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Biomedical subjects

D A Pearson

Publications and source records attributed to D A Pearson.

At least 55 records · Page 3Linked to original sources
PubMed1994

Interleukin-2 inhibits graft-versus-host disease-promoting activity of CD4+ cells while preserving CD4- and CD8-mediated graft-versus-leukemia effects.

We have recently shown that a short course of high-dose interleukin-2 (IL-2) can markedly inhibit the graft-versus-host disease (GVHD)-promoting activity of donor CD4+ T cells. The difficulty in dissociating GVHD-promoting from graft-versus-leukemia (GVL) effects of alloreactive donor T cells currently prevents clinical bone marrow transplantation (BMT) from fulfilling its full potential. To test the capacity of IL-2 treatment to promote such a dissociation, we have developed a new murine transplantable acute myelogenous leukemia model using a class II major histocompatibility complex-positive BALB/c Moloney murine leukemia virus-induced promonocytic leukemia, 2B-4-2. BALB/c mice receiving 2.5 x 10(5) 2B-4-2 cells intravenously 1 week before irradiation and syngeneic BMT died from leukemia within 2 to 4 weeks after BMT. Administration of syngeneic spleen cells and/or a 2.5-day course of IL-2 treatment alone did not inhibit leukemic mortality. In contrast, administration of non-T-cell-depleted fully allogeneic B10 (H-2b) spleen cells and T-cell-depleted B10 marrow led to a significant delay in leukemic mortality in IL-2-treated mice. In these animals GVHD was inhibited by IL-2 treatment. GVL effects were mediated entirely by donor CD4+ and CD8+ T cells. Remarkably, IL-2 administration did not diminish the magnitude of the GVL effect of either T-cell subset. This was surprising, because CD4-mediated GVHD was inhibited in the same animals in which CD4-mediated GVL effects were not reduced by IL-2 treatment. These results suggest a novel mechanism by which GVHD and GVL effects of a single unprimed alloreactive T-cell subset can be dissociated; different CD4 activities promote GVHD and GVL effects, and the former, but not the latter activities are inhibited by treatment with IL-2.

Animals↗
PubMed1994

Ratings of hyperactivity and developmental indices: should clinicians correct for developmental level?

This study assessed the relationship between parent and teacher ratings of hyperactivity and developmental indices (chronological age, IQ, and mental age) in two groups of children. Subjects were drawn separately from two psychiatric clinics: (a) a general clinical sample, largely of normal ability, seen for a multitude of psychiatric and behavioral problems, and (b) a developmental clinic sample, comprising children with cognitive delays and seen for ADHD or the absence of ADHD. The results showed consistent negative correlations between chronological age and severity of hyperactivity symptoms; however, these occurred mainly within the developmental clinic sample. Only 4 of 27 comparisons (15%) between mental age and hyperactivity ratings (all confined to the developmentally delayed sample) showed a significant correlation. When chronological age was first partialled out, the correlations between ratings of hyperactivity and mental age ceased to be significant. Findings suggest that chronological age should be taken into consideration when behavior ratings are used to assess cognitively delayed children for ADHD. However, the results do not support guidelines stating that mental age must be used to determine which norms should be applied when such children are evaluated clinically.

Adolescent↗
PubMed1994

Strain dependence of interleukin-2-induced graft-versus-host disease protection: evidence that interleukin-2 inhibits selected CD4 functions.

Treatment of lethally irradiated mice with a short course of high-dose interleukin (IL)-2 markedly inhibits acute and chronic graft-versus-host disease (GVHD), while preserving a graft-versus-leukemia (GVL) effect of allogeneic T-cells. We recently demonstrated that this GVL effect, observed with the EL4 leukemia/lymphoma in the A/J-->B10 strain combination, was mediated by CD8+ A/J T-cells in a CD4-independent fashion. IL-2 inhibited only the activity of CD4+ cells, and not that of CD4-independent CD8+ T-cells in A/J spleen cell inocula. This inhibition of CD4 function was sufficient to markedly inhibit GVHD, thus explaining the dissociation of GVHD and GVL in IL-2-treated mice. We have now performed studies to determine the capacity of IL-2 to inhibit GVHD induced across a variety of different histocompatibility barriers. IL-2 significantly delayed GVHD mortality in three of four additional fully major histocompatibility complex (MHC) plus minor-disparate strain combinations when CD4+ T-cells were given. Numbers of CD8+ T-cells comparable to those that might contaminate human marrow demonstrated a relatively poor capacity to produce acute GVHD when given without CD4+ cells in all of three additional strain combinations evaluated. In one of these strain combinations (B10-->BALB/c), IL-2 protected against acute but not chronic GVHD mortality when CD4+ cells were given with or without CD8+ cells. In one fully allogenic strain combination, B10-->A/J, IL-2 did not inhibit the GVHD produced by CD4+ cells given with or without CD8+ cells. IL-2 was unable to inhibit CD8-mediated GVHD in strain combinations differing at isolated class I MHC loci. In a strain combination differing only at multiple minor histocompatibility antigen (HA) loci, B10-->C3H.SW, GVHD was largely CD8-dependent, but IL-2 did not inhibit the small CD4-mediated component of GVHD. Together, these results suggest that IL-2 inhibits a restricted subset of CD4 cells or functions, and that the type of CD4 activities mediating GVHD is determined by the particular histoincompatibilities between donor and host.

