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Biomedical subjects

J Myers

Publications and source records attributed to J Myers.

At least 91 records · Page 5Linked to original sources
PubMed1997

Effect of exercise training on myocardial remodeling in patients with reduced left ventricular function after myocardial infarction: application of magnetic resonance imaging.

BACKGROUND: There are conflicting reports on the effects of training on the remodeling process in post-myocardial infarction patients with ventricular damage. METHODS AND RESULTS: Twenty-five patients with reduced ventricular function (mean ejection fraction, 32.3+/-6%) after an anteroseptal or inferolateral myocardial infarction were randomized to an exercise group (n=12) or a control group (n=13). Patients in the exercise group resided in a rehabilitation center for 2 months and underwent a training program consisting of two 1-hour sessions of walking daily, along with four monitored 45-minute sessions of stationary cycling weekly. Before and after the study period, maximal exercise testing and cardiac MRI were performed. Oxygen uptake increased 26% at maximal exercise (19.7+/-3 to 23.9+/-5, P<.05) and 39% at the lactate threshold (P<.01) in the exercise group, whereas control values did not change. No differences were observed within or between groups in MRI measures of end-diastolic (187+/-47 pre versus 196+/-35 mL post in the exercise group and 179+/-52 pre versus 180+/-51 mL post in the control group), end-systolic volume (118+/-41 pre versus 121+/-33 mL post in the exercise group and 119+/-54 pre versus 116+/-56 mL post in the control group), or ejection fraction (38.0+/-9 pre versus 38.2+/-10% post in the exercise group and 37.0+/-10 pre versus 38.3+/-13% post in the control group). Myocardial wall thickness measurements at end diastole and end systole and their difference in 80 myocardial segments determined by MRI yielded no significant interactions between groups. When myocardial wall thickness measurements were classified by infarct or noninfarct areas, no differences were observed between groups over the study period. CONCLUSIONS: A high-intensity, 2-month residential cardiac rehabilitation program resulted in substantial increases in exercise capacity among patients with reduced left ventricular function. In contrast to some recent reports, the training program had no deleterious effects on left ventricular volume, function, or wall thickness regardless of infarct area.

Exercise Test↗
PubMed1997

Flow cytometrical and genotypic analysis of primary non-Hodgkin's lymphoma of bone.

Primary malignant lymphoma of bone presents both diagnostic and therapeutic problems. No previous study has addressed the use of flow cytometry in the immunophenotypic evaluations of bone lymphomas. A 41-year-old Japanese female presented with a large lytic lesion in the right femur. Biopsies from the lesion were examined by light microscopy, immunohistochemistry, 3-color flow cytometry and Southern blotting. Microscopic examination showed a diffuse, noncleaved large cell lymphoma. The lymphoid cells were positive for mature B cell antigens and the phenotype was: CD5-, CD10-, CD19+, 20+, CD22+, IgG+, IgA-, IgM-, kappa-, lambda+, CD1-, CD2-, CD3-, CD4-, CD7-, CD8-. Southern blot analysis revealed rearranged bands on both heavy- and lambda light-chain genes, in contrast to germline configuration on T cell antigen receptor (beta, gamma and delta) genes. Flow cytometry, in conjunction with morphologic and other molecular techniques, can provide a rapid and accurate means of diagnosing primary lymphoma of bone. In addition, the capabilities of flow cytometry to assess cell properties/constituents can be utilized in detailed analysis of adhesion molecules and activation antigen which may lead to better prediction of the prognosis of this group of lymphomas, and may provide further important data for the therapeutic decision making process.

Adult↗
PubMed1997

Effect of high intensity exercise training on central hemodynamic responses to exercise in men with reduced left ventricular function.

