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Biomedical subjects

Daniel Gold

Publications and source records attributed to Daniel Gold.

12 recordsLinked to original sources
PubMed2006

Mapping of the complement C9 binding domain in paramyosin of the blood fluke Schistosoma mansoni.

Schistosomes are believed to evade complement-mediated damage by expression of complement inhibitory proteins. Our previous results [Deng, J., Gold, D., LoVerde, P.T., Fishelson, Z., 2003. Inhibition of the complement membrane attack complex by Schistosoma mansoni paramyosin. Infect. Immun. 71, 6402-6410.] have demonstrated that paramyosin (Pmy) of the blood fluke S. mansoni binds to the human complement proteins C8 and C9, inhibits complement activation at the terminal stage and protects the parasite from complement-mediated damage. In order to locate the Pmy binding site to C8 and C9, various fragments of Pmy cDNA were PCR-cloned into a pET28a bacterial expression vector. Recombinant His-tagged Pmy fragments were expressed in BL21 Escherichia coli and purified over a nickel-nitrilotriacetic acid column. Binding assays by Western blotting with monoclonal anti-His antibody demonstrated that PmyCC (Pmy amino acids (744)Asp-(866)Met) was the only Pmy fragment that bound to human C8 and C9. Functional analyses demonstrated that PmyCC inhibited hemolysis of rabbit erythrocytes and of antibody-sensitized sheep erythrocytes by human complement. Importantly, PmyCC inhibited in vitro killing of trypsin-sensitized schistosomula of S. mansoni by human complement. In the presence of PmyCC, Zn(2+)-induced C9 polymerization was inhibited. Most of the immunodominant B-cell antigenic epitopes of Pmy are present in the PmyCC region, as antibodies collected from mice immunized with recombinant Pmy bound primarily to PmyCC. Taken together, this study has mapped the complement regulatory domain in Pmy, capable of binding to C8 and C9 and preventing polyC9 formation, to its C-terminal region.

Animals↗
PubMed2005

Differential infectivity of Transversotrema patialense for naive fish.

The discovery of Transversotrema patialense cercariae in an aquarium harboring tropical fish triggered the present study. The purpose was to estimate the potential range of infection of local freshwater and fishpond populations by T. patialense. Experimental infection of T. patialense differed among 3 species employed: 76.5% for Tilapia zillii, 37.8% for Gambusia affinis, and none for 2 varieties of Cyprinus carpio. These patterns of infectivity are different from those published previously for T. patialense infections, and they may be attributed to the origin of the fish (temperate water vs. tropical and subtropical waters) and the size of their scales. In G. affinis, but not in the other species, worm load and fish length were closely related, and the left side harbored heavier worm burdens than the right side. Taken together, these results suggest that imported T. patialense may spread to various indigenous natural and cultured fish populations, with ensuing potential harm to these populations.

Animals↗
PubMed2005

Ecto- and exo-protein kinases in Schistosoma mansoni: regulation of surface phosphorylation by acetylcholine and identification of the alpha subunit of CKII as a major secreted protein kinase.

The Schistosoma mansoni parasite life cycle involves complex developmental processes that enable it to cause severe hepatic damage. Protein phosphorylation has previously been implicated in the transformation of cercariae to schistosomula of S. mansoni. Here, we studied the possible involvement of surface (ecto) and shed (exo) protein kinases (PKs) in this developmental process. We found that ecto-PKs are indeed located on the surface of the schistosomula and can phosphorylate up to 5 distinct proteins at this location. Surface phosphorylation was sensitive to acetylcholine, which increased phosphorylation of 3 proteins and reduced phosphorylation of the other 2. The ecto-PKs can be shed from the surface into the incubation medium during parasite differentiation. The main exo-PK is CKII, as concluded from the substrate specificity of the PK, its inhibition by heparin, activation by spermin, and recognition by antibody directed to the anti--alpha-subunit of CKII in the incubation medium of the schistosomula. In spite of its similarity to the ecto-PKs, the activity of the exo-PK is not affected by addition of acetylcholine. These results indicate that ecto- and exo-PKs could be involved in the parasite's development or host-parasite interactions.

