Five-year prospective study of the effects of anxiety and depression in patients with coronary artery disease.

Anxiety and depression have significant and widespread effects on daily function and symptoms of patients with coronary artery disease over a 5-year period. This may partially explain why results of treadmill stress testing and angiography poorly predict the daily functioning of patients with coronary artery disease.

Molecular biology of Burkitt's lymphoma.

The diagnostic category of Burkitt's lymphoma encompasses a closely related group of aggressive B-cell tumors that includes sporadic, endemic, and human immunodeficiency virus-associated subtypes. All subtypes are characterized by chromosomal rearrangements involving the c-myc proto-oncogene that lead to its inappropriate expression. This review focuses on the roles of c-myc dysregulation and Epstein-Barr virus infection in Burkitt's lymphoma.

Delta 469 mutation in the type 3 repeat calcium binding domain of cartilage oligomeric matrix protein (COMP) disrupts calcium binding.

Cartilage oligomeric matrix protein (COMP/TSP5), a large glycoprotein found in the territorial matrix surrounding chondrocytes, is the fifth member of the thrombospondin (TSP) gene family. While the function of COMP is unknown, its importance is underscored by the finding that mutations in the highly conserved type 3 repeat domain causes two skeletal dysplasias. Pseudoachondroplasia (PSACH) and Multiple Epiphyseal Dysplasia, Fairbanks type (EDM1).

Application of motivational interviewing to prenatal smoking cessation: training and implementation issues.

Objective: Three of the Smoke-Free Families projects incorporated motivational interviewing (MI) into prenatal smoking cessation interventions. This paper describes the process involved in training healthcare providers to use MI and the issues encountered in implementing the protocols.

Design: Health care providers at all three sites attended local training workshops in which they learned to apply the basics of MI to their study protocol.

The ALS6 and ALS7 genes of Candida albicans.

ALS genes of Candida albicans encode a family of cell-surface glycoproteins that are composed of an N-terminal domain, a central domain of a tandemly repeated motif, and a relatively variable C-terminal domain. Although several ALS genes have been characterized, more ALS-like sequences are present in the C. albicans genome.

Cartilage oligomeric matrix protein is a calcium-binding protein, and a mutation in its type 3 repeats causes conformational changes.

Mutations in residues in the type 3 calcium-binding repeats and COOH-terminal globular region of cartilage oligomeric matrix protein (COMP) lead to two skeletal dysplasias, pseudoachondroplasia and multiple epiphyseal dysplasia. It has been hypothesized that these mutations cause COMP to misfold and to be retained in the endoplasmic reticulum. However, this hypothesis is not supported by previous reports that COMP, when purified in the presence of EDTA, shows no obvious difference in electron microscopic appearance in the presence or absence of calcium ions.

Confirmation of the mapping of the Camurati-Englemann locus to 19q13. 2 and refinement to a 3.2-cM region.

Camurati-Englemann syndrome (DPD1) is an autosomal dominant condition associated with progressive cortical sclerosis of the diaphyses of all the long bones. Clinical features include abnormal gait, muscle weakness and wasting, and generalized fatigue. The DPD1 gene was recently mapped to a 15.

Neurobiology of receptor-mediated lysophospholipid signaling. From the first lysophospholipid receptor to roles in nervous system function and development.

Identification of the first lysophospholipid receptor, LPA1/Vzg-1, cloned by way of neurobiological analyses on the embryonic cerebral cortex, has led to the realization and demonstration that there exist multiple, homologous LP receptors, including those encoded by a number of orphan receptor genes known as "Edg," all of which are members of the G-protein-coupled receptor (GPCR) superfamily. These receptors interact with apparent high affinity for lysophosphatidic acid (LPA) or sphingosine-1-phosphate (S1P or SPP), and are referred to based upon their functional identity as lysophospholipid receptors: LPA and LPB receptors, respectively, with the expectation that additional subgroups will be identified (i.e.

Cytoskeletal abnormalities in chondrocytes with EXT1 and EXT2 mutations.

