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Biomedical subjects

M Leonard

Publications and source records attributed to M Leonard.

At least 73 records · Page 4Linked to original sources
PubMed1996

Comparison of idarubicin to daunomycin in a randomized multidrug treatment of childhood acute lymphoblastic leukemia at first bone marrow relapse: a report from the Children's Cancer Group.

The outcome of children with acute lymphoblastic leukemia (ALL) and bone marrow relapse has been unsatisfactory largely because of failure to prevent subsequent leukemia relapses. Ninety-six patients were enrolled and received vincristine, prednisone, L-asparaginase, and an anthracycline as reinduction therapy. Ninety-two patients were randomized to receive either daunomycin (DNR) or idarubicin (IDR). After achievement of second complete remission (CR2), maintenance chemotherapy included the same anthracycline, IDR or DNR, high-dose cytarabine, and escalating-dose methotrexate. Compared to DNR (45 mg/m2/week x 3), IDR (12.5 mg/m2/week x 3) was associated with prolonged myelosuppression and more frequent serious infections. Halfway through the study, the dose of IDR was reduced to 10 mg/m2. Overall, second remission was achieved in 71% of patients. Reinduction rate was similar for IDR and DNR. Reasons for induction failure differed; none of 15, 1 of 5, and 5 of 7 reinduction failures were due to infection for DNR, IDR (10 mg/m2), and IDR (12.5 mg/m2), respectively. Two-year event-free survival (EFS) was better among patients who received IDR (12.5 mg/m2) (27 +/- 18%) compared to DNR (10 +/- 8%, P = 0.05) and IDR (10 mg/m2) (6 +/- 12%, P = 0.02). However, after 3 years of follow-up, late events in the high-dose IDR group result in a similar EFS to the lower-dose IDR and DNR groups. In conclusion, IDR is an effective agent in childhood ALL. When used weekly at 12.5 mg/m2 during induction, the EFS outcome during the first 2 years of treatment appears better than lower-dose IDR or DNR (45 mg/m2), although this difference was not sustained at longer periods of follow-up. Increased hematopoietic toxicity seen at this dose might be reduced through the use of supportive measures, such as hematopoietins and intestinal decontamination.

Antibiotics, Antineoplastic↗
PubMed1995

Polyvinyl alcohol-coated macroporous polystyrene particles as stationary phases for the chromatography of proteins.

A method is described for the hydrophilization of macroporous poly(styrene-divinylbenzene) (PS-DVB) beads by adsorption of polyvinyl alcohol (PVA). PVA adsorbs strongly to PS-DVB surfaces but partially desorbs when exposed to protein solutions. To overcome this problems, the polymeric adsorbed layer was stabilized by crosslinking. We report the effect of polymer adsorption and crosslinking conditions on the amount of adsorbed PVA, on the stability of the polymeric layer and on the hydrophilization efficiency with regard to bovine serum albumin-a strongly hydrophobic protein. The properties of the coated supports were also evaluated by size-exclusion chromatography. PVA coating was shown to greatly reduce hydrophobic interactions. The pore size of modified PS-DVB particles was found to decrease significantly with increasing amounts of adsorbed PVA.

Absorption↗
PubMed1995

Disclosure of imaging findings to patients directly by radiologists: survey of patients' preferences.

OBJECTIVE: The purpose of this study was to determine if patients prefer to have radiologists tell them imaging findings immediately after the examination or if they prefer to hear the results later from their referring physician. SUBJECTS AND METHODS: A simple questionnaire was devised and distributed to 261 consecutive patients in the radiology department of a large university hospital. During a 10-day period, patients seen in several departmental sections (gastrointestinal, genitourinary, CT, sonography, mammography, chest, musculoskeletal) completed the questionnaire. Patients were asked if they wanted the radiologist to tell them if the results were normal; if the results were abnormal; if they would prefer to hear the results from their family doctor, internist, or other primary care provider; and if they felt entitled to an explanation of their test results. Results were tabulated and expressed as percentages. RESULTS: Analysis of the 261 questionnaires disclosed that 92% of patients wanted the radiologist to tell them if the results are normal. An additional 7% answered "Yes, but only if I ask." If the results are abnormal (cancer, for example), 87% wanted the radiologist to tell them. An additional 7% answered "Yes, but only if I ask." CONCLUSION: Our results show that most patients prefer to hear the results of imaging examinations from the radiologist at the time of the procedure rather than to hear them later from the referring physician, regardless of the findings.

