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S J Weiss

Publications and source records attributed to S J Weiss.

At least 127 records · Page 7Linked to original sources
PubMed1991

Interstitial collagenase (matrix metalloproteinase-1) expresses serpinase activity.

Human endothelial cells treated with either interleukin-1 beta, tumor necrosis factor-alpha, or phorbol myristate acetate secreted a metalloproteinase that hydrolyzed and inactivated the two major serine proteinase inhibitors (Serpins) found in plasma, alpha 1-proteinase inhibitor and alpha 1-antichymotrypsin. Surprisingly, the responsible metalloproteinase was identified as human interstitial collagenase (matrix metalloproteinase-1), an enzyme whose only known physiologic substrate has heretofore been believed to be the extracellular matrix molecule, collagen. The metalloproteinase inactivated the Serpins by cleaving peptide bonds at sites unrelated to those hydrolyzed in collagenous macromolecules. NH2-terminal sequence analysis localized the cleavage sites in the Serpins to regions near their respective reactive site centers at three distinct peptide bonds on the amino-terminal side of bulky, hydrophobic residues. Together, these data indicate that matrix metalloproteinase-1 displays an expanded substrate repertoire that supports the existence of a new interface between connective tissue turnover and Serpin function.

Amino Acid Sequence↗
PubMed1991

Malassezia furfur fungemia associated with central venous catheter lipid emulsion infusion.

Malassezia furfur has been associated with fungemias in infants after prolonged intravenous lipid emulsion alimentation. Most cases of M. furfur fungemia reported in the literature involved neonates and required catheter removal for cure. M. furfur is probably an underreported problem in neonates as well as adults with central venous catheters, receiving lipid emulsions, because the organism requires selective enrichment media for growth, for example, Sabouraud's dextrose agar with sterile olive oil overlay. This case report of M. furfur fungemia in a neonates is unique because the neonate recovered on discontinuation of the lipid emulsion, without removal of the central venous catheter.

Catheterization, Central Venous↗
PubMed1990

Regulation of proteolysis at the neutrophil-substrate interface by secretory leukoprotease inhibitor.

Human neutrophils can initiate the rapid degradation of extracellular matrix macromolecules by localizing the destructive process to sites of cell-substrate contact. Although plasma and its filtrates contain multiple proteinase inhibitors, these inhibitors did not prevent neutrophils from attacking either underlying fibronectin or elastin. However, subjacent substrates could be protected from neutrophils by recombinant secretory leukoprotease inhibitor, a structurally unique serine proteinase inhibitor whose natural counterpart is normally confined to human mucous secretions. The identification of this extravascular proteinase inhibitor as a potent regulator of subjacent proteolysis could lead to the development of a new class of anti-inflammatory therapeutics.

Cell Adhesion↗
PubMed1990

Effects of chlordiazepoxide and flumazenil on preference for punished and unpunished response alternatives in rats.

Male food-restricted hooded rats were trained to respond on a two-component multiple schedule. Reinforcement density was several times higher in one component than in the other. However, responses were intermittently punished with shock in the richer reinforcement component (conflict situation). Shock intensities were adjusted to produce mild and strong suppression of responding in two separate phases. Half of the rats controlled which component was operating (Preference group) and half did not (Yoked group). The effect of chlordiazepoxide (CDZ; 0, 1, 3, and 10 mg/kg; IP) was measured on component preference and response rate. Chlordiazepoxide increased both time spent in the conflict situation and response rate in that component. This is the first study employing a schedule that permitted these two behavioral indices to be measured independently in a conflict paradigm. Response rates were also increased in the unpunished response alternative, but to a lesser degree than in the conflict situation. The effects of CDZ were at least partially mediated by the benzodiazepine receptor because CDZ's effects were diminished by flumazenil (10 mg/kg; IP), a benzodiazepine antagonist.

Animals↗
PubMed1990

Effects of differential touch on nervous system arousal of patients recovering from cardiac disease.

