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Biomedical subjects

A Peterson

Publications and source records attributed to A Peterson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Elevated intracellular calcium levels in cerebellar granule neurons of weaver mice.

Weaver mice carry a mutation in the pore domain of the Girk2 (Kcnj6) gene. The mutation causes GIRK2 containing channels to lose ion selectivity and to become constitutively active. It is not known how this alteration in ion channel activity causes in cerebellar granule cells the defects in neurite extension, cell migration and induction of cell death that are characteristic of weaver mice. One possibility is that the mutation causes an inability to regulate intracellular calcium levels properly. We tested this hypothesis by measuring intracellular calcium levels in granule cells and Purkinje cells in slices from the cerebellum of weaver mice. We report here that weaver mice have increases in resting calcium levels in their granule cells, which may account for the multiple effects of the weaver mutation upon these cells.

Animals↗
PubMed1998

Myelin associated glycoprotein modulates glia-axon contact in vivo.

Myelin-associated glycoprotein (MAG) was postulated to play an important role in myelination. However, we showed previously that MAG null mutants exhibited no gross abnormality in myelination. Ultrastructural studies revealed subtle alterations in periaxonal organisation, indicating a restricted structural role for MAG in the formation and maintenance of periaxonal structures (Li et al., 1994). Here we show that myelination in MAG deficient mice is not as finely controlled as it is in wild type mice. The abnormalities manifest themselves as a decrease in the proportion of myelinated axons and a reciprocal increase in the proportion of unmyelinated axons in mutants' optic nerves. In addition, dysregulated myelination is occasionally observed in the form of multiply myelinated fibres, grouping of myelinated axons and myelin debris by a large myelin sheath, redundant myelin loops and, very rarely, massive myelin surrounding relatively small axons. Thus, in the absence of MAG, some glial cells seem unable to determine when, where and how much myelin should be laid down. These data support the notion of MAG being a glial recognition/adhesion molecule. A model is proposed regarding the roles MAG could play in the formation and maintenance of myelin structure.

Animals↗
PubMed1998

Interferon-gamma in progression to chronic demyelination and neurological deficit following acute EAE.

The cytokine interferon-gamma (IFNgamma) is implicated in the induction of acute CNS inflammation, but it is less clear what role if any IFNgamma plays in progression to chronic demyelination and neurological deficit. To address this issue, we have expressed IFNgamma in myelinating oligodendrocytes of transgenic mice. MHC I immunostaining and iNOS mRNA were upregulated in their CNS, but such transgenic mice showed no spontaneous CNS inflammation or demyelination, and the incidence, severity, and histopathology of experimental autoimmune encephalomyelitis (EAE) were similar to nontransgenic controls. In contrast to control mice, which remit from EAE with resolution of glial reactivity and leukocytic infiltration, transgenics showed chronic neurological deficits. While activated microglia/macrophages persisted in demyelinating lesions for over 100 days, CD4(+) T lymphocytes were no longer present in CNS. IFNgamma therefore may play a role in chronic demyelination and long-term disability following the induction of demyelinating disease. Because IFNgamma may have neural as well as immune-infiltrating origins, these findings generate a new perspective on its role in the CNS.

Animals↗
PubMed1998

The effect of WIC participation on small-for-gestational-age births: Michigan, 1992.

OBJECTIVE: This study examined the relationship between enrollment in the Special Supplemental Nutrition Program for women, Infants, and Children (WIC) and delivery of small-for-gestational-age infants. METHODS: WIC records were linked with birth certificates for 1992 full-term births; 41,234 WIC records and 18,34 non-WIC records were identified. Length of participation was defined by gestational age at enrollment. Logistic regression was used to examine the association between WIC participation and small-for-gestational-age births. RESULTS: Odds ratios for small-for-gestational-age birth decreased with increasing length of enrollment in WIC. CONCLUSIONS: Enrollment in WIC is associated with a lower prevalence of small-for-gestational-age deliveries.

