A Phase I, First-In-Human Study of CBA-1205, an Anti-DLK1 Monoclonal Antibody, in Patients With Advanced Solid Tumors.

CBA-1205 is a novel humanized antibody targeting delta-like 1 homolog (DLK1) that enhances antibody-dependent cellular cytotoxicity activity. DLK1 overexpression has been reported in various cancer types, such as hepatocellular carcinoma and neuroblastoma. CBA-1205 demonstrates potent antitumor activity in multiple tumor models, making it a potential treatment option for DLK1-expressing cancers.

Systematic review of strategies to increase men's HIV-testing in sub-Saharan Africa.

Objective: This systematic review summarizes evidence on the effectiveness of strategies to increase men's HIV-testing in sub-Saharan Africa.

Methods: Medline, EmBase, Africa-Wide Information and Global Health were searched. Cluster and individually randomized trials evaluating interventions to increase the proportion of adults (≥ 15 years) testing for HIV were eligible if they were conducted in sub-Saharan Africa, included men in the study population, and reported HIV-testing data by sex.

Cell bank characterization and fermentation optimization for production of recombinant heavy chain C-terminal fragment of botulinum neurotoxin serotype E (rBoNTE(H(c)): antigen E) by Pichia pastoris.

A process was developed for production of a candidate vaccine antigen, recombinant C-terminal heavy chain fragment of the botulinum neurotoxin serotype E, rBoNTE(H(c)) in Pichia pastoris. P. pastoris strain GS115 was transformed with the rBoNTE(H(c)) gene inserted into pHILD4 Escherichia coli-P.

Dynamics of carbon monoxide binding to cystathionine beta-synthase.

Cystathionine beta-synthase (CBS) condenses homocysteine, a toxic metabolite, with serine in a pyridoxal phosphate-dependent reaction. It also contains a heme cofactor to which carbon monoxide (CO) or nitric oxide can bind, resulting in enzyme inhibition. To understand the mechanism of this regulation, we have investigated the equilibria and kinetics of CO binding to the highly active catalytic core of CBS, which is dimeric.

Cancer in the Republic of Palau (Belau).

This study, funded by the National Cancer Institute, assessed cancer awareness and service needs in the Republic of Belau (Belau) in April 2003. Cancer prevention and control is a concern for Belau, and this country maintains a cancer registry to track cases and outcomes. However, assistance is needed to strengthen and expand existing cancer-related services.

Cancer in Yap State, Federated States of Micronesia.

Little is known about the impact of cancer and the extent of cancer-related services in Yap. The purpose of this study, funded by the National Cancer Institute, was to document the state of cancer awareness and services in Yap and to prioritize cancer-care needs. Findings suggest that cancer is the leading cause of death in Yap, yet cancer-related awareness, prevention, detection, and treatment services are limited.

Reaction mechanism and regulation of cystathionine beta-synthase.

In mammals, cystathionine beta-synthase catalyzes the first step in the transsulfuration pathway which provides an avenue for the conversion of the essential amino acid, methionine, to cysteine. Cystathionine beta-synthase catalyzes a PLP-dependent condensation of serine and homocysteine to cystathionine and is unique in also having a heme cofactor. In this review, recent advances in our understanding of the kinetic mechanism of the yeast and human enzymes as well as pathogenic mutants of the human enzyme and insights into the role of heme in redox sensing are discussed from the perspective of the crystal structure of the catalytic core of the human enzyme.

Human cystathionine beta-synthase is a heme sensor protein. Evidence that the redox sensor is heme and not the vicinal cysteines in the CXXC motif seen in the crystal structure of the truncated enzyme.

Elevated levels of homocysteine, a sulfur-containing amino acid, are correlated with increased risk for cardiovascular diseases and Alzheimers disease and with neural tube defects. The only route for the catabolic removal of homocysteine in mammals begins with the pyridoxal phosphate- (PLP-) dependent beta-replacement reaction catalyzed by cystathionine beta-synthase. The enzyme has a b-type heme with unusual spectroscopic properties but as yet unknown function.

Stopped-flow kinetic analysis of the reaction catalyzed by the full-length yeast cystathionine beta-synthase.

