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Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 397 records · Page 22Linked to original sources
PubMed1999

The life, legacy, and premature death of Felix Mendelssohn.

Felix Mendelssohn is one of the great classical composers of all time. During his short lifetime in the first half of the nineteenth century, he reached enormous heights as a composer, conductor, and leader in the world of music. Nearly one hundred years after his death, the Nazi regime attempted, unsuccessfully, to erase his music and his memory from history. Since the end of World War II, there has been a resurgence in interest in the life and music of Felix Mendelssohn and that of his sister, Fanny. Felix Mendelssohn died in 1947 at the age of 38. Both of his sisters died suddenly at the ages of 42 and 45. There is insufficient laboratory or post-mortem data to make a medical diagnosis with certainty. However, based on the information available to us, we speculate that Mendelssohn suffered a subarachnoid or intracerebral hemorrhage. The differential diagnosis of familial stroke syndrome is discussed.

Famous Persons↗
PubMed1999

Alteration in enterocyte gene expression may explain structural and functional changes following glutamine supplemented parenteral nutrition.

Following extensive bowel resection, the intestinal tract undergoes a variety of adaptive responses to enhance bowel function. The purpose of this study was to determine the effect of glutamine-supplemented parenteral nutrition on mucosal cellularity and gut function. In addition, enterocyte gene expression of two relevant systems was also characterized and related to the structural and functional changes that occurred. Male Wistar rats underwent a 60% small bowel resection and jugular vein catheterization and were randomized into two groups. The control group (n = 10) received a standard intravenous nutritional solution and the study group (n = 10) received a similar solution but enriched with alanylglutamine dipeptide. After 7 days blood was taken for amino acid analysis, and bowel was harvested to determine mucosal morphology and expression of mucosal cell glutaminase and IGF-I mRNA. Mesentery lymphnodes were cultured to determine the presence of bacteria and thus access bacteria translocation. Serum glutamine concentration and mucosal architecture were maintained in the study group compared to the controls. Seventy percent of lymphnodes were cultured positive in control vs. only 20% in the study group (P < 0.05). Jejunal mucosal glutaminase and ileum mucosal IGF-I mRNA increased twofold and threefold respectively compared to control animals. Parenteral nutrition supplemented with alanyl-glutamine dipeptide supports mucosal cellularity and regional immune function in rodents following intestinal resection, These alterations are associated with enhanced enterocyte expression of glutaminase and IGF-I. These changes may facilitate the structural and functional alterations which were observed in the glutamine treated animals.

Animals↗
PubMed1998

Infanticide and expulsion of females in a cooperative mammal.

In cooperative groups of suricates (Suricata suricatta), helpers of both sexes assist breeding adults in defending and feeding pups, and survival rises in larger groups. Despite this, dominant breeding females expel subordinate females from the group in the latter half of their (own) pregnancy apparently because adult females sometimes kill their pups. Some of the females that have been expelled are allowed to rejoin the group soon after the dominant female's pups are born and subsequently assist in rearing the pups. Female helpers initially resist expulsion and repeatedly attempt to return to their natal group, indicating that it is unlikely that dominant females need to grant them reproductive concessions to retain them in the group.

Animals↗
PubMed1998

Adjuvant 5-fluorouracil and leucovorin with or without interferon alfa-2a in colon carcinoma: National Surgical Adjuvant Breast and Bowel Project protocol C-05.

BACKGROUND: National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol C-03 showed a benefit from leucovorin (LV)-modulated 5-fluorouracil (5-FU) adjuvant therapy (5-FU + LV) in patients with Dukes' stage B or C carcinoma of the colon. Preclinical and clinical phase I/II data suggested that interferon alfa-2a (IFN) enhanced the efficacy of 5-FU therapy. Accordingly, in NSABP protocol C-05, the addition of recombinant IFN to 5-FU + LV adjuvant therapy was evaluated. METHODS: Data are presented for 2176 patients with Dukes' stage B or C cancer entered onto protocol C-05 during the period from October 1991 through February 1994. Individuals with an Eastern Cooperative Oncology Group performance status of 0-2 (ranges from fully active to ambulatory and capable of self-care but unable to work), a life expectancy of at least 10 years, and curative resection were stratified by sex, disease stage, and number of involved lymph nodes and were randomly assigned to receive either 5-FU + LV or 5-FU + LV + IFN; the mean time on the study as of June 30, 1997, was 54 months. All statistical tests were two-sided. RESULTS: There was no statistically significant difference in either disease-free survival (5-FU + LV, 69%; 5-FU + LV + IFN, 70%) or overall survival (5-FU + LV, 80%; 5-FU + LV + IFN, 81%) at 4 years of follow-up. Toxic effects of grade 3 or higher were observed in 61.8% of subjects in the group treated with 5-FU + LV and in 72.1% of subjects in the group treated with 5-FU + LV + IFN; fewer patients in the latter group completed protocol-mandated 5-FU + LV therapy than in the former group (77.1% versus 88.5%). CONCLUSION: The addition of IFN to 5-FU + LV adjuvant therapy confers no statistically significant benefit, but it does increase toxicity.

