Alternating paroxysmal dystonia and hemiplegia in childhood as a symptom of basal ganglia disease.
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Adolescent↗
Biomedical subjects
K Farrell
Publications and source records attributed to K Farrell.
Genetic control of programmed cell death in Drosophila.
A gene, reaper (rpr), that appears to play a central control function for the initiation of programmed cell death (apoptosis) in Drosophila was identified. Virtually all programmed cell death that normally occurs during Drosophila embryogenesis was blocked in embryos homozygous for a small deletion that includes the reaper gene. Mutant embryos contained many extra cells and failed to hatch, but many other aspects of development appeared quite normal. Deletions that include reaper also protected embryos from apoptosis caused by x-irradiation and developmental defects. However, high doses of x-rays induced some apoptosis in mutant embryos, and the resulting corpses were phagocytosed by macrophages. These data suggest that the basic cell death program is intact although it was not activated in mutant embryos. The DNA encompassed by the deletion was cloned and the reaper gene was identified on the basis of the ability of cloned DNA to restore apoptosis to cell death defective embryos in germ line transformation experiments. The reaper gene appears to encode a small peptide that shows no homology to known proteins, and reaper messenger RNA is expressed in cells destined to undergo apoptosis.
Amino Acid Sequence↗
Cranial neuropathy, polyneuropathy and thrombocytopenia with Epstein-Barr virus infection.
Neurological involvement is an uncommon complication of Epstein-Barr virus infection, and the long incubation period may complicate the diagnosis. A 15-year-old boy is described with Epstein-Barr virus infection complicated by prolonged life-threatening thrombocytopenia, cranial neuropathy and peripheral sensorimotor neuropathy. The abnormal platelet count was unresponsive to multiple-drug therapy and splenectomy, but normalized 13 months after presentation. Neurological recovery was slow; the patient continues to have a mild peripheral sensorimotor neuropathy three years after the onset of the illness. Infection with Epstein-Barr virus should be considered in patients with acute neurological problems associated with thrombocytopenia. Measurement of antibodies to individual Epstein-Barr virus proteins facilitates the diagnosis of Epstein-Barr virus infection.
Adolescent↗
Glycosylation-dependent inactivation of the ecotropic murine leukemia virus receptor.
The ecotropic murine leukemia virus (E-MuLV) receptor expressed on Mus dunni tail fibroblast (MDTF) cells is a receptor for all E-MuLVs with the notable of Moloney murine leukemia virus (Mo-MuLV). Substitution of isoleucine for valine at position 214 in the third extracellular region (the putative E-MuLV binding site) of the MDTF receptor molecule allows this molecule to function as a Mo-MuLV receptor (M.V. Eiden, K. Farrell, J. Warsowe, L. A. Mahan, and C. A. Wilson, J. Virol. 67:4056-4061, 1993). We have now determined that treating MDTF cells with tunicamycin, an inhibitor of N-linked glycosylation, also renders them susceptible to Mo-MuLV infection. Two potential N-linked glycosylation sites are present in the third extracellular regions of both the NIH 3T3 and MDTF ecotropic receptors. The glycosylation site at position 229 of the MDTF receptor cDNA was eliminated by substituting a threonine codon for the asparagine codon. Mo-MuLV-resistant human HOS cells, expressing this form of the receptor, are susceptible to Mo-MuLV infection. Thus, our studies suggest that without a glycan moiety at position 229, the valine residue at 214 is no longer restrictive for Mo-MuLV infection. BHK-21 and CHO K1 hamster cells also express glycosylation-inactivated forms of the ecotropic receptor. Sequence analysis of these receptors together with our analysis of MDTF receptor function suggests that a single asparagine-linked glycosylation site is responsible for glycosylation inactivation of these receptors.
Amino Acid Sequence↗
Sweat gland vacuoles in Unverricht-Lundborg disease: a clue to diagnosis?
There has been no reported pathologic abnormality outside the central nervous system in patients with Unverricht-Lundborg disease (ULD). We report membrane-bound vacuoles with clear contents in eccrine clear cells and dark cells in five of seven patients with ULD, as well as in one clinically unaffected sibling. Vacuoles were not seen in the biopsies of two patients and of eight controls with Lafora's disease. These findings, though not entirely specific, suggest that skin biopsy may serve as a diagnostic aid to give supportive evidence for ULD.
Adolescent↗
Pulse oximetry in the field. A breath of fresh air?
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Emergency Medical Services↗
Case study: integrated voice and data services.
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Hospital Communication Systems↗
Radiation inactivation studies of the dopamine reuptake transporter protein.