Animals↗
PubMed1993

Hematopoietic cells and radioresistant host elements influence natural killer cell differentiation.

Radioresistant host elements mediate positive selection of developing thymocytes, whereas bone marrow-derived cells induce clonal deletion of T cells with receptors that are strongly autoreactive. In contrast to T cell development, little is known about the elements governing the natural killer (NK) cell repertoire, which, similar to the T cell repertoire, differs between individuals bearing different major histocompatibility complex (MHC) phenotypes. We have used murine bone marrow transplantation models to analyze the influence of donor and host MHC on an NK cell subset. We examined the expression of Ly-49, which is strongly expressed on a subpopulation of NK cells of H-2b mice, but not by NK cells of H-2a mice, probably because of a negative effect induced by the interaction of Ly-49 with Dd. To evaluate the effect of hematopoietic cell H-2a expression on Ly-49 expression of H-2b NK cells, we prepared mixed allogeneic chimeras by administering T cell-depleted allogeneic (B10.A, H-2a) and host-type (B10, H-2b) marrow to lethally irradiated B10 mice, or by administering B10. A marrow to B10 recipients conditioned by a nonmyeloablative regimen. Expression of H-2a on bone marrow-derived cells was sufficient to downregulate Ly-49 expression on both H-2a and H-2b NK cells. This downregulation was thymus independent. To examine the effect of H-2a expressed only on radioresistant host elements, we prepared fully allogeneic chimeras by administering B10 bone marrow to lethally irradiated B10.A recipients. B10 NK cells of these fully allogeneic chimeras also showed downregulation of Ly-49 expression. The lower level of H-2a expressed on H-2b x H-2a F1 cells induced more marked downregulation of Ly-49 expression on B10 NK cells when presented on donor marrow in mixed chimeras than when expressed only on radioresistant host cells. Our studies show that differentiation of NK cells is determined by interactions with MHC molecules expressed on bone marrow-derived cells and, to a lesser extent, by MHC antigens expressed on radioresistant host elements.

Animals↗
PubMed1993

IL-2 reduces graft-versus-host disease and preserves a graft-versus-leukemia effect by selectively inhibiting CD4+ T cell activity.

We have recently demonstrated, in a fully MHC-mismatched murine bone marrow transplantation model, that administration of a short course of high dose IL-2 markedly diminishes graft-vs-host disease (GVHD) without compromising alloengraftment or the graft-vs-leukemia (GVL) effect of allogeneic T cells. We have now evaluated the mechanism of the dissociation of GVL and GVHD observed in this model. We demonstrate that CD4+ T cells were required to produce severe, acute GVHD in the fully MHC-mismatched plus minor histocompatibility Ag-mismatched A/J-->B10 strain combination. The GVHD-producing activity of A/J CD4+ T cells administered without CD8+ T cells was inhibited by IL-2 treatment. In contrast, CD8+ T cells alone mediated the GVL effect observed in the EL4 leukemia/lymphoma model, and CD4+ cells did not contribute to this effect. This CD8-mediated GVL activity was not inhibited by IL-2 treatment. Because naive A/J CD8+ T cells administered without CD4+ T cells did not produce acute GVHD, we were unable to evaluate the effect of IL-2 in this model. However, when A/J donors were presensitized with B10 skin grafts, CD4-depleted A/J spleen cells were capable of causing acute GVHD in B10 recipients. This CD8-mediated GVHD was not inhibited by treatment with IL-2. However, IL-2 did partially inhibit the GVHD produced by nondepleted presensitized A/J spleen cells, probably due to selective inhibition of the function of presensitized A/J CD4+ T cells. The dissociation of GVHD and GVL against the EL4 leukemia/lymphoma in IL-2-treated mice can therefore be explained by selective inhibition by IL-2 of CD4 activity.

Animals↗
PubMed1993

Specific prolongation of skin graft survival following retroviral transduction of bone marrow with an allogeneic major histocompatibility complex gene.

