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K Campbell

Publications and source records attributed to K Campbell.

At least 73 records · Page 4Linked to original sources
PubMed1999

Retinoids are produced by glia in the lateral ganglionic eminence and regulate striatal neuron differentiation.

In order to identify molecular mechanisms involved in striatal development, we employed a subtraction cloning strategy to enrich for genes expressed in the lateral versus the medial ganglionic eminence. Using this approach, the homeobox gene Meis2 was found highly expressed in the lateral ganglionic eminence and developing striatum. Since Meis2 has recently been shown to be upregulated by retinoic acid in P19 EC cells (Oulad-Abdelghani, M., Chazaud, C., Bouillet, P., Sapin, V., Chambon, P. and Dollé, P. (1997) Dev. Dyn. 210, 173-183), we examined a potential role for retinoids in striatal development. Our results demonstrate that the lateral ganglionic eminence, unlike its medial counterpart or the adjacent cerebral cortex, is a localized source of retinoids. Interestingly, glia (likely radial glia) in the lateral ganglionic eminence appear to be a major source of retinoids. Thus, as lateral ganglionic eminence cells migrate along radial glial fibers into the developing striatum, retinoids from these glial cells could exert an effect on striatal neuron differentiation. Indeed, the treatment of lateral ganglionic eminence cells with retinoic acid or agonists for the retinoic acid receptors or retinoid X receptors, specifically enhances their striatal neuron characteristics. These findings, therefore, strongly support the notion that local retinoid signalling within the lateral ganglionic eminence regulates striatal neuron differentiation.

Animals↗
PubMed1999

The major vault protein (MVP), a new multidrug resistance associated protein, is frequently expressed in multiple myeloma.

The major vault protein (MVP), a ribonucleoprotein complex which mediates the transport of xenobiotic toxins, has been implicated in multidrug resistance (MDR) not mediated by p-glycoprotein (P-gp) or multidrug resistance related protein (MRP). We evaluated, via immunohistochemistry, the presence of MVP in plasma cells of myeloma patients. Among 73 patients registered with the Southwest Oncology Group (SWOG), 52 patients (74%) were positive for MVP. The presence of MVP and P-gp were significantly associated (p < 0.01). A univariate analysis of response versus MVP positivity showed borderline statistical significance (p = 0.043) with no association with OS or PFS. In particular, MVP positivity at first biopsy was associated with non-responsiveness to therapy (7/7 patients, 100%). MRP was not present in any of 23 samples tested. An increased proliferative rate (Ki-67 > 5%) was significantly associated with shorter OS (log rank p-value = 0.0002). The collective work indicates that MVP protein is common and abundant in myeloma with potential relevance to therapeutic response.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

HOLON/CADSE: integrating open software standards and formal methods to generate guideline-based decision support agents.

This paper describes the efforts of a consortium that is trying to develop and validate formal methods and a meta-environment for authoring, checking, and maintaining a large repository of machine executable practice guidelines. The goal is to integrate and extend a number of open software standards so that guidelines in the meta-environment become a resource that any vendor can plug their applications into and run in their proprietary environment provided they conform to the interface standards.

Computer Communication Networks↗
PubMed1998

Homozygous deletions of methylthioadenosine phosphorylase (MTAP) are more frequent than p16INK4A (CDKN2) homozygous deletions in primary non-small cell lung cancers (NSCLC).

Homozygous deletions of the tumor suppressor gene p16INK4A and deficiency of methylthioadenosine phosphorylase (MTAP), both located on chromosome 9p21, have been independently reported in non-small cell lung cancer (NSCLC). To determine the frequency of co-deletion of these two genes, we investigated 50 samples of primary NSCLC using a quantitative PCR-ELISA. All specimens were fixed in formalin, paraffin embedded and stored until assayed. Histologic subtypes included 25 adenocarcinomas (50%), 21 squamous cell carcinomas (42%) and four large cell carcinomas (8%). Homozygous deletions of MTAP exon 8 could be detected in 19 of 50 NSCLC samples (38%). Adenocarcinoma (11 of 25, 44%) showed a higher deletion frequency than squamous cell carcinoma (six of 21, 29%). In contrast, homozygous p16INK4A deletions were detected in only nine of 50 (18%) samples using specific primers for p16INK4A exon 1alpha. No difference between the histological subtypes and p16INK4A deletion frequency was observed. We further investigated the ten samples with MTAP deletions but intact p16INK4A exon 1alpha with primers specific for p16INK4A exon 3, the exon nearest to MTAP exon 8. Interestingly, none of the ten samples had deletion of the p16INK4A exon 3 coding region. Fine mapping analysis performed in ten samples showed a frequent breakpoint between MTAP exon 4 and exon 5. In addition, p16 protein expression could not be detected in five out of six samples with intact p16 but deleted MTAP locus. These data show a high frequency of homozygous MTAP deletions in NSCLC which is associated with detectable co-deletion of p16INK4A in only half of the cases. This result suggests the existence either of another tumor suppressor gene telomeric of p16INK4A or of deletions involving 3'-untranslated (3'-UTR) regulatory regions of p16INK4A that can interfere with its expression or function.

