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Biomedical subjects

K H Fife

Publications and source records attributed to K H Fife.

At least 19 recordsLinked to original sources

Incidence of HIV infection in monocyte subpopulations characterized by CD4 and HLA-DR surface density.

OBJECTIVE: The purpose of this study was to determine any correlation between the expression of CD4 antigen on the surface of monocytes, and the frequency with which these cells are infected with HIV. DESIGN: CD4 surface expression on monocytes is significantly less than that expressed on CD4+ lymphocytes. Nevertheless, all monocytes express the HIV CD4 receptor and infected individuals have a significant decrease in the number of monocytes that express a higher density of CD4 surface fluorescence. METHODS: Three-color flow cytometric analysis was used to characterize monocyte-enriched peripheral blood mononuclear cells (PBMC) in terms of surface expression of CD4, CD14 (macrophage antigen), and class II major histocompatibility antigen (HLA-DR). HLA-DR+ monocytes from HIV-positive individuals were sorted into two subpopulations based on either 'bright' or 'dim' CD4 surface expression. A polymerase chain reaction (PCR) assay was used to detect the presence of proviral HIV sequences within the DNA from 10(5) cells from each sorted population. RESULTS: Post-sort analysis revealed that the dim CD4+ monocyte subset expressed dim HLA-DR surface antigen, while the bright CD4+ monocyte subset contained both bright and dim HLA-DR+ cells. PCR results showed that four out of eight dim CD4+ monocyte subsets contained proviral HIV DNA, compared with one out of eight bright CD4+ monocyte subsets.

Adult

Human papillomavirus infections of the genital tract.

Infection of the genital tract by HPV is a sexually transmitted disease of increasing prevalence. The association of HPV infection with genital tract malignancies is of great concern, and further studies are needed to clarify this association. Few investigators believe at this time that proof of a direct causative role exists for HPV in these cancers, but indirect evidence of such a role is abundant. There are many clinical forms of HPV infection of the genital tract, and few clinicians can easily recognize them all. Treatment of condyloma acuminatum is difficult and frustrating. Cryotherapy with liquid nitrogen is the safest and most effective therapy for most forms of condyloma acuminatum. Recurrence of condyloma acuminatum is common with all presently used forms of therapy, probably owing to latent HPV infection in normal-appearing skin. No form of treatment is ideal for all forms of condyloma acuminatum, but without continued efforts to find better therapeutic modalities and preventative measures, the epidemic of genital HPV infection will continue unchecked.

Condylomata Acuminata

Human papillomavirus type 6 long control region and human cellular DNA contain related sequences.

We have identified a region of human papillomavirus type 6 (HPV-6) DNA that hybridizes with human cellular DNA containing no detectable HPV DNA sequences. The region of hybridization has been localized to a segment of the viral long control region between the end of the L1 open reading frame and the late polyadenylation signal and is likely contained within a 94-base-pair insertion at nucleotide 7350 which is present in the cloned HPV-6b DNA used for these studies. Restriction fragments of HPV-6 DNA from seven patients suggested that this insert was present in these naturally occurring viral genomes as well. The presence of this insert was confirmed by direct sequence analysis of polymerase chain reaction-amplified segments from four naturally occurring HPV-6 genomes. By analogy with other systems, this insert and surrounding sequences may function to destabilize the HPV-6 late mRNA.

Base Sequence

Differences among mononuclear cell subpopulations in HIV seropositive or seronegative homosexual and heterosexual men as determined by four-color flow cytometry.