Adolescent↗
PubMed1997

Selective degeneration fo Purkinje cells with Lewy body-like inclusions in aged NFHLACZ transgenic mice.

Transgenic (NFHLacZ) mice expressing a fusion protein composed of a truncated high-molecular-weight mouse neurofilament (NF) protein (NFH) fused to beta-galactosidase (LacZ) develop inclusions in neurons throughout the CNS. These inclusions persist from birth to advanced age and contain massive filamentous aggregates including all three endogenous NF proteins and the NFHLacZ fusion protein. Further, the levels of endogenous NF proteins are selectively reduced in NFHLacZ mice. Because these inclusions resemble NF-rich Lewy bodies (LBs) in Parkinson's disease and LB dementia, we asked whether these lesions compromised the viability of affected neurons during aging. We studied hippocampal CA1 neurons, nearly all of which harbored inclusions (type I) devoid of cellular organelles, and cerebellar Purkinje cells, nearly all of which accumulated inclusions (type II) containing numerous entrapped organelles. Purkinje cells with type II inclusions began to degenerate in the NFHLacZ mice at approximately 1 year of age, and most were eliminated by 18 months of age. In contrast, there was no significant loss of type I inclusion-bearing CA1 neurons with age. These data suggest that the sequestration of cellular organelles in type II inclusions may isolate and impair the function of these organelles, thereby rendering Purkinje cells selectively vulnerable to degeneration with age as in neurodegenerative diseases of the elderly characterized by accumulation of LBs.

Aging↗
PubMed1997

The motor neuron degeneration (mnd) gene acts intrinsically in motor neurons and peripheral fibroblasts.

In motor neuron degeneration (mnd/mnd) mice, multiple cell types develop cytopathology and motor neurons degenerate prematurely. Here, to investigate whether the expression of mnd within affected cells is responsible, we analyzed the evolution of cellular pathology in aggregation chimeras containing cells of both mnd/mnd and +/+ genotypes. In addition, skin fibroblasts were maintained in vitro in the absence of other cell types and examined for their disease manifestation. In the chimeras, neuronal genotype was identified by expression of an unrelated transgene. Consistent with an intrinsic action of mnd, the genotype and phenotype of motor neurons correlated perfectly. In addition, abnormal lipopigment accumulation, signifying the disease phenotype, evolved in the cultured fibroblasts. We conclude that neurons and fibroblasts develop pathological abnormalities in response to intrinsic expression of the mnd mutation. Further, as cellular pathology is not attenuated in the chimeric environment, it is unlikely that mnd and its human counterparts, neuronal caroid lipofuscinoses, will be responsive to a treatment strategy involving transplantation of normal cells.

Animals↗
PubMed1997

Patient evaluation. Laboratory and imaging studies.

The evaluation of urolithiases, in terms of calculus detection and evaluation of the morphology and function of the kidneys, continues to be refined with advances in imaging technology. The most significant recent advance is use of helical or spiral CT scan for the accurate delineation of renal and ureteral calculi in the acute setting. This may provide an accurate, rapid, and cost-effective method of patient evaluation. The alternative approach is to use plain abdominal radiography to detect renal or ureteral calculi. Noncontrast-enhanced helical or spiral CT scanning has its greatest impact in patients with negative abdominal radiographs or in those patients with suspected urinary colic in whom renal but not ureteral calculi are seen. A supplemental intravenous urogram can be used, as appropriate, to evaluate renal function and degree of obstruction on both the involved and uninvolved side. Combined abdominal radiography and sonography may be used for calculus detection and demonstration of obstruction. Sonography is an operator-dependent technique requiring expertise, experience, and adequate imaging equipment for satisfactory results. Physiologic study of renal blood flow and urinary dynamics using Doppler techniques are possible, though considered to be in the realm of clinical investigation at this time. Sonography has a valuable role in the serial evaluation of chronic stone formers with a history of recurrent urinary infections related to obstruction or reflux. Radiography, fluoroscopy, and sonography are the imaging, methods used in ESWL treatment in preprocedure and postprocedure.

