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Biomedical subjects

R J Whitley

Publications and source records attributed to R J Whitley.

At least 163 records · Page 9Linked to original sources
PubMed1988

Neonatal herpes simplex virus infections.

The natural are history and pathogenesis of neonatal HSV infections are discussed. Reference to maternal risk factors is developed. Status of therapy is defined.

Antiviral Agents↗
PubMed1987

Analysis of immune function in herpes zoster patients: demonstration and characterization of suppressor cells.

We sought to identify imbalances of immune regulatory cells that might contribute to the depression of cell-mediated immunity that occurs during an episode of herpes zoster. Peripheral blood mononuclear cells (PBMC) were obtained from patients with herpes zoster during the acute (less than 7 days after disease onset) and convalescent (more than 10 days after disease onset) phases of illness and from healthy seropositive donors. The PBMC were analyzed for: lymphoproliferative responses to varicella-zoster virus (VZV) antigens, Leu-3 (helper/inducer):Leu-2 (cytotoxic/suppressor) ratios, and percentages of suppressor cells as defined by coexpression of the Leu-2 and OKM1 antigens. Significantly depressed proliferative responses of VZV antigens and Leu-3:Leu-2 ratios, and increased percentages of Leu-2+ OKM1+ suppressor cells were observed in PBMC of acute phase herpes zoster patients as compared with the PBMC of convalescent patients or healthy donors. These differences were also observed in individual patients sequentially studied during both phases of disease. Cryopreserved acute phase PBMC suppressed the proliferative response of autologous convalescent phase PBMC to VZV antigens, but not to herpes simplex virus (HSV) antigens. The acute phase PBMC suppressor cell was radiation sensitive and was identified as a Leu-2+ cell by fluorescence-activated cell sorting. Thus, depression of cell-mediated immunity during the acute phase of herpes zoster was associated with a relative increase of lymphocytes expressing a suppressor cell phenotype and the activation of a radiosensitive Leu-2+ suppressor cell with some degree of antigen specificity.

Acute Disease↗
PubMed1987

Congenital cytomegalovirus: immunological alterations.

Immunological studies on 29 children with congenital cytomegalovirus (CMV) infection were performed. Two groups of patients were considered according to the presence or absence of clinical symptoms. Asymptomatic patients had increased numbers of natural killer (NK) cells (CD 16+), activated NK cells (CD16+/HLA-DR+), and activated suppressor/cytotoxic cells (CD8+/HLA-DR+/TAC+). In addition, cells from this group of patients showed increased NK activity against fibroblasts infected with CMV and a significant proliferative response to CMV antigens. In contrast, cells from symptomatic patients had reduced NK activity against fibroblasts infected with CMV and a defective proliferative response to CMV antigens. In both groups, the number of total T, T-helper, and T-suppressor/cytotoxic cells was normal, as was the ratio of helper/suppressor. The reported differences in the immunological parameters between the asymptomatic and symptomatic patients suggest that cell-mediated immunity may play an important role in determining the outcome of the infection.

Adolescent↗
PubMed1987

Condyloma acuminatum: epidemiological, clinical and therapeutic aspects.

Condyloma acuminatum, CA or genital warts, are benign fibro-epithelial tumors with a predilection for moist environments, especially mucosal surfaces. This sexually transmitted disease (STD) is increasing rapidly in incidence. The lesions are associated with a number of human papillomavirus (HPV) types. Some HPV types are closely linked with genital (especially cervical) dysplasia and neoplasia. Treatment consists of such traditional modalities as podophyllin, cryotherapy or surgical excision and, more recently, administration of interferon (IFN).

Condylomata Acuminata↗
PubMed1987

Patients with condyloma acuminatum exhibit decreased interleukin-2 and interferon gamma production and depressed natural killer activity.

Peripheral blood mononuclear cells were obtained from 20 untreated condyloma acuminatum patients and from an equal number of sex- and age-matched controls and assayed for cell surface antigen expression, natural killer activity, and lymphokine production. Patient peripheral blood mononuclear cells had significantly lower helper-to-suppressor T-cell ratios (Leu3/Leu2) (P less than 0.05) and significantly higher percentages of Leu 2+ Tac+ cells (activated suppressor/cytotoxic cells) (P less than 0.05) and Leu 2+ OKM1+ cells (suppressor cells) (P less than 0.01). Natural killer activity of condyloma acuminatum patients was significantly lower (P less than 0.05) than that of controls. Production of interleukin-2 and interferon gamma, but not interferon alpha, was significantly (P less than 0.01) decreased in condyloma acuminatum patients. There was an inverse correlation between the in vitro production of interleukin-2 and interferon gamma and the percentage of Leu 2+ OKM1+ cells (suppressor) (P less than 0.01). Thus, patients with condyloma acuminatum differ from controls by demonstrating decreased natural killer-cell activity, decreased production of lymphokines which enhance natural killer-cell activity (i.e., interferon gamma and interleukin-2), and an increased proportion of T cells with a suppressor phenotype.

