Basic statistical concepts in quality improvement.
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Biometry↗
Biomedical subjects
D Grossman
Publications and source records attributed to D Grossman.
Dual roles for class II major histocompatibility complex molecules in staphylococcal enterotoxin-induced cytokine production and in vivo toxicity.
The staphylococcal enterotoxins (SE) specifically bind to class II major histocompatibility complex (MHC) proteins, resulting in activation of monocytes and T cells. The SE cause weight loss in mice, which is dependent on T-cell stimulation and tumor necrosis factor alpha (TNF-alpha) production. Here we use a mutant of staphylococcal enterotoxin A that binds class II MHC molecules and activates monocytes but not T cells to evaluate the relative contributions of monocyte- and T-cell-stimulatory activities to in vivo toxicity. The mutant toxin did not cause weight loss in B10. BR mice but did stimulate monocyte TNF-alpha production in vitro, as did the wild-type toxin. Addition of a supernatant from toxin-activated T cells enhanced monocyte-stimulatory activity of both mutant and wild-type toxins fivefold. The effect of the supernatant could be mimicked by recombinant gamma interferon (IFN-gamma) and was inhibited by antibody to IFN-gamma. These results suggest that toxin-induced monocyte TNF-alpha production is upregulated by IFN-gamma, which likely represents the T-cell requirement in SE-mediated weight loss. Our studies thus implicate two distinct class II MHC-dependent signaling pathways for SE, the first involving direct signal transduction through class II MHC molecules mediated by either mutant or wild-type toxin and the second requiring T-cell stimulation by toxin-class II MHC complexes with consequent production of IFN-gamma. We suggest that both pathways are required for optimal monocyte TNF-alpha production in vitro and SE-induced toxicity in vivo.
Animals↗
Mutation of the disulfide loop in staphylococcal enterotoxin A. Consequences for T cell recognition.
The hallmark of T cell responses to staphylococcal enterotoxins (SE) and other super-Ag is a selective stimulation of cells expressing particular TCR-V beta segments. Our previous studies suggested that the disulfide loop in SE is critical for their interaction with the TCR. To investigate this concept in further detail we constructed disulfide loop mutants of staphylococcal enterotoxin A (SEA), and examined these altered toxins for mitogenicity, class II MHC binding, and V beta specificity. We found that substitutions of either Cys-96 or Cys-106 decreased mitogenicity by 100-fold without significantly affecting class II binding or resistance of the molecule to proteolysis. Several mutants lost the capacity to stimulate V beta 11+ cells, except a Cys-106----Gln mutant for which V beta 11-stimulatory activity was increased. By contrast, mutants containing Cys----Ala substitutions acquired the capacity to stimulate V beta 6+ cells. Despite these effects of V beta specificity, all mutants retained the predominant preference of SEA for V beta 3+ cells. Neither exchange of regions flanking the loop in SEA with corresponding residues in SEB, nor conversion of the entire loop region of SEA to that of SEE, were associated with transfers of V beta specificity. Our results suggest that the disulfide loop in SEA contributes to toxin avidity for the TCR, rather than specificity for particular V beta.
Amino Acid Sequence↗
Anti-CD4 mediates clonal anergy during transplantation tolerance induction.
Depletion of CD4+ cells using anti-CD4 monoclonal antibodies leads to allograft tolerance. Here we show that anti-CD4-mediated tolerance to pancreatic islets of Langerhans transplanted from an A/J (IEk) donor to a diabetic C57B1/6 (B6) (IE-) recipient occurs in the absence of clonal deletion of the potentially IE-reactive V beta 11+ T cells. Instead, a state of clonal anergy is induced in both the CD4+V beta 11+ and CD8+V beta 11+ T cell subsets. This clonal anergy can be partially overcome in vitro by the addition of recombinant interleukin 2.
Animals↗
Episodic occurrence of antibodies against the bovine leukemia virus Rex protein during the course of infection in sheep.
Infection by bovine leukemia virus (BLV) is characterized by a long clinical latency after which some individuals develop B-cell tumors. The contributions of the viral regulatory proteins Tax and Rex during clinical latency and disease are incompletely understood. To learn about Rex expression in the host, we used a sensitive immunoprecipitation assay to detect Rex antibodies throughout the course of BLV infection in sheep. Sixty percent of the infected animals produced Rex antibodies in intermittent episodes. This pattern differed markedly from that of antibodies to virion structural proteins, which were maintained in all animals throughout infection. Only one of two animals that developed tumors had detectable Rex antibodies at the time, although the other had previously demonstrated an especially strong Rex antibody response. We examined the Rex response in the context of BLV infection by comparing it with the frequency of circulating mononuclear blood cells that could transcribe BLV RNA or produce infectious virus. Episodes of Rex antibody occurrence followed some but not all increases in the number of BLV-transcribing cells. Since the appearance of circulating antibodies requires that the intracellular Rex protein be available to serve as antigen, the episodic pattern of occurrence of Rex antibodies could result from intermittent killing by virus-specific cytotoxic cells. Fluctuations in titer that were observed during some episodes of Rex response could be due to antibody retention by antigen present in lymphoid tissue.
