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Biomedical subjects

B Bell

Publications and source records attributed to B Bell.

At least 19 recordsLinked to original sources
PubMed2000

Evidence that synaptically-released zinc contributes to neuronal injury after traumatic brain injury.

Prior evidence indicates that synaptically-released zinc enters postsynaptic neurons in toxic excess during ischemia and seizures. In addition, prevention of this zinc translocation has been shown to be neuroprotective in both ischemia and seizures. Here we show evidence that the same translocation of zinc from presynaptic boutons into postsynaptic neurons occurs after mechanical injury to the brain. Specifically, using a rat model of traumatic brain injury, we show that trauma is associated with (i) loss of zinc from presynaptic boutons (ii) appearance of zinc in injured neurons, and (iii) neuroprotection by intraventricular administration of a zinc chelator just prior to brain impact. The possible use of zinc chelators for neuroprotection after head trauma is considered.

Aminoquinolines↗
PubMed2000

Identity in adolescent survivors of childhood cancer.

OBJECTIVE: To investigate identify formation among adolescent survivors of childhood cancer. Family functioning, perceived emotional support from family and peers, life stress, and anxiety produced by the cancer experience also were examined as they influenced identity development. METHOD: Participants were 52 adolescent survivors and their mothers recruited from a medical center and 42 healthy adolescent counterparts and their mothers recruited from the community. RESULTS: A greater frequency of survivors than their healthy peers was found within the foreclosed identity status. Factors associated with the foreclosed identity status included the cancer diagnosis, symptoms of posttraumatic stress disorder (PTSD), and family functioning characterized by greater levels of conflict. CONCLUSIONS: Data were interpreted to suggest that the foreclosed identity status may serve a protective function in assisting survivors to cope with the stressors of the cancer experience.

Adolescent↗
PubMed2000

Psychiatric comorbidity in chronic epilepsy: identification, consequences, and treatment of major depression.

The purpose of this article is to review the topic of interictal psychiatric comorbidity among adult patients with chronic epilepsy, focusing specifically on those studies that have used contemporary psychiatric nosology. Five specific issues are addressed: (a) the risk and predominant type(s) of psychiatric comorbidity in chronic epilepsy, (b) adequacy of recognition and treatment of psychiatric comorbidity, (c) the additional burdens that comorbid psychiatric disorders impose upon patients with chronic epilepsy, (d) the etiology of these disorders, and (e) strategies for treatment. Current appreciation for these issues in epilepsy is contrasted to related fields (e.g., primary care, psychiatry, and epidemiology), where considerable attention has been devoted to the identification, consequences, and treatment of psychiatric comorbidity. The issue of psychiatric comorbidity in epilepsy is reviewed with the aim of identifying a clinical and research agenda that will advance understanding of at least one important psychiatric condition associated with epilepsy-namely, major depression.

Absenteeism↗
PubMed1999

The N-terminal domain of human TAFII68 displays transactivation and oncogenic properties.

In Ewing tumor, the (11;22) chromosomal translocation produces a chimeric molecule composed of the amino-terminal domain of EWS fused to the carboxyl-terminal DNA-binding domain of FLI-1. Previously, we have identified a novel protein TAFII68, which is highly similar to EWS and another closely related protein TLS (also called FUS). We demonstrate that the N-terminus of TAFII68 efficiently stimulates transcription when fused to two different DNA binding domains and that overexpression of TAFII68-FLI-1 chimeras in NIH3T3 cells leads to oncogenic transformation. We have also investigated the molecular mechanisms which could account for the transcriptional activation and the oncogenic transformation potential of the N-termini of TAFII68 and EWS. Thus, we have tested whether the artificial recruitment of components of the preinitiation complex (PIC) or a histone acetyltransferase (HAT) could bypass the requirement for the activation domains of either EWS or TAFII68. Recruitment of individual components of the transcription machinery or the GCN5 HAT is not sufficient to promote activation from FLI-1 responsive genes either in transfection experiments or in oncogenic transformation assays. These results suggest that the TAFII68 or EWS activation domains enhance a step after PIC formation in the transcriptional activation process.

3T3 Cells↗
PubMed1999

KSR-1 binds to G-protein betagamma subunits and inhibits beta gamma-induced mitogen-activated protein kinase activation.