Previous research suggests that the neural properties of certain types of touch as well as their perceived significance to the disease state may be related to heightened activation of the nervous system. In this study the effects of different types of touch on nervous system arousal were examined in 59 adult patients who were receiving treatment for coronary artery disease. They were exposed to a standardized protocol that systematically varied the neural properties and procedural nature of the touch received. Measures of cardiovascular reactivity (heart rate and rhythm data as well as blood pressure measurements) and state anxiety were used as indexes of arousal. The results indicated that all types of touch evoked heart rate deceleration in contrast to both baseline and verbal conditions. However, there were no differential effects related to either the neural properties or procedural nature of touch. Diastolic blood pressure and state anxiety were also lower as a result of the touch. No changes were observed for systolic blood pressure or heart rhythm. In general, findings suggested that touch served to reduce arousal rather than to produce negative psychophysiologic consequences for recovery.

Adult↗
PubMed1989

Functional inactivation and structural disruption of human alpha 2-macroglobulin by neutrophils and eosinophils.

Human alpha 2-macroglobulin (alpha 2M) rapidly lost functional and structural integrity in the course of a short-term incubation with either triggered neutrophils or eosinophils. In contrast to native alpha 2M, the modified antiproteinase was unable to bind neutrophil elastase or pancreatic elastase in a manner that restricted the enzymes' access to high molecular weight substrates. In addition to the complete loss of its antiproteolytic potential, the conformation of the dysfunctional inhibitor was radically altered and susceptible to further modification by exogenous proteinases as assessed by polyacrylamide gel electrophoresis. Analysis of the mechanism by which alpha 2M was inactivated by neutrophils revealed that the process was dependent on the generation of hypochlorous acid, an oxidant generated by the hydrogen peroxide-myeloperoxidase-chloride system. In contrast to the neutrophil, maximal eosinophil-dependent inactivation required the presence of physiologic concentrations of bromide and appeared to involve the generation of hypobromous acid. The ability of either hypochlorous acid or hypobromous acid to directly disrupt alpha 2M function and structure was confirmed under cell-free conditions. These results demonstrate that alpha 2M, an antiproteinase heretofore considered to be resistant to physiologic inactivation, could be destroyed by two populations of human phagocytes via oxidative modifications mediated by hypophalous acids.

Cell-Free System↗
PubMed1989

Recognition and binding of template-primers containing defined abasic sites by Drosophila DNA polymerase alpha holoenzyme.

Human DNA polymerase alpha holoenzyme follows an ordered sequential terreactant mechanism of substrate recognition and binding (Wong, S. W., Paborsky, L. R., Fisher, P. A., Wang, T. S.-F., and Korn, D. (1986) J. Biol. Chem. 261, 7958-7968). We confirmed this mechanism for the DNA polymerase alpha holoenzyme purified from Drosophila melanogaster embryos and studied the interaction of Drosophila pol alpha with synthetic oligonucleotide template-primers containing modified tetrahydrofuran moieties as model abasic lesions chemically engineered at a number of defined sites. Abasic lesions in the template had relatively little effect on the polymerase incorporation reaction at sites proximal to the lesion. However, incorporation opposite an abasic site was undetectable relative to that which occurred opposite a normal template nucleotide. Moreover, abasic residues in the primer region of the template-primer construct as far as 4 base pairs removed from the 3'-primer terminus prevented detectable nucleotide incorporation relative to that seen on an unmodified template-primer. Primer-region lesions had qualitatively similar effects whether they were located on the primer strand itself or on the complementary template strand. Data from polymerase incorporation experiments were corroborated by competitive binding assays performed under steady state reaction conditions. Results of these experiments suggested that polymerase binding to synthetic oligonucleotide template-primers was essentially unaffected by lesions located at sites that did not block incorporation. Lesions that did block incorporation apparently did so by abrogating template-primer binding. These observations have implications for understanding the mechanisms whereby DNA polymerase alpha recognizes noninformational template sites in vivo and prevents DNA synthesis from proceeding past these points.

Animals↗
PubMed1989

Disruption of the subendothelial basement membrane during neutrophil diapedesis in an in vitro construct of a blood vessel wall.

