Publications

 

PAPER

ABSTRACT

SUMMARY

1970s - The Beginning

Pulseless idioventricular rhythm during CPR: an indication for massive intravenous bolus glucocorticoids.White BC. JACEP. 1976 Jun;5(6):449-54.

Abstract

Very early paper suggesting a possible use of steroids in pulseless idioventricular rhythm.

Effects of sodium bicarbonate administration during cardiopulmonary resuscitation. White BC, Tintinalli JE. JACEP. 1977 May;6(5):187-90.

Abstract

Early indication that maybe bicarb in arrest wasn't so spiffy after all.

Unilateral catecholamine depletion of the corpus striatum and amphetamine-induced turning: an ontogenetic study. White BC, Tapp WN. Psychopharmacology (Berl). 1977 Jul 18;53(2):211-2.

Abstract

Speed kills.

Monoamine synthesis and caffeine-induced locomotor activity. White BC, Simpson CC, Adams JE, Harkins D Jr. Neuropharmacology. 1978 Jul;17(7):511-3.

No Abstract Available

 

Incidence, etiology, and outcome of pulseless idioventricular rhythm treated with dexamethasone during advanced CPR.JACEP. White BC, Petinga TJ, Hoehner PJ, Wilson RF. 1979 May;8(5):188-93.

Abstract

More early work on idioventricular rhythm.

His electrocardiographic characterization of terminal arrhythmias of hemorrhagic shock in dogs. White BC, Hoehner PJ, Petinga TJ, Moeser JC, Wilson RF. JACEP. 1979 Aug;8(8):298-303.

Abstract

Early work with Robert Wilson, one of the founders of the modern concept of shock.

Early 80s - No-Reflow, Java and Crank

Mitochondrial O2 use and ATP synthesis: kinetic effects of Ca++ and HPO4(-2) modulated by glucocorticoids. White BC, Hoehner PJ, Wilson RF.Ann Emerg Med. 1980 Aug;9(8):396-403.

Abstract

Even this early on, Blaine was looking at the role of mitochondria. Nearly 30 years later, we've come full circle.

Transthoracic pacing during CPR.Tintinalli JE, White BC. Ann Emerg Med. 1981 Feb;10(2):113-6.

Abstract

Bottom line: it didn't work.

Peripheral vs central circulation times during CPR: a pilot study. Kuhn GJ, White BC, Swetnam RE, Mumey JF, Rydesky MF, Tintinalli JE, Krome RL, Hoehner PJ. Ann Emerg Med. 1981 Aug;10(8):417-9.

Abstract

During cardiac arrest and CPR, blood doesn't go round and round so well. Neither do drugs.

Canine cerebral cortical blood flow and vascular resistance post cardiac arrest. Gadzinski DS, White BC, Hoehner PJ, Hoehner T, Krome C, White JD.Ann Emerg Med. 1982 Feb;11(2):58-63.

Abstract

An early study of cerebral perfusion during CPR. The results were sobering.

Effect of flunarizine on canine cerebral cortical blood flow and vascular resistance post cardiac arrest. White BC, Gadzinski DS, Hoehner PJ, Krome C, Hoehner T, White JD, Trombley JH Jr. Ann Emerg Med. 1982 Mar;11(3):119-26.

Abstract

Flunarizine transiently improved cerebral blood flow in a dog model of cardiac arrest.

Determination of cerebral cortical blood flow: a thermal technique. Hoehner PJ, Krause GS, White BC, Gadzinski DS. Ann Emerg Med. 1983 Jan;12(1):2-7.

Abstract

Evaluation of a thermodilution method for measuring CBF.

Prolonged hypoperfusion in the cerebral cortex following cardiac arrest and resuscitation in dogs. White BC, Winegar CP, Henderson O, Jackson RE, Krause G, O'Hara T, Goodin T, Vigor DN. Ann Emerg Med. 1983 Jul;12(7):414-7.

Abstract

Demonstration of prolonged post  -resuscitation perfusion failure in the cortex, with serious implications for prospective therapies.

Early amelioration of neurologic deficit by lidoflazine after fifteen minutes of cardiopulmonary arrest in dogs. Winegar CP, Henderson O, White BC, Jackson RE, O'Hara T, Krause GS, Vigor DN, Kontry R, Wilson W, Shelby-Lane C. Ann Emerg Med. 1983 Aug;12(8):471-7.

