The Acute Ischemic Penumbra: Topography, Life Span, and Therapeutic Response

Ginsberg, Myron D.,Ginsberg,Zhao, Weizhao,Huh, Pil-Woo,Busto, Raul 가톨릭대학교 2000 Bulletin of The Catholic Research Institutes of Me Vol.28 No.-

Recent advances in computerized image-averaging, used in conjunction with refined techniques for engendering hghly reproducible rodent models of focal ischemia, now make it possible to derive topographically precise, quantitative descriptors of the ischemic penumbraits localization, lifespan, metabolic and hemodynamic features, and responses to therapy. Physiologically monitored normothermic rats received 2-h middle cerebral artery occlusion (MCAo) by means of a poly-L-lysine-coated intraluminal suture. In matched groups. local cerebral blood Row (LCBF) or glucose utilization(LCMRglc) were measured autoradiographically at either 2-h MCAo or at 1-h recirculation and were correlated on a pixel-by-pixel basis with histopathological infarction after 3-day survival. A large, consistent ischemic penumbra (defined as LCBF 20~40% of control) surrounded the core (0-20% of control) Penumbral LCMRgle at 2-h MCAo was near-normal, and its metabolism/flow ratio was elevated 4-fold above normal. By 1-h recirculation, however, LCMRglc throughout the prior zone of ischemia was depressed Infarctive histopathology was precisely determined by the antecedent LCBF decrement during ischemia: 70%, and 89% of infracted pixels had antecedent LCBF values below the upper-core and upper-penumbral ranges, respectively. at 2-h MCAo. High-dose albumin therapy at the onset of recirculation dramatically attenuated cortical infarction and brain edema and appeared. by LCBF analysis at 1-h recirculation to increase postischemic LCBF; primarily in the former penumbra. (Acta Neurochirurgica Supplementum 73:45-50, 1999)

Endoscopic Stenting for Pancreatic and Biliary Diseases

Ginsberg, Gregory G. 大韓消化器內視鏡學會 2003 Clinical Endoscopy Vol.27 No.5

High-Dose Albumin Therapy Administered Protects Against Both Fluid-Percussion Brain Injury and Global Ischemia in Rats

Ginsberg, Myron D.,Belayev, Ludmila,Alonso, Ofelia F.,Saul, Isabel,Huh, Pil-Woo,Femandez. G.,Zhao, Weizhao,Finotti, Nicoletta,Busto, Raul 가톨릭대학교 2000 Bulletin of The Catholic Research Institutes of Me Vol.28 No.-

Introduction : We have recently shown that high-dose human serum albumin (HAS) therapy confers marked histological protection in experimental middle cerebral artery occlusion. The effects of high-dose HAS therapy on traumatic brain injury and global ischemia have not been assessed. Thus, the purpose of this study was to determine whether treatment with high-dose Has would protect in rat models of traumatic brain injury and global ischemia. Methods : Fluid-percussion traumatic brain injury (TBI): These studies were carried out on 18 fasted male Sprague-Dawley rats, weighing between 310 and 405g. Animals were initially anesthetized with 3% halothane, 70% nitrous oxide and a balance of oxygen and received right parieto-occipital parasagittal fluid-percussion injury (1.5-2.0 atm) as previously described. Cranial temperature was monitored throughout the experiment by a thermistor probe inserted into the left temporalis muscle and held at normothermic levels (36.5-37.5℃) by a warming lamp above the animal's head. Rectal temperature was also monitored and was maintained at 37-38℃ throughout the study. The agent (25% human serum albumin, HSA) or vehicle (sodium chloride 0.9%) was administered i.v. (1% of body weight) 15 min after trauma. Behavioral function was evaluated at all rats before and after TBI (at 2h, 24h. 48h, 72h and 7 days). Neurological function was graded on a scale of 0-12 (normal score = 0, maximal score = 12). Seven days after TBI, brains were perfusion-fixed, coronal sections at various levels were digitized, and contusion areas in superficial, middle and deep layers of cortex and in fimbria were measured. Global cerebral ischemia : Twenty-six fasted Wistar rats underwent bilateral common carotid artery occlusion for 10 min with simultaneous reduction of MABP to 50 mmHg by withdrawal of arterial blood, as previously described. Five min after termination of ischemia, animals were treated the same manner as described above. Neurological function was evaluated before ischemia, as well as 3h, 1, 2, 3 and 7 days after ischemia (normal score=16, maximal deficit=0), as previously described. Seven days after ischemia, brains were perfusion-fixed and ischemic neuronal injury in the hippocampal CA 1 area was assessed quantitatively and graded on a O to 3 scale (O=no damage; 1=minimal; 2=moderate; 3=severe damage). Results : Rectal and cranial (temporalis muscle) temperatures, arterial blood pressure, plasma glucose and blood gases in all animals of this study showed no significant differences between groups. TBI : HSA significantly improved the neurological score compared to saline at 24h after TBI(6.4 ± 0.7 and 8.4 ±0.5, respectively; p=0.03). HSA therapy also significantly reduced total contusion area (Fig. 1). (Data in figures represent mean values ±S.E.M.). Global cerebral ischemia : A significant improvement of neurological deficits by treatment with HSA was observed at 3h, 1, 2, 3 and 7 days after global ischemia (Fig 2). The cumulative histological lesion score for the left and right hippocampi was 2.9 in the saline group and 1.9 in the HSA-treated group (p<00002, Students t-test). Conclusions : Our findings document that high-concentration albumin therapy instituted 15 min after trauma or 5 min after global ischemia significantly improves the neurological score and reduces histological damage. This pharmacological agent has promising potential for the treatment of brain injury. (Journal of Cerebral Blood Flow and Metabolism [Suppl.1]19:S187, 1999)

