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Biomedical subjects

R Ashley

Publications and source records attributed to R Ashley.

At least 73 records · Page 4Linked to original sources
PubMed1991

Clinical and serologic features of herpes simplex virus infection in patients with AIDS.

We studied the natural history of herpes simplex virus (HSV) infection and its association with specific serum antibody in a sample of 68 HIV-infected patients with a first episode of Pneumocystis carinii pneumonia at San Francisco General Hospital in 1986. Seroprevalence was 66 and 77% for HSV-1 and HSV-2 antibody, respectively, by immunoblot assay. Twenty-seven patients had 45 HSV outbreaks diagnosed during 739 patient-months of follow-up. Median frequency of recurrence resulting in a medical visit was once every 6.5 months, and median duration of treated outbreak was 10 days. Fourteen of 48 evaluable patients seropositive for HSV-2 had no outbreak of HSV during a median follow-up of 7.5 months. Our data suggests that neither frequency nor severity of HSV were substantially increased in this group of patients, despite severe immunosuppression caused by HIV. However, validation of these results by a prospective study is required.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Chronic fatigue. A prospective clinical and virologic study.

To evaluate the clinical and virologic course of patients with chronic fatigue who had elevated Epstein-Barr virus (EBV) titers, we prospectively followed up 26 patients with serial cultures for EBV in blood and saliva and serial EBV serologic and clinical and psychiatric evaluations, and we compared these results with those for healthy controls. The frequency of isolating EBV in blood or demonstrating EBV infection by in situ hybridization in blood lymphocytes or in saliva was similar in patients and controls. The prevalence and titers of antibody to human herpesvirus type 6 were also similar in the two populations. Patients with chronic fatigue did demonstrate higher in vitro natural killer activity and lower in vitro interleukin 2 production than controls, and patients had a high frequency of DSM-III depressive illness. Over 50% of patients with chronic fatigue improved over the course of follow-up. Improvement was not associated with any discernible change in titers of EBV proteins. No evidence of ongoing EBV infection with either transforming or nontransforming strains was demonstrated in this population of patients with chronic fatigue. Clinically, most patients gradually improve over time.

Adult↗
PubMed1990

Double-blind, placebo-controlled trial of a herpes simplex virus type 2 glycoprotein vaccine in persons at high risk for genital herpes infection.

To determine the efficacy of a herpes simplex virus type 2 (HSV-2) glycoprotein subunit vaccine, vaccine (50 micrograms) or placebo was administered intramuscularly at weeks 0, 4, and 22 to 161 persons who lacked HSV-2 antibodies and were sex partners of persons with recurrent genital herpes. The annual rate of acquisition of HSV infection was similar among vaccine and placebo recipients (10.7% and 8%, respectively) but was higher in initially seronegative subjects (15.5%) than in those with HSV-1 at entry (5.9%). Eleven (79%) of the 14 HSV infections acquired during follow-up were symptomatic. Vaccination elicited ELISA antibody titers to glycoproteins gD2 and gB2 that were only 10% and 5%, respectively, of titers found in persons with recurrent genital HSV-2 infection. This vaccine failed to provide protection from acquisition of genital HSV infection. The lack of efficacy appears to be related, in part, to the poor immunogenicity of the vaccine.

Adult↗
PubMed1990

Serotypes and electropherotypes of human rotavirus in the USA: 1987-1989.

The epidemiology of rotavirus gastroenteritis was investigated for two consecutive seasons (1987-1988 and 1988-1989) in seven locales in the continental USA. The 281 representative fecal samples obtained from children with diarrhea were electropherotyped and serotyped by an enzyme immunoassay with serotype-specific monoclonal antibodies and a new amplification typing technique (polymerase chain reaction typing). Serotype 1 was predominant in both years, particularly in the North and East; serotype 3 was second in frequency and found most often in the South; serotype 2 was detected only occasionally; serotypes 4, 8, and 9 were never found. Rotavirus strains were grouped into five major electropherotypes, each corresponded to a single serotype, and the relative migration of the gene segments 7-9 could be used to distinguish serotype 1 from serotype 3. The amplification typing technique proved to be of great value in typing the 17% of rotavirus-positive specimens untypable by the serologic technique.

Antibodies, Monoclonal↗
PubMed1989

Development of clinically recognizable genital lesions among women previously identified as having "asymptomatic" herpes simplex virus type 2 infection.