Abstract

This calcium antagonist seemed to  improve neurologic recovery in the first 12 hours after cardiopulmonary arrest in dogs. Ultimately, White et al would come to abandon calcium antagonist therapy.

Calcium blockers in cerebral resuscitation. J Trauma. 1983 Sep;23(9):788-94. White BC, Winegar CD, Wilson RF, Krause GS.

Abstract

More on calcium blockers and their ability to maintain CBF after cardiac arrest.

Cerebral cortical perfusion during and following resuscitation from cardiac arrest in dogs. White BC, Winegar CD, Jackson RE, Joyce KM, Vigor DN, Hoehner TJ, Krause GS, Wilson RF. Am J Emerg Med. 1983 Sep;1(2):128-38.

Abstract

Basically a review of the lab's early data on the "no-reflow" phenomenon and the potential to ameliorate it with calcium antagonists.

Caffeine pretreatment: enhancement and attenuation of d-amphetamine-induced activity. White BC, Keller GE 3rd. Pharmacol Biochem Behav. 1984 Mar;20(3):383-6.

Abstract

Paper on the interaction between speed and caffeine. For tweakers only.

Caffeine reduces amphetamine-induced activity in asymmetrical interaction. White BC, Haswell KL, Kassab CD, Harkins D Jr, Crumbie PM. Pharmacol Biochem Behav. 1984 Mar;20(3):387-9.

Abstract

More on caffeine and amphetamine.

Blood flow in the cerebral cortex during cardiac resuscitation in dogs. Jackson RE, Joyce K, Danosi SF, White BC, Vigor D, Hoehner TJ.  Ann Emerg Med. 1984 Sep;13(9 Pt 1):657-9.

Abstract

More on derangements of cerebral blood flow in cardiac arrest.

Perfusion of the cerebral cortex by use of abdominal counterpulsation during cardiopulmonary resuscitation. Walker JW, Bruestle JC, White BC, Evans AT, Indreri R, Bialek H. Am J Emerg Med. 1984 Sep;2(5):391-3.

Abstract

Comparison of traditional CPR with counterpulsation +/- epi, with special focus, of course, on cerebral perfusion.

Post resuscitation iron delocalization and malondialdehyde production in the brain following prolonged cardiac arrest. Nayini NR, White BC, Aust SD, Huang RR, Indrieri RJ, Evans AT, Bialek H, Jacobs WA, Komara J. J Free Radic Biol Med. 1985;1(2):111-6.

Abstract

Here we see the beginning of what was to follow: increased emphasis on biochemical processes in brain ischemia, rather than physiological measurements. But the emphasis on potential therapies remains unchanged.

Prolonged cardiac arrest and resuscitation in dogs: brain mitochondrial function with different artificial perfusion methods. Ann Emerg Med. 1985 May;14(5):383-8. White BC, Hildebrandt JF, Evans AT, Aronson L, Indrieri RJ, Hoehner T, Fox L, Huang R, Johns D.

Abstract

Again, an early look at mitochondrial dysfunction, and a very early identification of the connection between mitochondrial dysfunction and ROS during brain ischemia-reperfusion.

Late 80s - The Metallica Years

Myocardial tissue iron delocalization and evidence for lipid peroxidation after two hours of ischemia. Holt S, Gunderson M, Joyce K, Nayini NR, Eyster GF, Garitano AM, Zonia C, Krause GS, Aust SD, White BC. Ann Emerg Med. 1986 Oct;15(10):1155-9.

Abstract

The "Metallica Era" begins, appropriately, with another demonstration of iron delocalization after ischemia. This is part of a continuing shift toward molecular investigations.

Brain cortex tissue Ca, Mg, Fe, Na, and K following resuscitation from cardiac arrest in dogs. Hoehner TJ, Garritano AM, Dilorenzo RA, O'Neil BJ, Kumar K, Koehler J, Nayini NR, Huang RR, Krause GS, Aust SD, et al. Am J Emerg Med. 1987 Jan;5(1):19-23.

Abstract

Comprehensive evaluation of metal species after cardiac arrest.

Natural course of iron delocalization and lipid peroxidation during the first eight hours following a 15-minute cardiac arrest in dogs. Krause GS, Nayini NR, White BC, Hoenher TJ, Garritano AM, O'Neil BJ, Aust SD. Ann Emerg Med. 1987 Nov;16(11):1200-5.

Abstract

More on iron delocalization. The reason for this all this focus on iron was the growing realization of the role of lipid peroxidation in ischemic brain damage, and the role of iron in catalyzing this damage, in part through the Fenton reaction.

