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Biomedical subjects

S J Weiss

Publications and source records attributed to S J Weiss.

At least 19 recordsLinked to original sources
PubMed1992

Interaction of Drosophila DNA polymerase alpha holoenzyme with synthetic template-primers containing mismatched primer bases or propanodeoxyguanosine adducts at various positions in template and primer regions.

We studied recognition and binding of synthetic template-primers by Drosophila DNA polymerase alpha (pol alpha) holoenzyme. The template-primers used contained either mismatched base pairs at various positions in the primer region or exocyclic propanodeoxyguanosine (PdG) adducts at various positions in both template and primer.pol alpha requires primer-terminal complementarity of greater than or equal to 4 base pairs for efficient binding and incorporation. When a mismatched base pair is at the -4 position relative to the 3'-primer terminus, minimal but detectable binding occurs. This is consistent with the ability of pol alpha to incorporate a single nucleotide on a template-primer containing a mismatch at this position, but at a rate of only 7% relative to incorporation on a perfectly matched template-primer. No binding or incorporation (less than 1% of incorporation on a perfectly matched template-primer) was evident when a mismatched base pair was at the -3 position or closer, relative to the 3'-primer terminus. Similar results were obtained when PdG was placed at various positions in the primer region. When a PdG residue was located in the template region (+ 3 position relative to the 3'-primer terminus), single-nucleotide incorporation was stimulated 3-4-fold. These observations suggest that there are intrinsic aspects to the mechanism of nucleotide incorporation by pol alpha which ensure the fidelity of DNA synthesis by this enzyme and may provide novel insights into the fundamental mechanism of polymerase translocation along templates.

Animals↗
PubMed1992

Proteolytic inactivation of alpha 1-proteinase inhibitor and alpha 1-antichymotrypsin by oxidatively activated human neutrophil metalloproteinases.

Human neutrophils use the H2O2-myeloperoxidase-chloride system to generate chlorinated oxidants capable of activating metalloproteinase zymogens that hydrolyze not only native and denatured collagens, but also the serine proteinase inhibitor (serpin) alpha 1-proteinase inhibitor (alpha 1 PI). To identify the metalloenzyme that hydrolyzes and inactivates alpha 1 PI, neutrophil releasates were chromatographed over gelatin-Sepharose and divided into fractions containing either progelatinase or procollagenase. The gelatinase-containing fraction cleaved alpha 1 PI in a manner inhibitable by native type V, but not type I, collagen. Conversely, while the collagenase-containing fraction also cleaved alpha 1 PI, this activity was inhibited by type I, but not type V, collagen. Because type I and V collagens are competitive substrates for collagenase and gelatinase, respectively, each of the metalloproteinase zymogens were purified to apparent homogeneity and examined for alpha 1 PI-hydrolytic activities. Both purified gelatinase and collagenase inactivated alpha 1PI by hydrolyzing the serpin within its active-site loop at the Phe352-Leu353 and Pro357-Met358 bonds, albeit with distinct kinetic properties. Furthermore, purified collagenase, but not gelatinase, cleaved a second serpin, alpha 1-antichymotrypsin, by hydrolyzing the Ala362-Leu363 bond within its active-site loop. These data demonstrate that human neutrophils use chlorinated oxidants to activate collagenolytic metalloproteinases whose substrate specificities can be extended to members of the serpin superfamily.

Blotting, Western↗
PubMed1992

Psychophysiologic and behavioral effects of tactile stimulation on infants with congenital heart disease.

A within-subjects, counterbalanced, repeated measures design was employed to determine the effects of gender and six different types of verbal and tactile stimuli on the arousal of 24 infants hospitalized for congenital heart disease during their first 6 months of life. Infants were systematically assigned to different sequences of the various stimuli. Measures of arousal included heart rate, blood pressure, respiration, and activity level. Results indicated that the use of touch conducive to neural excitation (i.e., intense, vigorous, extensive touching of highly innervated body areas) produced higher heart rates (p less than .01) and systolic blood pressure (p less than .002) as well as greater activity (p less than .01) than did other types of tactile stimulation or soothing verbal stimulation. Girls appeared more physiologically responsive to touch than boys and a subset of infants showed evidence of distress during more arousing stimulation.

Arousal↗
PubMed1992

FG 7142 selectively decreases nonpunished responding, but has no anxiogenic effects on time allocation in a conflict schedule.

Previous work (Thomas et al. 1990) showed that an anxiolytic benzodiazepine increased the time allocated to responding in a conflict situation (where responses were both food-reinforced and shock-punished) versus a nonpunishment situation. The present experiment tested whether a benzodiazepine-receptor inverse agonist (FG 7142, 1-30 mg/kg) would have the opposite effect (i.e., decrease time spent responding in a punishment situation). Chain pulls determined whether a rat's lever presses were reinforced on 1) a lean variable-interval schedule, or 2) a richer variable-interval schedule in which responding also produced shock intermittently. FG 7142 dose-dependently decreased nonpunished lever responding, but did not affect punished responding. The drug nonselectively decreased chain pulling (the schedule-switching response). Like chlordiazepoxide, FG 7142 increased the time spent in the punishment component, showing that not all effects of benzodiazepine-receptor agonists and inverse agonists are opposite. These results are inconsistent with expectations that anxiogenic actions of FG 7142 should 1) decrease punished responding; 2) increase the rate of responses that terminate the punishment condition; and 3) decrease time spent in the punishment component. Rather, nonsuppressed responding seems most sensitive to decreases by FG 7142.

