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M Singer

Publications and source records attributed to M Singer.

At least 163 records · Page 9Linked to original sources

The complement binding-like domains of the murine homing receptor facilitate lectin activity.

The leukocyte homing receptor (HR), the endothelial leukocyte adhesion molecule, and gmp140/platelet activation-dependent granule membrane protein are members of a family of adhesion molecules, termed the lectin cell adhesion molecules (LEC-CAMS) which are unified by a multi-domain structure containing a lectin motif, an epidermal growth factor-like (egf) motif, and variable numbers of a complement binding-like (CB) motif. Previous data have indicated a predominant role for the lectin motif in cell adhesion directed by the LEC-CAMS, although the egf-like domain of the HR may also play a potential role in cell binding. While the role(s) of the CB domains in the LEC-CAMS is currently not understood, they have been hypothesized to act as rigid spacers or stalks for lectin and perhaps, egf domain presentation. In this paper, we analyze the functional characteristics of murine HR-IgG chimeras containing the lectin, lectin plus egf, and lectin plus egf plus CB domains. The Mel 14 mAb, an adhesion blocking antibody which recognizes a conformational determinant in the N-terminus of the HR lectin domain, shows a significantly decreased affinity for a HR construct which lacks the CB motifs, consistent with the possibility that the CB domains are involved with lectin domain structure. In agreement with this conjecture, HR mutants lacking the CB domains show a profound decrease in lectin-specific interaction with the carbohydrate polyphosphomannan ester, suggesting that the changes in Mel 14 affinity for the lectin domain are reflected in lectin functionality. Various assays investigating the interactions between the HR deletion mutants and the peripheral lymph node high endothelium, including cell blocking, immunohistochemical staining, and radioactively labeled ligand binding, all showed that removal of the CB domains results in a lack of HR adhesive function. These results imply that the CB domains of the HR, and, by analogy, the other members of the LEC-CAM family, may play important structural roles involving induction of lectin domain conformation and resultant functionality.

Antibodies, Monoclonal↗

Noninvasive optimization of left ventricular filling using esophageal Doppler.

OBJECTIVE: To confirm whether the descending aortic blood flow velocity waveform variable of flow time corrected for heart rate, measured using an esophageal Doppler transducer, can be used for noninvasive optimization of left ventricular (LV) filling. SETTING: ICU and operating theater. SUBJECTS: Forty-three mechanistically ventilated patients in the ICU or undergoing cardiothoracic surgery in whom a pulmonary arterial catheter was in situ. INTERVENTIONS: LV preload was a) increased from hypovolemic states (pulmonary arterial occlusion pressure [PAOP] less than 8 mm Hg) by fluid challenge, b) decreased from normovolemic states (PAOP 10 to 15 mm Hg) by either iv nitrates or intravascular fluid loss, and c) decreased from heart failure or fluid overload states (PAOP greater than 20 mm Hg) by iv nitrates. No other maneuver was performed concurrently. MEASUREMENTS AND MAIN RESULTS: Descending aortic blood flow was measured by an esophageal Doppler transducer. Corrected flow time was calculated by dividing systolic flow time by the square root of the cycle time. PAOP and corrected flow time increased after fluid challenges in hypovolemic states, and decreased when LV preload was decreased from normovolemic states. However, when preload was decreased from overload states, PAOP always decreased, but the corrected flow time usually increased before any subsequent decrease. The greatest value of corrected flow time corresponded with the maximal stroke volume seen. CONCLUSIONS: Esophageal Doppler measurement of aortic blood flow can be used for rapid, noninvasive optimization of LV filling in mechanically ventilated patients.

Aorta↗

Effects of alterations in left ventricular filling, contractility, and systemic vascular resistance on the ascending aortic blood velocity waveform of normal subjects.

