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Biomedical subjects

R R Redfield

Publications and source records attributed to R R Redfield.

At least 73 records · Page 4Linked to original sources

Patterns of antibody recognition of selected conserved amino acid sequences from the HIV envelope in sera from different stages of HIV infection.

A total of six amino acid sequences encoded in conserved regions of the HIV-env (three from gp120 and three from gp41) were selected as potential antigenic domains. These sequences (11-20 amino acids) were fused to the NH2 terminus of beta-galactosidase by recombinant DNA techniques, and the purified chimeric proteins were used to titer (by immunodots) 75 sera from HIV-infected individuals of various stages. All the HIV antigens were recognized by some or all the HIV-seropositive sera but by none of the control sera. Of the three conserved domains in gp41, two are highly immunodominant. All (100%) HIV-seropositive sera reacted with one of these immunodominant domains in titers (approximately 1:100,000) almost two orders of magnitude higher than any other tested domain. This emphasizes the diagnostic value of the epitopes (ERYLKDQLLGIWGCSGKLIC) previously (see Refs. 11 and 12) identified in this domain. A decrease in average antibody titers is observed in late stages of infection for all the antigens tested, yet distribution of antibody reactivity was independent of stage for only three of the six domains. A significantly higher proportion of reactivity of seropositive sera in early stage (62%) compared with late stage (11%) of infection was found for a domain (NVTENFNMWKN) mapped at the NH2 terminus of gp120; serum antibody reactivity with this domain also correlated with a lack of culturable HIV in blood mononuclear cells.

Amino Acid Sequence↗

Measurement of the false positive rate in a screening program for human immunodeficiency virus infections.

In a program screening civilian applicants for U.S. military service for human immunodeficiency virus (HIV) infection, we studied the frequency of false positive diagnoses retrospectively among applicants seropositive for HIV in a subpopulation with a very low prevalence of infection. That subpopulation was defined as consisting of all applicants tested between October 16, 1985, and June 30, 1987, who were young (17 or 18 years of age) and resided in a rural county in a state with a low incidence of reported acquired immunodeficiency syndrome (n = 135,187). Serum specimens from 15 applicants positive for HIV in this low-prevalence subpopulation were retrieved from a serum bank and retested by two Western blot methods, radioimmunoprecipitation, and an immunoassay constructed from a molecularly cloned and expressed viral envelope polypeptide. Fourteen of the 15 samples were unequivocally positive on all retest assays, and 1 was negative. Thus, the measured rate of false positive diagnoses in this program was 1 in 135,187 persons tested. Factors important in achieving a low false positive rate were redundant, multistep testing algorithm, conservative criteria for interpreting Western blots, the requirement that a second, newly drawn serum specimen be tested for verification before a diagnosis of HIV was considered established, and tight quality control of laboratory testing procedures. We conclude that a screening program for HIV infection in a low-prevalence population can have an acceptably low false positive rate.

Acquired Immunodeficiency Syndrome↗

Type-restricted neutralization of molecular clones of human immunodeficiency virus.

In a study of the immunologic significance of the genetic diversity present within single isolates of human immunodeficiency virus type 1 (HIV-1), the neutralization of viruses derived from molecular clones of the HIV-1 strain HTLV-IIIB by an extensive panel of sera was compared. Sera from HIV-1-infected patients and from goats immunized with polyacrylamide gel-purified HIV-1 envelope glycoprotein (gp120), native gp120, or gp120-derived recombinant peptides, showed marked heterogeneity in neutralizing activity against these closely related viruses. The change of a single amino acid residue in gp120 may account for such "clonal restriction" of neutralizing activity.

Amino Acid Sequence↗

Human immunodeficiency virus infections among civilian applicants for United States military service, October 1985 to March 1986. Demographic factors associated with seropositivity.

During the six months from October 1985 through March 1986, blood samples from 306,061 civilian applicants for military service from the United States were tested for antibody to the human immunodeficiency virus (HIV). Four hundred sixty subjects were positive for the antibody as determined by Western (immune) blot reactivity. The mean prevalence of HIV infection in this population of teenagers and young adults was thus 1.50 per 1000. According to multivariate analysis, the following demographic factors were found to be significant independent predictors of a positive HIV-antibody test: age (adjusted odds ratio = 1.10 per year), black race (adjusted odds ratio = 2.04), male sex (adjusted odds ratio = 1.84), residence in a densely populated county (adjusted odds ratio = 1.05 per 1000 per square mile), and residence in a metropolitan area with a high incidence of the acquired immunodeficiency syndrome (adjusted odds ratio = 1.53). Antibody-positive applicants were identified in 43 of the 50 states. Counties with high prevalence rates for HIV (greater than 5 per 1000) were located in New York State (four counties), New Jersey (three counties), California (two counties), Maryland (two counties), and Texas, Colorado, and Washington, D.C.