Engrafted allogeneic hematopoietic cells have a unique capacity to induce a state of donor-specific transplantation tolerance across major histocompatibility complex barriers. This state allows permanent acceptance of donor-type organ grafts, with otherwise normal immunocompetence. We hypothesized that introduction of allogeneic MHC genes into autologous bone marrow which is then returned to recipient mice might similarly induce specific tolerance to products of the introduced MHC genes, without the risk of graft-vs-host disease. We demonstrate here that the introduction of MHC class I Kb cDNA by retrovirus-mediated gene transfer into B10.AKM (Kk) hematopoietic cells confers specific hyporesponsiveness to allogeneic skin grafts expressing Kb.

Amino Acid Sequence↗
PubMed1992

Integrating a curriculum: the role and function of a capstone course.

The rationale for establishing a strategy to integrate learning within a health administration curriculum is presented. Strengths and weaknesses associated with six models are presented which examine the student, market, internship/practicum, case course, and thesis/major paper as integrators as well as the self-integrating curriculum. The capstone course is presented as a hybrid of multiple models with a unique educational philosophy. The concept of the capstone course is examined with specific reference to design parameters associated with the capstone course used in the health management and policy curriculum at the University of New Hampshire. Suggestions and issues for faculty to consider as they develop a capstone course are also included.

Curriculum↗
PubMed1992

Alloengraftment in IL-2-treated mice.

Despite major advances, graft-versus-host disease (GVHD) remains a major obstacle to clinical bone marrow transplantation. Prophylaxis by T cell depletion is associated with increased rates of engraftment failure and leukemic relapse. Treatment with high-dose IL-2 can markedly protect lethally irradiated mice from GVHD-related mortality, especially when T cell-depleted (TCD) syngeneic bone marrow cells (BMC) are co-administered. In these IL-2-protected animals, allogeneic reconstitution is observed, and a graft-versus-leukemia effect of allogeneic T cells is preserved. To determine whether IL-2 might increase alloresistance under conditions in which alloengraftment is more difficult to achieve, we have now evaluated the possible effect of IL-2 on: (1) competitive repopulation of lethally irradiated mice by mixtures of TCD allogeneic and TCD syngeneic BMC; (2) radiation protection by TCD allogeneic BMC; (3) timing of hematologic recovery; and (4) allogeneic engraftment in sublethally irradiated recipients. The results show that IL-2 has only a limited and strain-restricted effect on alloengraftment. This effect may reflect activation of alloresistant host natural killer cells, a cell population which is not essential for the protective effect of IL-2 against GVHD.

Animals↗
PubMed1991

Auditory attention switching in hyperactive children.

The ability to rapidly reorient attention in the auditory modality was studied in hyperactive children. Hyperactive and nonhyperactive subjects matched on age, sex, and IQ listened to dichotically presented lists for prespecified targets. Reorientation was studied by comparing performance on trials requiring subjects to reorient their attention during a list to performance on trials requiring no switching of attention. The results indicate that although nonhyperactive children were temporarily disrupted by the switch, they eventually reoriented to the cued ear. In contrast, once hyperactive children were disrupted by the switch, they did not reorient to the cued ear. As the pattern in performance comparing hyperactive and nonhyperactive subjects resembles the pattern previously found in comparing younger and older subjects, these results are consistent with the hypothesis that the auditory reorientation skills of hyperactive children are developmentally immature.

Acoustic Stimulation↗
PubMed1991

Auditory attention switching: a developmental study.

The developmental course of the ability to rapidly allocate attention was studied using a dichotic listening task with 8-year old, 11-year old and college age subjects. In this task, subjects were instructed to listen to one ear for predescribed targets and then were later signaled (on some trials) to switch their attention to the other ear. Reorientation was assessed by comparing the pattern of subjects' omission and intrusion errors on trials following a command to switch ears with the pattern of errors on no-switch trials. Older subjects were better able to reallocate their attention in accordance with task demands, with the greatest gains in performance occurring between ages 8 and 11. This developmental change appears to be generally continuous and quantitative in nature. Since successful performance of this task requires flexibility in subjects' ability to control their focus of attention, these results support the hypothesis that the basis of the developmental improvement in the ability to ignore irrelevant information is linked to the ability to use active attentional strategies.

Adolescent↗
PubMed1991

The development of psychiatric symptomatology in patients with cystic fibrosis.

Psychiatric symptomatology was compared in 61 cystic fibrosis patients, ages 8 to 15 years, and 36 cystic fibrosis patients, ages 16 to 40 years. When the prevalence of psychiatric symptomatology was compared in the two groups, a developmental pattern emerged: Symptoms of depression and anxiety were more frequent in the older group, while symptoms associated with eating disorders were more frequent in the younger group. Although duration of illness was longer and severity of illness was greater in the older group, these factors were largely unrelated to psychiatric symptomatology in either group. It is hypothesized that younger patients may express psychological distress through less direct means than older patients.

