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D V Dawson

Publications and source records attributed to D V Dawson.

At least 55 records · Page 3Linked to original sources
PubMed1993

Characterization of T cells expressing the gamma/delta antigen receptor in human renal allografts.

To investigate the role of gamma/delta+ T cells in allograft rejection, we have studied the TCR phenotype and function of lymphocytes infiltrating rejecting, rejected, and nonrejecting human renal allografts. Two-color immunohistologic staining showed that 19% of rejecting biopsies and 40% of rejected nephrectomies had significant infiltration (> 10% of the total T-cell population) with gamma/delta+ T cells. No biopsies from nonrejecting kidneys showed > 10% gamma/delta+ T cells. Flow-cytometry analysis of T-cell populations expanded from rejecting and rejected allografts demonstrated that 33% of biopsy- and 40% of nephrectomy-derived populations had significant percentages (> 10%) of gamma/delta+ T cells. Six cell lines with increased numbers of gamma/delta+ T cells were tested for cytolytic activity against the NK target cell line K562 and compared with cytotoxic activity of exclusively alpha/beta T-cell populations. Lysis was noted by all gamma/delta+, but no gamma/delta-, populations. To confirm that the cytotoxicity of these gamma/delta+ T-cell populations was not MHC directed, one nephrectomy-derived population with 69% gamma/delta+ T cells by cytometry and > 50% by immunohistology was studied extensively. High levels of killing were seen against the NK targets K562 and Daudi as well as other malignant, benign, and third-party renal cell lines, but relevant alloantigen-expressing targets were not killed. Sterile cell sorting was used to isolate the gamma/delta+ T cells. The gamma/delta+ cells displayed enhanced killing of K562 while the gamma/delta- cells showed no cytolytic activity. Cytotoxicity mediated by gamma/delta+ T cells was also demonstrated against donor-derived, untransformed renal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytotoxicity, Immunologic↗
PubMed1993

Deficit of HLA homozygotes in a Caucasian isolate.

Deficits of HLA-A, -B homozygotes observed many years ago in two inbred populations suggested negative selection against HLA homozygotes. To determine whether a similar deficiency would be observed in the S-leut Hutterites, a well-characterized Caucasian isolate of European ancestry, and to determine whether selection operated at the allele, locus, or haplotype level, observed and expected numbers of homozygotes were compared in 852 adult Hutterites. Deficits ranging from 11% to 24% were observed for all five loci examined (HLA-A, -B, -C, -DR, and -DQ). However, these deficits were secondary to, and almost completely accounted for by, a 64% loss of individuals homozygous for the haplotype. There was no evidence of deficits affecting only a single allele or locus. The data indicate strong negative selection against HLA homozygotes. This could be due, at least in part, to decreased fecundability among couples sharing HLA-DR. However, these data suggest that additional selective factors acting at the level of the haplotype also operate in this population.

Adult↗
PubMed1993

Evaluation times for patients with in-hospital strokes.

BACKGROUND: Each year at least 35,000 people suffer a stroke while hospitalized, but little is known about the clinical characteristics of such patients or how rapidly they are identified and evaluated. With a recent emphasis on the very early treatment of stroke, in-hospital stroke patients may be candidates for some early interventions. METHODS: This was a retrospective study using the stroke registries at two academic medical centers. Data were collected about the clinical characteristics of patients with an in-hospital stroke and who recognized the stroke. Detailed time data were analyzed to determine the time of stroke recognition, medical evaluation, and neurological evaluation. These specific time epochs were analyzed to determine which were responsible for any delays in stroke identification and assessment. Data were analyzed using nonparametric methods, including the Wilcoxon rank sum and Kruskal-Wallis procedure. RESULTS: Sixty-three patients were identified with in-hospital strokes and adequate time data. In-hospital stroke patients were recognized most frequently by nurses (63%) and by the patient (16%). Patients on a cardiology service and general surgery service accounted for 48% of all in-hospital strokes. The mean and median times from stroke recognition to a neurology evaluation were 14.5 and 2.5 hours, respectively. Total delays differed significantly with service and locale (P = .004). Patients on the Duke neurology service were evaluated significantly sooner (median delay, 0.5 hour) than patients on the Duke medical (median delay, 5.8 hours) or Duke surgical (median delay, 20.5 hours; P < .01 by Wilcoxon rank sum) services. Patients on the Yale surgical service were evaluated significantly sooner than patients on the Duke medical (P = .0006) or surgical (P = .0001) services. The time between physician notification and calling for a neurology evaluation accounted for > 60% of the total time delay for patients not on a neurology service. CONCLUSIONS: A substantial number of in-hospital stroke patients experience a long delay between symptom recognition and a neurological evaluation. While medical personnel are usually notified very soon after an in-hospital stroke is recognized, such patients often do not receive a rapid neurological evaluation. Additional education of hospital staff may reduce these time delays.

