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Biomedical subjects

L Kushner

Publications and source records attributed to L Kushner.

31 records · Page 2Linked to original sources

Inhibition of mammalian pyruvate dehydrogenase complex by metabolites of 3-mercaptopropanoic acid.

3-Mercaptopropanoyl-CoA and S-acetyl-3-mercaptopropanoyl-CoA, physiological metabolites of the known convulsant 3-mercaptopropanoic acid, were found to be inhibitors of purified pyruvate dehydrogenase complex from porcine and bovine heart. Under optimal conditions, 50% inhibition was obtained at 12.6 microM 3-mercaptopropanoyl-CoA or 5 microM S-acetyl-3-mercaptopropanoyl-CoA. The inhibition caused by S-acetyl-3-mercaptopropanoyl-CoA was irreversible. Maximal inhibition of the complex was observed when it was preincubated with the inhibitor under conditions which promote reduction of the endogenous lipoate.

3-Mercaptopropionic Acid↗

Crosslinked polyether/polysiloxane networks for blood-interfacing applications.

The interaction of blood with new artificial surfaces is an area of continual medical interest. In this study, a series of polyether/polysiloxane networks were synthesized, characterized in terms of both bulk and surface compositions, and evaluated for blood compatibility. The crosslinked networks were produced by reacting the epoxy groups of polyglycidoxy propyl methyl siloxane (PGPMS) with the hydroxyl end groups of polypropylene glycol (PPG). Blood compatibility was evaluated using an in vitro platelet retention test and fibrinogen adsorption experiments from human plasma and buffered saline. The PPG/PGPMS networks exhibit low fibrinogen adsorption and low platelet activation. Such properties make the networks potentially attractive as materials for blood-interfacing applications.

Adsorption↗

Fibrinogen adsorption and platelet adhesion at the surface of modified polypropylene glycol/polysiloxane networks.

The protein film adsorbed at an artificial surface ultimately affects platelet adhesion and activation. This study examines the role of fibrinogen in platelet adhesion at the surface of crosslinked polypropylene glycol (PPG)/polyglycidoxy propyl methyl siloxane (PGPMS) networks which contain polyethylene glycol monomethyl ether (PEGME) chains. These crosslinked networks were produced by reacting the epoxy groups of PGPMS with the hydroxyl groups of the polyethers. PEGME chains were attached covalently to the network at only one end while PPG chains were attached at both ends. The incorporation of PEGME resulted in a substantial reduction in fibrinogen adsorption as compared to the model network (PPG + PGPMS only), but the expected concomitant decrease in platelet adhesion was not observed.

Adsorption↗

Does the conformation of adsorbed fibrinogen dictate platelet interactions with artificial surfaces?

Platelet activation by polymer surfaces is thought to require preliminary adsorption of fibrinogen and perhaps changes in fibrinogen conformation. We measured fibrinogen adsorption by a series of polymers by two methods, using either 125I-labeled fibrinogen or 125I-labeled antifibrinogen antibodies, and correlated the results with platelet reactivity (retention and secretion) in columns of beads coated with the polymers. For polyalkyl methacrylates with 1 to 4 carbon side chains, platelet reactivity varied directly with increasing length of the alkyl side chain and with the quantity of bound fibrinogen recognizable by antifibrinogen antibody but not with the total quantity of fibrinogen adsorbed. The same pattern of results was seen with five antibody preparations, including affinity-purified Fab fragments against the D or E domain of fibrinogen. Tests of platelet retention and fibrinogen binding to four polyalkyl acrylates and to three unrelated polymers (polystyrene, polymethyl methacrylate, and a polyether polyurethane) indicated that platelet retention correlated positively with both total fibrinogen binding and with the amount of antibody-recognizable fibrinogen bound. Drugs that block platelet aggregation, but not adhesion, did not alter the hierarchy of platelet retention to the polyalkyl methacrylates. These data suggest that, contrary to previous views, platelet adhesion to artificial surfaces increases with increasing surface coverage of adsorbed fibrinogen if the bound fibrinogen maintains a conformation such that its functional domains remain recognizable by antibody probes.

Adsorption↗

The activity of 3-hydroxyacyl-CoA epimerase is insufficient to account for the rate of linoleate oxidation in rat heart mitochondria. Evidence for a modified pathway of linoleate degradation.