Four-color cell surface immunofluorescence and flow cytometry analysis was used to quantitate mononuclear cell subpopulations from HIV seropositive (HIV+) and seronegative (HIV-) homosexual men and heterosexual men. HIV+ men were divided into two groups based on peripheral blood CD4/mm3 of greater than 500 or less than 500. CD4+ cells that were simultaneously CD45R-, CDw29-, and 13- were significantly less in HIV+ men with less than 500 CD4/mm3 (17%) compared to heterosexual men (34%). This lower percentage of "CD4 only" cells in HIV+ males with less than 500 CD4/mm3 correlated with a significantly higher percentage of CD4+ cells that were CD45R+, CDw29+, and 13+ in these individuals. CD8+ cells that were CD45R+, 13+, but CD38-, were significantly less in HIV+ men with less than 500 CD4 as compared to HIV- homosexual men. In contrast, a second CD8+ subpopulation that was CD45R-, CD38+, and either 13+ or 13- was significantly greater in less than 500 HIV+ men as compared to both HIV- homosexual men and heterosexual men. A significant difference in this subpopulation was observed between the less than 500 and greater than 500 HIV+ groups and correlated with seropositivity for viral p24 antigen. Interestingly, CD8+ cells that were CD45R+, as well as CD38+, and either 13+ or 13- were significantly greater in the less than 500 HIV+ group compared to the greater than 500 HIV+ group, and did not correlate with p24 seropositivity. The percentage of monocyte/macrophages that were CD4- or expressed dim CD4 immunofluorescence, but were 13+, was significantly greater in HIV+ men (43%) compared to HIV- homosexual men (27%). In summary, we have identified previously undescribed mononuclear cell subpopulations that were altered with HIV infection and, in some cases, correlated with the stage of disease.

ADP-ribosyl Cyclase

Human papillomaviruses: are we ready to type?

The issue of determining which human papillomavirus (HPV) is present in a clinical specimen (typing specimens for HPVs) is receiving attention because HPVs cause condyloma acuminata and are associated with the continuum of disease which ranges from dysplasia to invasive genital cancer. Morphological inspection of precancerous lesions is not sufficient to determine which lesions will progress and which will not. A number of research tools based primarily on deoxyribonucleic acid hybridization have been developed. These permit identification and typing of HPV in genital tract scrapings or biopsies. Some HPV types (e.g., HPV-16 and HPV-18) have been identified in high-grade dysplasias and carcinomas more commonly than other types (e.g., HPV-6) and have been designated "high risk" types for cervical cancer. Thus, the question arises whether HPV typing would improve patient management by providing increased sensitivity for detection of patients at risk or by providing a prognostic indicator. In this review, the available typing methods are reviewed from the standpoint of their sensitivity, specificity, and ease of application to large-scale screening programs. Data implicating HPVs in the genesis of genital tract cancers are reviewed, as is the association of specific HPV types with specific outcomes. We conclude that there is currently no simple, inexpensive assay for HPV types, although such assays may be developed in the future. Analysis of the typing data indicates that, while HPV types can be designated high risk and low risk, these designations are not absolute and thus the low-risk group should not be ignored. In addition, interpretation of the data is complicated by finding high-risk types in individuals with no indication of disease. Insufficient data exist to indicate whether knowledge of the presence of a given HPV type is a better prognostic indicator than cytological or histological results. Thus, more research is needed before it can be determined whether typing information will augment the method currently in use for deciding treatment regimen and whether it warrants widespread use.

DNA Probes, HPV

Long-term acyclovir suppression of frequently recurring genital herpes simplex virus infection. A multicenter double-blind trial.

Normal adults with six or more episodes of genital herpes in the previous year were enrolled in a one-year, multicenter, double-blind trial comparing placebo with 400 mg of acyclovir administered orally twice daily. Patients with episodes during the study were offered 200 mg of acyclovir administered orally five times daily for five days; this allowed comparison of suppressive and episodic treatment. After one year, 227 (44%) of 519 patients receiving suppressive treatment and seven (2%) of 431 receiving placebo (episodic) treatment remained free of recurrences, and the mean numbers of recurrences per year were 1.8 and 11.4, respectively. Among 67 patients who had received suppressive therapy for one year, the mean duration of lesions in the first episode following the discontinuation of treatment was 9.3 days compared with 7.3 days among 45 patients who had received episodic therapy for one year. Treatment was well tolerated, and no changes were noted in the in vitro susceptibility to acyclovir of herpes simplex virus cultured during or after the one-year trial. Continuous or episodic oral acyclovir therapy for one year remained safe and effective.