Humans↗
PubMed1996

A complete genome screen for genes predisposing to severe bipolar disorder in two Costa Rican pedigrees.

Bipolar mood disorder (BP) is a debilitating syndrome characterized by episodes of mania and depression. We designed a multistage study to detect all major loci predisposing to severe BP (termed BP-I) in two pedigrees drawn from the Central Valley of Costa Rica, where the population is largely descended from a few founders in the 16th-18th centuries. We considered only individuals with BP-I as affected and screened the genome for linkage with 473 microsatellite markers. We used a model for linkage analysis that incorporated a high phenocopy rate and a conservative estimate of penetrance. Our goal in this study was not to establish definitive linkage but rather to detect all regions possibly harboring major genes for BP-I in these pedigrees. To facilitate this aim, we evaluated the degree to which markers that were informative in our data set provided coverage of each genome region; we estimate that at least 94% of the genome has been covered, at a predesignated threshold determined through prior linkage simulation analyses. We report here the results of our genome screen for BP-I loci and indicate several regions that merit further study, including segments in 18q, 18p, and 11p, in which suggestive lod scores were observed for two or more contiguous markers. Isolated lod scores that exceeded our thresholds in one or both families also occurred on chromosomes 1, 2, 3, 4, 5, 7, 13, 15, 16, and 17. Interesting regions highlighted in this genome screen will be followed up using linkage disequilibrium (LD) methods.

Bipolar Disorder↗
PubMed1995

Influence of hepatic artery occlusion and desferrioxamine on liver-tumour growth.

The mechanisms behind tumour regression during ischaemic therapy of liver malignancy are not thoroughly elucidated. Ischaemia-reperfusion injury and release of free radicals is one mechanism suggested. The aim of the present study was to explore whether inhibition of hydroxyl radicals, by complex binding Fe with desferrioxamine (DFO), counteracted the retardation in tumour growth rate after HAL and whether DFO in itself had an effect on tumour growth in 2 experimental rat liver tumours. Rats with a hepatoma or an adenocarcinoma were subjected to HAL or to a sham procedure with or without additional injections of DFO daily for 2 or 7 days. HAL had an inhibitory effect on tumour growth rate. The effect of HAL was not counteracted by DFO, while DFO alone caused a decrease in tumour volume. There was an additive effect of DFO and HAL on tumour growth rate in both tumour systems. In vitro there was a growth inhibitory effect of DFO in both tumours, more pronounced in the hepatoma than in the adenocarcinoma. Our findings indicate that the effect of HAL is not mediated by release of oxygen free radicals. In the adenocarcinoma system, an additive effect of DFO and HAL was seen. As a rate-limiting enzyme for DNA synthesis is dependent on iron, depletion of iron can decrease mitotic activity, a mechanism that could explain the effect of DFO on tumour growth.

Adenocarcinoma↗
PubMed1995

Sodium-dependent glutamate uptake as an activator of oxidative metabolism in primary astrocyte cultures from newborn rat.

In the present report we describe the effect of glutamate on respiratory activity in primary cultures of astrocytes, derived from cerebral cortex of newborn rat. Glutamate (100 microM) caused an increased oxygen consumption. This effect could not be inhibited by antagonists to the NMDA or AMPA/kainate receptors. Neither trans-ACPD (an agonist to the metabotropic glutamate receptor) nor the Krebs cycle intermediate alpha-ketoglutarate had any effect on the respiratory rate. An uncontrolled influx of Na+, caused by gramicidin, could mimic the glutamate effect on respiratory activity. In addition, the glutamate effect was abolished by addition of ouabain or replacement of Na+ by Li+ in the perfusion buffer. We conclude that the co-transport of Na+, in the Na(+)-dependent high-affinity glutamate uptake system, mediated the glutamate-induced increase in oxygen consumption through an increased activity of Na+/K(+)-ATPases.