OBJECTIVES: The aim of this study was to evaluate the effects of high intensity exercise training on left ventricular function and hemodynamic responses to exercise in patients with reduced ventricular function. BACKGROUND: Results of studies on central hemodynamic adaptations to exercise training in patients with chronic heart failure have been contradictory, and some research has suggested that training causes further myocardial damage in these patients after a myocardial infarction. METHODS: Twenty-five men with left ventricular dysfunction after a myocardial infarction or coronary artery bypass graft surgery were randomized to an exercise training group (mean age +/- SD 56 +/- 5 years, mean ejection fraction [EF] 32 +/- 7%, n = 12) or a control group (mean age 55 +/- 7 years, mean EF 33 +/- 6%, n = 13). Patients in the exercise group performed 2 h of walking daily and four weekly sessions of high intensity monitored stationary cycling (40 min at 70% to 80% peak capacity) at a residential rehabilitation center for a period of 2 months. Ventilatory gas exchange and upright hemodynamic measurements (rest and peak exercise cardiac output; pulmonary artery, wedge and mean arterial pressures; and systemic vascular resistance) were performed before and after the study period. RESULTS: Maximal oxygen uptake (VO2max) increased by 23% after 1 month of training, and by an additional 6% after month 2. The increase in VO2max in the trained group paralleled an increase in maximal cardiac output (12.0 +/- 1.8 liters/min before training vs. 13.7 +/- 2.5 liters/min after training, p < 0.05), but maximal cardiac output did not change in the control group. Neither stroke volume nor hemodynamic pressures at rest or during exercise differed within or between groups. Rest left ventricular mass, volumes and EF determined by magnetic resonance imaging were unchanged in both groups. CONCLUSIONS: High intensity exercise training in patients with reduced left ventricular function results in substantial increases in VO2max by way of an increase in maximal cardiac output combined with a widening of maximal arteriovenous oxygen difference, but not changes in contractility. Training did not worsen hemodynamic status or cause further myocardial damage.

Cardiac Output↗
PubMed1997

Three-color flow cytometry in the diagnosis of malignant lymphoma based on the comparative cell morphology of lymphoma cells and reactive lymphocytes.

This study examines the identification of unusual cell populations highly associated with lymphoma cells (UCP-L) in diagnostic biopsy specimens using three-color flow cytometry (3-FCM). Patterns of surface antigen expression were used to compare the morphology of distinct lymphoid cell populations present in biopsy specimens and determine the presence or absence of UCP-L. UCP-L were identified by their larger size as compared to admixed reactive lymphocytes, and the method is based on the concept that neoplastic lymphoma cells are larger than reactive lymphocytes. The comparison of relative cell sizes was determined by overlaying forward scatter histograms by multicolor gating using PAINT-A-GATE software. In order for separate gates to be set on UCP-L and reactive cell populations, UCP-L had to fulfill one or more immunophenotypic criteria. These included: (1) belonging to a subset of B cell antigen-positive cells showing restricted expression of kappa or lambda light chains; (2) belonging to a subset of CD4-positive cells having dim or absent expression of CD45RA; (3) showing alterations in antigen expression (loss, dimmer or brighter); or (4) expressing an immunophenotype that is present on only rare cell populations or is absent from reactive lymph nodes. The immunophenotypic profiles of the respective cell populations were demonstrated by cubic representations to assess more easily the co-expression of three antigens. The common morphology of UCP-L as defined by forward and side scatter grams was consistent with a 'lymphoid appearance' except in several cases of HTLV-I-positive T cell lymphoma and gammadelta T cell lymphoma. The immunophenotypic profiles of UCP-L were confirmed to correspond to the presumptive lymphoma cell population by use of a live gating procedure on the large cells, which eliminated interference by reactive cells or necrotic tissue fragments. Using this method, we identified UCP-L in 208 of 293 (71%) consecutive cases of non-Hodgkin's lymphomas, while no UCP-L were seen in 72 cases of non-specific hyperplasia of lymph nodes. Twenty-seven cases could not properly be examined about the existence of UCP-L because of massive necrosis, extensive fibrosis or strong non-specific staining reactions of unknown cause. When those cases were eliminated from the analysis, 80% of non-Hodgkin's lymphoma were found to contain UCP-L. In B cell lymphoma, the incidence of UCP-L in nodal lymphomas (80%) was much higher than in extranodal lymphomas (47%). Only one of 21 cases of Hodgkin's lymphoma was found to have UCP-L. The 3-FCM procedure was validated by the combined use of immunohistochemistry, morphologic examination, cytogenetic and antigen receptor gene rearrangement analysis by Southern blot hybridization. Our findings indicate that detection of UCP-L by 3-FCM is a reliable method to distinguish non-Hodgkin lymphomas from reactive hyperplasias in the majority of cases, even when the reactive cell population predominates over the malignant cell population.

