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S Carpenter

Publications and source records attributed to S Carpenter.

At least 55 records · Page 3Linked to original sources
PubMed1999

Myopathy with hexagonally cross-linked tubular arrays: a new autosomal dominant or sporadic congenital myopathy.

We describe a slowly progressive myopathy with unique crystalloid inclusions in type 2 muscle fibers in a father and his son, as well as one more unrelated individual. The inclusions were strongly eosinophilic and purple by the Gomori method. They were composed of vesicular profiles, approximately 20 nm in cross-diameter, connected by radially arranged double spokes arising at 60 degrees angles. The inclusions were not related to any normal cellular organelle. Extensive immunohistochemical studies failed to reveal their chemical nature. It is suggested that this is a new congenital myopathy with characteristic intracytoplasmic inclusions, occurring sporadically or with an autosomal dominant pattern of inheritance.

Adult↗
PubMed1998

AnkyrinG is required for clustering of voltage-gated Na channels at axon initial segments and for normal action potential firing.

Voltage-gated sodium channels (NaCh) are colocalized with isoforms of the membrane-skeletal protein ankyrinG at axon initial segments, nodes of Ranvier, and postsynaptic folds of the mammalian neuromuscular junction. The role of ankyrinG in directing NaCh localization to axon initial segments was evaluated by region-specific knockout of ankyrinG in the mouse cerebellum. Mutant mice exhibited a progressive ataxia beginning around postnatal day P16 and subsequent loss of Purkinje neurons. In mutant mouse cerebella, NaCh were absent from axon initial segments of granule cell neurons, and Purkinje cells showed deficiencies in their ability to initiate action potentials and support rapid, repetitive firing. Neurofascin, a member of the L1CAM family of ankyrin-binding cell adhesion molecules, also exhibited impaired localization to initial segments of Purkinje cell neurons. These results demonstrate that ankyrinG is essential for clustering NaCh and neurofascin at axon initial segments and is required for physiological levels of sodium channel activity.

Action Potentials↗
PubMed1998

Structural requirements for association of neurofascin with ankyrin.

This paper presents the first structural analysis of the cytoplasmic domain of neurofascin, which is highly conserved among the L1CAM family of cell adhesion molecules, and describes sequence requirements for neurofascin-ankyrin interactions in living cells. The cytoplasmic domain of neurofascin dimerizes in solution, has an asymmetric shape, and exhibits a reversible temperature-dependent beta-structure. Residues Ser56-Tyr81 are necessary for ankyrin binding but do not contribute to either dimerization or formation of structure. Transfected neurofascin recruits GFP-tagged 270-kDa ankyrinG to the plasma membrane of human embryo kidney 293 cells. Deletion mutants demonstrate that the sequence Ser56-Tyr81 contains the major ankyrin-recruiting activity of neurofascin. Mutations of the FIGQY tyrosine (Y81H/A/E) greatly impair neurofascin-ankyrin interactions. Mutation of human L1 at the equivalent tyrosine (Y1229H) is responsible for certain cases of mental retardation (Van Camp, G., Fransen, E., Vits, L., Raes, G., and Willems, P. J. (1996) Hum. Mutat. 8, 391). Mutations F77A and E73Q greatly impair ankyrin binding activity, whereas mutation D74N and a triple mutation of D57N/D58N/D62N result in less loss of ankyrin binding activity. These results provide evidence for a highly specific interaction between ankyrin and neurofascin and suggest that ankyrin association with L1 is required for L1 function in humans.

Amino Acid Sequence↗
PubMed1998

Mutations in a gene encoding a novel protein tyrosine phosphatase cause progressive myoclonus epilepsy.

