Spontaneous reversion of human immunodeficiency virus type 1 neutralization-resistant variant HXB2thr582: in vitro selection against cytopathicity highlights gp120-gp41 interactive regions.

Spontaneous revertants of the immune-selected variant HXB2thr582, which resists neutralization by certain conformationally dependent antibodies specific for the CD4-binding site on gp120 (such as F105), appeared after long-term culture in the absence of immune-selecting serum. Molecular analysis showed some of the viruses in the revertant stock contained a simple back mutation, whereas others retained the Thr-582 codon but contained a substitution of serine for phenylalanine in gp41 at position 673. Neutralization sensitivity to the selecting serum and to F105 of infectious clones containing either the back mutation or the compensatory mutation, HXB2thr582ser673, was confirmed. HXB2thr582-infected cells have a greater propensity for syncytium formation and single cell killing than do either the parental HXB2 or the revertant HXB2thr582ser673. This suggests that the revertant arose by selection in vitro for a less cytopathic virus. Our results link three envelope regions shown to influence virus-cell fusion as well as neutralization by antibody: the CD4-binding region, the leucine zipper domain, and a region hidden to antipeptide antibodies upon envelope oligomerization. Taken together they illustrate the functional importance of the gp120-gp41 interaction and emphasize the impact of the interplay between envelope regions on overall conformation and function and on recognition by neutralizing antibodies.

Subgroup G HIV type 1 isolates from Nigeria.

PIP: Nucleotide sequences were obtained for portions of the envelope and gag genes of 4 HIV-1 isolates from Nigeria. The gag gene sequences clustered with previously described gag sequences from Gabon, Zaire, and Taiwan, which form the G clade of HIV-1. This documented for the first time the presence of subgroup G viruses in Nigeria. The env gene sequences were most closely related to env sequences reported from 2 isolates previously classified as gag subgroup G and, with those 2 env sequences, defined the subgroup G env genotype. Virus isolates were obtained by cocultivation of peripheral blood mononuclear cells (PBMCs) from Nigerian AIDS patients (isolates JV1018 and JP88) or healthy prostitutes (G3 and G9) with normal uninfected PBMCs (JV1083, JP88, and G3) or GEM-SS, a T cell line (G9). Clones containing env and gag gene sequences were obtained by polymerase chain reaction amplification, using DNA from these cultures. The region of gag amplified by primers SK37 and SK39 containing BamHI and KpnI sites, respectively, in 5' tails, was cloned into the KpnI-BamHI site of pKSBluescript and sequenced. When the gag sequences from 2 of the Nigerian viruses were subtyped by weighted parsimony, both viruses grouped with others of the gag G subgroup. A similar analysis of env sequences from all 4 Nigerian isolates showed that they were most closely related to 2 env sequences that had been assigned to env subgroup G. The Nigerian env sequences clustered more closely with each other than they did with the other 2 subgroup G viruses. Consensus of the inferred amino acid sequences of the 4 env genes showed that the V3 loop closely resembled the A to F consensus. 8 positions in the Nigerian consensus sequence appeared to be unique. However, whether these are signature residues for Nigerian subgroup G isolates or for subgroup G isolates will require the characterization of more isolates.^ieng

Cross-neutralization of human immunodeficiency virus type 1 and 2 and simian immunodeficiency virus isolates.

In contrast to infrequent and low-titer cross-neutralization of human immunodeficiency virus type 1 (HIV-1) isolates by HIV-2- and simian immunodeficiency virus (SIV)-positive sera, extensive cross-neutralization of HIV-2NIH-Z, SIVMAC251, and SIVAGM208K occurs with high titer, suggesting conservation of epitopes and mechanism(s) of neutralization. The V3 regions of HIV-2 and SIV isolates, minimally related to the HIV-1 homolog, share significant sequence homology and are immunogenic in monkeys as well as in humans. Whereas the crown of the V3 loop is cross-reactive among HIV-1 isolates and elicits neutralizing antibodies of broad specificity, the SIV and especially HIV-2 crown peptides were not well recognized by cross-neutralizing antisera. V3 loop peptides of HIV-2 isolates did not elicit neutralizing antibodies in mice, guinea pigs, or a goat and together with SIV V3 peptides did not inhibit serum neutralization of HIV-2 and SIV. Thus, the V3 loops of HIV-2 and SIV do not appear to constitute simple linear neutralizing epitopes. In view of the immunogenicity of V3 peptides, the failure of conserved crown peptides to react with natural sera implies a significant role of loop conformation in antibody recognition. Our studies suggest that in addition to their grouping by envelope genetic relatedness, HIV-2 and SIV are neutralized similarly to each other but differently from HIV-1. The use of linear peptides of HIV-2 and SIV as immunogens may require greater attention to microconformation, and alternate subunit approaches may be needed in exploiting these viruses as vaccine models. Such approaches may also be applicable to the HIV-1 system in which conformational epitopes, in addition to the V3 loop, participate in virus neutralization.

Hospital privileges for graduates of family practice residency programs.