Antigens, CD↗
PubMed1997

The illness behavior of patients with gastroesophageal reflux disease with and without endoscopic esophagitis.

The aim of this study was to determine if patients who experience heartburn but have no objective evidence of gastroesophageal reflux disease are responding appropriately to their symptoms. One hundred and forty patients who had been referred for investigations of heartburn (75 males, 65 females, mean age 48 years) answered an Illness Behavior Questionnaire. All patients underwent pH monitoring tests, and endoscopy results were obtained for 119 patients. There was objective evidence of reflux disease on endoscopy or pH monitoring in 105 patients and no objective evidence of reflux in 35 patients. Sixty-six patients were endoscopy-'positive' while 53 patients were endoscopy-'negative'. The Illness Behavior Questionnaires for the four groups were analysed for seven scales of illness behavior and these were compared with reference populations. Patients with heartburn but no objective reflux were similar to those with heartburn and objective reflux on all scales of the Illness Behavior Questionnaire. The reflux group without endoscopic esophagitis also responded to their symptoms in the same way as those with endoscopic esophagitis. It is concluded that a patient's perception of symptoms in gastroesophageal reflux is probably not related to the degree of esophageal mucosal damage.

Adolescent↗
PubMed1997

Gas exchange and neurohumoral response to exercise: influence of the exercise protocol.

Maximal oxygen uptake varies with the exercise protocol, but the extent to which hormonal and metabolic responses to exercise are influenced by the exercise protocol has not been precisely defined. Twelve healthy subjects underwent maximal exercise testing using two incremental bicycle tests with individualized, identical work rate increments between 40 and 70 W. One protocol employed a 1-min and the other a 3-min duration per stage. Expiratory gas and venous blood were sampled at regular intervals for metabolic and hormonal analysis. Exercise duration for the 1-min and 3-min protocols was 6.0 +/- 0.1 and 14.3 +/- 0.3 min, respectively (P < 0.001). Significantly higher values were observed for peak VO2 and maximal ventilation during the 3-min protocol compared with the 1-min protocol (41.1 +/- 1.8 vs 38.3 +/- 1.6 ml.kg-1.min-1, P < 0.001; and 104.9 +/- 8.0 vs 97.2 + 5.7 l.min-1, P < 0.05, for peak VO2 and peak ventilation, respectively). However, the maximal workload achieved was higher during the 1-min versus the 3-min protocol (330 + 24 vs 280 + 21 W, P < 0.01). No differences were observed for maximal heart rate or blood pressure, whereas maximal plasma lactate was roughly twice as high during the 3-min compared with the 1-min protocol (7.5 +/- 0.8 vs 3.8 +/- 0.5 mmol.l-1, P < 0.001). Norepinephrine, epinephrine, dopamine, and growth hormone levels were generally higher throughout exercise during the 3-min compared with the 1-min protocol. When expressed as a percentage of peak VO2, however, differences in catecholamine levels were not observed. Endothelin levels did not change. We conclude that the exercise protocol profoundly influences exercise capacity as well as the metabolic and hormonal response to exercise and should be considered when using these variables to evaluate an intervention.

Adult↗
PubMed1997

Dangerous curves. A perspective on exercise, lactate, and the anaerobic threshold.

