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Biomedical subjects

C Walsh

Publications and source records attributed to C Walsh.

At least 19 recordsLinked to original sources
PubMed1996

Chronic arterial responses to stent implantation: a serial intravascular ultrasound analysis of Palmaz-Schatz stents in native coronary arteries.

OBJECTIVES: We used intravascular ultrasound (IVUS) imaging to evaluate the chronic vessel responses to Palmaz-Schatz stents. BACKGROUND: Palmaz-Schatz stents have been shown to inhibit early elastic recoil and late arterial remodeling while triggering neointimal hyperplasia. However, changes occurring in native vessels surrounding stent struts have not been well studied. METHODS: Postintervention and follow-up (mean [+/-SD] 5.4 +/- 3.8 months) serial IVUS imaging was performed in 25 stents without restenosis and 24 with in-stent restenosis. Intravascular ultrasound imaging using automatic transducer pullback at 0.5 mm/s allowed measurement at 1-mm axial increments of external elastic membrane (EEM), stent and lumen cross-sectional areas (CSAs) and calculation of peristent plaque plus media (P + M = EEM - stent) CSA, intrastent plaque (stent-lumen) CSA, arterial remodeling (delta EEM CSA), tissue growth outside the stent (delta P + M CSA) and tissue growth within the stent (delta stent-lumen CSA). Volumes were calculated using the Simpson rule. RESULTS: Mean EEM CSA increased significantly from 16.9 +/- 5.0 mm2 after intervention to 18.4 +/- 4.9 mm2 at follow-up (p < 0.0001), reflecting an increase in P + M CSA surrounding the stent (1.6 +/- 1.3 mm2). Greater tissue growth within the stent (2.4 +/- 2.2 mm2) correlated weakly, but directly with tissue growth surrounding the stent (r = 0.356, p = 0.0121). The ratio of peristent/intrastent tissue growth correlated weakly with arterial remodeling (r = 0.282, p = 0.0525). Restenotic stents had more tissue growth both within and surrounding the stent than did nonrestenotic stents. Volumetric measurements, which could be obtained in 15 lesions, showed similar results. CONCLUSIONS: After implantation there is a chronic increase in plaque mass both within and surrounding the stents. The increase in peristent plaque mass is associated with adaptive remodeling.

Aged↗
PubMed1996

Analysis of polyglutamine-coding repeats in the TATA-binding protein in different human populations and in patients with schizophrenia and bipolar affective disorder.

A new class of disease (including Huntington disease, Kennedy disease, and spinocerebellar ataxias types 1 and 3) results from abnormal expansions of CAG trinucleotides in the coding regions of genes. In all of these diseases the CAG repeats are thought to be translated into polyglutamine tracts. There is accumulating evidence arguing for CAG trinucleotide expansions as one of the causative disease mutations in schizophrenia and bipolar affective disorder. We and others believe that the TATA-binding protein (TBP) is an important candidate to investigate in these diseases as it contains a highly polymorphic stretch of glutamine codons, which are close to the threshold length where the polyglutamine tracts start to be associated with disease. Thus, we examined the lengths of this polyglutamine repeat in normal unrelated East Anglians, South African Blacks, sub-Saharan Africans mainly from Nigeria, and Asian Indians. We also examined 43 bipolar affective disorder patients and 65 schizophrenic patients. The range of polyglutamine tractlengths that we found in humans was from 26-42 codons. No patients with bipolar affective disorder and schizophrenia had abnormal expansions at this locus.

Africa↗
PubMed1996

Analysis of thirteen trinucleotide repeat loci as candidate genes for schizophrenia and bipolar affective disorder.

A group of diseases are due to abnormal expansions of trinucleotide repeats. These diseases all affect the nervous system. In addition, they manifest the phenomenon of anticipation, in which the disease tends to present at an earlier age or with greater severity in successive generations. Many additional genes with trinucleotide repeats are believed to be expressed in the human brain. As anticipation has been reported in schizophrenia and bipolar affective disorder, we have examined allele distributions of 13 trinucleotide repeat-containing genes, many novel and all expressed in the brain, in genomic DNA from schizophrenic (n = 20-97) and bipolar affective disorder patients (23-30) and controls (n = 43-146). No evidence was obtained to implicate expanded alleles in these 13 genes as causal factors in these diseases.

Base Sequence↗
PubMed1996

Evaluation of a HIV/AIDS education program for adolescents.