OBJECTIVES: To confirm the consistent effects on Doppler-measured aortic blood flow velocity waveform variables of alterations in left ventricular preload, afterload, and inotropy using pharmacologic and physiologic maneuvers. SETTING: Medical school laboratory. SUBJECTS: Healthy volunteers. INTERVENTIONS: Increasing infusion rates of dobutamine (1.25 to 5 micrograms/kg.min), esmolol (1.25 to 5 mg/min), phentolamine (1.25 to 5 mg/min), methoxamine (1.25 to 5 mg/min), metaraminol (1.25 to 5 mg/min), and placebo (1.25 to 5 mL of 0.9% saline/min) and increasing plasma removal (0.5 to 1 L) in awake, rested, supine subjects. MEASUREMENTS AND MAIN RESULTS: Ascending aortic blood flow was measured by the suprasternal Doppler approach allowing calculation of waveform variables of stroke distance and minute distance (linear measures of stroke volume and cardiac output), peak velocity, mean acceleration and flow time corrected for heart rate. An index of systemic vascular resistance was obtained by dividing mean systemic BP by the minute distance. Inotropic changes predominantly affected peak velocity and mean acceleration. Changes in preload mainly affected the flow time corrected for heart rate, whereas afterload changes had an intermediate effect. Unsuspected but subsequently confirmed hemodynamic effects were seen with esmolol and metaraminol. CONCLUSIONS: Aortic blood flow velocity waveform variables measured by Doppler ultrasound can be used to noninvasively follow changes in left ventricular preload, afterload, and inotropy.

Adrenergic beta-Antagonists↗

Haemodynamic evidence for per-operative cardiac stress during transurethral prostatectomy. Preliminary communication.

Haemodynamic changes were measured during routine transurethral prostatectomy (TURP). The heart rate and stroke volume fell progressively over the first 30 min of surgery, resulting in a steady reduction in cardiac output. There was a significant increase in left ventricular afterload from commencement of the procedure. These findings demonstrate that haemodynamic responses, which are not detectable using conventional methods of monitoring, occur during TURP. Increased left ventricular afterload indicates increased myocardial work and oxygen demand which could result in myocardial ischaemia. This may contribute to the increased cardiovascular morbidity and mortality which have been reported to occur after TURP. The possible underlying mechanisms are discussed.

Aged↗

The Escherichia coli ts8 mutation is an allele of fda, the gene encoding fructose-1,6-diphosphate aldolase.

The ts8 mutant of Escherichia coli has previously been shown to preferentially inhibit stable RNA synthesis when shifted to the nonpermissive temperature. We demonstrate in this report that the ts8 mutation is an allele of fda, the gene that encodes the glycolytic enzyme fructose-1,6-diphosphate aldolase. We show that ts8 and a second fda mutation, h8, isolated and characterized by A. Böck and F. C. Neidhardt, are dominant mutations and that they encode a thermolabile aldolase activity.

Alleles↗

Physiological effects of the fructose-1,6-diphosphate aldolase ts8 mutation on stable RNA synthesis in Escherichia coli.

The conditional lethal mutations ts8 and h8 are located in fda, the gene encoding aldolase, and they inhibit RNA synthesis upon shift to the nonpermissive temperature. We demonstrate that both mutations preferentially inhibit stable RNA synthesis and that this inhibition occurs at the level of transcription initiation. The susceptibility of a promoter to the inhibitory effects of ts8 is correlated with the ability of the promoter to be growth rate regulated. This effect is independent of relA and spoT function. Inhibition is dependent upon glucose metabolism past the generation of glucose-6-phosphate; however, the mechanism of this effect is unknown.

Escherichia coli↗

Independence of question-answering strategy and searched representation.

Because many studies of question answering, recall, and recognition have examined script-based messages, a spurious link between answering strategy and searched representation has emerged: Direct retrieval has been associated with the episodic representation of a discourse or a learned list, whereas plausibility judgment has been associated with general knowledge structures. Evidence of the independence of answering strategy and searched representation is presented. First, previous research and intuition both provide examples of the application of either strategy to either type of representation. Second, there is empirical evidence of the application of either strategy to both message text bases and general knowledge. Third, the effects of factors influencing strategy selection are independent of the type of searched representation. It is concluded that answering strategy is independent of the representation to which it is applied.

Cognition↗

Confronting the AIDS epidemic among i.v. drug users: does ethnic culture matter?

