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Biomedical subjects

M Goldsmith

Publications and source records attributed to M Goldsmith.

At least 19 recordsLinked to original sources

Platelet transfusion for patients with cancer: clinical practice guidelines of the American Society of Clinical Oncology.

OBJECTIVE: To determine the most effective, evidence-based approach to the use of platelet transfusions in patients with cancer. OUTCOMES: Outcomes of interest included prevention of morbidity and mortality from hemorrhage, effects on survival, quality of life, toxicity reduction, and cost-effectiveness. EVIDENCE: A complete MedLine search was performed of the past 20 years of the medical literature. Keywords included platelet transfusion, alloimmunization, hemorrhage, threshold and thrombocytopenia. The search was broadened by articles from the bibliographies of selected articles. VALUES: Levels of evidence and guideline grades were rated by a standard process. More weight was given to studies that tested a hypothesis directly related to one of the primary outcomes in a randomized design. BENEFITS/HARMS/COST: The possible consequences of different approaches to the use of platelet transfusion were considered in evaluating a preference for one or another technique producing similar outcomes. Cost alone was not a determining factor. RECOMMENDATIONS: Appendix A summarizes the recommendations concerning the choice of particular platelet preparations, the use of prophylactic platelet transfusions, indications for transfusion in selected clinical situations, and the diagnosis, prevention, and management of refractoriness to platelet transfusion. VALIDATION: Five outside reviewers, the ASCO Health Services Research Committee, and the ASCO Board reviewed this document. SPONSOR: American Society of Clinical Oncology

Cost-Benefit Analysis↗

The credibility of children's testimony: can children control the accuracy of their memory reports?

In previous work with adults (A. Koriat & M. Goldsmith, 1994, 1996c), it was shown that people can enhance the accuracy of their testimony substantially when they (a) are effective in monitoring the correctness of their answers, (b) are free to control their reporting accordingly (i.e., to decide which pieces of information to volunteer and which to withhold), and (c) are given incentives for accurate reporting. A theoretical model was developed, which specifies the critical role of metacognitive monitoring and control processes in mediating free-report memory accuracy. The present study applies that model to examine the strategic regulation of memory accuracy by children. Three experiments indicate that both younger (ages 7 to 9) and older (ages 10 to 12) children can enhance the accuracy of their testimony by screening out wrong answers under free-report conditions but suggest a developmental trend in the level of memory accuracy that is thereby achieved. The implications of the results for the dependability of children's testimony in legal settings are discussed.

Age Factors↗

Plasmid-encoded MucB protein is a DNA polymerase (pol RI) specialized for lesion bypass in the presence of MucA', RecA, and SSB.

Replication through damaged sites in DNA requires in Escherichia coli the SOS stress-inducible DNA polymerase V (UmuC), which is specialized for lesion bypass. Homologs of the umuC gene were found on native conjugative plasmids, which often carry multiple antibiotic-resistant genes. MucB is a UmuC homolog present on plasmid R46, and its variant plasmid pKM101 has been introduced into Salmonella strains for use in the Ames test for mutagens. Using a translesion replication assay based on a gapped plasmid carrying a site-specific synthetic abasic site in the single-stranded DNA region, we show that MucB is a DNA polymerase, termed pol RI, which is specialized for lesion bypass. The activity of pol RI requires the plasmid-encoded MucA' protein and the E. coli RecA and single-strand DNA binding proteins. Elimination of any of the proteins from the reaction abolished lesion bypass and polymerase activity. The unprocessed MucA could not substitute for MucA' in the bypass reaction. The presence of a lesion bypass DNA polymerase on a native conjugative plasmid, which has a broad host range specificity and carries multiple antibiotic-resistant genes, raises the possibility that mutagenesis caused by pol RI plays a role in the spreading of antibiotic resistance among bacterial pathogens.

Bacterial Proteins↗

Inhibition of glioma cells in vitro and in vivo using a recombinant adenoviral vector containing an astrocyte-specific promoter.

Gene therapy using the herpes simplex virus thymidine kinase (HSV-TK) gene in combination with the drug ganciclovir (GCV) is a promising approach for the treatment of cancer-inducing gliomas, a tumor with a poor prognosis. In an attempt to limit the toxic effects on normal tissues, we constructed a recombinant adenoviral vector, Adgfa2TK, in which the HSV-TK gene is driven by the promoter for the gene encoding glial fibrillary acidic protein, an intermediate filament protein expressed primarily in astrocytes. Infection by Adgfa2TK of a glial cell line (C6) and a non-glial cell line (MDA-MB-231) revealed markedly increased expression of HSV-TK in glial cells as determined by Western blot. In comparison, high HSV-TK protein levels were produced in both cell lines after infection with a control virus, AdCMVTK, in which the constitutive cytomegalovirus viral promoter was used to direct HSV-TK expression. Infection of two glial cell lines (C6, U251) and two non-glial cell lines (HepG2, MDA-MB-231) with Adgfa2TK followed by GCV treatment revealed high toxicity in glial cell lines (50% growth inhibitory concentration: <2 microg/mL of GCV) with little or no toxicity (50% growth inhibitory concentration: >75 microg/mL) in the non-glial cell lines. In vivo, injection of Adgfa2TK into C6 tumors grown in nude mice followed by intraperitoneal GCV treatment significantly repressed tumor growth compared with the controls. Adgfa2TK may be useful for directing expression of the HSV-TK gene to gliomas.