The activities of cis-delta 3-trans-delta 2-enoyl-CoA isomerase (EC 5.3.3.8), 3-hydroxyacyl-CoA epimerase (EC 5.1.2.3), and 2,4-dienoyl-CoA reductase, all of which have been proposed to function as auxiliary enzymes in the beta-oxidation of polyunsaturated fatty acids, have been determined in mitochondria from rat heart and rat liver. In heart mitochondria the activity of 3-hydroxyacyl-CoA epimerase was lower, whereas that of 2,4-dineoyl-CoA reductase was higher than the observed rate of linoleate degration. This observation suggests that 2,4-dienoyl-CoA reductase and not 3-hydroxyacyl-CoA epimerase functions as an auxiliary enzyme in the metabolism of polyunsaturated fatty acids in heart. A modified pathway of linoleate degradation is presented.

Acyl Coenzyme A↗

Healing responses of human intraosseous lesions following the use of debridement, grafting and citric acid root treatment. I. Clinical and histologic observations six months postsurgery.

Three block sections of treated human intraosseous lesions within one individual are presented. These lesions were debrided, filled with autogenous grafts and at two sites the root was treated with citric acid. The treated sites were lightly root planed once a month and the blocks were removed 6 months after surgery. In addition, the root accretions within two lesions were notched with a bur prior to root planing in order to positively identify the position of these root accretions in the histologic sections. Clinically, the lesions closed by marginal shrinkage and limited pocket closure. Histologically, regeneration of new cementum, osteogenesis at bone and graft spicule seams and reformation of functionally oriented ligament fibers were present at sites within lesions where accretions had covered the root. Such a healing phenomenon was observed close to the base of the lesions and seemed to be related to this spatial configuration rather than to the notching of the root itself. No specific increased healing responses could be attributed to citric acid root treatment. Thus, "regeneration" of new attachment is possible within human intraosseous lesions even at root sites previously covered by accretions. However, such responses seem to be limited to areas near the base of the intraosseous lesion.

Adult↗

Healing responses of human intraosseous lesions following the use of debridement, grafting and citric acid root treatment. II. Clinical and histologic observations: one year postsurgery.

This report details histologic healing responses at intrabony sites within two patients about 1 year after surgery. Treatment consisted of open flat debridement of the lesions. At specific sites, augmenting procedures such as autogenous grafts, allografts, synthetic grafts and citric acid root treatment were utilized. In addition, notches were made through calculus prior to root planing at specific root surfaces. These notches were placed at varying distances from the base of the lesion. Patients were followed postsurgically with frequent maintenance visits. Block sections were removed at the end of the experimental period. Clinical reduction in pocket depth was noted at all treated sites. This reduction consisted of limited pocket closure, marginal gingival recession and repocketing. Histologically, all specimens showed evidence of repair. The most mature repair appeared at sites treated with debridement and autogenous grafts. "Regeneration" of lost periodontal attachment was demonstrated by evidence of cementogenesis, osteogenesis and the presence of functionally oriented ligaments. However, the coronal regeneration appeared spatially limited. Allografts showed a similar, but less mature healing response. Synthetic graft material acted essentially as a "filler" within the defect. Citric acid root treatment did not demonstrate clear evidence of augmentation of the repair process. Of particular note in these human specimens was further histologic demonstration that "regeneration" potential apparently can only take place in close proximity to histologically viable periodontal ligament cells which may act as "donor sites" for coronal "regeneration" of lost periodontal attachment. This histologic response was observed regardless of treatment modalities used.

Adult↗

Periodontal healing following open debridement flap procedures. II. Histologic observations.

Four tooth-containing blocks were obtained from patients being treated for infraosseous lesions of significant depth as part of their periodontal therapy. Treatment consisted of open flap debridement and professional cleansing at least every 4 weeks. Teeth in block were removed for histologic study 4 to 6 months after surgery. Histologic evaluation of the repair process showed pocket closure by epithelial and connective tissue adhesions in the form of an elongated junction epithelium, beneath which parallel-oriented fibers adhered to the root for a limited distance. Apical to this adhesion, functionally inserted fibers were present. Since no cementogenesis was seen at these latter areas, it must be assumed that the inserted fibers were present before the surgery and were not significantly affected by the procedure. No significant evidence of crestal osteogenesis was noted. However, comparison of the clinical osseous profile recorded at the time of surgical debridement with the flat crest seen in two of our cases histologically, suggests that significant crestal resorption had taken place postsurgically in some of these lesions.

Adult↗

Periodontal healing following open debridement flap procedures. I. Clinical assessment of soft tissue and osseous repair.

