ABSTRACT
The hematopoietic cell-specific adaptor protein, SLP-76, is critical for T cell development and mature T cell receptor (TCR) signaling; however, the structural requirements of SLP-76 for mediating thymopoiesis and mature T cell function remain largely unknown. In this study, transgenic mice were generated to examine the requirements for specific domains of SLP-76 in thymocytes and peripheral T cells in vivo. Examination of mice expressing various mutants of SLP-76 on the null background demonstrates a differential requirement for specific domains of SLP-76 in thymocytes and T cells and provides new insight into the molecular mechanisms underlying SLP-76 function.
Subject(s)
Adaptor Proteins, Signal Transducing , Membrane Proteins , Phosphoproteins/physiology , T-Lymphocytes/cytology , Amino Acid Motifs , Amino Acid Substitution , Animals , Binding Sites , CD3 Complex/immunology , Calcium Signaling , Carrier Proteins/physiology , Cell Differentiation , Clonal Deletion/physiology , Immunophenotyping , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Mutation, Missense , Phosphoproteins/chemistry , Phosphoproteins/deficiency , Phosphoproteins/genetics , Protein Structure, Tertiary , Receptors, Antigen, T-Cell/immunology , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/physiology , Sequence Deletion , Signal Transduction/physiology , Spleen/immunology , Structure-Activity Relationship , T-Lymphocytes/immunology , Thymus Gland/immunology , src Homology DomainsABSTRACT
BACKGROUND: Vancomycin anaphylaxis is a major management problem in patients with methicillin-resistant Staphylococcus aureus (MRSA) sepsis. Lerner et al in 1984 have described a protocol for desensitization to vancomycin; however, antibiotic blood levels have never been used as a guide in this process. CASE REPORT: A 46-year-old female with ESRD on hemodialysis who developed a dialysis-catheter related MRSA sepsis was found to have anaphylaxis to vancomycin. She underwent successful desensitization to vancomycin using Lerner's protocol. Periodic antibiotic blood levels were used to guide the amount and frequency of vancomycin infusion to successfully maintain desensitization thereafter. DISCUSSION: Lerner described loss of desensitization to vancomycin when antibiotic infusion was stopped after 18 hours followed by successful desensitization to the same drug via the same protocol. This observation points out that desensitization to vancomycin appears to be dependent on some minimal drug level. In our case report, we have for the first time used the concept of blood levels to maintain successful desensitization to an antibiotic. CONCLUSION: We hypothesize that desensitization to vancomycin can be induced and maintained by keeping a minimum antibiotic blood level. Further studies are needed to quantify this.
Subject(s)
Kidney Failure, Chronic/therapy , Vancomycin/immunology , Anaphylaxis/chemically induced , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/immunology , Anti-Bacterial Agents/metabolism , Desensitization, Immunologic , Female , Humans , Kidney Failure, Chronic/metabolism , Methicillin Resistance/physiology , Middle Aged , Renal Dialysis , Vancomycin/adverse effectsABSTRACT
BACKGROUND: The relationship between sex hormones and asthma has not been clarified. Studies have suggested a potential beneficial effect of exogenous sex hormones and/or contraceptive pills on asthma in premenopausal females whereas the data for postmenopausal females are inconsistent. CASE REPORT: A 33-year-old woman suffering from asthma with premenstrual exacerbations had a stable course until she began taking oral contraceptives. At that time she experienced clinical deterioration of her asthma associated with decline of pulmonary function tests. No other precipitating factors were identified. After discontinuing the contraceptives, her condition returned to baseline. CONCLUSION: We found only two reports of worsening of asthma related to hormonal therapy (estrogen in one case, contraceptive pills in the other) in premenopausal women. Our report, together with these observations, suggests that in some premenopausal women exogenous sex hormones and/or contraceptive pills may, contrary to expected, produce exacerbation of asthma.
PIP: Although the mechanism of premenstrual asthma has not been established, hormonal variations during the menstrual cycle are believed to play an important role. About 30-40% of female asthmatics report worsening of asthma symptoms during the premenstrual and/or menstrual period. This article presents a case in which oral contraceptives (OCs) appeared to precipitate an asthma attack. The patient, a 33-year-old White US woman, first developed asthma at age 27 years. The strongest trigger to her asthma attacks was her menstrual period. All periods were associated with a worsening of asthma, typically extending from 1 week before to 2-3 days after the onset of menstrual bleeding. Subsequently, the patient's asthma was stabilized by continuous inhaled steroids. However, clinical deterioration of asthma and a decline of pulmonary function occurred immediately after the woman initiated OC use. There was a rapid stabilization in clinical status once OC use was discontinued. Although the weight of scientific evidence points to a possible beneficial effect of OCs or exogenous sex hormones on premenstrual asthma, this case suggests there may be a subset of women in whom sex hormones exacerbate asthma.