Cerebral Infarction↗
PubMed1993

The effects of nonsteroidal antiinflammatory drug therapy in early rheumatoid arthritis on serum levels of soluble interleukin 2 receptor, CD4, and CD8.

OBJECTIVE: Cell surface molecules can be shed by activated T lymphocytes and measured in serum to assess in vivo T cell activation. To evaluate the relationship between these serum markers and disease activity in rheumatoid arthritis (RA), we determined levels of soluble interleukin 2 receptor (sIL-2R), CD4 (sCD4), and CD8 (sCD8) in sera from a well characterized group of 26 patients with active RA treated with a nonsteroidal antiinflammatory drug (NSAID) alone. METHODS: A retrospective, blinded determination of sIL-2R, sCD4, and sCD8 levels in serum samples from patients with early, active RA participating in 2 trials of NSAID therapy. Commercially available enzyme linked immunosorbent assays were employed. Data analysis included nonparametric techniques and correction for multiple comparisons. RESULTS: The patients with RA had significantly elevated levels of sIL-2R at baseline compared with age matched healthy controls. During NSAID therapy, mean sIL-2R levels among responders decreased to lower levels while nonresponder levels increased, although these trends did not reach statistical significance. Patients with RA did not differ from controls in baseline measures of serum sCD4 or sCD8 levels. Moreover, the serum sIL-2R, sCD4, and sCD8 levels among patients did not vary significantly from their baseline measures during NSAID therapy, irrespective of response. CONCLUSION: Our results suggest that elevated levels of serum sIL-2R in early RA likely reflect generalized immune system activation, not always associated with elevated serum sCD4 or sCD8 levels or varying with other measures of disease activity in RA.

Adult↗
PubMed1993

Differential infiltration by CD45RO and CD45RA subsets of T cells associated with human heart allograft rejection.

Subsets of T cells express different isoforms of the leukocyte common antigen CD45; those expressing the glycoprotein 220 isoform (CD45RA) have been characterized as naive in their response to antigens, and those expressing the glycoprotein 180 isoform (CD45RO) as memory T cells. The association between the rejection status of human cardiac allograft recipients and the relative infiltration of the CD45 subsets of both CD8+ and CD4+ T cells was examined using two-color immunohistological labeling techniques on 33 heart transplant biopsies, categorized by routine histological and clinical criteria as mild (requiring no treatment) or moderate (requiring antirejection therapy) rejection. Double-labeling was performed using pairs of monoclonal antibodies to define the following populations: CD4+ CD45RA+, CD4+ CD45RO+, CD8+ CD45RA+, and CD8+-CD45RO+. The number of cells per high-power field (HPF) for each of these cell subsets was counted in every biopsy. In cases with mild rejection, infiltration was predominant for CD4+ CD45RA+ cells (median = 5.0 cells/HPF) relative to CD4+ CD45RO+ (3.12 cells/HPF), CD8+ CD45RA+ (2.14 cells/HPF), and especially CD8+ CD45RO+ (1.22 cells/HPF) populations. In cases with moderate rejection, all four subpopulations increased but were essentially equivalent in intensity, such that in comparison to cases with mild rejection, the smallest increase was seen for CD4+ CD45RA+ cells (6.67 cells/HPF, P < 0.09) and the greatest for CD8+ CD45RO+ cells (7.00 cells/HPF, P < 0.002). A majority of CD8 cells expressed CD45RA in 14 of 16 (88%) cases of mild rejection compared to only 2 of 17 cases of moderate rejection. Moreover, the ratio of CD45RO+ to CD45RA+ cells in each biopsy was higher in moderate versus mild rejection for both CD4 (median ratios = 1.13 versus 0.68, respectively; P < 0.008) and CD8 (1.43 versus 0.58, respectively; P < 0.005) subsets. A majority of T cells expressed CD45RO in cases of moderate rejection (11 of 14 or 79%), compared to only 1 of 13 (8%) cases of mild rejection. These findings indicate that during generally self-limited mild acute cardiac allograft rejection there is a predominance of naive CD45RA+ T cells, especially of the CD4 phenotype, whereas during moderate rejection there is a significant shift toward activated CD45RO+ T cells, especially in the CD8 population.