In 1979 the American Academy of Family Physicians, as the first phase of a long-range study of family practice residency outcomes, surveyed graduates for the years 1970 through 1978 who were diplomates of the American Board of Family Practice. This report is limited to an overview analysis of the hospital admission and practice privileges of the 3,021 respondents actively practicing family medicine in the United States. A higher percentage of respondents in census regions west of the Mississippi River were more likely to have privileges in obstetrics and surgery than were respondents in eastern regions. Respondents in nonmetropolitan areas were more likely to have hospital privileges than were respondents in metropolitan areas.

Hospital privileges for family physicians: a national study of office based members of the American Academy of Family physicians.

In 1980 the American Academy of Family Physicians sampled those active members who were nonfederal, office based physicians in direct patient care to ascertain the characteristics of their hospital practices. The sample was stratified by the nine US census regions: 83.7 percent of the 5,216 active members in the sample responded. The vast majority of family physician/general practitioners in direct patient care in an office based setting have hospital admission privileges in one or more hospitals. A higher percentage of family physicians/general practitioners in census regions west of the Mississippi River were likely to have privileges in obstetrics and surgery than those in eastern regions. Moreover, family physicians/general practitioners in the nonmetropolitan areas of each census region were more likely to have hospital privileges at any level than were their colleagues in the metropolitan areas of the same region. Although there were disparities in the proportions of family physician/general practitioners with certain hospital privileges among regions, the vast majority in each region indicated that the privileges afforded them were appropriate.

Practice locations of family practice residency graduates.

The purpose of this study was to examine the practice location patterns of 1970-1978 graduates of family practice residency programs. Comparisons were made between the number of graduates practicing in a region in 1979 with the number of all graduates during 1970-1978 from family practice residency programs in that region and with the number of all graduates from medical schools in that region who eventually completed family practice residencies elsewhere. The Middle Atlantic and West North Central regions showed marked decreases, while the Mountain, Pacific, and New England regions showed increases. The majority practiced more than 100 miles from their residency program. Most respondents practicing in a nonmetropolitan area moved outside of a 100-mile radius from their residencies. Most respondents practicing in a metropolitan area practiced within the 100-mile radius. Physicians were likely to be practicing in a community similar to their backgrounds.

The Residency Assistance Program in family practice.

The Residency Assistance Program in family practice was inaugurated in September 1975 as a plan to mobilize and finance the matching of consultant expertise in family practice residency education with program directors desiring to improve the quality of their residency programs through consultative assistance. The Residency Assistance Program is administered by a Project Board composed of representatives of four national family practice organizations. A panel of 30 consultants, carefully selected by the Project Board, are prepared for rendering effective consultative services through intensive training in consultative skills. They operate under the guidance of concensually developed standards for quality graduate education in family practice. Consultations are only scheduled at the written request of a residency program director. The confidential, nonpunitive, and voluntary nature of a Residency Assistancy Program consultation is carefully guarded, because it is felt that these qualities enhance the information-sharing, collaborative problem-solving nature of the consultative process. This paper describes the development, features, and operational process of this Program.

The effect of the organization and status of family practice undergraduate programs on residency selection.

Family practice, as a medical specialty, is designed to help fill the void in primary care availability. In order to expose medical students to family practice and provide a basis for choosing a residency in the field, many medical schools have developed undergraduate programs in family practice. This paper reports the results of a survey conducted in March 1975 on the status of undergraduate programs with particular focus on the relationships between administrative status, size of program, faculty size, and type of undergraduate curricula to the number of graduates choosing family practice as a specialty. The data indicate that there is a relationship between the commitment of the school to family practice, the size of the program, and the presence of required courses in the curriculum to the success of the program, as measured by the proportion of students in each school who choose family practice residencies.

The Teacher Interest Profile Registry of AAFP: implementation and effectiveness.

In order to assist in the recruitment of physicians from practice into teaching during a period of rapid expansion in family practice education in the United States, the Division of Education of the American Academy of Family Physicians developed a computerized listing of members of the Academy who were interested in being contacted about available faculty positions. This computerized list, containing pertinent information about the professional qualifications of the registrants, became known as the Teacher Interest Profile Registry and was made available upon request to recruiting program administrators in 1974-1975. An evaluation of the utilization and effectiveness of the registry was conducted by staff of the Division of Education in the spring of 1975 by means of mailed questionnaries to the two groups utilizing the service: program administrators and physician-registrants. Results of these surveys revealed that one out of every eight programs using the registry was successful in recruiting one or more new faculty members, with a total of 27 new faculty reported as having been recruited through the use of this service. In view of the relative success of this program in identifying potential faculty members and the continued interest and utilization of the service, academy leaders have decided to continue this service until it is no longer effective and/or needed.

Continuing medical education in America.

Some of what may be perceived as today's failures in continuing medical education may have been caused by lack of sound educational principles in the medical education process. Others may be due to changing times and expanding knowledge. New methods need to be established which include education based on physician audit and self-assessment. Learning outcomes should be evaluated in order to assess physicians' abilities to render better patient care. The formal graduate educational program is seen as the base for the new method of delivery of continuing medical education. The residency has the ability to evaluate advances in medicine and distill them for the practicing clinician. It may also assist him with office systems which will enable him to monitor his practice and needs. Linkages with residency programs will benefit the practitioner and resident alike. In the future, other community facilities may be needed to handle problem-centered continuing medical education.