Sparsity-constrained Extended Kalman Filter concept for damage localization and identification in mechanical structures

Ginsberg, Daniel,Fritzen, Claus-Peter,Loffeld, Otmar Techno-Press 2018 Smart Structures and Systems, An International Jou Vol.21 No.6

Structural health monitoring (SHM) systems are necessary to achieve smart predictive maintenance and repair planning as well as they lead to a safe operation of mechanical structures. In the context of vibration-based SHM the measured structural responses are employed to draw conclusions about the structural integrity. This usually leads to a mathematically illposed inverse problem which needs regularization. The restriction of the solution set of this inverse problem by using prior information about the damage properties is advisable to obtain meaningful solutions. Compared to the undamaged state typically only a few local stiffness changes occur while the other areas remain unchanged. This change can be described by a sparse damage parameter vector. Such a sparse vector can be identified by employing $L_1$-regularization techniques. This paper presents a novel framework for damage parameter identification by combining sparse solution techniques with an Extended Kalman Filter. In order to ensure sparsity of the damage parameter vector the measurement equation is expanded by an additional nonlinear $L_1$-minimizing observation. This fictive measurement equation accomplishes stability of the Extended Kalman Filter and leads to a sparse estimation. For verification, a proof-of-concept example on a quadratic aluminum plate is presented.

Impact identification and localization using a sample-force-dictionary - General Theory and its applications to beam structures

Ginsberg, Daniel,Fritzen, Claus-Peter Techno-Press 2016 Structural monitoring and maintenance Vol.3 No.3

Monitoring of impact loads is a very important technique in the field of structural health monitoring (SHM). However, in most cases it is not possible to measure impact events directly, so they need to be reconstructed. Impact load reconstruction refers to the problem of estimating an input to a dynamic system when the system output and the impulse response function are usually known. Generally this leads to a so called ill-posed inverse problem. It is reasonable to use prior knowledge of the force in order to develop more suitable reconstruction strategies and to increase accuracy. An impact event is characterized by a short time duration and a spatial concentration. Moreover the force time history of an impact has a specific shape, which also can be taken into account. In this contribution these properties of the external force are employed to create a sample-force-dictionary and thus to transform the ill-posed problem into a sparse recovery task. The sparse solution is acquired by solving a minimization problem known as basis pursuit denoising (BPDN). The reconstruction approach shown here is capable to estimate simultaneously the magnitude of the impact and the impact location, with a minimum number of accelerometers. The possibility of reconstructing the impact based on a noisy output signal is first demonstrated with simulated measurements of a simple beam structure. Then an experimental investigation of a real beam is performed.

