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Biomedical subjects

B Bell

Publications and source records attributed to B Bell.

At least 37 records · Page 2Linked to original sources
PubMed1998

Cognitive and academic late effects among children previously treated for acute lymphocytic leukemia receiving chemotherapy as CNS prophylaxis.

OBJECTIVE: Examine cognitive and academic late effects among children and adolescents who had received central nervous system (CNS) prophylactic chemotherapy alone for acute lymphocytic leukemia (ALL); none had received whole brain radiation therapy (RT). METHOD: Subjects included 47 children and adolescents from 5 to 22 years of age who were treated on the same protocol and had been off treatment from 2 to 7 years at the time of assessment. RESULTS: As a group the survivors displayed generally average performance on measures of cognitive and academic abilities, although they differed from normative means on tests of nonverbal skills. Girls performed more poorly than the normative sample on nonverbal tasks, while no differences were found for boys. Age at diagnosis and time off treatment were not significantly associated with cognitive and academic functioning for survivors of this particular chemotherapy-only protocol. CONCLUSIONS: Data were interpreted to support generally modest potential late effects in specific areas for children and adolescents surviving ALL. These findings suggest a need for monitoring nonverbal cognitive skills for childhood survivors of ALL, particularly for girls.

Achievement↗
PubMed1998

Naturally occurring human immunodeficiency virus type 1 long terminal repeats have a frequently observed duplication that binds RBF-2 and represses transcription.

Approximately 38% of human immunodeficiency virus type 1 (HIV-1)-infected patients within the Vancouver Lymphadenopathy-AIDS Study have proviruses bearing partial 15- to 34-nucleotide duplications upstream of the NF-kappaB binding sites within the 5' long terminal repeat (LTR). This most frequent naturally occurring length polymorphism (MFNLP) of the HIV-1 5' LTR encompasses potential binding sites for several candidate transcription factors, including TCF-1alpha/hLEF, c-Ets, AP-4, and Ras-responsive binding factor 2 (RBF-2) (M. C. Estable et al., J. Virol. 70:4053-4062, 1996). RBF-2 and an apparently related factor, RBF-1, bind to at least four cis elements within the LTR which are required for full transcriptional responsiveness to protein-tyrosine kinases and v-Ras (B. Bell and I. Sadowski, Oncogene 13:2687-2697, 1996). Here we demonstrate that representative MFNLPs from two patients specifically bind RBF-2. In both cases, deletion of the MFNLP caused elevated LTR-directed transcription in cells expressing RBF-2 but not in cells with undetectable RBF-2. RBF-1, but not RBF-2, appears to contain the Ets transcription factor family member GABPalpha/GABPbeta1. Taken together with the fact that every MFNLP from a comparative study of over 500 LTR sequences from 42 patients contains a predicted binding site for RBF-2, our data suggest that the MFNLP is selected in vivo because it provides a duplicated RBF-2 cis element, which may limit transcription in monocytes and activated T cells.

DNA Replication↗
PubMed1998

Phase I study of topotecan in combination with cyclophosphamide in pediatric patients with malignant solid tumors: a Pediatric Oncology Group Study.

PURPOSE: To determine the maximum-tolerated dose (MTD) and dose-limiting toxicity of topotecan when combined with cyclophosphamide in pediatric patients with recurrent or refractory malignant solid tumors. PATIENTS AND METHODS: A total of 33 patients received cyclophosphamide (250 mg/m2/dose) followed by topotecan in escalating doses (0.6 to 0.75 mg/m2/dose), each given as a 30-minute infusion daily for 5 days. A total of 154 fully assessable treatment courses were given to these patients. RESULTS: Neutropenia was the dose-limiting toxicity of the therapy at both topotecan dose levels. The addition of filgrastim allowed escalation of the topotecan dose to the 0.75-mg/m2 level with acceptable neutropenia. Other significant toxicities were anemia and thrombocytopenia. Nonhematopoietic toxicity of grades > or = 3 was not observed. Responses were reported in patients with Wilms' tumor (one complete response [CR], one partial response [PR]), neuroblastoma (one CR, one PR), rhabdomyosarcoma (one PR), and osteosarcoma (one PR). Pharmacokinetic studies indicate that cyclophosphamide administered on the schedule used in this study did not alter topotecan disposition on day 5. As with previous studies, a pharmacodynamic relation between systemic exposure and myelosuppression was noted. CONCLUSION: The combination of topotecan and cyclophosphamide shows activity in a wide variety of pediatric solid tumors and can be given with acceptable hematopoietic toxicity with the use of filgrastim support. We recommend that pediatric phase II trials use cyclophosphamide 250 mg/m2 followed by topotecan 0.75 mg/m2 daily for 5 days with filgrastim for amelioration of neutropenia.