Acyclovir

Spontaneous and induced interferon production by peripheral blood leucocytes from control population and patients with herpes genitalis.

The spontaneous and PHA induced levels of interferon were measured in peripheral blood leucocyte cultures of twenty-eight individuals diagnosed as positive for herpes genitalis, and in a group of control subjects. As reported by Cunningham and Merigan [1983] for herpes labialis, leucocytes from individuals with herpes genitalis produced low levels of interferon spontaneously; however, similar results were found for individuals within the control population. No statistically significant difference could be found for PHA induced interferon levels, antigen induced interferon levels, or helper/suppressor cell ratios between the herpes genitalis population and control population. Our results indicate that interferon does not play a major role in the latency or recurrence of herpes genitalis.

Antigens, Viral

Symptomatic and asymptomatic cervical infections with human papillomavirus during pregnancy.

The prevalence of human papillomavirus (HPV) infection of the cervix was determined in an unselected population of pregnant women presenting to an inner-city Obstetrics Clinic in the first trimester. Cervical scrape specimens were screened for the presence of HPV types 6, 11, 16, 18, and 31 DNA by using three different blot hybridization methods. Specimens from 26 (11.1%) of 234 patients contained HPV DNA sequences. HPV-16 and -31 were detected in six specimens each, whereas HPV-6, -11, and -18 were each identified in three specimens. Five additional specimens contained HPV DNA sequences of undetermined type. Only two of the 26 positive specimens were obtained from patients with genital warts; an additional 12 specimens were from patients with cytological abnormalities. We conclude that cervical HPV infections in some pregnant populations are common and that many such infections are not clinically apparent.

Adult

A one-step method for detecting and typing human papillomavirus DNA in cervical scrape specimens from women with cervical dysplasia.

We studied 66 women with a previous dysplastic cervical cytological smear who were referred for colposcopy and biopsy for the presence of human papillomavirus (HPV) types 6, 11, 16, 18, and 31 DNA in cervical specimens. The specimens were analyzed by a novel hybridization method termed reverse blotting, in which cellular DNA is radiolabeled and used to probe a battery of cloned HPV DNAs immobilized on nitrocellulose. Reconstruction experiments demonstrated that this method could detect about one HPV genome equivalent per cell. HPV DNA sequences were detected in 52 (96%) of 54 patients who showed either condylomatous changes or dysplasia by cervical biopsy. HPV-16 was most commonly detected overall and was detected in 61% of moderate or severe dysplastic samples. HPV DNA was also detected in seven of 12 cervical scrapes from women with a history of dysplasia but with either normal or inflammatory changes noted on cervical biopsy. Our results indicate that the reverse-blot method can detect DNA homologous to various HPV types in a single experiment using DNA from the small numbers of cells obtained by cervical scraping.

Cervix Uteri

Genomic variation of adenovirus type 5 isolates recovered from bone marrow transplant recipients.

We characterized the genomic variation of adenovirus type 5 isolates recovered from bone marrow transplant recipients in Seattle between 1976 and 1982. By restriction endonuclease analysis, we identified three new adenovirus genomic variants, each associated with a single invasive adenovirus infection. In addition, we were able to obtain suggestive evidence for a nosocomial spread of a particular group of isolates within this population. This study demonstrates that the technique of restriction endonuclease analysis is an important epidemiological tool for investigating viral infections.

Adenoviridae Infections

Genital herpes simplex virus infections.

