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Biomedical subjects

E Nelson

Publications and source records attributed to E Nelson.

At least 55 records · Page 3Linked to original sources
PubMed1998

Phase I trial of anti-CD3-stimulated CD4+ T cells, infusional interleukin-2, and cyclophosphamide in patients with advanced cancer.

PURPOSE: We performed a phase I trial to determine whether in vivo expansion of activated CD4+ T cells was possible in cancer patients. 111Indium labeling was used to observe trafficking patterns of the infused stimulated CD4+ T cells. The influence of cyclophosphamide (CTX) dosing on immunologic outcome was also examined. PATIENTS AND METHODS: Patients with advanced solid tumors or non-Hodgkin's lymphoma received CTX at 300 or 1,000 mg/m2 intravenously (i.v.). Leukapheresis was performed to harvest peripheral-blood mononuclear cells (PBMCs) either just before the CTX dose, or when the patient was either entering or recovering from the leukocyte nadir induced by CTX. An enriched population of CD4+ T cells was obtained by negative selection. The CD4+ T cells were activated ex vivo with anti-CD3, cultured with interleukin-2 (IL-2) for 4 days, and adoptively transferred. After adoptive transfer, patients received IL-2 (9.0 x 10(6) IU/m2/d) by continuous infusion for 7 days. RESULTS: The absolute number of CD4+, CD4+/DR+, and CD4+/CD45RO+ T cells increased in a statistically significant fashion in all cohorts after the first course of therapy. The degree of CD4 expansion was much greater than CD8 expansion, which resulted in a CD4:CD8 ratio that increased in 26 of 31 patients. The greatest in vivo CD4 expansion occurred when cells were harvested as patients entered the CTX-induced nadir. One complete response (CR), two partial responses (PRs), and eight minor responses were observed. Trafficking of 111Indium-labeled CD4 cells to subcutaneous melanoma deposits was also documented. CONCLUSION: CD4+ T cells can be expanded in vivo in cancer patients, which results in increased CD4:CD8 ratios. The timing of pheresis in relation to CTX administration influences the degree of CD4 expansion. Tumor responses with this regimen were observed in a variety of tumors, including melanoma and non-Hodgkin's lymphoma; a high percentage of patients had at least some tumor regression from the regimen that produced the greatest CD4+ T-cell expansion.

Adult↗
PubMed1997

Construction of a full-length Ca2+-sensitive adenylyl cyclase/aequorin chimera.

Ca2+-sensitive adenylyl cyclases are key integrators of Ca2+ and cAMP signaling. To selectively probe dynamic changes in [Ca2+]i at the plasma membrane where adenylyl cyclases reside, a full-length, Ca2+-inhibitable type VI adenylyl cyclase/aequorin chimera has been constructed by a two-stage polymerase chain reaction method. The expressed adenylyl cyclase/aequorin chimera was appropriately localized to the plasma membrane, as judged by biochemical fractionation and functional analysis. The chimera retained full adenylyl cyclase activity and sensitivity to inhibition by physiological [Ca2+]i elevation. The aequorin portion of the chimeric construct was also capable of measuring changes in [Ca2+] both in vitro and in vivo. When the plasma membrane-tagged aequorin and cytosolic aequorin were compared in their measurement of [Ca2+]i, they showed contrasting sensitivities depending on whether the [Ca2+]i originated from internal stores or capacitative entry. This is the first full-length enzyme-aequorin chimera that retains the full biological properties of both aequorin and a Ca2+-sensitive adenylyl cyclase. This novel chimeric Ca2+ sensor provides the unique ability to directly report the dynamics of [Ca2+]i that regulates this Ca2+-sensitive enzyme under a variety of physiological conditions. Since this chimera is localized to the plasma membrane, it can also be used to assess local changes in [Ca2+]i at the plasma membrane as distinct from global changes in [Ca2+]i within the cytosol.

Adenylyl Cyclases↗
PubMed1997

Exploring the TPQ as a possible predictor of antidepressant response to nefazodone in a large multi-site study.