The healing response of the periodontium was evaluated after periodontal flap and debridement procedures in patients with different levels of postsurgical plaque control. Thirty-one sites in 19 patients were included. Measurements were performed from a fixed reference point presurgically and before reentry surgery. All reentries were performed 24 to 28 weeks after surgery. Surgery consisted of elevating an inverse bevel mucoperiosteal flap, debriding root accretions and osseous defects, penetrating into the marrow, and suturing with interrupted sutures at or near the presurgical level. All patients were recalled at least once every 4 weeks after surgery fof professional maintenance. The number of postsurgical maintenance visits and plaque scores (NPI) before reentry were recorded for each surgical site. Average pocket depth at the 31 sites was 7.4 mm initially and 4.1 mm at the time of reentry. This reduction in pocket depth consisted of gingival recession, which averaged 2.0 mm, and a gain in attachment level, which averaged 1.4 mm. At no site was there a loss in attachment level. Average osseous depth of the 31 defects was 3.7 mm presurgically and 1.7 mm at reentry. In addition, there was an average crestal resorption of 0.8 mm and an average osseous fill of 1.2 mm. A significant positive correlation (P less than 0.001) was found between gain in attachment, osseous fill and number of postsurgical maintenance visits. A significant negative correlation was found between the amount of plaque (NPI) at the study site and both gain in soft tissue attachment and osseous fill. Multiple measurements at various points within several osseous defects revealed that osseous remodeling and fill varied significantly at different locations within the same defect.

Adult↗

Human clinical and histologic responses to Durapatite implants in intraosseous lesions. Case reports.

The healing response following implantation of a nonresorbable ceramic (durapatite) into human periodontal osseous defects was evaluated clinically and histologically. Four tooth-containing blocks were obtained from four patients who had received durapatite implants in osseous defects, each exceeding 4 mm in depth. Each patient was seen for 5 to 13 postsurgical maintenance visits. Teeth in block section were removed between 8 weeks and 8 months postgraft surgery. Clinical evaluation of the repair process demonstrated that pocket depth decreased in all four cases. Histological evaluation of the repair process showed no indication of new periodontal attachment, osteogenesis or cementogenesis, in the host tissues adjacent to the graft particles. Pocket closure appeared to occur by means of a long junctional epithelium and connective tissue adhesions. There was minimal or no evidence of inflammation in all sections associated with the implant. The graft material therefore acted as a biocompatible foreign body within the gingival tissue.

Adult↗

Platelet-compatible hydrophilic segmented polyurethanes from polyethylene glycols and cyclohexane diisocyanate.

A new type of segmented polyurethane (SPU) was synthesized from alpha, omega polyethylene oxide diols (PEG) of MW varying from 600 to 4500, by end capping with 1,4 trans cyclohexane diisocyanate (CHDI) and chain extending with ethylene diamine (ED) in toluene with dibutyl tin dilaurate as catalyst. These SPU are cast as films and coatings from hexafluroisopropanol (HFIP). Depending on PEG MW, these SPU swell two- to tenfold in water. Examined by an in vitro platelet retention test, these SPU are more bland (platelet retention -rho around 0.05) than most other polymers, whereas an alternating copolymer of CHDI and ED shows -rho around 0.80 (very active); x-ray photoelectron spectroscopy shows that the surfaces of these SPU to a depth of about 40 Ao are nearly pure PEO, unlike SPU synthesized from aromatic diisocyanates TDI and MDI.

Biocompatible Materials↗

Possible late potentials in 4 dogs with sustained ventricular tachycardia.

Signal-averaged electrocardiograms (SAEKGs) were performed on 4 dogs with sustained ventricular tachycardia. Quantitative and qualitative analyses of SAEKGs were consistent with the presence of late potentials. Two of the 4 dogs subsequently died suddenly, and ventricular tachycardia and ventricular fibrillation were observed in 1 dog. High-frequency QRS durations (75-90 milliseconds), duration of low amplitude (less than 40 microV) signals during the terminal QRS complex (LAS40) (28-40 milliseconds), root mean square voltages of the terminal 40 milliseconds of the QRS complex (RMS40) (124-6.5 microV), and root mean square voltages of the terminal 30 milliseconds of the QRS complex (RMS30) (13-2.1 microV) differed from results obtained in 68 of 70 control dogs. Echocardiographic data suggested dilated cardiomyopathy in 2 dogs and the cause of the arrhythmia in 2 dogs was not determined. The SAEKG may be a useful adjunct in identifying a subset of dogs with ventricular tachyarrhythmias that are at high risk for sustained ventricular tachycardia and sudden death. The sensitivity, specificity, and predictive accuracies of the technique remain to be determined.

Animals↗