Biomedical subjects

D P Fan

Publications and source records attributed to D P Fan.

At least 19 recordsLinked to original sources

PubMed1996

Impact of the mass media on calls to the CDC National AIDS Hotline.

This paper considers new computer methodologies for assessing the impact of different types of public health information. The example used public service announcements (PSAs) and mass media news to predict the volume of attempts to call the CDC National AIDS Hotline from December 1992 through to the end of 1993. The analysis relied solely on data from electronic databases. Newspaper stories and television news transcripts were obtained from the NEXIS electronic database and were scored by machine for AIDS coverage. The PSA database was generated by computer monitoring of advertising distributed by the Centers for Disease Control and Prevention (CDC) and by others. The volume of call attempts was collected automatically by the public branch exchange (PBX) of the Hotline telephone system. The call attempts, the PSAs and the news story data were related to each other using both a standard time series method and the statistical model of ideodynamics. The analysis indicated that the only significant explanatory variable for the call attempts was PSAs produced by the CDC. One possible explanation was that these commercials all included the Hotline telephone number while the other information sources did not.

Acquired Immunodeficiency Syndrome↗

PubMed1996

News media framing sets public opinion that drugs is the country's most important problem.

Responses by the public to the question of whether drugs was the United States' most important problem ranged from under 5% to over 60% during the 9 years from 1985 to 1994. Time series analysis showed that changes in this opinion could be explained by the press describing drugs as a crisis. Other types of drug discussion contributed negligibly. In the reverse direction, public opinion about drugs was a weak but significant contributor to press coverage.

Data Collection↗

PubMed1995

Glial reaction after pyramidotomy in mice and rats.

Adult mice and rats were sacrificed by perfusion between 2 and 90 days after right pyramidotomy to study the microglial and astroglial response in the brain and spinal cord. The microglia were detected immunohistochemically with OX-42, OX-18 and OX-6 to assess respectively the expression of complement type 3 receptor, and major histocompatibility class I and class II antigens. Cell counting was also carried out in some animals to determine the possible proliferation of glial cells in the corticospinal tract and around layer V neurons in the cerebral cortex. Some operated animals were given rhodamine B isothiocyanate injection to investigate whether macrophages/monocytes could have migrated from the blood stream to the reactive area. The glial response around the cell bodies of layer V neurons in the ipsilateral cerebral cortex did not display any noticeable difference compared with that of the contralateral side and of the cerebral cortex of the sham-operated and normal control animals. In the cervical and lumbar cord segments of the operated animals, reactive microglial cells in the contralateral corticospinal tract appeared as early as 2 days post pyramidotomy (PP) in rats and 4 days PP in mice. Activation of microglial cells lasted up till 35 days PP, showing gradual increase in immunoreactive staining and hypertrophy. After that, the microglial immunoreactivity subsided and the cells assumed normal appearance by 90 days PP. Quantitative analysis showed a marked increase in the number of microglial cells in the contralateral CST up till 60 days PP. In mice, at 6 days PP, astroglial cells were hypertrophic and more intensely stained but showed no increase in number. No noticeable changes were noted in the astroglia of the rats throughout the period studied. Rhodamine-labelled cells were found at the lesion site, but not in layer V of the cerebral cortex, nor in the corticospinal tract. Though different glial reactions in the degenerating corticospinal tract were noted in mice and rats, there was the same apparent lack of glial reaction around the cell bodies of layer V neurons in the two animal species. Such lack of significant glial response is different from the vigorous glial response around the cell bodies of peripherally projecting neurons demonstrated in previous work. The possible mechanisms for such difference and the implication of the difference in axonal regeneration were discussed.

Animals↗

PubMed1994

Optimization of simulation models with GADELO: a multi-population genetic algorithm.

In this paper, a new Genetic Algorithm based on the Dynamic Exploration of Local Optima (GADELO) was used to estimate the parameters of the MRD (Micro-population model of Risk-group Dynamics) micro-population model for smoking cessation by minimizing a deviation function between the model's predictions and the smoking cessation data of the Multiple Risk Factor Intervention Trial (MRFIT). The efficiency and accuracy of the GADELO estimations were consistently superior to those obtained using the standard genetic algorithm or the simplex algorithm of Nelder-Mead.

