A postmenopausal woman with early-stage breast cancer and borderline hormone-receptor staining.
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Biomedical subjects
Publications and source records attributed to Jyoti Arya.
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OBJECTIVE: Host immune responses are unable to fully suppress HIV-1 replication in lymphoid tissues. Microanatomic relationships between HIV-1-producing cells and CD8+ cells in lymphoid tissues were analyzed to determine whether there was evidence for an immune privileged site or impaired recognition of virus-producing cells. METHODS: CD8+ cell phenotypes were determined on disaggregated inguinal lymph node cells by flow cytometry for seven untreated HIV-1-infected subjects. Microanatomic relationships between HIV-1-producing cells and CD8+ cells were analyzed in lymph node sections from 15 HIV-1-infected individuals using in situ hybridization and immunohistochemical staining. RESULTS: Most (median, 96%) lymph node CD8+ cells coexpressed CD3. Frequencies of virus-producing cells detected by in situ hybridization correlated with plasma HIV-1 RNA concentration (Spearman rho = 0.70; p =.02; n = 11). The percentage of lymph node cells adjacent to virus-producing cells that were CD8+ (median, 29%) was not statistically different from the percentage of CD8+ cells in lymphoid tissue overall (median, 34%; p =.09). CONCLUSIONS: Multiple explanations could account for the observation that CD8+ cells do not preferentially accumulate around virus-producing cells including the possibility that HIV-1-specific CD8+ cells cannot recognize virus-producing cells. Further studies are necessary to determine whether HIV-1-specific CD8+ T cells aggregate around virus-producing cells in lymphoid tissue.
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All cells maintain continuous communication. Hormones derive constitutively from specialized cells to effect total body homeostasis. Conversely, cytokines are produced sporadically from almost all nucleated cells in response to surgical ischemia/septic challenge. Surgical patients are a stew of pulsating cytokines, which serve as the language between all surgically stressed somatic and myeloid cells. Therapeutic manipulation of cytokines has already generated some exhilarating success stories and some crushing disappointments. This introduction to surgically relevant cytokines is presented with the conviction that cytokine-based therapies of surgical patients will (in the future) prove as beneficial to our patients as antibiotics have in the past.
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Fifteen years ago, an experimental effort to magnify a myocardial infarction, with preinfarction episodes of transient ischemia, proved paradoxically protective. In the ensuing years, surgeons have learned to discriminate a biochemical/metabolic/functional spectrum of cardiac states ranging from healthy myocardium to "stunned" or "hibernating" heart to the modes of "apoptotic" or "necrotic" cardiomyocyte death. It is now clear that "protective cardiac preconditioning" influences all of these cardiac states. The cellular mechanisms of preconditioning (PC) are now sufficiently understood to permit clinical application. Ligation of adrenergic, adenosine, bradykinin or opioid receptors involves signaling via both tyrosine and calcium-dependent protein kinases (PKC), which activate mitochondrial ATP-dependent potassium channels. Subsequently, the release of oxygen radicals induces nuclear translocation of transcriptional regulators, which transform the cardiomyocyte into a more resilient cell. Although preconditioning was initially recognized as protecting only against infarction, PC also limits postischemic dysrhythmias and enhances contractile function. Phase I (safety) and phase II (efficacy) clinical trials now persuasively support pharmacological preconditioning as a safe mode of preventing postcardiac surgical complications. Indeed, preconditioning is currently being proposed as adjunctive to hypothermic perfusates in protecting against the obligate organ ischemia during transplantation.