Acetylcholine↗
PubMed2003

A novel Arabidopsis acetyltransferase interacts with the geminivirus movement protein NSP.

Protein acetylation is important in regulating DNA-templated processes specifically and protein-protein interactions more generally in eukaryotes. The geminivirus movement protein NSP is essential for virus movement, shuttling the viral DNA genome between the nucleus and the cytoplasm. We have identified a novel Arabidopsis protein, AtNSI, that interacts with NSP. AtNSI is highly conserved among widely divergent plants. Biochemical studies show that its interaction with NSP is direct and that AtNSI acetylates histones, but not NSP, in vitro. Rather, AtNSI specifically acetylates the viral coat protein. AtNSI is a nuclear protein but does not act as a transcriptional coactivator in vitro, which distinguishes it from known eukaryotic histone acetyltransferases. Its overexpression enhances the efficiency of infection by Cabbage leaf curl virus. These findings suggest a role for protein acetylation in coordinating replication of the viral DNA genome with its export from the nucleus.

Acetyltransferases↗
PubMed2003

Inhibition of the complement membrane attack complex by Schistosoma mansoni paramyosin.

Larvae and adults of the parasitic blood fluke Schistosoma mansoni are resistant to killing by human complement. An earlier search by Parizade et al. for a schistosome complement inhibitor identified a 94-kDa surface protein which was named SCIP-1 (M. Parizade, R. Arnon, P. J. Lachmann, and Z. Fishelson, J. Exp. Med. 179:1625-1636, 1994). Following partial purification and analysis by mass spectrometry, we have determined SCIP-1 to be a surface-exposed form of the muscle protein paramyosin. As shown by immunofluorescence, anti-paramyosin antibodies label the surface of live schistosomula and adult worms. Like SCIP-1, purified native paramyosin reacts with a polyclonal rabbit anti-human CD59 antiserum, as shown by Western blot analysis. Also, the human complement components C8 and C9 bind to recombinant and native paramyosin. Analysis of paramyosin binding to fragments of C9 generated by thrombin or trypsin has demonstrated that paramyosin binds to C9 at a position located between Gly245 and Arg391. Paramyosin inhibited Zn(2+)-induced C9 polymerization and poly-C9 deposition onto rabbit erythrocytes (E(R)). In addition, paramyosin inhibited lysis of E(R) and of sensitized sheep erythrocytes by human complement. Finally, anti-paramyosin antibodies enhanced in vitro killing of schistosomula by normal and C4-depleted human complement. Taken together, these findings suggest that an exogenous form of S. mansoni paramyosin inhibits activation of the terminal pathway of complement and thus has an important immunomodulatory role in schistosomiasis.

Animals↗
PubMed2003

Killing of schistosomes by elastase and hydrogen peroxide: implications for leukocyte-mediated schistosome killing.

Activated leukocytes participate in immunity to infection by the parasitic blood fluke Schistosoma mansoni. They attach to the surface of schistosomes and secrete schistosomicidal substances. Cationic proteins, hydrolytic enzymes, and oxidants, produced by the leukocytes, have been implicated in the damage to the schistosomes. To examine the possible involvement of elastase in the killing of schistosomes by leukocytes, young and adult stages of S. mansoni were treated in vitro with pancreatic elastase (PE) and neutrophil elastase (NE). Schistosomula, lung-stage schistosomula (LSS), and adult worms (AW) have been found to be sensitive to both PE and NE. Male AW were more sensitive to PE than female AW. The enzymatic activity of elastase is essential for its toxic effect because heat-inactivation and specific elastase inhibitors prevented elastase-mediated schistosome killing. Thus, alpha1-antitrypsin and the chloromethyl ketone (CMK)-derived tetrapeptides Ala-Ala-Pro-Val-CMK and Ala-Ala-Pro-Ala-CMK but not Ala-Ala-Pro-Phe-CMK and Ala-Ala-Pro-Leu-CMK blocked PE caseinolytic and schistosomulicidal activities. As shown previously, schistosomes are also efficiently killed by hydrogen peroxide. LSS appear to be more resistant than AW and early-stage schistosomula to the lytic effects of hydrogen peroxide. Cotreatment experiments with both elastase and hydrogen peroxide indicated that they exert an additive toxic effect and that hydrogen peroxide sensitizes schistosomula to the toxic effect of elastase but not vice versa. These results demonstrate, for the first time, that elastases may be toxic molecules used by neutrophils, eosinophils, and macrophages to kill various developmental stages of S. mansoni.