Adaptation, Psychological↗
PubMed1990

Infection control practices in Connecticut's skilled nursing facilities.

Questionnaires were sent to all skilled nursing homes in Connecticut as part of a larger study of nosocomial infections, infection risks, and infection control programs. This article describes surveillance practices, isolation practices, control measures, and employee health activities of skilled nursing homes in Connecticut. The overwhelming majority of skilled nursing homes used written criteria to determine nosocomial infections, and all undertook surveillance; the majority did surveillance at least weekly and 21% did on a daily basis. The most frequent source of information for reporting infections were microbiology reports and information from the charge nurse. Three fourths of the skilled nursing homes stated that the responsibility of reporting communicable disease is that of the infection control practitioner. Two thirds of the skilled nursing homes stated that they had policies on the reporting of isolation practices, including the refusal or acceptance of patients with infections; 38% had residents under isolation precautions. Of all the patient care control measures, only that of changing urinary catheters on a routine basis was associated with facility size. More than 90% of facilities reported having an employee health program, but the benefit was limited.

Connecticut↗
PubMed1990

Infection control practitioners and committees in skilled nursing facilities in Connecticut.

All skilled nursing facilities (SNFs) in Connecticut were surveyed and more than 71% responded to a Centers for Disease Control-funded project, a component of which is reported herein. The study describes the infection control practitioner (ICP), assistance provided ICPs from external sources, and infection control committees. Almost all ICPs received some training in infection control and worked in the field for an average of 3 1/2 years. Both the number of hours devoted to infection control and the percentage of time spent by the ICP on infection control activities increased with the size of the facility. More than one half of the ICPs in SNFs have relationships with hospital ICPs. The majority of SNF infection control committees met quarterly. The chairperson most often was a physician, although ICPs held this office in almost one third of the reporting SNFs. We conclude that ICPs in Connecticut SNFs have increased in number and that they devote more time and effort to infection control than in previous years.

Aged↗
PubMed1990

Visual attention movements: a developmental study.

The pattern of attention movements underlying reorientation of visual selective attention independent of eye movements was studied developmentally in 2 experiments. In Experiment 1, 8-year-old, 11-year-old, and college-age subjects first oriented their attention to a central location and were then cued to direct their attention either to the left or the right peripheral field. Following variable intervals, the target appeared at the cued location and reaction times were recorded. The data were interpretable in terms of the attentional spotlight theory since there was an interaction between distance of the target from fixation and SOA. In terms of this theory, the data indicate that the velocity of attention movements increases throughout the age range studied. Experiment 2, in contradiction to attentional spotlight theory, failed to find evidence of an interaction between distance and SOA. This experiment suggested that young children can covertly orient their attention by including valid, neutral, and invalid cues, and that these cues can both facilitate and inhibit attentional orientation. This experiment also extended the findings to central as well as peripheral cues.

Adolescent↗
PubMed1989

"Red man syndrome" with vancomycin: report of case.

Vancomycin is a recommended alternative prophylactic antibiotic for penicillin-allergic patients with prosthetic mitral valves. During the course of recommended treatment, a drug reaction known as "red man syndrome" was encountered. Because vancomycin is appropriate for some dental situations, the general practitioner should be acquainted with its use and possible side effects.

Adult↗
PubMed1983

Synthesis and bacterial metabolism of cis- and trans-2-alkyl analogues of sodium cyclamate.

Sodium cyclamate is an effective artificial sweetner, which has been banned from the U.SD. market because of alleged carcinogenic properties. It appears that cyclohexylamine, liberated from cyclamate as a result of bacterial mtabolism, is the proximate carcinogen. In an effort to elucidate the extent to which analogues of cyclamate would enter into the bacterial metabolic pathway, as well as any stereochemical requirements which might exist, several 2-alkaly analogues of sodium cyclamate were prepared. It was found that trans-N-(2-methylcyclohexyl)sulfamate (trans-2a) and trans-N-(2-ethylcyclohexyl)sulfamate were hydrolyzed by freshly collected fecal suspensions from rats fed cyclamate, but not from control rats, at the same rate as cyclamate itself. trans-N-(2-Isopropylcyclohexyl)sulfamate (trans-2c) was not hydrolyzed at all. Surprisingly, two of the analogous cis compounds (cis-2a and cis-2c, respectively) were hydrolyzed by fecal suspensions from control, as well as from cyclamate-fed, rats. Moreover, cis-2a was hydrolyzed by incubating it in medium only. Thus, it is apparent that stereochemical influences on the chemical properties of these compounds are substantial. These results do not appear to point the way toward a safe, nonmetabolizable sweetening agent.

Animals↗