The protein kinase KSR-1 is a recently identified participant in the Ras signaling pathway. The subcellular localization of KSR-1 is variable. In serum-deprived cultured cells, KSR-1 is primarily found in the cytoplasm; in serum-stimulated cells, a significant portion of KSR-1 is found at the plasma membrane. To identify the mechanism that mediates KSR-1 translocation, we performed a yeast two-hybrid screen. Three clones that interacted with KSR-1 were found to encode the full-length gamma10 subunit of heterotrimeric G-proteins. KSR-1 also interacted with gamma2 and gamma3 in a two-hybrid assay. Deletion analysis demonstrated that the isolated CA3 domain of KSR-1, which contains a cysteine-rich zinc finger-like domain, interacted with gamma subunits. Coimmunoprecipitation experiments demonstrated that KSR-1 bound to beta1 gamma3 subunits when all three were transfected into cultured cells. Lysophosphatidic acid treatment of cells induced KSR-1 translocation to the plasma membrane from the cytoplasm that was blocked by administration of pertussis toxin but not by dominant-negative Ras. Finally, transfection of wild-type KSR-1 inhibited beta1 gamma3-induced mitogen-activated protein kinase activation in cultured cells. These results demonstrate that KSR-1 translocation to the plasma membrane is mediated, at least in part, by an interaction with beta gamma and that this interaction may modulate mitogen-activated protein kinase signaling.

Animals↗
PubMed1999

Prevalence of dysthymic disorder in primary care.

BACKGROUND: Dysthymic disorder is characterised as a chronic state of depressed mood which is not otherwise attributable to physical, psychological or social events. While it can occur alone, there is increasing evidence that the majority of individuals who meet criteria for dysthymic disorder also experience more severe episodic mood disorders throughout their lifetime, and there is also an aggregation of mood disorders within their family members. Patients with dysthymic disorder are most often seen in primary care. Some researchers suggest that the majority of these individuals are never diagnosed or are not diagnosed until a more severe episodic mood disorder develops. The objective of this study was to determine the 12-month prevalence of Axis I psychiatric disorders, and in particular dysthymic disorder, in a primary care Health Service Organization in Ontario, Canada. METHODS: Eligible and consenting adults registered with a primary care Health Service Organization were screened using the modified form of the University of Michigan Composite International Diagnostic Interview. RESULTS: Of the 6280 eligible subjects, 4327 (69%) consented to screening. Two hundred and twenty-two (5.1%) subjects screened positive for dysthymic disorder. In addition, 90% of those who screened positive for dysthymic disorder also screened positive for other Axis I disorders including major depressive disorder, panic, simple phobia, and generalized anxiety disorder. CONCLUSIONS: There is much potential for the primary care physician to play a pivotal role in the recognition and treatment of dysthymic disorder and associated Axis I disorders. A focus on the family as a unit for care may be especially important given the reported aggregation of dysthymic disorder within families.

Adolescent↗
PubMed1999

Visual confrontation naming outcome after standard left anterior temporal lobectomy with sparing versus resection of the superior temporal gyrus: a randomized prospective clinical trial.

PURPOSE: Intraoperative mapping of eloquent cortex during left (speech dominant) anterior temporal lobectomy has shown a significant proportion of patients to have sites on the anterior superior temporal gyrus at which visual confrontation naming can be disrupted by electrical stimulation. The purpose of this investigation was to conduct a randomized clinical trial to determine whether sparing versus resection of the superior temporal gyrus affected visual confrontation naming outcome after standard left anterior temporal lobectomy. Also examined was the degree to which inherent patient characteristics were associated with language outcome regardless of surgical technique. METHODS: Thirty patients with intractable left temporal lobe epilepsy undergoing standard anterior temporal lobectomy were randomized in regard to whether the superior temporal gyrus was resected or spared. Patients were tested preoperatively and 6-8 months postoperatively by using two conventional tests of visual confrontation naming ability. RESULTS: No significant differences were found between the groups in either confrontation naming or surgical outcome. Postoperative decline in nominal speech was most closely associated with later age at onset of epilepsy/absence of hippocampal sclerosis. CONCLUSIONS: It appears that specific types of localization-related temporal lobe epilepsy are more closely associated with the risk of adverse language outcome after anterior temporal lobectomy than with the surgical variations investigated in this study.