The adolescent population has recently been recognized as one of the groups at risk for human immunodeficiency virus (HIV) infection. Statistics are beginning to document the extent of this trend. This study is aimed at determining adolescent sexual behaviors and the efficacy of a medical student-run acquired immune deficiency syndrome (AIDS) education program. Medical students taught 2,169 high school students in the St. Louis area with a pre- and post- intervention questionnaire administered to record levels of HIV/AIDS knowledge and sexual practices. Data revealed that 56.4% of the respondents were sexually active with 70.4% having multiple partners and 61.0% admitting to unprotected sex. These students demonstrated a significant increase in their knowledge about HIV infection after the educational program. The results show that, adolescents are sexually active and more importantly, they are practicing behaviors that put them at risk for HIV/AIDS, a risk which they recognize. Finally, the educational intervention did increase students' knowledge of HIV/AIDS. This may not translate into a change in behaviors, but it is a first step.

Adolescent↗
PubMed1996

cDNA cloning of a human homologue of the Caenorhabditis elegans cell fate-determining gene mab-21: expression, chromosomal localization and analysis of a highly polymorphic (CAG)n trinucleotide repeat.

The two most consistent features of the diseases caused by trinucleotide repeat expansion-neuropsychiatric symptoms and the phenomenon of genetic anticipation-may be present in forms of dementia, hereditary ataxia, Parkinsonism, bipolar affective disorder, schizophrenia and autism. To identify candidate genes for these disorders, we have screened human brain cDNA libraries for the presence of gene fragments containing polymorphic trinucleotide repeats. Here we report the cDNA cloning of CAGR1, originally detected in a retinal cDNA library. The 2743 bp cDNA contains a 1077 bp open reading frame encoding 359 amino acids. This amino acid sequence is homologous (56% amino acid identify and 81% amino acid conservation) to the Caenorhabditis elegans cell fate-determining protein mab-21. CAGR1 is expressed in several human tissues, most prominently in the cerebellum, as a message of approximately 3.0 kb. The gene was mapped to 13q13, just telomeric to D13S220. A 5'-untranslated CAG trinucleotide repeat is highly polymorphic, with repeat length ranging from six to 31 triplets and a heterozygosity of 87-88% in 684 chromosomes from several human populations. One allele from an individual with an atypical movement disorder and bipolar affective disorder type II contains 46 triplets, 15 triplets longer than any other allele detected. Though insufficient data are available to link the long repeat to this clinical phenotype, an expansion mutation of the CAGR1 repeat can be considered a candidate for the etiology of disorders with anticipation or developmental abnormalities, and particularly any such disorders linked to chromosome 13.

Amino Acid Sequence↗
PubMed1996

Genetic association between monoamine oxidase A microsatellite and RFLP alleles and bipolar affective disorder: analysis and meta-analysis.

The monoamine oxidase A locus (MAOA) at Xp11 was considered a good candidate to investigate in bipolar affective disorder since this enzyme plays an important role in the degradation of various neurotransmitters and a mutation in this gene has been associated with borderline mental retardation and a behavioural phenotype that has some resemblance to the manic syndrome. Previous association studies comparing allele frequencies of a microsatellite and RFLP at the monoamine oxidase A locus in bipolar affective disorder cases and controls in the UK have yielded conflicting results: Lim and colleagues reported a positive association, while no evidence for allelic association was obtained by Cradock and co-workers. A significant allelic association was observed between Japanese bipolar cases and controls at the MAOA microsatellite but different alleles seemed to be overrepresented in the bipolar cases in this population compared to the UK. In order to resolve these differences, we have examined this locus in our series of unrelated bipolar cases and age- and sex-matched controls and found significantly different MAOA microsatellite allele frequencies. In addition, we have pooled the data from the two previous UK studies with ours to create a total data set including 67 males and 113 females with bipolar affective disorder and a similar number of matched controls. No evidence for heterogeneity was observed for the control MAOA microsatellite or RFLP allele frequencies in these three studies. However, we found a significant difference between the pooled normal and bipolar allele frequencies both for the microsatellite and the RFLP at MAOA.

Alleles↗
PubMed1996

Linkage analysis of the fragile X gene FMR-1 and schizophrenia: no evidence for linkage but report of a family with schizophrenia and an unstable triplet repeat.

We have examined 23 families multiply affected with schizophrenia for linkage to the FMR-1 gene on the X chromosome. Alleles at the FMR-1 CGG triplet repeat were analysed by the polymerase chain reaction, and methylation status at the FMR-1 locus in individuals with evidence of expanded or unstable repeats was analysed by Southern hybridization. Two-point LOD score analyses with a range of X-linked single gene models and a non-parametric affected sib-pair method revealed no evidence for linkage. In one family, however, a fragile X premutation was found, and one individual with schizophrenia and developmental delay was a mosaic for the full and premutation. We conclude that although mutations within the FMR-1 gene do not have a major aetiological role in schizophrenia in our collection of pedigrees, it is possible that FMR-1 mutations can modify the clinical phenotype of schizophrenia.

