Biomedical subjects
L J Peterson
Publications and source records attributed to L J Peterson.
Journal evolution continues.
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What about the evidence?
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Scholarship player or walk-on.
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Academic responsibility for research.
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Radiology and oral and maxillofacial surgery.
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Severe combined immunodeficient mice engrafted with human splenocytes have functional human T cells and reject human allografts.
Previous studies have shown that human hemopoietic cells can be adoptively transferred into immunodeficient C.B-17 scid/scid (SCID) mice that lack autologous T and B lymphocytes, to generate chimeric animals. The future development of novel immunomodulatory drugs in transplantation will depend increasingly on experimental animal models to investigate the properties of the agents on human cells before starting clinical trials. However, in previous models of SCID mice engrafted with human PBLs, human T cells have been found either to be in an unresponsive state, unable to respond to mitogenic stimulations in vitro, or to mediate skin graft rejection only when HLA-primed in vivo before their adoptive transfer into SCID mice. In addition, T cells and other leukocyte subsets engraft quite poorly in the lymphoid tissues of the animals. In an attempt to develop a useful model for transplantation research, we have inoculated SCID mice with fresh human splenocytes from cadaveric organ donors (hu-Spl-SCID mice). In this model, various leukocyte subsets engraft effectively in different lymphoid compartments. In addition, human T cells retain their proliferative responses to mitogens and to alloantigens when tested 3 wk after engraftment into SCID mice. Finally, mice engrafted with unprimed human spleen cells acutely reject human foreskin allografts. Treatment of hu-Spl-SCID mice with OKT3, an immunosuppressive mAb directed against the human CD3 complex associated with the TCR, prevents the rejection of most human skin allografts, indicating a major role for human T cells in this phenomenon. Thus, this hu-Spl-SCID model may be useful for the study of immunosuppressive therapies in a preclinical in vivo setting.
A non-activating "humanized" anti-CD3 monoclonal antibody retains immunosuppressive properties in vivo.
OKT3, a mouse anti-human CD3 mAb, is a potent immunosuppressive agent used in clinical transplantation to prevent or treat allograft rejection. Associated with this therapy is the systemic release of several cytokines that result in a series of adverse side effects. This release of cytokines is dependent on the cross-linking mediated by OKT3 between T cells and the Fc gamma R-bearing cells. To generate an anti-human CD3 mAb with reduced activating properties as compared with OKT3, we have transferred the complementary determining regions of OKT3 onto human IgG frameworks and then performed point mutations that reduce the affinity of the "humanized" anti-CD3 mAbs for Fc gamma Rs. Initial, in vitro, studies showed that whereas OKT3 and the parental humanized anti-CD3 mAbs activated T cells similarly, a humanized Fc variant failed to do so. Both the Fc variant and the activating anti-CD3 mAbs induced comparable modulation of the TCR and suppression of cytolytic T cell activity, in vitro. In the current study, we exploited an experimental model in which human splenocytes from cadaveric organ donors were inoculated into severe combined immunodeficient mice (hu-SPL-SCID mice) to test the activating and immunosuppressive properties of these anti-human CD3 mAbs in vivo. Unlike injection of OKT3 or of the parental humanized mAb, administration of the Fc variant did not result in T cell activation in vivo, as evidenced by the lack of induction of surface markers of activation, and of systemic human cytokines, including IL-2. Importantly, similar prolongation of human allograft survival was achieved with all anti-CD3 mAbs, indicating that the nonactivating anti-CD3 mAbs retained significant immunosuppressive properties in vivo. Thus, the use of an Fc variant in clinical transplantation should result in fewer side effects than observed with OKT3, while maintaining its clinical efficacy.
Are they still miracle drugs.
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Contemporary management of deep infections of the neck.
Odontogenic infections rarely lead to involvement of the lateral and retropharyngeal spaces. When this does occur, the microbiology of the infection is similar to the typical odontogenic infection, ie, Streptococcus and oral anaerobes including Peptostreptococcus, Bacteroides, and Fusobacterium. There is an increased incidence of Fusobacterium seen in the more severe infections, as well as a higher incidence of Streptococcus milleri. Many patients who have deep cervical infections also have some compromise in their host defense mechanism, such as diabetes. The signs and symptoms of deep cervical space infections are similar to those of the severe submandibular space infection, but also includes sialorrhea, respiratory distress, odynophagia, and dysphagia. Lateral soft-tissue radiographs of the neck are useful in assisting with the diagnosis of retropharyngeal infections, and CT scans can provide definitive information regarding lateral pharyngeal space involvement. Treatment includes the use of high-dose intravenous bacteriocidal antibiotics. The recommended antibiotics are penicillin-metronidazole, ampicillin-sulbactam, or clindamycin. Certain cephalosporins may also be useful in selected patients. Early surgical intervention is also indicated. Aggressive incision and drainage of all of the involved spaces is necessary to assure early resolution of the infection. Continual airway monitoring and the establishment of surgical airways is the final portion of the treatment triad.
A systematic approach to management of high-flow vascular malformations of the mandible.
High-flow vascular malformations of the mandible are associated with significant morbidity and mortality. As these lesions are rare, the experience that a clinician has with treatment may be limited. To facilitate understanding and treatment of such lesions in a controlled and efficient manner, a treatment protocol is presented that includes careful preoperative planning, embolization, and surgery.
Etiology of implant complications: anecdotal reports vs prospective clinical trials.
The dental profession has in the past overreacted to anecdotal reports of both positive and negative outcomes involving implants. Because implant complications usually involve multiple variables, it is necessary to isolate these variables as much as possible when structuring a study to assess implant success vs failure. The methodology used in a study of Omniloc implants is reported, including detailed criteria for patient exclusion, patient demographics, statistical method, measurement indices, control procedures, and success criteria.
Which antibiotic?
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Acid-base changes in the running greyhound: contributing variables.
To determine the factors responsible for changes in [H+] during and after sprint exercise in the racing greyhound, Stewart's quantitative acid-base analysis was applied to arterial blood plasma samples taken at rest, at 8-s intervals during exercise, and at various intervals up to 30 min after a 402-m spring (approximately 30 s) on the track. [Na+], [K+], [Cl-], [total Ca], [lactate], [albumin], [Pi], PCO2, and pH were measured, and the [H+] was calculated from Stewart's equations. This short sprint caused all measured variables to change significantly. Maximal changes were strong ion difference decreased from 36.7 meq/l at rest to 16.1 meq/l; [albumin] increased from 3.1 g/dl at rest to 3.7 g/dl; PCO2, after decreasing from 39.6 Torr at rest to 27.9 Torr immediately prerace, increased during exercise to 42.8 Torr and then again decreased to near 20 Torr during most of recovery; and [H+] rose from 36.6 neq/l at rest to a peak of 76.6 neq/l. The [H+] calculated using Stewart's analysis was not significantly different from that directly measured. In addition to the increase in lactate and the change in PCO2, changes in [albumin], [Na+], and [Cl-] also influenced [H+] during and after sprint exercise in the running greyhound.
Rationale for removing impacted teeth: when to extract or not to extract.
Age, crowding, disease and root resorption all influence the decision to remove impacted teeth. While not every impacted tooth causes a significant problem, each has that potential.