Attitude to Health↗
PubMed1994

Band 1 subunit of Escherichia coli preportein translocase and integral membrane export factor P12 are the same protein.

Escherichia coli preprotein translocase consists of the peripheral membrane protein SecA and the integral membrane domain SecY/E. SecY/E, whether isolated chromatographically or by immunoprecipitation, was found to be complex of three polypeptides, SecY, SecE, and band 1. Band 1 did not correspond to a known sec gene product. The independent purification of the separate integral membrane polypeptides needed for reconstitution of translocation yielded SecY, SecE, and a protein that we termed P12. Based on the sequence of P12, we have prepared antisera to a carboxyl-terminal peptide domain and shown that this antiserum specifically labels only P12 on immunoblots of inner membrane vesicles. We now report that affinity-purified anti-P12 antibodies specifically label the band 1 subunit of the SecY/E complex, whether the SecY/E was isolated chromatographically or by precipitation with antibodies to an epitope-tagged SecY subunit. In addition, the antiserum to P12 can specifically immunoprecipitate the full three-subunit SecY/E complex from detergent extracts. This finding completes the identification of the polypeptides that are essential for catalysis of preprotein translocation.

Adenosine Triphosphatases↗
PubMed1994

Traction forces generated by locomoting keratocytes.

Traction forces produced by moving fibroblasts have been observed as distortions in flexible substrata including wrinkling of thin, silicone rubber films. Traction forces generated by fibroblast lamellae were thought to represent the forces required to move the cell forwards. However, traction forces could not be detected with faster moving cell types such as leukocytes and growth cones (Harris, A. K., D. Stopak, and P. Wild. 1981. Nature (Lond.). 290:249-251). We have developed a new assay in which traction forces produced by rapidly locomoting fish keratocytes can be detected by the two-dimensional displacements of small beads embedded in the plane of an elastic substratum. Traction forces were not detected at the rapidly extending front edge of the cell. Instead the largest traction forces were exerted perpendicular to the left and right cell margins. The maximum traction forces exerted by keratocytes were estimated to be approximately 2 x 10(-8) N. The pattern of traction forces can be related to the locomotion of a single keratocyte in terms of lamellar contractility and area of close cell-substratum contact.

Animals↗
PubMed1994

Impaired cardiovascular reflexes precede deoxycorticosterone acetate-salt hypertension.

We hypothesized that impaired cardiopulmonary reflexes but not altered baroreceptor reflexes precede deoxycorticosterone acetate (DOCA)-salt hypertension. Uninephrectomized rats were given either DOCA and 0.9% NaCl as drinking water, 0.9% NaCl alone, or tap water. We measured mean blood pressure, heart rate, and renal sympathetic nerve activity. After 8 days, mean blood pressure was not different in DOCA-salt and control rats. Volume-sensitive cardiopulmonary reflexes were tested by intravenous volume loading with saline (10% body weight in 15 minutes), which decreased renal sympathetic nerve activity without changing mean blood pressure or heart rate. This response was blunted in DOCA-salt rats. Chemosensitive cardiopulmonary reflexes were tested by 15-minute infusions of the serotonin 5-HT3 agonist phenylbiguanide, which decreased renal sympathetic nerve activity without changing mean blood pressure or heart rate. Sustained decreases in renal sympathetic nerve activity occurred during phenylbiguanide infusion in controls but were blunted over time in DOCA-salt rats. The arterial baroreflex responses to graded infusions of methoxamine and nitroprusside were analyzed by sigmoidal curve fitting. There were no differences in gain of renal sympathetic nerve activity or heart rate between the groups. Thus, DOCA-salt rats exhibit impaired cardiopulmonary reflexes before the onset of hypertension; the volume-sensitive reflexes are more severely affected than chemosensitive reflexes. The arterial baroreceptor reflex is unaltered. The decreased sensitivity of cardiopulmonary reflexes may contribute to DOCA-salt hypertension.

Analysis of Variance↗
PubMed1994

Levels of political participation and political expectations among nurses in New York State.