Adult↗
PubMed1999

Detection of pathological zinc accumulation in neurons: methods for autopsy, biopsy, and cultured tissue.

It has been repeatedly shown that synaptically released zinc contributes to excitotoxic neuronal injury in ischemia, epilepsy, and mechanical head trauma. Such zinc-induced injury leaves an unmistakable "footprint" in the injured neurons, allowing an easy and unambiguous postmortem diagnosis. This footprint is the presence of weakly bound, histochemically reactive zinc in the cytoplasm of the perikaryon and proximal dendrites. Such staining appears to be a necessary and sufficient marker for zinc-induced neuronal injury. Here we show how to prepare and stain tissue from biopsy, autopsy, or experimental animal sources for maximal contrast and visibility of zinc-injured neurons.

Animals↗
PubMed1998

Surviving social assistance: 12-month prevalence of depression in sole-support parents receiving social assistance.

BACKGROUND: Although it is generally recognized that poverty and depression can coexist among single parents receiving social assistance, there is insufficient research on this topic. The goals of this study therefore were to investigate the prevalence, correlates and health care expenditures associated with depression among sole-support parents receiving social assistance. METHODS: Sole-support parents who had applied for social assistance in 2 regions of southwestern Ontario were included in the study. Depression was diagnosed with the 1994 University of Michigan Composite International Diagnostic Interview short forms. RESULTS: The 12-month prevalence rate of depressive disorder among the parents interviewed was 45.4% (345/760). A total of 247 (32.5%) had major depressive disorder alone, 19 (2.5%) had dysthymia, and 79 (10.4%) had both major depressive disorder and dysthymia ("double depression"). Those with major depressive disorder, particularly double depression, had significantly higher rates of coexisting psychiatric disorder than those without depressive disorders. Parents with depression reported higher rates of developmental delay and behaviour problems in their children than parents without depression. Expenditures for health care services were higher for parents with depression and for their children than for parents without depressive disorder and their children. INTERPRETATION: Single parents receiving social assistance have high rates of depression. Such parents with depression also have higher rates of other psychiatric disorders and higher expenditures for health care services, and their children have higher rates of developmental delay and behaviour problems.

Adaptation, Psychological↗
PubMed1998

Laser assisted soldering: microdroplet accumulation with a microjet device.

BACKGROUND AND OBJECTIVE: We investigated the feasibility of a microjet to dispense protein solder for laser assisted soldering. STUDY DESIGN: Successive micro solder droplets were deposited on rat dermis and bovine intima specimens. Fixed laser exposure was synchronized with the jetting of each droplet. After photocoagulation, each specimen was cut into two halves at the center of solder coagulum. One half was fixed immediately, while the other half was soaked in phosphate-buffered saline for a designated hydration period before fixation (1 hour, 1, 2, and 7 days). After each hydration period, all tissue specimens were prepared for scanning electron microscopy (SEM). RESULTS: Stable solder coagulum was created by successive photocoagulation of microdroplets even after the soldered tissue exposed to 1 week of hydration. CONCLUSIONS: This preliminary study suggested that tissue soldering with successive microdroplets is feasible even with fixed laser parameters without active feedback control.

Animals↗
PubMed1998

Isolation of the zebrafish homologues for the tie-1 and tie-2 endothelium-specific receptor tyrosine kinases.

Several characteristics of the zebrafish embryo make it an attractive model in which to study the development of the cardiovascular system. The utility of the zebrafish as a model of mammalian vascular development will depend on the conservation of molecular and morphogenetic mechanisms of vessel growth. Here, we report the cloning of the zebrafish homologues of the endothelium-specific receptor tyrosine kinases tie-1 and tie-2. The Z tie-2 clone represents the first report of a full-length zebrafish endothelium-specific gene. The zebrafish tie family members have significant structural homology with their murine and human counterparts. In addition, like the murine tie-1 and tie-2 genes, expression was found predominantly in endothelial cells. At 24-hr postfertilization (HPF), Z tie-1 was expressed in all observed populations of endothelial cells. Interestingly, Z tie-2 exhibited a similar, although slightly more restricted, expression pattern. Taken together, these data strongly suggest that mechanisms of vascular development are highly conserved across species and that zebrafish will continue to be a useful model for the investigation of vertebrate embryonic vascular development.

Amino Acid Sequence↗
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↗