Lafora's disease (LD; OMIM 254780) is an autosomal recessive form of progressive myoclonus epilepsy characterized by seizures and cumulative neurological deterioration. Onset occurs during late childhood and usually results in death within ten years of the first symptoms. With few exceptions, patients follow a homogeneous clinical course despite the existence of genetic heterogeneity. Biopsy of various tissues, including brain, revealed characteristic polyglucosan inclusions called Lafora bodies, which suggested LD might be a generalized storage disease. Using a positional cloning approach, we have identified at chromosome 6q24 a novel gene, EPM2A, that encodes a protein with consensus amino acid sequence indicative of a protein tyrosine phosphatase (PTP). mRNA transcripts representing alternatively spliced forms of EPM2A were found in every tissue examined, including brain. Six distinct DNA sequence variations in EPM2A in nine families, and one homozygous microdeletion in another family, have been found to cosegregate with LD. These mutations are predicted to cause deleterious effects in the putative protein product, named laforin, resulting in LD.

Alternative Splicing↗
PubMed1998

Endotoxin treatment of equine infectious anaemia virus-infected horse macrophage cultures decreases production of infectious virus.

Lentiviruses replicate in cells of the immune system, and activation of immune cells has been shown to modulate virus replication. To determine the effects of macrophage activation on replication of equine infectious anaemia virus (EIAV), primary horse macrophage cultures (HMCs) were established from 20 different horses, infected with an avirulent strain of EIAV, and stimulated with 5 microg/ml of bacterial endotoxin. Supernatants collected from HMCs were assayed for the presence of tumour necrosis factor (TNF-alpha) and for production of infectious virus. Results indicated that EIAV replication in vitro varied significantly (P < or = 0.0001) from horse to horse, regardless of the treatment of HMCs. Also, EIAV replication was significantly (P < or = 0.0001) decreased in HMCs stimulated with bacterial endotoxin as compared to untreated HMCs. No significant correlation was found between virus replication and production of TNF-alpha following treatment of virus-infected cells with bacterial endotoxin. However, when HMCs were treated with endotoxin prior to virus infection, inhibition of EIAV replication was proportional to increasing levels of endotoxin. PCR and RT-PCR were used to amplify EIAV proviral DNA and mRNA sequences, respectively, at various time-points following infection. The results indicated that the early events of EIAV replication, up to and including transcription of multiple-spliced mRNAs, were not inhibited by treatment of EIAV-infected macrophages with bacterial endotoxin. This suggests that endotoxin treatment inhibits a posttranscriptional step in the virus replication cycle.

Animals↗
PubMed1998

Biological characterization of Rev variation in equine infectious anemia virus.

Sequence analysis identified significant variation in the second exon of equine infectious anemia virus (EIAV) rev. Functional analysis indicated that limited amino acid variation in Rev significantly altered the export activity of the protein but did not affect Rev-dependent alternative splicing. EIAV Rev can mediate export through two independent cis-acting Rev-responsive elements (RREs), and differences among Rev variants were more pronounced when both RREs were present. Variation in Rev may be an important mechanism for regulation of virus replication in vivo and may contribute to changes in clinical disease.

Alternative Splicing↗
PubMed1998

Diffuse craniospinal seeding from a benign fourth ventricle choroid plexus papilloma. Case report.

Choroid plexus papillomas can metastasize to the subarachnoid space, but extensive metastasis has only been reported when the tumors are malignant. The authors report a case of diffuse, extensive metastasis to the craniospinal leptomeninges from a benign fourth ventricular choroid plexus papilloma in an adult. This 19-year-old woman presented with a 2-year history of headache, blurred vision, diplopia, and ataxia. Magnetic resonance imaging of the brain and spinal cord revealed obstructive hydrocephalus caused by a 4-cm, partially calcified, inhomogeneously enhancing tumor of the fourth ventricle that was displacing the pons, medulla oblongata, and cerebellum. Innumerable cystic lesions of varying size were also seen in the cranial and spinal leptomeninges. Histological examination of the resected fourth ventricular tumor and of a few of the leptomeningeal lesions revealed a benign choroid plexus papilloma and leptomeningeal choroid plexus cysts. This singular case of diffuse and extensive metastasis to the craniospinal leptomeninges from a histologically benign fourth ventricular papilloma adds to the available information about the biological potential of these tumors and expands the differential diagnosis of posterior fossa lesions with subarachnoid metastasis.