Animals↗
PubMed1992

Combined cardiac operation and carotid endarterectomy during aortic cross-clamping.

We present a surgical technique that we believe provides superior cerebral protection for simultaneous correction of carotid and cardiac pathology with low operative mortality and stroke rate. Our study population consists of 23 consecutive patients undergoing cardiac operation between August 1989 and April 1991 who also had associated critical (greater than 85%) carotid artery stenosis. Using 20 degrees C systemic hypothermia for cerebral protection, we performed simultaneous correction of both lesions during the aortic cross-clamp period, using continuous retrograde blood cardioplegia for myocardial protection. Mean patient age was 69.4 years; 83% were 65 years or older. Eighty-seven percent had angina, 35% had recent myocardial infarctions (within 30 days), and 52% had congestive heart failure. Asymptomatic bruit was found in 39%, and 61% had previous strokes, neurologic symptoms, or both. All had 85% or greater luminal narrowing on cerebral angiography, with 65% having severe or critical contralateral disease as well. Sixty-one percent had associated other vascular pathology, including peripheral vascular occlusive disease, renal artery stenosis, or abdominal aortic aneurysm. There were no postoperative strokes or neurologic events. One early vein graft occlusion resulted in postoperative myocardial infarction and subsequent death (4.3%).

Aged↗
PubMed1992

Generalization peak shift for autoshaped and operant key pecks.

Pigeons acquired discriminated key pecking between 528- and 540-nm stimuli by either a response-reinforcer (operant group) or a stimulus-reinforcer (autoshaped group) contingency, with other training-schedule parameters comparable over groups. For the birds in the operant group, key pecks intermittently produced grain in the presence of one hue on the key (positive stimulus) but not in the other (negative stimulus). For the birds in the autoshaped group, pecking emerged when grain was intermittently presented independently of key pecking during one key color but was not presented during the other key color. Two independent contingency assays, peck-location comparisons and elimination of differences in reinforcement rate, confirmed the effectiveness of the two training procedures in establishing operant or respondent control of key pecking. After reaching a 10:1, or better, discrimination ratio between key pecks during the two key colors, the birds received a wavelength generalization test. Criterion baseline key-peck rates were comparable for operant and autoshaped groups prior to testing. On the generalization test, performed in extinction, all birds pecked most at a stimulus removed from the positive training stimulus in the direction away from the negative stimulus. In testing, autoshaped "peak" rates (24.5 to 64.9 pecks per minute) were from 33% to 80% higher than rates in the presence of the training stimuli. Respondent peak shift rarely has been reported heretofore, and never this consistently and robustly. These results further confirm the similarity of perceptual processing in classical and operant learning. They are discussed in terms of Spence's gradient-interaction theory and Weiss' (1978) two-process model of stimulus control.

Animals↗
PubMed1991

Regulation of transendothelial neutrophil migration by endogenous interleukin-8.

Movement of neutrophils from the bloodstream to inflamed tissue depends on the activation of both the neutrophil and the endothelial cell. Endothelial cells lining the postcapillary venule respond to proinflammatory mediators by expressing adhesion molecules and synthesizing a variety of neutrophil-activating factors. Endothelial cell production of a 77-amino acid variant of interleukin-8 (IL-8) was found to be a requirement for the invasion of neutrophils through a vessel wall model. IL-8 secreted by cytokine- or lipopolysaccharide-stimulated endothelial cells induced the rapid shedding of neutrophil lectin adhesion molecule-1, the up-regulation of leukocyte beta 2 integrins, and the attachment and transmigration of the neutrophils. Thus, endogenous endothelial IL-8 regulates transvenular traffic during acute inflammatory responses.

Antigens, CD↗
PubMed1991

Stressors experienced by family caregivers of children with pervasive developmental disorders.

The purpose of this study was to identify the perceived stressors experienced by parents who care for children with Pervasive Developmental Disorders. The relationship between demographics and overall stress was also examined. The most frequently cited stressor was difficulty arranging for and collaborating with professional and support services. Problems associated with the child's emotional and mental state were viewed as the most stressful of all. No demographic variables showed a significant relationship to degree of overall stress.

Adult↗
PubMed1991

Personality adjustment and social support of parents who care for children with pervasive developmental disorders.

The goal of this study was to examine the degree of personality adjustment and perceived social support of parents who care for children with pervasive developmental disorders. Data were collected with the California Q-Set (a personality measure) and the Norbeck Social Support Questionnaire. Personality adjustment of the parents was found to be significantly less than optimal, with a high degree of anxiety, minimal ego resilience, and use of defensive coping processes. Siblings of the child with the disorder and mothers of the parents were those most frequently identified as providing support to the caregiver, although friends, special education teachers, and daycare staff were the individuals whose support was most significantly related to greater amounts of perceived affection and affirmation, tangible aid, and concrete caregiving assistance. In fact, the more the caregivers depended upon their families for support, the less well adjusted were the caregivers on the personality measure. The implications of the findings for caregivers and their families are discussed.

Adaptation, Psychological↗
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↗