Adenoviridae↗

Toward a psychology of memory accuracy.

There has been unprecedented interest in recent years in questions pertaining to accuracy and distortion in memory. This interest, catalyzed in part by real-life problems, marks a significant departure from the quantity-oriented approach that has characterized much of traditional memory research. We outline a correspondence metaphor of memory underlying accuracy-oriented research, and show how the features of this metaphor are manifested across the disparate bodies of research reviewed here. These include work in the Gestalt tradition, spatial memory, memory for gist, schema theory, source monitoring, fluency misattributions, false recall and recognition, postevent misinformation, false memories, eyewitness research, and autobiographical memory. In examining the dynamics of memory accuracy, we highlight the importance of metacognitive monitoring and control processes. We end by discussing some of the methodological, theoretical, and metatheoretical issues inherent in accuracy-oriented research, attempting to prepare the groundwork for a more coherent psychology of memory accuracy.

Humans↗

External review for promotion and tenure in schools of nursing.

To obtain information about external review for tenure and/or promotion, the faculty affairs committee in a large nursing program located in the southeastern United States conducted a survey among programs that award a doctoral degree in nursing. Research questions focused on general tenure and promotion policies, policies and procedures regarding the use of external review, and perceived advantages and disadvantages of external review. A 22-item survey was sent to 53 institutions with a total of 34 usable surveys being returned. Findings revealed that a majority of the schools used external review, especially for tenure decisions and promotion to the associate and professor rank. Promotion and tenure criteria from individual schools were usually sent to reviewers along with the candidates' curriculum vitae and manuscripts. Candidates usually participated in the selection of external reviewers, but contact with reviewers was usually instituted by the administration within the institution. It was also felt that the advantage of external review far outweighed any disadvantages.

Career Mobility↗

Monitoring and control processes in the strategic regulation of memory accuracy.

When people are allowed freedom to volunteer or withhold information, they can enhance the accuracy of their memory reports substantially relative to forced-report performance. A theoretical framework addressing the strategic regulation of memory reporting is put forward that delineates the mediating role of metamemorial monitoring and control processes. Although the enhancement of memory accuracy is generally accompanied by a reduction in memory quantity, experimental and simulation results indicate that both of these effects depend critically on (a) accuracy incentive and (b) monitoring effectiveness. The results are discussed with regard to the contribution of meta-memory processes to memory performance, and a general methodology is proposed that incorporates these processes into the assessment of memory-accuracy and memory-quantity performance.

Achievement↗

Antiemetic therapy in managed care oncology: roundtable discussion.

Few diagnoses are feared more by patients than cancer. In addition to the life-threatening nature of many cancers, the spectre of very difficult the treatment provides patients with little or no level of comfort. However, recent advances in the treatment of the side effects of cancer chemotherapy are helping to change these attitudes. On April 4, 1996, a panel of experts was convened to discuss these issues and how they affect MCOs.

Antiemetics↗

Memory in naturalistic and laboratory contexts: distinguishing the accuracy-oriented and quantity-oriented approaches to memory assessment.

A distinction is drawn between the quantity-oriented approach to memory that has dominated traditional laboratory research, and the accuracy-oriented approach that is emerging in the study of everyday memory. This distinction is shown to underlie some troubling confusions in the interpretation of empirical findings. In particular, the recall-recognition paradox, which involves the claimed superiority of recall over recognition memory in naturalistic settings, is shown to stem from the common confounding between memory property (quantity vs. accuracy) and 2 other variables that have not generally been distinguished--test format (production vs. selection) and report option (free vs. forced reporting). Three laboratory experiments reveal the fundamentally different roles played by report option and test format in accuracy-based and quantity-based memory research. Implications for memory assessment, metamemory, and the everyday-laboratory controversy are discussed.

Female↗

Physician knowledge of the CAGE alcohol screening questions and its impact on practice.

A cross-sectional survey of physicians (n = 301) and patients (n = 321) at a university-based department of medicine was completed to determine physician's ability to list CAGE alcohol screening questions and how this knowledge is associated with practice patterns. Forty-five percent of the physicians had heard of the CAGE, but only 14% could list all four of the questions correctly. Physicians who knew the CAGE were more likely to report counseling and referral of their patients who abuse alcohol. However, as assessed by patient interview and chart review, patients with an alcohol abuse problem were no more likely to have been recognized by or to have received more aggressive care from residents who knew the CAGE than patients cared for by residents who did not know the CAGE. Knowledge of an alcohol screening test is not sufficient to change physician practice related to care of patients with an alcohol abuse problem. More attention must be directed towards the development of effective strategies which integrate into clinical practice screening and initial treatment of patients who abuse alcohol.