Algorithms↗

PubMed1993

Quantitative estimates for the effects of AIDS public education on HIV infections.

Previous projections of HIV infection have not accounted explicitly for AIDS public information. The present analysis does so, using computer content analysis of AIDS news stories to make time trend forecasts of both HIV infection and knowledge, attitudes, and sexual behaviors relevant to AIDS. The data show that there was a rapid rise in infections before public information took effect. Then news about AIDS, its modes of transmission and high risk groups led to a 3-4-fold decrease in high risk sex among gay/bisexual men by the late 1980s. The result was a diminished infection rate saving 580,000 to 1.9 million lives. In more recent times, rates of HIV infection are forecast to increase again, although slowly, in small part because people are less prudent and in large part because the pool of infected individuals has greatly expanded.

Acquired Immunodeficiency Syndrome↗

PubMed1992

Time trends of smoking cessation: a micro-population computer simulation model.

The Micro-population model of Risk-group Dynamics (MRD) approaches smoking behavior at the level of the individual and integrates physiological and social factors to describe the evolution of behavior change in the population. MRD is innovative in several ways: (1) the model describes mathematically the interactions among these behavioral factors; (2) the model accounts for both the variability of these factors among different persons and the universality of basic rules describing these factors in all individuals; and (3) the model can be applied to various types of populations and a wide range of intervention strategies. MRD combines the physiological, psychological and social determinants into a hazard function for relapse to smoking. This hazard function is then organized into a three term expression incorporating: a baseline hazard characteristic to each individual, a decreasing term for the diminishing aspect of the initial hazard and an effect of external interventions. The model gives promising results when applied to the Multiple Risk Factors Intervention Trial (MRFIT) data using the assumptions of a Weibull distribution for the baseline hazard, a negative exponential for the decrease in the initial hazard and a constant intensity for the external intervention.

Algorithms↗

PubMed1992

The media and the fate of the Medicare Catastrophic Extension Act.

We examine the Medicare Catastrophic Extension Act of 1988, which was repealed in 1989, finding a broad range of messages on this controversial legislation in the press. The time needed to craft compromise legislation in response to objections to the original bill was cut short by the impending deadline for payments by the elderly, January 1990. Outright repeal rather than modification was the result. Our study confirms earlier studies, which show that trends of opinion--in this case that of senior citizens over 65 years of age--could be forecast from mass media stories, and is consistent with the notion that legislation occurs in a climate shaped by the media. In addition to being a key conduit for passing information and pressures to the public and lawmakers, the media could also serve to indicate the impact of messages passed through other channels, such as direct mailings.

Aged↗

PubMed1990

Use of open-ended essays and computer content analysis to survey college students' knowledge of AIDS.

This study used computer content analysis of written essays to explore university students' knowledge and attitudes about AIDS. Because the essays were long, averaging 650 words each, and were on the very general topics of what individuals and society should do about AIDS, it was possible to study a wide variety of subjects. Computer scoring of the essays showed that education and individual changes in sexual behavior were the two methods of prevention mentioned most often. The majority of students accurately identified the most important methods of transmitting the disease. Only one fourth of the respondents discussed casual contact; a majority of those knew that the disease could not be transmitted in this manner. A minority of the students advocated isolating people infected with HIV or marking these individuals in ways that are accessible to others in society. The new computer methods used to analyze the essays offer flexible and efficient procedures for analyzing text on a variety of topics.

Acquired Immunodeficiency Syndrome↗

PubMed1989

Mathematical model for addiction: application to multiple risk factor intervention trial data for smoking.

Describes habituation and addiction, both psychological and physiological, using the simple equations of the mathematical model of ideodynamics. The parameters in these equations were optimized to smoking data from the Multiple Risk Factor Intervention Trial (MRFIT) program. With only 4 constant parameters, it was possible to calculate accurate time trends for recidivism to smoking among quitters, time trends for secondary cessation among recidivists, and final percentage of smokers in a population with both recidivism and secondary cessation occurring simultaneously. These same parameters further permit predictions for the long-range success of intervention programs to decrease substance dependency. Ideodynamics can also predict time trends of public opinion based on stories in the mass media.