Carcinoma, Non-Small-Cell Lung↗
PubMed1998

The role of the CD40 pathway in alloantigen-induced hyporesponsiveness in vivo.

Resting B (rB) cells are known to be incompetent APCs in vitro, which alone can induce specific unresponsiveness to single minor histocompatibility (miH) Ags and, when combined with CD40 pathway blockade, can induce hyporesponsiveness to MHC molecules in vivo. Here we show that anti-CD40 ligand (CD40L) mAb does not prevent the expression of B7-2 on allogeneic rB cells in vivo but did prolong donor-specific cardiac allograft survival. Moreover, pretreatment with professional APCs combined with anti-CD40L mAb induced hyporesponsiveness to alloantigens in vivo. rB cells from CD40 knockout mice were unable to induce unresponsiveness, while graft prolongation was achieved in CD40L knockout recipients pretreated with wild-type rB cells. These data suggest that CD40-CD40L interactions in the recipient play a critical role in the induction of hyporesponsiveness to alloantigens in vivo and that the effect of the CD40 pathway may be independent of its effect on the B7 costimulatory pathway.

Abatacept↗
PubMed1998

Contact-dependent regulation of N-type calcium channel subunits during synaptogenesis.

The developmental regulation of the N-type calcium channel during synaptogenesis was studied using cultured rat hippocampal neurons to elucidate the roles of extrinsic versus intrinsic cues in the expression and distribution of this channel. Prior to synapse formation, alpha1B and beta3 subunits of the N-type calcium channel were distributed diffusely throughout neurites, growth cones, and somata. As synaptogenesis proceeded, the subunit distributions became punctate and colocalized with the synaptic vesicle protein synaptotagmin. Isolated neurons were also examined to test for the requirement of extrinsic cues that control N-type calcium channel expression and distribution. These neurons expressed N-type calcium channel subunits, but their distributions remained diffuse. Functional omega-conotoxin GVIA-sensitive channels were expressed in isolated neurons, although the distribution of alpha1B subunits was diffuse. The distribution of the alpha1B subunit and synaptotagmin only became punctate when neuron-neuron contact was allowed. Thus, the expression of functional N-type calcium channels is the result of an intrinsic program while extrinsic regulatory cues mediated by neuron-neuron contact are required to control their distribution during synaptogenesis.

Animals↗
PubMed1998

Early specification of striatal projection neurons and interneuronal subtypes in the lateral and medial ganglionic eminence.

The striatum is thought to be generated from two transient swellings in the ventral telencephalon, the lateral and medial ganglionic eminences, present at mid-stages of embryonic rat development. We have studied the relative contribution of these structures to the specific generation of striatal neuronal subtypes such as projection neurons and cholinergic and somatostatin-containing interneurons at an early stage and a mid stage in striatal neurogenesis. Dissociated progenitors isolated from the embryonic day 12.5 and embryonic day 15.5 rat lateral ganglionic eminence grafted into the previously ibotenic acid lesioned adult striatum, produce grafts containing extensive numbers of neurons expressing messenger RNA for the striatal projection neuron marker, DARPP-32, whereas grafts of the embryonic day 12.5 and embryonic day 15.5 medial ganglionic eminences do not. While preprosomatostatin messenger RNA-expressing neurons were observed in grafts from each of the lateral ganglionic eminence and medial ganglionic eminence at both embryonic day 12.5 and embryonic day 15.5, choline acetyltransferase messenger RNA-expressing cholinergic neurons were largely found in grafts derived from the embryonic day 12.5 medial ganglionic eminence. These results suggest that the neuronal diversity of the adult striatum may derive both from the lateral ganglionic eminence, providing DARPP-32-expressing projection neurons as well as somatostatin-containing interneurons, and the early stage medial ganglionic eminence specifically contributing the cholinergic interneurons.

Animals↗
PubMed1998

Two- to six-year controlled-trial stuttering outcomes for children and adolescents.

