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Biomedical subjects

M R Gold

Publications and source records attributed to M R Gold.

177 records · Page 10Linked to original sources
PubMed1981

Modification of the discharge of vagal cardiac neurons during learned heart rate change.

Visually conditioned heart rate change in the pigeon has been developed as a vertebrate model system for the cellular neurophysiological analysis of associative learning. In previous studies of the "final common path," it was shown that both the vagal and sympathetic cardiac innervations contribute to this response. The present experiments indicate that, prior to any behavioral training, the visual stimulus elicits a small decrease in the discharge of vagal cardiac neurons. During conditioning, this stimulus evokes a progressively greater decrease in discharge that parallels the acquisition of the conditioned cardioacceleration. In contrast, nonassociative control animals show habituation of the initial decrease in discharge. These data confirm the involvement of the vagal cardiac innervation in conditioned heart rate change, indicate that the vagal innervation acts synergistically with the sympathetic to produce cardioacceleration, and suggest that a short-latency pathway mediates the conditioned response.

Action Potentials↗
PubMed1981

Heart rate conditioning in the pigeon immobilized with alpha-bungarotoxin.

Previous in vitro studies have yielded conflicting results concerning the physiological effects of alpha-bungarotoxin (alpha-BTX) at avian autonomic ganglia. In the present study heart rate change was classically conditioned in pigeons immobilized with alpha-BTX to assess the effects of this agent on autonomic function in the intact animal. When compared with non-immobilized controls, alpha-BTX had no significant effect on basal heart rate or on the rate of acquisition, magnitude or dynamics of conditioned heart rate change. Furthermore, a significant difference in performance between groups receiving conditioning and sensitization paradigms clearly indicated the establishment of conditioned responding. It is concluded that alpha-BTX has little or no effect on the cardiac innervation at doses sufficient to block neuromuscular transmission. The irreversible blockade of neuromuscular transmission by alpha-BTX without the side-effects produced by most other paralytics makes it an ideal choice as an immobilizing agent in acute preparations.

Animals↗
PubMedDate not supplied

Recommendations for reporting cost-effectiveness analyses. Panel on Cost-Effectiveness in Health and Medicine.

OBJECTIVE: This article, the third in a 3-part series, describes recommendations for the reporting of cost-effective analyses (CEAs) intended to improve the quality and accessibility of CEA reports. PARTICIPANTS: The Panel on Cost-Effectiveness in Health and Medicine, a nonfederal panel with expertise in CEA, clinical medicine, ethics, and health outcomes measurement, convened by the US Public Health Service. EVIDENCE: The panel reviewed the theoretical foundations of CEA, current practices, alternative methods, published critiques of CEAs, and criticisms of general CEA methods and reporting practices. CONSENSUS PROCESS: The panel developed recommendations through 2 1/2 years of discussions. Comments on preliminary drafts were solicited from federal government methodologists, health agency officials, and academic methodologists. CONCLUSIONS: These recommendations are proposed to enhance the transparency of study methods, assist analysts in providing complete information, and facilitate the presentation of comparable cost-effectiveness results across studies. Adherence to reporting conventions and attention to providing information required to understand and interpret study results will improve the relevance and accessibility of CEAs.

Cost-Benefit Analysis↗
PubMedDate not supplied

Purification and identification of tyrosine-phosphorylated proteins from B lymphocytes stimulated through the antigen receptor.

The activation of protein tyrosine kinase (PTKs) and subsequent tyrosine phosphorylation of cellular proteins is a critical initial signal in the response of eukaryotic cells to mitogens, differentiative signals, and other stimuli. A number of PTK substrates have been identified and many of these are components of signal transduction pathways that regulate cell function. However, the majority of proteins that are tyrosine-phosphorylated in response to receptor signaling remain unidentified. As some of these unidentified PTK substrates may also be signal-transducing proteins, their identification and functional characterization is an important objective towards understanding receptor signaling. We describe the development of a comprehensive and general process for the isolation and structural characterization of tyrosine-phosphorylated proteins. The method involves enrichment by anti-phosphotyrosine affinity chromatography, electrophoretic concentration and separation, and proteolytic fragmentation of individual purified phosphoproteins. Resulting peptide fragments are separated by microbore reverse-phase high performance liquid chromatography (RP-HPLC) and a portion of the eluted peptides are subjected to electrospray-mass spectrometry (ES/MS) for accurate determination of peptide masses. Proteolytic fragmentation of a protein produces a characteristic set of peptide masses that can be used to rapidly identify the protein by searching databases containing the peptide mass "fingerprints" for all known proteins. The identity of the protein established by this method can be confirmed by sequence analysis of selected peptides. We have applied this procedure to the analysis of PTK substrates from B lymphocytes that have been stimulated through the B cell antigen receptor (BCR). Signaling by this receptor is involved in the generation of antibodies against foreign molecules (antigens). The BCR activates multiple PTKs which phosphorylate at least 30 different proteins. We have identified several of these tyrosine-phosphorylated proteins, including Syk, a PTK that is known to be tyrosine-phosphorylated in activated B cells. Thus, the procedure described here can be used to identify regulatory proteins of low abundance. The process consists of a logical succession of compatible steps that avoids pitfalls inherent to prior attempts to characterize low abundance phosphoproteins and should find wide use for the identification of tyrosine-phosphorylated proteins in other cell types.

