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Biomedical subjects

B Bell

Publications and source records attributed to B Bell.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1993

Ifosfamide with mesna uroprotection and etoposide in recurrent, refractory acute leukemia in childhood. A Pediatric Oncology Group Study.

BACKGROUND: Ifosfamide has previously been shown to be active as a single agent and in combination with doxorubicin, etoposide, and teniposide in pediatric solid tumors and adult acute leukemia. The authors performed a dose-escalation trial of ifosfamide with a fixed dosage of etoposide, with mesna uroprotection, in children with multiply recurrent acute leukemia. METHODS: Chemotherapy was administered daily for 5 days. Etoposide 100 mg/m2 was followed by ifosfamide at an initial dosage of 1.6 g/m2. The ifosfamide was escalated in 20% increments to the maximum tolerated dosage in cohorts of three patients. Mesna 400 mg/m2 was given immediately before the ifosfamide and then at 3 and 6 hours after ifosfamide in the initial patients. Subsequent patients were treated with mesna 400 mg/m2 just before ifosfamide, and then every 2 hours to a total dosage equal to the ifosfamide dosage. RESULTS: Forty-four heavily pretreated patients were entered on study. Forty were evaluable for toxicity and 36 for response as well. The maximum tolerated dosage of ifosfamide was 4.0 g/m2/d for 5 days (20 g/m2/course). Overall, 10 patients achieved complete remission, and 3 achieved partial remission. Remissions were brief, although four patients went on to bone marrow transplant while in remission. One patient is still alive. CONCLUSIONS: The combination of etoposide and ifosfamide with mesna uroprotection showed promising activity in children with multiply recurrent acute leukemia.

Acute Disease↗
PubMed1993

Familial adenomatous polyposis (Gardner's syndrome) and thyroid carcinoma. A case report and review of the literature.

The case history of a 24-year-old woman with Gardner's syndrome [familial adenomatous polyposis (FAP)] and papillary thyroid carcinoma is presented, representing the 37th report of this association. Although FAP is transmitted as an autosomal dominant trait with similar penetrance in both sexes, thyroid carcinoma has been found almost exclusively in women (94.3%). The majority have been papillary carcinomas (88.5%), which have become apparent during the third decade (average 23.6, range 16-40 years). Most (55.5%) thyroid carcinomas have been discovered 1-17 years after FAP was identified, although some have been found before (29.6%), or at the same time (14.8%) FAP was diagnosed. Multicentric papillary carcinomas have been reported in 64% (14 of 22) of FAP patients, a frequency at least twofold greater than usual. Although papillary carcinoma found before age 30 (as it was in most patients with FAP) typically has an excellent prognosis, one patient with FAP developed distant metastases from thyroid carcinoma and a 28-year-old woman's death was attributed to papillary carcinoma. The high frequency of multicentric papillary thyroid carcinoma in young patients with FAP and the potential for metastases and death due to thyroid carcinoma warrant aggressive diagnostic screening at regular intervals with neck palpation, ultrasonography, and if necessary, fine-needle aspiration biopsy. When thyroid carcinoma is found, total or near-total thyroidectomy should be considered because of the tumor's high likelihood of being multifocal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Phase I clinical trial of recombinant human tumor necrosis factor in children with refractory solid tumors: a Pediatric Oncology Group study.

PURPOSE: A phase I study was undertaken to determine the toxicity and maximum-tolerated dose (MTD) of recombinant human tumor necrosis factor (rTNF) in children. PATIENTS AND METHODS: Twenty-seven patients with recurrent or refractory solid tumors were enrolled on the study. rTNF was administered daily for 5 days by 30-minute intravenous (IV) infusion, and doses were escalated in cohorts of three to six patients. Courses were repeated after a 9-day rest period, if toxicity was tolerable. Daily doses ranged from 100 to 350 micrograms/m2. RESULTS: Most courses were associated with grade I/II fever, rigors, nausea, or vomiting. Three patients experienced moderate dyspnea that responded to supplemental oxygen. All abnormalities resolved on discontinuation of the infusion. One patient had a cardiac arrest 90 minutes after receiving the first dose of rTNF and died 10 days later of related complications. In two other patients, rTNF was discontinued due to persistent grade IV hypotension. Toxicities were not consistently related to dose and no cumulative effects were noted. The dose-limiting toxicity was transient hepatic dysfunction, which occurred in three of six patients receiving 350 micrograms/m2; this toxicity was rapidly reversed on discontinuation of the rTNF. One patient, whose non-Hodgkin's lymphoma had recurred after bone marrow transplantation, had a partial response. Disease was stabilized in two patients. CONCLUSION: We recommend that phase II testing proceed at a dose of 300 micrograms/m2/d on the schedule described.

Adolescent↗
PubMed1993

Racial differentials in the identification of hypercholesterolemia.

BACKGROUND: African Americans have higher rates of cardiovascular disease than white Americans. To address this differential, barriers to cardiovascular risk reduction need to be identified. This study examines the association of race with the likelihood of screening for and diagnosis of hypercholesterolemia. METHODS: Possible associations between demographic variables and screening for and diagnosis of hypercholesterolemia were examined on data gathered in a prospective fashion in an office-based family medicine residency training program in Rochester, New York. A consecutive sample of all patients seen between December 15, 1988, and April 15, 1990, about whom there was complete data collection (age, sex, insurance, race, and other cardiovascular risk factors) were included in the multivariate analyses (N = 4256). RESULTS: After controlling for age, sex, insurance status, socioeconomic status, number of visits, and other cardiovascular risk factors, it was found that minorities were less likely to have been screened for cholesterol levels than whites (adjusted odds ratio [AOR] = 0.84, 95% confidence interval [CI] = 0.98 to 0.72). The mean cholesterol level did not differ by race (mean cholesterol for whites, 204 mg/dL [5.28 mmol/L], and for minorities, 203 mg/dL [5.25 mmol/L], t = 0.7, P = .47). Among those screened, minorities were less likely than whites to have been diagnosed with hypercholesterolemia (AOR = 0.62, 95% CI = 0.86 to 0.44; and 0.47 (95% CI = 0.28 to 0.78] in those with a cholesterol level greater than 240 mg/dL [6.2 mmol/L]). CONCLUSIONS: Our data suggest that provider behavior in diagnosing hypercholesterolemia varies by the race of the patient.

Adult↗