A number of general observations can be made from these recent studies. Lactate is a ubiquitous substance that is produced and removed from the body at all times, even at rest, both with and without the availability of oxygen. It is now recognized that lactate accumulates in the blood for several reasons, not just the fact that oxygen supply to the muscle is inadequate. Lactate production and removal is a continuous process; it is a change in the rate of one or the other that determines the blood lactate level. Rather than a specific threshold, there is most likely a period of time during which lactate production begins to exceed the body's capacity to remove it (through buffering or oxidation in other fibers). It may be appropriate to replace the term "anaerobic threshold" to a more functional description, since the muscles are never entirely anaerobic nor is there always a distinct threshold ("oxygen independent glycolysis" among others has been suggested) Lactate plays a major role as a metabolic substrate during exercise, is the preferred fuel for slow-twitch muscle fibers, and is a precursor for liver gluconeogenesis. The point at which lactate begins to accumulate in the blood, causing an increase in ventilation, is important to document clinically. Irrespective of the underlying mechanism or specific model that describes the process, the physiologic changes associated with lactate accumulation have significant import for cardiopulmonary performance. These include metabolic acidosis, impaired muscle contraction, hyperventilation, and altered oxygen kinetics, all of which contribute to an impaired capacity to perform work. Thus, any delay in the accumulation of blood lactate which can be attributed to an intervention (drug, exercise training, surgical, etc) may add important information concerning the efficacy of the intervention. A substantial body of evidence is available demonstrating that lactate accumulation occurs later (shifting to a higher percentage of Vo2max) after a period of endurance training. In athletes, the level of work that can be sustained prior to lactate accumulation, visually determined, is an accurate predictor of endurance performance. Presumably, these concepts have implications related to vocation/disability among patients with cardiovascular and pulmonary disease, but few such applied studies have been performed outside the laboratory. Blood lactate during exercise and its associated ventilatory changes maintain useful and interesting applications in both the clinical exercise laboratory and the sport sciences. However, the mechanism, interpretation, and application of these changes continue to rely more on tradition and convenience than science.

Anaerobic Threshold↗
PubMed1997

Monitoring and diagnosis of cytomegalovirus infection in renal transplantation.

In this study, the utility of the cytomegalovirus antigen (CMV-AG) and the shell vial (SV) tests in the diagnosis and monitoring of posttransplant CMV infection were compared. Previous retrospective studies from the authors' center suggested that the CMV-AG test, which uses monoclonal antibodies to detect viral antigen in circulating peripheral blood leukocytes (PBL) may be both a more sensitive and specific test. A cohort of 32 renal transplant recipients was followed-up prospectively with serial CMV-AG testing, as well as conventional culture and SV for blood and urine and tests for immunoglobulin M (IgM) antibody. It was discovered that the CMV-AG test was not only more sensitive than the SV test in detecting CMV infection, but that the degree of antigenemia as expressed by the number of positive cells per 50,000 PBL correlated with the likelihood and degree of symptomatic infection. All patients with a count > 10 positive cells/50,000 PBL developed clinical symptoms; therefore, this threshold could be useful in deciding clinically whether fever is related to CMV infection. Alternatively, if antigenemia were monitored serially after transplant, the same threshold could be used as a trigger for instituting antiviral therapy, because it was often reached prior to the onset of symptoms and had a high specificity for subsequent symptomatic infection. Such an approach could obviate unnecessary treatment of patients not destined to become symptomatic. Based upon the findings in this study, the CMV-AG test is superior to the SV assay because the actual count helps determine the likelihood that symptoms are a result of the virus and the processing time is shorter, it can be used to monitor the response to therapy and as a guide to the institution of preemptive therapy.

Antigens, Viral↗
PubMed1997

Biological profile of L-745,870, a selective antagonist with high affinity for the dopamine D4 receptor.

L-745,870,(3-([4-(4-chlorophenyl)piperazin-1-yl]methyl)-1H- pyrollo[2,3-b] pyridine, was identified as a selective dopamine D4 receptor antagonist with excellent oral bioavailability and brain penetration. L-745,870 displaced specific binding of 0.2 nM [3H] spiperone to cloned human dopamine D4 receptors with a binding affinity (Ki) of 0. 43 nM which was 5- and 20-fold higher than that of the standard antipsychotics haloperidol and clozapine, respectively. L-745,870 exhibited high selectivity for the dopamine D4 receptor (>2000 fold) compared to other dopamine receptor subtypes and had moderate affinity for 5HT2, sigma and alpha adrenergic receptors(IC50 < 300 nM). In vitro, L-745,870 (0.1-1 microM) exhibited D4 receptor antagonist activity, reversing dopamine (1 microM) mediated 1) inhibition of adenylate cyclase in hD4HEK and hD4CHO cells; 2) stimulation of [35S] GTPgammaS binding and 3) stimulation of extracellular acidification rate, but did not exhibit any significant intrinsic activity in these assays. Although standard antipsychotics increase dopamine metabolism or plasma prolactin levels in rodents, L-745,870 (</=30 mg/kg p.o.) had no effect in these assays. The lack of a suitable in vivo assay for D4 receptor activation prompted the use of in vivo surrogate marker assays which confirmed that doses of 5-60 microg/kg L-745,870 would be sufficient to occupy 50% D4 receptors in the brain. These results show that dopamine D4 receptor antagonism in the brain does not result in the same neurochemical consequences (increased dopamine metabolism or hyperprolactinemia) observed with typical neuroleptics.

