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Biomedical subjects

Jonathan D Katz

Publications and source records attributed to Jonathan D Katz.

11 recordsLinked to original sources

NKT cells and IFN-gamma establish the regulatory environment for the control of diabetogenic T cells in the nonobese diabetic mouse.

In type 1 diabetes mellitus (T1DM), T cell-mediated destruction of insulin-producing pancreatic beta cells leads to the acute onset of hyperglycemia. The nonobese diabetic mouse model of human T1DM reveals that T cells capable of inducing diabetes can escape normal central tolerance, and can cause T1DM if left unchecked. However, several regulatory T cell subsets can temper autoaggressive T cells, although it remains undetermined when and how, and by which subset, homeostatic control of diabetogenic T cells is normally achieved in vivo. Using a cotransfer model, we find that NKT cells efficiently dampen the action of diabetogenic CD4+ T cells, and do so in an indirect manner by modifying the host environment. Moreover, the NKT cell-containing population modifies the host via production of IFN-gamma that is necessary for driving the inhibition of diabetogenic T cells in vivo.

Animals↗

Anesthesiologists are living longer: mortality experience 1992 to 2001.

STUDY OBJECTIVE: To determine whether there has been any recent change in the mortality experience of American anesthesiologists. DESIGN: Retrospective analysis of obituary reports to the Physician Master File (PMF) of the American Medical Association. MEASUREMENTS: Data were collected from the PMF of anesthesiologists and obstetricians. All data were identified from the PMF. A total of 1525 obituaries of anesthesiologists and 2773 obituaries of obstetricians during the study period, 1992 to 2001, were reviewed. Mean age of living or mean age at death of anesthesiologists and obstetricians, as well as age-adjusted death rates was calculated. MAIN RESULTS: A gradual increase in age at death was noted from 1992 (65.30 +/- 15.61 years) to 2001 (78.13 +/- 12.89 years) for anesthesiologists (P < 0.005). There was a significant linear decrease from 4.3 deaths per thousand to 2.3 deaths per thousand for anesthesiologists in this same period. CONCLUSIONS: We observed a significant increase in the average age at death and a decreased risk of death among anesthesiologists who died in the years 1992 to 2001. Parallel changes were observed in the control population of obstetricians.

Adult↗

Dynamic interaction between T cell-mediated beta-cell damage and beta-cell repair in the run up to autoimmune diabetes of the NOD mouse.

In type 1 diabetes mellitus (T1DM), also known as autoimmune diabetes, the pathogenic destruction of the insulin-producing pancreatic beta-cells is under the control of and influenced by distinct subsets of T lymphocytes. To identify the critical genes expressed by autoimmune T cells, antigen presenting cells, and pancreatic beta-cells during the evolution of T1DM in the nonobese diabetic (NOD) mouse, and the genetically-altered NOD mouse (BDC/N), we used functional genomics. Microarray analysis revealed increased transcripts of genes encoding inflammatory cytokines, particularly interleukin (IL)-17, and islet cell regenerating genes, Reg3alpha, Reg3beta, and Reg3gamma. Our data indicate that progression to insulitis was connected to marked changes in islet antigen expression, beta-cell differentiation, and T cell activation and signaling, all associated with tumor necrosis factor-alpha and IL-6 expression. Overt diabetes saw a clear shift in cytokine, chemokine, and T cell differentiation factor expression, consistent with a focused Th1 response, as well as a significant upregulation in genes associated with cellular adhesion, homing, and apoptosis. Importantly, the temporal pattern of expression of key verified genes suggested that T1DM develops in a relapsing/remitting as opposed to a continuous fashion, with insulitis linked to hypoxia-regulated gene control and diabetes with C/EBP and Nkx2 gene control.

Animals↗

Radiation exposure to anesthesia personnel: the impact of an electrophysiology laboratory.

Anesthesia care providers are vulnerable to radiation exposure during a number of diagnostic and therapeutic procedures. In this study I examined the radiation exposure to members of a small department of anesthesiology. The aggregate radiation exposure to all members of the department doubled subsequent to the introduction of an electrophysiology laboratory.

Anesthesiology↗

Microarray and comparative genomics-based identification of genes and gene regulatory regions of the mouse immune system.

BACKGROUND: In this study we have built and mined a gene expression database composed of 65 diverse mouse tissues for genes preferentially expressed in immune tissues and cell types. Using expression pattern criteria, we identified 360 genes with preferential expression in thymus, spleen, peripheral blood mononuclear cells, lymph nodes (unstimulated or stimulated), or in vitro activated T-cells. RESULTS: Gene clusters, formed based on similarity of expression-pattern across either all tissues or the immune tissues only, had highly significant associations both with immunological processes such as chemokine-mediated response, antigen processing, receptor-related signal transduction, and transcriptional regulation, and also with more general processes such as replication and cell cycle control. Within-cluster gene correlations implicated known associations of known genes, as well as immune process-related roles for poorly described genes. To characterize regulatory mechanisms and cis-elements of genes with similar patterns of expression, we used a new version of a comparative genomics-based cis-element analysis tool to identify clusters of cis-elements with compositional similarity among multiple genes. Several clusters contained genes that shared 5-6 cis-elements that included ETS and zinc-finger binding sites. cis-Elements AP2 EGRF ETSF MAZF SP1F ZF5F and AREB ETSF MZF1 PAX5 STAT were shared in a thymus-expressed set; AP4R E2FF EBOX ETSF MAZF SP1F ZF5F and CREB E2FF MAZF PCAT SP1F STAT cis-clusters occurred in activated T-cells; CEBP CREB NFKB SORY and GATA NKXH OCT1 RBIT occurred in stimulated lymph nodes. CONCLUSION: This study demonstrates a series of analytic approaches that have allowed the implication of genes and regulatory elements that participate in the differentiation, maintenance, and function of the immune system. Polymorphism or mutation of these could adversely impact immune system functions.