Biopsy↗
PubMed1992

The usefulness of the Western Aphasia Battery for differential diagnosis of Alzheimer dementia and focal stroke syndromes: preliminary evidence.

We assessed the usefulness of the Western Aphasia Battery for distinguishing the language disturbances caused by Alzheimer dementia (AD) from those caused by stroke. Using discriminant function analyses, the multiple variable "aphasia quotient--reading quotient--writing quotient" classified 29 (72.5%) of the 40 patients correctly. These 29 patients included 8 of 10 patients with left hemisphere infarction and fluent aphasia; 6 of 10 with AD; 5 of 10 patients with right hemisphere infarction; and all 10 of the neurologically normal control subjects. The patients with AD and those with right hemisphere stroke were the most difficult to classify using the aphasia battery.

Alzheimer Disease↗
PubMed1992

Renal allograft-infiltrating lymphocytes. A prospective analysis of in vitro growth characteristics and clinical relevance.

One-hundred consecutive human renal allograft Tru-cut needle biopsies were studied for in vitro proliferation of T lymphocytes under restrictive culture conditions containing low-dose recombinant interleukin 2. Each biopsy was entered into a blinded code and evaluated prospectively for visual evidence of growth at 24 hr and for sustained growth. Those T cell populations exhibiting sustained growth were then evaluated for cell surface phenotype by FACS; for allospecific cytotoxicity by 51Cr release; for a proliferative response to alloantigen by incorporation of [3H]-thymidine; and for secretion of IL-2, IL-4, IFN-gamma, and TNF-alpha in response to alloantigenic stimulation by ELISA. All results were compared with clinical diagnosis, immunosuppression at time of biopsy, diagnosis and phenotype by immunopathology, short-term outcome and long-term graft survival. Growth at 24 hr was predictive of acute cellular rejection (P less than 0.0005), unrelated to chronic rejection (P = 0.663) or maintenance immunosuppression (P = 0.911), and inversely correlated with cyclosporine toxicity (P = 0.051) and treatment with OKT3 (P = 0.014). The CD4/CD8 ratio of the sustained T cell populations was unrelated to that seen on histological examination (correlation coefficient = -0.098 and 0.044 for diffuse and aggregate infiltrates, respectively). Cytotoxic specificity for HLA class II was mediated by CD4+ cells and for HLA class I by CD8+ cells. Enhanced secretion of IL-2 in response to alloantigen distinguished those cells associated with irreversible allograft damage from those associated with complete functional recovery (P = 0.01). This study demonstrates that early evaluation of T cell proliferation in vitro identifies activated T cell infiltrates mediating acute cellular allograft rejection in a time frame suitable for clinical diagnostic application. It strengthens the concept that donor-specific cytotoxicity is governed by the stabilization of the alloantigen-T-cell receptor interaction by the accessory molecules CD4 and CD8, but either interaction is equally able to participate in an episode of acute rejection. Irreversible graft injury is associated with infiltrating cells that are capable of amplifying their responsiveness through secretion of IL-2.

CD4 Antigens↗
PubMed1992

Effects of public and professional education on reducing the delay in presentation and referral of stroke patients.

BACKGROUND AND PURPOSE: Several emerging stroke therapies require patients to be treated within several hours of symptom onset. Past studies have documented a significant delay between symptom onset and hospital presentation. As part of an experimental treatment study using tissue-type plasminogen activator, we began a multifaceted program of public and professional education to reduce the delay in presentation and referral of acute stroke patients. METHODS: The educational efforts focused on improving the recognition of stroke symptoms, the study enrollment criteria, and the need for rapid treatment of stroke patients. This program included 1) interviews on television and radio, 2) newspaper articles, 3) lectures to local and regional primary care and emergency department physicians, 4) mailings to several thousand local physicians, 5) having neurologists on-call for referrals 24 hrs/day, and 6) use of the Duke Life-Flight helicopter. RESULTS: Since starting our program, 139 of 159 (86%) patients with cerebral infarction presented primarily to our were referred to our facility within 24 hours of symptom onset, compared with 70 of 187 (37%) before our educational efforts (p less than 0.00001). No significant change was seen in patients with intracerebral hemorrhage (23 of 30 +AD77%+BD within 24 hours after program, compared with 25 of 40 +AD63%+BD before educational efforts; p = 0.30). CONCLUSIONS: These findings suggest that educational efforts aimed at the public and health professionals may increase recognition of stroke symptoms and reduce the delay in presentation and referral of stroke patients.

