A Tribute to Justice Byron R. White

Of 107 Justices in 205 years, only twelve have served longer than thirty years, and every long-serving Justice has made a substantial contribution to the institution - offering a steady and dedicated response to the judicial challenges of an era, asserting leadership at a time of national crisis, or articulating a large constitutional vision. The personal qualities and life experiences that a new Justice brings to the Court contain the seeds of the individual\u27s judicial service. Justice White, a skeptical but unflinching democrat, was no exception

Clinical Manifestations of IgE Hypogammaglobulinemia

Background: Although IgE has been shown to play a role in the expulsion of intestinal parasites in experimental animals, its overall contribution to host defense in humans remains a subject of controversy. In order to clarify the potential role of IgE in host defense, we have studied the clinical characteristics of patients with serum IgE levels of \u3c2.5 IU/mL, using patients with normal or elevated IgE levels as controls. Objective: To determine the clinical characteristics of IgE deficiency. Methods: Serum IgE levels were measured in 420 adult patients seen in our Allergy-Immunology Clinic over a period extending from January, 1990 to March, 1996. All subjects were examined by one of the authors (JKS or GHK) using a standardized history and physical examination form. Patients with IgE levels of \u3c2.5 IU/mL also had measurements of serum IgG, IgG subclasses, IgA and IgM. All IgE-deficient patients and 73% of those with normal to elevated IgE levels underwent RAST and/or skin testing for Type I hypersensitivity, and, where clinically indicated, had serum drawn for autoimmune serologic profiles. Infectious complications were documented by culture. The American Rheumatology Association criteria were used to establish a diagnosis of autoimmune disease. Results: Forty-four patients were found to have IgE levels of \u3c2.5 IU/mL; 57% of these had depressed serum levels of other immunoglobulins, and 43% had isolated IgE deficiencies. Respiratory symptoms were equally common in IgE-deficient patients and in patients with normal to elevated IgE levels. IgE-deficient patients, however, were more likely to complain of arthralgias (P \u3c .0001), chronic fatigue (P \u3c .0001), and symptoms suggestive of airway infection (P = .0119). Compared with controls, patients with IgE deficiency had a higher prevalence of autoimmune disease (46% versus 15%) (P \u3c .0001) and nonallergic reactive airway disease (73% versus 20%) (P \u3c .0001). There was no difference in the prevalence of these diseases in patients with selective IgE deficiency as compared with those with IgE deficiency complicated by deficits in other immunoglobulin classes. IgE-deficient patients with multiple immunoglobulin deficiencies, however, were more likely to have serious infection involving both the upper and lower respiratory tract than those with isolated IgE deficiency. Conclusions: IgE- deficient patients have an increased prevalence of multiple immunoglobulin deficits, autoimmune disease, and nonallergic reactive airway disease when compared with a clinic population of patients with normal to elevated IgE levels

A Tribute to Justice Byron R. White

Of 107 Justices in 205 years, only twelve have served longer than thirty years, and every long-serving Justice has made a substantial contribution to the institution - offering a steady and dedicated response to the judicial challenges of an era, asserting leadership at a time of national crisis, or articulating a large constitutional vision. The personal qualities and life experiences that a new Justice brings to the Court contain the seeds of the individual\u27s judicial service. Justice White, a skeptical but unflinching democrat, was no exception

Cycle Training Increased GLUT4 and Activation of Mammalian Target of Rapamycin in Fast Twitch Muscle Fibers

Purpose: To determine whether cycle training of sedentary subjects would increase the expression of the principle muscle glucose transporters, six volunteers completed 6 wk of progressively increasing intensity stationary cycle cycling. Methods: In vastus lateralis muscle biopsies, changes in expression of GLUT1, GLUT4, GLUT5, and GLUT12 were compared using quantitative immunoblots with specific protein standards. Regulatory pathway components were evaluated by immunoblots of muscle homogenates and immunohistochemistry of microscopic sections. Results: GLUT1 was unchanged, GLUT4 increased 66%, GLUT12 increased 104%, and GLUT5 decreased 72%. A mitochondrial marker (cytochrome c) and regulators of mitochondrial biogenesis (peroxisome proliferator-activated receptor γ coactivator 1 α and phospho-5′-adenosine monophosphate-activated protein kinase) were unchanged, but the muscle hypertrophy pathway component, phospho-mammalian target of rapamycin (mTOR), increased 83% after the exercise program. In baseline biopsies, GLUT4 by immunohistochemical techniques was 37% greater in Type I (slow twitch, red) muscle fibers, but the exercise training increased GLUT4 expression in Type II (fast twitch, white) fibers by 50%, achieving parity with the Type I fibers. Baseline phospho-mTOR expression was 50% higher in Type II fibers and increased more in Type II fibers (62%) with training but also increased in Type I fibers (34%). Conclusion: Progressive intensity stationary cycle training of previously sedentary subjects increased muscle insulin-responsive glucose transporters (GLUT4 and GLUT12) and decreased the fructose transporter (GLUT5). The increase in GLUT4 occurred primarily in Type II muscle fibers, and this coincided with activation of the mTOR muscle hypertrophy pathway. There was little impact on Type I fiber GLUT4 expression and no evidence of change in mitochondrial biogenesis

The Electron Bifurcating FixABCX Protein Complex from <i>Azotobacter vinelandii</i>: Generation of Low-Potential Reducing Equivalents for Nitrogenase Catalysis

The biological reduction of dinitrogen (N₂) to ammonia (NH₃) by nitrogenase is an energetically demanding reaction that requires low-potential electrons and ATP; however, pathways used to deliver the electrons from central metabolism to the reductants of nitrogenase, ferredoxin or flavodoxin, remain unknown for many diazotrophic microbes. The FixABCX protein complex has been proposed to reduce flavodoxin or ferredoxin using NADH as the electron donor in a process known as electron bifurcation. Herein, the FixABCX complex from <i>Azotobacter vinelandii</i> was purified and demonstrated to catalyze an electron bifurcation reaction: oxidation of NADH (<i>E</i>_m = −320 mV) coupled to reduction of flavodoxin semiquinone (<i>E</i>_m = −460 mV) and reduction of coenzyme Q (<i>E</i>_m = 10 mV). Knocking out <i>fix</i> genes rendered Δ<i>rnf A. vinelandii</i> cells unable to fix dinitrogen, confirming that the FixABCX system provides another route for delivery of electrons to nitrogenase. Characterization of the purified FixABCX complex revealed the presence of flavin and iron–sulfur cofactors confirmed by native mass spectrometry, electron paramagnetic resonance spectroscopy, and transient absorption spectroscopy. Transient absorption spectroscopy further established the presence of a short-lived flavin semiquinone radical, suggesting that a thermodynamically unstable flavin semiquinone may participate as an intermediate in the transfer of an electron to flavodoxin. A structural model of FixABCX, generated using chemical cross-linking in conjunction with homology modeling, revealed plausible electron transfer pathways to both high- and low-potential acceptors. Overall, this study informs a mechanism for electron bifurcation, offering insight into a unique method for delivery of low-potential electrons required for energy-intensive biochemical conversions