Antimetabolites, Antineoplastic↗
PubMed1998

Prevalence of and risk factors for fecal shedding of Cryptosporidium parvum oocysts in horses.

OBJECTIVE: To determine prevalence of and risk factors for fecal shedding of Cryptosporidium parvum oocysts among 3 populations of horses. DESIGN: Cross-sectional study. ANIMALS: 152 horses participating in the 1996 Texas State 4-H Horse Show, 144 horses examined by the veterinary teaching hospital, and 70 broodmares and their 10- to 21-day-old foals. PROCEDURE: Information on signalment and potential risk factors for fecal shedding of oocysts was obtained. Fecal samples were evaluated for oocysts by means of acid-fast (AF) staining, immunofluorescence assay (IFA), and, for selected samples, flow cytometry (FC). RESULTS: Results of the 3 diagnostic tests were significantly different. The best agreement was between results of the IFA and FC; AF staining and FC were more sensitive than the IFA, but AF staining was less specific. Fecal samples from 13 horses were classified as positive for oocysts. Risk factors for fecal shedding of oocysts included residence on 2 of 4 breeding farms involved in the study, age < 6 months, and history of diarrhea during the preceding 30 days. A municipal water source was implicated as a risk but could not be verified because of insufficient data. CLINICAL IMPLICATIONS: Mature horses and exposure to cattle did not appear to be important sources of cryptosporidial infection for foals. Overall prevalence of C parvum infection among these horses was low, and C parvum infection appeared to be associated with particular farms, rather than an endemic opportunistic infection in horses.

Animals↗
PubMed1998

Aryl hydrocarbon receptor-mediated antiestrogenicity in MCF-7 cells: modulation of hormone-induced cell cycle enzymes.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) inhibits 17beta-estradiol (E2) mammary tumor growth in rodents and in MCF-7 human breast cancer cells; however, the cell cycle genes/proteins which are inhibited have not been determined. Initial studies showed that treatment of MCF-7 cells with 10 nM E2 significantly increased cyclin D1 (protein and mRNA), cdk2- and cdk4-dependent kinase activities, and hyperphosphorylation of retinoblastoma (RB) protein. In contrast to results of recent studies (M. D. Planas-Silva and R. A. Weinberg, 1997, Mol. Cell. Biol. 17, 4059-4069), E2 induced dissociation of both cdk2 and cdk4 proteins from the p21 protein complex and significantly increased cdk7-dependent kinase activity. Treatment of MCF-7 cells with E2 also induced cdc25A phosphatase protein, which was accompanied by increased cdk2 and cdk4 proteins containing unphosphorylated tyrosine residues. Although TCDD alone has minimal effects on cell cycle proteins/enzymes, several E2-induced responses were significantly inhibited in MCF-7 cells cotreated with E2 plus TCDD. For example, TCDD significantly inhibited E2-induced hyperphosphorylation of RB, cyclin D1 protein, and cdk2-, cdk4-, and cdk7-dependent kinase activities. Inhibition of E2-induced cdk4-dependent kinase activity by TCDD may be related to the parallel decrease of E2-induced cyclin D1 protein, and inhibition of induced cdk2- and cdk4-dependent kinase activities may be due to significantly increased p21 levels in cells cotreated with TCDD plus E2. These results demonstrate that the antiestrogenic activity of TCDD is due to downregulation of several E2-induced cell cycle proteins/activities and this illustrates the complex cross talk between the aryl hydrocarbon and the E2 receptor signaling pathways.

Breast Neoplasms↗
PubMed1998

Folding, calcium binding, and structural characterization of a concatemer of the first and second ligand-binding modules of the low-density lipoprotein receptor.

The ligand-binding domain of the low-density lipoprotein (LDL) receptor is comprised of seven tandemly repeated ligand-binding modules, each being approximately 40 amino acids long and containing six conserved cysteine residues. We have expressed and characterized a concatemer of the first two modules (LB1 and LB2) of the human LDL receptor. Oxidative folding of the recombinant concatemer (rLB1-2), in the presence of calcium ions, gave a single dominant isomer with six disulfide bonds. Peptic cleavage of the short linker region that connects the last cysteine residue of LB1 and the first cysteine residue of LB2 yielded two discrete fragments, thus excluding the presence of intermodule disulfide bonds. The N-terminal module, LB1, reacted with a conformation-specific monoclonal antibody (IgG-C7) made to LB1 in the native LDL receptor. From this, we concluded that the first module was correctly folded, with the same set of disulfide bonds as LB1 of the LDL receptor. The disulfide bond connections of LB2 were identified from mass spectral analysis of fragments formed by digestion of the C-terminal peptic fragment with elastase. These data showed that the disulfide bonds of LB2 connected Cys(I) and Cys(III), Cys(II) and Cys(V), and Cys(IV) and Cys(VI). This pattern is identical to that found for recombinant LB1 and LB2. The concatemer has two high-affinity calcium-binding sites, one per module. An analysis of the secondary chemical shifts of Calpha protons shows that the conformations of LB1 and LB2 in the concatemer are very similar to those of the individual modules, with no evidence for strong interactions between the two modules.

