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.     

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.     

Donor insemination: child development and family functioning in lesbian mother families

Findings are presented of a comparative study investigating the family relationships and the emotional and gender development of children raised in lesbian mother families. A total of 30 lesbian mother families with 4-8 year old children created as a result of donor insemination (DI) were compared with 38 heterosexual families with a DI child and with 30 heterosexual families who had a naturally conceived child. A variety of assessment measures, including a standardized interview and questionnaires from the parents and psychological testing of the child were used to collect the data. The quality of the couples' relationships and the quality of the mother-child interaction did not differ between lesbian mother families and either of the heterosexual family groups. The quality of the interaction between the social mother and the child in lesbian families was superior to that between the father and the child in both groups of heterosexual families. Childrens' own perception of their parents was similar in all family types; the social mother in lesbian families was regarded by the child to be as much a 'parent' as the father in both types of heterosexual families. With regard to their emotional/behavioural development, boys and girls raised in lesbian mother families were well adjusted and their gender role development did not differ from that of children raised in heterosexual families. These results indicate that child and family development in lesbian mother families is similar to that of heterosexual families.      

Donor insemination: Dutch parents' opinions about confidentiality and donor anonymity and the emotional adjustment of their children

Results from a comparative study investigating 38 donor insemination (DI) Dutch families with 4-8 year old children are presented. The aims of this study were to investigate parents' opinions on the issues of confidentiality and donor anonymity, to assess the emotional development of the children, and to examine in DI families the association between secrecy with regard to the use of a donor and the emotional adjustment of the children. The DI families were compared to families with a child conceived by in-vitro fertilization (IVF) and to families with a naturally conceived child. Secrecy appeared to be associated with DI and not with IVF: 74% of the DI parents intended not to inform the child about the way in which she/he was conceived, whereas none of the IVF parents intended to keep the secret. Only one set of DI parents and two sets of IVF parents had actually told the child. As to donor anonymity, a spread of opinions appeared among DI parents; 57% preferred an anonymous donor, 31% would have liked non- identifying information about the donor, 9% preferred the donor's identity to be registered and 3% remained unsure. Parents' major concern was to know more about the medical/genetic background of the donor. Mothers and fathers in the DI families differed in their opinions concerning the issues of confidentiality and donor anonymity: fathers, more often than mothers, were secretive with regard to the use of a donor and husbands, more often than their wives, were in favour of donor anonymity. With regard to the emotional development of the children, more emotional/behavioural problems were revealed among DI children than among children who were naturally conceived. No association was found between secrecy and the emotional/behavioural adjustment of the children.      

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.