Using radiation inactivation, we have estimated the target size for the neuronal dopamine transporter protein. The specific binding of several radioligands previously shown to label the dopamine transporter was determined in an irradiated striatal membrane preparation. The apparent target size of the 1-[1-(2-[3H]benzo[b]thienyl)cyclohexyl]piperidine site was approximately 98 kDa. However, the apparent target size of the "cocaine binding site," as measured with the cocaine analogue 2 beta-[3H]carbomethoxy-3 beta-(4-fluorophenyl)tropane in the same assays, was approximately 140 kDa. Radiation inactivation of the binding of other ligands (GBR-12935 and mazindol) led to target size estimates in the same range (94 kDa and 133 kDa, respectively). All of these target sizes are significantly larger than the estimate of 70 kDa derived from the deduced amino acid sequence for the cloned dopamine reuptake transporter cDNA. Larger target sizes than expected have also been reported for ligand binding to the sodium-dependent serotonin transporter and glucose transporter. The estimated sizes for the ligand binding site(s) associated with the dopamine transporter protein are difficult to reconcile with a single transporter protein of 70 kDa. We conclude that the dopamine transporter protein is a homo- or hetero-oligomer when occupied in situ by uptake-blocking drugs like cocaine.
Animals↗
Unverricht-Lundborg disease: absence of nonallelic genetic heterogeneity.
Unverricht-Lundborg disease is a clinically recognizable form of progressive myoclonus epilepsy. Recently, in several families of both Finnish and Mediterranean extraction segregating Unverricht-Lundborg disease, the gene for this disease was linked to the same region of the long arm of chromosome 21. We performed linkage analysis in eight families, including four of neither Baltic nor Mediterranean origin, using a polymorphic (CA)n repeat marker for the human liver-type 6 phosphofructokinase (PFKL) gene, previously mapped to 21q22.3. No recombinations were observed between the disease phenotype and the PFKL marker and a maximum lod score of 5.63 was obtained. These findings confirm tight linkage between PFKL and the gene for Unverricht-Lundborg disease and strongly suggest a lack of nonallelic genetic heterogeneity of the disease.
Adolescent↗
Intravenous immunoglobulin induces interferon-gamma and interleukin-6 in vivo.
Immunoglobulin is known to be an immunomodulator. It can induce protein mediators from mononuclear cells, particularly monocytes in vitro. Intravenous immunoglobulin (IVIg) has been used as a therapy in several clinical situations. In this study, the influence of IVIg infusion on the plasma levels of two protein mediators, interferon-gamma (IFN-gamma) and interleukin-6 (IL-6), was assessed in patients with secondary generalized epilepsy. Compared to preinfusion levels, plasma interferon-gamma was increased in 18 of 18 patients 20 min after the 6- to 8-hr infusion of IVIg. Plasma interferon-gamma levels reached their peak at various times from 20 min to 3 days post IVIg infusion, dependent upon the individual patient. Plasma IL-6 levels also increased after IVIg infusion. Generally, IL-6 reached its peak level after IFN-gamma. No activated T cells or B cells were observed as determined by the expression of surface CD25, CD23, and HLA-DR 20 min following the infusion when the IFN-gamma and IL-6 levels were assessed. The expression of the high-affinity receptor for IgG, CD64, on monocytes was significantly enhanced after IVIg infusion, while the low-affinity receptor for IgG, CD32, was only slightly increased. Cytoplasmic staining of PBMC indicates that both CD16-positive and CD16-negative cells may contribute to the increase seen in plasma IFN-gamma. These data raise the possibility that the therapeutic effects of intravenous immunoglobulin may be related, at least in part, to the immunomodulatory activity as demonstrated by the changes in plasma levels of IFN-gamma and IL-6.
Adolescent↗
Failure to recognize status epilepticus in a paralysed patient.
Paralysis induced by neuromuscular blocking agents facilitates ventilation of seriously ill patients but may preclude clinical recognition of seizures. We describe the occurrence of severe cognitive impairment in a 14-year-old girl in whom status epilepticus was recognized only when pancuronium was withdrawn after 14 hours of paralysis. This patient emphasizes a potential danger of paralysis from drugs in patients with acute cerebral dysfunction.
Adolescent↗
Characterization of a naturally occurring ecotropic receptor that does not facilitate entry of all ecotropic murine retroviruses.
A fibroblast cell line (MDTF) derived from the feral mouse Mus dunni is resistant to infection by Moloney murine leukemia virus (Mo-MuLV), an ecotropic murine leukemia virus (E-MuLV) (M. R. Lander and S. K. Chattopadadhyay, J. Virol. 52:695-698, 1984). MDTF cells can be infected by other E-MuLVs such as Friend MuLV and Rauscher MuLV, which have been demonstrated to use the same receptor as Mo-MuLV in NIH 3T3 cells (A. Rein and A. Schultz, Virology 136:144-152, 1984). We have now shown that the block to Mo-MuLV infection of MDTF cells occurs at the level of the envelope-receptor interaction. We have cloned the ecotropic receptor cDNA from MDTF cells (dRec) and compared its sequence with that of the NIH 3T3 cell receptor (mRec). Although the deduced dRec and mRec proteins differ at only four amino acid residues, we demonstrate that these changes account for the resistance of MDTF cells to Mo-MuLV infection. Our findings suggest that retroviruses in the same receptor class can exhibit different host ranges due to single amino acid differences in their cellular receptor.