Animals↗
Anti-CD8 abrogates effect of anti-CD4-mediated islet allograft survival in rat model.
We studied the effects of anti-CD4 treatment of diabetic ACI rats on the induction of tolerance to allogeneic (Lewis) islet allografts. When given as a 4-day treatment regimen, OX38, a mouse anti-rat CD4 antibody, caused depletion of greater than 80% of CD4+ cells from the peripheral blood of treated rats. After induction of diabetes (a single high-dose bolus of streptozocin) and 3 days after the initiation of anti-CD4 immunotherapy, recipient ACI rats were transplanted with fully allogeneic (Lewis) islets of Langerhans via the portal circulation. These transplanted islets were capable of returning the anti-CD4-treated ACI recipients to normoglycemia, which was maintained indefinitely in the absence of further immunosuppression. In contrast, treatment of recipient rats with OX8, an anti-CD8 monoclonal antibody (MoAb), induced only a slight prolongation of graft survival (less than or equal to 30 days). Further characterization of the cellular requirements for the induction of long-term transplantation survival revealed that successful pretransplantation anti-CD4 therapy could be ablated by the coincident treatment of recipient rats with depleting levels of anti-CD8 MoAb. These data point to the necessity of a regulator CD8+ cell in the induction of anti-CD4-mediated transplantation survival in this rat model of islet transplantation.
Animals↗
Dissociation of the stimulatory activities of staphylococcal enterotoxins for T cells and monocytes.
The staphylococcal enterotoxins (SEs) are homologous proteins related in their capacity for stimulating both T cells and monocytes. To assess the importance of conserved structure and sequence to functional activity, the role of the disulfide loop and adjacent sequence in these toxins was evaluated. Contrary to previous reports, we demonstrate here that the disulfide loop was required for the mitogenic activity of SEA and SEB. While T cell-stimulatory activity was compromised, reduced and alkylated SEs retained major histocompatibility complex class II-binding and monocyte-stimulatory activities, suggesting that their inability to induce T cell proliferation was due to failure to interact with T cell receptor (TCR) rather than with class II molecules. Reduction and alkylation did not affect the far-ultraviolet circular dichroic spectrum of SEA, suggesting that the loss of mitogenic activity was not associated with significant changes in secondary structure. The disulfide linkage imparts considerable stability to these toxins as peptide cleavages within the loop of SEB were not associated with detectable loss of function, although cleavage in the conserved sequence outside the loop of SEA resulted in loss of mitogenic activity. This report thus establishes a functional role for a conserved element in SEs, the disulfide loop, and further indicates that their class II- and TCR-binding activities can be dissociated.
Amino Acid Sequence↗
Humoral immune response of experimentally infected sheep defines two early periods of bovine leukemia virus replication.
We have correlated the virus-specific humoral immune response of sheep newly infected with bovine leukemia virus (BLV) with the appearance in their blood of cells that transcribe BLV RNA or produce virus in culture. Neutralizing antibodies and antibodies binding to the viral capsid protein were present in most animals early after infection, often before BLV-expressing cells were first detected in blood. Neutralizing antibodies increased rapidly during the period when the number of cells that expressed BLV was also increasing. However, the titers developed by individual animals were independent of the maximum number of BLV-expressing cells. Antibodies that bound to the viral surface glycoprotein on immunoblots became evident at the same time as large peaks in the numbers of BLV-expressing cells. Despite ensuing sharp drops in BLV-expressing cells, neutralizing titers remained relatively constant through the rest of the first 8 months after infection. Two early phases of BLV replication were thus defined: initial, low-level replication that induced neutralizing and capsid-specific antibodies followed by a second period of intense replication that induced sharp increases in antiviral antibodies and preceded the release of many infected cells into the blood.
Animals↗
Complete heart block due to interleukin-2 therapy.
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Carcinoma, Renal Cell↗
High school students' perceptions of nursing as a career: a pilot study.