To examine the course of physiologic interactions between extravasating neutrophils and the subendothelial basement membrane, a model of the venular vessel wall was constructed by culturing human umbilical vein endothelial cells on a collagen matrix. After 21 d in culture, the endothelial cell monolayer displayed in vivo-like intercellular borders and junctions, deposited a single-layered, continuous basement membrane that was impenetrable to colloidal particles, and supported neutrophil extravasation in a physiologic manner. Using this model, we demonstrate that neutrophil transmigration in a plasma milieu was associated with a significant disruption of the retentive properties of the basement membrane in the absence of discernable morphologic changes. The loss of basement membrane integrity associated with neutrophil diapedesis was not dependent on neutrophil elastase or cathepsin G and was resistant to inhibitors directed against neutrophil collagenase, gelatinase, and heparanase. Despite the fact that this loss in matrix integrity could not be prevented, basement membrane defects were only transiently expressed before they were repaired by the overlying endothelium via a mechanism that required active protein and RNA synthesis. These data indicate that neutrophil extravasation and reversible basement membrane disruption are coordinated events that occur as a consequence of vessel wall transmigration.

Basement Membrane↗
PubMed1989

Intra-aortic balloon-pump rupture and entrapment.

The authors report a case of intra-aortic balloon rupture and entrapment in a patient with extensive vascular disease. The balloon was subsequently removed percutaneously. A review of the diagnosis and management of this unusual complication is presented.

Equipment Failure↗
PubMed1988

Singlet oxygen production by human eosinophils.

Human eosinophils, stimulated with phorbol myristate acetate, were found to produce 1268 nm chemiluminescence characteristic of singlet oxygen. Singlet oxygen generation required the presence of bromide ion. A bromide ion concentration of 100 microM, comparable to the total bromine content of whole blood, was sufficient for the eosinophils to generate measurable amounts of singlet oxygen. For the conditions used (10(7) cells/ml and 10 micrograms/ml phorbol myristate acetate), the duration of the singlet oxygen generation was brief, about 5 min, and the total yield of singlet oxygen was modest, 1.0 +/- 0.1 microM. The cells remained viable after the singlet oxygen production ceased. This is the first demonstration of singlet oxygen production from living cells. The singlet oxygen generated by eosinophils likely results from a peroxidase-catalyzed mechanism, since a purified eosinophil peroxidase-hydrogen peroxide-bromide system was also shown to produce singlet oxygen. The unique properties of eosinophil peroxidase are illustrated by the fact that at p2H 7.0 and with 100 microM bromide, eosinophil peroxidase generated 20 +/- 2% of the theoretical yield of singlet oxygen, whereas under identical conditions, myeloperoxidase and lactoperoxidase produced only 1.0 +/- 0.1% and -0.1 +/- 0.1%, respectively.

Bromides↗
PubMed1988

Expression of Mo3e antigen by cultured human umbilical vein endothelial cells (HUVEC) stimulated by phorbol myristate acetate (PMA) and related pharmacological inducers of protein kinase C.

Mo3e is a protease-sensitive membrane antigen (p75,50) selectively expressed by human monocytic cells (monocytes and U-937 cells) stimulated in vitro by exposure to a variety of activating factors, including phorbol diester compounds, bacterial lipopolysaccharide (LPS), and muramyl dipeptide (MDP)(R.F. Todd et al., J. Immunol. 135, 3869, 1985). Here we report that primary and multiply-passaged cultures of HUVEC also express the Mo3e determinant after stimulation by phorbol myristate acetate (PMA) and related inducers of protein kinase C. As measured in a radioimmunoassay of anti-Mo3e antibody binding to monolayer cultures of HUVEC, unstimulated cells bore little if any Mo3e. After culture for 4-120 hr in medium containing PMA, 4 beta-phorbol dibutyrate, 4 beta-phorbol didecanoate, or mezerein (each at a concentration of 81 nM), or 1-oleoyl-2-acetoyl-sn-3-glycerol (1 mM), HUVEC were found to selectively express the Mo3e determinant. The magnitude of expression was dependent upon the concentration of the stimulus, maximal by 24 hr, and inhibited by cycloheximide. The combination of PMA and the calcium ionophore, ionomycin, had an additive or synergistic effect on HUVEC Mo3e expression. The biologically inactive phorbol compounds 4 beta-phorbol and 4 alpha-phorbol didecanoate failed to stimulate Mo3e expression. Also inactive as inducers of HUVEC Mo3e expression were crude lymphokine and monokine supernatants, recombinant human lymphokines (interferon-gamma and interleukin-2), recombinant human monokines (interleukin-1 and tumor necrosis factor), bacterial cell wall products including LPS and MDP, pharmacologic agents that increase intracellular cyclic adenosine monophosphate (prostaglandin E2, cholera toxin, theophylline, isoproterenol and isobutylmethylxanthine), lectins (Con A and PHA), and heparin. These results indicate that Mo3e is an inducible plasma membrane antigen of not only mononuclear phagocytes but also cultured HUVEC.