The purpose of this study was to investigate the relationship of area of practice, educational level, and membership in a professional organization to political participation and political expectations among a group of 108 registered nurses. "The Political Expectations and Participation Questionnaire" (PEPQ) (Daffin, 1988) was used to identify the nine political roles of voter, campaigner, player, monitor, networker, spokesperson, negotiator, leader, and lobbyist. It was found that nurses with master's or doctoral degrees had significantly higher levels of political participation than did nurses with baccalaureates, associate degrees, or diplomas. Nurse educators were found to have significantly higher levels of political participation than nurses in clinical practice. Members of professional organizations had significantly higher levels of political participation with respect to campaigner, player, and leader roles. No significant differences in levels of political expectation were found with respect to area of practice or membership in a professional organization.

Education, Nursing↗
PubMed1993

Dynamics of GATA transcription factor expression during erythroid differentiation.

Although the formation of terminally differentiated erythroid cells has been shown to require the presence of a functional GATA-1 gene in vivo, the role of this transcription factor and other members of the GATA family at earlier stages of erythroid differentiation is unclear. In this report, the expression of GATA-1, GATA-2, and GATA-3 has been examined in enriched peripheral blood progenitors before and after culture in a well-characterized liquid culture system. In addition primary leukemic cells as well as several erythroleukemic and nonerythroid cell lines were analyzed for GATA factor expression. The results show that the profile of GATA factor expression in erythroid cells is distinct from that of myeloid or lymphoid lineages. Erythroleukemic cell lines express little or no GATA-3, but high levels of GATA-1 and GATA-2. When they are induced to display the terminal erythroid phenotype, little change in the level of GATA-1 is detected but a significant decline in the levels of GATA-2 is observed commensurate with the degree of maturation achieved by the cells. Enrichment of erythroid progenitors from peripheral blood leads to selection of cells that express both GATA-1 and GATA-2. As the enriched populations are cultured in suspension in the presence of multiple cytokines, the levels of both GATA-1 and GATA-2 initially increase. However, in cultures containing only erythropoietin, which show exclusive erythroid differentiation, the levels of GATA-1 continue to increase, whereas GATA-2 expression declines as erythroid maturation progresses. In contrast, cultures lacking Epo (ie, with interleukin-3 and kit ligand) display limited progression towards both the myeloid and erythroid pathways, and high levels of expression of both GATA-1 and GATA-2 are maintained. Despite the initial upregulation of GATA-1 expression in the latter cultures, terminal erythroid differentiation does not occur in the absence of erythropoietin. These results indicate that GATA-1 upregulation is associated with both the initiation and the maintenance of the erythroid program, but that these two processes appear to be under separate regulatory control. Thus, the dynamic changes in the levels of different GATA factors that occur during primary erythroid differentiation suggest that the levels of these factors may influence the progression to specific hematopoietic pathways.

Base Sequence↗
PubMed1993

A highly selective cardiorenal serotonergic 5-HT3-mediated reflex in rats.

To elucidate whether prolonged stimulation of cardiopulmonary serotonergic (5-HT3) receptors could play a role in the control of renal sympathetic nerve activity (RSNA), we compared 15-min intravenous infusions to bolus administrations of the 5-HT3 receptor agonist phenyl biguanide (PBG) and to a 0.9% saline load (5% body wt) in rats. Short-term and prolonged stimulation of 5-HT3-sensitive cardiopulmonary reflexes caused dose-related decreases in RSNA but not in lumbar sympathetic nerve activity (LSNA); only short-term stimulation caused decreases in blood pressure (BP) and heart rate (HR). Saline loading lowered RSNA but not LSNA, BP, or HR. Baroreceptor denervation did not influence any of these responses. Scopolamine attenuated BP and HR but not RSNA responses to bolus PBG. Pretreatment with a 5-HT3 receptor antagonist inhibited responses to PBG but not to saline. Vagotomy abolished all responses to all interventions. Thus 1) the prolonged stimulation of cardiopulmonary 5-HT3 receptors caused sustained suppression of RSNA, 2) decreased BP and HR were manifest only during short-term stimulation (3 min), and 3) blockade of 5-HT3 receptors did not influence responses to cardiopulmonary mechanoreceptor stimulation.

Animals↗