A pilot survey of 300 high school junior students was implemented to elicit their perceptions of nursing and to explore the relationship between the experience of having a nursing role model and the decision to consider nursing as a career. The results indicated that the majority of students in the sample were aware of the caring and helping aspects of nursing, but there seemed to be a lack of knowledge about expanded roles and opportunities for advancement. High school students had significantly different mean opinion scores according to their sex (F = 17.03, p less than 0001) and the decision to consider nursing as a career (F = 10.00, p less than 002). There appeared to be a significant relationship between the experience of having a nurse role model and consideration of nursing as a career option (chi 2 = 8.23, p less than .0041). These findings have important implications for recruitment of young people into the nursing profession.
Adolescent↗
Comparison of preoperative skin preparations for the face.
Antiseptic preparation of the skin before dermatologic surgical procedures should provide maximal reduction of cutaneous microflora for the duration of the operation. No data currently exist concerning the efficacy of topical antimicrobials on the most common site of cutaneous surgery, the face. In this study the potency and temporal characteristics of three antimicrobials were tested on the faces of 14 volunteers. A 10-second wipe of 70% isopropyl alcohol was as effective in reducing aerobic microflora at the 5-minute postoperative period as a 60-second alcohol wipe or a 60-second povidone-iodine or chlorhexidine tincture application. At 60 minutes after the application, aerobic bacterial reduction possibly was better maintained by the povidone than by the 10- or 60-second alcohol preparation. None of the antiseptics tested were capable of a profound reduction of the anaerobic flora present on the sebaceous facial regions.
1-Propanol↗
Wilson's disease: a genetic disorder of copper metabolism.
This article provides an overview of Wilson's disease, a rare genetic disorder of copper metabolism. The etiology, pathogenesis, clinical manifestations, diagnosis, and treatment of the disease are discussed. A nursing care plan is presented.
Copper↗
DERM/RX. A computer aid to the management of diseases of the skin.
DERM/RX (dermatologic therapy) is a computerized data base representing a compendium of therapeutic management options for over 600 diseases of the skin. This data base is housed in the National Headquarters of the American Academy of Dermatology in Evanston, Illinois. It is accessible via DERM/INFONET to members of the American Academy of Dermatology via telephonic communication lines that blanket the United States. The data base is constantly updated by the Task Force on DERM/RX of the Committee on Biomedical Communications of the American Academy of Dermatology.
Humans↗
Mutant alleles at the locus elav in Drosophila melanogaster lead to nervous system defects. A developmental-genetic analysis.
We report a developmental and genetic analysis of the X-linked vital locus l(1)EC7 in Drosophila melanogaster. The locus maps in the salivary band region 1B4-5 to 1B8-9, a part of the X chromosome previously shown to be essential for normal neural development. Certain mutant alleles at the locus can cause embryonic lethality, indicating that the function provided by the gene is essential during embryogenesis. A developmental analysis of gynandromorphic genetic mosaics shows that: (1) the gene function is autonomously essential in the eye; (2) the gene function is essential for normal development of the optic lobes; and (3) the gene function is not necessary in most major imaginal-disc cell derivatives with the exception of the eye disc. Conclusions from the developmental analysis of a temperature sensitive allele are consistent with those from the mosaic analysis. The embryonic lethality caused by the mutant alleles and abnormalities observed in the genetic mosaics have led us to rename the locus l(1)EC7 to elav (embryonic lethal, abnormal visual system).
Alleles↗
Rapid identification of enterococci.
A 4-h method was devised to differentiate the non-beta-hemolytic streptococci into three categories: enterococci, group D nonenterococci, and viridans streptococci. All of the Streptococcus faecalis, 90% of the Streptococcus faecium (enterococci), and 96% of the Streptococcus bovis biotype I (group D nonenterococci) cultures were correctly identified by the 4-h method. The less commonly isolated group D cultures had lower rates of correct identification by this method. None of the viridans streptococci was identified incorrectly.
Humans↗
Solvolysis of a substituted imidazoline, mazindol.
Hydrolysis of mazindol to form 2-(2-aminoethyl)-3-(p-chlorophenyl)-3-hydroxyphthalimidine was followed spectro-photometrically in aqueous solutions at temperatures between 37 and 70degree, pH values up to 7.6, and an ionic strength of 0.2. The effects of acetate, formate, and phosphate buffers as well as ionic strength on the observed rate constants were investigated. An interesting nonlinear dependency of the kobs with buffer concentration was noted. The velocity constants declined with increasing hydrogen-ion concentration; the log k-pH profile and rate law are given along with other relevant data.
Buffers↗
Parental mosaicism in trisomy 18.
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Adult↗
Fetal wastage and maternal mosaicism.
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Abortion, Habitual↗