3T3 Cells↗
Classifying epileptic syndromes: problems and a neurobiologic solution.
Because the effectiveness of an antiepileptic drug in controlling a particular seizure type and the prognosis for remission may differ between epileptic syndromes, accurate syndrome classification is crucial. However, a lack of universally accepted diagnostic criteria for some syndromes makes precise classification impossible in many patients. When syndromic classification is not possible, it is often more useful to consider genetic, clinical, electroencephalographic, neuropsychologic, radiologic, and other laboratory factors in characterizing the epileptic condition and selecting the optimal treatment.
Child, Preschool↗
Acute encephalomyelitis: extending the neurological manifestations of acute rheumatic fever?
The clinical course of a five-year-old boy who developed meningeal irritation, encephalomyelitis, and optic neuritis four weeks after Streptococcus pyogenes pharyngitis is detailed. The patient responded to therapy with corticosteroids and recovered fully. Review of the literature reveals that a wide range of neurological disorders have been described in association with rheumatic fever. We suggest that disseminated encephalomyelitis in this child most probably was related to the streptococcal infection and that the spectrum of post-infectious neurological disorders associated with Streptococcus pyogenes may be broader than is currently appreciated.
Acute Disease↗
Magnetic resonance imaging in pseudotumor cerebri.
The pathophysiology of pseudotumor cerebri is unclear, but may relate to an abnormality in water transport in the brain. The authors performed MR imaging in seven children with pseudotumor cerebri; the signal intensity in the white matter was normal in all patients. These data suggest that periventricular brain water content is not increased markedly in children with pseudotumor cerebri. The authors speculate that this may relate to the establishment of an equilibrium between increased resistance to cerebrospinal fluid outflow and increased brain stiffness, occurring as a consequence of increased cerebral blood-volume and/or interstitial pressure.
Adolescent↗
Continuous intrathecal baclofen treatment of severe spasms in two children with spinal-cord injury.
This study reports the use of intrathecal baclofen in two ventilator-dependent children with severe spasms secondary to spinal-cord injury. Baclofen was delivered via a subcutaneously implanted, programmable pump. The children were followed for 12 and 24 months. Baclofen dramatically reduced spasms, resulting in more stable ventilation, improved ease of care, reduced distress and better integration into the community. Although effective, intrathecal baclofen represents a significant intervention; careful consideration must be given to potential complications and the need for long-term management. Full effectiveness was dependent on free CSF flow.
Adolescent↗
Line defects in gel phase lipid monolayers.
We investigate various models of the hydrolysis of gel-phase phosphatidylcholine monolayers by phospholipase A2 (Grainger et al. (1989) FEBS Lett. 252, 73-82). We assume that the probability of hydrolysis of a given lipid depends only upon how many of its nearest neighbour lipids have already been hydrolysed. We find that the experimental data are consistent with a model in which line defects exist in the gel phase and that lipids on such defects are more easily hydrolysed than the other gel-phase lipids. Based on this model, we calculate the course of hydrolysis of a gel-phase region possessing line defects, and we suggest how such a structure might be made and the model tested. An experiment, similar to that proposed by us, has been carried out by Grainger et al. (1990) Biochim. Biophys. Acta 1023, 365-379). We also calculate the fractal dimension, df, of the interface created by the hydrolytic process and show that a measurement of df might identify how this process proceeds.
Computer Simulation↗
'Pure' and 'complicated' forms of hereditary spastic paraplegia presenting in childhood.
Of 23 children with hereditary spastic paraplegia (HSP), spasticity was the only neurological abnormality in eight patients (pure form). Additional neurological abnormalities in the 15 with complicated HSP included cognitive impairment, pseudo-bulbar palsy, cerebellar dysfunction and polyneuropathy. 19 children presented with abnormal gait, recognised at a mean age of three years in the pure form and five years in the complicated form. These forms were distinguished at a mean age of 11 years. Early non-motor developmental delay or rapidly ascending paraparesis, with spread of spasticity to the arms and with involvement of bulbar structures, predicted development of the complicated form. The pure form was inherited in an autosomal dominant manner in five patients. The autosomal recessive form was commonly associated with additional neurological abnormalities and a more rapid rate of progression.
Activities of Daily Living↗