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T N Sims

Publications and source records attributed to T N Sims.

13 recordsLinked to original sources

The role of the class II transactivator (CIITA) in MHC class I and II regulation and graft rejection in kidney.

Class II transactivator (CIITA) induces transcription of MHC class II genes, and induces class I in some cell lines. We examined the effect of CIITA deficiency on class I and II expression in mouse kidney. In CIITA knockout (CIITAKO) mice, basal class II was absent, but class I levels were mildly but significantly increased. Allogeneic stimulation or ischemic injury increased class I and II expression in kidneys of control (wild-type, WT) mice but induced only class I in CIITAKO mice. Thus, in kidney, all basal and induced class II expression was CIITA-dependent, but neither basal nor induced class I was CIITA-dependent. Rejecting kidney allografts from CIITAKO mice in CBA hosts manifested intense induction of donor class I but no donor class II expression. Rejecting kidneys from both WT and CIITAKO donors showed predominantly CD8 T-cell infiltration at days 7 and 21, with increasing tubulitis and arteritis at day 21. CIITAKO kidneys showed fewer infiltrating cells than WT kidneys at day 21. Thus CIITA-deficient kidneys have no basal and induced class II expression but display intense induction of class I expression, and evoke typical rejection lesions, although some indices of infiltration are reduced at day 21.

Animals↗

The immunological synapse.

The adaptive immune response is initiated by the interaction of T cell antigen receptors with major histocompatibility complex molecule-peptide complexes in the nanometer scale gap between a T cell and an antigen-presenting cell, referred to as an immunological synapse. In this review we focus on the concept of immunological synapse formation as it relates to membrane structure, T cell polarity, signaling pathways, and the antigen-presenting cell. Membrane domains provide an organizational principle for compartmentalization within the immunological synapse. T cell polarization by chemokines increases T cell sensitivity to antigen. The current model is that signaling and formation of the immunological synapse are tightly interwoven in mature T cells. We also extend this model to natural killer cell activation, where the inhibitory NK synapse provides a striking example in which inhibition of signaling leaves the synapse in its nascent, inverted state. The APC may also play an active role in immunological synapse formation, particularly for activation of naïve T cells.

Animals↗

In vivo class II transactivator expression in mice is induced by a non-interferon-gamma mechanism in response to local injury.

BACKGROUND: Tissue injury induces MHC class II expression, which could be important in the recognition of that tissue as an allograft. The class II transcriptional activator (CIITA) is the major regulator of basal and induced MHC class II expression and is essential for antigen presentation. The role of CIITA in the induction of class II by tissue injury is unknown. In this study, we examined CIITA induction in the course of acute ischemic or toxic renal injury in mice, including the role of interferon (IFN)-gamma and of the transcription factor, interferon regulatory factor (IRF)-1. METHODS: Kidneys were injured by ischemia or by gentamicin toxicity and were then studied for changes in gene expression using Northern blot, reverse transcriptase-polymerase chain reaction, radioimmunoassay, and tissue staining. We compared wild-type (WT) mice to IFN-gamma knockout (GKO) or IRF-1 knockout mice. RESULTS: Ischemic injury induced CIITA and class II expression in the kidney, in WT and GKO mice. Gentamicin injury also induced both CIITA and class II expression, independent of IFN-gamma, in WT and GKO mice. After ischemic injury, the induction of class II protein levels and CIITA and class II mRNA levels were induced, to a lesser degree, in IRF-1 knockout mice. CONCLUSIONS: These data indicate that CIITA is induced by tissue injury, and probably accounts for class II induction during tissue injury. CIITA induction by injury is largely IFN-gamma independent but requires IRF-1. The similarities of the pattern of CIITA and class II induction in ischemic and toxic injury suggest that this is a stereotyped response of injured tissue and not a consequence of a particular mechanism of injury.

Animals↗

Assessment of ST segment depression in patients with cardiac disease after local anesthesia.

This study found that dental treatment with 2% lidocaine with 1:100,000 epinephrine did not provoke myocardial ischemia, as assessed by greater than or equal to 1 mm of ST segment depression. Although in some cases systolic and diastolic blood pressure and rate pressure product increased slightly after local anesthetic administration, these changes were not statistically significant. Because these patients were medically supervised and compliant with cardiac therapy, this study suggests that such patients are not at great risk while receiving local anesthesia with 1:100,000 epinephrine for routine dental care.

Aged↗

Assessment of stress during periodontal surgery with intravenous sedation and with local anesthesia only.

Ten patients with moderate to advanced periodontal disease were subjected to two similar periodontal surgical procedures. Each patient received either intravenous conscious sedation with local anesthesia or local anesthesia only. The stress-reducing effects of a conscious sedation regimen consisting of pentobarbital, meperidine, and diazepam were evaluated in these patients. Stress was evaluated by monitoring changes in serum cortisol, human growth hormone, and vital signs. Blood samples were obtained at 15- to 30-minute intervals throughout each procedure and were evaluated for serum cortisol and growth hormone. The conscious sedation group had significantly lower serum cortisol levels and lower systolic blood pressure, indicating that the patients having periodontal surgery with conscious sedation experienced reduced stress. Physiologic stability was maintained for each patient, indicating that this conscious sedation regimen can be used to reduce measurable parameters of stress that patients develop during periodontal surgery.

Anesthesia, Dental↗

Value of antibiotic prophylaxis in periodontal surgery.

THE MORBIDITY and incidence of bacteremia in periodontal surgery with or without cephalexin prophylaxis were assessed in adults on the basis of clinical evaluations and blood cultures. Cephalexin reduced the incidence of polymicrobic bacteremias. There was no correlation between objective signs of tissue healing and antibiotic coverage in treated or nontreated patients. In vitro antibiotic susceptibility data showed that cephalexin was active against the aerobic and anaerobic bacteria isolated from blood specimens taken during surgery.

Adult↗

Clinical and antimicrobial effect of stannous fluoride on periodontitis.

The antimicrobial effect of stannous fluoride (SnF2) on suspected pathogenic morphotypes of bacterial plaque in chronic periodontal disease was assessed. Alterations in morphological groups of subgingival and supragingival plaque bacteria from three diseased sites and one periodontally healthy site were determined by darkfield microscopy in 10 male patients with advanced periodontitis. In addition, clinical indices were also measured. The three diseased sites received either 1.64% SnF2, 0.4% SnF2 or sterile saline by subgingival irrigation. The healthy site received sterile saline only. The patients were seen weekly over a 10-week period and at each appointment bacterial sampling and clinical indices were measured. Results indicated that 1.64% SnF2 caused a dramatic and sustained decrease of subgingival motile bacteria and spirochetes following irrigation. By the sixth week these bacteria returned to 50% of their original concentration. Bleeding index scores, which were significantly reduced, correlated positively to the reduction in motile bacteria and spirochetes. Sites irrigated with 0.4% SnF2 also demonstrated a similar pattern of reduction of motile bacteria and spirochetes but without their total elimination and a more rapid return to original levels. In the diseased sites receiving sterile saline there was a decrease in motile bacteria and spirochetes, corresponding with saline irrigation, which rapidly returned to baseline levels. The healthy control sites were unchanged. Supragingival plaque index scores did not correlate with the bleeding index, motile bacteria and spirochetes, or with subgingival irrigation.

Adult↗