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Biomedical subjects

D E Lewis

Publications and source records attributed to D E Lewis.

At least 109 records · Page 6Linked to original sources
PubMed1990

HLA-DR peptide inhibits HIV-induced syncytia.

The infectivity of the human immunodeficiency virus (HIV) is related to the structure of its envelope protein, gp160, which is responsible for viral entry. We considered the possibility that a structural homology between gp160 and major histocompatibility complex (MHC) molecules might be associated with the extraordinary affinity that gp120 has for its receptor, CD4. Amino acid sequence comparisons revealed five regions of structural similarity between the HLA-DR beta molecule and gp160. The DR2 beta synthetic peptides containing these regions were examined for their ability to block HIV-induced syncytia formation using a 51Cr release assay. The peptide beta 141-155 inhibited the formation of syncytia whereas the other four DR beta peptides with gp160 similarity did not. Our results indicate that this region in gp120, which is similar to an HLA-DR region, is crucial to T cell-gp120 interactions, and should be considered in the design of future vaccines.

Amino Acid Sequence↗
PubMed1990

Speech perception in low-pass filtered noise for normal and hearing-impaired listeners.

Two experiments were conducted concerning speech perception in noise. In Experiment 1, a comparison was made between adaptive and fixed-level procedures to estimate the S/N ratio at which 50% correct performance occurred for nonsense syllables for normal-hearing listeners. The two methods yield similar S/N ratio estimates, but the consonant confusions found with the fixed-level method could not be predicted accurately from the adaptive procedure. In Experiment 2, the adaptive procedure was used to estimate the S/N ratio for a 50% performance level in low-pass filtered noise with a range of cutoff frequencies. Data were obtained from 5 normal-hearing listeners at two speech levels (50 and 75 dB SPL) and 4 hearing-impaired listeners at one speech level (75 dB SPL). The hearing-impaired listeners required a better S/N ratio than the normal listeners at either presentation level for all except the widest bandwidth, where their S/N ratios began to converge with the normal values. In addition, the S/N ratios for the hearing-impaired listeners plateaued at relatively narrow bandwidths (0.75 to 2.5 kHz) compared to the normal-hearing group (3.0 to 5.0 kHz). That is, the addition of high-frequency components to the noise did not alter performance. These findings suggest that the hearing-impaired listeners may have relied upon either low-frequency cues or prosodic cues in the perception of these test items.

Adaptation, Physiological↗
PubMed1990

Complex and pure-tone signals in the evaluation of hearing-aid characteristics.

In recent years, a number of commercially available systems have been developed to analyze the electroacoustic characteristics of hearing aids. In addition to pure-tone signals, these systems often use a wide variety of complex signals such as broadband noise, clicks, and multitonal complexes. In this paper, a number of practical and theoretical issues concerning the use of pure-tone and complex signals in the evaluation of hearing-aid characteristics are described. The circumstances under which discrepancies in estimated gain and maximum output might occur using these two types of signals are described and the clinical implications of these differences are discussed.

Algorithms↗
PubMed1990

Confocal microscopic detection of human immunodeficiency virus RNA-producing cells.

A central anomaly in the pathogenesis of AIDS is that few actively infected CD4+ cells (1 in 10(4)-10(5) have been detected in the peripheral blood, even though dramatic depletion (often greater than 90%) of CD4+ cells is the hallmark of disease progression. A sensitive, 35S-based human immunodeficiency virus (HIV) RNA in situ hybridization technique was coupled with a new detection method, confocal laser scanning microscopy, to examine transcriptionally active HIV-infected cells from individuals at different disease stages. In 35 symptomatic HIV-infected individuals (AIDS and AIDS related complex), an average of 1 in 350 mononuclear cells produced HIV RNA. In contrast, in an asymptomatic group of 30 individuals, an average of 1 in 2000 mononuclear cells produced HIV RNA. These data, obtained using this improved detection method, suggest there are more HIV RNA-producing cells in HIV-infected individuals than previously reported. In addition, increased numbers of HIV transcribing cells were found to correlate with declining clinical condition as assessed by Karnofsky performance score. These data suggest that viremia per se may account for the pathologic consequences in HIV infection.

AIDS-Related Complex↗
PubMed1990

Immunology of HIV infection.