The EXT genes are a group of putative tumor suppressor genes that previously have been shown to participate in the development of hereditary multiple exostoses (HME), HME-associated and isolated chondrosarcomas. Two HME disease genes, EXT1 and EXT2, have been identified and are expressed ubiquitously. However, the only known effect of mutations in the EXT genes is on chondrocyte function as evidenced by aberrant proliferation of chondrocytes leading to formation of bony, cartilage-capped projections (exostoses).

The cell wall architecture of Candida albicans wild-type cells and cell wall-defective mutants.

In Candida albicans wild-type cells, the beta1, 6-glucanase-extractable glycosylphosphatidylinositol (GPI)-dependent cell wall proteins (CWPs) account for about 88% of all covalently linked CWPs. Approximately 90% of these GPI-CWPs, including Als1p and Als3p, are attached via beta1,6-glucan to beta1,3-glucan. The remaining GPI-CWPs are linked through beta1,6-glucan to chitin.

8 tumor models for evaluation of p450 gene therapy in vivo.

P450 prodrug activation-based cancer gene therapy strategies have been developed and show striking effectiveness in both in vitro cell culture and preclinical antitumor animal models (1,2). In vivo tumor models play an important role in the evaluation of the therapeutic efficacy of these strategies, and complement in vitro approaches (see Chapter 7) designed to evaluate and compare different P450 genes and different P450 gene/prodrug combinations. This chapter describes methods required for in vivo tumor models and their use in evaluating the therapeutic impact of intratumoral P450 gene expression on a tumor's chemosensitivity to cancer chemotherapeutic agents.

Construction of p450-expressing tumor cell lines using retroviruses.

Studies of tumor cell lines expressing individual cytochrome P450 genes are essential for evaluation of the utility of P450 prodrug activation-based cancer gene therapy (1). P450-expressing tumor cells may also be useful to identify novel P450 gene /prodrug combinations (see Chapter 5). The evaluation of candidate P450 genes for use in prodrug activation gene therapy is greatly facilitated by the availability of P450-expressing tumor cell lines, which can be prepared by the retroviral transduction methods described in this chapter.

Selection of cytochrome p450 genes for use in prodrug activation-based cancer gene therapy.

Prodrug activation-based cancer gene therapy is a molecular strategy to improve the efficacy of cancer chemotherapy by conferring upon tumor cells the capability to metabolize specific anticancer prodrugs into lethal intracellular toxins. The overall goal of this strategy is to increase the generation of cytotoxic drug metabolites locally, at their site of action within the tumor. This therapy can provide for an increase in drug efficacy and potentially also a reduction in host toxicity, which may be achieved by a lowering of the therapeutically effective drug dosage, thereby reducing the need to expose host tissues to high cytotoxic plasma drug concentrations.

Lack of IRF-1 expression in acute promyelocytic leukemia and in a subset of acute myeloid leukemias with del(5)(q31).

One allele of interferon regulatory factor-1 (IRF-1), a transcriptional activator of genes critical for growth suppression, differentiation, and apoptosis, is usually deleted in acute myeloid leukemias (AML) and myelodysplasias (MDS) with deletion of chromosome 5q31. Accelerated exon skipping of IRF-1, resulting in transcripts lacking a translation initiation site, has been hypothesized as a means of functional inactivation of IRF-1 in AML/MDS. To test this hypothesis, we developed quantitative competitive RT-PCR assays to measure levels of full length and exon-skipped IRF-1 transcripts and measured IRF-1 proteins by Western blotting in a series of 45 samples of AML (13: -5/del5(q); 11: t(15;17); 7: t(8;21); and 7: inv(16)), normal blood and marrow, and myeloid cell lines.

Nonsyndromic cleft lip and palate is not associated with cancer or other birth defects.

Nonsyndromic cleft lip with or without cleft palate (NSCLP) is one of the most common human malformations with an average prevalence of 1 in 1,000 live births. The cause(s) of NSCLP remain unclear as the relative roles of genes, of the environment, and/or of chance alone are unknown. The purpose of this study was to evaluate the potential role of environmental factors in the cause of NSCLP, to determine if other birth defects aggregate in families with at least one individual affected with NSCLP, and to investigate the frequency of cancer in the first- and second-degree relatives of NSCLP index-cases.