Cystathionine beta-synthase found in yeast catalyzes a pyridoxal phosphate-dependent condensation of homocysteine and serine to form cystathionine. Unlike the homologous mammalian enzymes, yeast cystathionine beta-synthase lacks a second cofactor, heme, which facilitates detailed kinetic studies of the enzyme because the different pyridoxal phosphate-bound intermediates can be followed by their characteristic absorption spectra. We conducted a rapid reaction kinetic analysis of the full-length yeast enzyme in the forward and reverse directions.

Mercuric chloride-induced spin or ligation state changes in ferric or ferrous human cystathionine beta-synthase inhibit enzyme activity.

Cystathionine beta-synthase is a key heme and pyridoxal phosphate-dependent enzyme involved in homocysteine metabolism in humans. The role of the recently discovered heme in this protein remains an important open question. The axial ligands to the heme in both the ferrous and ferric states have been assigned as cysteine and histidine residues, respectively.

Characterization of NO binding to human cystathionine beta-synthase: possible implications of the effects of CO and NO binding to the human enzyme.

Homocysteine is a key junction metabolite that can be converted to cystathionine in a reaction catalyzed by the heme and pyridoxal phosphate-dependent cystathionine beta-synthase. The heme has unusual spectroscopic properties and the axial ligands have been assigned as histidine and cysteine, respectively. Its role in the protein is not obvious from the chemistry of the beta-replacement reaction that is catalyzed.

Coronary artery bypass performed without the use of cardiopulmonary bypass is associated with reduced cerebral microemboli and improved clinical results.

Study Objectives: Strokes and neurocognitive dysfunction have been correlated with cerebral microemboli produced during cardiopulmonary bypass (CPB). The purpose of this study was to determine whether, and to what extent, off-pump coronary artery bypass (OPCAB) reduces the occurrence of cerebral microemboli compared with traditional coronary artery bypass grafting (CABG) with CPB and to compare clinical results.

Design And Patients: A retrospective review of 137 patients undergoing elective CABG was performed, 70 of whom underwent traditional CABG and 67 of whom underwent OPCAB.

Resonance Raman characterization of the heme cofactor in cystathionine beta-synthase. Identification of the Fe-S(Cys) vibration in the six-coordinate low-spin heme.

Human cystathionine beta-synthase (CBS) is an essential enzyme for the removal of the toxic metabolite homocysteine. Heme and pyridoxal phosphate (PLP) cofactors are necessary to catalyze the condensation of homocysteine and serine to generate cystathionine. While the role for the PLP cofactor is thought to be similar to that in other PLP-dependent enzymes that catalyze beta-replacement reactions, the exact role for the heme remains unclear.

Coronary artery bypass grafting performed with or without a bypass pump: early results.

Introduction: Traditionally, heart bypass surgery has required stopping of the heart and the use of cardiopulmonary bypass. Numerous complications have been associated with exposure to this extracorporeal circuit. Newer techniques of local cardiac wall stabilization now enable this operation to be performed safely "Off Pump".

Vital immunohistochemical staining for a novel method of diagnosing micro-cancer. Examination of immunohistochemical staining of non-fixed fresh tissue.

It becomes possible to establish a novel diagnostic method for micro-cancer by modulating the signals from the lesion, if lesions can be labeled with substances which can be detected by video endoscopy. The authors have already succeeded in synthesizing indocyanine green (ICG) derivatives for a fluorescent labeling substance which emits near-infrared rays. Before the antibodies labeled by these substances can be used, it is necessary to establish a method of vital immunohistochemical staining.

Assignment of enzymatic functions to specific regions of the PLP-dependent heme protein cystathionine beta-synthase.

Cystathionine beta-synthase is a unique heme protein that catalyzes a pyridoxal phosphate (or PLP)-dependent beta-replacement reaction. The reaction involves the condensation of serine and homocysteine and constitutes one of the two major avenues for detoxification of homocysteine in mammals. The enzyme is allosterically regulated by S-adenosylmethionine (AdoMet).

Labeled carcinoembryonic antigen antibodies excitable by infrared rays: a novel diagnostic method for micro cancers in the digestive tract.

Object: An indocyanine green derivative (ICG-sulfo-OSu) was used as the labeling substance for monoclonal antibody, and a fluorescence imaging system appropriate for ICG-sulfo-OSu excitable by infrared rays (IR) was developed. The goal of this study was to demonstrate antibody labeling at the tissue level using this new imaging system.

