Search PubMed⌕ Search

Biomedical subjects

L Corey

Publications and source records attributed to L Corey.

At least 325 records · Page 18Linked to original sources
PubMed1988

Herpes simplex virus (HSV)-specific proliferative and cytotoxic T-cell responses in humans immunized with an HSV type 2 glycoprotein subunit vaccine.

Studies were undertaken to determine whether immunization of humans with a herpes simplex virus type 2 (HSV-2) glycoprotein-subunit vaccine would result in the priming of both HSV-specific proliferating cells and cytotoxic T cells. Peripheral blood lymphocytes (PBL) from all eight vaccines studied responded by proliferating after stimulation with HSV-2, HSV-1, and glycoprotein gB-1. The PBL of five of these eight vaccines proliferated following stimulation with gD-2, whereas stimulation with gD-1 resulted in relatively low or no proliferative responses. T-cell clones were generated from HSV-2-stimulated PBL of three vaccinees who demonstrated strong proliferative responses to HSV-1 and HSV-2. Of 12 clones studied in lymphoproliferative assays, 9 were found to be cross-reactive for HSV-1 and HSV-2. Of the approximately 90 T-cell clones isolated, 14 demonstrated HSV-specific cytotoxic activity. Radioimmunoprecipitation-polyacrylamide gel electrophoresis analyses confirmed that the vaccinees had antibodies only to HSV glycoproteins, not to proteins which are absent in the subunit vaccine, indicating that these vaccinees had not become infected with HSV. Immunization of humans with an HSV-2 glycoprotein-subunit vaccine thus results in the priming of T cells that proliferate in response to stimulation with HSV and its glycoproteins and T cells that have cytotoxic activity against HSV-infected cells. Such HSV-specific memory T cells were detected as late as 2 years following the last boost with the subunit vaccine.

Cell Line↗
PubMed1988

Survival of antigen-specific antibody following administration of intravenous immunoglobulin in patients with primary immunodeficiency diseases.

To measure the survival of IgG, IgG subclasses and antigen-specific antibody in immune-deficient patients, we infused 4 patients with X-linked agammaglobulinemia (XLA) and 6 patients with common variable immune deficiency (CVID) with modified immunoglobulin at a dose of 400 mg/kg per month until steady state was reached. Following the 8th monthly infusion, serial samples were obtained and analyzed for serum concentration of IgG, IgG subclasses and for specific antibody activities against a battery of antigens. Half-lives for IgG and IgG subclasses were between 30 and 40 days except for IgG3 which appeared to consist of two populations of molecules, one showing a rapid decay, the other disappearing at a rate suggesting a half life of 22-24 days. Antigen-specific antibodies, including antibodies to HBsAg, cytomegalovirus, pneumococcal polysaccharides and streptococcal group A carbohydrate were similar to that for total IgG. These studies demonstrate that protective antibody titers to infective agents can be maintained for several weeks following high-dose intravenous immunoglobulin infusion.

Adolescent↗
PubMed1987

Effects on infants of a first episode of genital herpes during pregnancy.

Although genital herpes simplex virus (HSV) infections occurring during pregnancy are known to be associated with neonatal and maternal complications, their frequency and contributing risk factors are not well understood. We prospectively followed 29 patients who acquired genital herpes during pregnancy, to evaluate the perinatal effects of the infection. The patients were classified on the basis of clinical or serologic criteria. Fifteen patients had a primary first episode of genital HSV Type 2 (HSV-2), and 14 had a nonprimary first episode. Although no patient had disseminated disease, 6 of the 15 with primary genital herpes but none of 14 with nonprimary first-episode infection had infants with serious perinatal morbidity (P less than 0.01). Four of the five infants whose mothers acquired primary HSV-2 in the third trimester had perinatal morbidity such as prematurity, intrauterine growth retardation, and neonatal infection with HSV-2. Perinatal complications occurred in one of five infants whose mothers acquired primary HSV-2 during the first trimester, as well as in one of five infants whose mothers had primary HSV-2 during the second trimester. Asymptomatic cervical shedding of HSV-2 was detected at 10.6 percent of weekly visits made after a primary first episode, as compared with 0.5 percent of visits after a nonprimary first episode (P less than 0.01). We conclude that infants born to women who acquire primary genital herpes during pregnancy are at high risk of exposure to HSV, either during premature labor at the time of the primary episode or subsequently because of asymptomatic cervical shedding of the virus. The 40 percent incidence of serious perinatal morbidity in such women suggests that studies of preventive measures such as the use of antiviral chemotherapy are warranted.