Adolescent↗
PubMed1998

Passive transfer of growth-inhibitory antibodies raised against yeast-expressed recombinant Plasmodium falciparum merozoite surface protein-1(19).

Purified rabbit immunoglobulin raised against yeast-expressed recombinant FVO or 3D7 Plasmodium falciparum merozoite surface protein-1 (MSP-1) 19k-D C terminal fragment (MSP-1(19)) was transfused into malaria-naive Aotus nancymai monkeys that were immediately challenged with FVO asexual stage malaria parasites. Control monkeys received rabbit immunoglobulin raised against the sexual stage antigen Pfs25 or Aotus hyperimmune serum obtained from monkeys immunized by P. falciparum infection and drug cure. Passive transfer of rabbit anti-MSP-1(19) failed to protect against homologous or heterologous challenge and, when compared with negative controls, there were no differences in prepatent periods or time to treatment. Interestingly, rabbit anti-MSP-1(19), but not anti-Pfs25, immunoglobulin, and immune monkey serum prevented the development of antibodies directed against MSP-1(19) fragment by infected monkeys, indicating that the antibodies were reactive with native MSP-1(19) antigen in vivo. The prepatent period and time to treatment was greatly delayed in the two monkeys that received Aotus immune serum, both of which developed a chronic intermittent low level infection. In vitro parasite growth inhibition assays (GIAs) confirmed the presence of inhibitory activity (40% maximum inhibition) in concentrated anti-MSP-1(19) immunoglobulin (4.8 mg/ml), but the peak concentrations we achieved in vivo (1 mg/ml) were not inhibitory in vitro. Subinhibitory levels of anti-MSP-1(19) antibodies achieved by passive transfer were not protective against P. falciparum challenge.

Animals↗
PubMed1998

PM and D1S80 loci gene frequencies in the Zaragoza population of northern Spain.

LDLR, GYPA, HBGG, D7S8, GC (PM loci) and D1S80 are widely used in forensic casework analyses and population data are required to estimate the frequency of a DNA profile. This paper presents the results of a survey aimed at investigating the allele and genotype frequency distribution of these loci in an important Spanish population (Zaragoza, North Spain). Statistical analysis to determine whether allele frequencies were in Hardy-Weinberg equilibrium was carried out as well as to obtain some parameters of medicolegal interest. There was no evidence of association between the alleles of the loci. The Zaragoza sample does not differ substantially from other Caucasian populations.

Alleles↗
PubMed1998

Prospective care of elderly patients in family practice. Is screening effective?

OBJECTIVE: To evaluate cost and benefits of screening for and treating health and lifestyle risks among community-dwelling elderly. DESIGN: Randomized controlled trial. SETTING: Primary care. PARTICIPANTS: An opportunistic and prompted sample of 619 rostered elderly patients presenting for treatment who screened positive. INTERVENTIONS: One third (209) of experimental subjects had screening questionnaires placed in their charts with concerns highlighted for referrals. Two control groups received usual care. MAIN OUTCOME MEASURES: Yearly assessments of health service use and multidimensional functional capacity. RESULTS: Overall, screening and treatment of functionally active, elderly, middle-class people had no significant beneficial effect. Almost half of the experimental sample was ineligible because of treatment noncompliance. Generally ineligible subjects were older and more severely impaired. Subjects 75 years and older with risk factors showed improvement in daily living activities, and those living alone were found to have improved mental health and social functions (11% and 22%, respectively). CONCLUSIONS: Screening and treatment was ineffective in improving total functional capacity of all seniors 65 years and older. Elderly people 75 years and older, however, who were living alone or lonely did benefit from screening and treatment showing an improvement in daily activities, mental health scores, and social functions. This finding has implications for selective preventive health care spending for the elderly. A 2-year follow-up period could be too brief to detect long-term effects of early intervention with younger, middle-class seniors, especially those who are already functionally active.