The goal of finding an effective vaccine against the human immunodeficiency virus (HIV) is hampered by our uncertainty of the mechanism(s) responsible for the pathogenesis as well as the lack of knowledge of protective mechanisms. The effects of HIV on the immune system are myriad and thus the truly significant manifestations of the pathology are difficult to dissociate from those more peripheral. In this article we will initially characterize the natural history of HIV infection which shows a chronic and perhaps inexorable course. The second part will deal with the immune response mounted against this assault and the final section is a discussion of the possible unfavorable consequences of the immune response that humans muster against this agent.

CD4-Positive T-Lymphocytes↗
PubMed1989

Interleukin 2 receptor expression by T cells in human aging.

Aged individuals have depressed cell-mediated immunity and diminished T cell proliferation to mitogenic and antigenic stimuli. Because T cell responses depend on the surface expression and normal function of interleukin 2 receptors, we measured the quantities and affinities of cell surface IL-2R and the amount of soluble IL-2R alpha chain (p55) release in vitro in PHA-stimulated mononuclear cells from healthy aged (greater than or equal to 65 years old) and young (less than or equal to 39 years old) donors. At the peak of the PHA response, the fraction of cells expressing IL-2R alpha chain (CD25+) was lower in the aged (43% vs 56%, P = 0.033). Relative to the lower proliferation and CD25 expression, old donor cells released unexpectedly high quantities of soluble alpha chain into culture supernatants. However, the average affinities and the mean numbers of high- and low-affinity surface receptors per CD25+ cell were equivalent in cells from eight pairs of aged and young donors (1850 vs 1586 high affinity, and 20,655 vs 23,466 low affinity, P greater than 0.2 for both). The soluble IL-2R released by stimulated cells had no effect on proliferative responses, because addition of saturating doses of exogenous recombinant IL-2 did not increase cellular proliferation, and addition of soluble anchor-minus recombinant IL-2R alpha chain did not suppress it. These results indicate that in healthy older individuals, diminished numbers of T cells can be induced to express cell surface IL-2R following mitogenic stimulation, although aged CD25+ can express a normal complement of IL-2R molecules. In the aged, either CD25+ cells release excessive quantities or a subset of cells synthesizes and releases soluble IL-2R alpha chain into the extracellular environment without expressing it on the cell surface.

Adult↗
PubMed1989

Abnormalities of immunoregulation in juvenile rheumatoid arthritis.

Immunoregulatory imbalances are thought to be involved in the pathogenesis of juvenile rheumatoid arthritis (JRA). We have found that a subset of patients with JRA demonstrate a marked expansion of B cells without an alteration in B cell subset distribution. However, there was actually decreased in vitro immunoglobulin production in response to stimulation with either pokeweed mitogen or hydrocortisone. These B cell abnormalities were found to correlate with a marked increase in the percentage of CD4 + CD45R + T cells, a T cell subset thought to be responsible for inducing suppression. In addition, there was a significant decrease in the percentage of CD4 + CD29 + T cells, a T cell subset thought to be responsible for inducing B cell immunoglobulin production. Our results suggest that the B cell abnormalities seen in JRA may be related to defects in T cell immunoregulation.

Adolescent↗
PubMed1989

Cocaine and pregnancy: clinical and toxicological implications for the neonate.

Recent studies show that the rate of cocaine use by pregnant women in the United States is much higher than realized hitherto, and an increasing number of infants are being born to cocaine-using mothers. In an ongoing research project to study the effects of cocaine on pregnancy outcome, we studied 70 infants born to cocaine-using women. These infants were matched to a drug-free comparison group selected from the population of the same hospital: children of pregnant women of a similar racial and socioeconomic distribution, but with no history or evidence of licit or illicit drug use during pregnancy. Cocaine-exposed infants had lower birth weight, shorter gestation, and a smaller head circumference than control infants. Cocaine-exposed infants also had neurobehavioral abnormalities at initial evaluation and a higher rate of perinatal complications. Toxicological evaluation of urines of neonates born to cocaine-using women showed that benzoylecgonine, a primary metabolite of cocaine, persisted in the urines for as long as 120 h after delivery. We discuss the role of the immature fetal and neonatal system in the clinical and toxicological outcome of the infant, and emphasize that further long-term studies of this will be needed.

Abnormalities, Drug-Induced↗
PubMed1988

Human immunodeficiency virus-induced pathology favored by cellular transmission and activation.