Materials And Methods: ICG-sulfo-OSu labeled mouse anti-human carcinoembryonic antigen (CEA) monoclonal antibody, a newly developed imaging system, and an infrared ray microscope were employed in this experiment.

Characterization of the heme and pyridoxal phosphate cofactors of human cystathionine beta-synthase reveals nonequivalent active sites.

Cystathionine beta-synthase is an unusual enzyme that requires the cofactors heme and pyridoxal phosphate (PLP) to catalyze the condensation of homocysteine and serine to generate cystathionine. This transsulfuration reaction represents one of two major cellular routes for detoxification of homocysteine, which is a risk factor for atherosclerosis. While the beta-replacement reaction catalyzed by this enzyme suggests a role for the pyridoxal phosphate, the role of the heme is uncertain.

Evidence for heme-mediated redox regulation of human cystathionine beta-synthase activity.

Human cystathionine beta-synthase catalyzes the first step in the catabolic removal of the toxic metabolite, homocysteine. It is unique in being dependent on both pyridoxal phosphate (PLP) and heme for activity. The reaction involves condensation of serine and homocysteine to give cystathionine.

Antibodies labeled with fluorescence-agent excitable by infrared rays.

Endoscopy is not significantly better than fiberoscopy for the diagnosis of minute cancers of the digestive tract. However, labeling of these lesions with an agent that can be detected videoendoscopically, with subsequent computer processing of the electronic signals, should facilitate endoscopic diagnosis of microlesions. We developed an antibody labeled with an indocyanine green(ICG) derivative that has a specific fluorescence emission at 807 nm upon excitation at 768 nm.

Development of agents for reinforcement of fluorescence on near-infrared ray excitation for immunohistological staining.

Fluorescence intensity of indocyanine green (ICG) derivative (ICG-sulfo-OSu) was too low for its use to detect microlesions. Therefore, we examined the effects of reinforcement agents on ICG-sulfo-OSu labeled antibodies. Solutions of distearoylphosphatic acid sodium salt (DSPA) and octylglucoside (OG) in physiological phosphate buffered saline (PBS) were found to increase the intensity of fluorescence of ICG-sulfo-OSu labeled antibodies, with shift in the fluorescence peak wavelength from 804 to 821 nm.

Magnetic field effects on coenzyme B12-dependent enzymes: validation of ethanolamine ammonia lyase results and extension to human methylmalonyl CoA mutase.

Enzymes with radical-pair intermediates have been considered as a likely target for purported magnetic field effects in humans. The bacterial enzyme ethanolamine ammonia lyase and the human enzyme methylmalonyl-CoA mutase catalyze coenzyme B12-dependent rearrangement reactions. A common step in the mechanism of these two enzymes is postulated to be homolysis of the cobalt-carbon bond of the cofactor to generate a spin-correlated radical pair consisting of the 5'-deoxyadenosyl radical and cob(II)alamin [Ado.

Structural and electronic similarity but functional difference in methylmalonyl-CoA mutase between coenzyme B12 and the analog 2',5'-dideoxyadenosylcobalamin.

The cofactor analog 2',5'-dideoxyadenosylcobalamin (ddAdoCbl) differs from the natural cofactor coenzyme B12 [5'-deoxyadenosylcobalamin (dAdoCbl)] by lacking only one oxygen atom. The 1H and 13C NMR spectra of ddAdoCbl have been assigned unambiguously by homonuclear and heteronuclear 2D NMR techniques. The 1H, 13C, and 31P chemical shift values for ddAdoCbl were compared with those of another organocobalamin, namely dAdoCbl.

Inhibition of the human methylmalonyl-CoA mutase by various CoA-esters.

Human methylmalonyl-CoA mutase is inhibited by ethylmalonyl-CoA, cyclopropylcarbonyl-CoA carboxylate, and methylenecyclopropylacetyl-CoA, which are substrate, intermediate, and product analogs, respectively. The mode of inhibition by each analog is reversible and mixed with respect to the substrate, methylmalonyl-CoA. This implies that the inhibitors are able to bind to both free enzyme and to the enzyme-substrate complex, although with affinities that are 4.