STUDY OBJECTIVE: To determine if patients initially identified by history, clinical examination, and serologic status as having asymptomatic herpes simplex virus type 2 infection report clinically recognizable genital lesions after having a detailed instructional session on the clinical signs and symptoms of genital herpes. DESIGN: Prospective follow-up of two groups of women. SETTING: Outpatient clinic of an urban city-county hospital. PATIENTS: Two populations of women were recruited. One group was referred because they had documented asymptomatic genital herpes or were suspected of asymptomatically transmitting genital herpes to a sex partner. The other group was recruited from the hospital's general gynecologic clinic and consisted of women with herpes simplex virus type 2 antibodies who denied a history of genital herpes. INTERVENTION: Patients had a one-on-one interview describing the clinical symptoms of genital herpes. MEASUREMENTS AND MAIN RESULTS: Twelve of nineteen women with herpes simplex virus type 2 antibodies who had documented asymptomatic genital herpes or were suspected of asymptomatically transmitting infection to a sex partner, and 18 of 43 women with herpes simplex virus type 2 antibodies who were recruited from the gynecologic clinic developed clinically recognizable genital lesions during a 5-month follow-up. Symptomatic genital herpes was the most frequent gynecologic complaint identified during follow-up. CONCLUSIONS: Approximately 50% of women with herpes simplex virus type 2 antibodies who do not initially report a history of genital lesions do indeed have clinically symptomatic genital herpes. These women can be accurately counseled and taught to distinguish genital herpes from other genitourinary infections. Identification of symptomatic recurrences and counseling to avoid sexual activity during these episodes may help reduce transmission of genital herpes.

Adolescent↗
PubMed1989

Comparison of monoclonal antibodies for rapid detection of cytomegalovirus in spin-amplified plate cultures.

Cytomegalovirus (CMV) was detected in 56 of 275 specimens (20%); 50 of 56 (89%) were detected by conventional culture, and 37 (66%) were detected by rapid assay at 72 h with a commercial monoclonal antibody and a pooled monoclonal antibody. Although the two antibodies were equally sensitive at 72 h, the pooled antibody gave a brighter, more easily detected signal. Other viruses were isolated from 9 specimens (3.3%) by conventional culture. Use of rapid assays alone fails to detect slow-growing CMV and non-CMV viral pathogens.

Antibodies, Monoclonal↗
PubMed1988

Differential effect of systemic acyclovir treatment of genital HSV-2 infections on antibody responses to individual HSV-2 proteins.

Western blot and reflectance densitometry were used to evaluate the antibody response from patients treated with systemic acyclovir during their primary episodes of genital HSV-2 infection. Of 39 patients studied, 10 received oral acyclovir, 10 received intravenous acyclovir, and 19 received placebo. Total antibody levels as well as levels of antibodies to individual HSV-2 proteins (gB, gG, gC/gE, VP16, gD, and p45) were determined in convalescent phase sera. The median number of HSV-2 proteins recognized and the total amount of HSV-2 antibody were significantly lower in acyclovir than placebo treated patients (P less than or equal to 0.01). Levels of antibodies to individual proteins were also lower in sera from acyclovir versus placebo treated patients: gB (P = 0.013), gC/gE (P = 0.017), VP16 (P = 0.001), gD (P = 0.009), and p45 (P = 0.015). Antibody response to gG-92 and to a newly described gG species, gG-70, was not significantly different among treatment groups. A low number of proteins recognized by convalescent serum antibodies were associated with a higher number of lesions at first recurrence (P = 0.02) and with a longer duration of the first recurrent episode (P = 0.02). Low levels of total antibody were associated with shorter times to first recurrence (P = 0.05). Low levels of antibody to VP16 (P = 0.05) and gD (P = 0.01) were associated with longer duration of the first recurrence.

Acyclovir↗
PubMed1988

Analysis of a major target of the human immune response to cytomegalovirus using monoclonal antibodies.

Two murine monoclonal antibodies (C6D1 and D2B1) were found to react with a set of cytomegalovirus (CMV)-infected cell polypeptides, which comprise a major target of the human immune response to CMV. C6D1 reacted with proteins of 50 kilodaltons (KD) and 40KD molecular weight; D2B1 reacted with these two proteins plus a third of 35KD. Western blot analysis demonstrated that these protein targets also react with serum antibody from patients with acute or latent CMV infection. Immunofluorescence staining of CMV-infected diploid fibroblast cells by C6D1 and D2B1 showed that the protein targets are found in the nucleus throughout the course of viral infection. The proteins were shown to be late proteins dependent on viral DNA synthesis for their expression. Not all wild-type CMV strains tested expressed proteins that react with C6D1 and D2B1. Using an immunofluorescence stain of diploid fibroblasts infected with CMV strains from infected patients, we found that 70 of 76 (92%) wild-type strains reacted with C6D1 and 23 of 24 (96%) with D2B1. One strain was not reactive with either C6D1 or D2B1. Western blot analysis of 11 wild-type strains revealed that two isolates either lack the C6D1 and D2B1 protein targets or have forms of these proteins that migrate at different molecular weights.