Adult↗

A unique tubulin antiserum attenuates the rate of poleward chromosome movement in anaphase.

An antiserum against tubulin, NS20, was previously shown to specifically attenuate both fast axonal transport in vivo (Johnston, K. M. et al., Brain Res. 385, 38-45 (1986)) and in vitro (Johnston, K. M. et al., Cell Motil. Cytoskel. 7, 110-115 (1987)) and flagellar motility (Goldsmith, M. et al., Cell Motil. Cytoskel. 20, 249-262 (1991)). We hypothesized that NS20 blocked motility by binding to a multifunctional motor binding domain on the microtubules (MTs), or axonemes. Here we have examined the effect of microinjecting NS20, at metaphase, into dividing PtK2 cells. Plotting chromosome separation (CS) as a function of time, we report here that CS rates for anaphase A (chromosome-to-pole movement) were reduced by approximately 50% relative to uninjected controls. CS rates for anaphase B (spindle pole elongation) were unaffected by the NS20 antiserum. The inhibition of CS rate during anaphase A by NS20 was significantly greater than the inhibition caused by a control antitubulin serum (PC5). Two possible mechanisms underlying NS20's inhibition of CS during anaphase A were considered. NS20 could block the binding of a kinetochore-associated motor to kinetochore MTs (kMTs) or, alternatively, NS20 could stabilize kMTs against depolymerization. Our results favor the first alternative. In a cold-induced depolymerization assay, NS20 had no selective stabilizing effect on MTs. Moreover, we show that NS20 can selectively block the binding of a well characterized MT-associated motor (kinesin) to MTs, in vitro. These results suggest that NS20 may be defining a unique tubulin binding domain common to the motors underlying vesicle transport, flagellar motility, and chromosome movements during anaphase A.

Anaphase↗

Conserved beta-tubulin binding domain for the microtubule-associated motors underlying sperm motility and fast axonal transport.

An antiserum against tubulin, NS20, has been previously shown to inhibit anterograde and retrograde axonal transport by 50% in vivo and in vitro. We report here that Protein A purified NS20 antibodies also attenuate sperm motility by 50% in demembranated sea urchin sperm. This inhibition is absorbed out by preincubating the NS20 antibodies with a biochemically purified porcine microtubule preparation, with recombinant Trypanosoma beta- (but not alpha-) tubulin and most specifically, with a 37 amino acid (a.a.) synthetic peptide corresponding to a domain near (but not including) the porcine beta-tubulin C terminus. Furthermore, addition of this beta-tubulin peptide alone is sufficient to attenuate motility by 50% in demembranated sperm, indicating that this critical 37a.a. NS20 antigen is a motor binding domain. Together, the results suggest that at least two phenotypically distinct forms of microtubule-based motility, axonal transport and flagellar beating, are homologous at the fundamental level of the microtubule domains (the beta-tubulin peptide and we suggest a distinct but similarly located alpha-tubulin domain) mediating the attachment of tubulin-associated motors.

Amino Acid Sequence↗

Chemotherapy of metastatic Merkel cell cancer.

Out of 16 cases of Merkel cell cancer identified in the records of the Mt. Sinai Medical Center or affiliates, 11 patients developed systemic metastases. Literature review confirms the substantial possibility of dissemination. Both in our series and in the literature, cytotoxic chemotherapy produced a high rate of usually short-lived response, although one of our patients with disseminated metastases achieved complete remission for two years.

Adult↗

Metastasizing pleomorphic adenoma with myoepithelial cell predominance.

The biological behavior of pleomorphic adenomas (mixed tumors) of salivary gland origin is complex. Tumors with benign histologic features may exhibit recurrence and locally aggressive behavior especially after incomplete excision. A small percentage of pleomorphic adenomas have obvious malignant components in epithelial or in both epithelial and mesenchymal components and can metastasize. There are also rare case reports which appear to document typical pleomorphic adenomas of salivary gland with histologically identical visceral and lymph node metastases. Recently myoepithelial cell proliferation has been identified as a possible predictor of aggressive clinical behavior in otherwise histologically benign pleomorphic adenomas. We report such a parotid gland lesion with local recurrence and retroperitoneal spread. DNA-flow cytometry of cells from the paraffin-embedded primary and metastasis showed similar aneuploid populations. Aneuploidy appeared to reflect the malignant potential of this particular pleomorphic adenoma and suggests that DNA-flow cytometry of salivary gland tumors may yield important prognostic information.

Adenoma, Pleomorphic↗

Separate non-cholinergic descending projections and cholinergic ascending projections from the nucleus tegmenti pedunculopontinus.

A substantial population of cells from the nucleus tegmenti pedunculopontinus was demonstrated to have descending projections to the spinal cord using fluorescent retrograde axonal tracers. Double-labeling studies showed that separate perikarya in this region have descending versus ascending projections. The distributions of the cell bodies with ascending or descending projections were spatially distinct, but partially overlapping. Some ascending, but not the descending, projections were cholinergic.

Acetylcholine↗