Brain cell death following ischemia and reperfusion: a proposed biochemical sequence. Krause GS, White BC, Aust SD, Nayini NR, Kumar K. Crit Care Med. 1988 Jul;16(7):714-26.

No Abstract Available.

Early review of the field.

A quantitative morphological assessment of the effect of lidoflazine and deferoxamine therapy on global brain ischaemia. Kumar K, White BC, Krause GS, Indrieri RJ, Evans AT, Hoehner TJ, Garritano AM, Koestner A.  Neurol Res. 1988 Sep;10(3):136-40.  

Abstract

A very early stab at combine therapy. Not only did the combination not perform as hoped, the experiment failed to confirm the lab's early, hopeful findings vis-a-vis lidoflazine. Moving on....

Effect on biochemical markers of brain injury of therapy with deferoxamine or superoxide dismutase following cardiac arrest.  White BC, Nayini NR, Krause GS, Aust SD, March GG, Bicknell JS 4th, Goosmann M. Am J Emerg Med. 1988 Nov;6(6):569-76.

Abstract

Another look at deferoxamine.

Early 90s - The Long March Begins

Brain nuclear DNA survives cardiac arrest and reperfusion.White BC, DeGracia DJ, Krause GS, Skjaerlund JM, O'Neil BJ, Grossman LI. Free Radic Biol Med. 1991;10(2):125-35.

Abstract

In the early 90's, the lab became highly focused on the problem of protein synthesis inhibition. Thus began a "Long March" from the nucleus to the ribosome, looking for the lesion in translation. DNA damage was not the answer.

Thymine glycols and pyrimidine dimers in brain DNA during post-ischemic reperfusion. O'Neil BJ, Krause GS, White BC.Resuscitation. 1991 Feb;21(1):41-55.

Abstract

Molecular markers of DNA damage were not detected in this study, either.

The effect of EMHP on post-cardiac arrest survival of rats. Skjaerlund JM, Krause GS, Feldman DM, O'Neil BJ, White BC.Resuscitation. 1991 Oct;22(2):139-49.

Abstract

Another promising monotherapy that failed to work, this one directed at the iron delocalization.

Assessment of free radical-induced damage in brain proteins after ischemia and reperfusion.Krause GS, DeGracia DJ, Skjaerlund JM, O'Neil BJ.Resuscitation. 1992 Feb;23(1):59-69.Links

Abstract

Free radical reactions do not involve cellular proteins or RNAs.

Brain mitochondrial DNA is not damaged by prolonged cardiac arrest or reperfusion. White BC, Tribhuwan RC, Vander Laan DJ, DeGracia DJ, Krause GS, Grossman LI. J Neurochem. 1992 May;58(5):1716-22.

Abstract

Having already demonstrated that nuclear DNA was not damaged by reperfusion, this paper showed the same for mitochondrial DNA.

Fluorescent histochemical localization of lipid peroxidation during brain reperfusion following cardiac arrest. White BC, Daya A, DeGracia DJ, O'Neil BJ, Skjaerlund JM, Trumble S, Krause GS, Rafols JA. Acta Neuropathol. 1993;86(1):1-9.

Abstract

This paper "mapped" lipid peroxidation during reperfusion and demonstrated that it hits the selectively vulnerable neurons the hardest, primarily in the perikaryal regions.

Studies of the protein synthesis system in the brain cortex during global ischemia and reperfusion. DeGracia DJ, O'Neil BJ, Frisch C, Krause GS, Skjaerlund JM, White BC, Grossman LI. Resuscitation. 1993 Apr;25(2):161-70.

Abstract

Another stop on the Long March--the inhibition of translation could not be attributed to ribosomal damage.

Suppression of protein synthesis in the reperfused brain. Krause GS, Tiffany BR. Stroke. 1993 May;24(5):747-55; discussion 755-6.

Abstract

Review.

Brain injury and repair mechanisms: the potential for pharmacologic therapy in closed-head trauma. White BC, Krause GS. Ann Emerg Med. 1993 Jun;22(6):970-9.

 

Abstract

Review, and more early speculation on combination therapy, including growth factor therapy.

Potential role of growth factors in global brain ischemia and reperfusion. Observation of insulin-driven tyrosine phosphorylation of a 90-kDa protein during reperfusion. White BC, Krause GS, O'Neil BJ, DeGracia DJ, Tiffany BR, Grossman LI, Grunberger G.Ann N Y Acad Sci. 1993 Aug 27;692:281-3.