Adult↗
PubMed1987

Factors indicative of outcome in a comparative trial of acyclovir and vidarabine for biopsy-proven herpes simplex encephalitis.

A total of 208 patients underwent brain biopsy for presumptive herpes simplex encephalitis and were randomized to receive either vidarabine, vira-A, at 15 mg/kg/day, or acyclovir, at 30 mg/kg/day for ten days. 69 patients (33%) had biopsy-proven disease; 37 received vira-A and 32 acyclovir. With the exception of age, patient populations were balanced for demographic characteristics. Overall survival for acyclovir recipients was 72% compared with 46% for vira-A-treated patients 18 months after therapy (p = 0.008). After adjustment for differences of age between treatment populations by multivariant regression analyses, acyclovir treatment remained superior to vidarabine therapy (p = 0.041). Mortality varied according to the level of consciousness at the onset of therapy. For lethargic, semicomatose and comatose patients, mortality was 42%, 46%, and 67%, respectively, for the vira-A-treated patients and 0%, 25% and 25%, respectively, for acyclovir-treated patients. Six months post-therapy morbidity assessments revealed five (14%) vira-A versus 12 (38%) acyclovir recipients who had returned to normal function, while eight (22%) and three (9%), respectively, had moderate debility. Outcome differences were significant (p = 0.02; Wilcoxon, 2-sample test) using an adapted scoring system. Age and Glasgow coma scale greater than 10 predicted the best outcome following acyclovir treatment. Disoriented patients who flex and respond by eye to pain had no mortality and 50% returned to normal. These data indicate that acyclovir is the treatment of choice for biopsy-proven herpes simplex encephalitis.

Acyclovir↗
PubMed1987

Identification of a herpes simplex virus 1 glycoprotein gene within a gene cluster dispensable for growth in cell culture.

The genome of herpes simplex virus 1 consists of two components, L and S, each containing unique sequences flanked by inverted repeats. Current and earlier studies have shown that 11 of the 12 open reading frames contained in the unique sequences of the S component can be deleted and are dispensable for growth in cell culture. Analyses of one recombinant virus containing a deletion in the open reading frame US7 permitted the identification of a monoclonal antibody specific for the product of this gene. The protein encoded by this gene has a predicted translated molecular weight of 41,366 and an apparent molecular weight of approximately 65,000 in denaturing polyacrylamide gels. The electrophoretic mobility of the protein synthesized by cells in the presence of inhibitory concentrations of tunicamycin is faster than that of the protein accumulating in lysates of untreated infected cells. We conclude that the product of US7 is glycoprotein subject to N-linked glycosylation, and we have designated it glycoprotein I. These studies indicate that the unique sequences of the S component encode four glycoproteins (G, D, I, and E) of which at least three (G, I, and E) are dispensable for growth in continuous lines of primate cells.

Animals↗
PubMed1987

T-cell imbalances and NK activity in varicella-zoster virus infections.

Samples of peripheral blood lymphocytes (PBMC) were serially obtained from 30 patients with herpes zoster (HZ) and 10 patients with chickenpox (CP). Cells were assayed for NK-cell function and for the expression of surface membrane antigens which identify T-cell and NK-cell subsets. During the acute phase of disease (less than 7 days from onset), PBMC from patients with HZ had low proportions of T-helper (CD 4+) cells and a large number of T-suppressor (CD 8+) cells, resulting in a low T-helper/T-suppressor ratio. There was an increased percentage of nonspecific suppressor cells (GD 8+-CD 11+ cells) and increased expression of HLA-DR determinants on both CD 8+ and CD 4+ cells. The NK activity was depressed with no concomitant decrease in NK cells (CD 16+ or Leu 7+ cells). In the early convalescing phase of disease (8-14 days), there was a significant increase in CD 16+ cells and increased expression of HLA-DR on these cells, correlating with increased NK activity. In the late recovery phase (greater than 14 days), NK activity and levels of T-cell subpopulations were normal with the exception of increased CD 4+ cells and, consequently, of the helper/suppressor ratios. In the acute phase of CP (less than 7 days), the T-cell imbalances were similar to those encountered with HZ patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Detection of antibodies to herpes simplex virus in the cerebrospinal fluid of patients with herpes simplex encephalitis.