Animals↗
PubMed1997

Importance of decreased heart rate in predicting transplant coronary artery disease.

Studies in animals and humans have demonstrated that an increased heart rate is a predictor for the development of coronary atherosclerosis and overall cardiovascular mortality. In contrast, we have previously reported that the need for pacemaker implantation because of bradycardia in heart transplant recipients is associated with an increased prevalence of transplant coronary artery disease (TxCAD). Hence, the relevance of changes in heart rate to the development of TxCAD remains unclear. Intra-coronary ultrasound examinations (ICUS) were therefore analyzed in 130 heart transplant recipients (age 50 +/- 11 yr) studied at annual evaluations (3.7 +/- 3.0 yr after transplantation). Quantitative ultrasound measurements were obtained by calculating mean coronary artery intimal thickness (MIT) obtained by examination of the left anterior descending artery. The presence of TxCAD was defined as MIT > 0.3 mm. Resting heart rates (HR) were recorded with the patients in the supine position during routine echocardiography. Based on HR recordings, two groups were defined: group 1, HR below; or group 2, HR above the median. TxCAD was detected in 40% of the ICUS studies overall. The prevalence of TxCAD was higher in group 1 (49%) compared with group 2 (33%), p < 0.05. There was no significant difference in donor ischemic time or donor gender, recipient age, gender, body weight, CMV status, creatinine, total cholesterol, use of lipid lowering drugs or diltiazem. Donor age and use of beta-blockers were higher in group 1 compared with group 2 (29 +/- 10 vs. 25 +/- 9 yr, and 15% vs. 5%, for donor age and beta-blocker use, respectively). By multivariate regression analysis only donor age and years after transplantation were independently correlated with TxCAD. After excluding patients taking beta-blockers and diltiazem, the prevalence of CAD was still higher in group 1 (50%) vs. group 2 (34%). In conclusion, transplant coronary artery disease is more prevalent in patients with lower, rather than higher, heart rates. The reason for this is unclear, but may reflect impaired blood flow to the sinoatrial node.

Adult↗
PubMed1996

The human neuroblastoma cell line, IMR-32, expresses functional corticotropin-releasing factor receptors.

Corticotropin-releasing factor (CRF) receptors in IMR-32 human neuroblastoma cells were characterized after differentiation with 2.5 microM 5'-bromo-2'-deoxyuridine for 10 days. Scatchard analysis of [125I-Tyr0]ovine CRF binding revealed a high affinity binding site with a dissociation constant of 0.59 nM and a maximum binding capacity of 142 fmol/mg, the affinity of which was decreased by guanosine 5'-o-(3-thiotriphosphate). This binding was displaced in the following order of potency: human/rat CRF > ovine CRF > urotensin I > sauvagine > bovine CRF > [D-Phe12, Nle21,38, C alpha-MeLeu37]human/rat CRF-(12-41) > alpha-helical CRF-(9-41), indicative of the CRF1 receptor subtype. Functional coupling of this receptor was confirmed by CRF-induced increases in cyclic AMP, which were antagonised by alpha-helical CRF-(9-41) and [D-Phe12,Nle21,38,C alpha-MeLeu37] human/rat CRF-(12-41).

Animals↗
PubMed1996

p53 mutations do not predict response to paclitaxel/radiation for nonsmall cell lung carcinoma.