Cerebral Hemorrhage↗
PubMed1991

Ratings of personality change in patients being evaluated for memory disorders.

Caregivers of 35 mildly to moderately memory-impaired patients rated current and premorbid personalities with the NEO Personality Inventory. We then examined changes in the five domains of personality tapped by the NEO. There were significant changes in four of the five domains of normal personality functioning toward less conscientiousness, lower extraversion, higher neuroticism, and lower openness. The difference toward lower agreeableness was not significant when controlling for multiple comparisons. Spearman rank correlation coefficients indicated that changes in conscientiousness and vulnerability were not related to rated premorbid personality patterns and thus appear to describe shifts for all patients evaluated for memory disorders. These data suggest that personality inventories may be helpful in characterizing caregivers' observations of memory-impaired patients and thus represent a critical source of information for the clinician in charge of care.

Adult↗
PubMed1991

Serum immunoglobulin levels in systemic lupus erythematosus: the effects of age, sex, race and disease duration.

To determine whether factors other than disease activity influence immunoglobulin levels in patients with systemic lupus erythematosus (SLE), the effect of age, sex, race, and duration of disease on serum IgG and IgM levels in 170 patients with SLE were investigated. Serum IgM and IgG levels did not differ between men and women, while IgM levels were higher in whites. Serum IgG levels did not vary with age or duration of SLE. In contrast, serum IgM levels were negatively correlated with both age (r = -0.236; p = 0.002) and duration of SLE (r = 0.248; p = 0.001), and demonstrated a U-shaped age relationship, being higher in children and older patients. These patterns of immunoglobulin expression in patients with SLE contrast with those exhibited in populations of healthy individuals, suggesting that the immunoregulatory disturbances of SLE predominate over the normal mechanisms regulating levels of IgM and IgG.

Adult↗
PubMed1990

An analysis of time of presentation after stroke.

The recent development of potential therapies for acute stroke has focused attention on the time delay between stroke onset and presentation. We used the Duke/Veterans Administration stroke registry to collect data about this delay. Results were analyzed using Fisher's Exact Test and ridit analysis. Data from 457 patients at two hospitals were used. Only 42% (192/457) of patients presented within 24 hours of stroke onset, while 25% (116/457) presented within 48 hours and 33% (149/457) presented after 48 hours. Presentation time varied significantly with stroke type. A majority of patients with infarcts (64% [176/276]), stroke-in-evolution (54% [44/81]), and subarachnoid hemorrhage (54% [25/46]) did not present within 24 hours of stroke onset. Most patients with intracerebral hemorrhage (63% [34 of 54]) did present within 24 hours. Reasons for this delay may include patients' lack of awareness about the symptoms of stroke and lack of recognition of early signs by medical personnel. Because of this delay in presentation, a majority of patients may not be candidates for some therapies for acute stroke.

Acute Disease↗
PubMed1990

Extensions to sib-pair linkage tests applicable to disorders characterized by delayed onset.

Extensions of the approach to sib-pair linkage tests developed by Haseman and Elston [Behav Genet 2:3-19, 1972] are proposed which incorporate information on age of onset and age at examination. Alternate sources for the age of onset corrections are described, including models for the estimation of parameters associated with the age of onset distribution. Simulation is used to examine the performance of the approach when applied to a dominant disorder of late onset for a range of recombination fractions ranging from very tight linkage to free recombination. For each set of genetic parameters, 2,000 samples of 50 four-member sibships were generated under a complete ascertainment model to investigate power and Type I error, and to compare variants of the proposed technique. Results with and without age-of-onset correction are compared to each other and to those obtainable if penetrance were complete, i.e., if there were no intervening age-of-onset phenomenon. Results from simulation studies show that significance probabilities are enhanced in the presence of linkage when age-of-onset extensions are used. The proposed methods are associated with acceptable levels of Type I error, and substantive gains in power are obtained when data related to age of onset and age at examination are incorporated into the analysis.

Age Factors↗
PubMed1990

Expression of IgM and IgG autoantibodies in pediatric and adult systemic lupus erythematosus.