Amino Acid Chloromethyl Ketones↗
PubMedDate not supplied

The Eye in the Old Testament and Talmud.

The Old Testament and Talmud contain references to the eye and its diseases. Ancient ophthalmology, emanating from Egyptian and Greek medicine, was confined to diseases of the external eye. Blindness was widespread in biblical times. We present some descriptions of the eye, its parts and disorders, as they appear in the Bible and Talmud. At times, there are other references that provide interesting clues as to possible systemic disorders associated with the visual problems experienced by the people who appear in the Biblical narrative. Did Isaac have diabetic retinopathy, Jacob hypermature cataract, and Elijah absolute glaucoma?

Bible↗
PubMedDate not supplied

Visual field defects after radial optic neurotomy for central retinal vein occlusion.

PURPOSE: Surgical decompression of the vein in central retinal vein occlusion (CRVO) by radial optic neurotomy (RON) was recently proposed as being surgically feasible, safe, and beneficial. The effect of RON on the visual field has not been systematically reported, although possible visual field defects are expected due to iatrogenic cutting of the optic nerve fibers. The authors report the results of visual field testing in patients who underwent RON at the Tel Aviv Medical Center. METHODS: Twelve consecutive patients (8 men, mean age of all patients 68 years) with nonperfused or indeterminate CRVO whose initial visual acuity (VA) was < or =20/400 underwent RON. Nine of these patients were able to perform visual field tests at 6 months post-RON and their visual field results are presented. RESULTS: : VA improved by > or =3 lines in 5 patients (42%). Three (25%) patients had a final VA of > or =20/200 and another had a final VA > or =20/50. Fundus and VA improvement were relatively slow. Two patients had clearing of the intraretinal blood, resolution of the venous dilation, and improved VA at the 2-month follow-up visit. Temporal visual field defects consisting of temporal ones that could be correlated to the site of the RON incision were detected in five out of the nine patients who were able to perform visual field tests. No temporal visual field defects were found in the remaining four patients, and three other patients were unable to perform visual field tests due to inability to identify the largest target size. CONCLUSION: VA improvement in 5 of 12 patients with ischemic or indeterminate CRVO following RON may be better than the natural history of CRVO. The risk of visual field defects may, however, be heightened by possibly cutting off blood supply to the optic nerve head and possible damage to nerve fibers in the optic nerve head, both inherent to the surgical procedure and both likely to produce visual loss.

Adult↗
PubMedDate not supplied

Building program participation: strategies for recruitment and retention in worksite health promotion programs.

Building program participation is vital for all health promotion programs. There are a large variety of strategies that have been used to enhance recruitment and retention in worksite health promotion programs. Many of these strategies are examined and their significance in the design and operation of health promotion programs in worksite settings is reviewed.

Community Participation↗
PubMedDate not supplied

Best practices for an integrated population health management (PHM) program.

Large employers are beginning to create much more robust and potentially effective systems of integrated health management interventions. This organization-wide activity is referred to as a "Population Health Management" (PHM) approach. Best practices are also beginning to emerge in this area, and a number of technical developments are helping shape the patterns of response from innovative employers. This initiative is rapidly emerging as a critical part of overall business and health care strategy.

Behavior Therapy↗