Acquired Immunodeficiency Syndrome↗

Chronic vaginal candidiasis in women with human immunodeficiency virus infection.

Twenty-four percent (7/29) of human immunodeficiency virus-infected women seen at Walter Reed Army Medical Center between 1983 and 1986 presented with a history of chronic refractory vaginal candidiasis. In addition to vaginal candidiasis, all patients were found to have oral thrush on physical examination, severe T-helper cell depletion (mean T-helper cell count of 90), and markedly decreased T4/T8 ratios (mean, 0.3); six of seven women were anergic by delayed-type hypersensitivity skin testing. The conditions of six (86%) of these seven women have progressed to acquired immunodeficiency syndrome (WR6 classification). Chronic refractory vaginal candidiasis may be a presenting symptom of human immunodeficiency virus infection. Women with human immunodeficiency virus infection and unexplained oral and vaginal candidiasis are at high risk to develop other opportunistic infections.

Acquired Immunodeficiency Syndrome↗

Oral hairy leukoplakia. A distinctive marker of human T-cell lymphotropic virus type III (HTLV-III) infection.

Oral hairy leukoplakia (HL) is a newly described lesion occurring principally on the lateral borders of the tongue in immunosuppressed homosexual men infected with human T-cell lymphotropic virus type III (HTLV-III). Clinically, HL appears as a slightly raised, poorly demarcated lesion with a corrugated or "hairy" surface. Histologically, the lesion is characterized by keratin projections on the surface (which often resemble hairs), parakeratosis, and acanthosis. In addition, large pale-staining cells with pyknotic nuclei are seen in the upper stratum malpighii, which appear similar to the koilocytes described in uterine condylomata. Candida organisms are frequently observed on the lesion surface. Little, if any, subepithelial inflammation is present. Human papillomavirus and Epstein-Barr virus have been identified in biopsy specimens from lesions of oral HL. The association of this lesion in patients with HTLV-III infection has been established. We saw a patient with HTLV-III infection and HL, in whom the immunochemical and ultrastructural findings revealed the presence of a mixed viral infection. Because oral HL may be of diagnostic value as an early indicator of HTLV-III infection, awareness of its characteristic clinical, histologic, immunochemical, and ultrastructural features is important.

Acquired Immunodeficiency Syndrome↗

Variations in Western blot banding patterns of human T-cell lymphotropic virus type III/lymphadenopathy-associated virus.

Serum samples from 27 patients infected with human T-cell lymphotropic virus type III (14 with acquired immune deficiency syndrome [AIDS] and 13 with AIDS-related complex) were examined for antibodies to viral proteins by the Western blot method and with four different commercial solid-phase enzyme-linked immunosorbent assays (ELISAs). Virus-specific bands on blots at molecular masses of 64, 55, 53, 41, 31, 24, and 17 kilodaltons were observed. Rank correlation matrices were calculated to relate the intensity of viral bands, stage of illness, and ELISA kit optical densities (ODs). Groups of bands tended to covary in intensity: p17, p24, and p55 (gag gene products); p53 and p64 (pol gene products); and p31 (pol/endonuclease gene product) and p41 (env gene product). Blots of sera from AIDS-related complex patients usually showed strong activity against all viral proteins, while those of sera from AIDS patients characteristically showed strong reactivity only at the pol/endonuclease and env bands. For one ELISA kit (Abbott Laboratories, North Chicago, Ill.), ODs correlated well with the env and pol band intensity scores, while ELISA ODs with other kits (from Litton Industries, Sunnyvale, Calif.; Electro-Nucleonics, Inc., Fairfield, N.J.; and E.I. du Pont de Nemours & Co., Inc., Wilmington, Del.) correlated closely with gag band intensity scores. We conclude that human T-cell lymphotropic virus type III Western blot patterns are determined by (i) viral protein processing pathways and (ii) the stage of illness of the patient and may reflect (iii) the ELISA method used for serum screening.

AIDS-Related Complex↗

Lack of attenuation of a candidate dengue 1 vaccine (45AZ5) in human volunteers.

A dengue type 1, candidate live virus vaccine (45AZ5) was prepared by serial virus passage in fetal rhesus lung cells. Infected cells were treated with a mutagen, 5-azacytidine, to increase the likelihood of producing attenuated variants. The vaccine strain was selected by cloning virus that produced only small plaques in vitro and showed reduced replication at high temperatures (temperature sensitivity). Although other candidate live dengue virus vaccines selected for similar growth characteristics have been attenuated for humans, two recipients of the 45AZ5 virus developed unmodified acute dengue fever. Viremia was observed within 24 hr of inoculation and lasted 12 to 19 days. Virus isolates from the blood produced large plaques in cell culture and showed diminished temperature sensitivity. The 45AZ5 virus is unacceptable as a vaccine candidate. This experience points out the uncertain relationship between in vitro viral growth characteristics and virulence factors for humans.

Adult↗