Activities of Daily Living↗
PubMed1997

Frequencies of the five PCR-based genetic markers LDLR, GYPA, HBGG, D7S8 and GC in the population of Asturias (North Spain).

Allele and genotype frequencies of the loci LDLR, GYPA, HBGG, D7S8 and GC (PM loci) were investigated in a population sample of 215 unrelated individuals from Asturias (North Spain). Multiplex amplification and simultaneous typing of the five loci was carried out using the polymarker PCR amplification and typing kit. All loci met Hardy-Weinberg expectations. The Asturian sample does not differ significantly from other Caucasians, but significant differences were observed between this population and SW Hispanic, Afro-american and Korean populations.

Alleles↗
PubMed1997

The zebrafish gene cloche acts upstream of a flk-1 homologue to regulate endothelial cell differentiation.

The zebrafish cloche mutation affects both the endothelial and hematopoietic lineages at a very early stage (Stainier, D. Y. R., Weinstein, B. M., Detrich, H. W., Zon, L. I. and Fishman, M. C. (1995). Development 121, 3141-3150). The most striking vascular phenotype is the absence of endocardial cells from the heart. Microscopic examination of mutant embryos reveals the presence of endothelial-like cells in the lower trunk and tail regions while head vessels appear to be missing, indicating a molecular diversification of the endothelial lineage. Cell transplantation experiments show that cloche acts cell-autonomously within the endothelial lineage. To analyze further the role of cloche in regulating endothelial cell differentiation, we have examined the expression of flk-1 and tie, two receptor tyrosine kinase genes expressed early and sequentially in the endothelial lineage. In wild-type fish, flk-1-positive cells are found throughout the embryo and differentiate to form the nascent vasculature. In cloche mutants, flk-1-positive cells are found only in the lower trunk and tail regions, and this expression is delayed as compared to wild-type. Unlike the flk-1-positive cells in wild-type embryos, those in cloche mutants do not go on to express tie, suggesting that their differentiation is halted at an early stage. We also find that the cloche mutation is not linked to flk-1. These data indicate that cloche affects the differentiation of all endothelial cells and that it acts at a very early stage, either by directly regulating flk-1 expression or by controlling the differentiation of cells that normally develop to express flk-1. cloche mutants also have a blood deficit and their hematopoietic tissues show no expression of the hematopoietic transcription factor genes GATA-1 or GATA-2 at early stages. Because the appearance of distinct levels of flk-1 expression is delayed in cloche mutants, we examined GATA-1 expression at late embryonic stages and found some blood cell differentiation that appears to be limited to the region lined by the flk-1-expressing cells. The spatial restriction of blood in the ventroposterior-most region of cloche mutant embryos may be indicative of a ventral source of signal(s) controlling hematopoietic differentiation. In addition, the restricted colocalization of blood and endothelium in cloche mutants suggests that important interactions occur between these two lineages during normal development.

Amino Acid Sequence↗
PubMed1997

Distribution of types for six PCR-based loci; LDLR, GYPA, HBGG, D7S8, GC and HLA-DQA1 in central Pyrenees and Teruel (Spain).

The PCR-based DNA loci LDLR, GYPA, HBGG, D7S8, GC and HLA DQA1 are widely used in forensic casework analyses. Population data on the distribution of allele frequencies are desired to estimate the rarity of a DNA profile. We studied the allele distributions at these forensically important DNA markers in two Spanish populations (Central Pyrenees and Teruel). Results were in agreement with Hardy-Weinberg expectations. Furthermore, there was little evidence for departures from expectation of independence between loci within the two sample populations. Tests for homogeneity were carried out between the two Spanish populations and a U.S. Caucasian population.

Alleles↗
PubMed1996

Ras-responsiveness of the HIV-1 LTR requires RBF-1 and RBF-2 binding sites.