Behavior Therapy↗

PubMed1986

Differences in antigen presentation to MHC class I-and class II-restricted influenza virus-specific cytolytic T lymphocyte clones.

We have examined requirements for antigen presentation to a panel of MHC class I-and class II-restricted, influenza virus-specific CTL clones by controlling the form of virus presented on the target cell surface. Both H-2K/D- and I region-restricted CTL recognize target cells exposed to infectious virus, but only the I region-restricted clones efficiently lysed histocompatible target cells pulsed with inactivated virus preparations. The isolated influenza hemagglutinin (HA) polypeptide also could sensitize target cells for recognition by class II-restricted, HA-specific CTL, but not by class I-restricted, HA-specific CTL. Inhibition of nascent viral protein synthesis abrogated the ability of target cells to present viral antigen relevant for class I-restricted CTL recognition. Significantly, presentation for class II-restricted recognition was unaffected in target cells exposed to preparations of either inactivated or infectious virus. This differential sensitivity suggested that these H-2I region-restricted CTL recognized viral polypeptides derived from the exogenously introduced virions, rather than viral polypeptides newly synthesized in the infected cell. In support of this contention, treatment of the target cells with the lysosomotropic agent chloroquine abolished recognition of infected target cells by class II-restricted CTL without diminishing class I-restricted recognition of infected target cells. Furthermore, when the influenza HA gene was introduced into target cells without exogenous HA polypeptide, the target cells that expressed the newly synthesized protein product of the HA gene were recognized only by H-2K/D-restricted CTL. These observations suggest that important differences may exist in requirements for antigen presentation between H-2K/D and H-2I region-restricted CTL. These differences may reflect the nature of the antigenic epitopes recognized by these two CTL subsets.

Animals↗

PubMed1984

Chromatographic separation from known cytokines of a helper factor necessary for the generation of murine cytolytic T lymphocytes.

A helper factor (CHF) necessary for the generation of primary allospecific CTL using BALB/c (H-2d) responder spleen cell and x-irradiated RDM4 (H-2k) stimulator tumor cells was obtained from cultures of mouse spleen cells stimulated for the production of secondary anti-Sendai virus CTL and fractionated by gel filtration chromatography to obtain a 30,000 m.w. species (CHF30). DEAE-cellulose chromatography separated CHF activity from the majority of interleukin 1 (IL 1), interleukin 2 (IL 2), granulocyte-macrophage colony-stimulating factor (CSF), and interferon (IFN). Interleukin 3 (IL 3) and CHF co-eluted when this procedure was used. Reverse-phase high performance liquid chromatography (HPLC) of CHF30 with a variety of elution conditions allowed the separation of CHF activity from IL 1, IL 2, IL 3, CSF, and IFN. IL 3 and CSF in the CHF30 preparation were stable at 80 degrees C for more than an hour, whereas CHF activity decreased rapidly during the first 10 min of incubation. Trypsin treatment of the same material showed that CHF activity was resistant to digestion for 40 min, whereas IL 3 and CSF lost most of their activities during the first 5 min of incubation. These results indicate that CHF activity is mediated by molecules biologically and biochemically distinct from the well characterized cytokines.

Animals↗

PubMed1984

Stimulation of anti-influenza cytolytic T lymphocytes by a synthetic peptide of the influenza hemagglutinin can be modulated by at least three independent helper factors.