Epidemiological data suggest that transmission of human immunodeficiency virus (HIV) occurs primarily by transference of virally infected cells. However, the efficiency of lytic productive infection induced by HIV after transmission of cell-associated virus vs. free virus is difficult to assess. The present studies compare the extent of depletion of CD4+ (helper/inducer) T cells after mixing uninfected cells with either free HIV or irradiated HIV-infected allogeneic or autologous cells in vitro. Rapid CD4+ cellular depletion occurred only in cultures containing allogeneic infected cells or after addition of a nonspecific T cell activation signal to cultures with autologous infected cells. These in vitro observations strongly support the epidemiological implication that interactions between infected and uninfected cells are the most efficient means of transmission and HIV-induced cytopathology in vivo. They also provide direct support for the concept that immunological stimulation by foreign cells infected with HIV dramatically increases the likelihood of transmission. These in vitro observations suggest a model for the acquisition of HIV in vivo and the role of cellular activation in dissemination of the virus to uninfected cells in an infected individual.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Some theoretical considerations concerning the relation between functional gain and insertion gain.

Three examples in which insertion gain and functional gain measures of hearing aid response do not agree are illustrated. In two of the cases, functional gain measures overestimate the true real-ear gain for average conversational speech and in the third example, insertion gain measures are shown to provide an inaccurate estimate of aided benefit. Reasons for these discrepancies are discussed, and an alternative method for measuring real-ear hearing-aid response is described.

Acoustics↗
PubMed1988

Functional versus phenotypic analysis of T cells in subjects seropositive for the human immunodeficiency virus: a prospective study of in vitro responses to Cryptococcus neoformans.

We performed a prospective study of 50 subjects at high risk for human immunodeficiency virus (HIV) infection to determine if assays of antigen-specific T cell function provide an earlier indication of future progression to AIDS or a better assessment of immune function than do current methods of evaluation. We measured in vitro T cell responses to Cryptococcus neoformans and tetanus toxoid, response to mitogens, HIV p24 antigenemia, and clinical parameters. Progression to AIDS was significantly associated with loss of T cell response to cryptococci (P = .015), HIV antigenemia (P = .001), and low CD4+ cell numbers (P = .001). Most importantly, we found that loss of antigen-specific responses to cryptococci and tetanus can occur before changes in CD4 cell number. Abnormal response to mitogens and marked depletion of CD4+ cells were late signs of progressive HIV infection. Measurement of antigen-specific T cell function may be useful for assessing the efficacy of antiviral therapy in HIV infection before onset of symptoms.

Acquired Immunodeficiency Syndrome↗
PubMed1987

T suppressor cell growth factor and anti-CD3 antibodies stimulate reciprocal subsets of T lymphocytes.

Because of the central role of IL-2 in clonal expansion of T cells, we have postulated that lymphocyte subpopulations with opposing regulatory functions might be independently regulated by differential requirements for expression of cell-surface IL-2-R. Purified CD4+ and CD8+ cells proliferated in an IL-2-dependent manner to crosslinked anti-T cell receptor antibodies (anti-CD3-Seph). Similarly, both CD4+ and CD8+ cells became IL-2 responsive after incubation in T suppressor cell growth factor (TsGF), a newly described approximately 8,000 Mr product of activated CD4+ cells. In support of our hypothesis, however, we observed that subpopulations of CD4+ and CD8+ cells, possessing distinct cell-surface antigens, showed differential responses to these stimuli. Those cells of suppressor-inducer or suppressor-effector phenotype failed to proliferate when cultured in anti-CD3-Seph plus IL-2, but did proliferate in an IL-2-dependent manner to TsGF. Furthermore, the suppressor-effector population was unresponsive to TsGF plus IL-2 when cocultured in anti-CD3-Seph, suggesting that functionally induced Ts may be refractory to growth stimuli. Conversely, cells with helper-inducer or cytolytic phenotype proliferated when incubated in anti-CD3-Seph and IL-2, while remaining essentially unresponsive to TsGF and IL-2. The results could not be explained by differences in the level of CD3 expression by the T cell subsets. Thus, cells within the helper and suppressor lineages appear to have distinct and reciprocal patterns for the induction of IL-2 responsiveness.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Studies of the mechanism by which gangliosides inhibit the proliferative response of murine splenocytes to concanavalin A.