Lentiviruses characteristically form latent integrated proviruses whose transcription can be induced by cell regulatory signals. The HIV-1 LTR responds to multiple signals, including the Ras pathway. We report here that Ras-responsive HIV-1 transcription requires two previously undescribed factors, RBF-1 and RBF-2 in Jurkat T cells. RBF-1 binds to Ets-like motifs located between nucleotides -151 and -142, and within the NF-kappaB binding sites, but is distinct from Ets-1 or Elf-1. RBF-2 binds the HIV-1 LTR at nucleotides -131 and -121 and immediately 3' of the TATA box. Both RBF-1 and RBF-2 contain DNA binding subunits of relative molecular weight 100 kilodaltons. Mutation of the RBF-1 and RBF-2 binding elements (RBEs) prevents Ras stimulation of HIV-1 LTR-directed transcription. These data define a mechanism for Ras responsiveness of HIV-1 transcription that involves the previously uncharacterized factors RBF-1 and RBF-2.

Base Sequence↗
PubMed1996

Contralateral suppression of transient-evoked otoacoustic emissions in humans: intensity effects.

Transient evoked otoacoustic emissions (TEOAEs) were recorded to clicks presented at peak sound pressures of 50, 55, 60, 65 and 70 dB while continuous contralateral white noise was varied from 10 dB below to 10 dB above the click level. Suppression increased predictably with suppressor noise level for any given click level. However, when the suppressor noise level was held constant, suppression was greater for lower click levels. This observation is consistent with the association of suppression of otoacoustic emissions with active cochlear processes and efferent function at low intensity levels.

Acoustic Stimulation↗
PubMed1996

Optical characterization and coagulation performance of side-emitting fiber delivery systems for laser therapy of benign prostatic hyperplasia: a comparative study.

OBJECTIVES: Currently, various side-emitting optical fibers with different tip geometry are used transurethrally to deliver laser radiation for treatment of benign prostatic hyperplasia (BPH). Since fiber tip design could profoundly affect the size and profile of the emitted laser beam, and consequently the tissue response and the extent of tissue coagulation, we evaluted commercially available fibers in regard to their optical characteristics and their ability to coagulate tissue in a controlled experimental setting. METHODS: Thirteen fibers manufactured by different companies and clinically used at the present time were tested using a surgical neodymium: yttrium-aluminum-garnet laser. The profile of the laser beam delivered via each fiber was imaged on a CCD camera at various distances and evaluated by means of a laser beam analyzer. Beam divergence angle was then calculated for each tip. Tissue coagulation effects were assessed by irradiating samples of beef muscle immersed in water at 37 degrees C. The fiber tip was kept 2.5 mm away from the tissue and irrigation was maintained at flow rate of 350 to 400 cc/min during irradation. Laser powers of 20, 40, and 60 W were used for 180, 90, and 60 seconds, respectively, delivering a total energy of 3600 J. RESULTS: The results of the optical evaluation divided the fibers into two major groups: broad beam with large divergence angle and narrow beam with small divergence angle. Statistical analysis of the data (using analysis of variance) showed that volumes of coagulated tissue were significantly larger for broad beam fibers than for narrow beam fibers (1.15 +/- 0.32 versus 0.89 +/- 0.34 cm 3; P < 0.05). Also, significantly larger volumes were obtained for 20 W when compared with 60 W (1.08 +/- 0.43 versus 0.88 +/- 0.27 cm 3; P < 0.05). CONCLUSIONS: The laser power density delivered by individual fibers to the prostate tissue may vary significantly, thus greatly affecting the extent of tissue coagulation. Therefore, irradiation parameters must be optimized for each fiber type.

Animals↗
PubMed1996

Phase I trial and pharmacokinetic (PK) and pharmacodynamics (PD) study of topotecan using a five-day course in children with refractory solid tumors: a pediatric oncology group study.

