Search PubMed⌕ Search

Biomedical subjects

W C Saxinger

Publications and source records attributed to W C Saxinger.

At least 19 recordsLinked to original sources

A simple method for measurement of cell-substrate attachment forces: application to HIV-1 Tat.

In order to understand the importance of cell attachment to HIV-1 Tat, we quantified the strength of cell attachment to immobilized Tat in microtiter plate wells by the application of buoyant force. By replacing the attachment medium with dense medium, and subjecting the attached cells in the microtiter plates to centrifugal force in the conventional upright position, weakly binding and strongly binding cells could be discriminated (and separated) by varying the centrifugal speed. The strength of attachment of HT1080 cells to Tat was compared with that of the well-known extracellular matrix (ECM) proteins fibronectin and vitronectin. We observed that all three proteins mediated significant attachment of HT1080 cells both at 4 degrees C and 37 degrees C. However, unlike the ECM proteins, Tat was unable to engage in higher strength binding when the temperature was raised to 37 degrees C. The relatively weak binding of HT1080 cells to Tat (in the order of 3.0 mudynes/picomole of coated Tat) and lack of strengthening of binding to Tat at physiologic temperature suggests that this protein does not mimic adhesion molecule function. We anticipate that the methodology developed and described here will be useful in a wide variety of cell-matrix and cell-cell interaction studies.

Dose-Response Relationship, Drug↗

Phylogenetic associations of human and simian T-cell leukemia/lymphotropic virus type I strains: evidence for interspecies transmission.

Homologous env sequences from 17 human T-leukemia/lymphotropic virus type I (HTLV-I) strains from throughout the world and from 25 simian T-leukemia/lymphotropic virus type I (STLV-I) strains from 12 simian species in Asia and Africa were analyzed in a phylogenetic context as an approach to resolving the natural history of these related retroviruses. STLV-I exhibited greater overall sequence variation between strains (1 to 18% compared with 0 to 9% for HTLV-I), supporting the simian origin of the modern viruses in all species. Three HTLV-I phylogenetic clusters or clades (cosmopolitan, Zaire, and Melanesia) were resolved with phenetic, parsimony, and likelihood analytical procedures. Seven phylogenetic clusters of STLV-I were resolved with the most primitive (deeply rooted) divergence involving several STLV-I strains from Asian primate species. Combined analysis of HTLV-I and STLV-I revealed that neither STLV-I clusters nor HTLV-I clusters recapitulated host species specificity; rather, multiple clades from the same species were closer to clades from other species than to each other. We interpret these evolutionary associations as support for the occurrence of multiple discrete interspecies transmissions of ancestral viruses between primate species (including human) that led to recognizable phylogenetic clades that persist in modern species. Geographic concordance of divergent host species that harbor closely related viruses reinforces that physical feasibility for hypothesized interspecies virus transmission in the past and in the present.

Amino Acid Sequence↗

Antibodies to human herpes virus-6 and clinical course in patients with Hodgkin's disease.

Serial serum samples from 37 patients with Hodgkin's disease (HD) and 39 healthy controls were studied for antibodies to human herpes virus-6 (HHV-6) using ELISA and indirect immunofluorescent antibody (IFA) tests and to the Epstein-Barr virus (EBV) using a radio-complement fixation assay. Antibodies to HHV-6 in the pre-treatment sera from the HD patients were not significantly different from those of controls, but significant changes in titers related to clinical course were noted among the HD patients. HHV-6 IFA titers increased significantly in the course of follow-up in patients who relapsed and decreased significantly over time in patients who did not. These serologic studies support tissue-based investigations indicating that EBV plays a greater etiologic role in HD than HHV-6, although HHV-6 serology may be of prognostic value or may assist in identifying individuals with immunologic abnormalities. The identification of diverse HHV-6 antibody patterns using different assays may reflect the presence of a number of antibodies with varying implications, similar to those identified for EBV.

Adolescent↗

In vivo genetic variability of the human immunodeficiency virus type 2 V3 region.