Abstract

A 90 kDa protein got phosphorylated by insulin during brain ischemia. Nobody ever figured out what that protein was, though, so the signficance of this paper is primarily historical.

Brain injury by global ischemia and reperfusion: a theoretical perspective on membrane damage and repair. White BC, Grossman LI, Krause GS. Neurology. 1993 Sep;43(9):1656-65.Links

No Abstract Available. Another review.

Global brain ischemia and reperfusion: Golgi apparatus ultrastructure in neurons selectively vulnerable to death.  Acta Neuropathol. 1995;90(1):17-30. Rafols JA, Daya AM, O'Neil BJ, Krause GS, Neumar RW, White BC.

Abstract

An early collaboration with our colleague, neuroanatomist Jose Rafols. This paper fit in with the lab's focus on translational control, and in this case showed that a downstream element in the processing of proteins (Golgi) was affected both structurally and chemically by ischemia.

Nuclear-envelope nucleoside triphosphatase kinetics and mRNA transport following brain ischemia and reperfusion. Tiffany BR, White BC, Krause GS. Ann Emerg Med. 1995 Jun;25(6):809-17.

Abstract

This study, by the lab's first MD-PhD fellow (Brian Tiffany), demonstrated that inhibition of protein synthesis could not be attributed to failure of message to get out of the nucleus.

Eukaryotic initiation factor 4E degradation during brain ischemia. Neumar RW, DeGracia DJ, White BC, McDermott PJ, Evans DR, Krause GS.J Neurochem. 1995 Sep;65(3):1391-4.

Abstract

Our second MD-PhD fellow (Neumar) was a pioneer in the role of calpain in ischemia, and showed that calpain degraded 4E in this study.

Late 90s - eIF2-alpha and Calpain

Brain mu-calpain autolysis during global cerebral ischemia. Neumar RW, Hagle SM, DeGracia DJ, Krause GS, White BC. J Neurochem. 1996 Jan;66(1):421-4.

Abstract

More calpain work from Bob Neumar, demonstrating that calpain undergoes autolysis during ischemia.

Ultrastructural consequences of radical damage before and after differentiation of neuroblastoma B-104 cells. O'Neil BJ, Alousi SS, White BC, Rafols JA. Acta Neuropathol. 1996 Jul;92(1):75-89.

Abstract

Hitting NB-104 cells with cumene hydroperoxide produced a cytopathologic phenotype with remarkable similarity to those seen in neurons during reperfusion.

Global brain ischemia and reperfusion. White BC, Grossman LI, O'Neil BJ, DeGracia DJ, Neumar RW, Rafols JA, Krause GS. Ann Emerg Med. 1996 May;27(5):588-94.

Abstract

Review.

Global brain ischemia and reperfusion: modifications in eukaryotic initiation factors associated with inhibition of translation initiation. DeGracia DJ, Neumar RW, White BC, Krause GS.J Neurochem. 1996 Nov;67(5):2005-12.

Abstract

The Long March arrives at eIF2-alpha phosphorylation.

Effect of brain ischemia and reperfusion on the localization of phosphorylated eukaryotic initiation factor 2 alpha. DeGracia DJ, Sullivan JM, Neumar RW, Alousi SS, Hikade KR, Pittman JE, White BC, Rafols JA, Krause GS. J Cereb Blood Flow Metab. 1997 Dec;17(12):1291-302.

Abstract

eIF2-alpha phosphorylation "maps" to selectively vulnerable neurons.

Calpain mediates eukaryotic initiation factor 4G degradation during global brain ischemia. Neumar RW, DeGracia DJ, Konkoly LL, Khoury JI, White BC, Krause GS. J Cereb Blood Flow Metab. 1998 Aug;18(8):876-81.

Abstract

Bringing together Bob Neumar's calpain work with the translational control investigations.

Suppression of protein synthesis in brain during hibernation involves inhibition of protein initiation and elongation. Frerichs KU, Smith CB, Brenner M, DeGracia DJ, Krause GS, Marrone L, Dever TE, Hallenbeck JM. Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14511-6.

Abstract

How do squirrels do it? The answer lies within.

Eukaryotic initiation factor 2alpha kinase and phosphatase activity during postischemic brain reperfusion. DeGracia DJ, Adamczyk S, Folbe AJ, Konkoly LL, Pittman JE, Neumar RW, Sullivan JM, Scheuner D, Kaufman RJ, White BC, Krause GS. Exp Neurol. 1999 Feb;155(2):221-7.

