Abstract:
:The blood-brain barrier (BBB) is the rate-limiting step in the translation of neurotrophin neuroscience into clinically effective neurotherapeutics. Since neurotrophins do not cross the BBB, these proteins cannot be used for neuroprotection following intravenous administration, and it is not feasible to administer these molecules by intra-cerebral injection in human stroke. The present studies describe the development of the chimeric peptide brain drug targeting technology and the use of brain-derived neurotrophic factor (BDNF) chimeric peptides in either global or regional brain ischemia. The BDNF chimeric peptide is formed by conjugation of BDNF to a monoclonal antibody (MAb) to the BBB transferrin receptor, and the MAb acts as a molecular Trojan Horse to ferry the BDNF across the BBB via transport on the endogenous BBB transferrin receptor. High degrees of neuroprotection in transient forebrain ischemia, permanent middle cerebral artery occlusion, or reversible middle cerebral artery occlusion are achieved with the delayed intravenous administration of BDNF chimeric peptides. In contrast, no neuroprotection is observed following the intravenous administration of unconjugated BDNF, because the neurotrophin does not cross the BBB in vivo.
journal_name
Adv Exp Med Bioljournal_title
Advances in experimental medicine and biologyauthors
Pardridge WMdoi
10.1007/978-1-4615-0123-7_15subject
Has Abstractpub_date
2002-01-01 00:00:00pages
397-430eissn
0065-2598issn
2214-8019journal_volume
513pub_type
杂志文章,评审abstract::Screening of chromogenic peptide substrates have shown that FXIIa readily splits substrates of D-Pro-Phe-Arg-pNA (S-2302) and -Gly-Arg-pNA (e.g. S-2222) types. The latter type is preferred in a system where kallikrein is present. By using the substrate S-2222 a method for the determination of beta FXIIa inhibitors has...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4757-0154-8_7
更新日期:1986-01-01 00:00:00
abstract::Major congenital anomalies are detectable in 2-3 % of the newborn population. Some of their genetic causes are attributable to copy number variations identified by array comparative genomic hybridization (aCGH). The value of aCGH screening as a first-tier test in children with multiple congenital anomalies has been st...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/5584_2016_235
更新日期:2016-01-01 00:00:00
abstract::Carcinogens occur naturally in the foods we eat, including a number of HCAs that have been identified in foods (beef, pork, poultry and fish) as a result of cooking. These compounds are formed during the normal cooking process by the reaction of creatine with various amino acids. The HCAs have been identified as a res...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4615-1957-7_20
更新日期:1995-01-01 00:00:00
abstract::Oxygen plays a key role in tumor therapy and may be related to tumor development: e.g., angiogenesis and metastasis. Using noninvasive techniques to accurately measure tumor oxygenation could assist in developing novel therapies. Here, we have used the FREDOM (Fluorocarbon Relaxometry using Echo planar imaging for Dyn...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4615-0075-9_22
更新日期:2003-01-01 00:00:00
abstract::Evidence continues to accumulate that strengthens the proposal of heterogeneity within both the AT1 and the AT2 receptor subtypes. Pharmacologic, biochemical and immunological studies of AT2 receptors expressed in N1E-115 cells strengthen the hypothesis of AT2 receptor heterogeneity. However, it is important to reasse...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4899-1376-0_21
更新日期:1996-01-01 00:00:00
abstract::Cell-free protein synthesis based on E. coli cell extracts has been described for the first time more than 50 years ago. To date, cell-free synthesis is widely used for the preparation of toxic proteins, for studies of the translation process and its regulation as well as for the incorporation of artificial or labeled...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-3-319-27216-0_6
更新日期:2016-01-01 00:00:00
abstract::This article reviews the factors influencing myocardial oxygen supply and demand. The regulative mechanisms in coronary blood flow, especially in critical conditions, are explained. Myocardial oxygenation in coronary artery disease is discussed with special reference to pharmacological intervention. An extensive evalu...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4615-3428-0_63
更新日期:1992-01-01 00:00:00
abstract::Throughout evolution, eukaryotic cells have devised different mechanisms to cope with stressful environments. When eukaryotic cells are exposed to stress stimuli, they activate adaptive pathways that allow them to restore cellular homeostasis. Most types of stress stimuli have been reported to induce a decrease in ove...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-3-030-19966-1_6