The principal neutralizing epitope of the human immunodeficiency virus type 1 (HIV-1) lies between two invariant cysteines in the third variable region (V3) of the viral envelope (gp120), and its amino acid sequence varies among different HIV-1 isolates. HIV-2 carries an analogous amino acid sequence between two cysteines of the V3 regions, but its functional similarity with the HIV-1 principal neutralizing epitope is uncertain. We studied the degree of genetic variation of the HIV-2 V3 region in fresh blood samples from 12 HIV-2-seropositive individuals from Guinea-Bissau. Polymerase chain reaction was used to amplify viral fragments of 465 bp containing the V3 region from cellular DNA. Nucleotide sequence analysis of the entire envelope fragment from each patient revealed that the degree of variation among field isolates of HIV-2 is comparable to that observed in the analogous region of HIV-1. Most of the HIV-2 isolates studied were highly related, suggesting the existence of a limited number of different viral strains in the cohort studied. Thus, the HIV-2 and HIV-1 V3 regions vary to a similar degree and may also have analogous functions.

Amino Acid Sequence↗

Antibodies to human herpes virus-6 in patients with acute lymphocytic leukemia.

Human herpesvirus-6 (HHV-6), a ubiquitous virus that causes exanthem subitum and occasional cases of infectious mononucleosis, hepatitis and other viral syndromes, has also been associated with acute lymphocytic leukemia (ALL) in children. To further investigate this association, we obtained sera from 50 patients with ALL and 50 age-sex matched controls. Antibodies to HHV-6 were determined using ELISA and indirect immunofluorescent antibody (IFA) tests. No significant difference between antibody titers in the cases and controls was observed. Since seroepidemiologic studies have demonstrated higher HHV-6 antibody titers in young children than in adults, this serologic study suggests that the previous association reported for HHV-6 and ALL was a result of the age of the population rather than a relationship between the virus and the disease.

Adolescent↗

Seroepidemiology of human T cell lymphotropic virus in the Republic of Panama.

The human T-lymphotropic virus (HTLV) and associated diseases, adult T cell leukemia and spastic paraparesis, appear to be endemic in southwestern Japan and the Caribbean. This cross-sectional population-based study was conducted to describe the seroepidemiology of HTLV in the Republic of Panama. HTLV antibody was measured by first generation and commercial ELISA tests and confirmed by competitive binding ELISA, a radioimmunoassay for anti-p 24, and Western blot. Of 3,231 subjects greater than or equal to 15 years of age, 135 (4.2%) had antibody detected in ELISA screening tests, but because only 20% were confirmed positive, HTLV seroprevalence varied from 0.2-2% throughout the Republic. Infection with HTLV clustered in Guaymi Indians living in Bocas del Toro province (9.9% prevalence rate). With the exception of Guaymi Indians, no major geographic, urban/rural, male/female or racial differences in antibody prevalence were observed; specifically, HTLV infection rates were not elevated in black Panamanians. Clustering of infection in an isolated Amerind population must be further investigated. The small proportion of screen-positive sera which confirmed positive illustrates the importance of strict uniform criteria for seropositivity.

Binding, Competitive↗

Human T-cell leukemia virus-I and hematologic malignancies in Panama.

Serum samples were obtained in a 2-year period (November 1, 1984-December 31, 1986) from 136 Panamanian patients with hematologic malignancies identified by a population-based registry designed for studies investigating human T-cell lymphotropic virus (HTLV)-I. Only three patients had clinical and serologic findings of HTLV-I-associated adult T-cell leukemia/lymphoma (ATLL). The authors conclude that although classical HTLV-I-associated ATLL occurs in the Panamanian population, it is not as prevalent as in other Caribbean populations.

Aged↗

Cross-sectional study of immunologic abnormalities in intravenous drug abusers on methadone maintenance in New York City.

One hundred and ninety-nine patients with a history of intravenous drug abuse, and enrolled on the St Luke's-Roosevelt Hospital Center Methadone Program, had baseline evaluations performed from September 1984 to April 1987. The study was designed to examine immunologic parameters associated with HIV seropositivity and those predictive of progression to AIDS-related complex (ARC) and AIDS. Sixty-four patients (32%) had antibodies to HIV by enzyme-linked immunosorbent assay (ELISA), with confirmation by Western blot and none of these patients had ARC or AIDS at the time of initial evaluation. The mean values for white blood-cell count, absolute lymphocyte count, proportion and absolute CD4, and CD4/CD8 ratio were decreased significantly in the HIV-seropositive group compared with the HIV-seronegative group. On the other hand, levels of circulating beta 2-microglobulin, SCD8, SIL-2R, and HIV p24 antigen were significantly elevated in the HIV-seropositive group compared with the HIV-seronegative group.