This research is a long-term follow-up of a previously published, controlled trial on the effectiveness of 3 stuttering treatments (intensive smooth speech, parent-home smooth speech, and intensive electromyography feedback) for children and adolescents, aged 11 to 18 years, who stutter. The previous controlled trial showed all 3 treatments to be effective compared to nontreatment after 12 months. This paper reports on the treatment effectiveness after an average of 4 years post-treatment. Results demonstrate that treatment gains were maintained in the long term, with rates of stuttering similar to the 1-year postoutcomes. There were no significant differences among the 3 treatments in long-term effectiveness. This controlled study substantiates the claim that the treatments investigated will more than likely have substantial long-term benefits for the fluency and personality of children and adolescents who stutter.

Adolescent↗
PubMed1998

Incorporation of mouse neural progenitors transplanted into the rat embryonic forebrain is developmentally regulated and dependent on regional and adhesive properties.

During development, telencephalic neural progenitors acquire positional specification and give rise to distinct structures such as the striatum and cortex. Here, we examine, in vivo, the influence of developmental stage, cell-surface molecules and regional differences along the dorso-ventral and antero-posterior axes on the selective incorporation of neural progenitors derived from different regions of the developing brain, utilizing a cross-species in utero transplantation paradigm. Striatal progenitors derived from the embryonic day (E) 12-14 mouse lateral ganglionic eminence (LGE) were observed consistently to incorporate into the developing striatum as early as 24-48 h following intraventricular injection into the E15-17 rat host. By removing cell-surface molecules from the LGE progenitors, the pattern of incorporation was remarkably different with no preferential striatal incorporation. Cortical progenitors with intact cell-surface molecules, by contrast, displayed little telencephalic (including striatal) incorporation as compared with precursors from the LGE. However, both progenitors from cortex and LGE incorporated widely into diencephalic and mesencephalic structures. The capacity for integration of precursors derived from the LGE and cortex gradually decreased during development of the host and was minimal in the postnatal day (P) 1 host. Unlike the telencephalic precursors, the vast majority of progenitors derived from the midbrain and cerebellar primordium (with cell-surface molecules intact) incorporated into diencephalic and midbrain nuclei with only a few cells observed in the telencephalon. These results demonstrate that incorporation of neural progenitors across the ventricular wall in the embryonic host is strictly developmentally regulated, dependent on their position along the antero-posterior axes and in the case of progenitors from the LGE is mediated by cell-surface molecules expressed on the transplanted cells.

Animals↗
PubMed1998

Beta-adrenergic blockade accelerates conversion of postoperative supraventricular tachyarrhythmias.

BACKGROUND: Postoperative supraventricular tachyarrhythmia is a common complication of surgery. Because chemical cardioversion is often ineffective, ventricular rate control remains a principal goal of therapy. The authors hypothesized that patients with supraventricular tachyarrhythmia after major noncardiac surgery who receive intravenous beta-adrenergic blockade for ventricular rate control would experience conversion to sinus rhythm at a rate that differs from those receiving intravenous calcium channel blockade. METHODS: The rate of conversion to sinus rhythm at 2 and 12 h after treatment was examined in 64 cases of postoperative supraventricular tachyarrhythmia. After adenosine administration, patients who remained in supraventricular tachyarrhythmia were prospectively randomized to receive either intravenous diltiazem or intravenous esmolol for ventricular rate control (unblinded). Loading and infusion rates were adjusted to achieve equivalent degrees of ventricular rate control. RESULTS: Patients were similar with regard to age and Apache III score. Most patients in both groups had atrial fibrillation (esmolol, 79%; diltiazem, 81%), and none experienced stable conversion with adenosine. Patients randomized to receive esmolol experienced a 59% rate of conversion to sinus rhythm within 2 h of treatment, compared with only 33% for patients randomized to receive diltiazem (intention to treat, P = 0.049; odds ratio, 2.9; 95% confidence interval, 1.046 to 7.8). After 12 h of therapy, the number of patients converting to sinus rhythm increased in both groups (esmolol, 85%; diltiazem, 62%), and the rates of conversion no longer differed significantly. Ventricular rates when supraventricular tachyarrhythmia began and after 2 and 12 h of rate control therapy were similar in the two treatment groups. The in-hospital mortality rate and length of stay in the intensive care unit were not significantly influenced by treatment group. CONCLUSIONS: Among adenosine-resistant patients in the intensive care unit with atrial fibrillation after noncardiac surgery, intravenous esmolol produced a more rapid (2-h) conversion to sinus rhythm than did intravenous diltiazem.