Genital HSV infection is an important sexually transmitted disease that is becoming more common. The primary infection typically is associated with systemic signs and symptoms and painful genital lesions, with a high rate of complications. Recurrences are much milder, with less frequent complications. Although many rapid diagnostic tests for genital herpes are now available, none is as sensitive or reliable as tissue culture. Dilemmas still exist regarding the best management strategy for the expectant mother at risk for transmitting HSV to the neonate, in part because of limitations in current diagnostic techniques. Although current treatment regimens with acyclovir can effectively control most symptoms and improve healing of lesions, they appear to have no effect on decreasing the frequency of subsequent recurrences. Short-term chronic suppression with acyclovir is effective in preventing symptomatic recurrences and appears to be relatively free of toxicity, but long-term studies are only now in progress. Asymptomatic viral shedding associated with either primary or recurrent infections and its contribution to sexual transmission of the disease are just now being fully appreciated, and the effect of therapy on subsequent transmission of disease remains to be determined. HSV genital infection in the immunocompromised host can produce a more severe and prolonged illness than in the normal host, but reactivation of the infection can be prevented with acyclovir suppression. Further research is needed on many aspects of the host-HSV interaction, especially regarding the factors involved in recurrences and the importance of the host's immune response to the manifestations of disease.

Female

Adenovirus infections in patients undergoing bone-marrow transplantation.

Viral infection is commonly observed after bone-marrow transplantation. We isolated adenovirus from 51 of 1051 patients undergoing marrow transplantation between 1976 and 1982. Of the 46 isolates available for typing, 13 (27.7 per cent) were of the closely related species 11, 34, or 35 (subgenus B). All 13 of the patients with these species had positive urine cultures. The species have previously been associated with the acquired immunodeficiency syndrome or with renal transplantation but are not commonly found in community surveys. Invasive infection was confirmed by biopsy or autopsy in 10 of 51 patients. Seven of the 10 had virus isolated from lung, and 4 died from pneumonia attributed to adenovirus. Two of the five patients with renal isolates had evidence of virally induced renal impairment, and both patients with liver isolates had adenovirus hepatitis. There was no common source that accounted for these adenovirus infections, and the most likely source of infection appeared to be endogenous viral reactivation. The only identifiable risk factor for the development of infection and for severe disease was the presence of moderate to severe graft versus host disease.

Adenoviridae Infections

Isolation and characterization of six new genome types of human adenovirus types 1 and 2.

Several of the 41 types of human adenovirus have been divided into genome types based on aberrant restriction endonuclease digestion patterns of viral DNA. In the process of screening a large number of clinical adenovirus isolates by restriction endonuclease digestion of viral DNA, we have identified nine isolates from eight patients which were identified by neutralization as adenovirus type 1 or 2 but had aberrant cleavage patterns. Cleavage sites for the enzymes SmaI, EcoRI, HindIII, KpnI, and HpaI were mapped. The variants could be placed in six distinct groups based on cleavage patterns. The designation genome types 1a, 1b, 1c, 2b, 2c, and 2d are proposed for these isolates.

Adenoviridae Infections

Comparison of neutralization and DNA restriction enzyme methods for typing clinical isolates of human adenovirus.

Sixty-five adenovirus isolates collected over a 3.5-year period were typed by both standard microneutralization techniques and restriction endonuclease digestion of viral DNA. Of the 65 isolates, 47 (72.3%) representing six adenovirus types could be typed by microneutralization. Eighteen isolates demonstrated partial neutralization with standard antisera to two or more adenovirus serotypes and thus could not be definitively typed. DNA analysis permitted typing of 64 of the 65 isolates (98.5%) (including four isolates which contained mixtures of two adenovirus types), and 12 different types were identified. Neutralization and DNA typing disagreed for five isolates, and in each case, digestion with multiple restriction endonucleases and DNA hybridization studies were consistent with the type assigned by DNA analysis. In addition, the DNA analysis method allowed the identification of genomic variants (genome types) of five adenovirus types. We conclude that typing clinical isolates of adenovirus by restriction endonuclease digestion of viral DNA can be done rapidly, provides additional epidemiological and typing information, and provides fewer ambiguous results than does typing by neutralization.

Adenoviruses, Human