To compare patterns of autoantibody responses in pediatric and adult patients with systemic lupus erythematosus (SLE). IgG and IgM antibodies to single-stranded DNA (ssDNA), Sm, and the 70-kDa protein component of the RNP antigen (70-kDa RNP) were measured in 29 pediatric and 36 adult patients by enzyme-linked immunosorbent assays. Antibodies of either isotype to ssDNA, Sm, and 70-kDa RNP were present in 64, 58, and 79% of pediatric patients, respectively, comparable to prevalences of these autoantibodies in the adult SLE patients. Pediatric SLE patients were more likely than adult patients to have IgM anti-Sm antibodies (41.4% vs 13.9%, P = 0.02) and tended to more commonly express IgM anti-70-kDa RNP and IgM anti-ssDNA antibodies. The prominence of IgM autoantibody responses among pediatric SLE patients was shown by multiple logistic regression analysis to be related to total IgM concentrations and not related to age or duration of disease. Sequential serum samples available from several pediatric patients revealed the maintenance of similar patterns of isotype responses over time in approximately one-half of patients. In those patients whose responses changed over time, the variations in isotype expression were consistent with maturation of antibody responses of each specificity. While these results demonstrate similarities in autoimmune reactivities between pediatric and adult SLE patients, the serologic study of pediatric patients may provide an opportunity to more readily investigate the evolution of autoantibody responses.

Adolescent↗
PubMed1990

The probabilistic determination of identity-by-descent sharing for pairs of relatives from pedigrees.

Methods for detecting genetic linkage are more powerful when they fully use all of the data collected from pedigrees. We first discuss a method for obtaining the probability that a pedigree member has a given genotype, conditional on the phenotypes of his relatives. We then develop a rapid method to obtain the conditional probabilities of identity-by-descent sharing of marker alleles for all related pairs of individuals from extended pedigrees. The method assumes that the individuals are noninbred and that the relationship between genotype and phenotype is known for the marker locus studied. The probabilities of identity-by-descent sharing among relative pairs, conditional on marker phenotype information, can then be used in any of the model free tests for linkage between a trait locus and a marker locus.

Alleles↗
PubMed1989

Differential induction by interferons of major histocompatibility complex-encoded and non-major histocompatibility complex-encoded antigens in human breast and ovarian carcinoma cell lines.

Treatment of cancer cells with interferons can modulate expression of cell surface antigens, particularly those of the major histocompatibility complex (MHC). To examine the effect of recombinant gamma- and alpha-interferons on expression of non-MHC antigens, murine monoclonal antibodies have been used to quantitate 14 distinct tumor-associated cell surface antigens from five breast cancer cell lines and five ovarian cancer cell lines using a live cell radioimmunoassay. Both Class I and Class II MHC antigens could be augmented or induced with gamma-interferon. Significantly increased expression of MHC antigens was observed in nine of 10 cell lines with induction indices as high as 11-fold. When 17 non-MHC epitopes were measured on 10 cell lines, minimal (1.3-2.7-fold) induction was observed in 10 of the 170 instances evaluated. Expression of only two epitopes, 2G3 and 735B11, was increased on more than one cell line. On six cell lines expression of non-MHC epitopes could not be increased. Consequently, among many different cell surface determinants, interferons produced a highly selective augmentation or induction of MHC antigens, whereas augmentation or induction of other tumor-associated antigens was apparently restricted to a few epitopes.

Antigens, Neoplasm↗
PubMed1989

Heterogeneity of antigen expression in benign and malignant breast and ovarian epithelial cells.

Expression of II distinct antigen families has been studied in normal and malignant epithelial cells from breast and ovary by avidin-biotin immunoperoxidase staining of frozen tissue sections. Each of the antigens was expressed in a fraction of the normal and malignant breast tissues from different individuals. Among breast and ovarian cancers, a similar fraction of tumors expressed each of the determinants. An epitope on a 42-kDa glycoprotein was expressed significantly more often by ovarian carcinomas than by benign ovarian epithelium. Several determinants on 66-, 240-kDa or high-molecular-weight proteins or glycoproteins were expressed significantly more often on benign breast epithelium than on normal ovarian epithelium. Substantial heterogeneity in antigen expression was observed among different tumor specimens. Each of 14 epithelial ovarian cancers expressed a distinctive combination of antigens. Among 18 breast cancers, 16 distinct antigenic phenotypes were observed. Interestingly, comparable heterogeneity was observed in the expression of epitopes on benign breast and ovarian epithelium, compatible with the possibility that the monoclonal reagents recognized polymorphic determinants. Substantial variations in antigen expression were also observed among cells within each neoplasm. However, when antibodies against 5 different determinants were used in combination, a majority of cells could be stained intensely in all 13 breast carcinomas tested and more than 95% of tumor cells could be stained in 10 of the 13.

Antigens, Neoplasm↗