Amino Acid Sequence↗
PubMed1998

What makes a good reviewer and a good review for a general medical journal?

CONTEXT: Selecting peer reviewers who will provide high-quality reviews is a central task of editors of biomedical journals. OBJECTIVES: To determine the characteristics of reviewers for a general medical journal who produce high-quality reviews and to describe the characteristics of a good review, particularly in terms of the time spent reviewing and turnaround time. DESIGN, SETTING, AND PARTICIPANTS: Surveys of reviewers of the 420 manuscripts submitted to BMJ between January and June 1997. MAIN OUTCOME MEASURES: Review quality was assessed independently by 2 editors and by the corresponding author using a newly developed 7-item review quality instrument. RESULTS: Of the 420 manuscripts, 345 (82%) had 2 reviews completed, for a total of 690 reviews. Authors' assessments of review quality were available for 507 reviews. The characteristics of reviewers had little association with the quality of the reviews they produced (explaining only 8% of the variation), regardless of whether editors or authors defined the quality of the review. In a logistic regression analysis, the only significant factor associated with higher-quality ratings by both editors and authors was reviewers trained in epidemiology or statistics. Younger age also was an independent predictor for editors' quality assessments, while reviews performed by reviewers who were members of an editorial board were rated of poorer quality by authors. Review quality increased with time spent on a review, up to 3 hours but not beyond. CONCLUSIONS: The characteristics of reviewers we studied did not identify those who performed high-quality reviews. Reviewers might be advised that spending longer than 3 hours on a review on average did not appear to increase review quality as rated by editors and authors.

Data Collection↗
PubMed1998

Effect of blinding and unmasking on the quality of peer review: a randomized trial.

CONTEXT: Little research has been conducted into the quality of peer review and, in particular, the effects of blinding peer reviewers to authors' identities or masking peer reviewers' identities. OBJECTIVE: To determine whether concealing authors' identities from reviewers (blinding) and/or revealing the reviewer's identity to a coreviewer (unmasking) affects the quality of reviews, the time taken to carry out reviews, and the recommendation regarding publication. DESIGN AND SETTING: Randomized trial of 527 consecutive manuscripts submitted to BMJ, which were randomized and each sent to 2 peer reviewers. INTERVENTIONS: Manuscripts were randomized as to whether the reviewers were unmasked, masked, or uninformed that a study was taking place. Two reviewers for each manuscript were randomized to receive either a blinded or an unblinded version. MAIN OUTCOME MEASURES: Mean total quality score, time taken to carry out the review, and recommendation regarding publication. RESULTS: Of the 527 manuscripts entered into the study, 467 (89%) were successfully randomized and followed up. The mean total quality score was 2.87. There was little or no difference in review quality between the masked and unmasked groups (scores of 2.82 and 2.96, respectively) and between the blinded and unblinded groups (scores of 2.87 and 2.90, respectively). There was no apparent Hawthorne effect. There was also no significant difference between groups in the recommendations regarding publication or time taken to review. CONCLUSIONS: Blinding and unmasking made no editorially significant difference to review quality, reviewers' recommendations, or time taken to review. Other considerations should guide decisions as to the form of peer review adopted by a journal, and improvements in the quality of peer review should be sought via other means.

Authorship↗
PubMed1998

Evaluating the BMJ guidelines for economic submissions: prospective audit of economic submissions to BMJ and The Lancet.

CONTEXT: Editorial management of articles on health economics may benefit from guidelines for peer review and revision. OBJECTIVE: To assess whether publication (in August 1996) of the BMJ guidelines on peer review of economics submissions made any difference to editorial and peer review processes, quality of submitted manuscripts, and quality of published manuscripts. DESIGN AND SETTING: Before-after study conducted in the editorial offices of BMJ and The Lancet of the effect of the BMJ guidelines on review and revision of economics submissions, defined as those making explicit comments about resource allocation and/or costs of interventions. MAIN OUTCOME MEASURES: Editorial fate and changes in the quality of submissions. RESULTS: A total of 2982 manuscripts were submitted to the 2 journals during the before periods, 105 (3.5%) of which were economics submissions. Of these, 27 (24.3%) were full economics evaluations, and 78 (75.7%) were other economics submissions. Overall acceptance rate was 11.6% (12/105). During the after period 2077 manuscripts were submitted to the 2 journals, 87 (4.2%) of which were economics submissions. Eighteen (20.7%) were full economics evaluations, and 69 (79.3%) were other economics submissions. Overall acceptance rate was 6.9% (6/87). Although a number of manuscripts could not be traced to determine whether they were economics submissions, there appeared to be little difference between the 2 journals in numbers or editorial fate of the manuscripts. There was no change in the quality of submitted manuscripts, but BMJ editors found the guidelines and checklists useful and sent fewer economics submissions for external peer review in the after phase. CONCLUSIONS: Publication of the guidelines helped the BMJ editors improve the efficiency of the editorial process but had no impact on the quality of economics evaluations submitted or published.

Economics↗