更新日期:2019-01-01 00:00:00
abstract::The results of selective breeding for differential impairment of motor activity after alcohol injection is shown for the first 13 generations of the LA and MA rat strains. In F13 rats, the mean decrement of activity after 1.5 g ethanol per kg i/p. is 90% for MA rats and 42% for LA rats, the strain difference significa...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4899-5181-6_5
更新日期:1977-01-01 00:00:00
abstract::Heart disease is widely believed to develop from two pathological processes. Circulating lipoproteins containing the nondegradable lipid, cholesterol, accumulate within the arterial wall and perhaps are oxidized to more toxic lipids. Both lipid accumulation and vascular reaction to the lipids lead to the gradual thick...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4614-0650-1_2
更新日期:2011-01-01 00:00:00
abstract::We have developed an approach termed '2D hybrid analysis' for building three-dimensional (3D) structures from electron microscopy (EM) images of biological molecules. The key advantage is that it is applicable to flexible molecules, which are difficult to analyze by the approach in which 3DEM maps are reconstructed. I...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-981-13-2200-6_12
更新日期:2018-01-01 00:00:00
abstract::The mechanism of the enhancement and the deficit of isometric force in response to slow length changes in tetanized frog muscle fibers was studied by recording the stiffness changes with sinusoidal vibrations (0.5-1.9 kHz, peak-to-peak amplitude 0.1% of L0). When a tetanized fiber was slowly stretched, the fiber stiff...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract::Cancer metabolism is a well-known target of cancer therapeutics. Classically, cancer metabolism has been studied in terms of the dependence of cancer cells on crucial metabolites, such as glucose and glutamine. But, the accumulating data show that iron metabolism in tumor microenvironment is also an important factor i...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-3-030-43093-1_3
更新日期:2020-01-01 00:00:00
abstract::Before any clinical signs of diabetic retinopathy can be detected, two major histopathological lesions occur in the walls of retinal capillaries: basement membrane thickening; and loss of intramural pericytes (mural cells). A decrease in the number of pericyte to endothelial cell junctions also occurs under diabetic c...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4684-5616-5_45
更新日期:1988-01-01 00:00:00
abstract::The primary function of the mammalian lung is to facilitate diffusion of oxygen to venous blood and to ventilate carbon dioxide produced by catabolic reactions within cells. However, it is also responsible for a variety of other important functions, including host defense and production of vasoactive agents to regulat...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4614-1222-9_11
更新日期:2012-01-01 00:00:00
abstract::Non-coding RNAs mediated core elements of pathways contributes to the disorder of biological function in diseases. Identification of non-coding RNAs mediated subpathways not only can help for deciphering the pathogenic mechanism of complex diseases, but also can gain insight into the functional roles of non-coding RNA...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-981-13-0719-5_9
更新日期:2018-01-01 00:00:00
abstract::We have briefly discussed immunogenetic studies of families with hyperglycemia which suggest the existence of at least four types of the disease: a) juvenile, insulin-dependent, ketosis prone diabetes determined by an autosomal recessive gene with 50% penetrance and in linkage with the HLA; b) juvenile, insulin-depend...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4615-9110-8_9
更新日期:1979-01-01 00:00:00
abstract::A rapid, non-invasive urine test for early stage alcohol-induced liver disease (ALD) would permit risk stratification and treatment of high-risk individuals before ALD leads to irreversible liver damage and death. Urinary metabolomic studies were carried out to identify ALD-associated metabolic biomarkers using Ppara-...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-3-319-09614-8_13
更新日期:2015-01-01 00:00:00
abstract::For many years it has been known that developing cells of Dictyostelium discoideum show periodic surges as they aggregate. When it was discovered that the cells were responding chemotactically to cAMP gradients produced within the populations, experiments were carried out that demonstrated similar periodic changes in ...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-0-387-09794-7_3
