and Their Families

Physical illness is a life experience which challenges an individual'ssense of control and thus represents a potential threat to mentalhealth. For children, a serious illness threatens not only theirsense of physical and psychological well-being but also threatensthe psychological well-being of their family. In this study,severely ill patients (n = 15) and a member of their family(n = 15) were interviewed. The patients, who ranged in age from12 to 21 years, were being treated for metastatic solid tumorsor lymphoma that failed to respond to conventional therapeuticregimens. Correlates of control for the patients and familymembers, the relationship between control and developmentalstage of the patients, and the difference between levels ofcontrol in patients and family member were examined. The findingsare discussed in relation to development and their implicationsfor medical management.     

Cholinergic fiber aberrations in nucleus basalis lesioned rat and Alzheimer's disease.

Innervation density and morphological aberrations of cholinergic fibers were studied with choline acetyltransferase (ChAT) immunocytochemistry and acetylcholinesterase (AChE) histochemistry in 30-35 month-old aged rats and rats with long-term bilateral lesions of the magnocellular basal nucleus (MBN). In addition, AChE histochemistry was performed on human cortical sections derived from autopsy brains of normal aged and Alzheimer's disease (AD) patients. A limited but variable number of morphological alterations were observed in ChAT-immunoreactive fibers in the cortex and the hippocampus of the aged control rats. The aged MBN-lesioned rats displayed a severely reduced number of cholinergic fibers in the denervated areas of the neocortex, whereas the surviving fibers showed a strongly increased number of aberrations. Fiber anomalies were also observed in the cortex of the aged human subjects and Alzheimer patients, the latter showing a higher incidence of such aberrations. Only a part of these distended profiles were seen in close association with senile plaques as detected in the AChE-stained material. These findings suggest that experimental MBN lesions combined with aging share with AD the induction of large quantities of fiber malformations. Implications of possible mechanisms in both conditions are discussed.     

Choline acetyltransferase immunoreactivity in neuritic plaques of Alzheimer brain

We have observed dystrophic choline acetyltransferase (ChAT)-positive processes surrounding the amyloid core of neuritic plaques in human neocortex, amygdala and hippocampus, using a polyclonal anti-human ChAT antiserum. These data, and those from studies of the aged monkey by other investigators, provide a morphologic counterpart for the biochemical abnormality of the cholinergic system in Alzheimer's disease and senile dementia of the Alzheimer type.     

Prophylaxis and treatment of experimental lung metastases in mice after treatment with liposome-encapsulated 6-O-stearoyl-N-acetylmuramyl-L-α-aminobutyryl-D-isoglutamine

A new lipophilic muramyl dipeptide analog, 6-O-stearoyl-N-acetylmuramyl-L--aminobutyryl-D-isoglutamine, when incorporated in liposomes, was effective in both the prevention and eradication of experimental pulmonary metastases in mice. Multilamellar vesicles composed of synthetic phospholipids (phosphatidylglycerol and phosphatidylcholine) containing saturated myristoyl or unsaturated dioleoyl acyl chains were found to potentiate the antimetastatic activity of this glycopeptide. Prophylactic and therapeutic efficacy was observed against the three murine tumors tested: FSa, an immunogenic fibrosarcoma; NFSa, a nonimmunogenic fibrosarcoma; and B16 melanoma. Neither the administration of empty liposomes or free glycopeptide, nor their coadministration, had a significant antimetastatic effect. This approach is promising for the therapy of cancer metastases in humans, particularly in the prevention of metastatic seeding and in the treatment of micrometastases.This is contribution No. 180 from the Institute of Bio-Organic Chemistry, Syntex Research.     

Cholinergic divergent projections from rat basal forebrain to the hippocampus and olfactory bulb

Cholinergic neurons in the basal forebrain which project to both the hippocampus and olfactory bulb were identified in the rat by using twin fluorescent retrograde tracers combined with fluorescence immunohistochemistry for choline acetyltransferase (ChAT). The majority of neurons simultaneously labeled with the two tracers were also identified as being ChAT-positive. They were located at the border between the horizontal and vertical limbs of the diagonal band of Broca. Their numbers were very small compared with neurons singly labeled from each of the projection areas.