Adrenergic beta-Antagonists↗
PubMed1998

The role of compositionality in standardized problem list generation.

Compositionality is the ability of a Vocabulary System to record non-atomic strings. In this manuscript we define the types of composition, which can occur. We will then propose methods for both server based and client-based composition. We will differentiate the terms Pre-Coordination, Post-Coordination, and User-Directed Coordination. A simple grammar for the recording of terms with concept level identification will be presented, with examples from the Unified Medical Language System's (UMLS) Metathesaurus. We present an implementation of a Window's NT based client application and a remote Internet Based Vocabulary Server, which makes use of this method of compositionality. Finally we will suggest a research agenda which we believe is necessary to move forward toward a more complete understanding of compositionality. This work has the promise of paving the way toward a robust and complete Problem List Entry Tool.

Humans↗
PubMed1997

Rate constant of muscle force redevelopment reflects cooperative activation as well as cross-bridge kinetics.

The rate of muscle force redevelopment after release-restretch protocols has previously been interpreted using a simple two-state cross-bridge cycling model with rate constants for transitions between non-force-bearing and force-bearing states, f, and between force-bearing and non-force-bearing states, g. Changes in the rate constant of force redevelopment, as with varying levels of Ca2+ activation, have traditionally been attributed to Ca(2+)-dependent f. The current work adds to this original model a state of unactivated, noncycling cross-bridges. The resulting differential equation for activated, force-bearing cross-bridges, Ncf, was Ncf = -[g+f(K/(K + 1))] Ncf+f(K/(K + 1))NT, where K is an equilibrium constant defining the distribution between cycling and noncycling cross-bridges and NT is the total number of cross-bridges. Cooperativity by which force-bearing cross-bridges participate in their own activation was introduced by making K depend on Ncf. Model results demonstrated that such cooperativity, which tends to enhance force generation at low levels of Ca2+ activation, has a counter-intuitive effect of slowing force redevelopment. These dynamic effects of cooperativity are most pronounced at low Ca2+ activation. As Ca2+ activation increases, the cooperative effects become less important to the dynamics of force redevelopment and, at the highest levels of Ca2+ activation, the dynamics of force redevelopment reflect factors other than cooperative mechanisms. These results expand on earlier interpretations of Ca2+ dependence of force redevelopment; rather than Ca(2+)-dependent f, Ca(2+)-dependent force redevelopment arises from changing expressions of cooperativity between force-bearing cross-bridges and activation.

Animals↗
PubMed1997

Glutamic acid decarboxylase gene expression in the dopamine-denervated striatum: effects of intrastriatal fetal nigral transplants or chronic apomorphine treatment.

Glutamic acid decarboxylase mRNA expression was studied in the striatum of rats subjected to a unilateral 6-hydroxydopamine lesion of the nigrostriatal dopamine projection, followed by either intrastriatal transplants of fetal nigral neurons or chronic apomorphine treatment. For in situ hybridization histochemistry, a 35S-labelled cRNA probe selective for the mRNA encoding the 67-kDa isoform of the enzyme (GAD67) was used. The results show that fetal dopaminergic grafts in the dopamine-denervated striatum restore an inhibitory control on GAD67 gene expression in the host neurons and also counteract the up-regulation of GAD67 mRNA levels induced by chronic apomorphine treatment.

Animals↗
PubMed1997

Evaluation of the acceptability of a needleless vascular-access system by nurses.

BACKGROUND: Needleless intravenous-access devices have been introduced in an effort to reduce needlestick injuries and possible transmission of blood-borne pathogens to health care workers. However, there are no data on the acceptance of these devices by nursing personnel. METHODS: A survey of nursing personnel was taken at Indiana University Medical Center after introduction of a needleless intravenous device to determine their opinion after use of the needleless device. RESULTS: The majority of the nurses (72 of 94, 70%) had a favorable overall opinion of the device. Among those with a favorable opinion, 76% (55/72) responded that reduced risk of needlestick injury was the most important reason. Among those who had a negative opinion about the needleless-device system, 32% (7/22) reported that contamination risk was their major concern. Those who were trained before device use were more likely to properly use and maintain the needleless intravenous-access system. Of 89 respondents, 75.3% (67/89) believed that the initial training was adequate; however, 43% (29/67) thought that additional training after using the device for some time would have been beneficial. CONCLUSIONS: Comprehensive education programs that include training before and after device use are necessary if new needleless intravenous-access systems are to be successfully introduced and accepted by nursing personnel.

Attitude of Health Personnel↗