Cervix Uteri↗
PubMed1987

Sexual practices, sexually transmitted diseases, and the incidence of anal cancer.

To elucidate the risk factors for anal cancer, we interviewed and obtained blood specimens from 148 persons with anal cancer and from 166 controls with colon cancer in whom these diseases were diagnosed during 1978-1985. We found that in men, a history of receptive anal intercourse (related to homosexual behavior) was strongly associated with the occurrence of anal cancer (relative risk, 33.1; 95 percent confidence interval, 4.0 to 272.1). Anal intercourse was only weakly associated with the risk of anal cancer in women (relative risk, 1.8; 95 percent confidence interval, 0.7 to 4.2). Among the subjects with squamous-cell anal cancer, 47.1 percent of homosexual men, 28.6 percent of heterosexual men, and 28.3 percent of women gave a history of genital warts, as compared with only 1 to 2 percent of controls and no patients with transitional-cell anal cancer. In patients without a history of warts, anal cancer was associated with a history of gonorrhea in heterosexual men (relative risk, 17.2; 95 percent confidence interval, 2.0 to 149.4) and with seropositivity for herpes simplex type 2 (relative risk, 4.1; 95 percent confidence interval, 1.9 to 8.8) and Chlamydia trachomatis (relative risk, 2.3; 95 percent confidence interval, 1.1 to 4.8) in women. Current cigarette smoking was a substantial risk factor in both women (relative risk, 7.7; 95 percent confidence interval, 3.5 to 17.2) and men (relative risk, 9.4; 95 percent confidence interval, 2.3 to 38.5). We conclude that homosexual behavior in men is a risk factor for anal cancer, and that squamous-cell anal cancer is also associated with a history of genital warts, an association suggesting that papillomavirus infection is a cause of anal cancer. Certain other genital infections and cigarette smoking are also associated with anal cancer.

Anus Neoplasms↗
PubMed1987

Recurrences after oral and genital herpes simplex virus infection. Influence of site of infection and viral type.

We prospectively followed 39 adults with concurrent primary herpes simplex virus (HSV) infection (12 with HSV type 1 and 27 with HSV type 2) of the oropharynx and genitalia, caused by the same virus in each person, to evaluate the influence of viral type (HSV-1 vs. HSV-2) and site of infection (oropharyngeal vs. genital) on the frequency of recurrence. The subsequent recurrence patterns of HSV infection differed markedly according to viral type and anatomical site. Oral-labial recurrences developed in 5 of 12 patients with HSV-1 and 1 of 27 patients with HSV-2 (P less than 0.001). Conversely, genital recurrences developed in 24 of 27 patients with HSV-2 and 3 of 12 patients with HSV-1 (P less than 0.01). The mean rate of subsequent genital recurrences (due to HSV-1 and HSV-2) was 0.23 per month, whereas the mean rate of oral-labial recurrences was only 0.04 per month (P less than 0.001). The mean monthly frequencies of recurrence were, in order, genital HSV-2 infections, 0.33 per month; oral-labial HSV-1 infections, 0.12 per month; genital HSV-1 infections, 0.020 per month; and oral HSV-2 infections, 0.001 per month (P less than 0.01 for each comparison). We conclude that the likelihood of reactivation of HSV infection differs between HSV-1 and HSV-2 infections and between the sacral and trigeminal anatomical sites. The sixfold more frequent clinical recurrence rate of genital HSV infections as compared with oral-labial HSV infections may account for the relatively rapid increase in the prevalence of clinically recognized genital herpes in recent years.

Adult↗
PubMed1987

Cytomegalovirus infection in homosexual men. Relationship to sexual practices, antibody to human immunodeficiency virus, and cell-mediated immunity.