更新日期:2008-01-01 00:00:00
abstract::Four new triterpene saponins of the oleanan series-melilotosides I, II, III, IV and nonglycosylated soyasapogenol B have been isolated from roots of Melilotus albus Medik. (Leguminosae) and four steroid saponins were isolated from M. tauricus (Bieb.) ser. seeds. The chemical structure of the saponins and of their agly...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4613-0413-5_18
更新日期:1996-01-01 00:00:00
abstract::Malignant epithelial tumors of the upper digestive tract are a major cause of cancer-related death worldwide. The most common of these cancers are head and neck squamous cell carcinomas (HNSCC) and esophageal cancers (EC), which are both characterized by early dissemination and poor prognosis. Although patients with e...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-3-319-97746-1_4
更新日期:2018-01-01 00:00:00
abstract::The sensory basis upon which judgments of force are made during fatiguing isometric contractions is reviewed. At issue is whether the perception of force is based on centrally generated sensations arising from the motor command, known as the sense of effort, or from peripheral sensations originating in the muscle, and...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4899-1016-5_24
更新日期:1995-01-01 00:00:00
abstract::Mammary gland homeostasis is regulated by both endogenous and exogenous signals, creating a balance between proliferation and apoptosis. It is thought that breast cancer develops from the acquisition of multiple genetic changes. The function of tumor suppressor p53 is fequently lost in cancers; however, not all cells ...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-0-387-69080-3_35
更新日期:2008-01-01 00:00:00
abstract::The human Usher syndrome (USH) is the most frequent cause of combined hereditary deaf-blindness. USH is genetically and clinically heterogeneous: 15 chromosomal loci assigned to 3 clinical types, USH1-3. All USH1 and 2 proteins are organized into protein networks by the scaffold proteins harmonin (USH1C), whirlin (USH...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4614-3209-8_67
更新日期:2014-01-01 00:00:00
abstract:OBJECTIVE:To assess the role of cholinergic angonists and antagonists on the growth control of cultured rabbit detrusor smooth muscle cells. DESIGN:Dosage dependent growth curve analysis of smooth muscle cells in standard media to bethanechol and atropine at concentrations from 1 x 10(-5) to 1 x 10(-9) mMol. RESULTS:...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4899-1585-6_33
更新日期:1995-01-01 00:00:00
abstract::This chapter summarized the taxonomy and typing works of Yersinia pestis since it's firstly identified in Hong Kong in 1894. Phenotyping methods that based on phenotypic characteristics, including biotyping, serotyping, antibiogram analysis, bacteriocin typing, phage typing, and plasmid typing, were firstly applied in...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-94-024-0890-4_3
更新日期:2016-01-01 00:00:00
abstract::Quantitative analysis of the interactions between nanomaterials and their surrounding environment is crucial for safety evaluation in the application of nanotechnology as well as its development and standardization. In this chapter, we demonstrate the importance of the adsorption of surrounding molecules onto the surf...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-3-319-47754-1_8
更新日期:2017-01-01 00:00:00
abstract::As longevity expands, women are spending a third of their existence in menopause and beyond. The vast majority suffer from symptoms that negatively impact their quality of life. Systemic vasomotor symptoms (VMS) are the classic cluster affecting 80% of peri- and post-menopausal women. Once thought to be relatively bri...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-3-030-38474-6_6
更新日期:2020-01-01 00:00:00
abstract::The first purpose of this work was to obtain direct evidence that tissue kallikreins cleave arginyl bonds when the leaving group is Arg-Val, and on the contrary, do not split them when it is Arg-Pro; the second aim was to ascertain whether this specificity could be used as a criterion, for characterizing tissue kallik...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4684-5143-6_33
更新日期:1986-01-01 00:00:00
abstract::Kinins are potent myotropic agents acting on a variety of smooth muscle preparations: isolated arteries, veins, intestines, tracheae, urinary bladders, uteri, etc. In these tissues, kinins activate at least two different receptor types, B1 and B2. B1 and B2 receptors for kinins have been identified by measuring the or...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4684-5143-6_73
更新日期:1986-01-01 00:00:00