Subjects in the midst of a major depressive episode completed the Tridimensional Personality Questionnaire (TPQ) prior to beginning an open trial of nefazodone. A multiple regression analysis was used to further examine the finding of Joyce et al. (1994; Temperament predicts clomipramine and desipramine response in major depression, J. Affect. Disord. 30 (1994) 35-46) that a model involving TPQ Reward Dependence and Harm Avoidance scores, and their interaction, significantly predicted treatment response. The model was found to have significant predictive value (R2 = 0.011, P = 0.0053), but to account for a trivial 1.1% of the variance. Individuals with high Reward Dependence scores had a significantly lower response rate when response was defined as a 60% reduction from baseline HAM-D score. Although the clinical utility of the present findings is uncertain, this line of investigation attempting to link temperament to pharmacological response represents a potentially useful future strategy.

Antidepressive Agents↗
PubMed1997

Management of the suicidal patient with schizophrenia..

No matter what the course of treatment determined to be most appropriate, suicidal behavior must be considered thoroughly, and it must be conveyed to the patient that the clinician can assist him or her through this period of increased distress. Hopelessness must be viewed as a symptom with the assumption that a more meaningful sense of purpose will emerge despite the chronic and potentially limiting nature of schizophrenia. Most people with schizophrenia are not suicidal, and most who are suicidal can be offered interventions that will reduce their symptomatology and thereby dissipate their suicidal behavior.

Combined Modality Therapy↗
PubMed1997

Stability of diagnosis of obsessive-compulsive disorder in the Epidemiologic Catchment Area study.

OBJECTIVE: This study examined the 1-year temporal stability of a National Institute of Mental Health Diagnostic Interview Schedule (DIS) lifetime diagnosis of obsessive-compulsive disorder in the Epidemiologic Catchment Area (ECA) study. METHOD: In that study, 20,862 individuals, aged 18 years and over, at five sites were evaluated by lay interviewers using the DIS (wave 1). All of those who were available 12 months later were reinterviewed (wave 2). In the present study, the temporal stability of wave 1 obsessive-compulsive disorder diagnoses at wave 2 was examined, as well as relationships with comorbid diagnoses. The consistency of reports of "new-onset" illness was also examined. Factors contributing to these measures were evaluated. RESULTS: The temporal stability of the diagnosis of obsessive-compulsive disorder was very low. Subjects with a stable diagnosis of obsessive-compulsive disorder had a higher rate of both obsessions and compulsions, an earlier age at onset, and more comorbid anxiety, affective, and alcohol abuse/dependence disorders at initial assessment. The originally reported 1-year incidence estimates for obsessive-compulsive disorder primarily reflect data from subjects at wave 2 who reported the onset of symptoms as preceding the wave 1 interview. Older and less-educated subjects had significantly higher error rates in reporting onset. CONCLUSIONS: The DIS diagnosis of obsessive-compulsive disorder has poor validity, leaving the true incidence and prevalence of the disorder unknown. Older and less-educated subjects require special attention in the design of instruments for use with community samples.

Adolescent↗
PubMed1996

Important elements of outpatient care: a comparison of patients' and physicians' opinions.

OBJECTIVE: To compare patients' and physicians' opinions on the importance of discrete elements of health care as determinants of the quality of outpatient care. DESIGN: Analysis of results of a mailed survey. SETTING: Community-based internal medicine practices. PARTICIPANTS: 74 general internists and 814 patients randomly selected from the practices of these internists. MEASURES: 125 elements of care that covered nine domains were identified: physician clinical skill, physician interpersonal skill, support staff, office environment, provision of information, patient involvement, nonfinancial access, finances, and coordination of care. Participants rated each element on its importance to high-quality care on a 4-point scale: 1 = not important; 2 = of medium importance; 3 = of high importance; and 4 = essential. Patients' and physicians' ratings were compared for individual elements of care and for elements aggregated into domains. RESULTS: Survey response rates were 93% for physicians and 60% for patients. In an element-by-element comparison of ratings, ratings by the two groups differed substantially for 58% of the attributes. The most striking difference was seen in the domain of provision of information (median ratings, 3.56 for patients and 2.85 for physicians; P < 0.001). Ratings by the two groups also differed in the domains of clinical skill (3.75 for patients and 3.35 for physicians; P < 0.001), nonfinancial access (3.00 for patients and 2.87 for physicians; P < 0.001), and finances (3.00 for patients and 2.80 for physicians; P = 0.006). When relative rankings of the domains were compared, both groups agreed that clinical skill is most important; however, patients ranked provision of information second in importance whereas physicians ranked it sixth. CONCLUSIONS: Patients and physicians agreed that the most crucial element of outpatient care is clinical skill, but they disagreed about the relative importance of other aspects of care, particularly effective communication of health-related information. These differences in perception may influence the quality of interactions between physicians and patients.