To investigate the relationships among cytomegalovirus infection, sexual behavior, human immunodeficiency virus (HIV) seropositivity, and indexes of cellular immunity, 180 homosexual men and 26 heterosexual men were studied. Among the homosexual men, cytomegalovirus seropositivity was associated with increased T8 lymphocyte counts (p less than 0.001) and reduced T4/T8 ratios (p = 0.006); these results were independent of HIV infection. Cytomegalovirus seropositivity was also associated with increasing age, numbers of sexual partners, and the practice of anal-receptive intercourse. At the first visit, cytomegalovirus was isolated from none of 13 cytomegalovirus-seropositive heterosexual subjects, compared with 62 (36 percent) of 171 seropositive homosexual men (p less than 0.005). Viral isolation was most common from semen. Among 32 cytomegalovirus-seropositive homosexual subjects from whom culture specimens were obtained more than four times over 10 to 30 months, 72 percent of the specimens were culture-positive. The mean duration of cytomegalovirus excretion in semen was 22 months, and in urine, the duration was nine months. Cytomegalovirus excretion was associated with younger age and reduced lymphocyte proliferation in response to cytomegalovirus, but not with antibody to HIV. Cytomegalovirus infection is sexually transmitted among homosexual men, perhaps by rectal intercourse, and is associated with alterations in T lymphocyte subsets. Most seropositive homosexual men excrete cytomegalovirus intermittently, primarily in the semen.

Adult↗
PubMed1987

Acyclovir prophylaxis for herpes simplex virus infection.

ACV is an effective agent for the treatment and prophylaxis of HSV infections in both IC and immunologically normal individuals. The drug is well tolerated in both populations and is not significantly associated with clinical or laboratory toxicities. Because of the great potential benefit and low risk, organ transplant recipients and patients with hematologic malignancies undergoing induction chemotherapy should be screened routinely for HSV antibodies; seropositive individuals should receive prophylactic ACV during the period of most profound immunosuppression. Immunologically normal individuals with frequently recurring genital HSV or serious complications associated with outbreaks are candidates for long-term suppression with ACV.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Diagnosis of herpes simplex virus by direct immunofluorescence and viral isolation from samples of external genital lesions in a high-prevalence population.

One hundred thirty specimens from 108 consecutive patients with a history of recurrent genital ulcerations were used in a study comparing herpes simplex virus (HSV) isolation with a direct fluorescent-antibody (DFA) technique using mouse monoclonal antibodies. HSV was isolated from 70% of vesicular lesions, 67% of pustular lesions, 32% of ulcerative lesions, and 17% of crusted lesions, whereas the DFA technique detected HSV antigen in 87, 67, 30, and 10% of lesions in similar stages, respectively. When both methods were used, HSV was identified in 97, 79, 45, and 17% of vesicles, pustules, ulcers, and crusted lesions, respectively. The overall sensitivity and specificity of the DFA technique in comparison with virus isolation (VI) were 74 and 85%, respectively. Of the 17 patients from whom DFA-positive, VI-negative samples were obtained, HSV was subsequently isolated from a genital lesion in 14, suggesting that they were not DFA false-positives. Similarly, of the 46 patients whose initial lesion samples were DFA and VI negative, 37 (80%) had HSV identified from subsequent genital lesions during follow-up. Thus, a single sample for VI or DFA testing from a recurrent genital lesion had a sensitivity of only 53 and 51%, respectively. Combining the DFA technique and VI increased the sensitivity of laboratory diagnosis of a single recurrent episode of genital HSV; however, repetitive laboratory testing was often required to confirm the diagnosis of recurrent genital HSV infection.

Antibodies, Monoclonal↗
PubMed1987

Detection of asymptomatic herpes simplex virus infections after vaccination.