Adolescent↗
PubMed1995

Effects of a cAMP analogue simulate the distinct components of long-term potentiation in CA1 region of rat hippocampus.

Bath application of the cAMP analogue, dibutyryl cyclic adenosine 3',5'-monophosphate (dibutyryl cyclic AMP; dbcAMP) to rat hippocampal slices was found to potentiate both the CA1 population spike and population excitatory post-synaptic potential (EPSP) slope. dbcAMP (500-1000 microM) was applied to slices for 30 min; following washout the population EPSP slope was potentiated for at least 30 min to a mean value of 51% above the drug-free baseline value. The population spike was similarly potentiated to a mean value of 64% above baseline after dbcAMP washout. dbcAMP-induced population EPSP slope potentiation occluded long-term potentiation (LTP) induced by high frequency electrical stimulation, and LTP occluded dbcAMP-induced EPSP slope potentiation. Earlier investigations (Pockett et al., Neuroscience, 52 (1993) 229-236) using 200 microM dbcAMP reported similar potentiation of population spike but no potentiation of EPSP slope. These experiments support the hypothesis that the two components of LTP (Bliss and Lynch, In P.W. Landfield and S.A. Deadwyler (Eds.), Long-term Potentiation: from Biophysics to Behaviour, Alan R. Liss, New York, 1988, pp. 3-72) in the CA1 area of rat hippocampus both involve distinct cAMP-dependent mechanisms.

Animals↗
PubMed1995

Paternally derived H19 is differentially expressed in malignant and nonmalignant trophoblast.

The paternal allele of the H19 gene has been shown to be transcriptionally inactive in the developing human embryo. Using reverse transcription PCR and RNase protection assays, we demonstrate that expression of H19 is predominantly, but not exclusively, from the maternal allele in the human placenta. In situ hybridization analysis shows strong expression of the H19 gene in eight complete hydatidiform moles, hyperplastic tissues consisting of trophoblasts which contain only paternally derived genetic material, indicating that H19 is not functionally imprinted in this tissue. H19, a putative growth suppressor, is oppositely imprinted to the neighboring insulin-like growth factor II (IGF2) gene and an up-regulation of IGF2 expression has been linked previously to a down-regulation of H19 expression in the progression to Wilms' tumor. Two cases of complete hydatidiform mole which progressed to choriocarcinoma show high levels of expression of both H19 and IGF2. The choriocarcinomas which developed from these complete hydatidiform moles showed similar expression of IGF2 but a decreased number of H19-positive cells, which may reflect selection for cells expressing IGF2 and against those expressing H19 in this tissue.

Alleles↗
PubMed1995

Cell lineage and patterns of migration in the developing cortex.

Knowledge of cell lineage in the cortex is important for understanding normal development as well as brain malformations. We studied cell lineage in rats by injecting a library of up to 3400 retroviruses, distinguishable by PCR analysis and encoding alkaline phosphatase, at E14-19. Histological analysis at P15 revealed normal cell morphology and allowed identification of about 80% of all labelled cells. PCR amplification of DNA tags allowed clonal analysis. Cortical cells labelled at E15 formed clustered or widespread clones with equal frequency. Clustered clones contained one to four cells within about 1 mm that had similar morphology and laminar location. However, 48% of cortical clones contained multiple cell types with widely different locations (2.1-6.7 mm; mean, 3.8 mm). Widespread clones contained two to four 'subunits' (one to five neurons each), spaced at apparent intervals of 2-3 mm, with each subunit morphologically indistinguishable from a clustered clone. Distinct subunits in the same clone usually differed in laminar location suggesting sequential formation. Clones labelled at E17 contained fewer neurons and up to two subunits. Clustered clones seem to be produced by stationary progenitors, whereas progenitors of clusters may themselves be produced by migratory, multipotential cells.

Animals↗
PubMed1995

Systematic widespread clonal organization in cerebral cortex.

Cell lineage analysis in the cortex has revealed two clonal patterns, clustered and widespread clones. To determine the relationship of these patterns, progenitor cells were infected with a retroviral library encoding alkaline phosphatase, and cortical sibling cells were identified using PCR. Clones labeled at E15 consisted of single cells or small cells clusters (52%) or of widespread cells (48%). However, widespread clones consisted of multiple neuronal or glial cell types, spaced systematically at 2-3 mm intervals. The data suggest that migratory multipotential progenitors divide asymmetrically at intervals defined by cell cycle length, producing single cells or clusters of cells in different cortical regions. Transition from multipotentiality to more restricted potential may correspond to changes in migratory behavior.