Animals↗
PubMed1988

Proteolytic inactivation of alpha-1-proteinase inhibitor by a neutrophil metalloproteinase.

Human neutrophils triggered with phorbol myristate acetate or opsonized zymosan particles released a metalloproteinase (MP) capable of cleaving and inactivating alpha-1-proteinase inhibitor (alpha-1-PI). Sequence analysis of the amino acids in proteolyzed, native alpha-1-PI revealed a unique single cleavage site between Phe-352 and Leu-353. An analysis of the process regulating the enzyme's activity revealed that the neutrophil MP was released from cells in a latent form whose activation was tightly linked to the generation of hypochlorous acid. These results indicate that human neutrophils use chlorinated oxidants to activate a latent MP that is capable of proteolytically inactivating alpha-1-PI by cleaving the antiproteinase at a unique point in its inhibitory site region.

Amino Acid Sequence↗
PubMed1988

The integration of habits maintained by food and water reinforcement through stimulus compounding.

In Experiment 1, a light and a tone were correlated independently with water reinforcement of bar pressing by rats. With different naive subjects in Experiment 2, one of these stimuli was correlated with food and the other with water reinforcement (counterbalanced). In both experiments the absence of tone and light signaled extinction. Tests of stimulus-reinforcer independence in Experiment 2 indicated that tone and light controlled behavior whose rate was specifically affected by deprivation state. In the stimulus-compounding tests of both experiments, response rates were higher to tone-plus-light than to tone or light presented alone (additive summation). This is the first report of additive summation produced through compounding stimuli paired with different reinforcers. The results are discussed in the context of the effects of incentive motivation on operant performance.

Animals↗
PubMed1988

Touch.

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Arousal↗
PubMed1987

Interpretation of the results of methacholine inhalation challenge tests.

Methacholine inhalation challenge studies are conventionally expressed as the provocative cumulative dose of methacholine that causes a 20% fall in FEV1 (PD20). This method is widely used and most suitable for expressing results for challenges in subjects with asthma. However, it is impossible to present results in this manner in other circumstances. Normal subjects and many subjects with allergic rhinitis do not have significant bronchial reactivity and will not reach a 20% fall during standard challenge protocols. This limitation precludes the use of this large population in the quantitative analysis necessary in epidemiologic, genetic, or drug studies. To compound this difficulty, a subset of patients with allergic rhinitis may demonstrate a 20% drop but have a subsequent plateau drop in FEV1. Expressing the results of their methacholine challenge with only a PD20 loses valuable information available in the test. We demonstrate that expressing results as the area beneath a dose-response curve provides useful parametric data on all studied subjects and distinguishes among subjects who might otherwise be classified as equivalent when results are expressed solely as a PD20.

Adolescent↗
PubMed1986

Brominating oxidants generated by human eosinophils.

Eosinophils are white blood cells that in humans are found in association with helminthic infections and various inflammatory disease processes. These cells contain a unique lysosomal peroxidase that oxidizes halides to generate highly reactive and toxic hypohalous acids. Although chloride is found in vivo at concentrations at least 1000-fold greater than those of other halides, human eosinophils did not preferentially oxidize chloride under physiologic conditions. Instead, eosinophils used bromide, a halide with a hitherto unknown function in humans, to generate a halogenating oxidant with characteristics similar, if not identical, to those of hypobromous acid. These results indicate that physiological concentrations of bromide arm human eosinophils with the ability to generate and release an unusual oxidant capable of destroying a wide range of prokaryotic and eukaryotic targets.

Bromates↗