Animals↗
PubMed1988

Immunoblot analysis of the humoral immune response in primary cytomegalovirus infection.

Cytomegalovirus is a common infection in immunologically normal adults. It may cause an asymptomatic infection or may manifest symptomatically as heterophilic-negative mononucleosis. Studies of CMV infection in immunocompromised patients indicate that humoral immune response plays a role in modulating disease severity; however, the effect of antibodies to CMV in modifying disease expression and transmission in immunologically normal individuals has not been well characterized. Using immunoblot technology, we have demonstrated that immune serum from normal adults contains antibodies to at least 15 CMV-associated proteins and that there is strain-to-strain variation in the expression of these immunogens. The kinetics of the immune response were evaluated by using serial sera collected from normal adults after primary CMV infection; analysis of immunoblots of these sera identified one group of antibodies to CMV proteins that arise early and are stable over time, a second group that appear late after infection, and a third group that are variable among patients and over time.

Adult↗
PubMed1988

Transmission of genital herpes in couples with one symptomatic and one asymptomatic partner: a prospective study.

To determine the risk of transmission of genital herpes simplex virus (HSV) infection, we prospectively studied, for a median of six months, 38 couples who had been together for a median of 10 mo. In each couple, one partner had a history of symptomatic genital herpes and one did not. At entry, of the 38 asymptomatic, exposed partners, 21 were seronegative, and results of western blot analysis showed that seven had antibody to HSV type 1 (HSV-1), four to HSV type 2 (HSV-2), and six to both HSV-1 and HSV-2. One of the 28 exposed partners without antibody to HSV-2 at enrollment asymptomatically acquired HSV-2 infection, but four of 10 with antibody to HSV-2 at enrollment developed culture-proven HSV-2 infection during follow-up. Restriction endonuclease analysis of DNA from paired isolates revealed identical strains in three couples and different strains in one. In this group of asymptomatic sex partners of persons with genital herpes, asymptomatic and unrecognized acquisition of HSV-2 infection was common, but more than half of the exposed partners remained free of HSV-2 infection after a median of 16 mo of sexual contact.

Adult↗
PubMed1988

Chronic-dose acyclovir to suppress frequently recurring genital herpes simplex virus infection: effect on antibody response to herpes simplex virus type 2 proteins.

To determine the effect of prolonged suppressive acyclovir therapy on the antibody response to herpes simplex virus type 2 (HSV-2) proteins, we studied sequential sera from 33 patients with frequently recurring (six or more recurrences per year) genital herpes. Twenty-two patients received 400 mg of oral acyclovir and 11 received placebo, twice daily for one year. Sera collected at enrollment, after six months and 12 months of therapy, and during the first recurrence after cessation of therapy were evaluated by western blot for levels of antibodies to HSV-2, gB, gG, gC/gE, VP16, and gD. Mean levels declined by 27%-39% after one year of acyclovir. The magnitude of the decrease in antibody levels was not correlated with disease severity either during or after therapy. Patients with high relative antibody levels to gB after therapy had more-severe first recurrences after therapy than did patients with antibody levels to gB less than or equal to the median. Antibody levels were not restored after the first untreated recurrence.

Acyclovir↗
PubMed1988

Comparison of diploid fibroblast and rabbit kidney tissue cultures and a diploid fibroblast microtiter plate system for the isolation of herpes simplex virus.

We evaluated the relative sensitivities of two cell systems (rabbit kidney [RK] and human diploid fibroblast [DF; human embryonic tonsil]) in standard tube cultures versus DF cells in a 48-well microtiter plate system for the detection of both symptomatic and asymptomatic herpes simplex virus (HSV) infection. At least one system isolated HSV in 111 of 809 specimens (13.7%). HSV was isolated in RK tube cultures from 110 specimens (99%), in DF tube cultures from 91 specimens (82%), and in DF microtiter plates from 95 specimens (86%). The frequency of HSV isolation varied with the anatomic site and the presence or absence of a herpetic lesion. The sensitivities of the three culture systems remained similar whether the specimens were obtained from lesions or whether the specimens were taken to determine if asymptomatic excretion of HSV was present. While RK tube cultures were more sensitive than DF tube cultures, the DF microtiter plate system was as sensitive as DF tube cultures and its use is supported as a cheaper and less labor-intensive method for the detection of HSV.

Animals↗
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↗
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↗