PURPOSE: A phase I trial was conducted in children with refractory solid tumors to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics, and pharmacodynamics for topotecan administered by a 30-min infusion for 5 consecutive days. PATIENTS AND METHODS: Forty children with a variety of recurrent solid tumors, including nine patients with neuroblastoma and 10 with brain tumors, were given topotecan as a 30-min infusion for 5 consecutive days, beginning with a dose of 1.4 mg/m2/day. The dose was escalated in 20% increments after establishing that DLT was not present at the prior dose. Drug toxicity was graded using standard criteria. Dose-limiting toxicity was defined as grade 3 or 4 nonhematopoietic toxicity or grade 4 hematopoietic toxicity lasting > 7 days. Pharmacokinetic studies were performed during the first infusion course. RESULTS: The DLT was hematopoietic and involved both platelets and neutrophils. Grade 4 hematopoietic toxicity of brief duration was seen at all dose levels. Over half of the patients received red blood cell transfusion support, and 19/40 received platelet transfusions. Hospital admissions for fever and neutropenia or for documented infections occurred in 32 of 169 courses of therapy. Gastrointestinal symptoms with nausea and vomiting or diarrhea were mild to moderate in 12 of the 40 patients. Antitumor responses were seen in three patients with neuroblastoma. An additional four patients (one with neuroblastoma, two with anaplastic astrocytomas, one with Ewing) had stable disease with continued therapy for > 6 months. Using a limited sampling model, pharmacokinetic studies were performed in 36 of the 40 patients. Topotecan lactone and total clearance were similar to those reported in other pediatric populations receiving topotecan by continuous infusion. A pharmacodynamic relation between systemic exposure to topotecan lactone and myclosuppression was observed. CONCLUSIONS: In heavily pretreated children, the MTD for topotecan given by intermittent 30-min infusion for 5 days is 1.4 mg/m2 without GCSF and 2.0 mg/m2/day with GCSF. The dose-limiting toxicity is hematopoietic. Data from this study provide the basis for further studies of topotecan in children with cancer.

Adolescent↗
PubMed1996

Molecular probe for typing strains of Candida albicans.

A method for separating strains of Candida albicans into nine possible groups was devised by using a cDNA probe for enolase and Southern blot analysis. Twenty-three isolates of C. albicans were found to be distributed among eight of the groups. Fifteen isolates from a single hospital segregated into four of the groups.

Blotting, Southern↗
PubMed1996

Human immunodeficiency virus type 1 long terminal repeat variants from 42 patients representing all stages of infection display a wide range of sequence polymorphism and transcription activity.

Despite extensive in vitro studies identifying a myriad of cellular transcription factors that bind the human immunodeficiency virus type 1 5' long terminal repeat (LTR), the relative contribution of these factors to human immunodeficiency virus type 1 replication in infected individuals remains obscure. To address this question, we investigated 478 proviral quasispecies derived from uncultured peripheral blood mononuclear cells of 42 patients representing all stages of infection. In addition to highly conserved TATA box, SP-1, and NF-kappaB sites, the Ets core and an adjacent 5'-ACYGCTGA-3' motif were extremely conserved. Importantly, the most frequent naturally occurring length polymorphism (MFNLP) duplicated 5'-ACYGCTGA-3' motifs in LTRs in which this same motif was disrupted or in LTRs in which a single point mutation to the Ets core ablated binding of c-Ets 1 and another factor distinct from both c-Ets 1 and Elf 1. The MFNLP's location was precise (position -121) and surprisingly frequent (38% of patients) and demarcated LTR Nef-coding sequences from LTR noncoding sequences that appear to be evolving independently. Aside from these features, we found no definitive clinical or transcription phenotype common to all MFNLP LTRs. We also found previously described and novel point polymorphisms, including some conferring TAR-dependent and TAR- independent Tat unresponsiveness, and showed that differential binding of nuclear factor(s) to a TCTAA TATA box variant may be the mechanism for the latter.

Acquired Immunodeficiency Syndrome↗
PubMed1995

A phase I study of acivicin in refractory pediatric solid tumors. A Pediatric Oncology Group study.

Forty-two patients with progressive solid tumors and brain tumors were entered in this Phase I study of the glutamine antagonist acivicin given intravenously over thirty minutes daily for five days. The major toxicities encountered were myelosuppression and central nervous system toxicity (nightmares and somnolence). The maximum tolerated dosage on this schedule was 26 mg/M2 daily for five days. Six patients including three patients with brain tumor had stable disease.

Adolescent↗