BACKGROUND: Mutations in the tumor suppressor gene p53 have been associated with resistance to ionizing radiation and chemotherapy. Paclitaxel and concurrent radiation (paclitaxel/RT) achieve high response rates with locally advanced nonsmall cell lung carcinoma (NSCLC). In vitro data and animal studies suggest that paclitaxel may have a unique ability to activate tumor cell apoptosis in the absence of wild-type p53 function. The authors sought to determine whether p53 mutations affect response to paclitaxel/RT in patients with locally advanced NSCLC. METHODS: Thirty patients with Stage IIIA or IIIB NSCLC who participated in Brown University Oncology Group protocols utilizing paclitaxel/RT had tumor tissue that was adequate for analysis. Mutations were detected in tumor tissue by single-strand conformation polymorphism analysis of exons 5 through 8 of the p53 gene, and confirmed by direct sequencing. RESULTS: Mutations in p53 were found in 12 of 30 patients (40%). The response rates (complete plus partial) of 75% for patients with tumors with p53 mutations, and 83% for patients with wild-type p53, did not differ significantly (P = 0.70). CONCLUSIONS: p53 mutations do not predict response of patients with NSCLC to paclitaxel/RT. This finding is in striking contrast to results with other chemotherapeutic agents and ionizing radiation. These clinical data support in vitro data and animal studies regarding the unique mechanism of the action of paclitaxel. Further investigation is needed to determine the mechanism of lung tumor cell death after paclitaxel/RT. These results suggest that paclitaxel/RT may be an active regimen for patients with other locally advanced neoplasms with high rates of p53 gene mutations.

Aged↗
PubMed1996

Thymic lymphoblastic lymphoma of committed natural killer cell precursor origin: a case report.

BACKGROUND: Recently, it was demonstrated that the human fetal thymocyte contains a bipotential progenitor capable of both T lymphocyte and natural killer (NK) cell differentiation. However, prior to this report a malignant neoplasm arising from these cells had not been documented. METHODS: A Japanese female age 38 years was examined by morphology of light and electron microscopy, immunohistochemistry, 3-color flow cytometry, cytotoxic assay, and Southern blotting. RESULTS: The patient presented with a mediastinal mass and pleural effusion. Leukemic progression was identified following chemotherapy and complete clinical remission. Immunophenotyping of lymphoma revealed CD45++, c-kit dim+, terminal deoxynucleotidyl transferase (TdT)-<+, CD38++, CD34+<++, CD33+<-, CD13dim+approximately+, HLA-DR+, CD7+, cytoplasmic CD3 (cCD3)+, surface CD3 (sCD3)-, CD2dim+, CD56+, CD16-, CD11b+, CD57-, CD1a-, CD5-, TCR alpha beta-, TCR gamma delta-, CD4-, CD8-, CD28-, CD10-, CD19-, CD20-, CD22-, surface immunoglobulins-, and CD14-. Functional NK activity of the lymphoma cells was extremely low. DNA analysis revealed no gene rearrangement in TCR beta, gamma, and delta or immunoglobulin heavy and light chain genes. CONCLUSIONS: Lymphoma cells of this case were derived from a distinct subtype of lymphocyte that originate from a thymic precursor committed to NK cell differentiation. This category is different from those of thymic T or precursor B cell pheno-/genotype.

Adult↗
PubMed1996

Peripheral CD4+ CD8- gammadelta T cell lymphoma: a case report with multiparameter analyses.

A 72-year-old Japanese man presented with CD4+ T cell receptor (TCR) gammadelta T cell lymphoma involving bilateral cervical lymph nodes. No involvement by tumor was observed in the liver, spleen, nasal cavity, or bone marrow throughout his clinical course. Although the tumor adequately responded to chemotherapy and irradiation, he relapsed with short remission and a slowly aggressive clinical course, and died 24 months after onset. Simultaneous expression of TCR gammadelta with other T-cell antigens on the lymphoma cells was analyzed by 3-color flow cytometry (3-FCM), and showed a unique phenotype CD3+ CD4+ CD8- CD7- CD5+ CD2++ TCR alphabeta (WT31)- betaF1-TCR gammadelta1 (11F2)+ TCR delta1+. Cytogenetic analysis showed 79-81 and structural abnormalities consisting of del(1)(p11) and i(17)(q10). But no abnormality was identified in chromosome 7. DNA analysis revealed gene rearrangements of TCRgamma and delta, while a nongerm line band in TCRbeta was aberrantly seen. These observations suggest a new subtype of gammadelta T-cell lymphoma, which is characterized by CD4 positivity and by a clinical course not as aggressive as other predominant subtypes.