Amino Acid Sequence↗
PubMedDate not supplied

Examination of B lymphoid cell lines for membrane immunoglobulin-stimulated tyrosine phosphorylation and src-family tyrosine kinase mRNA expression.

Crosslinking of membrane immunoglobulin (mIg) on B cells induces two signal transduction pathways: protein tyrosine phosphorylation and phosphoinositide turnover. A panel of murine and human B cell-lines, representing different stages of B cell development, was examined for the presence of anti-immunoglobulin-induced protein tyrosine phosphorylation. Of 10 B cell lines examined, only one, the human Raji cell line, had no detectably induced protein tyrosine phosphorylation. The pattern of proteins that were phosphorylated on tyrosine in response to mIg crosslinking differed somewhat in cell lines representing different stages of B cell development. Differences in the levels of constitutive phosphorylation of proteins were also observed between the cell lines. The identity of the tyrosine kinase(s) activated by membrane immunoglobulin ligation is not known. However, members of the src family of intracellular tyrosine kinases have been implicated as signal transduction molecules. As the tyrosine phosphorylation of proteins is a general phenomenon of signal transduction by membrane immunoglobulin, the tyrosine kinase(s) activated by it might be expected to be present in all cell lines in which the tyrosine phosphorylation signalling occurs. Therefore we examined these B cells for expression of mRNAs encoding the eight known src-like tyrosine kinases. Surprisingly, all eight kinase mRNAs were expressed in at least some of the B cell lines examined. The expression pattern of the fyn, hck, and lck genes suggests that expression of these kinases may be developmentally regulated in the B cell lineage. Three of the kinases, p55blk, p53/p56lyn and p60src, were detected in all 10 B cell lines. Whereas the src gene shows a ubiquitous pattern of expression, the expression of the blk and lyn genes is mostly restricted to cells of hematopoietic origin, and more especially B lymphoid cells. Thus, p55blk and p53/p56lyn may be particularly good candidates for the membrane immunoglobulin-activated tyrosine kinase.

Animals↗
PubMedDate not supplied

gamma-Aminobutyric acid and glycine activate Cl- channels having different characteristics in CNS neurones.

We have studied the properties of Cl- channels in Müller cells of the lamprey brain, which are activated by two putative neurotransmitters, glycine and gamma-aminobutyric acid (GABA). Previous studies have shown that in these cells the two ligands act through different receptors, and it was of interest to determine whether or not the two receptors, in turn, activate separate channels having different properties. We have shown previously that the channels activated by glycine have large conductances which decrease rapidly as the intracellular Cl- concentration [Cl-]i is increased above normal. We show here that GABA-activated channels have much smaller conductances which are independent of [Cl-]i over the experimental range and also that the response to a saturating application of glycine is not occluded by simultaneous GABA application. These observations indicate that the glycine and GABA receptors are coupled to separate Cl- channels having different characteristics.

Animals↗
PubMedDate not supplied

What drives Medicare managed care growth?

We conducted case studies of four markets--Los Angeles, New York City, Portland (OR), and Tampa-St. Petersburg--to learn more about why Medicare managed care develops differently across the country even when capitation rates are similar. Our analysis highlights the importance of prior managed care history, beneficiary characteristics, supplemental coverage patterns, the form of provider organization, practice patterns, care expectations, and other market characteristics to the development of Medicare managed care. Policymakers seeking to expand Medicare managed care need to go beyond national statistics to understand how local market forces affect its growth.

Attitude to Health↗
PubMedDate not supplied

Provider organizations at risk: a profile of major risk-bearing intermediaries, 1999.

Provider organizations have evolved to function as intermediaries between managed care plans and individual providers. These organizations assume much financial risk and care management responsibilities. We profile the characteristics of these organizations in markets across the country. The data, taken from a 1999 telephone survey of sixty-four entities in twenty markets and from interviews conducted during site visits to four markets, highlight the youth of many of these organizations, the large financial risk and functional responsibilities they bear, and the mixed views they hold about the health plans they contract with in terms of their willingness to delegate the authority, support, and collaboration that accompany risk. Policymakers need to evaluate what this means for oversight of managed care.

Capitation Fee↗