Alkaline Phosphatase↗
PubMed1995

H19 is imprinted in the choroid plexus and leptomeninges of the mouse foetus.

It has been proposed that either the Igf-2 gene or the H19 gene--but not both--can be expressed from a given chromosome. Igf-2 is known to be biallelically expressed in the choroid plexus and leptomeninges, however, raising the question of whether H19 is down-regulated or absent there. We found by in situ hybridization that H19 is indeed expressed in the choroid plexus and leptomeninges of the developing mouse foetus. Comparison with the expression pattern of Igf-2 showed that the genes are coexpressed in all areas, with the exception of the choroid plexus epithelium. To evaluate whether H19 is also biallelically expressed in these tissues, we microdissected embryos from interspecific crosses and performed RNAse protection analysis on the isolated RNA. This revealed that H19 maintains its imprint in the choroid plexus/leptomeninges, being transcribed from the maternal allele at a level comparable to that in normal liver. We discuss the significance of these results for current models of Igf-2 and H19 imprinting.

Alleles↗
PubMed1995

Predicting the one-year course of adolescent major depression.

OBJECTIVE: To identify specific clinical and social functioning variables that predict persistence of major depression over a 1-year period of follow-up. METHOD: The sample consisted of 67 adolescents with major depression, drawn from consecutive referrals to psychiatric clinics in a defined, geographic catchment area. Clinical interviews and questionnaires measuring behaviors, symptoms, and social functioning were administered to both the adolescent and a parent at inception and at follow-up. Discriminant function analyses were used to identify inception variables that predicted clinical course independent of severity of depressive symptoms and global functioning. RESULTS: At 1-year follow-up, major depression remitted in 66% of subjects. Persisters were characterized at inception as older, more likely to have substance use or anxiety disorders, less involved with fathers, and less responsive to mother's discipline compared with remitters. The effect of these prognostic factors was independent of symptom severity and global functioning. CONCLUSION: These variables appear to reflect perpetuating and ameliorating factors influencing the short-term course of major depression. The findings suggest that treatments for adolescent depression that aim to enhance parent-adolescent relationships, and that specifically target coexisting disorders, should be evaluated for effectiveness.

Adolescent↗
PubMed1995

Measurement of wall deformation and flow limitation in a mechanical trachea.

A mechanical model of the human trachea is investigated experimentally. A modified version of an earlier model, it consists of a square sectioned rigid tube in which part of one wall is removed, and replaced by a prestretched flat latex membrane. Air is drawn from atmosphere through an inlet into the rigid upstream tube; it then flows through the flexible section and finally through a rigid section into a plenum chamber where suction is applied. As the membrane collapses in response to flow, the transmural pressure and deflection are measured at the mid-point. These values are used in conjunction with a finite deformation membrane wall theory to determine the elastic constant in a nonlinear material constitutive equation. This equation is used to predict the tube law. Results show that the flow limits at the long wave speed predicted by this law. Thus it behaves as a conventional collapsible tube while having the advantage of a rational wall model.

Airway Resistance↗
PubMed1994

Recombinant adeno-associated virus-mediated gene transfer into hematopoietic progenitor cells.

Recombinant adeno-associated viruses (rAAV) containing only the inverted terminal repeats (ITR) from the wild-type virus are capable of stable integration into the host cell genome, and expression of inserted genes in cultured cells. We have now defined the ability of rAAV to introduce genes into primary hematopoietic progenitors. A vector was constructed containing the coding sequences for beta-galactosidase (beta-gal), including a nuclear localization signal, under the control of a strong viral promotor. Infectious vector particles were prepared by cotransfection of the vector plasmid with a second plasmid that contained the coding sequences for AAV proteins into adenovirus-infected human embryonic kidney cells. These vector preparations transferred and expressed the beta-gal gene in human K562 erythroleukemia and Detroit 6 cells. Positive immunoselection yielded a population of enriched CD34+ cells that were transduced with the rAAV beta-gal vector. Nuclear localized enzyme expression was documented in 60% to 70% of infected cells. Progenitor-derived colonies that developed after 2 weeks in clonogenic cultures were shown to have viral-associated DNA at an estimated copy number of 1 to 2 per cell using a semiquantitative polymerase chain reaction (PCR) method. Integration of AAV into hematopoietic progenitors was documented using wild-type virus, as its genome may integrate at a preferred site on chromosome 19. Our data suggest that rAAV will transfer and express genes in primitive hematopoietic progenitors with high frequency, and support the development of this vector system for therapeutic gene transfer.

Adenoviruses, Human↗