Animals↗

Regulation of autoimmune diabetes by non-islet-specific T cells - a role for the glucocorticoid-induced TNF receptor.

Diabetogenic BDC2.5 CD4 T cells induce diabetes when injected into NOD.scid mice. However, when co-transferred with the OVA-specific DO11.10 CD4 T cells, BDC2.5 T cells failed to cause diabetes. This inhibition depended upon the stimulation of DO11.10 T cells only with soluble OVA, which skewed their differentiation to a Th2-type pattern of cytokine secretion in vivo. However, in vivo neutralization of IL-4, IL-10 or TGF-beta using monoclonal antibodies did not prevent the inhibition whereas treatment with an antibody against the glucocorticoid-induced TNF receptor abrogated the protection from disease. In the protected mice, the diabetogenic T cells could be isolated from their spleens and shown to transfer diabetes when injected into new NOD.scid recipients. Thus, the inhibition took place without the physical or functional elimination of the diabetogenic T cells.

Adoptive Transfer↗

Hand washing and hand disinfection: more than your mother taught you.

Hand washing is considered the single most important intervention for prevention of nosocomial infections in patients and health care workers. Unfortunately, compliance with standard protocols for hand hygiene in the health care environment, and especially within intensive care areas such as operating rooms and post-anesthesia care units, has been generally poor. In this article, we consider the current standards for hand hygiene as they pertain to the practice of anesthesiology. We discuss the consequences of poor compliance with hand washing practices for patient and health care provider safety. And we describe modern innovations in hand washing procedures and products that improve the opportunities for anesthesiologists to employ safe hand hygiene.

Anti-Infective Agents, Local↗

Do anesthesiologists die at a younger age than other physicians? Age-adjusted death rates.

UNLABELLED: I designed this study to determine whether anesthesiologists are susceptible to premature death. Three specialty groups were studied: anesthesiologists, internists, and all other physicians. Records were examined of all American physicians who died in the years 1989, 1990, 1995, 2000, and 2001, and those who were alive at the end of 1989, 1995, 2000, and 2001. Anesthesiologists had a statistically significant younger mean age at death (crude mortality) (68.98 +/- 15.55 yr) (n = 723) than did internists (74.41 +/- 14.24 yr) (n = 2285) and all other physicians (75.21 +/- 13.3 yr) (n = 18,328) (P < 0.001). However, by factoring in the ages of the living members of the study populations, there was no statistical difference in age-specific mortality. IMPLICATIONS: It has been suggested that one of the potential occupational hazards of the practice of anesthesiology is premature death. This study disproves the notion that anesthesiologists die at a younger age than other physicians.

Adult↗

Anesthesiologists and acute perioperative stress: a cohort study.

UNLABELLED: Previous studies have indicated that many anesthesiologists exhibit symptoms of chronic stress. There is a paucity of data, however, regarding the existence of acute stress signs among anesthesiologists. Anesthesiologists from three practice settings (n = 38) were studied while they were anesthetizing 203 patients. Heart rate (HR) was recorded continuously and arterial blood pressure (BP) was measured hourly and immediately after each induction. Anxiety levels and salivary cortisol levels were also assessed after each induction. Comparison BP and HR data were obtained from the anesthesiologists during a nonclinical day. We found that anesthesiologists' HR increased during the anesthetic process compared with morning baseline HR (P = 0.008). This HR increase, however, was not clinically significant; the average HR during the anesthetic pro- cess ranged from 80 +/- 12 to 84 +/- 11 bpm. Similarly, although both systolic and diastolic BP after inductions were increased compared with baseline BP (P = 0.001), this increase was not clinically significant. In 9% of the inductions, however, systolic BP exceeded 140 mm Hg, and in 17% of all inductions, diastolic BP exceeded 90 mm Hg. Finally, the average BP of anesthesiologists during a clinical day was not different from the average BP during a nonclinical day (P = 0.9). Self-reported anxiety did not increase significantly after inductions (P = 0.15). An analysis of Holter tapes revealed no rhythm abnormalities and no signs of myocardial ischemia. We conclude that the practice of anesthesiology is associated with minor manifestations of acute physiologic stress during the perioperative process. IMPLICATIONS: Anesthesiologists experience minor psychologic stress while involved in the anesthetic process.

Acute Disease↗

Challenges for the aging physician.

Physiologic age is a significant factor in physician performance. Most reports on occupational concerns of physicians are focused on trainees while little attention has been paid to aging physicians. The following review will examine the issues that concern and challenge aging physicians.

Aging↗