Secondary murine anti-influenza cytolytic T lymphocytes (CTL) could be induced in vitro by the chemically synthesized peptide HA1(181-204), corresponding to amino acids 181-204 of the hemagglutinin molecule of influenza strain A/Japan/305/57. This stimulation required the addition of exogenous helper factors, termed CHFP, which could be obtained from supernatant fluids of the WEHI-3 cell line or spleen cells stimulated by either concanavalin A or Sendai virus. Because the activities from these three sources could reflect different molecules, they were referred to as CHFPW, CHFPC, and CHFPS, respectively. When CHFPS was fractionated by using reverse-phase high performance liquid chromatography (HPLC), the CHFP activity was found to elute at two hydrophobicities. The more hydrophilic factor(s) was designated CHFPS1, while the more hydrophobic factor(s) was called CHFPS2. Similarly, CHFPW could be separated into more hydrophilic (CHFPW1) and more hydrophobic (CHFPW2) molecules. In contrast, CHFPC molecules eluted at only one hydrophobicity (CHFPC1). Based on HPLC characteristics, CHFPS1, CHFPW1, and CHFPC1 all could reflect the same molecule. That molecule could be interleukin 3 (IL 3), because IL 3, purified to homogeneity, was also found to function in the CHFP assay. In contrast, CHFPW2 and CHFPS2 had different hydrophobicities. Therefore, a possibility exists that there are a minimum number of three factors functional in the CHFP assay: IL 3, CHFPW2, and CHFPS2. Based on HPLC separations, CHFPS2 represents a molecule distinct from biochemically characterized cytokines implicated previously in the generation of CTL:CHF, CSF, interferon, and interleukins 1, 2, and 3. The killer cells stimulated are both virus-specific and H-2-restricted as is characteristic of CTL.

Animals↗

PubMed1984

Cytolytic T lymphocyte and antibody responses to synthetic peptides of influenza virus hemagglutinin.

Two peptides corresponding to HA1(181-204) and HA2(103-123) of the A/Japan/305/57 influenza virus hemagglutinin (HA) were chemically synthesized by solid-phase methods and were tested for their ability to generate murine secondary anti-influenza cytolytic T lymphocytes (CTL) in vitro and to bind monoclonal anti-HA antibodies. Peptide HA1(181-204) could only generate CTL in the presence of helper factors contained in supernatant fluids from either Concanavalin A-stimulated mouse spleen cultures or WEHI-3 cells grown in vitro. Peptide HA2(103-123) stimulated the induction of anti-influenza CTL independent of helper factors, but the stimulation was also greatly increased if helper factors were added. A 10-fold molar excess of peptide HA2(103-123) was required to obtain optimal CTL activation over the quantities required in the HA1(181-204) system. This molar ratio remained unchanged, even in the presence of helper factors. Induction of influenza-specific CTL was antigen-dependent in both systems, even though some killing of noninfected target cells was also occasionally observed. Our results suggest that synthetic peptides can be recognized as antigenic determinants in the generation of H-2-restricted anti-viral CTL capable of killing appropriately infected target cells. The inability of peptide HA1(181-204) to generate sufficient help for CTL development suggests that certain regions of the HA can be recognized by CTL precursors, but not by all of the required helper cells. Peptide HA1(181-204) also reacted with three monoclonal anti-HA antibodies as well as mouse anti-influenza (A/Japan/305/57) immune sera. This antibody reactivity suggests the possibility of a shared antigenic epitope or region between T and B cells, and therefore provides new insight in our understanding of viral antigenicity.

Animals↗

PubMed1984

Interleukin 3 augments the murine primary cytolytic T lymphocyte response to allogeneic tumor cells.

The primary anti-H-2k allospecific cytolytic T lymphocyte (CTL) response by BALB/c (H-2d) spleen cells in vitro to x-irradiated RDM4 (H-2k) tumor cells is weak. This response has been shown to be augmented by CTL helper factor (CHF), a factor present in supernatants of spleen cells cultured with Sendai virus (SC-CM). Conditioned medium from WEHI-3 cells (WEHI-CM) also contains activity that augments the BALB/c anti- RDM4 CTL response. Attempts to separate the CHF activity from interleukin 3 (IL 3), also present in WEHI-CM, were unsuccessful. Purified IL 3 was then tested, and was found to increase the BALB/c anti- RDM4 CTL response by five- to 10-fold. IL 3 is apparently the only material in WEHI-CM that is active in this assay. The response is apparently a classical CTL response because: 1) the effector cells are sensitive to monoclonal anti-Thy-1.2 antibody plus C; 2) the response is dependent on antigen stimulation, and it peaks on day 5 or 6 of culture; and 3) the effector cells are specific for H-2k targets. IL 3 must be added very early during the in vitro culture period for maximal augmentation of the response, consistent with possible action of IL 3 as a differentiation factor.

Animals↗

PubMed1984

A helper factor needed for the generation of mouse cytolytic T lymphocytes is made by tumor cell lines, cloned T cells, and spleen cells exposed to a variety of stimuli.