Gangliosides are known to inhibit the proliferative response of murine and human lymphocytes to antigens and mitogens in vitro. In this study the response of murine spleen cells to concanavalin A (Con A) was used as a model system. Analysis of the cellular events by flow cytometry revealed that during the first 24 hr of culture the effect of gangliosides on Con A-treated cells was minimal. At 48 hr, however, more of the ganglioside-treated cells were in G0/G1, the cells contained more RNA, and fewer cells were in S phase. These data indicate that gangliosides inhibit the transition of the cells from G0/G1 into the S phase of the cell cycle. Expression of the interleukin 2 (IL-2) receptor, as measured by the binding of a monoclonal antibody to the receptor, was not inhibited by the gangliosides. Binding of 125I-labeled recombinant IL-2 to cells cultured for 48 hr with Con A was inhibited by ganglioside GD1a but not by asialo GM1. Inhibition was much more effective if the gangliosides were preincubated with IL-2 before addition of cells, but no inhibition was observed if the cells were preincubated with gangliosides and the unbound gangliosides were washed out prior to addition of the IL-2. These data suggest that interference with the binding of IL-2 to the high-affinity IL-2 receptor of activated T lymphocytes plays an important role in the inhibition of Con A-induced proliferation.

Animals↗
PubMed1987

Fusion as a mediator of cytolysis in mixtures of uninfected CD4+ lymphocytes and cells infected by human immunodeficiency virus.

We describe an unusual type of cytopathology in which uninfected CD4+ (helper/inducer) cells (cells expressing the human leukocyte antigen CD4) interact with cells persistently infected with the human immunodeficiency virus (HIV). Prior antigenic stimulation was not required, since CD4+ cells taken either from healthy persons without anti-HIV antibodies or from individuals with anti-HIV antibodies were capable of inducing cytolysis. Neither CD8+ (suppressor/cytotoxic) nor CD16+ (natural killer) cells mediated the reaction. Light microscopic and autoradiographic studies revealed that, prior to cytolysis, multinucleated giant cells were formed from fusions between HIV-infected cells and large numbers of uninfected CD4+ lymphocytes. These data may explain the paradox that exists in vivo in which a dramatic depletion of CD4+ lymphocytes occurs in the presence of a small number of HIV-infected CD4+ cells. These new insights into the pathogenesis of acquired immunodeficiency syndrome (AIDS) may lead to future therapeutic strategies.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Growth of masking as a measure of response growth in hearing-impaired listeners.

Growth-of-masking functions were obtained from 19 normal and 5 hearing-impaired listeners using a simultaneous-masking paradigm. When masker and probe frequency are identical, the slope of masking approximates 1.0 for both normal-hearing and impaired listeners. For masker frequencies less than or greater than probe frequency, the slopes for impaired listeners are shallower than those of normals. These findings are consistent with previously reported physiological data (single-fiber rate versus level and AP masking functions) for animals with induced cochlear lesions. Results are discussed in terms of a potential masking technique to estimate the growth of response in normal and impaired ears.

Adolescent↗
PubMed1987

Epstein-Barr virus-transformed B-cell line (DV-1) derived from bone marrow of a patient with severe combined immunodeficiency and immunoblastic lymphoma.

An Epstein-Barr virus-transformed B-cell line derived from a patient with severe combined immunodeficiency who died of a lymphoreticular malignancy has been characterized. The line derived from bone marrow cultures and designated DV-1 shows surface and cytoplasmic IgM and staining with fluorescent monoclonal antibodies against immunoglobulin heavy and light chains mu, delta, and kappa, Dr, and several other B-cell surface antigens. DV-1 secretes IgM kappa and demonstrates monoclonality on analysis of immunoglobulin heavy and light chain gene rearrangement patterns. Incubation with either phytohemagglutinin or pokeweed mitogen failed to cause significant stimulation of proliferation of DV-1 and another EBV-transformed B-cell line derived from an immunologically normal host (LA-350), whereas incubation with Staphylococcus aureus Cowan strain 1 led to significant inhibition of DV-1 and LA-350. Rabbit IgG antibody specific for human immunoglobulin mu-chains produced a dose dependent stimulation of both lines. The responses of DV-1 and LA-350 to mitogens and anti-mu were not as high as those of normal peripheral blood lymphocytes. This spontaneously derived Epstein-Barr virus-transformed B-cell line from a patient with severe combined immunodeficiency demonstrated functional characteristics similar to a B-cell line derived from an immune competent host. While these cells spontaneously incorporate 200 times more thymidine than normal resting peripheral blood lymphocytes, they retain their ability to be modulated by antiimmunoglobulin, and staphylococcal Cowan strain 1, but are unresponsive to the effects of B-cell growth factor.

B-Lymphocytes↗
PubMed1987

Cocaine intoxication in a breast-fed infant.

A case report of a 2-week-old infant girl who ingested cocaine via her mother's breast milk is presented. Because of the increasing prevalence of cocaine use, physicians should educate breast-feeding women concerning the hazards of cocaine use and its potential effects on the developing infant.

Breast Feeding↗