Adolescent↗
PubMed1996

Oxytocin mediates acquisition of maternally associated odor preferences in preweanling rat pups.

Three studies assessed the role of central oxytocin systems in maternal affiliation in preweanling rats. Fifteen-day-old rats were found to approach on odor faster and spend more time in contact with an odor when it had been paired with the mother on the previous day than when the odor was not paired with the mother, provided that the pairing occurred after either intracerebral administration of oxytocin (0.5 microgram) or saline. However, if rats were administered an oxytocin antagonist (OTA) prior to odor-mother pairing, neither the decreased odor approach latency nor the increased odor preference was apparent in the odor-mother group. OTA treatment did not attenuate a single-trial odor aversion learning task, nor did it disrupt interaction with the anesthetized mother. Results are discussed in terms of a possible reward-satiety role for oxytocin in the infant-mother context.

Animals↗
PubMed1996

Neonatology in the 'Pearl of the East'.

Clinicians practising in different regions of the world are often impressed at marked differences in disease patterns witnessed. The bases of most obvious differences are usually socio-economic and genetic, but culture and environment can be equally important. Documenting and assessing such differences is more than just a passing interest. Globalization has resulted in significant movement of people from one area to another. During the past decade, many young Chinese families have emigrated to Australia, Europe and North America for social and political reasons. Clinicians in these regions will need to be aware of the "Chinese disease patterns'. This overview highlights some of the more striking differences seen in neonatal medicine between the East (Hong Kong) and the West (Australia/Europe/North America). In addition to the immediate clinical relevance, it is hoped that this review can provide a background from which fruitful research ideas may emerge and to stimulate interest for trainee neonatologists who wish to seek sabbatical experience in Hong Kong.

China↗
PubMed1996

Laboratory probing of oncogenes from human liquid and solid specimens as markers of exposure to toxicants.

Recent discoveries regarding the mechanistic role of oncogenes and tumor suppressor genes in cancer development have opened a new era of molecular diagnosis. It has been observed repeatedly that genetic lesions serve as tumor markers in a broad variety of human cancers. The ras gene family, consisting of three related genes, H-ras, K-ras, and N-ras, acquires transforming activity through amplification or mutation in many tissues. If not all, then most types of human malignancies have been found to contain an altered ras gene. Because the ras oncogenes actively participate in both early and intermediate stages of cancer, several highly specific and sensitive approaches have been introduced to detect these genetic alterations as biomarkers of exposure to carcinogens. There is also mounting evidence that implicate chemical-specific alterations of the p53 tumor suppressor gene detected in most human tumors. Therefore, it seems a reliable laboratory approach to identify both altered p53 and ras genes as biomarkers of human chronic or intermittent exposure to toxicants in a variety of occupational settings.

Biomarkers↗
PubMed1995

Cellular adaptation to chronic cadmium exposure: intracellular localization of metallothionein protein in human trophoblast cells (JAr).

Trophoblast cells are the first embryonic cells that modulate the transfer of a variety of compounds (oxygen, amino acids, xenobiotics, metals) from the maternal to the fetal circulation in the human placenta. Human placental exposure to the toxic metal, cadmium (Cd) results in a decrease in the production of human chorionic gonadotropin (hCG), a decrease in the maternal to fetal transport of zinc (Zn), and trophoblastic necrosis. Thus, the ability of trophoblast cells to adapt to exposure to the toxic metal Cd has been considered crucial. In this study, the expression and intracellular localization of metallothionein (MT), a small molecular weight, metal binding protein, was examined in trophoblast cells (JAr) grown in normal media and in cells exposed chronically (6 months) to 2 microM CdCl2. Conventional and confocal fluorescence microscopy were used to examine the intracellular localization of MT protein in control cells and cells grown chronically in Cd. In unexposed trophoblast cells, MT protein was primarily perinuclear with low level, punctate expression in the cytosol. Following both chronic and 24 hour exposure to Cd, MT protein levels were increased (at least 3-fold in both chronic and acute exposures) and the protein was now concentrated inside the nucleus with a lacy, cytoskeletal pattern of expression in the cytosol. To determine if the nuclear accumulation of MT protein was dependent on new protein synthesis, control cells were exposed to CdCl2 (2 microM) and cycloheximide (2 micrograms/. ml) for 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Cadmium↗
PubMed1995