Twenty-two volunteers seronegative for antibodies to herpes simplex virus (HSV) were enrolled in a trial to determine tolerance and immunogenicity of an HSV-2 glycoprotein subunit vaccine. Vaccine was administered at days 0, 28, and 140, and sera were obtained on days 0, 7, 14, 21, 28, 35, 49, 56, 140, 147, and 365 for determination of HSV neutralizing antibody activity and antibody-dependent cell cytotoxicity (ADCC). Sera were also tested by immunoprecipitation of radiolabeled HSV-2-infected cell proteins and polyacrylamide gel electrophoresis to identify the viral proteins which elicited antibody responses in vaccine recipients. After vaccination two male volunteers presented with atypical first-episode genital herpes: patient 1 with a culture-negative genital lesion at day 53 and patient 3 with urethritis at day 68. Seroconversion to wild-type viral proteins not present in the vaccine was detectable by radioimmunoprecipitation-polyacrylamide gel electrophoresis within 10 days in both patients. Two additional volunteers, one a sex contact of patient 1, seroconverted asymptomatically to nonvaccine proteins during the trial. All four vaccine breakthrough patients were indistinguishable from the other volunteers in the time required to develop neutralizing and ADCC antibodies, in the titer of these antibodies, and the time to seroconversion to gB and gD vaccine proteins. However, only one of the four breakthrough patients had antibodies to g80 (a complex of gC-2 and gE) after vaccination as compared with 15 of the other 18 volunteers (P = 0.05). Neither neutralizing antibody nor ADCC titers consistently identified acquisition of wild-type viral infection; therefore, protein-specific serologies were required to detect wild-type antibodies in these four patients. These data underscore the importance of using serologic assays which will distinguish naturally acquired infection from the immune response to vaccination.

Adult↗
PubMed1987

Treatment of herpes simplex virus infections.

Herpes simplex virus infections cause considerable morbidity in immunocompromised and immunocompetent individuals. The development of immunomodulatory agents and nucleoside analog drugs has been responsible for important advances in the treatment of HSV infections. Acyclovir, an acyclic guanosine derivative, has played a major role in the treatment and suppression of HSV episodes in immunocompromised and immunocompetent patients.

Acyclovir↗
PubMed1987

Genital human papillomavirus infections.

In summary, the development of new techniques to identify HPV DNA in genital secretions and tissue, the recognition of subclinical HPV infection, and the remarkable association between HPV and genital neoplasia have markedly increased the concern of both patients and physicians about genital wart virus infections. The prevalence of this viral STD appears to be increasing and the clinical spectrum of disease appears to be expanding. New methods to diagnose genital HPV infection and techniques to treat these infections more effectively are under development. It is hoped that these techniques will provide the tools to understand and more effectively control this important infection.

Condylomata Acuminata↗
PubMed1986

IgG subclass of anti-HSV antibodies following neonatal HSV infections.

Ten survivors of neonatal HSV encephalitis had IgG1 and IgG3 antibodies to HSV 6 or more months after their infection. Six had IgG4 antibodies but only one had IgG2 antibodies. Titers of anti-HSV antibodies were similar following neonatal and later HSV infections. Antibody deficiency is thus not part of the selective deficiency of HSV-specific immunity following neonatal infection.

Adult↗
PubMed1986

Etiology of cervical inflammation.

We studied the relationships of selected microbial, clinical, demographic, and behavioral variables to mucopurulent cervicitis in two clinical settings, a sexually transmitted disease clinic and a student health clinic. From each clinic, we studied a group of women referred for suspected mucopurulent cervicitis and a representative sample of other women attending the clinic. After the women were stratified by patient group and summary odds ratios for all groups were obtained, mucopurulent cervicitis was most strongly associated with the isolation of Chlamydia trachomatis; other variables associated with mucopurulent cervicitis included the isolation of Ureaplasma urealyticum, Gardnerella vaginalis, and Trichomonas vaginalis, the presence of serum antibody to C. trachomatis, the clinical diagnosis of bacterial vaginosis, and oral contraceptive use (positive associations) or isolation of yeast (negative association). After adjustment for cervical culture results for C. trachomatis, mucopurulent cervicitis was positively associated with oral contraceptive use (p = 0.02) and isolation of U. urealyticum (p = 0.02) and negatively associated with isolation of yeast (p = 0.03). Among women with a positive cervical culture for C. trachomatis, isolation of U. urealyticum was significantly associated with mucopurulent cervicitis, while among the subgroup of women with a negative cervical culture for C. trachomatis and positive serum antibody to C. trachomatis, oral contraceptive use was strongly associated with mucopurulent cervicitis. These results confirm that in both clinical settings C. trachomatis is the major cause of mucopurulent cervicitis. The roles of U. urealyticum, T. vaginalis, G. vaginalis, bacterial vaginosis, and oral contraceptive use in the etiology of mucopurulent cervicitis deserve further study.

Adult↗