Cerebrospinal fluid (CSF) and serum specimens from patients with presumed herpes simplex encephalitis (HSE) were characterized for antibodies to herpes simplex virus (HSV) by immunoblot and other immunoassays. Specimens from patients proven to have HSE (biopsy-proven) were compared with those from patients with other diseases diagnosed by brain biopsy (biopsy-negative for HSV). Immunoblot of CSF demonstrated that antibodies to HSV-specific polypeptides, particularly to glycoprotein B, were present in a matched serum specimen. When purified glycoprotein B was used to detect CSF antibodies, 34 of 35 specimens from biopsy-proven patients were reactive (97% sensitivity) compared with only six of 22 specimens obtained from biopsy-negative patients (73% specificity). If leakage of antibodies to a marker virus (adenovirus) was determined and controlled, the specificity increased to 100%. These diagnostic assays provide useful tools for the retrospective assessment of CSF specimens obtained from patients with presumed HSE.

Adolescent↗
PubMed1987

Detection of antigen to herpes simplex virus in cerebrospinal fluid from patients with herpes simplex encephalitis.

Cerebrospinal fluid (CSF) specimens were obtained from patients with presumed herpes simplex encephalitis who underwent brain biopsy for diagnostic confirmation. Coded CSF specimens were fixed on nitrocellulose filter paper and probed with a pool of monoclonal antibodies directed against four herpes simplex virus glycoproteins (gB, gC, gD, and gE). Herpes simplex virus antigen was detected in 35 of 40 specimens obtained from 26 biopsy-positive patients. In contrast, only three of 25 specimens from 17 biopsy-negative patients gave positive results by this assay. An additional 30 CSF specimens from patients with proven bacterial and fungal infections were all negative by this assay. For all specimens tested, the sensitivity and specificity of the assay were both 88%. However, when results were evaluated by patient, the sensitivity was 92% (24 of 26) with a specificity of 82% (14 of 17). Among specimens collected one week or later after disease onset, the sensitivity was 100%, with a specificity of 93%.

Adult↗
PubMed1987

Pharmacokinetics and tolerance of desciclovir, a prodrug of acyclovir, in healthy human volunteers.

Because of the incomplete absorption of acyclovir (ACV) when given orally in humans, efforts have been made to develop a prodrug of ACV that would be better absorbed from the gastrointestinal tract and then converted in vivo to ACV. One such compound, desciclovir (DCV), is converted to acyclovir in vivo by xanthine oxidase. We gave each of 13 healthy volunteers 250 mg (about 3.25 mg/kg of body weight) of DCV orally thrice daily for 10 days, collected serial plasma and urine specimens, and measured DCV and ACV concentrations. The absorption of DCV was at least 75%, and almost two-thirds of the administered oral dose was recovered in the urine as ACV. Peak ACV levels in plasma were about 5 micrograms/ml and were reached in less than 1 h. The levels of ACV achieved in plasma were of the same magnitude as those reported for subjects given intravenous ACV at a dose of 2.5 mg/kg and approximately 10-fold higher than levels attained after administration of 200 mg of oral ACV every 4 h as measured in previous studies. The half-life of DCV was 0.85 +/- 0.16 h, compared with 2.6 +/- 0.5 h for ACV, indicating rapid conversion of DCV to ACV. There was no substantial increase in ACV levels in plasma on day 11 compared with day 2. No serious or consistent adverse effects were noted. In particular, the creatinine level in serum did not significantly rise in any subject and remained within the normal range in all.

Acyclovir↗
PubMed1987

Protective immunity against herpetic ocular disease in an outbred mouse model.

Immunization of outbred mice by subdermal (footpad) inoculation with the F strain of herpes simplex virus type 1 (HSV-1) induces an immune response which protects the animals against herpetic ocular disease and encephalitis, and reduces the incidence of latent trigeminal ganglion infections following corneal challenge with the RE strain of HSV type 1. The protective effects are proportional to the dose of virus used for immunization. Heat-killed virus preparations also protected the mice against encephalitis and stromal keratitis, but failed to prevent epithelial keratitis and establishment of latency.

Animals↗
PubMed1987

Passive immunization with monoclonal antibodies against herpes simplex virus glycoproteins protects mice against herpetic ocular disease.

The effects of passive immunization with specific monoclonal antibodies against herpes simplex virus glycoproteins gB, gC, gD, and gE on the course of herpetic keratitis, survival and the establishment of latency in an outbred mouse model are described. A total of nine monoclonal antibodies were tested in these experiments. Passive immunization at 24 or 48 hours post-inoculation had little effect on the severity of the initial epithelial infection of the cornea, but blocked dissemination of the virus to the central nervous system and periocular tissues and prevented development of blepharitis, iritis and stromal keratitis. Additional studies are needed to characterize these monoclonal antibodies in greater detail, and to define the mechanism of these protective effects.

Animals↗