CBFA1 mutation analysis and functional correlation with phenotypic variability in cleidocranial dysplasia.

Cleidocranial dysplasia (CCD) is a dominantly inherited skeletal dysplasia caused by mutations in the osteoblast-specific transcription factor CBFA1. To correlate CBFA1 mutations in different functional domains with the CCD clinical spectrum, we studied 26 independent cases of CCD and a total of 16 new mutations were identified in 17 families. The majority of mutations were de novo missense mutations that affected conserved residues in the runt domain and completely abolished both DNA binding and transactivation of a reporter gene.

Three oral formulations of methadone. A clinical and pharmacodynamic comparison.

This study was done to determine whether there were any differences in subjective symptoms of opiate withdrawal or methadone pharmacodynamics among patients as they were switched between three different oral formulations of methadone. Patients enrolled in a three-way double-blind crossover trial of three methadone formulations. Subjective symptoms and pharmacodynamic measures were assessed throughout the study period.

Has asthma medication use in children become more frequent, more appropriate, or both?

Objective: Despite national initiatives to improve asthma medical treatment, the appropriateness of physician prescribing for children with asthma remains unknown. This study measures trends and recent patterns in the pediatric use of medications approved for reversible obstructive airway disease (asthma medications).

Design: Population-based longitudinal and cross-sectional analyses.

Detection of Als proteins on the cell wall of Candida albicans in murine tissues.

A murine model of disseminated candidiasis was utilized to determine whether Candida albicans Als proteins are produced in vivo. The kidneys, spleen, heart, liver, and lungs were collected from mice inoculated with one of three C. albicans strains (SC5314, B311, or WO-1).

Identification of nine novel mutations in cartilage oligomeric matrix protein in patients with pseudoachondroplasia and multiple epiphyseal dysplasia.

Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (EDM1) are allelic disorders caused by mutations in the gene encoding cartilage oligomeric matrix protein (COMP). PSACH is a dominant condition characterized by disproportionate short stature, joint laxity, and early-onset osteoarthritis. EDM1 is a less severe skeletal dysplasia associated with average to mild short stature, joint pain, and early-onset osteoarthritis.

Expression of the heparan sulfate proteoglycan, perlecan, during mouse embryogenesis and perlecan chondrogenic activity in vitro.

Expression of the basement membrane heparan sulfate proteoglycan (HSPG), perlecan (Pln), mRNA, and protein has been examined during murine development. Both Pln mRNA and protein are highly expressed in cartilaginous regions of developing mouse embryos, but not in areas of membranous bone formation. Initially detected at low levels in precartilaginous areas of d 12.

Cytochrome P450-based cancer gene therapy: recent advances and future prospects.

Cytochrome P450-based cancer gene therapy is a novel prodrug activation strategy for cancer treatment that has substantial potential for improving the safety and efficacy of cancer chemotherapeutics. The primary goal of this strategy is to selectively increase tumor cell exposure to cytotoxic drug metabolites generated locally by a prodrug-activating P450 enzyme. This strategy has been exemplified for the alkylating agents cyclophosphamide and ifosfamide, which are bioactivated by select P450 enzymes whose expression is generally high in liver and deficient in tumor cells.

Genomic characterization of human DSPG3.

DSPG3, the human homolog to chick PG-Lb, is a mejrkp6of the small leucine-rich repeat proteoglycan (SLRP) family, including decorin, biglycan, fibromodulin, and lumican. In contrast to the tissue distribution of the other SLRPs, DSPG3 is predominantly expressed in cartilage. In this study, we have determined that the human DSPG3 gene is composed of seven exons: Exon 2 of DSPG3 includes the start codon, exons 4-7 code for the leucine-rich repeats, exons 3 and 7 contain the potential glycosaminoglycan attachment sites, and exon 7 contains the potential N-glycosylation sites and the stop codon.