문화 , 공동체 그리고 정체성

Allen Ginsberg 한국청소년문화연구소 2000 청소년 문화포럼 Vol.2 No.-

Invited Mini Review : Integrin activation

( Mark H Ginsberg ) 생화학분자생물학회 2014 BMB Reports Vol.47 No.12

Integrin-mediated cell adhesion is important for development, immune responses, hemostasis and wound healing. Integrins also function as signal transducing receptors that can control intracellular pathways that regulate cell survival, proliferation, and cell fate. Conversely, cells can modulate the affinity of integrins for their ligands a process operationally defined as integrin activation. Analysis of activation of integrins has now provided a detailed molecular understanding of this unique form of “inside-out” signal transduction and revealed new paradigms of how transmembrane domains (TMD) can transmit long range allosteric changes in transmembrane proteins. Here, we will review how talin and mediates integrin activation and how the integrin TMD can transmit these inside out signals.

New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk: Beyond Statins

김규호,Henry N. Ginsberg,최성희 대한당뇨병학회 2022 Diabetes and Metabolism Journal Vol.46 No.5

Corrigendum

The Rap1-RIAM-talin axis of integrin activation and blood cell function

Lagarrigue, Frederic,Kim, Chungho,Ginsberg, Mark H. American Society of Hematology 2016 Blood Vol.128 No.4

<P>Integrin adhesion receptors mediate the adhesion of blood cells, such as leukocytes, to other cells, such as endothelial cells. Integrins also are critical for anchorage of hematopoietic precursors to the extracellular matrix. Blood cells can dynamically regulate the affinities of integrins for their ligands ('activation'), an event central to their functions. Here we review recent progress in understanding the mechanisms of integrin activation with a focus on the functions of blood cells. We discuss how talin binding to the integrin beta cytoplasmic domain, in conjunction with the plasma membrane, induces long-range allosteric rearrangements that lead to integrin activation. Second, we review our understanding of how signaling events, particularly those involving Rap1 small guanosine triphosphate (GTP) hydrolases, can regulate the talin-integrin interaction and resulting activation. Third, we review recent findings that highlight the role of the Rap1-GTP-interacting adapter molecule (RIAM), encoded by the APBB1IP gene, in leukocyte integrin activation and consequently in leukocyte trafficking.</P>

New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk: Beyond Statins

김규호,Henry N. Ginsberg,최성희 대한당뇨병학회 2022 Diabetes and Metabolism Journal Vol.46 No.4

Statins are the cornerstone of the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). However, even under optimal statin therapy, a significant residual ASCVD risk remains. Therefore, there has been an unmet clinical need for novel lipid-lowering agents that can target low-density lipoprotein cholesterol (LDL-C) and other atherogenic particles. During the past decade, several drugs have been developed for the treatment of dyslipidemia. Inclisiran, a small interfering RNA that targets proprotein convertase subtilisin/kexin type 9 (PCSK9), shows comparable effects to that of PCSK9 monoclonal antibodies. Bempedoic acid, an ATP citrate lyase inhibitor, is a valuable treatment option for the patients with statin intolerance. Pemafibrate, the first selective peroxisome proliferator-activated receptor alpha modulator, showed a favorable benefit-risk balance but the large clinical phase 3 trial (Pemafibrate to Reduce Cardiovascular OutcoMes by Reducing Triglycerides IN patiENts With diabe- Tes [PROMINENT]) was recently stopped due to the underperformance from interim analysis. High dose icosapent ethyl, a modified eicosapentaenoic acid preparation, shows cardiovascular benefits. Evinacumab, an angiopoietin-like 3 (ANGPTL3) monoclonal antibody, reduces plasma LDL-C levels in patients with refractory hypercholesterolemia. Novel antisense oligonucleotides targeting apolipoprotein C3 (apoC3), ANGPTL3, and lipoprotein(a) have significantly attenuated the levels of their target molecules with beneficial effects on associated dyslipidemias. Apolipoprotein A1 (apoA1) is considered as a potential treatment to exploit the athero-protective effects of high-density lipoprotein cholesterol (HDL-C), but solid clinical evidence is necessary. In this review, we discuss the mode of action and clinical outcomes of these novel lipid-lowering agents beyond statins.