A helper factor termed cytolytic T lymphocyte helper factor (CHF) that is needed for the generation of allospecific mouse cytolytic T lymphocytes (CTL) in vitro was produced by mouse spleen cells 3 to 4 days after the time when interleukin 2 (IL 2) had reached its maximal production. These kinetics were observed by stimulation of immune spleen cells with allogeneic tumor or spleen cells, with Sendai or influenza viral peptides, with virus infected cells, or with concanavalin A (Con A). CHF produced by rat spleen cells was able to help in the generation of mouse CTL, indicating that this cytokine was not restricted genetically. CHF could also be made by WEHI-3 and EL4 cell lines, as well as cloned cytolytic and helper T cells. The production of CHF by WEHI-3 cells argues that CHF is not IL 2. In addition, if CHF was not present early in the in vitro stimulation no CTL were generated, suggesting that CHF participated in the activation of CTL precursors. The addition of IL 2-containing conditioned medium to the CHF assay resulted in no substantial CTL generation, although significant cellular proliferation was observed. In contrast, CHF-containing conditioned medium allowed the generation of CTL in the absence of the same level of proliferation.

Animals↗

PubMed1983

Characterization of helper factors distinct from interleukin 2 necessary for the generation of allospecific cytolytic T lymphocytes.

The in vitro generation of primary murine allospecific cytolytic T lymphocytes (CTL) from BALB/c (H-2d) spleen cell precursors in response to x-irradiated RDM4 (H-2k) tumor cells did not occur unless the cultures were supplemented with exogenous helper factors. Such CTL helper factors (CHF) could be provided by conditioned medium from cultures in which Sendai virus-immune BALB/c spleen cells were stimulated either with Sendai-infected cells (SC-CM) or with peptides cleaved by CNBr from intact virions (SP-CM). CHF activity stimulated by both antigens reached a maximum after day 3 of culture. In contrast, interleukin 2 (IL 2) activity peaked at day 2 and had essentially disappeared by day 4. Fractionation of day-4 SC-CM and SP-CM preparations by gel filtration revealed peaks of activity at apparent m.w. of 17,000 (CHF17) and 30,000 (CHF30). Under certain conditions, a peak of CHF activity appeared in the void volume with an apparent m.w. of 75,000 or greater. These results indicate that CHF activity is mediated by molecules distinct from IL 2.

Animals↗

PubMed1983

Isolation and characterization of a CNBr cleavage peptide of influenza viral hemagglutinin stimulatory for mouse cytolytic T lymphocytes.

A polypeptide fragment obtained by CNBr cleavage of the hemagglutinin from A/JAPAN/305/57 influenza virus has been purified by using high performance liquid chromatography. The first five N-terminal amino acids as determined by sequential Edman degradations have localized this peptide to the HA2 subunit of the hemagglutinin between residues 103 and 123. This peptide, denoted HA2(103-23), can generate both proliferative and cytolytic responses from spleen cells of BALB/c mice previously immunized with A/JAPAN/305/57. These results demonstrate that a single nonglycosylated fragment of the influenza hemagglutinin as small as 21 amino acid residues is capable of being recognized as an antigenic determinant to generate influenza CTL from primed precursors.

Amino Acid Sequence↗

PubMed1982

Purification of the peptidoglycan transglycosylase of Bacillus megaterium.

The peptidoglycan transglycosylase of Bacillus megaterium has been purified approximately 500-fold from a crude membrane fraction. This protein is likely to be the one previously called PG-II and was assayed by its ability to reconstitute with a crude phospho-N-acetyl-muramyl-pentapeptide translocase preparation and partially purified N-acetylglucosaminyl transferase to give peptidoglycan synthesis from nucleotide precursors. The protein was identified as the peptidoglycan transglycosylase by its ability to synthesize lysozyme-sensitive peptidoglycan from undecaprenylpyrophosphoryl-disaccharide-pentapeptide. The enzyme is inhibited by vancomycin but not by bacitracin, penicillin G, or tunicamycin. The enzyme has no detectable transpeptidase activity, but it does bind penicillin.

Anti-Bacterial Agents↗