Animals↗
PubMed1995

Retinol-binding protein mediates uptake of retinol to cultured human keratinocytes.

Retinol (vitamin A) circulates in the blood bound to retinol-binding protein (RBP). The process by which target cells acquire retinol is not fully elucidated, although a cell surface receptor for RBP has recently been identified. We show here that retinol is at least an order of magnitude more efficient at blocking the terminal differentiation of cultured normal human keratinocytes when administered as a complex with RBP than when administered free in solution. This inhibition of differentiation by RBP can be reversed by monoclonal antibody P142, reactive toward the RBP-binding membrane protein p63. These results demonstrate, at least in this in vitro system, the importance of the RBP receptor in the generation of a cellular response to retinol.

Cell Differentiation↗
PubMed1995

Accelerated and widespread neuronal loss occurs in motor neuron degeneration (mnd) mice expressing a neurofilament-disrupting transgene.

To examine the effects of multiple stressors on the onset and specificity of a neurodegenerative disease, we derived mnd/mnd mice expressing a neurofilament-H/lacZ transgene. The mnd mutation causes adult-onset motor dysfunction, and produces abnormal ubiquitous accumulation of autofluorescent lipopigment, with retinal degeneration and late-onset motor neuron degeneration. The neurofilament H-beta-galactosidase fusion protein causes endogenous neurofilament subunits to precipitate in perikarya, but shows neither significant neuronal degeneration nor behavioral changes until advanced age. In mnd/mnd-transgenic animals, neurological symptoms, lipopigment accumulation, and motor neuron loss were substantially accelerated. Newly vulnerable populations of neurons also degenerated, including cerebellar Purkinje cells and dorsal roots. This study exemplifies a synergistic interaction between a neuron-specific and a ubiquitous defect, leading to significant neurological consequences. It further indicates that cytoskeletal abnormalities similar to those observed in late-onset human neurodegenerative disorders can interact with other cellular defects and contribute to pathogenesis.

Animals↗
PubMed1995

T-brain-1: a homolog of Brachyury whose expression defines molecularly distinct domains within the cerebral cortex.

The mechanisms that regulate regional specification and evolution of the cerebral cortex are obscure. To this end, we have identified and characterized a novel murine and human gene encoding a putative transcription factor related to the Brachyury (T) gene that is expressed only in postmitotic cells. T-brain-1 (Tbr-1) mRNA is largely restricted to the cerebral cortex, where during embryogenesis it distinguishes domains that we propose may give rise to paleocortex, limbic cortex, and neocortex. Tbr-1 and Id-2 expression in the neocortex have discontinuities that define molecularly distinct neocortical areas. Tbr-1 expression is analyzed in the context of the prosomeric model. Topological maps are proposed for the organization of the dorsal telencephalon.

Amino Acid Sequence↗
PubMed1995

Use of primary cultures and continuous cell lines to study effects on astrocytic regulatory functions.

1. Current opinions on the mechanisms for glutamate-mediated neurotoxicity are reviewed. The protective role of astrocytic high-affinity glutamate transport is also discussed. 2. Low-density seeding of primary astrocytes from rat hemispheres was found to result in the development of reactive-like astrocytes. Typical glial signs of amyotrophic lateral sclerosis (ALS) could not be induced in astrocyte cultures by serum from ALS-patients. 3. Glutamate (100 mumol/L) was found to induce an increase in respiratory activity in primary cultures of astrocytes. This stimulation appeared to be related to the co-transport of Na2+ with glutamate and a resulting activation of Na2+/K(+)-ATPase. Both basal respiration and glutamate-stimulated oxygen consumption was inhibited by organic solvents. 4. Preliminary results show that heavy metals cause an increase in the mitochondrial DNA content at concentrations that have no effect on growth rate or morphology in a glial cell line. This increase was accompanied by an inhibition of oxygen consumption and an increased production of lactate at unaltered ATP levels.

Amyotrophic Lateral Sclerosis↗