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S Seidman

Publications and source records attributed to S Seidman.

42 records · Page 3Linked to original sources

Interaction between wheat germ RNA polymerase II and adenovirus 2 DNA. Evidence for two types of stable binary complexes.

Transcription of Adenovirus 2 DNA (Ad 2 DNA) by wheat germ RNA polymerase II in vitro satisfies criteria that have been used to establish that Escherichia coli or coliphage transcription in vitro is initiated at true promoters. (1) Wheat germ RNA polymerase forms highly stable complexes at specific sites on Ad 2 DNA, with a Kassoc of (4--5) X 10(10) M-1. (2) Electron microscopic visualization of enzyme bound to Ad 2 DNA reveals the location of eight strong binding sites, at least five of which appear to correspond to promoters that have been identified in studies of Ad 2 transcription in vivo [Evans, R. M., Fraser, N., Ziff, E., Weber, J., Wilson, M., & Darnell, J.E. (1977) Cell 12, 733--739; Berk, A.J., & Sharp, P.A. (1977) Cell 12, 45--55; Weinmann, R., & Aiello, L. O. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 1662--1666]. (3) Transcription of Ad 2 DNA from preformed complexes with wheat germ polymerase is capable of escaping the action of rifamycin AF/013 and is relatively resistant to polyriboinosinic acid. In addition, our results are consistent with a two-state model for the interaction of wheat germ RNA polymerase with Ad 2 DNA, indicating that the mechansisms of transcription initiation and promoter-site selection in eucaryotes may be very similar to mechanisms elucidated in procaryotic systems.

Adenoviruses, Human↗

Transgenic acetylcholinesterase induces enlargement of murine neuromuscular junctions but leaves spinal cord synapses intact.

Acetylcholinesterase (AChE) produced by spinal cord motoneurons accumulates within axo-dendritic spinal cord synapses. It is also secreted from motoneuron cell bodies, through their axons, into the region of neuromuscular junctions, where it terminates cholinergic neurotransmission. Here we show that transgenic mice expressing human AChE in their spinal cord motoneurons display primarily normal axo-dendritic spinal cord cholinergic synapses in spite of the clear excess of transgenic over host AChE within these synapses. This is in contrast to our recent observation that a modest excess of AChE drastically affects the structure and long-term functioning of neuromuscular junctions in these mice although they express human AChE in their spinal cord, but not muscle. Enlarged muscle endplates with either exaggerated or drastically shortened post-synaptic folds then lead to a progressive neuromotor decline and massive amyotrophy (Andres et al., 1997). These findings demonstrate that excess neuronal AChE may cause distinct effects on spinal cord and neuromuscular synapses and attribute the late-onset neuromotor deterioration observed in AChE transgenic mice to neuromuscular junction abnormalities.

Acetylcholinesterase↗

Ejaculatory dysfunction and depression: pharmacological and psychobiological interactions.

In recent years, increased attention has been focused on antidepressant-associated sexual dysfunction, largely because of the widespread use of serotonin-specific reuptake inhibitors (SSRIs) and the recognition that such side effects can have a negative impact on treatment compliance. Data suggest that serotonergic antidepressants are associated with delayed ejaculation and anorgasmia, although these sexual problems are also linked to depression and to age. In this review, we discuss central mediators of normal orgasmic functioning and dysfunction, the relationship between depression and sexual dysfunction, possible mechanisms for SSRI-associated sexual dysfunction, and evolving treatment strategies.

Antidepressive Agents↗

Synaptogenesis and myopathy under acetylcholinesterase overexpression.

Environmental, congenital, and acquired immunological insults perturbing neuromuscular junction (NMJ) activity may induce a variety of debilitating neuromuscular pathologies. However, the molecular elements linking NMJ dysfunction to long-term myopathies are unknown. Here, we report dramatically elevated levels of mRNA encoding c-Fos and the "readthrough" (R) variant of acetylcholinesterase (AChE) in muscles of transgenic mice overexpressing synaptic (S) AChE in motoneurons and in control mice treated with the irreversible cholinesterase inhibitor diisopropylfluorophosphonate (DFP). Tongue muscles from DFP-treated and AChE-S transgenic mice displayed exaggerated neurite branching and disorganized, wasting fibers. Moreover, diaphragm muscles from both transgenic and DFP-treated mice exhibited NMJ proliferation. 2'-O-methyl-protected antisense oligonucleotides targeted to AChE mRNA suppressed feedback upregulation of AChE and ameliorated DFP-induced NMJ proliferation. Our findings demonstrate common transcriptional responses to cholinergic NMJ stress of diverse origin, and implicate deregulated AChE expression in excessive neurite outgrowth, uncontrolled synaptogenesis, and myopathology.

Acetylcholinesterase↗

Experimental evaluation and clinical application of intraoperative counterpulsation without balloon pumping.

Cardiac assistance in the form of counterpulsation (CP), created by intraaortic balloon pumping (IABP), has recently been utilized to wean patients from cardiopulmonary bypass (CPB) after conventional modalities have failed. The use of IABP, however, is often delayed because it is not part of the standard CPB setup and requires an additional cutdown, an arterial graft, and the retrograde insertion of a foreign body into the arterial tree. To eliminate the disadvantages of IABP, an alternate technique for CP has been developed. A pneumatially actuated external blood reservoir connected via a "Y" connector to the standard arterial line of the CPB circuit can provide pulsatile flow, and when synchronized with the EKG, CP with or without CPB. Experimental evaluation with dogs comparing this technique with IABP has shown that the former can create comparable CP pressure curves to the latter. The technique was applied to 11 patients undergoing either aorto-coronary bypass surgery and/or valvular surgery. Two of the 11 patients could come off CPB only with the assistance of CP. Coronary bypass graft flow, when measured, increased by 25% due to CP in two out of seven patients. The arterial CP technique has proven to be easily adapted to clinical settings and provides immediate and effective CP when required.

Animals↗