Aged↗
PubMed1996

Infants' sensitivity to word boundaries in fluent speech.

Infants' sensitivity to word units in fluent speech was examined by inserting I sec pauses either at boundaries between successive words (Coincident versions) or between syllables within words (Noncoincident versions). In Experiment 1, 24 11-month-olds listened significantly longer to the Coincident versions. In Experiment 2, 24 four-and-a-half- and 24 nine-month-olds did not exhibit the preference for the Coincident versions that the 11-month-olds showed. When the stimuli were low-pass filtered in Experiment 3, 24 11-month-olds showed no preference for the Coincident versions, suggesting they rely on more than prosodic cues. New stimulus materials in Experiment 4 indicated that responses by 24 11-month-olds to the Coincident and Noncoindent versions did not depend solely on prior familiarity with the targets. Two groups of 30 11-month-olds tested in Experiment 5 were as sensitive to groups of 30 11-month-olds tested in Experiment 5 were as sensitive to boundaries for Strong/Weak words as for Weak/Strong words. Taken together, the results suggest that, by 11 months, infants are sensitive to word boundaries in fluent speech, and that this sensitivity depends on more than just prosodic information or prior knowledge of the words.

Age Factors↗
PubMed1996

Generation and characterisation of stable cell lines expressing recombinant human N-methyl-D-aspartate receptor subtypes.

Transfection of mouse L(tk-) cells with human N-methyl-D-aspartate (NMDA) receptor subunit cDNAs under the control of a dexamethasone-inducible promoter has been used to generate two stable cell lines expressing NR1a/NR2A receptors and a stable cell line expressing NR1a/NR2B receptors. The cell lines have been characterised by northern and western blot analyses, and the pharmacology of the recombinant receptors determined by radioligand binding techniques. Pharmacological differences were identified between the two NMDA receptor subtypes. The glutamate site antagonist D, L-(epsilon)-2-[3H]amino-4-propyl-5-phosphono-3-pentanoic acid ([3H]CGP 39653) had high affinity for NR1a/NR2A receptors (KD = 3.93 nM) but did not bind to NR1a/NR2B receptors. Glycine site agonists showed a 2.6-5.4-fold higher affinity for NR1a/NR2B receptors. Data from radioligand binding studies indicated that one of the cell lines, NR1a/NR2A-I, expressed a stoichiometric excess of the NR1a subunit, which may exist as homomeric assemblies. This observation has implications when interpreting data from pharmacological analysis of recombinant receptors, as well as understanding the assembly and control of expression of native NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMed1996

Preliminary experience with paclitaxel for the treatment of relapsed and refractory Hodgkin's disease.

PURPOSE: To determine the activity of paclitaxel (Taxol; Bristol-Myers Squibb Co., Princeton, NJ) in patients with relapsed and primary treatment-refractory Hodgkin's disease. PATIENTS AND METHODS: Fifteen patients with relapsed (n = 8) or primary treatment-refractory (n = 7) Hodgkin's disease were treated at two cancer centers. Patients received paclitaxel 200 mg/m2 intravenously over three hours every three weeks. All patients also received premedication with dexamethasone, cimetidine, and diphenhydramine. The median age was 33 years (range 19 to 69 years), and the median number of prior treatment regimens was three. Seven patients had previously received treatment with autologous bone marrow transplantation. RESULTS: Fourteen patients were evaluable for response after receiving one to six courses (median, two courses) of paclitaxel. Two patients (14%) had partial remissions; both of them had relapsed after achieving a complete remission with high-dose therapy and autologous bone marrow transplantation. One of these patients was given involved field radiation to consolidate the partial remission and remains free of disease two years after paclitaxel therapy. Three patients had stable disease, and nine had progressive disease. Therapy was well tolerated, with a toxicity profile similar to that previously reported for paclitaxel in patients with non-Hodgkin's lymphoma. CONCLUSION: Paclitaxel, at this dose and schedule, has modest activity in this group of heavily pretreated patients. Studying its activity in patients with more favorable disease characteristics is warranted.

Adult↗