Adult↗
PubMed1998

The role of oxygen in the antiviral activity of hypericin and hypocrellin.

The light-induced antiviral activity of hypericin and hypocrellin in the presence and absence of oxygen was examined under experimental conditions where the effect of oxygen depletion could be quantified. There was a significant reduction of light-induced antiviral activity of hypericin and hypocrellin under hypoxic conditions. Interestingly, antiviral activity of hypocrellin was not observed at low oxygen levels at which hypericin retained measurable virucidal activity. This suggests that additional pathways, such as the generation of protons from excited states of hypericin, may enhance the biological activity of activated oxygen species.

Adenosine Triphosphate↗
PubMed1997

Longitudinal studies of immune function in cattle experimentally infected with bovine immunodeficiency-like virus and/or bovine leukemia virus.

The effects of single or dual infection with bovine immunodeficiency-like virus (BIV) and/or, bovine leukemia virus (BLV) on bovine immune function were examined over a 4 year period. Holstein calves were infected with BIV (four calves), BLV (five calves), BIV and BLV (five calves), or sham inoculated (three calves). Lymphocyte blastogenesis to mitogens, seven tests of neutrophil function, and mononuclear cell subset analysis by flow cytometry (BoCD4, BoCD8, BoCD2, BoWC1, sIgM+, and monocytes) were performed at regular intervals to 49 months post-infection. These data were analyzed for main effects of each virus and interaction as a 2 x 2 factorial. BIV infected cattle had lower neutrophil antibody-dependent cell-mediated cytotoxicity and iodination responses during 2 of the 4 years post-infection (P < 0.05). BIV infection was not associated with any long-term significant changes in lymphocyte blastogenesis to mitogens or changes in mononuclear cell subset numbers in blood. There was a tendency for animals infected with BIV alone to have decreased lymphocyte blastogenic responses to mitogens, but this was not statistically significant. BLV infection caused an increase in total mononuclear cells with no dramatic shift in the relative proportions of the various subsets. Co-infection with BIV and BLV did not consistently cause a different response than either virus did individually. One BIV infected animal died of non-BLV lymphosarcoma 7 months after infection. All other animals had no unusual clinical signs. In summary, infection with BIV caused a significant, temporary decrease in neutrophil function with no consistent statistically significant alteration in lymphocyte blastogenesis or mononuclear cell numbers during the first 4 years after infection. BLV infection caused an increase in lymphocyte numbers, and there appeared to be no synergism between the viruses.

Animals↗
PubMed1997

Localized sequence heterogeneity in the long terminal repeats of in vivo isolates of equine infectious anemia virus.

The role of in vivo long terminal repeat (LTR) sequence variation of the lentivirus equine infectious anemia virus (EIAV) has not been explored. In this study, we investigated the heterogeneity found in the LTR sequences from seven EIAV-seropositive horses: three horses with clinical disease and four horses without any detectable signs of disease. LTR sequences were targeted in this study because the LTR U3 enhancer region of tissue culture-derived isolates has been identified as one of the few hypervariable regions of the EIAV genome. Furthermore, LTR variation may regulate EIAV expression in vivo. Both intra- and interanimal sequence variations were investigated. The intra-animal variation was low in seropositive, healthy horses (on average 0.44%). Intra-animal variation was consistently higher in clinically ill horses (0.99%), suggesting that greater numbers of quasispecies of EIAV are present when active virus replication is ongoing. Interanimal comparisons of consensus sequences generated from each horse demonstrated that the enhancer region is a hotspot of sequence variation in vivo. Thirty-seven of the 83 nucleotides that compose the U3 enhancer region were variable between the different in vivo-derived LTRs. The remainder of the LTR that was analyzed was more conserved, 8 of 195 nucleotide positions being variable. Results of electrophoretic mobility shift assays demonstrated that some nucleotide substitutions that occurred in the enhancer region eliminated or altered transcription factor binding motifs that are known to be important for EIAV LTR expression. These data suggested that the selective pressures exerted on the EIAV LTR enhancer sequences are different from those exerted on the remainder of the LTR. Our findings are consistent with the possibility that enhancer sequence hypervariability can alter expression of the virus in tissue macrophages and therefore contribute to clinical disease in infected horses.