The AIDS education and prevention literature contains numerous calls for the development of culturally relevant efforts to reach members of ethnic minority populations. In the AIDS literature on IV drug users (IVDUs), however, this issue finds less emphasis despite the disproportionate rate of human immunodeficiency virus (HIV) infection in minority IVDUs. The reason appears to be the sense in the drug field that the primary culture of the IVDU is drug culture rather than ethnic culture. This paper explores this issue in light of a review of recent research on IVDUs, ethnicity, and AIDS risk behavior. Specifically, this review covers literature on 6 topics in light of ethnic differences: changing patterns of IV drug use prevalence, AIDS prevalence among IVDUs, needle-related AIDS risk, polydrug use, sexual risk among IVDUs, and the drug subculture. Finding that ethnic culture does matter in infection patterns and risk behavior, this paper examines a typology for the analysis of discontinuities in intercultural communication and presents a framework for comparing alternative models for overcoming cultural barriers to effective AIDS education with IVDUs.

Acquired Immunodeficiency Syndrome↗

Cognitive correlates of adolescents' aspirations to leadership: a developmental study.

The study examined age and gender differences in leadership aspirations among teenage adolescents. It was hypothesized that adolescents' valence, self-efficacy and attribution perceptions about leadership would be predictive of their aspirations to leadership. Altogether 52 fourth form and 78 seventh form high school students completed a questionnaire measuring (a) overall leadership aspirations, (b) 13 valence-instrumentality expectancies for 13 leadership outcomes, (c) self-efficacy perceptions, and (d) attributions of effective leadership. The results revealed significant gender differences in valence scores and significant age differences in self-efficacy and attribution measures. Regression analyses indicated that fourth formers' leadership aspirations were significantly predicted from their "ease-of-success" self-efficacy expectation; whereas seventh formers from either valence perceptions (males) or self-efficacy and attribution scores (females). These results were discussed in the context of the valence and self-efficacy models of career decision-making processes and attribution theory.

Adolescent↗

Reinventing medical anthropology: toward a critical realignment.

Responding to the narrow focus, medicalization, and inattention to political-economy within conventional medical anthropology, a growing number of researchers are participating in a significant restructuring of the subdiscipline. The paper examines several shortcomings of contemporary medical anthropology and, building on the work of the emergent critical trend, identifies key areas of theory and practice for furthering the critical realignment of medical anthropology.

Anthropology↗

Enhanced c-myc gene expression during forelimb regenerative outgrowth in the young Xenopus laevis.

Analysis of the expression of the c-myc protooncogene has been carried out in the forelimb regenerate of the Xenopus laevis froglet. Northern blot hybridization analysis revealed the presence of a 2.5-kilobase c-myc transcript in the regenerate forelimb at a level at least 7-fold more than the one found in nonregenerating forelimbs or stumps of regenerating forelimbs. In situ hybridization analyses confirmed the relative abundance of c-myc RNA in the regenerate forelimb and provided evidence of spatial localization of high levels of c-myc RNA in specific cell layers. The deepest layers of the wound epithelium of epidermal origin showed a strong signal, whereas virtually no c-myc RNA was detected in the outermost layers. Labeling was also observed in mesenchymal cells of the blastema where it was relatively evenly distributed. This pattern of c-myc RNA in the regenerate might indicate that the expression of c-myc plays a role in the regulation of the continued proliferation of specific cells of the regenerate, whereas repression of this gene in the epidermis correlates with terminal differentiation of keratinocytes.

Amputation, Surgical↗

Postmodernism and medical anthropology: words of caution.

Of late, discourse in anthropology increasingly has been set within the frame of postmodernism. While debate continues as to whether postmodernism represents a particular period or an historically conditioned perspective (or interrelated set of perspectives) within the social sciences and beyond, it is clear that assessment is needed of the impact of postmodernism on work within the field. This paper represents a critique of the potential effect of postmodernism within medical anthropology. It is the argument of this paper that despite the postmodern eschewal of so-called grand theory, postmodern writers in anthropology smuggle a theoretical perspective into their work. The problems of this perspective in terms of the critical turn within medical anthropology are examined.

Anthropology↗

Severe anaphylactoid reaction to hydroxyethyl starch.

A case is presented of a severe anaphylactoid reaction to hydroxyethyl starch solution that occurred peri-operatively and required extended intensive management of the resultant bronchospasm and hypotension. Subsequent intradermal injection of hetastarch produced a delayed positive response, suggestive of a complement-mediated mechanism.

Aged↗