AIDS-Related Complex↗

Geographic distribution of HTLV-I and identification of a new high-risk population.

Epidemiologic studies indicate that human T-cell lymphotropic virus type I (HTLV-I), the causative agent of most cases of adult T-cell leukemia/lymphoma (ATLL) in Southeast Japan and the Caribbean islands and the probable cause of a progressive neurological disorder often referred to as tropical spastic paraparesis, occurs with unusual geographic clustering. The current large-scale serosurvey was undertaken to improve our understanding of HTLV-I prevalence in different parts of the world. We analyzed 43,445 serum samples collected from various geographic locales worldwide; 76% of these sera came from clinically healthy donors. Samples were initially screened by an enzyme-linked immunosorbent assay (ELISA) and 4,353 were further evaluated by means of competition assays. In this study, which did not include sera from endemic areas of Japan, a high prevalence of infection was observed in several countries in the Caribbean basin. A significant age-sex difference was observed between populations in the Caribbean and non-endemic regions of Japan. The reason for the male excess in non-endemic areas of Japan will require further study, while the female excess in the Caribbean basin is compatible with the previously described pattern for other HTLV-I-endemic areas. A newly recognized area of possible endemicity was southern Florida, where evidence of infection with HTLV-I or a related virus was found in a group of native Americans whose sera were collected in 1968. In certain parts of the world, particularly sub-Saharan Africa, important problems in determining specificity of reactivity occurred, probably because of cross-reacting antibodies. No pattern was detected that could explain the cross-reactivity solely on the basis of geographic areas, specific patterns of non-viral parasitic infection, or methods of handling the specimens. It is possible that these cross-reactivities are antibodies to proteins from HTLV-I-related retroviruses yet to be discovered.

Adult↗

HBLV is not ASFV.

Explore the source record for details and available documents.

African Swine Fever Virus↗

Transmission of HTLV-I and HIV among homosexual men in Trinidad.

Risk for human T-cell lymphotropic virus type (HTLV-I) and human immunodeficiency virus (HIV) infection was evaluated in 100 homosexual or bisexual men from Trinidad. High seropositivity for HTLV-I (15% vs 2.4% in the general population) was linked to duration of homosexuality and numbers of partners, suggesting that HTLV-I, like HIV, can be transmitted by homosexual sex. Forty percent of homosexuals compared with 0.19% of the general population were seropositive for HIV, and sexual contact with US homosexual men and prior history of gonorrhea were major risk factors. The seroprevalence of HIV was three times higher than that for HTLV-I, suggesting that HIV is more efficiently transmitted, especially since HIV appears to have been recently introduced into Trinidad. Altered immune status was prominent in individuals infected with HIV and coinfected with HIV and HTLV-I. Whether HIV/HTLV-I coinfection amplifies clinical effects is a hypothesis that will require further evaluation.

Acquired Immunodeficiency Syndrome↗

Epidemiology of human T cell leukemia virus type I infection in East Sepik Province, Papua New Guinea.

A serological survey of 317 healthy residents of rural Papua New Guinea (PNG) showed a 26% prevalence of antibodies to human T cell leukemia virus type I (HTLV-I). Antibody to HTLV-I was detected in 16% of children less than or equal to 10 years old (including an 18-month-old child) and increased to greater than or equal to 24% in subjects greater than 20 years old. Prospective examination for antibody in 104 residents of one village revealed a seroconversion rate of 13% over a one-year period. The mean titer of antibody in these subjects (1:183) was lower (P less than .0005) than that in persons who were persistently seropositive (1:718). Analysis for clustering of infected subjects suggested that personal contact within the home played a role in the horizontal spread of HTLV-I. These data indicate that HTLV-I infection has a higher prevalence in PNG than in other endemic parts of the world, exposure occurs at an early age, and infection and/or seroconversion is common in adults as well as in children.

Adolescent↗