Animals↗
PubMed1997

Compartmental analysis of the complete dynamic scan data for scintigraphic determination of effective renal plasma flow.

UNLABELLED: We have developed an image-based compartmental analysis for estimating effective renal plasma flow (ERPF in units of milliliters per minute) from the full time-activity curves of regions of interest (ROI) placed over the heart, kidneys and bladder. METHODS: Kidney or time-activity curves are corrected for physical attenuation using estimates of kidney depth derived from patient height and weight. Estimates of the calibration factors, Kp and Kb (mCl/counts/sec), for the plasma and bladder time-activity curves are determined by applying the following ROI analysis to each frame of the dynamic scan: (Kp)Pc(t) + (Kb)Bc(t) = Di - Rq(t), where P c(t) and Bc(t) represent the counting rates measured in ROI placed over the left ventricle blood pool and bladder at time t; Di is the known total injected dose, and Rq(t) represents the millicurie of tracer in the kidneys at time t. Once Kp and Kb have been determined by regression, the calibrated time activity curves are used to solve for the physiological parameter fERPF (min-1), which represents the fraction of the total body plasma cleared of mertiatide per min. The ERPF calculated by the product of fERPF and plasma volume, determined from patient weight, was compared to the ERPF as calculated by blood samples and the Schlegel and renal uptake plasma volume product scintigraphic techniques. RESULTS: Twenty-five adult patients with a wide range of ages and renal function were studied. The results of this image-based method for calculating ERPF correlated well with the values obtained from blood samples (linear regression slope = 1.06; y-int = -34.68 ml/min, r = 0.905) and offered a significant improvement over both the Schlegel and renal uptake plasma volume product estimates (p < 0.05). CONCLUSION: A scintigraphic estimation of ERPF without blood samples using time-activity data from the heart, kidneys and bladder acquired over the entire renogram is feasible and correlates well with more invasive techniques requiring blood samples.

Body Height↗
PubMed1996

A distinctive type of infantile inflammatory myopathy with abnormal myonuclei.

Four infants developed progressive muscle weakness after a normal initial postnatal development. All patients had a moderate elevation of serum creatine kinase (CK) activity. Muscle biopsies revealed, in addition to myopathic features, endomysial and perivascular inflammation. Electron microscopy disclosed prominent myonuclear abnormalities. Corticosteroids in 3 patients were moderately beneficial. This appears to be a clinicopathologically distinct form of inflammatory myopathy of infants.

Adrenal Cortex Hormones↗
PubMed1996

Chronic inflammatory demyelinating polyneuropathy (CIDP) in diabetics.

Seven diabetic patients developed a progressive, moderately severe, motor rather than sensory neuropathy predominantly affecting the legs. This met clinical and electrophysiological criteria for chronic inflammatory demyelinating polyneuropathy (CIDP). Nerve biopsies showed a variety of abnormalities, none of which clearly distinguished between diabetic polyneuropathy and CIDP. The patients were treated with combinations of corticosteroids, azathioprine, plasmapheresis and intravenous immune globulin; all improved substantially. We believe that CIDP may masquerade as unusually severe and progressive diabetic distal symmetric polyneuropathy. It is important to recognize CIDP in diabetics because, unlike diabetic polyneuropathy, CIDP is treatable.

Adult↗