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Biomedical subjects

C Walsh

Publications and source records attributed to C Walsh.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1996

Community nursing issues in Maori mental health.

This paper derives from the first study of its kind to explore the issues and implications of a new role for mental health nurses at a time when the health care system in New Zealand was undergoing rapid changes and a new Mental Health (Compulsory Assessment and Treatment) Act 1992 had been implemented. This praxis research study utilized interviews and focus groups to address a range of issues in the practice of mental health nurses. This paper reports on the competing cultural perspectives in the nursing care provided to Maoris. This is an important issue for the community in bicultural New Zealand, and has clear relevance to mental health nursing in multicultural communities.

Community Health Nursing↗
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↗
PubMed1994

Reasoning in middle childhood: a dynamic model of performance on transitivity tasks.

An overview of the models and data relevant to children's transitive reasoning is provided. We propose a new conceptual framework, one which is embedded in a dynamic model that accounts for children's failures to reason transitively. It is assumed that rather than reasoning in a transitive manner, children often encode both relational and absolute stimulus information and use stimulus generalization as a transfer mechanism. The model is applied to new and extant data. The model provides an adequate and parsimonious account of children's failures on these tasks. We conclude that progress in understanding children's reasoning is dependent on operationalizing constructs in formal models so that assumptions can be evaluated and rejected.

Age Factors↗
PubMed1994

Neuropsychology of maternal behavior in the rat: c-fos expression during mother-litter interactions.

This series of studies used the pattern of nuclear Fos-like immunoreactivity (Fos-lir) to map the functional pathways in the brain that mediate the onset and retention of maternal behavior. In the first two experiments, parturient rat dams were exposed to either pups or to other stimuli on Day 1 postpartum. Dams interacting with pups were either intact or sustained ventral somatosensory, olfactory, or combined desensitizations. Results showed that 1) all intact pup-interacting dams showed elevated levels of Fos-lir in the medial preoptic area (MPOA) and the medial and cortical amygdala as compared to control groups, and 2) olfactory and ventral somatosensory desensitization, either alone or in combination, did not decrease Fos-lir in the MPOA. However, olfactory desensitizations did decrease Fos-lir in the medial amygdala and the combined desensitizations significantly reduced Fos-lir in both the basolateral and central amygdala. In the third study, dams were either exposed to pups or to other stimuli and were subsequently reexposed to pups or to pup cues. Regardless of prior maternal experience, females who were able to interact with pups upon reexposure showed increased Fos-lir in the MPOA, the basolateral and central nuclei of the amygdala, and the nucleus accumbens when compared to females which did not interact with pups. Taken together, these studies suggest that the neuroanatomy of maternal behavior is a complex one, involving multiple systems that interconnect with the MPOA and that mediate the many behavioral processes activated when an animal responds maternally.

Amygdala↗
PubMed1994

The non-viability of uniparental mouse conceptuses correlates with the loss of the products of imprinted genes.

Diploid parthenogenetic or androgenetic mouse conceptuses produce characteristic and opposite mutant phenotypes and are non-viable, presumably due to different contributions from the maternal and paternal genomes. This is likely to be the result of the preferential expression of only one parent's copy of certain genes in the offspring. So far, four such endogenous imprinted genes are known: the paternal alleles of Igf2 and Snrpn and the maternal alleles of Igf2r and H19 are active, while their opposite parental alleles are inactive. Here we demonstrate that the expression patterns of the Igf2 and Igf2r genes in androgenetic and parthenogenetic conceptuses correlate with which parental alleles normally express them, implying that the imprint can be maintained in the absence of the other parent's genome for these genes. This also indicates that both types of uniparental conceptuses are lacking developmentally important gene products. We did find, however, that the H19 gene was highly expressed not only in the parthenogenetic conceptus, but also in giant trophoblasts and secondary giant cells in the androgenetic placenta, in spite of the imprinting of the H19 gene in normal mouse extra embryonic tissues. We discuss these observations with respect to the non-viability of uniparental conceptuses and the reciprocal imprinting patterns of the Igf2 and H19 genes.

Animals↗
PubMed1994

Laparoscopic appendectomy, is it worth it?

The recent experience with open appendectomy was compared to our initial experience with laparoscopic appendectomy. Thirty-eight patients had open appendectomy for acute appendicitis. Two major and four minor complications occurred. Concurrently, 39 patients had laparoscopic appendectomy. There was one major and one minor complication. Of the laparoscopic patients, 69% received less than 24 hours of parenteral postoperative analgesia, compared to 44% of the patients in the open group. Fifteen of 39 laparoscopic patients (38%) were discharged within 24 hours of operation versus 3 of 38 (8%) in the open group. Total mean hospital cost for the laparoscopic group, $7,500, was significantly greater than for the open group, $5,700, because of increased laparoscopic equipment charges. Both open and laparoscopic appendectomy procedures were performed with minimal morbidity. The benefits of laparoscopy were earlier hospital discharge and less parenteral analgesic use, but it was significantly more expensive.

Acute Disease↗
PubMed1994

Physical and functional interactions between SH2 and SH3 domains of the Src family protein tyrosine kinase p59fyn.

The Src family protein tyrosine kinases participate in signalling through cell surface receptors that lack intrinsic tyrosine kinase domains. All nine members of this family possess adjacent Src homology (SH2 and SH3) domains, both of which are essential for repression of the enzymatic activity. The repression is mediated by binding between the SH2 domain and a C-terminal phosphotyrosine, and the SH3 domain is required for this interaction. However, the biochemical basis of functional SH2-SH3 interaction is unclear. Here, we demonstrate that when the SH2 and SH3 domains of p59fyn (Fyn) were present as adjacent domains in a single protein, binding of phosphotyrosyl peptides and proteins to the SH2 domain was enhanced, whereas binding of a subset of cellular polypeptide ligands to the SH3 domain was decreased. An interdomain communication was further revealed by occupancy with domain-specific peptide ligands: occupancy of the SH3 domain with a proline-rich peptide enhanced phosphotyrosine binding to the linked SH2 domain, and occupancy of the SH2 domain with phosphotyrosyl peptides enhanced binding of certain SH3-specific cellular polypeptides. Second, we demonstrate a direct binding between purified SH2 and SH3 domains of Fyn and Lck Src family kinases. Heterologous binding between SH2 and SH3 domains of closely related members of the Src family, namely, Fyn, Lck, and Src, was also observed. In contrast, Grb2, Crk, Abl, p85 phosphatidylinositol 3-kinase, and GTPase-activating protein SH2 domains showed lower or no binding to Fyn or Lck SH3 domains. SH2-SH3 binding did not require an intact phosphotyrosine binding pocket on the SH2 domain; however, perturbations of the SH2 domain induced by specific high-affinity phosphotyrosyl peptide binding abrogated binding of the SH3 domain. SH3-SH2 binding was observed in the presence of proline-rich peptides or when a point mutation (W119K) was introduced in the putative ligand-binding pouch of the Fyn SH3 domain, although these treatments completely abolished the binding to p85 phosphatidylinositol 3-kinase and other SH3-specific polypeptides. These biochemical SH2-SH3 interactions suggest novel mechanisms of regulating the enzymatic activity of Src kinases and their interactions with other proteins.

Amino Acid Sequence↗