Genotoxicity of wood dust in a human embryonic lung cell line.

Wood dust exposure has been found to be an occupational hazard, being linked to an enhanced incidence of various neoplasias. Here we performed an experiment to evaluate the ability of solvent extracts of natural woods to induce chromosome aberrations in respiratory cells in culture. Human embryonic lung cells, MRC-5, grown in Dulbecco's medium were exposed to various concentrations of the dust extracts of pesticide-free (untreated) beech, oak and pine woods. Three concentrations per extract with and without metabolic activation (S9) and 100 metaphase cells per dose were examined for possible structural aberrations. Although no dose-dependent activity could be found with any extract in the presence of S9, most aberrations observed were of the chromatid type caused by oak wood. Dose-dependent chromosomal breaks caused by oak and chromatid breaks caused by both beech and oak were observed in the absence of S9. These data might support the early hypothesis that hard wood dust per se contains some in vivo genotoxic and thus possibly carcinogenic components.

Animals↗
PubMed1995

Squamous cell carcinoma of the prostate: a transformation from adenocarcinoma after the use of a luteinizing hormone-releasing hormone agonist and flutamide.

We report a primary squamous cell carcinoma of the prostate that developed in a 57-year-old man, 3 years after treatment with leuprolide and flutamide for Stage D1 adenocarcinoma of the prostate. This is the first case that describes this transformation from adenocarcinoma to squamous cell carcinoma following the use of luteinizing hormone agonists.

Adenocarcinoma↗
PubMed1995

White cell-reduced platelet concentrates prepared by in-line filtration of platelet-rich plasma.

BACKGROUND: The importance of white cell (WBC) reduction in platelet concentrates (PCs) for component quality is undetermined. STUDY DESIGN AND METHODS: Eleven paired components, each derived from one of two whole-blood units given by a single donor on the same day, were studied. One PC was WBC reduced by filtration with an in-line, integral, prototype filter, and the other was produced from unfiltered platelet-rich plasma (PRP) by a standard method. In vitro tests performed on Day 1 and Day 5 were blood gases, plasma lactate, glucose, platelet ATP, mean platelet volume, morphology score, hypotonic stress ratio, extent of shape change in response to ADP, and beta-thromboglobulin. After 5 days of storage, each component pair was labeled with 51Cr or 111In and transfused for the estimation of percent recovery and survival. RESULTS: PCs using the in-line, prototypic filter had a platelet loss of approximately 15 percent and a variable 1 to 3 log10 reduction (average, 95%) in WBC content. The variation in filter WBC removal was related to PRP WBC content and indicated that the filter did not have the capacity for a 3 to 4 log10 removal when PRP WBC content exceeded 1 x 10(8). The in vitro and in vivo measures of platelet quality showed no meaningful differences between filtered and unfiltered PCs by paired t test. The mean differences in posttransfusion percent recoveries and survivals were 0.9 +/- 2.9 percent and 4 +/- 13 hours, respectively. Additional studies were performed using a larger filter with improved capacity. Those studies (n = 18) showed a significant improvement in filtration time and platelet yield and a consistent 3 to 4 log10 reduction in WBCs. Filtration time was 6.6 +/- 2.7 minutes, total PC WBCs were 9.6 +/- 4.6 x 10(4), and total PC platelets were 7.8 +/- 1.8 x 10(10) (mean +/- SD). CONCLUSION: Prestorage filtration of PRP and the preparation of filtered platelets do not result in any significant beneficial or adverse effect on subsequent platelet quality. With the large-capacity filter, consistent WBC reduction and good platelet yields are achieved.

Blood Donors↗