Abstract

We had a bunch of ideas about how eIF2-alpha got phosphorylated during brain ischemia. In this paper, we proved ourselves mostly wrong.

Insulin induces dephosphorylation of eukaryotic initiation factor 2alpha and restores protein synthesis in vulnerable hippocampal neurons after transient brain ischemia. Sullivan JM, Alousi SS, Hikade KR, Bahu NJ, Rafols JA, Krause GS, White BC. J Cereb Blood Flow Metab. 1999 Sep;19(9):1010-9.

Abstract

Our long love-hate relationship with insulin begins in earnest.

2000's: PERK, the un-UPR, and more insulin

Brain ischemia and reperfusion: molecular mechanisms of neuronal injury. White BC, Sullivan JM, DeGracia DJ, O'Neil BJ, Neumar RW, Grossman LI, Rafols JA, Krause GS. J Neurol Sci. 2000 Oct 1;179(S 1-2):1-33.

Abstract

Aka "The Big Tamale." A major review of the field. Still used to orient fellows, intimidate resident rotators, and send med students into a coma.

Brain ischemia and reperfusion activates the eukaryotic initiation factor 2alpha kinase, PERK. Kumar R, Azam S, Sullivan JM, Owen C, Cavener DR, Zhang P, Ron D, Harding HP, Chen JJ, Han A, White BC, Krause GS, DeGracia DJ. J Neurochem. 2001 Jun;77(5):1418-21.

Abstract

Wherein we tracked down the kinase responsible for eIF2-alpha phosphorylation and the arrest of protein synthesis. But why? We'll get back to you on that.

Molecular pathways of protein synthesis inhibition during brain reperfusion: implications for neuronal survival or death. DeGracia DJ, Kumar R, Owen CR, Krause GS, White BC. J Cereb Blood Flow Metab. 2002 Feb;22(2):127-41.

Abstract

Yet another review, this time focused on mechanism of translation shutdown during early brain reperfusion.

Dysfunction of the unfolded protein response during global brain ischemia and reperfusion. Kumar R, Krause GS, Yoshida H, Mori K, DeGracia DJ. J. Cereb Blood Flow Metab. 2003 Apr;23(4):462-71.

Abstract

After finding that PERK was activated in the setting of transient global brain ischemia, we expected to see a classic unfolded protein response, which never materialized. In brain ischemia, it's an UN-unfolded protein response.

Persistent eIF2alpha(P) is colocalized with cytoplasmic cytochrome c in vulnerable hippocampal neurons after 4 hours of reperfusion following 10-minute complete brain ischemia. Page AB, Owen CR, Kumar R, Miller JM, Rafols JA, White BC, DeGracia DJ, Krause GS. Acta Neuropathol. 2003 Jul;106(1):8-16. Epub 2003 Apr 9.

Abstract

The title says it all.

PERK is responsible for the increased phosphorylation of eIF2alpha and the severe inhibition of protein synthesis after transient global brain ischemia. Owen CR, Kumar R, Zhang P, McGrath BC, Cavener DR, Krause GS. J Neurochem. 2005 Sep;94(5):1235-42. Epub 2005 Jul 5.

Abstract

This one nails PERK, definitively, for 2-alpha phosphorylation in brain ischemia.

Insulin blocks cytochrome c release in the reperfused brain through PI3-K signaling and by promoting Bax/Bcl-X(L) binding. Sanderson TH, Kumar R, Sullivan JM, Krause GS. J Neurochem. 2008 Jun 2.

Abstract

Insulin blocks the critical step in intrinisic apoptosis after brain ischemia. There's a funny behind-the-scenes story about this one. Just ask Sullydog if you want to be in on the joke.

Insulin Activates the PI3K-Akt Survival Pathway in Vulnerable Neurons following Global Brain Ischemia. Thomas H. Sanderson, Rita Kumar, Alina C. Murariu-Dobrin,  Andrea B. Page, Gary S. Krause,  Jonathon M. Sullivan. Neurol Res (accepted 8-15-08)

Abstract

High-dose insulin induces phosphorylation of Akt, a multi-purpose surival signaling kinase, by way of PI3K. The steps between Akt and inhibition of cytochrome c release seemed obvious to us. The data had other ideas, which means we still have a lot of questions to answer. Accepted 8-15-08; still at press.
More to Come....

 

 

 

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